{"id":803,"date":"2014-10-27T21:29:53","date_gmt":"2014-10-27T18:29:53","guid":{"rendered":"http:\/\/e-endocrinology.gr\/?page_id=803"},"modified":"2015-02-18T15:13:11","modified_gmt":"2015-02-18T12:13:11","slug":"10-22-%ce%bc%ce%bf%cf%81%ce%b9%ce%b1%ce%ba%ce%bf%ce%af-%ce%b4%ce%b5%ce%af%ce%ba%cf%84%ce%b5%cf%82-%ce%ba%ce%b1%ce%b9-%ce%ba%ce%b1%cf%81%ce%ba%ce%af%ce%bd%cf%89%ce%bc%ce%b1-%cf%84%ce%bf%cf%85-%ce%b8","status":"publish","type":"page","link":"https:\/\/e-endocrinology.gr\/?page_id=803","title":{"rendered":"10.22 \u039c\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2"},"content":{"rendered":"

\n \n \"Print\n <\/a>\n <\/div><\/p>\n


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\u0392. \u0394\u03b1\u03c1\u03ac\u03ba\u03b7<\/em>
\n\u0395\u03c0\u03b9\u03bc\u03b5\u03bb\u03b7\u03c4\u03c1\u03b9\u03b1 \u0392\u2019 \u0395\u03a3\u03a5, \u039a\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae \u0395\u03bd\u03b4\u03bf\u03ba\u03c1\u03b9\u03bd\u03bf\u03bb\u03bf\u03b3\u03af\u03b1\u03c2, \u0394\u03b9\u03b1\u03b2\u03ae\u03c4\u03b7 \u03ba\u03b1\u03b9 \u039c\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03ba\u03ce\u03bd \u039d\u03bf\u03c3\u03b7\u03bc\u03ac\u03c4\u03c9\u03bd,
\n\u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03b9\u03b1\u03ba\u03cc \u039d\u03bf\u03c3\u03bf\u03ba\u03bf\u03bc\u03b5\u03af\u03bf \u0397\u03c1\u03b1\u03ba\u03bb\u03b5\u03af\u03bf\u03c5
\n\u0395. \u039c\u03b1\u03bc\u03b1\u03bb\u03ac\u03ba\u03b7<\/em>
\n\u0394\u03b9\u03b5\u03c5\u03b8\u03cd\u03bd\u03c4\u03c1\u03b9\u03b1 \u0395\u03a3\u03a5,\u00a0\u039a\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae \u0395\u03bd\u03b4\u03bf\u03ba\u03c1\u03b9\u03bd\u03bf\u03bb\u03bf\u03b3\u03af\u03b1\u03c2, \u0394\u03b9\u03b1\u03b2\u03ae\u03c4\u03b7 \u03ba\u03b1\u03b9 \u039c\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03ba\u03ce\u03bd \u039d\u03bf\u03c3\u03b7\u03bc\u03ac\u03c4\u03c9\u03bd,
\n\u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03b9\u03b1\u03ba\u03cc \u039d\u03bf\u03c3\u03bf\u03ba\u03bf\u03bc\u03b5\u03af\u03bf \u0397\u03c1\u03b1\u03ba\u03bb\u03b5\u03af\u03bf\u03c5<\/p>\n

\u0395\u03b9\u03c3\u03b1\u03b3\u03c9\u03b3\u03ae <\/b><\/h4>\n

\u0397 \u03c0\u03c1\u03cc\u03bf\u03b4\u03bf\u03c2 \u03c4\u03b7\u03c2 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ae\u03c2 \u03b2\u03b9\u03bf\u03bb\u03bf\u03b3\u03af\u03b1\u03c2 \u03b5\u03c0\u03ad\u03c4\u03c1\u03b5\u03c8\u03b5 \u03c4\u03b1 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03c4\u03b7\u03bd \u03ba\u03b1\u03bb\u03cd\u03c4\u03b5\u03c1\u03b7 \u03ba\u03b1\u03c4\u03b1\u03bd\u03cc\u03b7\u03c3\u03b7 \u03c4\u03c9\u03bd \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03ce\u03bd \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03c1\u03cd\u03b8\u03bc\u03b9\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03ba\u03cd\u03ba\u03bb\u03bf\u03c5, \u03c4\u03bf\u03c5 \u03c0\u03c1\u03bf\u03b3\u03c1\u03b1\u03bc\u03bc\u03b1\u03c4\u03b9\u03c3\u03bc\u03ad\u03bd\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03b8\u03b1\u03bd\u03ac\u03c4\u03bf\u03c5 (\u03b1\u03c0\u03cc\u03c0\u03c4\u03c9\u03c3\u03b7), \u03c4\u03b7\u03c2 \u03b1\u03b3\u03b3\u03b5\u03b9\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2, \u03c4\u03b7\u03c2 \u03b4\u03b9\u03ae\u03b8\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03ad\u03bb\u03bf\u03c2 \u03c4\u03b7\u03c2 \u03bc\u03b5\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7\u03c2.<\/p>\n

\u0397 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03bc\u03af\u03b1 \u03c0\u03bf\u03bb\u03c5\u03c0\u03b1\u03c1\u03b1\u03b3\u03bf\u03bd\u03c4\u03b9\u03ba\u03ae \u03b4\u03b9\u03b1\u03b4\u03b9\u03ba\u03b1\u03c3\u03af\u03b1 \u03cc\u03c0\u03bf\u03c5 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b1\u03bb\u03bb\u03b1\u03b3\u03ad\u03c2 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03cc\u03bd\u03b1 (\u03c0.\u03c7 \u03c7\u03b7\u03bc\u03b9\u03ba\u03bf\u03af \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b5\u03c2, \u03c0\u03b5\u03c1\u03b9\u03b2\u03b1\u03bb\u03bb\u03bf\u03bd\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b5\u03c0\u03b9\u03b4\u03c1\u03ac\u03c3\u03b5\u03b9\u03c2, \u03b9\u03bf\u03af \u03ba.\u03b1) \u03c4\u03c1\u03bf\u03c0\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03c4\u03b7 \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03c5\u03c7\u03af\u03b1 \u03c4\u03bf\u03c5 DNA \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c5\u03c0\u03b5\u03cd\u03b8\u03c5\u03bd\u03c9\u03bd \u03b3\u03b9\u03b1 \u03c4\u03b1 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03cc\u03c1\u03b9\u03b1 (\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1) \u03bc\u03b5 \u03c3\u03c5\u03bd\u03ad\u03c0\u03b5\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b1\u03bd\u03b5\u03be\u03ad\u03bb\u03b5\u03b3\u03ba\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc (1). \u03a0\u03bf\u03bb\u03bb\u03ac \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b5\u03ba\u03c4\u03cc\u03c2 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 \u03bc\u03b5 \u03c4\u03bf\u03bd \u03c4\u03cd\u03c0\u03bf \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5, \u03c4\u03b7\u03bd \u03b9\u03ba\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2, \u03c4\u03b7\u03bd \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03bc\u03b5\u03c1\u03b9\u03ba\u03ad\u03c2 \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03b9\u03c2 \u03c4\u03b7\u03bd \u03b1\u03bd\u03c4\u03b1\u03c0\u03cc\u03ba\u03c1\u03b9\u03c3\u03ae \u03c3\u03b5 \u03b5\u03b9\u03b4\u03b9\u03ba\u03ad\u03c2 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b5\u03c2.<\/p>\n

\u039f \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03c4\u03b7 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ae \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03af\u03b1 \u03c4\u03bf\u03c5 \u03b5\u03bd\u03b4\u03bf\u03ba\u03c1\u03b9\u03bd\u03b9\u03ba\u03bf\u03cd \u03c3\u03c5\u03c3\u03c4\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03bc\u03b5 \u03c3\u03c5\u03bd\u03b5\u03c7\u03ce\u03c2 \u03b1\u03c5\u03be\u03b1\u03bd\u03cc\u03bc\u03b5\u03bd\u03b7 \u03b5\u03c0\u03af\u03c0\u03c4\u03c9\u03c3\u03b7 \u03c4\u03b9\u03c2 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b5\u03c2 \u03b4\u03b5\u03ba\u03b1\u03b5\u03c4\u03af\u03b5\u03c2 (2). \u0397 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ae \u03b2\u03ac\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ad\u03c7\u03b5\u03b9 \u03bc\u03b5\u03bb\u03b5\u03c4\u03b7\u03b8\u03b5\u03af \u03b5\u03ba\u03c4\u03b5\u03c4\u03b1\u03c4\u03b1\u03bc\u03ad\u03bd\u03b1 \u03c4\u03b1 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1. \u03a3\u03b5 \u03b1\u03c5\u03c4\u03ae\u03bd \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1) \u03c0\u03c1\u03c9\u03c4\u03bf\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 (proto-oncogenes) \u03c4\u03b1 \u03c0\u03c1\u03bf\u03ca\u03cc\u03bd\u03c4\u03b1 \u03c4\u03c9\u03bd \u03bf\u03c0\u03bf\u03af\u03c9\u03bd \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b1\u03cd\u03be\u03b7\u03c3\u03b7 \u03ae \u03c4\u03b7\u03bd \u03b4\u03b9\u03b1\u03af\u03c1\u03b5\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03b2) \u03bf\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03ac \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1(tumor suppressor genes) \u03c4\u03b1 \u03c0\u03c1\u03bf\u03ca\u03cc\u03bd\u03c4\u03b1 \u03c4\u03c9\u03bd \u03bf\u03c0\u03bf\u03af\u03c9\u03bd \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03ae \u03c4\u03b7\u03c2 \u03b1\u03cd\u03be\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03bf\u03cd \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03b3) \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1-\u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03ba\u03c4\u03b5\u03c2 \u03c4\u03b1 \u03c0\u03c1\u03bf\u03ca\u03cc\u03bd\u03c4\u03b1 \u03c4\u03c9\u03bd \u03bf\u03c0\u03bf\u03af\u03c9\u03bd \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03c4\u03b9\u03b3\u03c1\u03b1\u03c6\u03ae \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b5\u03c0\u03b9\u03b4\u03b9\u03cc\u03c1\u03b8\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 DNA. \u039f\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03b1 \u03bf\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03ac \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c0\u03bf\u03bb\u03b5\u03b9\u03c0\u03cc\u03bc\u03b5\u03bd\u03b5\u03c2 \u03ba\u03b1\u03b9 \u03b4\u03b5\u03bd \u03b1\u03c1\u03ba\u03bf\u03cd\u03bd \u03b1\u03c0\u03cc \u03bc\u03cc\u03bd\u03b5\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03bd\u03b1 \u03bf\u03b4\u03b7\u03b3\u03ae\u03c3\u03bf\u03c5\u03bd \u03c3\u03b5 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7. \u0391\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 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\u00a0\"10.22-figure1\"\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 1. <\/b><\/em>Mo\u03bd\u03c4\u03ad\u03bb\u03bf \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae. <\/b>\u0391\u03c5\u03c4\u03cc \u03c4\u03bf \u03bc\u03bf\u03bd\u03c4\u03ad\u03bb\u03bf \u03b2\u03b1\u03c3\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03ba\u03b1\u03b9 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ac \u03b3\u03bd\u03c9\u03c1\u03af\u03c3\u03bc\u03b1\u03c4\u03b1 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf \u03b2\u03b1\u03b8\u03bc\u03cc \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a4\u03bf \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ba\u03cc \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03bf \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b5\u03be\u03b5\u03bb\u03b9\u03c7\u03b8\u03b5\u03af \u03c3\u03b5 \u03ba\u03b1\u03bb\u03cc\u03b7\u03b8\u03b5\u03c2 \u03b1\u03b4\u03ad\u03bd\u03c9\u03bc\u03b1 \u03b5\u03af\u03c4\u03b5 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03cc \u03cc\u03b3\u03ba\u03bf. \u0391\u03c5\u03c4\u03cc\u03bd\u03bf\u03bc\u03b1 \u03c5\u03c0\u03b5\u03c1\u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03bf\u03cd\u03bd\u03c4\u03b1 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03c5\u03bd\u03b4\u03ad\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03c4\u03b7\u03c2 TSH (TSHR) \u03ae \u03c4\u03c9\u03bd G-\u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd(3). \u0395\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ba\u03bf\u03cd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03cc \u03bf\u03c6\u03b5\u03af\u03bb\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03ce\u03bd \u03c0\u03c1\u03c9\u03c4\u03bf\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03ba\u03b1\u03b9 \u03bf\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03ce\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd, \u03bc\u03b5 \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1 \u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03b9 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03c0\u03bb\u03b1\u03c3\u03c4\u03b9\u03ba\u03bf\u03cd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2.\u00a0 \u03a0\u03b7\u03b3\u03ae: (4).<\/p>\n

\n

1. <\/b>\u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2<\/b> <\/b>\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd<\/b> <\/b>\u03ba\u03b1\u03b9<\/b> <\/b>\u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03b9\u03c2<\/b> <\/b><\/h4>\n
1.1<\/b>. <\/b>\u0398\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2<\/b> <\/b>\u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1<\/b> <\/b>\u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2<\/b><\/h5>\n

\u03a4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03c4\u03bf\u03bd \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03cc \u03c4\u03cd\u03c0\u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03bb\u03bf\u03b3\u03b5\u03af \u03c3\u03c4\u03bf 80% \u03c0\u03b5\u03c1\u03af\u03c0\u03bf\u03c5 \u03c4\u03c9\u03bd \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03c9\u03bd (5). \u0388\u03bd\u03b1 \u03c5\u03c8\u03b7\u03bb\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (70%) \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03bf\u03c6\u03b5\u03af\u03bb\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ad\u03c2 \u03c0\u03bf\u03c5 \u03bf\u03b4\u03b7\u03b3\u03bf\u03cd\u03bd \u03c3\u03b5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd \u03bc\u03b5\u03c4\u03ac\u03b4\u03bf\u03c3\u03b7\u03c2 \u03c3\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 (6). \u0391\u03c5\u03c4\u03ad\u03c2 \u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03ac\u03bd\u03bf\u03c5\u03bd \u03c3\u03b7\u03bc\u03b5\u03b9\u03b1\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd BRAF \u03ba\u03b1\u03b9 RAS \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03ac \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1, \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c4\u03bf RET\/PTC \u03ba\u03b1\u03b9 \u03c3\u03c0\u03b1\u03bd\u03b9\u03cc\u03c4\u03b5\u03c1\u03b1 \u03c4\u03bf TRK1 (7,8,9) \u03ba\u03b1\u03b8\u03ad\u03bd\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b1 \u03bf\u03c0\u03bf\u03af\u03b1 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03bf\u03c5\u03bd \u03be\u03b5\u03c7\u03c9\u03c1\u03b9\u03c3\u03c4\u03ac \u03c4\u03bf \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1<\/b> 2<\/b>). \u039f\u03b9 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03bf\u03b4\u03b7\u03b3\u03bf\u03cd\u03bd \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF (45%) \u03ba\u03b1\u03b9 \u03b1\u03ba\u03bf\u03bb\u03bf\u03c5\u03b8\u03bf\u03cd\u03bd \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 RAS (15%) \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 \u03c7\u03b5\u03b9\u03bc\u03b5\u03c1\u03b9\u03ba\u03bf\u03cd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RET\/PTC (15%) (10). \u0397 \u03b5\u03c0\u03af\u03b4\u03c1\u03b1\u03c3\u03b7 \u03c4\u03c9\u03bd \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 BRAF \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 RET\/PTC \u03c3\u03c4\u03bf\u03bd \u03ba\u03bf\u03b9\u03bd\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03bc\u03b5\u03c4\u03ac\u03b4\u03bf\u03c3\u03b7\u03c2 \u03c3\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b4\u03b9\u03b1\u03c6\u03ad\u03c1\u03b5\u03b9 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03bf\u03b4\u03b7\u03b3\u03bf\u03cd\u03bd \u03c3\u03b5 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03c4\u03cd\u03c0\u03bf\u03c5\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (11).<\/p>\n

\n

\"10.22-figure2\"\u00a0<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 2.<\/b><\/em> \u038c\u03bb\u03b5\u03c2 \u03bf\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b4\u03c5\u03bd\u03b1\u03c4\u03cc\u03bd \u03bd\u03b1 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03bf\u03c5\u03bd \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c3\u03b7\u03bc\u03b1\u03c4\u03bf\u03b4\u03cc\u03c4\u03b7\u03c3\u03b7\u03c2 \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2. \u0391\u03c5\u03c4\u03cc \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03bc\u03b5\u03c4\u03b1\u03c6\u03ad\u03c1\u03b5\u03b9 \u03bc\u03b7\u03bd\u03cd\u03bc\u03b1\u03c4\u03b1 \u03b1\u03c0\u03cc \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ce\u03bd \u03ba\u03b9\u03bd\u03b1\u03c3\u03ce\u03bd \u03c4\u03b7\u03c2 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03ae\u03c2 \u03bc\u03b5\u03bc\u03b2\u03c1\u03ac\u03bd\u03b7\u03c2 (RTKs) \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 \u03b4\u03b9\u03b1\u03bc\u03ad\u03c3\u03bf\u03c5 \u03bc\u03b9\u03b1\u03c2 \u03c3\u03b5\u03b9\u03c1\u03ac\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd \u03ba\u03b1\u03b9 \u03b5\u03bd\u03b4\u03bf\u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ce\u03bd \u03ba\u03b9\u03bd\u03b1\u03c3\u03ce\u03bd \u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03b1\u03bd\u03bf\u03bc\u03ad\u03bd\u03c9\u03bd \u03c4\u03c9\u03bd RAS, RAF (\u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c4\u03bf BRAF \u03c3\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2), MEK, \u03ba\u03b1\u03b9 ERK. \u03a4\u03bf \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03bf \u03cc\u03c4\u03b1\u03bd \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03b8\u03b5\u03af \u03c1\u03c5\u03b8\u03bc\u03af\u03b6\u03b5\u03b9 \u03c4\u03b7\u03bd \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03ae \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 \u03c0\u03bf\u03c5 \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7, \u03c3\u03c4\u03bf\u03bd \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b5\u03c0\u03b9\u03b2\u03af\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5. \u03a0\u03b7\u03b3\u03ae: \u00a0(9).<\/p>\n

\n
\u00a01<\/b>.1.1. \u03a7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>RET<\/b>\/<\/b>PTC<\/b><\/h6>\n

\u03a4\u03bf \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RET \u03b2\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03c7\u03c1\u03c9\u03bc\u03cc\u03c3\u03c9\u03bc\u03b1 10 \u03ba\u03b1\u03b9 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03ad\u03bd\u03b1\u03bd \u03b4\u03b9\u03b1\u03bc\u03b5\u03bc\u03b2\u03c1\u03b1\u03bd\u03b9\u03ba\u03cc \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03c4\u03b7\u03c2 \u03c4\u03c5\u03c1\u03bf\u03c3\u03af\u03bd\u03b7\u03c2, \u03c0\u03bf\u03c5 \u03b1\u03bd\u03ae\u03ba\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03ad\u03bd\u03b5\u03b9\u03b1 \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03c4\u03bf\u03c5 \u03b1\u03c5\u03be\u03b7\u03c4\u03b9\u03ba\u03bf\u03cd \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 \u03c4\u03c9\u03bd \u03b1\u03b9\u03bc\u03bf\u03c0\u03b5\u03c4\u03b1\u03bb\u03af\u03c9\u03bd (PDGF-R) (12). \u03a5\u03c0\u03cc \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ad\u03c2 \u03c3\u03c5\u03bd\u03b8\u03ae\u03ba\u03b5\u03c2 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03ad\u03c3\u03c3\u03b5\u03c1\u03b5\u03b9\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b5\u03c2: GDNF (glial cell derived neurotrophic factor), Neurturin (NRTN), Artimin (ARTN), Persepin (PSPN) (13,14) \u03ba\u03b1\u03b9 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03ad\u03c7\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03c4\u03bf\u03c5 \u03c0\u03b5\u03c1\u03b9\u03c6\u03b5\u03c1\u03b9\u03ba\u03bf\u03cd \u03bd\u03b5\u03c5\u03c1\u03b9\u03ba\u03bf\u03cd \u03c3\u03c5\u03c3\u03c4\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7\u03bd \u03b5\u03bd\u03b4\u03bf\u03bc\u03ae\u03c4\u03c1\u03b9\u03bf \u03b6\u03c9\u03ae (15). \u03a4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RET \u03b5\u03ba\u03c6\u03c1\u03ac\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03c3\u03b5 \u03b9\u03c3\u03c4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ad\u03c1\u03c7\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b7 \u03bd\u03b5\u03c5\u03c1\u03b9\u03ba\u03ae \u03b1\u03ba\u03c1\u03bf\u03bb\u03bf\u03c6\u03af\u03b1 \u03cc\u03c0\u03c9\u03c2 \u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 C \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03bf \u03bc\u03c5\u03b5\u03bb\u03cc\u03c2 \u03c4\u03c9\u03bd \u03b5\u03c0\u03b9\u03bd\u03b5\u03c6\u03c1\u03b9\u03b4\u03af\u03c9\u03bd, \u03cc\u03c7\u03b9 \u03cc\u03bc\u03c9\u03c2 \u03c3\u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03c9\u03bd \u03b8\u03c5\u03bb\u03b1\u03ba\u03af\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (16).<\/p>\n

