| The resistance to chemotherapy in NSCLC is the main cause for low response to chemotherapy. Many drugs can bring about DNA damage , directly block DNA replication and kill the tumor cells. If tumor cells can hinder this effect of drugs or can repair the damaged DNA, then the tumor cells could increase constantly. Alkylation agent can combine with DNA of the tumor cells and form DNA adducts - 06 -methylguanine, which transfer the DAN into crossline and inhibit or kill the tumor cells. O6 - alkylguanine - DNA alkyltransferase ( MGMT) is an important DNA repair protein which can move the 06 -methylguanine form DNA of the tumor cells. In this way, DNA of the tumor cells could be repaired quickly. So MGMT is a drug resistance genes leading to resistance to chemotherapy. According to the level of MGMT in the cells, researchers divided the tumor cells into two groups: Mer + group with higher expression of MGMT and Mer -group with lower or no expression of MGMT. The former has the resistance to chemotherapy and is apt to being damaged by drugs, as well as sensitive to chemotherapy. In this study, we detected the MGMT expression in NSCLC to find out their clinical significance and weather they can be used as a mark of effect to chemotherapy and prognosis.Material and MethodsTumor samples were obtained from 128 patients who underwent resection of NSCLC. 45 cases with recurrent and metastasis focus treated by merely chemotherapy. Then we valued the statistics of effects to chemotherapy and prognosis. Expression of MGMT was examined byimmunohistochemistry S - P method: antigen repair---the sectionswere put in 10 mM sodium citrate (PH =6.0) and heated in pressure cooks for 2 min. The other experiment processes were same to the routine S - P method. To evaluate MGMT expression, a score corresponding to the sum of (a) the percentage of positive cells (0 = < 5% ; 1 = 6% -50% ; 2 = >50% ) and (b) the staining intensity (0= null; 1 = weak; 2 = strong) was established. The scores 0 ~ 1 were classified as negative, 2 ~4 as positive. Standards to value the effects of chemotherapy were as follows: complete response ( CR) ; partial response (PR); no change (NC); progressive (PD). Response rate= CR + PR. Statistical analysis was concluded through x2 test, Kaplan - Meier and log - rank test. A P - value <0.05 was considered to be significant. Drugs such as CTX, ADM, DDP, VP16 and so on were mainly used.ResultsThe expression of MGMT was negative in 10 cases of normal lung tissue, while positive in 61 cases of NSCLC. The positive rate was 47. 66% (61/128). The expression of MGMT had no relationship to patient age, sex, clinical stage and lymph node metastasis, histologicaltype, P>0. 05, but had an relationship to survival time, recurrence and metastasis, P <0.05. Of the 45 cases merely receiving post - operation chemotherapy, the efficiency of chemotherapy of Mer - group was much better than that of Mer + group. They were respectively 42. 86% (9/21) and 4. 17% ( 1/24) , P <0. 001. The average survival time and the 5 - year survival rate in Mer + group were 18 months and 8. 20% , which were significantly lower than those of Mer - group ( 36. 88 months and 29. 85% ) , P <0.01. The Kaplan - Meier survival curves have shown that the expression of MGMT was related to the survival (P<0.05).DiscussionStudies on mechanism of drug resistance genes have shown the molecule base of the resistance to chemotherapy. With the emergence of new drug for lung cancer, the whole curing rate is only about 10% present. Research works have proved that it is mainly because of the resistance to chemotherapy. Many drugs can bring about DNA damage , directly block DNA replication and kill the tumor cells. If tumor cells can hinder this effect of drugs or can repair the damaged DNA, than the tumor cells could increase constantly. Alkylating agents can combine with DNA of the tumor cells and form DNA adducts - 06 -methylguanine, which transfer the DAN into a crossed one and inhibit or kill the tumor cells. 06 - alkylguanine DNA -...
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