Clinical Researth Of EGFR Gene Mutations In Non Small Cell Lung Cancer

Part ⅠThe relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinomaABSTRACTObjective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:297 patients from July 2009 to May 2013 were chosen as objects, all of them were treated with Amplification Refractory Mutation System to detect EGFR gene mutation. Study the relevance of EGFR gene mutation with clinical and pathological features in patients, and compare the prognosis of EGFR-mutant-patients and that of EGFR-wide-type-patients.Results:There were 136 cases with mutation in all 297 patients, and The rate of EGFR mutation was 45.79%. Among them,8 cases(5.9%) had exon 18 mutation,82 cases (60.3%) had exon 19 mutation,52 cases (38.2%) had exon 21 mutation,2 cases had exon 18 and 19 mutations,4 cases had exon 19 and 21 mutations. There were 15 cases of exon 20 mutation in patients of wild type. EGFR gene mutation has no significant relevance with age, gender, smoking history, family history of cancer and clinical stage (P>0.05); the relevance between EGFR gene mutation and blood type, pathologic types, differentiation and diameter of cancer has statistical significance (P < 0.05). The difference between prognosis of EGFR-mutant-patients and that of EGFR-wide type-patients has statistical significance (P<0.05)Conclusion:EGFR gene mutation was common in patients who were female, non-smoking, in earlier tumor stage, with smaller size and higher degree of differentiation tumor. It was more common in patients with adenocarcinoma. And pathological features of patients were independent predictors of EGFR mutations.The prognosis of patients with EGFR mutation was significantly better than the one of wild-type patients.Part ⅡThe relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinomaABSTRACTAlthough patients with non-small cell lung cancer (NSCLC) experience an initial response to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib, those individuals with activating mutations in EGFR develop resistance. Gambogic acid (GA), a polyprenylated xanthone, has strong antitumor activities. In the present study, the therapeutic efficacy of gefitinib with GA was evaluated in a gefitinib-resistant NSCLC model. The NCI-H1975 cell line with EGFR-T790M mutation was subcutaneously injected into immunocompromised mice. The mice were randomly assigned to receive treatment with gefitinib, GA, gefitinib plus GA, or vehicle for 4 weeks, then all mice were sacrificed and their tumor tissues were subjected to caspase activity detection and western blot analysis. Gefitinib and GA alone slightly inhibited the tumor growth of NCI-H1975. However, the combined treat-ment significantly enhanced their antitumor effects, without any marked adverse events. In addition, gefitinib plus GA enhanced the level of apoptosis in the tumor tissues. Western blot analysis also revealed that the combination treatment reduced the phosphorylation level of AKT, MEK1/2 and ERK1/2, while an increased expression ratio of Bax/Bcl-2 was observed. In the current study, gefitinib in combination with GA resulted in antitumor growth in the EGFR-T790M secondary mutation NCI-H1975 tumor model due to an enhanced apoptotic effect.This novel therapeutic strategy may be a practical approach for the treatment of patients who show gefitinib resistance.