\u03a4\u03bf 1987 \u03b1\u03bd\u03b1\u03ba\u03b1\u03bb\u03cd\u03c6\u03c4\u03b7\u03ba\u03b5 \u03b3\u03b9\u03b1 \u03c0\u03c1\u03ce\u03c4\u03b7 \u03c6\u03bf\u03c1\u03ac \u03c4\u03bf \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RET\/PTC \u03c3\u03b5 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (17). \u0397 \u03ba\u03bb\u03c9\u03bd\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03ae \u03c4\u03bf\u03c5 3 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03b1\u03c1\u03b3\u03cc\u03c4\u03b5\u03c1\u03b1 \u03ad\u03b4\u03b5\u03b9\u03be\u03b5 \u03cc\u03c4\u03b9 \u03c0\u03c1\u03bf\u03ad\u03c1\u03c7\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b7 \u03c3\u03c5\u03b3\u03c7\u03ce\u03bd\u03b5\u03c5\u03c3\u03b7 \u03c0\u03b5\u03c1\u03b9\u03bf\u03c7\u03ae\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RET \u03c0\u03bf\u03c5 \u03c6\u03ad\u03c1\u03b5\u03b9 \u03c4\u03b7\u03bd \u03b9\u03b4\u03b9\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03b7\u03c2 \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03bc\u03b5 \u03c4\u03b7 \u03c1\u03c5\u03b8\u03bc\u03b9\u03c3\u03c4\u03b9\u03ba\u03ae \u03c0\u03b5\u03c1\u03b9\u03bf\u03c7\u03ae \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 CCD6 (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 3<\/b>) (18). \u03a3\u03ae\u03bc\u03b5\u03c1\u03b1 \u03ad\u03c7\u03bf\u03c5\u03bd \u03c0\u03b5\u03c1\u03b9\u03b3\u03c1\u03b1\u03c6\u03b5\u03af 13 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03bf\u03af \u03c4\u03cd\u03c0\u03bf\u03b9 RET\/PTC \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03c9\u03bd. \u03a4\u03b1 \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03c0\u03bf\u03c5 \u03c3\u03c5\u03b3\u03c7\u03c9\u03bd\u03b5\u03cd\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03bc\u03ae\u03bc\u03b1 \u03c4\u03bf\u03c5 RET \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03b2\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03af\u03b4\u03b9\u03bf \u03c7\u03c1\u03c9\u03bc\u03cc\u03c3\u03c9\u03bc\u03b1 \u03bc\u03b5 \u03c4\u03bf RET \u03ba\u03b1\u03b9 \u03ad\u03c7\u03bf\u03c5\u03bd \u03c5\u03c8\u03b7\u03bb\u03cc \u03b5\u03c0\u03af\u03c0\u03b5\u03b4\u03bf \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7\u03c2 \u03c3\u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b5\u03c2 \u03c0\u03bf\u03c5 \u03b5\u03be\u03c5\u03c0\u03b7\u03c1\u03b5\u03c4\u03bf\u03cd\u03bd \u03b2\u03b1\u03c3\u03b9\u03ba\u03ad\u03c2 \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b5\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5. \u03a4\u03bf \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03bd\u03b1 \u03c0\u03b1\u03c1\u03ac\u03b3\u03b5\u03c4\u03b1\u03b9 \u03b4\u03b9\u03b1\u03c1\u03ba\u03ce\u03c2 \u03b7 \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03ae \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 RET\/PTC \u03ba\u03b1\u03b9 \u03bd\u03b1 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03b5\u03af\u03c4\u03b1\u03b9 \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae\u03c2 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd RAS-RAF-MAPK \u03c0\u03bf\u03c5 \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c3\u03c4\u03bf\u03bd \u03b1\u03bd\u03b5\u03be\u03ad\u03bb\u03b5\u03b3\u03ba\u03c4\u03bf \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03af\u03b1\u03c2. \u039a\u03cd\u03c1\u03b9\u03bf \u03b1\u03af\u03c4\u03b9\u03bf \u03c4\u03b7\u03c2 \u03b4\u03b7\u03bc\u03b9\u03bf\u03c5\u03c1\u03b3\u03af\u03b1\u03c2 \u03c4\u03c9\u03bd \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03c9\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03ad\u03ba\u03b8\u03b5\u03c3\u03b7 \u03c3\u03b5 \u03b1\u03ba\u03c4\u03b9\u03bd\u03bf\u03b2\u03bf\u03bb\u03af\u03b1 \u03c0\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03b5\u03af \u03b2\u03bb\u03ac\u03b2\u03b5\u03c2 \u03c3\u03c4\u03bf DNA \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5, \u03cc\u03c0\u03c9\u03c2 \u03b1\u03c0\u03bf\u03b4\u03b5\u03af\u03c7\u03c4\u03b7\u03ba\u03b5 \u03c3\u03b5 in vitro \u03c0\u03b5\u03b9\u03c1\u03ac\u03bc\u03b1\u03c4\u03b1 (19, 20). \u03a9\u03c3\u03c4\u03cc\u03c3\u03bf \u03c4\u03b1 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03ad\u03c4\u03b7 \u03ad\u03c7\u03b5\u03b9 \u03c0\u03b5\u03c1\u03b9\u03b3\u03c1\u03b1\u03c6\u03b5\u03af \u03bf \u03c1\u03cc\u03bb\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03ac\u03bb\u03bb\u03c9\u03bd \u03c0\u03b9\u03b8\u03b1\u03bd\u03ce\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03cc\u03bd\u03c9\u03bd \u03cc\u03c0\u03c9\u03c2 \u03b7 \u03ba\u03b1\u03c6\u03b5\u0390\u03bd\u03b7, \u03b7 \u03b1\u03b9\u03b8\u03b1\u03bd\u03cc\u03bb\u03b7 \u03b7 \u03c5\u03c0\u03bf\u03be\u03af\u03b1 \u03ba.\u03b1. (21) \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c0\u03b1\u03c1\u03b1\u03b3\u03cc\u03bd\u03c4\u03c9\u03bd \u03c0\u03bf\u03c5 \u03b1\u03c5\u03be\u03ac\u03bd\u03bf\u03c5\u03bd \u03c4\u03b7 \u03c3\u03c5\u03b3\u03ba\u03ad\u03bd\u03c4\u03c1\u03c9\u03c3\u03b7 \u03b1\u03bd\u03b9\u03cc\u03bd\u03c4\u03c9\u03bd \u03c5\u03c0\u03b5\u03c1\u03bf\u03be\u03b5\u03b9\u03b4\u03af\u03bf\u03c5 \u03ba\u03b1\u03b9 H2<\/sub>O2 <\/sub>(22) \u03c3\u03c4\u03b7\u03bd \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7 \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03c9\u03bd RET\/PTC.<\/p>\n

\u03a4\u03bf RET\/PTC1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ae \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 (60-70% \u03c4\u03c9\u03bd \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03c9\u03bd). \u0388\u03c7\u03b5\u03b9 \u03c0\u03b5\u03c1\u03b9\u03b3\u03c1\u03b1\u03c6\u03b5\u03af \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 10-20% \u03c3\u03c0\u03bf\u03c1\u03b1\u03b4\u03b9\u03ba\u03ce\u03bd \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03bd \u03ba\u03b1\u03b9 \u03bf \u03b5\u03c0\u03b9\u03c0\u03bf\u03bb\u03b1\u03c3\u03bc\u03bf\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03c0\u03bf\u03b9\u03ba\u03af\u03bb\u03b5\u03b9 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ac \u03c3\u03b5 \u03b4\u03b9\u03ac\u03c6\u03bf\u03c1\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 (23) \u03ba\u03b1\u03b9 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b9\u03b4\u03b9\u03b1\u03af\u03c4\u03b5\u03c1\u03b1 \u03c7\u03b1\u03bc\u03b7\u03bb\u03cc\u03c2 \u03c3\u03b5 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7 (24). \u0397 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03ae \u03c4\u03bf\u03c5\u03c2 \u03c3\u03b5 \u03bc\u03b9\u03ba\u03c1\u03bf\u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b5\u03bd\u03b9\u03c3\u03c7\u03cd\u03b5\u03b9 \u03c4\u03b7\u03bd \u03c5\u03c0\u03cc\u03b8\u03b5\u03c3\u03b7 \u03cc\u03c4\u03b9 \u03c0\u03c1\u03cc\u03ba\u03b5\u03b9\u03c4\u03b1\u03b9 \u03b3\u03b9\u03b1 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae \u03b2\u03bb\u03ac\u03b2\u03b7 \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03b5\u03b9 \u03c0\u03c1\u03ce\u03b9\u03bc\u03b1 \u03c3\u03c4\u03b7 \u03b4\u03b9\u03b1\u03b4\u03b9\u03ba\u03b1\u03c3\u03af\u03b1 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 (25). \u0397 \u03b5\u03c0\u03af\u03c0\u03c4\u03c9\u03c3\u03ae \u03c4\u03bf\u03c5\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c8\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03b7 \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03bc\u03b5 \u03b9\u03c3\u03c4\u03bf\u03c1\u03b9\u03ba\u03cc \u03ad\u03ba\u03b8\u03b5\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03b1\u03ba\u03c4\u03b9\u03bd\u03bf\u03b2\u03bf\u03bb\u03af\u03b1 (50-80%) \u03cc\u03c0\u03c9\u03c2 \u03c3\u03b5 \u03b5\u03c0\u03b9\u03b2\u03b9\u03ce\u03c3\u03b1\u03bd\u03c4\u03b5\u03c2 \u03b1\u03c0\u03cc \u03b1\u03c4\u03bf\u03bc\u03b9\u03ba\u03ae \u03b2\u03cc\u03bc\u03b2\u03b1 (26) \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03bc\u03b5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03b8\u03c5\u03c1\u03b5\u03bf\u03bf\u03b5\u03b9\u03b4\u03ae \u03bc\u03b5\u03c4\u03ac \u03c4\u03bf \u03c0\u03c5\u03c1\u03b7\u03bd\u03b9\u03ba\u03cc \u03b1\u03c4\u03cd\u03c7\u03b7\u03bc\u03b1 \u03c4\u03bf\u03c5 Chernobil (27). \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c8\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03b7 \u03c3\u03b5 \u03c0\u03b1\u03b9\u03b4\u03b9\u03ac \u03ba\u03b1\u03b9 \u03bd\u03ad\u03bf\u03c5\u03c2 \u03b5\u03bd\u03ae\u03bb\u03b9\u03ba\u03b5\u03c2, \u03b1\u03bd\u03b5\u03be\u03ac\u03c1\u03c4\u03b7\u03c4\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03ad\u03ba\u03b8\u03b5\u03c3\u03b7 \u03c3\u03b5 \u03b1\u03ba\u03c4\u03b9\u03bd\u03bf\u03b2\u03bf\u03bb\u03af\u03b1 (40-70%) (28,29). \u0391\u03bd \u03ba\u03b1\u03b9 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c5\u03c8\u03b7\u03bb\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ce\u03bd \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03c9\u03bd (34), \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03ad\u03c7\u03b5\u03b9 \u03ba\u03b1\u03bb\u03ae \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 (35). E\u03c0\u03af\u03c3\u03b7\u03c2 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 Hurthle \u03bc\u03b5 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03b9\u03ce\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (36) \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf\u03c5\u03c2 \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03c4\u03cd\u03c0\u03bf\u03c5\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03bc\u03b5 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03cc \u03c6\u03b1\u03b9\u03bd\u03cc\u03c4\u03c5\u03c0\u03bf (sclerosing \u03ba\u03b1\u03b9 tall-cell variant (37) \u03c3\u03c4\u03bf\u03c5\u03c2 \u03b5\u03bd\u03ae\u03bb\u03b9\u03ba\u03b5\u03c2 \u03ba\u03b1\u03b9 solid variant \u03c3\u03c4\u03b1 \u03c0\u03b1\u03b9\u03b4\u03b9\u03ac (28).<\/p>\n

\u0397 \u03ba\u03b1\u03c4\u03b1\u03bd\u03bf\u03bc\u03ae \u03c4\u03b7\u03c2 \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7\u03c2 RET\/PTC \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03b1 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 (clonal RET\/PTC) \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5 -\u03b5\u03b9\u03b4\u03b9\u03ba\u03ae \u03b3\u03b9\u03b1 \u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (23,9) \u03ae \u03bd\u03b1 \u03b1\u03bd\u03b9\u03c7\u03bd\u03b5\u03cd\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bc\u03b9\u03ba\u03c1\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (<1%) \u03c4\u03c9\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ce\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd(nonclonal RET\/PTC) (30,31). \u0397 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03ad\u03c7\u03b5\u03b9 \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03b5\u03ba\u03c4\u03cc\u03c2 \u03b1\u03c0\u03cc \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c3\u03b5 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03ac\u03bb\u03bb\u03b5\u03c2 \u03ba\u03b1\u03bb\u03bf\u03ae\u03b8\u03b5\u03b9\u03c2 \u03b2\u03bb\u03ac\u03b2\u03b5\u03c2 (32) \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03af\u03c4\u03b9\u03b4\u03b1 Hashimoto (33).<\/p>\n

\n

\u00a0\"10.22-figure3\"<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 3<\/em>. <\/b>\u03a3\u03c7\u03b7\u03bc\u03b1\u03c4\u03b9\u03ba\u03ae \u03b1\u03bd\u03b1\u03c0\u03b1\u03c1\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RET \u03bc\u03b5 \u03c4\u03b7\u03bd \u03c0\u03b5\u03c1\u03b9\u03bf\u03c7\u03ae 5\u0384\u03ac\u03bb\u03bb\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03c0\u03bf\u03c5 \u03b5\u03ba\u03c6\u03c1\u03ac\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae. \u03a0\u03b7\u03b3\u03ae: (12).<\/p>\n

\n
1.1<\/b>.2. \u03a7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc o\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>TRK<\/b> <\/b><\/h6>\n

\u03a4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf NTRK1 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03bf\u03bd \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b1\u03c5\u03be\u03b7\u03c4\u03b9\u03ba\u03cc \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 \u03c4\u03c9\u03bd \u03bd\u03b5\u03cd\u03c1\u03c9\u03bd Trk-A. \u039f \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1\u03c2 \u03b1\u03c5\u03c4\u03cc\u03c2 \u03ad\u03c7\u03b5\u03b9 \u03b9\u03b4\u03b9\u03cc\u03c4\u03b7\u03c4\u03b5\u03c2 \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03cc\u03c4\u03b1\u03bd \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03b8\u03b5\u03af \u03b1\u03c5\u03c4\u03bf\u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03b9\u03ce\u03bd\u03b5\u03c4\u03b1\u03b9 \u03ba\u03b1\u03b9 \u03c4\u03b1\u03c5\u03c4\u03cc\u03c7\u03c1\u03bf\u03bd\u03b1 \u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03b9\u03ce\u03bd\u03b5\u03b9 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b5\u03c2 \u03b1\u03c0\u03cc \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2. \u03a0\u03b1\u03af\u03b6\u03b5\u03b9 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03ba\u03b1\u03b9 \u03c9\u03c1\u03af\u03bc\u03b1\u03bd\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c0\u03b5\u03c1\u03b9\u03c6\u03b5\u03c1\u03b9\u03ba\u03bf\u03cd \u03bd\u03b5\u03c5\u03c1\u03b9\u03ba\u03bf\u03cd \u03c3\u03c5\u03c3\u03c4\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03b5\u03c0\u03b9\u03c0\u03c1\u03cc\u03c3\u03b8\u03b5\u03c4\u03b1 \u03b5\u03c0\u03ac\u03b3\u03b5\u03b9 \u03c4\u03bf\u03bd \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc \u03bc\u03b5\u03b3\u03ac\u03bb\u03bf\u03c5 \u03b1\u03c1\u03b9\u03b8\u03bc\u03bf\u03cd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03cc\u03c0\u03c9\u03c2 \u03c4\u03b1 \u03bb\u03b5\u03bc\u03c6\u03bf\u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03ba\u03b1\u03b9 \u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03c0\u03c1\u03bf\u03c3\u03c4\u03ac\u03c4\u03b7 (34,35,36).<\/b><\/p>\n

\u0397 \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03c5\u03c7\u03af\u03b1 \u03c4\u03c9\u03bd \u03bd\u03bf\u03c5\u03ba\u03bb\u03b5\u03bf\u03c4\u03b9\u03b4\u03af\u03c9\u03bd \u03c4\u03bf\u03c5 NTRK1 \u03c0\u03bf\u03c5 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03b7\u03bd \u03c0\u03b5\u03c1\u03b9\u03bf\u03c7\u03ae \u03bc\u03b5 \u03b9\u03b4\u03b9\u03cc\u03c4\u03b7\u03c4\u03b1 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03c4\u03b7\u03c2 \u03c4\u03c5\u03c1\u03bf\u03c3\u03af\u03bd\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03b1\u03c5\u03c4\u03bf\u03cd, \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b5\u03bd\u03c9\u03b8\u03b5\u03af \u03bc\u03b5 \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03c5\u03c7\u03af\u03b5\u03c2 \u03bd\u03bf\u03c5\u03ba\u03bb\u03b5\u03bf\u03c4\u03b9\u03b4\u03af\u03c9\u03bd \u03ac\u03bb\u03bb\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03b4\u03b7\u03bc\u03b9\u03bf\u03c5\u03c1\u03b3\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b1 \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03ac \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 TRK, TRK-T1, TRK-T2, TRK-T3. \u03a4\u03b1 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 12% (\u03bc\u03b5 \u03c0\u03bf\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03cc \u03c4\u03bf TRK), \u03ba\u03b1\u03b9 \u03b4\u03b5\u03bd \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03ad\u03ba\u03b8\u03b5\u03c3\u03b7 \u03c3\u03c4\u03b7\u03bd \u03b1\u03ba\u03c4\u03b9\u03bd\u03bf\u03b2\u03bf\u03bb\u03af\u03b1 (37,38). \u039c\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03c3\u03b5 \u03c0\u03b5\u03c1\u03b9\u03bf\u03c1\u03b9\u03c3\u03bc\u03ad\u03bd\u03bf \u03b1\u03c1\u03b9\u03b8\u03bc\u03cc \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03c3\u03c5\u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03c5\u03bd \u03c4\u03b7\u03bd \u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03c4\u03c9\u03bd \u03c7\u03b5\u03b9\u03bc\u03b5\u03c1\u03b9\u03ba\u03ce\u03bd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd TRK \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03bd\u03b5\u03b1\u03c1\u03ae \u03b7\u03bb\u03b9\u03ba\u03af\u03b1 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03c7\u03b5\u03b9\u03c1\u03cc\u03c4\u03b5\u03c1\u03b7 \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 (39,40).<\/p>\n

\u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03c0\u03b5\u03b9\u03c1\u03ac\u03bc\u03b1\u03c4\u03b1 \u03c3\u03b5 \u03b6\u03ce\u03b1 \u03b4\u03b5\u03af\u03c7\u03bd\u03bf\u03c5\u03bd \u03cc\u03c4\u03b9 \u03c4\u03b1 \u03c7\u03b5\u03b9\u03bc\u03b5\u03c1\u03b9\u03ba\u03ac \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 TRK \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03c0\u03c1\u03ce\u03b9\u03bc\u03bf \u03b3\u03b5\u03b3\u03bf\u03bd\u03cc\u03c2 \u03c3\u03c4\u03b7\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 \u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b5\u03c0\u03b1\u03b3\u03c9\u03b3\u03ae \u03c4\u03b7\u03c2 \u03bf\u03c0\u03bf\u03af\u03b1\u03c2 \u03c7\u03c1\u03b5\u03b9\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c4\u03b7 \u03c3\u03c5\u03bd\u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03bf\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03ce\u03bd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd (41).<\/p>\n

1.1<\/b>.3. \u03a0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>Ras<\/b><\/h6>\n

\u03a4\u03b1 \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 RAS (HRAS, KRAS and NRAS) <\/b>\u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03bc\u03b9\u03ba\u03c1\u03ad\u03c2 \u03b5\u03bd\u03b4\u03bf\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03b5\u03c2 GTP\u03ac\u03c3\u03b5\u03c2 \u03bc\u03b5 \u03ba\u03b1\u03b8\u03bf\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7 \u03bc\u03b5\u03c4\u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03c9\u03bd \u03b5\u03bd\u03b4\u03bf\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03c9\u03bd \u03c3\u03b7\u03bc\u03ac\u03c4\u03c9\u03bd \u03b1\u03c0\u03cc \u03b4\u03b9\u03b1\u03bc\u03b5\u03bc\u03b2\u03c1\u03b1\u03bd\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03b5\u03af\u03c2 (42). \u0397 \u03bc\u03b7 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b7 RAS \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03c5\u03bd\u03b4\u03b5\u03b4\u03b5\u03bc\u03ad\u03bd\u03b7 \u03bc\u03b5 \u03c4\u03bf GDP. \u039c\u03b5\u03c4\u03ac \u03c4\u03b7\u03bd \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03ae \u03c4\u03b7\u03c2 \u03b1\u03c0\u03b5\u03bb\u03b5\u03c5\u03b8\u03b5\u03c1\u03ce\u03bd\u03b5\u03b9 GDP \u03ba\u03b1\u03b9 \u03c3\u03c5\u03bd\u03b4\u03ad\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 GTP \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03b1\u03bb\u03bb\u03ac \u03ba\u03b1\u03b9 \u03ac\u03bb\u03bb\u03b1 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ac \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 \u03cc\u03c0\u03c9\u03c2 \u03c4\u03bf PI3K\/AKT (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 4<\/b>). \u03a6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03b7 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b7 RAS-GTP \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03b7 \u03b1\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03b3\u03c1\u03ae\u03b3\u03bf\u03c1\u03b1 (43). \u03a3\u03b7\u03bc\u03b5\u03b9\u03b1\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RAS \u03b5\u03af\u03c4\u03b5 \u03b1\u03c5\u03be\u03ac\u03bd\u03bf\u03c5\u03bd \u03c4\u03b7\u03bd \u03b9\u03ba\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c3\u03cd\u03bd\u03b4\u03b5\u03c3\u03b7\u03c2 \u03bc\u03b5 \u03c4\u03bf GTP (\u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03b1 \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03b1 12 and 13), \u03b5\u03af\u03c4\u03b5 \u03b1\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03c4\u03b7\u03bd \u03b1\u03c5\u03c4\u03bf\u03ba\u03b1\u03c4\u03b1\u03bb\u03c5\u03c4\u03b9\u03ba\u03ae \u03b4\u03c1\u03ac\u03c3\u03b7 \u03c9\u03c2 GTPase (\u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03bf 61) (44). \u03a9\u03c2 \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1, \u03b7 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03b1\u03b3\u03bc\u03ad\u03bd\u03b7 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03c0\u03b1\u03c1\u03b1\u03bc\u03ad\u03bd\u03b5\u03b9 \u03b4\u03b9\u03b1\u03c1\u03ba\u03ce\u03c2 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b7 \u03ba\u03b1\u03b9 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03b5\u03af \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae \u03c3\u03b7\u03bc\u03b1\u03c4\u03bf\u03b4\u03cc\u03c4\u03b7\u03c3\u03b7 \u03bc\u03ad\u03c3\u03b1 \u03c3\u03c4\u03bf \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03bf \u03c4\u03c9\u03bd MAPK \u03ba\u03b1\u03b9 PI3K\/AKT \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03ce\u03bd \u03c0\u03b1\u03c1\u03ac \u03c4\u03b7\u03bd \u03b1\u03c0\u03bf\u03c5\u03c3\u03af\u03b1 \u03b5\u03be\u03c9\u03c4\u03b5\u03c1\u03b9\u03ba\u03ce\u03bd \u03b5\u03c1\u03b5\u03b8\u03b9\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd, \u03bf\u03b4\u03b7\u03b3\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c3\u03b5 \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 (42). <\/b>\u03a4\u03bf \u03c0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf Ras \u03b5\u03af\u03bd\u03b1\u03b9 \u03c4\u03bf \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf \u03c3\u03c4\u03bf\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b1\u03bd\u03b8\u03c1\u03ce\u03c0\u03bf\u03c5. <\/b>\u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 20-25% \u03cc\u03bb\u03c9\u03bd \u03c4\u03c9\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bd \u03ba\u03b1\u03b9 \u03c0\u03ac\u03bd\u03c9 \u03b1\u03c0\u03cc 90% \u03c3\u03b5 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03bf\u03c5\u03c2 \u03c4\u03cd\u03c0\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 (45). <\/b><\/p>\n

