臺灣博碩士論文加值系統

細胞訊息傳遞的通路對細胞的生長，分化，凋亡或抗凋亡有直接密切的關係。 當上皮細胞生長因子與上皮細胞生長因子接受體結合，造成酥胺酸激酶活化而把訊息下傳的通路，對上皮細胞的癌化有很大的影響。其中包括癌細胞的增生、癌細胞的抗凋亡、癌細胞的轉移、血管的新生、甚至引起對化學藥物治療或對放射線治療的抗藥性。
標靶治療是目前癌症治療的新發展。其中酥胺酸激酶抑制劑的臨床應用在慢性骨髓性白血病、腸胃基質瘤、以及非小細胞肺癌更是近兩三年來的熱門題目。特別是酥胺酸激酶抑制劑之所以對這些癌症有效，主要是酥胺酸激酶主體上有些基因的突變造成額外功能的增加或造成酥胺酸激酶的過度活化。相對的，也因此讓這些癌細胞對酥胺酸激酶抑制劑的作用特別敏感。
頭頸部癌是東方人比西方人較常發生的一種癌症。在台灣每年頭頸部癌患者死亡的人數是排行癌症的前幾名。而有70-90% 頭頸部癌的患者其癌細胞有上皮細胞生長因子接受體的表現(expression)。本研究即在找出頭頸部癌病人，在高上皮細胞生長因子接受體的基因表現下，其酥胺酸激酶主體及相關的基因ERBB2跟KRAS是否可能有著突變的存在。因為這關係到將來作為使用酥胺酸激酶抑制劑來治療頭頸部癌病人的重要依據。
我們總共分析106個病例的結果，對於在肺腺細胞癌病人常見的基因突變位置，如表皮細胞生長因子接受體表現序列19、21，ERBB2表現序列20，KRAS表現序列2等，幾乎很少有突變發生。顯示依據表皮細胞生長因子接受體有突變的情況，來決定表皮細胞生長因子接受體酥胺酸激酶抑制劑用在肺腺細胞癌的模式並不適合用在頭頸部鱗狀扁平細胞癌的病人身上。

Pathway of cellular signal transduction is important for proliferation, differentiation, apoptosis or anti-apoptosis.
Activation of the EGFR by EGF generates a cascade of intracellular signalling molecules, leading to cell survival and proliferation. However, up-regulated EGFR signalling may also result in progression to invasion and metastasis.
Target therapy is a new anti-cancer approache, which specifically inhibits processes required for tumer cell growth. Currently the tyrosine kinase inhibitor is used for the treatment of chronic myelocytic leukaemia, the gastro-intestinal stroma tumor, and non-small cell lung cancer with dramatic effect. Mutation on gene of EGFR in the tyrosine kinase domain which induced gain of function or hypersensitivity of tyrosine kinase is the mechanism why tyrosine kinase inhibitors work in these malignancies.
Head and neck cancer is more popular in orient people than western people. The mortality number of head and neck cancer in Taiwan is top five among all cancers. The expression of EGFR of head and neck cancer is very high up to 80-100%. In this study we look for mutation on EGFR in patients of head and neck cancers, as well as ERBB2 and KRAS, which will be important evidence to use tyrosine kinase inhibitor for treatment of head and neck cancer.
In this study, we analyzed the hotspot region of EGFR gene (exon19, 21), ERBB2 gene (exon20), and KRAS gene (exon2) in 121 squamous cell carcinoma of head and neck tissue samples from 106 patients. There are only one ERBB2 gene and one KRAS gene mutations noted. The conclusion is that common EGFR mutations conferring sensitivity to ERFG tyrosine inhibitors in lung adenocarcinoma are not prevalent in squamous cell carcinoma of head and neck.

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英文摘要-------------------------------------------------------------------------6.
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討論------------------------------------------------------------------------------31
結論------------------------------------------------------------------------------38
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