| Lung cancer is now most of the major causes of cancer deaths in China,the early diagnosis and early treatment,precisely targeted therapy of lung cancer is a hot spot in the present study.This thesis mainly divided into two parts,In the first part: large cell lung cancer as a rare type of lung cancer,its incidence is low,the diagnosis is difficult,its rapid growth,the whole body transfer occurs early,prognosis than other types of non-small cell lung cancer is poor,so improve the clinical diagnosis of large cell lung cancer has the very vital significance.Large cell lung cancer is to point to not have a scale cancer,gland cancer,small cell lung cancer pathological characteristics of non-small cell lung cancer.Syn,CD56 and Cg A pathological markers to distinguish large cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma,but the diagnosis of sensitivity,accuracy is not high.Secretagogin(SCGN)is a digestive system tumor markers for the newly found,the study found that the combination of clinical classic Maker can improve the accuracy of diagnosis.But in the large cell neuroendocrine carcinoma express few case studies.In this study,we examined in 33 cases of large cell lung cancer and lung cancer cell line SCGN expression,and further analysis SCGN express positive patients with the clinical features,explore it as a new neuroendocrine markers to detect large cell lung cancer.The second part: the epidermal growth factor receptor gene as an important driver lung adenocarcinoma,in plays an important role in the development of lung cancer.EGFR tyrosine kinase inhibitor has the tumor inhibition.In NSCLC patients with EGFR mutations,EGFR-TKI curative effect is superior to the traditional chemotherapy,and side effects of small patient tolerance.And Rb is important tumor-suppressor genes in the human body,through the process of cell cycle control,inhibit the excessive proliferation of cells.Rb-E2 F pathway is the key to the regulation of the cell cycle signal molecules and pathways,as is often the case,Rb and E2F1 combination,make the E2F1 is not active,but often is various factors lead to Rb inactivation in the tumor,the cell proliferation and lead to cancer.Several studies have confirmed that widespread Rb protein expression in lung cancer.For example,a study shows in non-small cell lung cancer is about 20%-20% Rb protein expression decreased.Therefore Rb anomalies are widespread in the lung cancer,is an important factor of lung cancer.By immunohistochemical detection of 23 cases of EGFR mutations in lung adenocarcinoma patients specimens in Rb,expression and lm-pRb lm-pRb-780-780,analysis of the relationship with the patient's clinical information,investigate whether the use of the cell cycle inhibitors can effectively inhibit EGFR mutations in the malignant cell proliferation.The first part:(1).In the first place we verificate the expression of CD56,SCGN Cg A,Syn in A549 H661 H1650,H292,H358,HEK293,3 t3 cell line by Western Blot,and,results shows Syn,SCGN with Cg A expressed high in H1650,in H358 H292 and H661 were lower expression or not,has a certain relevance,CD56 only high expression in A549 cell line.We verified cell immunohistochemical study further SCGN expression and expression in lung cancer cell line position,the results suggest: SCGN in immunohistochemical staining results are consistent with the result of immune protein imprinting.In HEK293 and A549 high expression and expression in the nucleus and cytoplasm.Further in the A549 cell line for immunofluorescence,a total of four Maker localization testing,the results shown in A549 cells exist in the localization expression(2)by immunohistochemistry and immunofluorescence test in 33 cases before surgery in the diagnosis of large cell lung cancer specimens of value SCGN expression and the expression with the other three kinds of Maker position relations.(2)by immunohistochemistry and immunofluorescence test in 33 cases before surgery in the diagnosis of large cell lung cancer specimens of value SCGN expression and the expression with the other three kinds of Maker position relations.The second part: in 23 cases of EGFR mutations in lung adenocarcinoma patients with cancers and lung cancer in normal lung tissue,respectively to Rb,pRb-780,pRb-795 immunohistochemical staining.Results in up to 69.6% of patients with Rb express lower/missing,pRb-780 staining enhancement in 73.9% of patients,69.6% of patients exist pRb-795 expression.Rb patients with clinical pathological physiological characteristics analysis found that in different age,sex,smoking history,clinical stage,tumor location and different EGFR mutations in patients with no significant difference.Further analysis of Rb,pRb-780,pRb-795 expression of the relationship with the patients' clinical information,Rb in lung cancer patients with clinical pathologic physiology characteristic analysis found that with age,sex,smoking history,clinical stage,tumor location and different EGFR mutations have no significant difference;pRb-780 protein in patients with stage III/IV,in comparison with patients with stage I/II pRb-780 protein expression rate higher,difference was statistically significant(P = 0.022).pRb-795 in patients with stage I/II,compared to patients with stage III/IV more existed expression,but the difference was not significant(P = 0.074).Conclusion:1.SCGN in lung cancer cell lines and large cell lung cancer in the high expression,we by immunofluorescence,immunohistochemical confirmed SCGN and CD56,Cg A,Syn,expression of positioning,moreover SCGN expression positive rate of dyeing was significantly higher than that of other neuroendocrine markers,these data explain SCGN can alone or with other markers for the diagnosis of neuroendocrine tumor.2.23 cases of EGFR mutations in patients with lung adenocarcinoma Rb protein absent or reduced,and the excessive phosphorylation of Rb,in EGFR mutations in lung adenocarcinoma patients,frequent expression of Rb absent/reduced or excessive phosphorylation,dysfunction of Rb EGFR mutations in patients with lung adenocarcinoma is important pathogenesis. |
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