\u038c\u03c3\u03bf\u03bd \u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03bf\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ad\u03c7\u03bf\u03c5\u03bd \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03c6\u03bf\u03c1\u03bf\u03cd\u03bd \u03ba\u03b1\u03b9 \u03c4\u03b9\u03c2 \u03c4\u03c1\u03b5\u03b9\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b5\u03c2 RAS \u03bc\u03b5 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03c4\u03b9\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03b1 \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 NRAS \u03ba\u03b1\u03b9 HRAS (43) \u03c9\u03c3\u03c4\u03cc\u03c3\u03bf \u03bf \u03c1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03c3\u03c4\u03b7\u03bd \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c4\u03c9\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03b9\u03ba\u03ce\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03b4\u03b5\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03b1\u03c6\u03ae\u03c2.<\/p>\n

\u03a3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RAS (\u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c3\u03c4\u03bf \u039a-RAS) \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03bf\u03c5\u03bd \u03c3\u03c4\u03bf 10-20% \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd (44,46,47). \u0391\u03c6\u03bf\u03c1\u03bf\u03cd\u03bd \u03c3\u03c7\u03b5\u03b4\u03cc\u03bd \u03b1\u03c0\u03bf\u03ba\u03bb\u03b5\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7 \u03c0\u03bf\u03c5 \u03c0\u03b5\u03c1\u03b9\u03b2\u03ac\u03bb\u03bb\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b5\u03be \u03bf\u03bb\u03bf\u03ba\u03bb\u03ae\u03c1\u03bf\u03c5 \u03ae \u03b1\u03c4\u03b5\u03bb\u03ce\u03c2 \u03b1\u03c0\u03cc \u03ba\u03ac\u03c8\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ce\u03bd \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03c9\u03bd \u03ba\u03b1\u03b9 \u03ba\u03b1\u03bb\u03cd\u03c4\u03b5\u03c1\u03b7 \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 (48,49). \u03a9\u03c3\u03c4\u03cc\u03c3\u03bf \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u039d-RAS \u03c3\u03c4\u03bf \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03bf 61 \u03b5\u03bd\u03bf\u03c7\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03b3\u03b9\u03b1 \u03b4\u03c5\u03c3\u03bc\u03b5\u03bd\u03ae \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03b1\u03bd\u03b5\u03be\u03ac\u03c1\u03c4\u03b7\u03c4\u03bf \u03c0\u03c1\u03bf\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 (50).<\/p>\n

1.1<\/b>.4. \u03a0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>BRAF<\/b> <\/b><\/h6>\n

\u03a4\u03bf \u03c0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03bd\u03af\u03b4\u03b9\u03bf BRAF \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03b7\u03bd \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03b9\u03ba\u03ae \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7 B-RAF \u03c4\u03b7\u03c2 \u03c3\u03b5\u03c1\u03af\u03bd\u03b7\u03c2\/\u03b8\u03c1\u03b5\u03bf\u03bd\u03af\u03bd\u03b7\u03c2 \u03bc\u03ad\u03bb\u03bf\u03c2 \u03c4\u03b7\u03c2 \u03bf\u03b9\u03ba\u03bf\u03b3\u03ad\u03bd\u03b5\u03b9\u03b1\u03c2 \u03c4\u03c9\u03bd RAF \u03ba\u03b9\u03bd\u03b1\u03c3\u03ce\u03bd, \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03ad\u03c7\u03bf\u03c5\u03bd \u03c3\u03c4\u03b7\u03bd \u03b5\u03bd\u03b4\u03bf\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03b1 \u03bc\u03b5\u03c4\u03b1\u03c6\u03bf\u03c1\u03ac \u03bc\u03b7\u03bd\u03c5\u03bc\u03ac\u03c4\u03c9\u03bd (9). \u0397 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b7 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03b4\u03ad\u03c7\u03b5\u03c4\u03b1\u03b9 \u03c4\u03bf \u03bc\u03b9\u03c4\u03bf\u03b3\u03cc\u03bd\u03bf \u03c3\u03ae\u03bc\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 RAS \u03ba\u03b1\u03b9 \u03c4\u03bf \u03c0\u03c1\u03bf\u03c9\u03b8\u03b5\u03af \u03c0\u03c1\u03bf\u03c2 \u03c4\u03b7\u03bd \u03bf\u03b4\u03cc \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03b7\u03c2 \u039c\u0391P \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2. \u039a\u03bb\u03b7\u03c1\u03bf\u03bd\u03bf\u03bc\u03bf\u03cd\u03bc\u03b5\u03bd\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03bf\u03cd\u03bd \u03c3\u03cd\u03bd\u03b4\u03c1\u03bf\u03bc\u03bf \u03c0\u03bf\u03c5 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c0\u03c1\u03bf\u03c3\u03c9\u03c0\u03b5\u03af\u03bf, \u03b1\u03bd\u03c9\u03bc\u03b1\u03bb\u03af\u03b5\u03c2 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03b4\u03b9\u03ac\u03c2 \u03ba\u03b1\u03b9 \u03b4\u03b9\u03b1\u03bd\u03bf\u03b7\u03c4\u03b9\u03ba\u03ae \u03ba\u03b1\u03b8\u03c5\u03c3\u03c4\u03ad\u03c1\u03b7\u03c3\u03b7 (51). \u0395\u03c0\u03af\u03ba\u03c4\u03b7\u03c4\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03b1\u03c5\u03c4\u03bf\u03cd \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03ad\u03c7\u03bf\u03c5\u03bd \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03c3\u03b5 \u03b1\u03c1\u03ba\u03b5\u03c4\u03ad\u03c2 \u03bc\u03bf\u03c1\u03c6\u03ad\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03cc\u03c0\u03c9\u03c2 \u03c4\u03bf non-Hodgkin \u03bb\u03ad\u03bc\u03c6\u03c9\u03bc\u03b1, \u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03c0\u03b1\u03c7\u03ad\u03bf\u03c2 \u03b5\u03bd\u03c4\u03ad\u03c1\u03bf\u03c5, \u03c4\u03bf \u03ba\u03b1\u03ba\u03cc\u03b7\u03b8\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ac\u03bd\u03c9\u03bc\u03b1, \u03c4\u03bf \u03bc\u03b7-\u03bc\u03b9\u03ba\u03c1\u03bf\u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03c0\u03bd\u03b5\u03cd\u03bc\u03bf\u03bd\u03b1, \u03ba\u03b1\u03b9 \u03c4\u03bf \u03b1\u03b4\u03b5\u03bd\u03bf\u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03c0\u03bd\u03b5\u03cd\u03bc\u03bf\u03bd\u03b1 (52).<\/p>\n

\u038c\u03c3\u03bf\u03bd \u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae, \u03c3\u03b7\u03bc\u03b5\u03b9\u03b1\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03c4\u03b9\u03c2 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ad\u03c2 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf 45% \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd \u03b1\u03c5\u03c4\u03ce\u03bd. \u0397 \u03c3\u03c5\u03bd\u03b7\u03b8\u03ad\u03c3\u03c4\u03b5\u03c1\u03b7 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 V600E \u03b7 \u03bf\u03c0\u03bf\u03af\u03b1 \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c3\u03b5 \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae \u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03af\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 MEK \u03ba\u03b1\u03b9 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 4<\/b>) (53). \u0391\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c5\u03c8\u03b7\u03bb\u03ae \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5 \u03c4\u03bf\u03bd \u03ba\u03bb\u03b1\u03c3\u03c3\u03b9\u03ba\u03cc \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03cc \u03c4\u03cd\u03c0\u03bf \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03cc\u03c4\u03c5\u03c0\u03bf\u03c5\u03c2 (\u03c5\u03c0\u03bf\u03c4\u03cd\u03c0\u03bf\u03c2 \u03bc\u03b5 \u03c5\u03c8\u03b7\u03bb\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 (tall-cell variant), \u03b4\u03b9\u03b7\u03b8\u03b7\u03c4\u03ba\u03cc \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7) (54) \u03b1\u03bb\u03bb\u03ac \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03c0\u03ac\u03bd\u03b9\u03bf \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7 \u03c0\u03bf\u03c5 \u03c0\u03b5\u03c1\u03b9\u03b2\u03ac\u03bb\u03bb\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03ba\u03ac\u03c8\u03b1 (55).<\/b><\/p>\n

\u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b1\u03bd\u03b9\u03c7\u03bd\u03b5\u03cd\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03bd\u03b1\u03c0\u03bb\u03b1\u03c3\u03c4\u03b9\u03ba\u03ac \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ad\u03c1\u03c7\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1. \u0397 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c4\u03cc\u03c3\u03bf \u03c3\u03c4\u03b1 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b1 \u03c4\u03bc\u03ae\u03bc\u03b1\u03c4\u03b1 \u03cc\u03c3\u03bf \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03c4\u03bc\u03ae\u03bc\u03b1\u03c4\u03b1 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03af\u03b4\u03b9\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03b7\u03bb\u03ce\u03bd\u03b5\u03b9 \u03cc\u03c4\u03b9 \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03b5\u03b9 \u03bd\u03c9\u03c1\u03af\u03c2 \u03c3\u03c4\u03b7\u03bd \u03b4\u03b9\u03b1\u03b4\u03b9\u03ba\u03b1\u03c3\u03af\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae (56). \u03a4\u03bf \u03b3\u03b5\u03b3\u03bf\u03bd\u03cc\u03c2 \u03cc\u03c4\u03b9 \u03b1\u03bd\u03b9\u03c7\u03bd\u03b5\u03cd\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c0\u03ac\u03bd\u03b9\u03b1 \u03c3\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ae \u03ba\u03b1\u03bb\u03bf\u03ae\u03b8\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c4\u03b7\u03bd \u03ba\u03b1\u03b8\u03b9\u03c3\u03c4\u03ac \u03b1\u03c1\u03ba\u03b5\u03c4\u03ac \u03b5\u03b9\u03b4\u03b9\u03ba\u03cc \u03b4\u03b5\u03af\u03ba\u03c4\u03b7 \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03c0\u03c1\u03bf\u03b5\u03c1\u03c7\u03cc\u03bc\u03b5\u03bd\u03c9\u03bd \u03b1\u03c0\u03cc \u03b1\u03c5\u03c4\u03cc (56).<\/p>\n

\u0386\u03bb\u03bb\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 1-2% \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd. \u03a4\u03ad\u03c4\u03bf\u03b9\u03b5\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 K601E \u03c3\u03b7\u03bc\u03b5\u03b9\u03b1\u03ba\u03ae \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7, \u03c0\u03bf\u03c5 \u03ad\u03c7\u03b5\u03b9 \u03c0\u03b5\u03c1\u03b9\u03b3\u03c1\u03b1\u03c6\u03b5\u03af \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03bc\u03af\u03b1 \u03c0\u03b5\u03c1\u03af\u03c0\u03c4\u03c9\u03c3\u03b7 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 (57), \u03bc\u03b9\u03ba\u03c1\u03ad\u03c2 \u03c0\u03c1\u03bf\u03c3\u03b8\u03ae\u03ba\u03b5\u03c2 \u03ae \u03b1\u03c0\u03b1\u03bb\u03bf\u03b9\u03c6\u03ad\u03c2 \u03b3\u03cd\u03c1\u03c9 \u03b1\u03c0\u03cc \u03c4\u03bf \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03bf 600 \u03ba\u03b1\u03b9 \u03b7 \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 AKAP9-BRAF \u03c0\u03bf\u03c5 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ae \u03c3\u03b5 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c0\u03bf\u03c5 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03ad\u03ba\u03b8\u03b5\u03c3\u03b7 \u03c3\u03b5 \u03b1\u03ba\u03c4\u03b9\u03bd\u03bf\u03b2\u03bf\u03bb\u03af\u03b1 (58).<\/p>\n

\u03a3\u03b5 \u03c0\u03bf\u03bb\u03bb\u03ad\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03b7 \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03af\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 BRAF \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03ac \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5, \u03cc\u03c0\u03c9\u03c2 \u03b5\u03be\u03c9\u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b9\u03ba\u03ae \u03b5\u03c0\u03ad\u03ba\u03c4\u03b1\u03c3\u03b7, \u03c0\u03c1\u03bf\u03c7\u03c9\u03c1\u03b7\u03bc\u03ad\u03bd\u03bf \u03c3\u03c4\u03ac\u03b4\u03b9\u03bf \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7 \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7, \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae, \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ad\u03c2 \u03ae \u03b1\u03c0\u03bf\u03bc\u03b1\u03ba\u03c1\u03c5\u03c3\u03bc\u03ad\u03bd\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2 (59). \u0395\u03b9\u03b4\u03b9\u03ba\u03ac \u03b7 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 BRAF V600E \u03ad\u03c7\u03b5\u03b9 \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03cc\u03c4\u03b9 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b1\u03bd\u03b5\u03be\u03ac\u03c1\u03c4\u03b7\u03c4\u03bf\u03c2 \u03c0\u03c1\u03bf\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae\u03c2 \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5, \u03b1\u03ba\u03cc\u03bc\u03b7 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03c3\u03b5 \u03c3\u03c4\u03ac\u03b4\u03b9\u03bf \u0399-\u0399\u0399 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 (59,60). \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b7 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 \u03b1\u03c5\u03c4\u03ae \u03ad\u03c7\u03b5\u03b9 \u03c3\u03c5\u03c3\u03c7\u03b5\u03c4\u03b9\u03c3\u03b8\u03b5\u03af \u03bc\u03b5 \u03bc\u03b5\u03b9\u03c9\u03bc\u03ad\u03bd\u03b7 \u03b9\u03ba\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd \u03bd\u03b1 \u03c0\u03c1\u03bf\u03c3\u03bb\u03b1\u03bc\u03b2\u03ac\u03bd\u03bf\u03c5\u03bd \u03c1\u03b1\u03b4\u03b9\u03b5\u03bd\u03b5\u03c1\u03b3\u03cc \u03b9\u03ce\u03b4\u03b9\u03bf \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03c0\u03bf\u03c4\u03c5\u03c7\u03af\u03b1 \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03b7\u03c2 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae\u03c2 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5, \u03c0\u03bf\u03c5 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03bf\u03c6\u03b5\u03af\u03bb\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03c0\u03bf\u03c1\u03c1\u03cd\u03b8\u03bc\u03b9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03b1\u03c6\u03bf\u03c1\u03ad\u03b1 \u03bd\u03b1\u03c4\u03c1\u03af\u03bf\u03c5-\u03b9\u03c9\u03b4\u03af\u03bf\u03c5 (NIS) \u03ba\u03b1\u03b9 \u03ac\u03bb\u03bb\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03ad\u03c7\u03bf\u03c5\u03bd \u03c3\u03c4\u03bf\u03bd \u03bc\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03c3\u03bc\u03cc \u03c4\u03bf\u03c5 \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 \u03c3\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (61).<\/p>\n

\u0397 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03bf\u03c7\u03ae \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03c3\u03c4\u03b7\u03bd \u03ad\u03bd\u03b1\u03c1\u03be\u03b7 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03c0\u03bf\u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03b7 \u03c3\u03c5\u03c3\u03c7\u03ad\u03c4\u03b9\u03c3\u03ae \u03c4\u03bf\u03c5\u03c2 \u03bc\u03b5 \u03c0\u03b9\u03bf \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03ac \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd \u03ad\u03c7\u03b5\u03b9 \u03c6\u03b1\u03bd\u03b5\u03af \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03c3\u03b5 \u03c0\u03bf\u03bd\u03c4\u03af\u03ba\u03b9\u03b1 \u03c0\u03bf\u03c5 \u03ad\u03c6\u03b5\u03c1\u03b1\u03bd \u03c4\u03b7\u03bd \u03b5\u03b9\u03b4\u03b9\u03ba\u03ae \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 V600E BRAF \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7\u03c2 (62).<\/p>\n

\n

\u00a0\"10.22-figure4\"<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 4.<\/b><\/em> \u0397 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 BRAF-V600E \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03ba\u03b1\u03b8\u03bf\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae. \u03a0\u03b7\u03b3\u03ae: (63).<\/p>\n

\n
\u00a01.1.5. \u03a0\u03c1\u03ce\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>met<\/b> <\/b><\/h6>\n

\u03a4\u03bf \u03c0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf met \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03ad\u03bd\u03b1\u03bd \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b7\u03c0\u03b1\u03c4\u03bf\u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03b1\u03c5\u03be\u03b7\u03c4\u03b9\u03ba\u03cc (HGF\/SF) \u03bc\u03b5 \u03b4\u03c1\u03ac\u03c3\u03b7 \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 (64). \u039f \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1\u03c2 \u03b1\u03c5\u03c4\u03cc\u03c2 \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03c0\u03b1\u03af\u03b6\u03b5\u03b9 \u03ba\u03b1\u03b8\u03bf\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7\u03bd \u03b5\u03bc\u03b2\u03c1\u03c5\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 (65), \u03b1\u03bb\u03bb\u03ac \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03b3\u03ad\u03bd\u03bd\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ae\u03c0\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b5\u03c0\u03bf\u03cd\u03bb\u03c9\u03c3\u03b7 \u03c0\u03bb\u03b7\u03b3\u03ce\u03bd \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7\u03bd \u03b5\u03bd\u03ae\u03bb\u03b9\u03ba\u03bf \u03b6\u03c9\u03ae (66). \u0397 \u03b4\u03ad\u03c3\u03bc\u03b5\u03c5\u03c3\u03ae \u03c4\u03bf\u03c5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03ac \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 \u03bc\u03b5\u03c4\u03ac\u03b4\u03bf\u03c3\u03b7\u03c2 \u03c3\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 (\u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 RAS (67), \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PI3K (68), \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 STAT (69), \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 beta-catenin (70), \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u039dotch (71), \u03bc\u03b5 \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03c4\u03bf \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03bc\u03cc\u03bd\u03b9\u03bc\u03b1 \u03bd\u03b1 \u03bf\u03b4\u03b7\u03b3\u03bf\u03cd\u03bd \u03c3\u03b5 \u03bc\u03b9\u03c4\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03bd\u03b1 \u03c0\u03c1\u03bf\u03ac\u03b3\u03bf\u03c5\u03bd \u03c4\u03b7\u03bd \u03ba\u03b9\u03bd\u03b7\u03c4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03bd \u03b4\u03b9\u03ae\u03b8\u03b7\u03c3\u03b7 (72). \u0397 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03c0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 c-Met \u03b5\u03af\u03bd\u03b1\u03b9 \u03ad\u03bd\u03b1\u03c2 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b7\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03c0\u03cc \u03c5\u03c8\u03b7\u03bb\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03ba\u03b1\u03b9 \u03c4\u03b7 \u03b4\u03b9\u03b7\u03b8\u03b7\u03c4\u03b9\u03ba\u03ae \u03c4\u03bf\u03c5 \u03c3\u03c5\u03bc\u03c0\u03b5\u03c1\u03b9\u03c6\u03bf\u03c1\u03ac \u03ba\u03b1\u03b9 \u03b5\u03bd\u03b5\u03b4\u03bf\u03bc\u03ad\u03bd\u03c9\u03c2 \u03ad\u03c7\u03b5\u03b9 \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7\u03bd \u03ad\u03b3\u03ba\u03b1\u03b9\u03c1\u03b7 \u03b1\u03bd\u03b1\u03b3\u03bd\u03ce\u03c1\u03b9\u03c3\u03b7 \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03c0\u03bf\u03c5 \u03c0\u03ac\u03c3\u03c7\u03bf\u03c5\u03bd \u03b1\u03c0\u03cc \u03b1\u03c5\u03c4\u03cc (73).<\/p>\n

1.1.6. \u039f \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03b5\u03c0\u03b9\u03b8\u03b7\u03bb\u03b9\u03b1\u03ba\u03bf\u03cd \u03b1\u03c5\u03be\u03b7\u03c4\u03b9\u03ba\u03bf\u03cd \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 (EGFR)<\/b><\/h6>\n

\u039f EGFR \u03b1\u03bd\u03ae\u03ba\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03ad\u03bd\u03b5\u03b9\u03b1 \u03c4\u03c9\u03bd \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03c9\u03bd \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2. \u0388\u03c7\u03b5\u03b9 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c3\u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03c3\u03c5\u03b3\u03ba\u03c1\u03b9\u03c4\u03b9\u03ba\u03ac \u03bc\u03b5 \u03c4\u03b1 \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a3\u03b5 \u03bc\u03af\u03b1 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 \u03cc\u03c0\u03bf\u03c5 \u03b4\u03b9\u03b5\u03c1\u03b5\u03c5\u03bd\u03ae\u03b8\u03b7\u03ba\u03b5 \u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03c9\u03bd \u03c4\u03b5\u03c3\u03c3\u03ac\u03c1\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03b1\u03c5\u03c4\u03bf\u03cd \u03c3\u03c4\u03bf\u03bd \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b2\u03c1\u03ad\u03b8\u03b7\u03ba\u03b5 \u03cc\u03c4\u03b9 \u03c4\u03bf\u03c5\u03bb\u03ac\u03c7\u03b9\u03c3\u03c4\u03bf\u03bd \u03ad\u03bd\u03b1 \u03c5\u03c0\u03b5\u03c1\u03b5\u03ba\u03c6\u03c1\u03b1\u03b6\u03cc\u03c4\u03b1\u03bd \u03ba\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03bc\u03cc\u03bd\u03bf \u03c4\u03bf HER3 \u03c3\u03c7\u03b5\u03c4\u03b9\u03b6\u03cc\u03c4\u03b1\u03bd \u03bc\u03b5 \u03c4\u03bf \u03c3\u03c4\u03ac\u03b4\u03b9\u03bf \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 (74). \u0391\u03bd \u03ba\u03b1\u03b9 \u03bc\u03ad\u03c7\u03c1\u03b9 \u03c0\u03c1\u03cc\u03c4\u03b9\u03bd\u03bf\u03c2 \u03b4\u03b5\u03bd \u03b8\u03b5\u03c9\u03c1\u03bf\u03cd\u03bd\u03c4\u03b1\u03bd \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c3\u03c4\u03b7 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ae \u03b2\u03b9\u03bf\u03bb\u03bf\u03b3\u03af\u03b1 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03c0\u03c1\u03cc\u03c3\u03c6\u03b1\u03c4\u03b7 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 \u03ad\u03b4\u03b5\u03b9\u03be\u03b5 \u03cc\u03c4\u03b9 EGFR \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03c0\u03bd\u03b5\u03cd\u03bc\u03bf\u03bd\u03b1 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03b1\u03bd\u03b5\u03c5\u03c1\u03b5\u03b8\u03bf\u03cd\u03bd \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03ad\u03bd\u03b1 \u03c5\u03c0\u03bf\u03c3\u03cd\u03bd\u03bf\u03bb\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ae \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b8\u03b9\u03c3\u03c4\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03b5\u03c5\u03b1\u03af\u03c3\u03b8\u03b7\u03c4\u03b1 \u03c3\u03b5 \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03b5\u03af\u03c2 \u03c4\u03bf\u03c5 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 (75).<\/p>\n

1.1.7. \u039f \u03b1\u03b3\u03b3\u03b5\u03b9\u03b1\u03ba\u03cc\u03c2 \u03b5\u03c0\u03b9\u03b8\u03b7\u03bb\u03b9\u03b1\u03ba\u03cc\u03c2 \u03b1\u03c5\u03be\u03b7\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 (VEGF) \u03ba\u03b1\u03b9 \u03bf \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1\u03c2 \u03c4\u03bf\u03c5<\/b><\/h6>\n

\u0397 \u03c5\u03c0\u03b5\u03c1\u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03bf\u03c5 VEGF \u03b5\u03af\u03bd\u03b1\u03b9 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03b5\u03cd\u03c1\u03b7\u03bc\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03b9\u03ce\u03bd \u03c3\u03c5\u03bc\u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03b1\u03bd\u03bf\u03bc\u03ad\u03bd\u03c9\u03bd \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03b8\u03b5\u03af \u03c9\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b7\u03c2 \u03c5\u03c0\u03bf\u03be\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5 (76). \u0397 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03bf\u03c5 VEGF \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03b1\u03c4\u03b9\u03ba\u03cc \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b1 \u03bc\u03b5 \u03c4\u03bf \u03bc\u03ad\u03b3\u03b5\u03b8\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5, \u03bc\u03b5 \u03b5\u03be\u03c9\u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b9\u03ba\u03ae \u03b5\u03c0\u03ad\u03ba\u03c4\u03b1\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03af\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 BRAF \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 (77), \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ce\u03bd \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03c9\u03bd (78).<\/p>\n

1.2<\/b>. \u0398\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2<\/b><\/h5>\n

\u03a4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03bd\u03b1\u03bb\u03bf\u03b3\u03bf\u03cd\u03bd \u03c3\u03c4\u03bf 10-15% \u03c4\u03c9\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03b9\u03ce\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u0395\u03af\u03bd\u03b1\u03b9 \u03c3\u03c5\u03bd\u03ae\u03b8\u03c9\u03c2 \u03bc\u03bf\u03bd\u03bf\u03b5\u03c3\u03c4\u03b9\u03b1\u03ba\u03ac. \u0391\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 \u03bc\u03b5 \u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03bf\u03b9 \u03b1\u03c0\u03bf\u03bc\u03b1\u03ba\u03c1\u03c5\u03c3\u03bc\u03ad\u03bd\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2 \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c3\u03c4\u03bf\u03bd \u03c0\u03bd\u03b5\u03cd\u03bc\u03bf\u03bd\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03bf\u03c3\u03c4\u03ac \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7 \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5\u03c2, \u03b5\u03bd\u03ce \u03bf\u03b9 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03c0\u03b1\u03bd\u03b9\u03cc\u03c4\u03b5\u03c1\u03b5\u03c2 (< 5%) (5).<\/p>\n

\u03a3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03ba\u03c4\u03cc\u03c2 \u03b1\u03c0\u03cc \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RAS (20-40%), \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03b9\u03c2 PAX8-PPAR\u03b3 (30-40%), \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b1\u03bb\u03bb\u03b1\u03b3\u03ad\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03c6\u03bf\u03c1\u03bf\u03cd\u03bd \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03bc\u03b5\u03c4\u03ac\u03b4\u03bf\u03c3\u03b7\u03c2 \u03c3\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 PI3K\/AKT \u03c3\u03b5 \u03c7\u03b1\u03bc\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03bf \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (15%). \u039f\u03b9 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b5\u03c2 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03c0\u03b1\u03af\u03b6\u03bf\u03c5\u03bd \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b1 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03c3\u03c4\u03ac\u03b4\u03b9\u03b1 \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b1\u03b6\u03af \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd the TP53 and CTNNB1, \u03bc\u03b5 \u03ac\u03bb\u03bb\u03bf\u03c4\u03b5 \u03ac\u03bb\u03bb\u03b7 \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03c0\u03bb\u03b1\u03c3\u03c4\u03b9\u03ba\u03ce\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd (3). \u03a0\u03bf\u03bb\u03bb\u03ad\u03c2 \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c5\u03bd\u03b4\u03ad\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03ac \u03c6\u03b1\u03b9\u03bd\u03bf\u03c4\u03c5\u03c0\u03b9\u03ba\u03ac \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd \u03ba\u03b1\u03b9 \u03bc\u03b5\u03c1\u03b9\u03ba\u03ad\u03c2 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03c0\u03b9\u03bf \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03ae\u03c2 \u03c3\u03c5\u03bc\u03c0\u03b5\u03c1\u03b9\u03c6\u03bf\u03c1\u03ac\u03c2. \u03a0\u03c1\u03cc\u03c3\u03c6\u03b1\u03c4\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03b4\u03b5\u03af\u03c7\u03bd\u03bf\u03c5\u03bd \u03cc\u03c4\u03b9 \u03b7 \u03c3\u03c5\u03bd\u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03ce\u03bd \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ce\u03bd \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ce\u03bd \u03c3\u03b5 \u03ad\u03bd\u03b1 \u03b1\u03c3\u03b8\u03b5\u03bd\u03ae \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03bd\u03b5\u03b1\u03c1\u03cc\u03c4\u03b5\u03c1\u03b7 \u03b7\u03bb\u03b9\u03ba\u03af\u03b1 (3).<\/p>\n

1.2<\/b>.1. \u03a7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>PAX<\/b>8\/<\/b>PPAR<\/b>\u03b3 <\/b><\/h6>\n

\u03a4\u03bf \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf PAX8\/PPAR\u03b3 \u03c0\u03c1\u03bf\u03ba\u03cd\u03c0\u03c4\u03b5\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 \u03bc\u03b5\u03c4\u03b1\u03be\u03cd \u03c4\u03c9\u03bd \u03c7\u03c1\u03c9\u03bc\u03bf\u03c3\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd 2 \u03ba\u03b1\u03b9 3, t(2;3)(q13;p25) \u03c0\u03bf\u03c5 \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c3\u03b5 \u03c3\u03c5\u03b3\u03c7\u03ce\u03bd\u03b5\u03c5\u03c3\u03b7 \u03c4\u03bc\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03bf\u03cd \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 PAX8 \u03ba\u03b1\u03b9 \u03c4\u03bc\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03bf\u03cd \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 PPAR\u03b3 (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 5<\/b>). \u039f \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 PAX8 \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03ba\u03b1\u03b9 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03c9\u03bd \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03c9\u03b4\u03ce\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (79), \u03b5\u03bd\u03ce \u03bf \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 PPAR\u03b3 \u03b1\u03bd\u03ae\u03ba\u03b5\u03b9 \u03c3\u03c4\u03bf\u03c5\u03c2 \u03c0\u03c5\u03c1\u03b7\u03bd\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03b5\u03af\u03c2 \u03ba\u03b1\u03b9 \u03ad\u03c7\u03b5\u03b9 \u03b1\u03bc\u03c6\u03af\u03b2\u03bf\u03bb\u03bf \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7 (80). \u0397 \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 PAX8\/PPAR\u03b3 \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c3\u03b5 \u03c5\u03c0\u03b5\u03c1\u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7\u03c2 PPAR\u03b3.<\/p>\n

\u03a4\u03bf \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf PAX8\/PPAR\u03b3 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf 30-40% \u03c4\u03c9\u03bd \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03c9\u03bd \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03b5\u03bd\u03ce \u03bf \u03b5\u03c0\u03b9\u03c0\u03bf\u03bb\u03b1\u03c3\u03bc\u03cc\u03c2 \u03c4\u03bf\u03c5 \u03c3\u03c4\u03b9\u03c2 \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03b9\u03c2 \u03bf\u03b3\u03ba\u03bf\u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 (\u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 Hurthe) \u03b5\u03af\u03bd\u03b1\u03b9 \u03c7\u03b1\u03bc\u03b7\u03bb\u03cc\u03c2 (81,82,83). \u039f\u03b9 \u03cc\u03b3\u03ba\u03bf\u03b9 \u03c0\u03bf\u03c5 \u03c6\u03ad\u03c1\u03bf\u03c5\u03bd \u03b1\u03c5\u03c4\u03ae\u03bd \u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 \u03c4\u03b5\u03af\u03bd\u03bf\u03c5\u03bd \u03bd\u03b1 \u03b5\u03bc\u03c6\u03b1\u03bd\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bd\u03b5\u03b1\u03c1\u03cc\u03c4\u03b5\u03c1\u03b7 \u03b7\u03bb\u03b9\u03ba\u03af\u03b1, \u03b5\u03af\u03bd\u03b1\u03b9 \u03bc\u03b9\u03ba\u03c1\u03cc\u03c4\u03b5\u03c1\u03bf\u03b9 \u03c3\u03b5 \u03bc\u03ad\u03b3\u03b5\u03b8\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c5\u03c7\u03bd\u03ac \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03b9\u03ac\u03b6\u03bf\u03c5\u03bd \u03b1\u03b3\u03b3\u03b5\u03b9\u03b1\u03ba\u03ae \u03b4\u03b9\u03ae\u03b8\u03b7\u03c3\u03b7 (82,81)<\/p>\n

\u03a4\u03bf \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf PAX8\/PPAR\u03b3 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03b5\u03c0\u03af\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03bc\u03b9\u03ba\u03c1\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (2-10%) \u03c3\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 0.5% \u03c3\u03b5 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7 (81,84,85). \u03a4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03b5\u03c4\u03b9\u03ba\u03ac \u03b3\u03b9 \u03b1\u03c5\u03c4\u03ae\u03bd \u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7 \u03ad\u03c7\u03bf\u03c5\u03bd \u03c0\u03b1\u03c7\u03b9\u03ac \u03ba\u03ac\u03c8\u03b1 \u03ba\u03b1\u03b9 \u03b5\u03bc\u03c6\u03b1\u03bd\u03af\u03b6\u03bf\u03c5\u03bd \u03b1\u03bd\u03bf\u03c3\u03bf\u03b9\u03c3\u03c4\u03bf\u03c7\u03b7\u03bc\u03b9\u03ba\u03ac \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03bf\u03b4\u03b7\u03b3\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c3\u03c4\u03b7\u03bd \u03c5\u03c0\u03cc\u03b8\u03b5\u03c3\u03b7 \u03cc\u03c4\u03b9 \u03c0\u03b9\u03b8\u03b1\u03bd\u03cc\u03bd \u03b1\u03bd\u03c4\u03b9\u03c0\u03c1\u03bf\u03c3\u03c9\u03c0\u03b5\u03cd\u03bf\u03c5\u03bd in situ \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ae \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03af\u03b5\u03c2 \u03cc\u03c0\u03bf\u03c5 \u03b7 \u03b4\u03b9\u03ae\u03b8\u03b7\u03c3\u03b7 \u03b4\u03b5\u03bd \u03c6\u03ac\u03bd\u03b7\u03ba\u03b5 \u03b1\u03c1\u03c7\u03b9\u03ba\u03ac \u03c3\u03c4\u03b7\u03bd \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ae \u03b5\u03be\u03ad\u03c4\u03b1\u03c3\u03b7. \u0393\u03b9 \u03b1\u03c5\u03c4\u03cc \u03b7 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03bf\u03cd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 PAX8\/PPAR\u03b3 \u03c3\u03b5 \u03c7\u03b5\u03b9\u03c1\u03bf\u03c5\u03c1\u03b3\u03b9\u03ba\u03ac \u03c0\u03b1\u03c1\u03b1\u03c3\u03ba\u03b5\u03c5\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c4\u03bf\u03bd \u03c0\u03b1\u03b8\u03bf\u03bb\u03bf\u03b3\u03bf\u03b1\u03bd\u03b1\u03c4\u03cc\u03bc\u03bf \u03bd\u03b1 \u03b1\u03bd\u03b1\u03b6\u03b7\u03c4\u03ae\u03c3\u03b5\u03b9 \u03bc\u03b5 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03b7 \u03c0\u03c1\u03bf\u03c3\u03bf\u03c7\u03ae \u03b4\u03ae\u03b8\u03b7\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03ba\u03ac\u03c8\u03b1\u03c2 \u03ae \u03c4\u03c9\u03bd \u03b1\u03b3\u03b3\u03b5\u03af\u03c9\u03bd \u03b5\u03be\u03b5\u03c4\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03c2 \u03bf\u03bb\u03cc\u03ba\u03bb\u03b7\u03c1\u03b7 \u03c4\u03b7\u03bd \u03ba\u03ac\u03c8\u03b1 \u03c4\u03bf\u03c5 \u03cc\u03b3\u03ba\u03bf\u03c5 \u03c3\u03b5 \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03ad\u03c2 \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ad\u03c2 \u03c4\u03bf\u03bc\u03ad\u03c2 (81,82).<\/p>\n

\n

\u00a0\"10.22-figure5\"<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 5.<\/b> \u03a3\u03c7\u03b7\u03bc\u03b1\u03c4\u03b9\u03ba\u03cc \u03b4\u03b9\u03ac\u03b3\u03c1\u03b1\u03bc\u03bc\u03b1 \u03c4\u03b7\u03c2 \u03b1\u03bd\u03b1\u03b4\u03b9\u03ac\u03c4\u03b1\u03be\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03be\u03cd \u03c4\u03bf\u03c5 PAX8 \u03c3\u03c4\u03bf \u03c7\u03c1\u03c9\u03bc\u03cc\u03c3\u03c9\u03bc\u03b1 2q13 \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 PPAR\u03b3 \u03c3\u03c4\u03bf \u03c7\u03c1\u03c9\u03bc\u03cc\u03c3\u03c9\u03bc\u03b1 3p25. \u03a0\u03b7\u03b3\u03ae: (86).<\/p>\n

\n
\u00a01.2.2. \u03a0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>RAS<\/b><\/h6>\n

\u0391\u03c1\u03c7\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03ad\u03b4\u03b5\u03b9\u03be\u03b1\u03bd \u03c0\u03b1\u03c1\u03cc\u03bc\u03bf\u03b9\u03bf \u03b5\u03c0\u03b9\u03c0\u03bf\u03bb\u03b1\u03c3\u03bc\u03cc \u03c3\u03b5 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 RAS \u03c0\u03c1\u03c9\u03c4\u03bf-\u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u03c4\u03cc\u03c3\u03bf \u03c3\u03b5 \u03ba\u03b1\u03bb\u03bf\u03ae\u03b8\u03b7 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1, \u03cc\u03c3\u03bf \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03af\u03b5\u03c2 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (87) \u03c5\u03c0\u03bf\u03b4\u03b5\u03b9\u03ba\u03bd\u03cd\u03bf\u03bd\u03c4\u03b1\u03c2 \u03cc\u03c4\u03b9 \u03b7 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03c9\u03bd RAS \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03ad\u03bd\u03b1 \u03c0\u03c1\u03ce\u03b9\u03bc\u03bf \u03b3\u03b5\u03b3\u03bf\u03bd\u03cc\u03c2 \u03c3\u03c4\u03b7 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ae \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03bf\u03cd \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (88,46). \u039c\u03b5\u03c4\u03b1\u03b3\u03b5\u03bd\u03ad\u03c3\u03c4\u03b5\u03c1\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03ad\u03b4\u03b5\u03b9\u03be\u03b1\u03bd \u03cc\u03c4\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03b5\u03b9\u03b4\u03b9\u03ba\u03ac \u03c3\u03c4\u03bf \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03bf 61 \u03c4\u03bf\u03c5 \u039d-RAS \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03c0\u03b5\u03c1\u03b1\u03b9\u03c4\u03ad\u03c1\u03c9 \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03b5 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03ae \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae \u03c3\u03c5\u03bc\u03c0\u03b5\u03c1\u03b9\u03c6\u03bf\u03c1\u03ac (89,90,91).<\/p>\n

\u03a3\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RAS \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03bf\u03c5\u03bd \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 20-40% \u03ba\u03b1\u03b9 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03c3\u03b5 \u03cc\u03c3\u03b1 \u03ad\u03c7\u03bf\u03c5\u03bd \u03bc\u03b9\u03ba\u03c1\u03bf\u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b5\u03c2 \u03c0\u03c1\u03cc\u03c4\u03c5\u03c0\u03bf \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7\u03c2 (87). \u03a4\u03b1 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b1\u03c5\u03c4\u03ac \u03b4\u03b5\u03bd \u03ad\u03c7\u03bf\u03c5\u03bd \u03bc\u03bf\u03c1\u03c6\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03ac \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 (81). \u03a3\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03bf\u03b9 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 40-50% \u03ba\u03b1\u03b9 \u03b1\u03c6\u03bf\u03c1\u03bf\u03cd\u03bd \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03ba\u03c9\u03b4\u03b9\u03ba\u03cc\u03bd\u03b9\u03bf 61 \u03c4\u03bf\u03c5 \u039d-RAS (89). \u03a7\u03b1\u03bc\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03b7 \u03b5\u03c0\u03af\u03c0\u03c4\u03c9\u03c3\u03b7 \u03c4\u03c9\u03bd \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03ad\u03c7\u03b5\u03b9 \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03c3\u03b5 \u03cc\u03b3\u03ba\u03bf\u03c5\u03c2 \u03b1\u03c0\u03cc \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 Hurthle \u03cc\u03c0\u03bf\u03c5 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03cc\u03bd\u03bf \u03c3\u03b5 0-4% \u03c4\u03c9\u03bd \u03b1\u03b4\u03b5\u03bd\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd \u03ba\u03b1\u03b9 15-25% \u03c4\u03c9\u03bd \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd (92, 93) .<\/p>\n

1.2.3. \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd \u03c4\u03bf\u03c5 \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd PI3K\/AKT<\/b><\/h6>\n

\u03a4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PTEN\/PI3K\/Akt \u03c1\u03c5\u03b8\u03bc\u03af\u03b6\u03b5\u03b9 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b5\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03cc\u03c0\u03c9\u03c2 \u03c4\u03bf \u03bc\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03c3\u03bc\u03cc \u03c4\u03b7\u03c2 \u03b3\u03bb\u03c5\u03ba\u03cc\u03b6\u03b7\u03c2, \u03c4\u03bf\u03bd \u03ba\u03cd\u03ba\u03bb\u03bf \u03c0\u03bf\u03bb\u03bb\u03b1\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03bd \u03b5\u03c0\u03b9\u03b2\u03af\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5. \u03a4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf PTEN \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03bc\u03af\u03b1 \u03c6\u03c9\u03c3\u03c6\u03b1\u03c4\u03ac\u03c3\u03b7 \u03c0\u03bf\u03c5 \u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03ad\u03bb\u03bb\u03b5\u03b9 \u03c4\u03bf \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 6<\/b>) (94). \u0391\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03bf\u03cd\u03bd \u03c4\u03bf \u03c3\u03cd\u03bd\u03b4\u03c1\u03bf\u03bc\u03bf Cowden \u03c0\u03bf\u03c5 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03b1\u03bc\u03b1\u03c1\u03c4\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c4\u03bf\u03c5 \u03b4\u03ad\u03c1\u03bc\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c4\u03bf\u03c5 \u03b5\u03bd\u03c4\u03ad\u03c1\u03bf\u03c5, \u03c4\u03bf\u03c5 \u03bc\u03b1\u03c3\u03c4\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03c0\u03cc \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03bf \u03ba\u03af\u03bd\u03b4\u03c5\u03bd\u03bf \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03bc\u03b1\u03c3\u03c4\u03bf\u03cd, \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 \u03b5\u03bd\u03b4\u03bf\u03bc\u03b7\u03c4\u03c1\u03af\u03bf\u03c5 (95). \u039a\u03b1\u03bb\u03bf\u03ae\u03b8\u03b7 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03bc\u03c6\u03b1\u03bd\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 50-75% \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03c0\u03bf\u03c5 \u03c0\u03ac\u03c3\u03c7\u03bf\u03c5\u03bd \u03b1\u03c0\u03cc \u03b1\u03c5\u03c4\u03cc \u03c4\u03bf \u03c3\u03cd\u03bd\u03b4\u03c1\u03bf\u03bc\u03bf \u03b5\u03bd\u03ce \u03bf \u03ba\u03af\u03bd\u03b4\u03c5\u03bd\u03bf\u03c2 \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7 \u03b4\u03b9\u03ac\u03c1\u03ba\u03b5\u03b9\u03b1 \u03c4\u03b7\u03c2 \u03b6\u03c9\u03ae\u03c2 \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03ba\u03c5\u03bc\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 10% (96). \u0391\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 PTEN \u03c0\u03b1\u03af\u03b6\u03b5\u03b9 \u03c1\u03cc\u03bb\u03bf \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03c3\u03c0\u03bf\u03c1\u03b1\u03b4\u03b9\u03ba\u03ac \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03c0\u03b1\u03bd\u03b9\u03cc\u03c4\u03b5\u03c1\u03b1 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 (2%), \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b5\u03c1\u03b1 \u03c3\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 (7%) \u03ba\u03b1\u03b9 \u03c0\u03bf\u03bb\u03cd \u03c3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c4\u03b1 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03b1 (12-50%) (97,98,99).<\/p>\n

\n

\u00a0\"10.22-figure6\"<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 6.<\/b><\/em> \u03a4\u03bf \u03ba\u03bb\u03b1\u03c3\u03c3\u03b9\u03ba\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PTEN \u0397 \u03ad\u03bd\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03c0\u03c1\u03bf\u03c3\u03b4\u03ad\u03c4\u03b7 \u03bc\u03b5 \u03bc\u03b5\u03bc\u03b2\u03c1\u03b1\u03bd\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03b5\u03af\u03c2 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03bf PI3K. \u03a4\u03bf \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf PI3K \u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03b9\u03ce\u03bd\u03b5\u03b9 \u03c4\u03bf PI(3,4)P \u00a0(PIP2) \u03b3\u03b9\u03b1 \u03bd\u03b1 \u03c0\u03b1\u03c1\u03b1\u03c7\u03b8\u03b5\u03af \u03c4\u03bf PI(3,4,5)P (PIP3). \u03a4\u03bf \u03c4\u03b5\u03bb\u03b9\u03ba\u03cc \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03af\u03c9\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03b7\u03c2 AKT, \u03b7 \u03bf\u03c0\u03bf\u03af\u03b1 \u03c1\u03c5\u03b8\u03bc\u03af\u03b6\u03b5\u03b9 \u03c0\u03bf\u03af\u03ba\u03b9\u03bb\u03b5\u03c2 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03ad\u03c2 \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b5\u03c2. \u03a4\u03bf PTEN \u03b4\u03c1\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c9\u03c2 \u03c6\u03c9\u03c3\u03c6\u03b1\u03c4\u03ac\u03c3\u03b7 \u03b1\u03c0\u03bf\u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03b9\u03ce\u03bd\u03b5\u03b9 \u03ba\u03b1\u03b9 \u03bc\u03b5\u03b9\u03ce\u03bd\u03b5\u03b9 \u03c4\u03b1 \u03b5\u03c0\u03af\u03c0\u03b5\u03b4\u03b1 \u03c4\u03bf\u03c5 PIP3 \u03ba\u03b1\u03b9 \u03b1\u03c5\u03be\u03ac\u03bd\u03b5\u03b9 \u03c4\u03b1 \u03b5\u03c0\u03af\u03c0\u03b5\u03b4\u03b1 \u03c4\u03bf\u03c5 PIP2, \u03bf\u03b4\u03b7\u03b3\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c3\u03b5 \u03bc\u03b5\u03af\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03b4\u03c1\u03b1\u03c3\u03c4\u03b7\u03c1\u03b9\u03cc\u03c4\u03b7\u03c4\u03b1\u03c2 \u03c4\u03b7\u03c2 AKT. \u03a0\u03b7\u03b3\u03ae: (94).<\/p>\n

\n
\u00a01.3. <\/b>Hurthle<\/b> \u03ae o\u03b3\u03ba\u03bf\u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2<\/b><\/h5>\n

\u0391\u03bd \u03ba\u03b1\u03b9 \u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b1\u03c5\u03c4\u03cc \u03b8\u03b5\u03c9\u03c1\u03bf\u03cd\u03bd\u03c4\u03b1\u03bd \u03c0\u03b1\u03bb\u03b9\u03ac \u03be\u03b5\u03c7\u03c9\u03c1\u03b9\u03c3\u03c4\u03ae \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae \u03bf\u03bd\u03c4\u03cc\u03c4\u03b7\u03c4\u03b1 \u03b7 \u03c0\u03c1\u03cc\u03c3\u03c6\u03b1\u03c4\u03b7 WHO\/AIRC (Italian Association for the Research against Cancer) \u03c4\u03b1\u03be\u03b9\u03bd\u03cc\u03bc\u03b7\u03c3\u03b7 \u03c4\u03bf \u03ba\u03b1\u03c4\u03b1\u03c4\u03ac\u03c3\u03b5\u03b9 \u03c3\u03b1\u03bd \u03c5\u03c0\u03bf\u03c4\u03cd\u03c0\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c3\u03c5\u03c3\u03c3\u03ce\u03c1\u03b5\u03c5\u03c3\u03b7 \u03c3\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03af\u03c9\u03bd \u03bc\u03b5 \u03bc\u03bf\u03c1\u03c6\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ad\u03c2 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ad\u03c2 (100). \u03a3\u03b5 \u03c3\u03cd\u03b3\u03ba\u03c1\u03b9\u03c3\u03b7 \u03bc\u03b5 \u03c4\u03bf \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03bf \u03b5\u03af\u03bd\u03b1\u03b9 \u03b1\u03bd\u03b8\u03b5\u03ba\u03c4\u03b9\u03ba\u03cc \u03c3\u03c5\u03bd\u03ae\u03b8\u03c9\u03c2 \u03c3\u03c4\u03b7 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03bc\u03b5 \u03b9\u03ce\u03b4\u03b9\u03bf \u03ba\u03b1\u03b9 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03b3\u03b1\u03bb\u03cd\u03c4\u03b5\u03c1\u03b7 \u03c0\u03c1\u03bf\u03b4\u03b9\u03ac\u03b8\u03b5\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2.<\/p>\n

\u0397 \u03ba\u03cd\u03c1\u03b9\u03b1 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ae \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ae \u03c4\u03c9\u03bd \u03cc\u03b3\u03ba\u03c9\u03bd Hurthle \u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03b9\u03c2 \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03b9\u03b1\u03ba\u03ad\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b5\u03c2 \u03c0\u03bf\u03c5 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03c4\u03cc\u03c3\u03bf \u03b1\u03c0\u03cc \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03b9\u03b1\u03ba\u03cc DNA(101,102) \u03cc\u03c3\u03bf \u03ba\u03b1\u03b9 \u03b1\u03c0\u03cc \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03c4\u03bf\u03c5 \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 (103). \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03c0\u03c5\u03c1\u03b7\u03bd\u03b9\u03ba\u03bf\u03cd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 GRIM-19 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03b9\u03b4\u03b9\u03ba\u03ad\u03c2 \u03b3\u03b9\u03b1 \u03cc\u03b3\u03ba\u03bf\u03c5\u03c2 Hurthle \u03c3\u03c0\u03bf\u03c1\u03b1\u03b4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03ae \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03b5\u03af\u03c2, \u03ba\u03b1\u03b8\u03ce\u03c2 \u03b7 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03c0\u03bf\u03c5 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03b5\u03c4\u03b1\u03b9 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf \u03bc\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03c3\u03bc\u03cc \u03c4\u03c9\u03bd \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03af\u03c9\u03bd \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf\u03bd \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03b8\u03ac\u03bd\u03b1\u03c4\u03bf (103).\u03a5\u03c0\u03ac\u03c1\u03c7\u03bf\u03c5\u03bd \u03c3\u03c4\u03bf\u03b9\u03c7\u03b5\u03af\u03b1 \u03cc\u03c4\u03b9 \u03b7 \u03b4\u03c5\u03c3\u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b1 \u03c4\u03b7\u03c2 \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03b9\u03b1\u03ba\u03ae\u03c2 \u03b1\u03bb\u03c5\u03c3\u03af\u03b4\u03b1\u03c2 (MRC) \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03c0\u03af\u03ba\u03c4\u03b7\u03c4\u03b7 \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7 \u03b4\u03b9\u03b1\u03b4\u03b9\u03ba\u03b1\u03c3\u03af\u03b1 \u03c4\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c4\u03c1\u03bf\u03c0\u03ae\u03c2 \u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac. \u0393\u03b9\u03b1 \u03c0\u03b1\u03c1\u03ac\u03b4\u03b5\u03b9\u03b3\u03bc\u03b1 \u03b7 \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae\u03c2 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03bf\u03b4\u03b7\u03b3\u03b5\u03af \u03c3\u03b5 \u03bc\u03b5\u03b9\u03c9\u03bc\u03ad\u03bd\u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03b5\u03bd\u03cc\u03c2 \u03c3\u03c5\u03bd\u03cc\u03bb\u03bf\u03c5 \u03b5\u03bd\u03b6\u03cd\u03bc\u03c9\u03bd \u03c4\u03bf\u03c5 complex 1 \u03c4\u03b7\u03c2 \u03b1\u03bd\u03b1\u03c0\u03bd\u03b5\u03c5\u03c3\u03c4\u03b9\u03ba\u03ae\u03c2 \u03b1\u03bb\u03c5\u03c3\u03af\u03b4\u03b1\u03c2 \u03c4\u03c9\u03bd \u03bc\u03b9\u03c4\u03bf\u03c7\u03bf\u03bd\u03b4\u03c1\u03af\u03c9\u03bd \u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2(104).<\/p>\n

1.4. \u039a\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2<\/b><\/h5>\n

\u03a4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03b4\u03b9\u03b7\u03b8\u03b7\u03c4\u03b9\u03ba\u03cc \u03c0\u03c1\u03cc\u03c4\u03c5\u03c0\u03bf \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7\u03c2, \u03bd\u03b5\u03ba\u03c1\u03ce\u03c3\u03b5\u03b9\u03c2, \u03c5\u03c8\u03b7\u03bb\u03cc \u03bc\u03b9\u03c4\u03c9\u03c4\u03b9\u03ba\u03cc \u03b4\u03b5\u03af\u03ba\u03c4\u03b7 \u03ba\u03b1\u03b9 \u03b1\u03b3\u03b3\u03b5\u03b9\u03b1\u03ba\u03ae \u03b4\u03b9\u03ae\u03b8\u03b7\u03c3\u03b7 (5). \u03a4\u03bf \u03b1\u03bd\u03b1\u03c0\u03bb\u03b1\u03c3\u03c4\u03b9\u03ba\u03cc \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c8\u03b7\u03bb\u03ae\u03c2 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 \u03cc\u03b3\u03ba\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03b1\u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c0\u03bf\u03c5 \u03b4\u03b9\u03b1\u03c4\u03b7\u03c1\u03bf\u03cd\u03bd \u03c4\u03bf\u03c5\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03b5\u03c0\u03b9\u03b8\u03b7\u03bb\u03b9\u03b1\u03ba\u03ae\u03c2 \u03c0\u03c1\u03bf\u03ad\u03bb\u03b5\u03c5\u03c3\u03b7\u03c2.<\/p>\n

1.4.1. \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c4\u03b7\u03c2 \u039c\u0391<\/b>PK<\/b> \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2<\/b><\/h6>\n

\u03a3\u03c4\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd RAS \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c5\u03c8\u03b7\u03bb\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (40-55%) (105). \u0391\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03b5\u03af\u03bd\u03b1\u03b9 \u03bb\u03b9\u03b3\u03cc\u03c4\u03b5\u03c1\u03bf \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 (12-17%), \u03c9\u03c3\u03c4\u03cc\u03c3\u03bf \u03b5\u03c0\u03af \u03c5\u03c0\u03ac\u03c1\u03be\u03b5\u03c9\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03b1\u03c5\u03be\u03ac\u03bd\u03b5\u03b9 \u03b7 \u03b8\u03bd\u03b7\u03c4\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd (105).<\/p>\n

\u03a3\u03c4\u03bf \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bf\u03b9 \u03ba\u03c5\u03c1\u03af\u03b1\u03c1\u03c7\u03b5\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c4\u03b7\u03c2 MAPK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03b1\u03c6\u03bf\u03c1\u03bf\u03cd\u03bd \u03c4\u03bf \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf BRAF, \u03bc\u03b5 \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 (25-50%) (105, 106). \u0391\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd RET\/PTC, NTRK \u03ba\u03b1\u03b9 PAX8\u2013PPAR\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c3\u03c0\u03ac\u03bd\u03b9\u03b1 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03c5\u03c0\u03bf\u03c3\u03c4\u03b7\u03c1\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b7\u03bd \u03c0\u03b1\u03c1\u03b1\u03c4\u03ae\u03c1\u03b7\u03c3\u03b7 \u03cc\u03c4\u03b9 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03bf\u03c6\u03b5\u03af\u03bb\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03ac \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03c3\u03c0\u03ac\u03bd\u03b9\u03b1 \u03b5\u03be\u03b5\u03bb\u03af\u03c3\u03c3\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03cc\u03b3\u03ba\u03bf\u03c5\u03c2 \u03c5\u03c8\u03b7\u03bb\u03ae\u03c2 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 (105).
\n<\/b><\/p>\n

1.4.2. \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PTEN\/PI3K\/Akt<\/b><\/h6>\n

\u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PTEN\/PI3K\/Akt \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c5\u03c8\u03b7\u03bb\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc \u03c3\u03c4\u03bf \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (98). \u0395\u03b9\u03b4\u03b9\u03ba\u03cc\u03c4\u03b5\u03c1\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf \u03c0\u03bf\u03c5 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03b7\u03bd \u03ba\u03b1\u03c4\u03b1\u03bb\u03c5\u03c4\u03b9\u03ba\u03ae \u03c5\u03c0\u03bf\u03bc\u03bf\u03bd\u03ac\u03b4\u03b1 \u03c4\u03b7\u03c2 \u03c6\u03c9\u03c3\u03c6\u03b1\u03c4\u03b9\u03b4\u03c5\u03bb\u03b9\u03bd\u03bf\u03c3\u03b9\u03c4\u03cc\u03bb\u03b7\u03c2-3 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2(PI3K) \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 23% \u03ba\u03b1\u03b9 \u03c3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c5\u03bd\u03c5\u03c0\u03ac\u03c1\u03c7\u03bf\u03c5\u03bd \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd RAS \u03ae BRAF (98). \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03bf\u03cd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 PTEN \u03c0\u03bf\u03c5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 PI3K\/Akt \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b5\u03c0\u03af\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03c5\u03c8\u03b7\u03bb\u03cc \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (12-50%) \u03c3\u03b5 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (99).<\/sup><\/p>\n

\u03a4\u03ad\u03bb\u03bf\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03b7\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 \u03c3\u03b5\u03c1\u03af\u03bd\u03b7\u03c2-\u03b8\u03c1\u03b5\u03bf\u03bd\u03af\u03bd\u03b7\u03c2 AKT1 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03c7\u03c9\u03c1\u03af\u03c2 \u03bd\u03b1 \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03ba\u03b1\u03bb\u03cd\u03c0\u03c4\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c4\u03b1\u03bb\u03c5\u03c4\u03b9\u03ba\u03ae\u03c2 \u03c5\u03c0\u03bf\u03bc\u03bf\u03bd\u03ac\u03b4\u03b1\u03c2 PI3K \u03ba\u03b1\u03b9 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03ad\u03bd\u03b1 \u03b5\u03bd\u03b1\u03bb\u03bb\u03b1\u03ba\u03c4\u03b9\u03ba\u03cc \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03b1\u03c5\u03c4\u03bf\u03cd \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd \u03c3\u03b5 \u03c0\u03c1\u03bf\u03c7\u03c9\u03c1\u03b7\u03bc\u03ad\u03bd\u03b5\u03c2 \u03bc\u03bf\u03c1\u03c6\u03ad\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c5\u03bd\u03b4\u03ad\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF (107).<\/p>\n

1.4.3. O\u03b3\u03ba\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03cc \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf <\/b>p<\/b>53<\/b><\/h6>\n

\u03a4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf TP53 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03bc\u03af\u03b1 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03c4\u03bf\u03c5 \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 \u03c0\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03b5\u03af \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03ae \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03bf\u03cd \u03ba\u03cd\u03ba\u03bb\u03bf\u03c5, \u03ba\u03b1\u03b9\/\u03ae \u03b1\u03c0\u03cc\u03c0\u03c4\u03c9\u03c3\u03b7 \u03c9\u03c2 \u03b1\u03bd\u03c4\u03b1\u03c0\u03cc\u03ba\u03c1\u03b9\u03c3\u03b7 \u03c3\u03b5 \u03b4\u03b9\u03ac\u03c6\u03bf\u03c1\u03b1 \u03b5\u03c1\u03b5\u03b8\u03af\u03c3\u03bc\u03b1\u03c4\u03b1. \u0391\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03bf\u03b4\u03b7\u03b3\u03ae\u03c3\u03b5\u03b9 \u03c3\u03b5 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7, \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03c4\u03af\u03c3\u03c4\u03b1\u03c3\u03b7 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03c4\u03b9\u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ae \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1. \u0391\u03bd \u03ba\u03b1\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 p53 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c0\u03ac\u03bd\u03b9\u03b1 \u03c3\u03b5 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (0-9%) \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03c3\u03c4\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03c7\u03b1\u03bc\u03b7\u03bb\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 (17-38%) \u03ba\u03b1\u03b9 \u03b9\u03b4\u03af\u03c9\u03c2 \u03c3\u03c4\u03b1 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b1 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03cc\u03c0\u03bf\u03c5 \u03c4\u03bf \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc \u03c6\u03c4\u03ac\u03bd\u03b5\u03b9 \u03c3\u03c4\u03bf 67-88% (108). \u03a6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03ad\u03bd\u03b1 \u03cc\u03c8\u03b9\u03bc\u03bf \u03b3\u03b5\u03b3\u03bf\u03bd\u03cc\u03c2 \u03c3\u03c4\u03b7 \u03b4\u03b9\u03b1\u03b4\u03b9\u03ba\u03b1\u03c3\u03af\u03b1 \u03c4\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ba\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c0\u03b9\u03bf \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03cc \u03c6\u03b1\u03b9\u03bd\u03cc\u03c4\u03c5\u03c0\u03bf.<\/p>\n

1.4.4. \u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03b7 <\/b>beta<\/b>–<\/b>catenin<\/b> \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9<\/b><\/h6>\n

\u0397 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b7 \u03b2-catenin \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf CTNNB1 \u03ba\u03b1\u03b9 \u03c0\u03b1\u03af\u03b6\u03b5\u03b9 \u03c1\u03cc\u03bb\u03bf \u03c4\u03cc\u03c3\u03bf \u03c3\u03c4\u03b7\u03bd \u03c3\u03cd\u03b6\u03b5\u03c5\u03be\u03b7 \u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03c9\u03bd \u03cc\u03c3\u03bf \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03ae \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 (109). \u03a3\u03c4\u03bf \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03cc \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03bf \u03b7 \u03b2-catenin \u03b5\u03af\u03bd\u03b1\u03b9 \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c0\u03c1\u03bf\u03c3\u03b4\u03b5\u03b4\u03b5\u03bc\u03ad\u03bd\u03b7 \u03c3\u03c4\u03b7\u03bd \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03ae \u03bc\u03b5\u03bc\u03b2\u03c1\u03ac\u03bd\u03b7 \u03bc\u03b5 \u03c4\u03b9\u03c2 \u03b4\u03b9\u03b1\u03bc\u03b5\u03bc\u03b2\u03c1\u03b1\u03bd\u03b9\u03ba\u03ad\u03c2 \u03c0\u03c1\u03c9\u03c4\u03b5\u0390\u03bd\u03b5\u03c2 cadherins. \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc \u03c3\u03c4\u03bf\u03b9\u03c7\u03b5\u03af\u03bf \u03c4\u03bf\u03c5 Wnt \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd \u03c3\u03b7\u03bc\u03b1\u03c4\u03bf\u03b4\u03cc\u03c4\u03b7\u03c3\u03b7\u03c2 \u03c4\u03bf \u03bf\u03c0\u03bf\u03af\u03bf \u03b5\u03af\u03bd\u03b1\u03b9 \u03b1\u03c0\u03b1\u03c1\u03b1\u03af\u03c4\u03b7\u03c4\u03bf \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03c4\u03bf\u03c5 \u03b5\u03bc\u03b2\u03c1\u03cd\u03bf\u03c5, \u03b1\u03bb\u03bb\u03ac \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03c0\u03bf\u03bb\u03bb\u03bf\u03cd\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5\u03c2 \u03c3\u03c4\u03bf\u03bd \u03ac\u03bd\u03b8\u03c1\u03c9\u03c0\u03bf (109).<\/p>\n

\u0397 b-catenin \u03b5\u03af\u03bd\u03b1\u03b9 \u03c4\u03bc\u03ae\u03bc\u03b1 \u03b5\u03bd\u03cc\u03c2 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03bf\u03cd \u03c3\u03c5\u03bc\u03c0\u03bb\u03ad\u03b3\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c0\u03bf\u03c5 \u03b5\u03c0\u03af\u03c3\u03b7\u03c2 \u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03ac\u03bd\u03b5\u03b9 \u03c4\u03b7\u03bd APC (adenomatosis polyposis coli) \u03ba\u03b1\u03b9 \u03c4\u03b7\u03bd \u03b1\u03be\u03af\u03bd\u03b7 \u03c0\u03bf\u03c5 \u03b1\u03c0\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03c3\u03c5\u03bd\u03b8\u03ac\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03b3\u03bb\u03c5\u03ba\u03bf\u03b3\u03cc\u03bd\u03bf\u03c5 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7-3 (GSK3b). To Wnt \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c3\u03c4\u03b1\u03b8\u03b5\u03c1\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03b7\u03bd \u03b2-catenin \u03b5\u03bc\u03c0\u03bf\u03b4\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b7\u03bd \u03c6\u03c9\u03c3\u03c6\u03bf\u03c1\u03c5\u03bb\u03af\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd GSK-3 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03bd \u03b5\u03c0\u03b1\u03ba\u03cc\u03bb\u03bf\u03c5\u03b8\u03b7 \u03b1\u03c0\u03bf\u03b4\u03cc\u03bc\u03b7\u03c3\u03ae \u03c4\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03b5\u03c0\u03b9\u03c4\u03c1\u03ad\u03c0\u03b5\u03b9 \u03bd\u03b1 \u03bc\u03b5\u03c4\u03b1\u03ba\u03b9\u03bd\u03b7\u03b8\u03b5\u03af \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 \u03cc\u03c0\u03bf\u03c5 \u03b4\u03c1\u03b1 \u03c9\u03c2 \u03c3\u03c5\u03bd\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03c4\u03ae\u03c2 \u03c4\u03c9\u03bd \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03ce\u03bd \u03c0\u03b1\u03c1\u03b1\u03b3\u03cc\u03bd\u03c4\u03c9\u03bd \u03c0\u03bf\u03c5 \u03b1\u03bd\u03ae\u03ba\u03bf\u03c5\u03bd \u03c3\u03c4\u03b7\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03ad\u03bd\u03b5\u03b9\u03b1 TCF\/LEF.<\/p>\n

\u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf \u03c0\u03bf\u03c5 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b5\u03af \u03c4\u03b7\u03bd APC \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c0\u03b5\u03cd\u03b8\u03c5\u03bd\u03b5\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03c4\u03b7\u03c2 \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03bf\u03cd\u03c2 \u03b1\u03b4\u03b5\u03bd\u03c9\u03bc\u03b1\u03c4\u03ce\u03b4\u03bf\u03c5\u03c2 \u03c0\u03bf\u03bb\u03c5\u03c0\u03bf\u03b4\u03af\u03b1\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03c0\u03bf\u03b9\u03ba\u03b9\u03bb\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03c4\u03bf \u03c3\u03cd\u03bd\u03b4\u03c1\u03bf\u03bc\u03bf Gardner \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bd\u03b4\u03c5\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03bf \u03ba\u03af\u03bd\u03b4\u03c5\u03bd\u03bf \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (110). \u0391\u03c0\u03cc \u03c4\u03b7\u03bd \u03ac\u03bb\u03bb\u03b7 \u03c0\u03bb\u03b5\u03c5\u03c1\u03ac \u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 e-cadherin \u03b5\u03af\u03bd\u03b1\u03b9 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03c3\u03c4\u03b1 \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03b1\u03bb\u03bb\u03ac \u03bc\u03b5\u03b9\u03c9\u03bc\u03ad\u03bd\u03b7 \u03c3\u03c4\u03bf \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 (111). \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03b7\u03c2 \u03b2-catenin, \u03c0\u03bf\u03c5 \u03bf\u03b4\u03b7\u03b3\u03bf\u03cd\u03bd \u03c3\u03c4\u03b7\u03bd \u03b5\u03bd\u03b1\u03c0\u03cc\u03b8\u03b5\u03c3\u03ae \u03c4\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf \u03c3\u03c5\u03bd\u03b5\u03c7\u03ae \u03c1\u03cc\u03bb\u03bf \u03c4\u03b7\u03c2 \u03c9\u03c2 \u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03cc \u03c3\u03c5\u03bd\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03b7\u03c4\u03ae \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 (25%) \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b1 \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03b1 (65%), \u03b1\u03bb\u03bb\u03ac \u03cc\u03c7\u03b9 \u03c3\u03c4\u03b1 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 (112,113)<\/p>\n

2. \u039c\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03b2\u03b1\u03c3\u03b9\u03c3\u03bc\u03ad\u03bd\u03bf\u03b9 \u03c3\u03c4\u03bf <\/b>RNA<\/b> <\/b><\/h4>\n
2.1. <\/b>M<\/b>icro<\/b>RNA<\/b> (<\/b>miRNA<\/b>)<\/b><\/h5>\n

\u03a4\u03b1 miRNA \u03b5\u03af\u03bd\u03b1\u03b9 \u03c4\u03bc\u03ae\u03bc\u03b1\u03c4\u03b1 21-22 \u03bd\u03bf\u03c5\u03ba\u03bb\u03b5\u03bf\u03c4\u03b9\u03b4\u03af\u03c9\u03bd \u03bc\u03b7 \u03ba\u03c9\u03b4\u03b9\u03ba\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf\u03c5 RNA \u03c0\u03bf\u03c5 \u03ad\u03c7\u03bf\u03c5\u03bd \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03b1\u03bd\u03b1\u03c3\u03c4\u03b1\u03bb\u03c4\u03b9\u03ba\u03cc \u03c3\u03c4\u03b7 \u03bc\u03b5\u03c4\u03b1-\u03bc\u03b5\u03c4\u03b1\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03ae \u03c1\u03cd\u03b8\u03bc\u03b9\u03c3\u03b7 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03bc\u03ad\u03c3\u03c9 \u03c3\u03c5\u03bc\u03c0\u03bb\u03b7\u03c1\u03c9\u03bc\u03b1\u03c4\u03b9\u03ba\u03ae\u03c2 \u03c0\u03c1\u03cc\u03c3\u03b4\u03b5\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf mRNA, \u03c0\u03bf\u03c5 \u03bc\u03b5\u03c3\u03bf\u03bb\u03b1\u03b2\u03b5\u03af \u03c3\u03c4\u03b7\u03bd \u03bc\u03b5\u03c4\u03ac\u03c6\u03c1\u03b1\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03b1\u03c0\u03bf\u03b4\u03cc\u03bc\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5. \u03a0\u03bf\u03bb\u03bb\u03ad\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03ad\u03c7\u03bf\u03c5\u03bd \u03b2\u03c1\u03b5\u03b9 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03b5\u03c4\u03b9\u03ba\u03ce\u03bd miRNA \u03c3\u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03c9\u03bc\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (\u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c4\u03b1 miR-221 \u03ba\u03b1\u03b9 -222) (114,115).<\/p>\n

\u039c\u03ad\u03c7\u03c1\u03b9 \u03c4\u03ce\u03c1\u03b1 \u03b4\u03b5\u03bd \u03c5\u03c0\u03ac\u03c1\u03c7\u03b5\u03b9 \u03bc\u03b5\u03b3\u03ac\u03bb\u03b7, \u03c0\u03c1\u03bf\u03bf\u03c0\u03c4\u03b9\u03ba\u03ae, \u03c0\u03bf\u03bb\u03c5\u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03ae \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b7 \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03c9\u03bd miRNA \u03ba\u03b1\u03b9 \u03c3\u03c5\u03bd\u03ae\u03b8\u03c9\u03c2 \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03bc\u03cc\u03bd\u03bf \u03c3\u03b5 \u03b5\u03c1\u03b5\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03ac \u03c0\u03c1\u03c9\u03c4\u03cc\u03ba\u03bf\u03bb\u03bb\u03b1.<\/p>\n

2.2. \u03a0\u03c1\u03bf\u03c3\u03b4\u03b9\u03bf\u03c1\u03b9\u03c3\u03bc\u03cc\u03c2 \u03c4\u03bf\u03c5 mRNA \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03c4\u03b7\u03c2 <\/b>TSH<\/b> (<\/b>TSHR<\/b>)<\/b><\/h5>\n

T\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03b5\u03ba\u03c6\u03c1\u03ac\u03b6\u03bf\u03c5\u03bd \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03b5\u03af\u03c2 \u03c4\u03b7\u03c2 TSH (TSHR). \u03a4\u03bf mRNA \u03c4\u03bf\u03c5 TSHR \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03b5\u03af\u03c4\u03b1\u03b9 \u03c9\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b7\u03c2 \u03c3\u03c4\u03bf \u03c0\u03b5\u03c1\u03b9\u03c6\u03b5\u03c1\u03b9\u03ba\u03cc \u03b1\u03af\u03bc\u03b1 \u03c3\u03c4\u03b7\u03bd \u03c0\u03b1\u03c1\u03b1\u03ba\u03bf\u03bb\u03bf\u03cd\u03b8\u03b7\u03c3\u03b7 \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03bc\u03b5 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2.<\/p>\n

\u038c\u03c3\u03bf\u03bd \u03b1\u03c6\u03bf\u03c1\u03ac \u03c4\u03b7\u03bd \u03c0\u03c1\u03bf\u03b5\u03b3\u03c7\u03b5\u03b9\u03c1\u03b7\u03c4\u03b9\u03ba\u03ae \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03af\u03b1\u03c2 \u03c3\u03b5 \u03cc\u03b6\u03bf\u03c5\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03bc\u03af\u03b1 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 \u03ad\u03b4\u03b5\u03b9\u03be\u03b5 \u03cc\u03c4\u03b9 \u03bf \u03c0\u03c1\u03bf\u03c3\u03b4\u03b9\u03bf\u03c1\u03b9\u03c3\u03bc\u03cc\u03c2 \u03c4\u03bf\u03c5 TSHR mRNA \u03ad\u03c7\u03b5\u03b9 \u03b5\u03c5\u03b1\u03b9\u03c3\u03b8\u03b7\u03c3\u03af\u03b1 90% \u03ba\u03b1\u03b9 \u03b5\u03b9\u03b4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1 80% \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03c0\u03c1\u03cc\u03b2\u03bb\u03b5\u03c8\u03b7 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 \u03b5\u03b9\u03b4\u03b9\u03ba\u03ac \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03bc\u03b5 \u03b1\u03b4\u03b9\u03b5\u03c5\u03ba\u03c1\u03af\u03bd\u03b9\u03c3\u03c4\u03b7 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ae \u03b5\u03be\u03ad\u03c4\u03b1\u03c3\u03b7(intermediate) \u03bc\u03b5\u03c4\u03ac FNA (116).<\/p>\n

2.3. \u0391\u03bd\u03ac\u03bb\u03c5\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7\u03c2 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd (<\/b>micro<\/b> <\/b>array<\/b> <\/b>analysis<\/b>)<\/b><\/h5>\n

A\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 \u03bc\u03b5 \u03c4\u03b9\u03c2 \u03c4\u03b5\u03c7\u03bd\u03b9\u03ba\u03ad\u03c2 \u03b1\u03bd\u03af\u03c7\u03bd\u03b5\u03c5\u03c3\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c3\u03b5 \u03ad\u03bd\u03b1 \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf \u03ae \u03b1\u03bd\u03b1\u03b4\u03b9\u03b1\u03c4\u03ac\u03be\u03b5\u03c9\u03bd \u03bf\u03b9 microarray \u03b4\u03b9\u03b1\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b4\u03bf\u03ba\u03b9\u03bc\u03b1\u03c3\u03af\u03b5\u03c2 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03b1\u03bd\u03b9\u03c7\u03bd\u03b5\u03cd\u03c3\u03bf\u03c5\u03bd \u03c4\u03b7\u03bd \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03b5\u03ba\u03b1\u03c4\u03bf\u03bd\u03c4\u03ac\u03b4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03b1\u03c0\u03cc \u03c4\u03bf mRNA \u03c0\u03bf\u03c5 \u03b1\u03c0\u03bf\u03bc\u03bf\u03bd\u03ce\u03bd\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03bf \u03be\u03ad\u03c0\u03bb\u03c5\u03bc\u03b1 \u03c4\u03b7\u03c2 \u03b2\u03b5\u03bb\u03cc\u03bd\u03b1\u03c2 \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7 \u03b4\u03b9\u03ac\u03c1\u03ba\u03b5\u03b9\u03b1 \u03c4\u03b7\u03c2 FNA.<\/p>\n

M\u03b5\u03b3\u03ac\u03bb\u03b7 \u03c0\u03c1\u03bf\u03bf\u03c0\u03c4\u03b9\u03ba\u03ae, \u03c0\u03bf\u03bb\u03c5\u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03ae \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 \u03c0\u03bf\u03c5 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7\u03c3\u03b5 \u03c4\u03b7\u03bd \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 167 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03bc\u03b5 \u03c4\u03b7\u03bd \u03c4\u03b5\u03c7\u03bd\u03b9\u03ba\u03ae \u03b1\u03c5\u03c4\u03ae \u03ad\u03b4\u03b5\u03b9\u03be\u03b5 \u03cc\u03c4\u03b9 \u03b5\u03af\u03c7\u03b5 \u03b5\u03c5\u03b1\u03b9\u03c3\u03b8\u03b7\u03c3\u03af\u03b1 92% \u03ba\u03b1\u03b9 \u03b5\u03b9\u03b4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1 52% \u03c3\u03c4\u03b7 \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 (117).<\/p>\n

3. \u0391\u03bd\u03bf\u03c3\u03bf\u03ca\u03c3\u03c4\u03bf\u03c7\u03b7\u03bc\u03b9\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 <\/b><\/h4>\n

\u03a4\u03b1 \u03c4\u03b5\u03bb\u03b5\u03c5\u03c4\u03b1\u03af\u03b1 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03b4\u03b9\u03ac\u03c6\u03bf\u03c1\u03bf\u03b9 \u03b1\u03bd\u03bf\u03c3\u03bf\u03b9\u03c3\u03c4\u03bf\u03c7\u03b7\u03bc\u03b9\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03c3\u03c4\u03bf\u03bd \u03bf\u03c1\u03cc \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03cc\u03c0\u03c9\u03c2 galectin-3, HBME-1, fibronectin-, CITED-1, \u03ba\u03b1\u03b9 cytokeratin-19 \u03ad\u03c7\u03bf\u03c5\u03bd \u03b4\u03b9\u03b5\u03c1\u03b5\u03c5\u03bd\u03b7\u03b8\u03b5\u03af \u03b3\u03b9\u03b1 \u03c4\u03bf \u03c1\u03cc\u03bb\u03bf \u03c4\u03bf\u03c5\u03c2 \u03c3\u03c4\u03b7 \u03b4\u03b9\u03ac\u03ba\u03c1\u03b9\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03be\u03cd \u03ba\u03b1\u03bb\u03bf\u03ae\u03b8\u03c9\u03bd \u03ba\u03b1\u03b9 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03c9\u03bd \u03bf\u03b6\u03b9\u03b4\u03af\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a9\u03c3\u03c4\u03cc\u03c3\u03bf \u03b4\u03b5\u03bd \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03b5\u03c5\u03c1\u03ad\u03c9\u03c2 \u03c3\u03c4\u03b7\u03bd \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae \u03c0\u03c1\u03ac\u03be\u03b7 \u03bc\u03b5 \u03b5\u03be\u03b1\u03af\u03c1\u03b5\u03c3\u03b7 \u03c4\u03b7\u03bd galectin-3 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03b4\u03b5\u03af\u03c7\u03bd\u03bf\u03c5\u03bd \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ae \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03b5\u03c0\u03b9\u03ba\u03ac\u03bb\u03c5\u03c8\u03b7 \u03bc\u03b5\u03c4\u03b1\u03be\u03cd \u03c4\u03b7\u03c2 \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7\u03c2 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (118).
\n<\/b><\/p>\n

Galectin<\/b>-3. <\/b>H Galectin-3 \u03b1\u03bd\u03ae\u03ba\u03b5\u03b9 \u03c3\u03c4\u03b7 \u03bc\u03b5\u03b3\u03ac\u03bb\u03b7 \u03bf\u03b9\u03ba\u03bf\u03b3\u03ad\u03bd\u03b5\u03b9\u03b1 \u03c4\u03c9\u03bd Galectins \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd \u03c0\u03bf\u03c5 \u03b1\u03bd\u03b1\u03b3\u03bd\u03c9\u03c1\u03af\u03b6\u03bf\u03c5\u03bd \u03ba\u03b1\u03b9 \u03c0\u03c1\u03bf\u03c3\u03b4\u03ad\u03bd\u03bf\u03c5\u03bd \u03c4\u03b9\u03c2 \u03b3\u03b1\u03bb\u03b1\u03ba\u03c4\u03bf\u03c3\u03af\u03b4\u03b5\u03c2 \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03ad\u03c2 \u03b3\u03bb\u03c5\u03ba\u03bf\u03c0\u03c1\u03c9\u03c4\u03b5\u03af\u03bd\u03b5\u03c2 \u03ba\u03b1\u03b9 \u03b3\u03bb\u03c5\u03ba\u03bf\u03bb\u03b9\u03c0\u03af\u03b4\u03b9\u03b1 (119). \u0395\u03ba\u03c6\u03c1\u03ac\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf\u03bd \u03c0\u03c5\u03c1\u03ae\u03bd\u03b1, \u03c3\u03c4\u03bf \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1, \u03c3\u03c4\u03b1 \u03bc\u03b9\u03c4\u03bf\u03c7\u03cc\u03bd\u03b4\u03c1\u03b9\u03b1, \u03c3\u03c4\u03b7\u03bd \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03ae \u03b5\u03c0\u03b9\u03c6\u03ac\u03bd\u03b5\u03b9\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03bf \u03b5\u03be\u03c9\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03bf \u03b4\u03b9\u03ac\u03c3\u03c4\u03b7\u03bc\u03b1 \u03ba\u03b1\u03b9 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03b5\u03bc\u03c0\u03bb\u03ad\u03ba\u03b5\u03c4\u03b1\u03b9 \u03b5\u03ba\u03c4\u03cc\u03c2 \u03c4\u03c9\u03bd \u03ac\u03bb\u03bb\u03c9\u03bd \u03c3\u03c4\u03b7\u03bd \u03b1\u03cd\u03be\u03b7\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5, \u03c3\u03c4\u03bf\u03bd \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03b9\u03ba\u03cc \u03ba\u03cd\u03ba\u03bb\u03bf \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03c0\u03cc\u03c0\u03c4\u03c9\u03c3\u03b7 (120). H Galectin-3 \u03b4\u03b5\u03bd \u03b5\u03ba\u03c6\u03c1\u03ac\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c6\u03c5\u03c3\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03bb\u03bb\u03ac \u03b5\u03af\u03bd\u03b1\u03b9 \u03b4\u03c5\u03bd\u03b1\u03c4\u03cc\u03bd \u03bd\u03b1 \u03b5\u03ba\u03c6\u03c1\u03b1\u03c3\u03c4\u03b5\u03af \u03c3\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03b1 (0-45%), \u03b5\u03bd\u03ce \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af \u03ad\u03bd\u03b1\u03bd \u03b1\u03c0\u03cc \u03c4\u03bf\u03c5\u03c2 \u03c0\u03b9\u03bf \u03b1\u03be\u03b9\u03cc\u03c0\u03b9\u03c3\u03c4\u03bf\u03c5\u03c2 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03cd\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 (76,121).<\/p>\n

\u03a3\u03c4\u03b9\u03c2 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03b1\u03bd\u03b1\u03c6\u03ad\u03c1\u03b5\u03c4\u03b1\u03b9 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 <\/b>Galectin-3 \u03c3\u03c4\u03bf 90-100% \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03ae \u03c4\u03b7\u03c2 \u03bd\u03b1 \u03c0\u03bf\u03b9\u03ba\u03af\u03bb\u03bb\u03b5\u03b9 \u03b1\u03bd\u03ac\u03bb\u03bf\u03b3\u03b1 \u03bc\u03b5 \u03c4\u03bf\u03bd \u03b9\u03c3\u03c4\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03cc \u03c5\u03c0\u03cc\u03c4\u03c5\u03c0\u03bf. \u03a3\u03c4\u03bf \u03ba\u03bb\u03b1\u03c3\u03c3\u03b9\u03ba\u03cc \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 82-100% \u03b5\u03bd\u03ce \u03c3\u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bc\u03b5 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03b4\u03b9\u03b1\u03bc\u03cc\u03c1\u03c6\u03c9\u03c3\u03b7 \u03b7 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03ae \u03c4\u03b7\u03c2 \u03ba\u03c5\u03bc\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc 33% \u03ad\u03c9\u03c2 100%.<\/p>\n

\u03a3\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03b7 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03b1 \u03b7 Galectin-3 \u03b5\u03ba\u03c6\u03c1\u03ac\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bc\u03b9\u03ba\u03c1\u03cc\u03c4\u03b5\u03c1\u03bf \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc (20-100%) \u03b1\u03c0\u03cc \u03cc\u03c4\u03b9 \u03c3\u03c4\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b7 (121).
\n<\/b><\/p>\n

4. \u03a1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03c9\u03bd \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03c3\u03c4\u03b7\u03bd \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 <\/b><\/h4>\n

\u039f\u03b9 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03c0\u03b1\u03af\u03be\u03bf\u03c5\u03bd \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b7\u03bd \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c0\u03bf\u03c1\u03b5\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u0395\u03af\u03bd\u03b1\u03b9 \u03b3\u03bd\u03c9\u03c3\u03c4\u03cc \u03cc\u03c4\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd RAS, PIK3CA, and PTEN \u03c3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03bf\u03c5\u03bd \u03ba\u03b1\u03b9 \u03c3\u03c5\u03bd\u03c5\u03c0\u03ac\u03c1\u03c7\u03bf\u03c5\u03bd \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7\u03bd \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03b5\u03bd\u03cc\u03c2 \u03cc\u03b3\u03ba\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03c0\u03cc \u03b1\u03c1\u03c7\u03b9\u03ba\u03cc \u03c3\u03b5 \u03c0\u03c1\u03bf\u03c7\u03c9\u03c1\u03b7\u03bc\u03ad\u03bd\u03bf \u03c3\u03c4\u03ac\u03b4\u03b9\u03bf (63). \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ac patterns, \u03b9\u03b4\u03af\u03c9\u03c2 \u03c3\u03c5\u03bd\u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03c4\u03c9\u03bd \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03b5 \u03ac\u03bb\u03bb\u03b5\u03c2 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ad\u03c2 (\u03c0.\u03c7. \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 \u0392RAF) \u03c0\u03bf\u03c5 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03bf\u03c5\u03bd \u03ba\u03b1\u03b9 \u03c4\u03b1 \u03b4\u03cd\u03bf \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ac \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 \u03c3\u03b7\u03bc\u03b1\u03c4\u03bf\u03b4\u03cc\u03c4\u03b7\u03c3\u03b7\u03c2 MAPK \u03ba\u03b1\u03b9 PI3K-AKT, \u03c3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c5\u03bc\u03b2\u03b1\u03af\u03bd\u03bf\u03c5\u03bd \u03ba\u03b1\u03c4\u03ac \u03c4\u03b7\u03bd \u03b5\u03be\u03ad\u03bb\u03b9\u03be\u03b7 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03c0\u03c1\u03bf\u03c7\u03c9\u03c1\u03b7\u03bc\u03ad\u03bd\u03bf \u03c3\u03c4\u03ac\u03b4\u03b9\u03bf (63,122). \u0391\u03c5\u03c4\u03ac \u03c4\u03b1 \u03b5\u03c5\u03c1\u03ae\u03bc\u03b1\u03c4\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03bd\u03b4\u03b5\u03b9\u03ba\u03c4\u03b9\u03ba\u03ac \u03cc\u03c4\u03b9 \u03c4\u03ad\u03c4\u03bf\u03b9\u03b1 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ac patterns \u03b8\u03b1 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03c3\u03b1\u03bd \u03bd\u03b1 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03ad\u03c3\u03bf\u03c5\u03bd \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2.<\/p>\n

\u039c\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RAS, \u03ba\u03c5\u03c1\u03af\u03c9\u03c2 \u03c4\u03bf\u03c5 NRAS, \u03c3\u03c5\u03bd\u03b4\u03ad\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03b9 \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03af\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c3\u03c5\u03bd\u03bf\u03bb\u03b9\u03ba\u03ae\u03c2 \u03b5\u03c0\u03b9\u03b2\u03af\u03c9\u03c3\u03b7\u03c2 \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd (123,124). \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03c9\u03bd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03cc\u03c0\u03c9\u03c2 \u03c4\u03bf p53 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03cc\u03bd\u03bf \u03c3\u03c4\u03bf \u03c6\u03c4\u03c9\u03c7\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03ae \u03c3\u03c4\u03bf \u03b1\u03bc\u03b5\u03c4\u03ac\u03c0\u03bb\u03b1\u03c3\u03c4\u03bf \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2, \u03b5\u03bd\u03ce \u03ac\u03bb\u03bb\u03b5\u03c2 \u03cc\u03c0\u03c9\u03c2 \u03c4\u03bf AKT1 \u03ad\u03c7\u03bf\u03c5\u03bd \u03b1\u03bd\u03b1\u03c6\u03b5\u03c1\u03b8\u03b5\u03af \u03bc\u03cc\u03bd\u03bf \u03c3\u03b5 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2 \u03ba\u03b1\u03b9 \u03cc\u03c7\u03b9 \u03c3\u03c4\u03b9\u03c2 \u03c0\u03c1\u03c9\u03c4\u03bf\u03c0\u03b1\u03b8\u03b5\u03af\u03c2 \u03b5\u03c3\u03c4\u03af\u03b5\u03c2 \u03c3\u03c4\u03bf \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae (107,102). \u0397 \u03c0\u03c1\u03bf\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03ae \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03c9\u03bd \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03b1\u03bd\u03b1\u03bc\u03ad\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03b4\u03b9\u03b5\u03c5\u03ba\u03c1\u03b9\u03bd\u03b9\u03c3\u03c4\u03b5\u03af.<\/p>\n

\u039f \u03c0\u03b9\u03bf \u03ba\u03b1\u03bb\u03ac \u03ba\u03b1\u03b8\u03bf\u03c1\u03b9\u03c3\u03bc\u03ad\u03bd\u03bf\u03c2 \u03c0\u03c1\u03bf\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03cc\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b7\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03c0\u03bf\u03c5 \u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03c4\u03bf \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9 \u03c4\u03b7\u03c2 \u039c\u0391PK \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2. \u039c\u03b5\u03b3\u03ac\u03bb\u03b7 \u03c0\u03bf\u03bb\u03c5\u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03ae \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7, \u03b1\u03bb\u03bb\u03ac \u03ba\u03b1\u03b9 \u03bc\u03b5\u03c4\u03b1\u03b3\u03b5\u03bd\u03ad\u03c3\u03c4\u03b5\u03c1\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2\u00a0 \u03ad\u03b4\u03b5\u03b9\u03be\u03b1\u03bd \u03b9\u03c3\u03c7\u03c5\u03c1\u03ae \u03c3\u03c5\u03c3\u03c7\u03ad\u03c4\u03b9\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 BRAF \u03bc\u03b5 \u03b1\u03bd\u03ac\u03c0\u03c4\u03c5\u03be\u03b7 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03ce\u03bd \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03c9\u03bd, \u03b5\u03be\u03c9\u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b9\u03ba\u03ae \u03b5\u03c0\u03ad\u03ba\u03c4\u03b1\u03c3\u03b7, \u03c0\u03c1\u03bf\u03c7\u03c9\u03c1\u03b7\u03bc\u03ad\u03bd\u03b1 \u03c3\u03c4\u03ac\u03b4\u03b9\u03b1 (\u0399\u0399\u0399, \u0399V) \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 (59,125) \u03b1\u03ba\u03cc\u03bc\u03b7 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03c7\u03b1\u03bc\u03b7\u03bb\u03bf\u03cd \u03ba\u03b9\u03bd\u03b4\u03cd\u03bd\u03bf\u03c5 (59,126).<\/p>\n

\u0395\u03c0\u03af\u03c3\u03b7\u03c2, \u03cc\u03c0\u03c9\u03c2 \u03ad\u03c7\u03b5\u03b9 \u03ae\u03b4\u03b7 \u03b1\u03bd\u03b1\u03c6\u03b5\u03c1\u03b8\u03b5\u03af \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03c3\u03c5\u03bd\u03b4\u03ad\u03bf\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03bd\u03b8\u03b5\u03ba\u03c4\u03b9\u03ba\u03cc \u03c3\u03c4\u03bf \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03c5\u03c4\u03b9\u03ba\u03cc \u03b9\u03ce\u03b4\u03b9\u03bf, \u03ba\u03b1\u03b8\u03ce\u03c2 \u03b7 \u03cd\u03c0\u03b1\u03c1\u03be\u03ae \u03c4\u03bf\u03c5\u03c2 \u03c3\u03c5\u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03af\u03c9\u03c3\u03b7 \u03ae \u03b1\u03c0\u03ce\u03bb\u03b5\u03b9\u03b1 \u03c4\u03b7\u03c2 \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b9\u03ba\u03cc \u03b9\u03c3\u03c4\u03cc \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c0\u03bf\u03c5 \u03b4\u03b5\u03c3\u03bc\u03b5\u03cd\u03bf\u03c5\u03bd \u03c4\u03bf \u03b9\u03ce\u03b4\u03b9\u03bf \u03cc\u03c0\u03c9\u03c2 \u03c4\u03b1 \u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf NIS, TSHR, pendrin, TPO \u03ba\u03b1\u03b9 TG (127).<\/p>\n

\u03a4\u03ad\u03bb\u03bf\u03c2, \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03bf\u03cd\u03bd \u03c5\u03c0\u03b5\u03c1\u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03ac\u03bb\u03bb\u03c9\u03bd \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03cc\u03c0\u03c9\u03c2 \u03c4\u03c9\u03bd VEGF \u03ba\u03b1\u03b9 MET (127). \u03a4\u03b1 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03b5\u03c5\u03c1\u03ae\u03bc\u03b1\u03c4\u03b1 \u03b5\u03be\u03b7\u03b3\u03bf\u03cd\u03bd \u03c4\u03b7 \u03c3\u03c5\u03c3\u03c7\u03ad\u03c4\u03b9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c5\u03c8\u03b7\u03bb\u03ae\u03c2 \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1\u03c2 \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03c6\u03ad\u03c1\u03bf\u03c5\u03bd \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 BRAF \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03b7 \u03c3\u03c5\u03c3\u03c7\u03ad\u03c4\u03b9\u03c3\u03ae \u03c4\u03bf\u03c5\u03c2 \u03bc\u03b5 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03b8\u03bd\u03b7\u03c4\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03c0\u03bf\u03c5 \u03c4\u03b9\u03c2 \u03ad\u03c7\u03bf\u03c5\u03bd, \u03cc\u03c0\u03c9\u03c2 \u03ad\u03c7\u03b5\u03b9 \u03c6\u03b1\u03bd\u03b5\u03af \u03c3\u03b5 \u03b4\u03b9\u03b5\u03b8\u03bd\u03ae \u03c0\u03bf\u03bb\u03c5\u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03ae \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7 (128).<\/p>\n

\u0393\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03ba\u03b1\u03b9 \u03bf \u03c0\u03c1\u03bf\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03c1\u03cc\u03bb\u03bf\u03c2 \u03c3\u03c4\u03bf\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03ae \u03ba\u03b1\u03bb\u03ac \u03b4\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03bf \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. <\/b>\u0391\u03c0\u03cc \u03c4\u03bf \u03c3\u03cd\u03bd\u03bf\u03bb\u03bf \u03c4\u03c9\u03bd \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03c9\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 5-10% \u03b5\u03bc\u03c6\u03b1\u03bd\u03af\u03b6\u03bf\u03c5\u03bd \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae \u03c0\u03c1\u03bf\u03b4\u03b9\u03ac\u03b8\u03b5\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03ba\u03bb\u03b7\u03c1\u03bf\u03bd\u03bf\u03bc\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03bf\u03bd \u03b1\u03c5\u03c4\u03bf\u03c3\u03c9\u03bc\u03b1\u03c4\u03b9\u03ba\u03cc \u03ba\u03c5\u03c1\u03af\u03b1\u03c1\u03c7\u03bf \u03c4\u03cd\u03c0\u03bf (129). \u03a4\u03bf 85% \u03c4\u03c9\u03bd \u03c0\u03b5\u03c1\u03b9\u03c0\u03c4\u03ce\u03c3\u03b5\u03c9\u03bd \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03bf\u03cd\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03ad\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c4\u03bf \u03bf\u03c0\u03bf\u03af\u03bf \u03b4\u03b9\u03b1\u03c6\u03ad\u03c1\u03b5\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u03c3\u03c0\u03bf\u03c1\u03b1\u03b4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03bf\u03c1\u03c6\u03ad\u03c2 \u03c3\u03c4\u03bf \u03cc\u03c4\u03b9 \u03b5\u03bc\u03c6\u03b1\u03bd\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bd\u03b5\u03b1\u03c1\u03cc\u03c4\u03b5\u03c1\u03b7 \u03b7\u03bb\u03b9\u03ba\u03af\u03b1, \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03b9\u03bf \u03c3\u03c5\u03c7\u03bd\u03ac \u03c0\u03bf\u03bb\u03c5\u03b5\u03c3\u03c4\u03b9\u03b1\u03ba\u03cc \u03ba\u03b1\u03b9 \u03ad\u03c7\u03b5\u03b9 \u03c5\u03c8\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03bf \u03b2\u03b1\u03b8\u03bc\u03cc \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1\u03c2 \u03ba\u03b1\u03b9 \u03c5\u03c8\u03b7\u03bb\u03cc\u03c4\u03b5\u03c1\u03b7 \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae\u03c2.<\/p>\n

\u0397 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae \u03b2\u03ac\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03bf\u03cd\u03c2 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03c4\u03b5\u03c1\u03bf\u03b3\u03b5\u03bd\u03ae\u03c2 (130,131). \u03a3\u03c9\u03bc\u03b1\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd BRAF \u03ae RAS \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03ad\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c3\u03b5 \u03af\u03b4\u03b9\u03b1 \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03bc\u03b5 \u03c4\u03b9\u03c2 \u03c3\u03c0\u03bf\u03c1\u03b1\u03b4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03bf\u03c1\u03c6\u03ad\u03c2 (129). \u03a9\u03c3\u03c4\u03cc\u03c3\u03bf \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03cc\u03c4\u03b9 \u03b7 \u03c3\u03c5\u03c7\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03b8\u03b7\u03bb\u03c9\u03b4\u03ce\u03bd \u03bf\u03b9\u03ba\u03bf\u03b3\u03b5\u03bd\u03ce\u03bd \u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03ac\u03c4\u03c9\u03bd \u03c3\u03c5\u03c3\u03c7\u03b5\u03c4\u03b9\u03b6\u03cc\u03bc\u03b5\u03bd\u03c9\u03bd \u03bc\u03b5 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 \u03c3\u03c4\u03bf BRAF \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf \u03b1\u03c5\u03be\u03ac\u03bd\u03b5\u03b9 \u03b1\u03c0\u03cc \u03c0\u03b5\u03c1\u03b9\u03b2\u03b1\u03bb\u03bb\u03bf\u03bd\u03c4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b5\u03c2, \u03cc\u03c0\u03c9\u03c2 \u03b7 \u03b1\u03c5\u03be\u03b7\u03bc\u03ad\u03bd\u03b7 \u03c0\u03c1\u03cc\u03c3\u03bb\u03b7\u03c8\u03b7 \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 (132).<\/p>\n

5. \u03a1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03c9\u03bd \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03c3\u03c4\u03b7\u03bd \u03c0\u03c1\u03bf\u03b5\u03b3\u03c7\u03b5\u03b9\u03c1\u03b7\u03c4\u03b9\u03ba\u03ae \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 <\/b><\/h4>\n

\u039f \u03ba\u03af\u03bd\u03b4\u03c5\u03bd\u03bf\u03c2 \u03ba\u03b1\u03ba\u03bf\u03ae\u03b8\u03b5\u03b9\u03b1\u03c2 \u03c3\u03b5 \u03b1\u03c1\u03bd\u03b7\u03c4\u03b9\u03ba\u03ac \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03b4\u03b5\u03af\u03b3\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5\u03c4\u03ac \u03b1\u03c0\u03cc \u03c0\u03b1\u03c1\u03b1\u03ba\u03ad\u03bd\u03c4\u03b7\u03c3\u03b7 \u03cc\u03b6\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03bc\u03b9\u03ba\u03c1\u03cc\u03c4\u03b5\u03c1\u03bf\u03c2 \u03b1\u03c0\u03cc 3% \u03b5\u03c0\u03bf\u03bc\u03ad\u03bd\u03c9\u03c2 \u03b7 \u03c7\u03c1\u03ae\u03c3\u03b7 \u03c4\u03c9\u03bd \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03c3\u03b5 \u03b1\u03c5\u03c4\u03bf\u03cd\u03c2 \u03c4\u03bf\u03c5\u03c2 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03b4\u03b5\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03c4\u03cc\u03c3\u03bf \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ae. \u0391\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 \u03c3\u03c4\u03b1 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ac \u03b4\u03b5\u03af\u03b3\u03bc\u03b1\u03c4\u03b1 \u03bc\u03b5 \u03b1\u03c4\u03c5\u03c0\u03af\u03b1 (indeterminate) \u03b7 \u03b1\u03bd\u03ac\u03bb\u03c5\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7 \u03c3\u03b5 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03cd\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b9\u03b4\u03b9\u03b1\u03af\u03c4\u03b5\u03c1\u03b1 \u03c7\u03c1\u03ae\u03c3\u03b9\u03bc\u03b7. \u03a3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b1 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7\u03c2 \u03c3\u03c4\u03bf \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf BRAF \u03b5\u03af\u03bd\u03b1\u03b9 \u03b4\u03b9\u03b1\u03b3\u03bd\u03c9\u03c3\u03c4\u03b9\u03ba\u03ae \u03b3\u03b9\u03b1 \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 133<\/sup>. \u03a4\u03bf \u03af\u03b4\u03b9\u03bf \u03b9\u03c3\u03c7\u03cd\u03b5\u03b9 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03c4\u03bf \u03c7\u03b9\u03bc\u03b1\u03b9\u03c1\u03b9\u03ba\u03cc \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf RET\/PTC \u03c0\u03bf\u03c5 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03b9\u03b4\u03b9\u03ba\u03cc \u03b3\u03b9\u03b1 \u03c4\u03bf \u03b8\u03b7\u03bb\u03ce\u03b4\u03b5\u03c2 \u03bd\u03b5\u03cc\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1. \u0391\u03bd\u03c4\u03af\u03b8\u03b5\u03c4\u03b1 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 RAS \u03b4\u03b5\u03bd \u03c0\u03c1\u03bf\u03c3\u03c6\u03ad\u03c1\u03bf\u03c5\u03bd \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03ac \u03ba\u03b1\u03b8\u03ce\u03c2 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b5\u03bd\u03b4\u03b5\u03b9\u03ba\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ae \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03bd\u03b5\u03bf\u03c0\u03bb\u03ac\u03c3\u03bc\u03b1\u03c4\u03bf\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03ae \u03ba\u03b1\u03bb\u03bf\u03ae\u03b8\u03bf\u03c5\u03c2 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03b1\u03b4\u03b5\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2. \u039c\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03ad\u03c7\u03bf\u03c5\u03bd \u03b4\u03b5\u03af\u03be\u03b5\u03b9 \u03cc\u03c4\u03b9 \u03b7 \u03c4\u03b1\u03c5\u03c4\u03cc\u03c7\u03c1\u03bf\u03bd\u03b7 \u03b1\u03bd\u03b1\u03b6\u03ae\u03c4\u03b7\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03b5\u03bd\u03cc\u03c2 \u03c3\u03c5\u03bd\u03cc\u03bb\u03bf\u03c5 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd (BRAF, RET\/PTC, Ras, \u03ba\u03b1\u03b9 PAX8\/PPARG1) \u03c3\u03b5 \u03b4\u03b5\u03af\u03b3\u03bc\u03b1\u03c4\u03b1 FNA \u03c0\u03bf\u03c5 \u03c7\u03b1\u03c1\u03b1\u03ba\u03c4\u03b7\u03c1\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c9\u03c2 \u03b8\u03c5\u03bb\u03b1\u03ba\u03b9\u03ce\u03b4\u03bf\u03c5\u03c2 \u03bc\u03bf\u03c1\u03c6\u03bf\u03bb\u03bf\u03b3\u03af\u03b1\u03c2 \u03ae \u03b1\u03b4\u03b9\u03b5\u03c5\u03ba\u03c1\u03af\u03bd\u03b9\u03c3\u03c4\u03b1, \u03b1\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03b8\u03b5\u03c4\u03b9\u03ba\u03ae, \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03ae\u03c3\u03b5\u03b9 \u03c3\u03c5\u03bc\u03c0\u03bb\u03b7\u03c1\u03c9\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03bf\u03c1\u03b8\u03ae \u03b4\u03b9\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03b7 \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd (134).<\/p>\n

\u039c\u03b9\u03b1 \u03b5\u03bd\u03b1\u03bb\u03bb\u03b1\u03ba\u03c4\u03b9\u03ba\u03ae \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03c4\u03c9\u03bd \u03b1\u03b4\u03b9\u03b5\u03c5\u03ba\u03c1\u03af\u03bd\u03b9\u03c3\u03c4\u03c9\u03bd \u03b4\u03b5\u03b9\u03b3\u03bc\u03ac\u03c4\u03c9\u03bd \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ae\u03c2 \u03b5\u03be\u03ad\u03c4\u03b1\u03c3\u03b7\u03c2 \u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03ac\u03bd\u03b5\u03b9 \u03c4\u03b7\u03bd \u03c0\u03c1\u03bf\u03c3\u03b8\u03ae\u03ba\u03b7 \u03c3\u03c4\u03b1 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9, \u03b1\u03bd\u03ac\u03bb\u03c5\u03c3\u03b7\u03c2 miRNA \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03c0\u03c1\u03bf\u03c3\u03b4\u03b9\u03bf\u03c1\u03b9\u03c3\u03bc\u03cc \u03b2\u03b9\u03bf\u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03c3\u03c4\u03bf\u03bd \u03bf\u03c1\u03cc \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd, \u03c0\u03b5\u03c1\u03b9\u03bb\u03b1\u03bc\u03b2\u03b1\u03bd\u03bf\u03bc\u03ad\u03bd\u03c9\u03bd \u03ba\u03b1\u03b9 \u03c0\u03c1\u03c9\u03c4\u03b5\u03ca\u03bd\u03ce\u03bd \u03c0\u03bf\u03c5 \u03c0\u03c1\u03bf\u03ad\u03c1\u03c7\u03bf\u03bd\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b1 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03b1 (135,136).<\/p>\n

6. \u03a1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03c9\u03bd \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03c3\u03c4\u03b7 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03c4\u03bf\u03c5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 <\/b><\/h4>\n

\u039f\u03b9 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03af \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2 \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03bd \u03bd\u03b1 \u03c0\u03b1\u03af\u03be\u03bf\u03c5\u03bd \u03ba\u03b1\u03b8\u03bf\u03c1\u03b9\u03c3\u03c4\u03b9\u03ba\u03cc \u03c1\u03cc\u03bb\u03bf \u03c3\u03c4\u03b9\u03c2 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03c5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b1\u03c0\u03bf\u03c6\u03ac\u03c3\u03b5\u03b9\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2.<\/p>\n

H \u03c0\u03c1\u03bf\u03b5\u03b3\u03c7\u03b5\u03b9\u03c1\u03b7\u03c4\u03b9\u03ba\u03ae \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03bc\u03b5\u03c4\u03ac\u03bb\u03bb\u03b1\u03be\u03b7\u03c2 \u03c3\u03c4\u03bf \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03af\u03b4\u03b9\u03bf BRAF \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03b2\u03bf\u03b7\u03b8\u03ae\u03c3\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03bd\u03b1\u03b3\u03bd\u03ce\u03c1\u03b9\u03c3\u03b7 \u03bc\u03b9\u03ba\u03c1\u03bf\u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03c9\u03bc\u03ac\u03c4\u03c9\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03c0\u03bf\u03c5 \u03b4\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03ac \u03ad\u03c7\u03bf\u03c5\u03bd \u03ba\u03b1\u03ba\u03ae \u03c0\u03c1\u03cc\u03b3\u03bd\u03c9\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03c3\u03c5\u03c7\u03bd\u03ad\u03c2 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ad\u03c2 \u03ba\u03b1\u03b9 \u03bd\u03b1 \u03bf\u03b4\u03b7\u03b3\u03ae\u03c3\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03c0\u03b9\u03bf \u03b5\u03c0\u03b9\u03b8\u03b5\u03c4\u03b9\u03ba\u03ae \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03ae \u03c4\u03bf\u03c5\u03c2. \u03a3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b1 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03bf\u03b4\u03b7\u03b3\u03ae\u03c3\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03c0\u03cc\u03c6\u03b1\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c7\u03bf\u03c1\u03ae\u03b3\u03b7\u03c3\u03b7 \u03c1\u03b1\u03b4\u03b9\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03cd \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 \u03b3\u03b9\u03b1 \u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03c1\u03bf\u03c6\u03ae \u03c4\u03bf\u03c5 \u03c5\u03c0\u03bf\u03bb\u03b5\u03af\u03bc\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03bc\u03b5\u03c4\u03ac \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b5\u03ba\u03c4\u03bf\u03bc\u03ae (ablation) \u03b1\u03ba\u03cc\u03bc\u03b7 \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03c7\u03b1\u03bc\u03b7\u03bb\u03bf\u03cd \u03ba\u03b9\u03bd\u03b4\u03cd\u03bd\u03bf\u03c5 (126) \u03b1\u03c0\u03bf\u03ba\u03b1\u03b8\u03b9\u03c3\u03c4\u03ce\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b7 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03c3\u03c6\u03b1\u03b9\u03c1\u03af\u03bd\u03b7 (Tg) \u03c9\u03c2 \u03b1\u03be\u03b9\u03cc\u03c0\u03b9\u03c3\u03c4\u03bf \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03b9\u03ba\u03cc \u03b4\u03b5\u03af\u03ba\u03c4\u03b7 \u03c0\u03b1\u03c1\u03b1\u03ba\u03bf\u03bb\u03bf\u03cd\u03b8\u03b7\u03c3\u03b7\u03c2. \u0395\u03c0\u03af\u03c3\u03b7\u03c2 \u03b5\u03bd\u03b4\u03ad\u03c7\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03b2\u03bf\u03b7\u03b8\u03ae\u03c3\u03b5\u03b9 \u03c3\u03c4\u03b7\u03bd \u03b1\u03c0\u03cc\u03c6\u03b1\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b1\u03c5\u03c4\u03cc\u03c7\u03c1\u03bf\u03bd\u03bf \u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03cc \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03b5\u03bd\u03b9\u03ba\u03cc \u03ba\u03b1\u03b8\u03b1\u03c1\u03b9\u03c3\u03bc\u03cc \u03bc\u03b1\u03b6\u03af \u03bc\u03b5 \u03bf\u03bb\u03b9\u03ba\u03ae \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03b5\u03ba\u03c4\u03bf\u03bc\u03ae, \u03ba\u03b1\u03b8\u03ce\u03c2 \u03b7 \u03cd\u03c0\u03b1\u03c1\u03be\u03b7 \u03c4\u03bf\u03c5 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c5\u03c0\u03bf\u03c4\u03c1\u03bf\u03c0\u03ae \u03b8\u03b7\u03bb\u03ce\u03b4\u03bf\u03c5\u03c2 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c3\u03c5\u03bd\u03ae\u03b8\u03c9\u03c2 \u03c3\u03b5 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03ad\u03bd\u03b5\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03b5\u03bd\u03c4\u03c1\u03b9\u03ba\u03bf\u03cd \u03b4\u03b9\u03b1\u03bc\u03b5\u03c1\u03af\u03c3\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c3\u03b5 \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc 75-95% \u03ba\u03b1\u03b9 \u03b5\u03c0\u03b1\u03bd\u03b5\u03b3\u03c7\u03b5\u03af\u03c1\u03b7\u03c3\u03b7 \u03c3\u03c4\u03b7\u03bd \u03c0\u03b5\u03c1\u03b9\u03bf\u03c7\u03ae (137,138).<\/p>\n

\u0388\u03bd\u03b1\u03c2 \u03ac\u03bb\u03bb\u03bf\u03c2 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03c9\u03bd \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03ce\u03bd \u03b4\u03b5\u03b9\u03ba\u03c4\u03ce\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03b7 \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03bc\u03b5 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03b1\u03c4\u03b9\u03ba\u03cc \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2 \u03b1\u03bd\u03b8\u03b5\u03ba\u03c4\u03b9\u03ba\u03cc \u03c3\u03c4\u03b7\u03bd \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03bc\u03b5 \u03c1\u03b1\u03b4\u03b9\u03b5\u03bd\u03b5\u03c1\u03b3\u03cc \u03b9\u03ce\u03b4\u03b9\u03bf. \u039f \u03c3\u03c4\u03cc\u03c7\u03bf\u03c2 \u03c4\u03c9\u03bd \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ce\u03bd \u03bc\u03b5\u03bb\u03b5\u03c4\u03ce\u03bd \u03c0\u03bf\u03c5 \u03b4\u03b9\u03b5\u03be\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03ae\u03bc\u03b5\u03c1\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03bc\u03af\u03b1\u03c2 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae\u03c2 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ae\u03c2 \u03ba\u03b1\u03b9 \u03b7 \u03c3\u03c4\u03bf\u03c7\u03b5\u03c5\u03bc\u03ad\u03bd\u03b7 \u03c6\u03b1\u03c1\u03bc\u03b1\u03ba\u03b5\u03c5\u03c4\u03b9\u03ba\u03ae \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03c3\u03c4\u03bf\u03c5\u03c2 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 (139). M\u03ad\u03c7\u03c1\u03b9 \u03c4\u03ce\u03c1\u03b1 \u03bc\u03b5\u03bb\u03b5\u03c4\u03ce\u03bd\u03c4\u03b1\u03b9 \u03b5\u03c5\u03c1\u03ad\u03c9\u03c2 \u03c6\u03ac\u03c1\u03bc\u03b1\u03ba\u03b1 \u03ad\u03bd\u03b1\u03bd\u03c4\u03b9 \u03c4\u03b7\u03c2 \u03b1\u03b3\u03b3\u03b5\u03b9\u03bf\u03b3\u03ad\u03bd\u03b5\u03c3\u03b7\u03c2 \u03ba\u03b1\u03b8\u03ce\u03c2 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03b5\u03af\u03c2 \u03c4\u03c9\u03bd \u03ba\u03b9\u03bd\u03b1\u03c3\u03ce\u03bd \u03c4\u03bf\u03c5 \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03bf\u03cd MAPK (\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 7<\/b>). H \u03b1\u03bd\u03c4\u03b9\u03bd\u03b5\u03bf\u03c0\u03bb\u03b1\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ae \u03b9\u03ba\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03b1\u03c5\u03c4\u03ce\u03bd \u03c4\u03c9\u03bd \u03c0\u03b1\u03c1\u03b1\u03b3\u03cc\u03bd\u03c4\u03c9\u03bd \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03bf \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ae \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u03ba\u03c5\u03c4\u03c4\u03b1\u03c1\u03bf\u03c4\u03bf\u03be\u03b9\u03ba\u03ad\u03c2 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b5\u03c2 \u03bc\u03b5 \u03bc\u03b5\u03c1\u03b9\u03ba\u03ae \u03b1\u03bd\u03c4\u03b1\u03c0\u03cc\u03ba\u03c1\u03b9\u03c3\u03b7 \u03c3\u03b5 0-59% \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03c3\u03b5 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03c6\u03ac\u03c3\u03b7\u03c2 2 \u03ba\u03b1\u03b9 \u03bc\u03b1\u03ba\u03c1\u03bf\u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03c3\u03c4\u03b1\u03b8\u03b5\u03c1\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 \u03c3\u03b5 \u03ac\u03bb\u03bb\u03bf \u03ad\u03bd\u03b1 \u03c4\u03c1\u03af\u03c4\u03bf \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd (140,141,142). \u03a4\u03b1 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03b1 \u03c6\u03ac\u03c1\u03bc\u03b1\u03ba\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03b9\u03bf \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03c3\u03b5 \u03bc\u03b5\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03b5\u03bd\u03c4\u03bf\u03c0\u03af\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03bb\u03b5\u03bc\u03c6\u03b1\u03b4\u03ad\u03bd\u03b5\u03c2, \u03ae\u03c0\u03b1\u03c1, \u03ba\u03b1\u03b9 \u03c0\u03bd\u03b5\u03cd\u03bc\u03bf\u03bd\u03b5\u03c2 \u03c0\u03b1\u03c1\u03ac \u03c3\u03c4\u03b1 \u03bf\u03c3\u03c4\u03ac. \u03a9\u03c3\u03c4\u03cc\u03c3\u03bf \u03b1\u03c0\u03b1\u03b9\u03c4\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03c0\u03b5\u03c1\u03b9\u03c3\u03c3\u03cc\u03c4\u03b5\u03c1\u03b5\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03c3\u03b5 \u03c0\u03b5\u03b9\u03c1\u03b1\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03bc\u03bf\u03bd\u03c4\u03ad\u03bb\u03b1 \u03b3\u03b9\u03b1 \u03bd\u03b1 \u03b4\u03b9\u03b5\u03c1\u03b5\u03c5\u03bd\u03b7\u03b8\u03b5\u03af \u03b7 \u03c3\u03c5\u03c3\u03c7\u03ad\u03c4\u03b9\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03be\u03cd \u03c4\u03b7\u03c2 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03c3\u03bc\u03b1\u03c4\u03b9\u03ba\u03cc\u03c4\u03b7\u03c4\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03c6\u03b1\u03c1\u03bc\u03ac\u03ba\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ae\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03bd\u03b5\u03c5\u03c1\u03af\u03c3\u03ba\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf\u03bd \u03cc\u03b3\u03ba\u03bf.<\/p>\n

\u0388\u03bd\u03b1\u03c2 \u03ac\u03bb\u03bb\u03bf\u03c2 \u03c4\u03c1\u03cc\u03c0\u03bf\u03c2 \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03b7\u03c2 \u03b1\u03c5\u03c4\u03ce\u03bd \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03b5\u03af\u03bd\u03b1\u03b9 \u03b7 \u03b1\u03c0\u03bf\u03ba\u03b1\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03b9\u03ba\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1\u03c2 \u03c0\u03c1\u03cc\u03c3\u03bb\u03b7\u03c8\u03b7\u03c2 \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 \u03b1\u03c0\u03cc \u03c4\u03b1 \u03ba\u03b1\u03c1\u03ba\u03b9\u03bd\u03b9\u03ba\u03ac \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1 \u03ba\u03b1\u03b9 \u03b1\u03ba\u03bf\u03bb\u03bf\u03cd\u03b8\u03c9\u03c2 \u03b7 \u03c7\u03bf\u03c1\u03ae\u03b3\u03b7\u03c3\u03b7 \u03c1\u03b1\u03b4\u03b9\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03cd \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 \u03bc\u03b5\u03c4\u03ac \u03c0\u03c1\u03bf\u03b5\u03c4\u03bf\u03b9\u03bc\u03b1\u03c3\u03af\u03b1 \u03bc\u03b5 TSH. \u0391\u03c5\u03c4\u03ae \u03b7 \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03c5\u03c0\u03bf\u03c3\u03c4\u03b7\u03c1\u03af\u03c7\u03c4\u03b7\u03ba\u03b5 \u03b1\u03c0\u03cc in vitro \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03cc\u03c0\u03bf\u03c5 \u03b7 \u03c7\u03bf\u03c1\u03ae\u03b3\u03b7\u03c3\u03b7 \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03ad\u03c9\u03bd \u03c4\u03c9\u03bd \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd BRAF, MEK, \u03ae AKT \u03c3\u03c4\u03b1 \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 MAPK \u03ba\u03b1\u03b9 PI3K-AKT \u03bc\u03c0\u03bf\u03c1\u03bf\u03cd\u03c3\u03b5 \u03bd\u03b1 \u03b1\u03c0\u03bf\u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03ae\u03c3\u03b5\u03b9 \u03c4\u03b7\u03bd \u03ad\u03ba\u03c6\u03c1\u03b1\u03c3\u03b7 \u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03c9\u03bd \u03c3\u03c4\u03bf\u03bd \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03ba\u03b1\u03b9 \u03c4\u03b7\u03bd \u03c0\u03c1\u03cc\u03c3\u03bb\u03b7\u03c8\u03b7 \u03c1\u03b1\u03b4\u03b9\u03b5\u03bd\u03b5\u03c1\u03b3\u03bf\u03cd \u03b9\u03c9\u03b4\u03af\u03bf\u03c5 (143). \u03a4\u03b1 \u03b5\u03c5\u03c1\u03ae\u03bc\u03b1\u03c4\u03b1 \u03b1\u03c5\u03c4\u03ac \u03b5\u03c0\u03b9\u03b2\u03b5\u03b2\u03b1\u03b9\u03ce\u03b8\u03b7\u03ba\u03b1\u03bd \u03b1\u03c1\u03b3\u03cc\u03c4\u03b5\u03c1\u03b1 \u03ba\u03b1\u03b9 \u03bc\u03b5 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 in vivo (144,145). T\u03b1 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ac \u03c3\u03c4\u03bf\u03b9\u03c7\u03b5\u03af\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b9\u03b4\u03b9\u03b1\u03af\u03c4\u03b5\u03c1\u03b1 \u03b5\u03bd\u03b8\u03b1\u03c1\u03c1\u03c5\u03bd\u03c4\u03b9\u03ba\u03ac \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03ad\u03b1 \u03c4\u03b7\u03c2 \u039c\u0395\u039a \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 selumetinib \u03b9\u03b4\u03b9\u03b1\u03af\u03c4\u03b5\u03c1\u03b1 \u03c3\u03b5 \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf\u03c5\u03c2 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03ae \u03c0\u03bf\u03c5 \u03c6\u03ad\u03c1\u03bf\u03c5\u03bd \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03c4\u03bf\u03c5 \u03bf\u03b3\u03ba\u03bf\u03b3\u03bf\u03bd\u03b9\u03b4\u03af\u03bf\u03c5 RAS (145).<\/p>\n

\u039f\u03b9 \u03b1\u03bd\u03b5\u03c0\u03b9\u03b8\u03cd\u03bc\u03b7\u03c4\u03b5\u03c2 \u03b5\u03bd\u03ad\u03c1\u03b3\u03b5\u03b9\u03b5\u03c2 \u03c4\u03c9\u03bd \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03ad\u03c9\u03bd \u03c4\u03c9\u03bd \u03ba\u03b9\u03bd\u03b1\u03c3\u03ce\u03bd (\u03ba\u03b1\u03ba\u03bf\u03c5\u03c7\u03af\u03b1, \u03b4\u03b9\u03ac\u03c1\u03c1\u03bf\u03b9\u03b1, \u03c5\u03c0\u03ad\u03c1\u03c4\u03b1\u03c3\u03b7 \u03ba\u03b1\u03b9 \u03b4\u03b5\u03c1\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03b5\u03be\u03b1\u03bd\u03b8\u03ae\u03bc\u03b1\u03c4\u03b1) \u03ad\u03c7\u03bf\u03c5\u03bd \u03bf\u03b4\u03b7\u03b3\u03ae\u03c3\u03b5\u03b9 \u03c3\u03b5 \u03bc\u03b5\u03af\u03c9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03b4\u03cc\u03c3\u03b7\u03c2 \u03c3\u03c4\u03bf 11-73% \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd \u03ba\u03b1\u03b9 \u03c3\u03b5 \u03b4\u03b9\u03b1\u03ba\u03bf\u03c0\u03ae \u03c4\u03bf\u03c5 \u03c6\u03b1\u03c1\u03bc\u03ac\u03ba\u03bf\u03c5 \u03c3\u03c4\u03bf 7-25% \u03c4\u03c9\u03bd \u03b1\u03c3\u03b8\u03b5\u03bd\u03ce\u03bd. \u0395\u03c0\u03bf\u03bc\u03ad\u03bd\u03c9\u03c2 \u03b8\u03b1 \u03c0\u03c1\u03ad\u03c0\u03b5\u03b9 \u03bd\u03b1 \u03c7\u03bf\u03c1\u03b7\u03b3\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03b5\u03c0\u03b9\u03bb\u03b5\u03b3\u03bc\u03ad\u03bd\u03bf\u03c5\u03c2 \u03b1\u03c3\u03b8\u03b5\u03bd\u03b5\u03af\u03c2 \u03bc\u03b5 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc \u03c6\u03bf\u03c1\u03c4\u03af\u03bf \u03cc\u03b3\u03ba\u03bf\u03c5 \u03ba\u03b1\u03b9 \u03b5\u03ba\u03c4\u03b5\u03c4\u03b1\u03bc\u03ad\u03bd\u03b7 \u03bd\u03cc\u03c3\u03bf \u03cc\u03c0\u03bf\u03c5 \u03b7 \u03c0\u03b9\u03b8\u03b1\u03bd\u03cc\u03c4\u03b7\u03c4\u03b1 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03b1\u03bd\u03c4\u03b1\u03c0\u03cc\u03ba\u03c1\u03b9\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b7 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c5\u03c8\u03b7\u03bb\u03ae \u03bc\u03b5 \u03b2\u03ac\u03c3\u03b7 \u03c4\u03b7\u03bd \u03b1\u03bd\u03b5\u03cd\u03c1\u03b5\u03c3\u03b7 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03c3\u03c4\u03bf\u03c5\u03c2 \u03b1\u03bd\u03c9\u03c4\u03ad\u03c1\u03c9 \u03bc\u03bf\u03c1\u03b9\u03b1\u03ba\u03bf\u03cd\u03c2 \u03b4\u03b5\u03af\u03ba\u03c4\u03b5\u03c2.<\/p>\n

\n

\u00a0\"10.22-figure7\"<\/b><\/p>\n

\u0395\u03b9\u03ba\u03cc\u03bd\u03b1 7.<\/em> <\/b>MAPK \u03ba\u03b1\u03b9 PI3K-AKT-MTOR \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 – \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03b9\u03c2 \u03ba\u03b1\u03b9 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03c5\u03c4\u03b9\u03ba\u03bf\u03af \u03c3\u03c4\u03cc\u03c7\u03bf\u03b9 \u03c3\u03c4\u03bf\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a4\u03b1 \u03b4\u03cd\u03bf \u03ba\u03bb\u03b1\u03c3\u03c3\u03b9\u03ba\u03ac \u03bc\u03bf\u03bd\u03bf\u03c0\u03ac\u03c4\u03b9\u03b1 \u03c3\u03b7\u03bc\u03b1\u03c4\u03bf\u03b4\u03cc\u03c4\u03b7\u03c3\u03b7\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03b5 \u03c3\u03cd\u03b6\u03b5\u03c5\u03be\u03b7 \u03bc\u03b5 \u03c4\u03bf\u03bd \u03c5\u03c0\u03bf\u03b4\u03bf\u03c7\u03ad\u03b1 \u03c4\u03c5\u03c1\u03bf\u03c3\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b9\u03bd\u03ac\u03c3\u03b7\u03c2 (RTK) \u03c3\u03c4\u03b7\u03bd \u03b5\u03c0\u03b9\u03c6\u03ac\u03bd\u03b5\u03b9\u03b1 \u03c4\u03bf\u03c5 \u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03bf\u03c5 \u03bf \u03bf\u03c0\u03bf\u03af\u03bf\u03c2 \u03bc\u03b5\u03c4\u03b1\u03c6\u03ad\u03c1\u03b5\u03b9 \u03c4\u03b1 \u03b5\u03be\u03c9\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03b1 \u03bc\u03b7\u03bd\u03cd\u03bc\u03b1\u03c4\u03b1 \u03b1\u03cd\u03be\u03b7\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03b5\u03bd\u03b4\u03bf\u03ba\u03c5\u03c4\u03c4\u03ac\u03c1\u03b9\u03b1 \u03bc\u03b7\u03bd\u03cd\u03bc\u03b1\u03c4\u03b1 \u03b4\u03b9\u03b1\u03bc\u03ad\u03c3\u03bf\u03c5 \u03c4\u03c9\u03bd \u03bc\u03bf\u03bd\u03bf\u03c0\u03b1\u03c4\u03b9\u03ce\u03bd \u03b1\u03c5\u03c4\u03ce\u03bd. *\u03a5\u03c0\u03bf\u03b4\u03b5\u03b9\u03ba\u03bd\u03cd\u03b5\u03b9 \u03c4\u03bf\u03c5\u03c2 \u03b8\u03b5\u03c1\u03b1\u03c0\u03b5\u03c5\u03c4\u03b9\u03ba\u03bf\u03cd\u03c2 \u03c3\u03c4\u03cc\u03c7\u03bf\u03c5\u03c2 \u03c0\u03bf\u03c5 \u03b5\u03be\u03b5\u03c4\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03ae\u03bc\u03b5\u03c1\u03b1 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ac \u03c3\u03c4\u03bf\u03bd \u03ba\u03b1\u03c1\u03ba\u03af\u03bd\u03bf \u03c4\u03bf\u03c5 \u03b8\u03c5\u03c1\u03b5\u03bf\u03b5\u03b9\u03b4\u03bf\u03cd\u03c2. \u03a0\u03b7\u03b3\u03ae: (146).<\/p>\n

\n

\u0392\u03b9\u03b2\u03bb\u03b9\u03bf\u03b3\u03c1\u03b1\u03c6\u03af\u03b1<\/h4>\n

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Created: October 27, 2014
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