| Background and objectiveCervical cancer is one of the most usual seen gynecological cancers that seriously threats women's health. Its incidence increases year by year and women who suffer this disease tend to be younger and younger. Although over the years we have been perfecting surgical techniques and radiation therapy and technology to improve the survival rate of cervical cancer patients, its therapeutic effect is still not satisfactory. With the development of cancer chemotherapy and clinical research, neoadjuvant chemotherapy (NACT) has begun to be used in clinic. NACT, also known as pre-chemotherapy, is a treatment in which Intravenous chemotherapy or arterial infusion chemotherapy is carried out first during the comprehensive treatment of the tumor and before the partial treatment. NACT is gradually used in the treatment of terminal cervical cancer and the short term effect is notable. It has become a tendency for young patients to choose the surgical treatment after NACT in order to reduce the probability of radiotherapy and reserve the vaginal function.At present, chemotherapy combined the use of taxane drug and platinum drug is a commonly used treatment scheme for preoperative chemotherapy. Though a great deal of clinical data has elaborated the effectiveness of adjuvant chemotherapy treatment of cervical cancer, an adjustment mechanism that is efficient to NACT or resist the molecular level has not yet been extensively studied. Patients who resist chemotherapy may delay the implementation of radical surgery or radiation treatment time. Therefore, finding a predictable chemotherapy sensitivity index is essential to the successful filtration of the treatment of patients. Former research says that regulatory factors affecting chemotherapy mainly include multidrug-resistance gene, cell proliferation and apoptosis factors, growth factors and their receptors, cell cycle protein and so on. Recent studies suggest that chemotherapy drugs clear most tumor cells by inducing the apoptosis of cells. Therefore, the detection of the expression of apoptosis and tumor drug resistance genes may help predict the efficacy of neoadjuvant chemotherapy and evaluate the prognosis and provide references for chemotherapy drug treatment of cervical cancer.The relationship between apoptosis and tumor has always been a hot research point of the medical community. The mutual balance between cell proliferation and apoptosis can maintain the normal physiologic function of tissue organs and the stability of the number of cells. Otherwise, it may result in tumor. Chemotherapy, radiotherapy and biological therapy mainly treat tumor by inducing apoptosis. Therefore, inducing apoptosis has become a new target of anticancer drugs. Bax, a gene that can foster apoptosis, can not only lower the threshold of apoptosis but also adjust apoptosis through a direct impact on the integrity of mitochondrial function and membrane. It plays a role in restraining tumor. PUMA (p53 up-regulated modulator of apoptosis) is a newly discovered member of the BH3-only subfamily which belongs to the Bcl-2 family. It is powerful in facilitating apoptosis. PUMA, as a pro-apoptotic factor, plays a rather important role in p53 dependent and p53-independent apoptosis pathway of both the normal cells and the abnormal cells as well as in the germination of tumor. The issues relating to the gene's regulation mechanism and its application in tumor treatment need further study.In recent years, chemotherapy has developed rapidly in the treatment of cervical cancer and neoadjuvant chemotherapy has gradually become the new trend in treating cervical cancer. However, the emergence of drug resistance to some extent limits the application of chemotherapy and has become a tough problem in cervical cancer chemotherapy. After resistance to one drug, tumor cells may resist other drugs whose drug action mechanism and structure are totally different from theirs, which is called multi-drug resistance (MDR). Multi-drug resistance often leads to an unsuccessful treatment of combined chemotherapy. TopoisomeraseⅡ(TopoII) is an important glycoprotein relevant to multi-drug resistance and also an important enzyme involved in the replication, transcription, and separation of DNA. The decrease of the expression level of TopoⅡis regarded as a sign of drug resistance of tumor cells to the inhibitor. The high level expression of TopoII, however, is considered as that tumor cells are sensitive to TopoII inhibitor.This experiment mainly adopts the immunohistochemical method and through the detection of Bax,PUMA and TopoII in cancer tissue before or after the cervical squamous cell carcinoma (SCC) neoadjuvant chemotherapy, it compares the expression level changes of Bax,PUMA and TopoII in squamous cell carcinoma of the cervix before and after chemotherapy. Then combining the clinical efficacy, it investigates whether Bax,PUMA and TopoII in cancer tissues are relevant or not before or after cervical cancer neoadjuvant chemotherapy so as to provide references for individualized treatment and chemotherapy scheme.Methods and SubjectsWe adopted the immunohistochemical staining method to detect the expression of Bax, PUMA and TopoII in the cancer tissues of the 50 cervical squamous cancer patients who were treated with TC program intravenous chemotherapy before and after chemotherapy and do research on the expression changes of these three factors as well as the relationship between the expression of the three factors and clinical efficacy. Immunolhistochemistry experimental procedures proceeded in accordance with the procedures of kit instructions. There were 50 patients aged 26-53 and the average age was 39.8 years old. Among them 38 patients were over 35 years old and 12 were no more than 35 years old. The clinical pathology characteristics were 17 cases of I b2,16 cases of II a1,16 cases of II a2, and 7 casesⅡb.There were 25 cases of high differentiation,16 cases of medium differentiation, and 9 cases of poor differentiation. None of those 50 patients had chemotherapy contraindication and all the specimens were confirmed by pathology.We adopted the SPSS 17.0 statistical analysis software to make a reasonable statistical analysis of the experimental data. Considerα=0.05 as the detection standard.Results1 46 of the 50 cervical squamous cell carcinoma patients reacted to NACT, among whom 7 cases were clinical complete remission while 39 cases were clinical partial remission. The total effective rate was 92% and the rest 4 patients showed stable disease. For patients at different clinical stages and pathological grade, there was no significant correlation of the efficacy of NACT (P> 0.05).2 The expression sites of Bax, PUMA and TopoⅡin cervical squamous cell carcinoma were all in the cytoplasm and (or) the nucleus. Before NACT, the positive expression of Bax and PUMA in the effective group was higher than that in the ineffective group and the difference was statistically significant (P<0.05).The positive expression of TopoⅡin the effective group was higher than that in the ineffective group but the difference was not statistically significant (P>0.05)3 The positive expressions of Bax and PUMA after chemotherapy in the NACT effective group and ineffective group were both higher than those before chemotherapy and the differences were statistically significant (P<0.05).However, the positive expressions of TopoⅡafter chemotherapy in the NACT effective group and ineffective group was lower than that before chemotherapy and the differences were statistically significant (P<0.05).4 Relevant detection showed that the expression of Bax,PUMA and TopoⅡin cervical squamous cell carcinoma had no significant correlation.Conclusion1 paclitaxel-carboplatin chemotherapy has a better curative effect in treating cervical squamous cell cancer. The pathological features of cervical squamous cell cancer have nothing to do with the efficacy of NACT.2 Bax,PUMA is expected to become the objective evaluation index in determining the efficacy of cervical cancer NACT. 3 paclitaxel-carboplatin may achieve anti-tumor effect through up-regulation of the expression of Bax and PUMA.4 Apoptosis pathway and drug resistance may simultaneously occur in the course of neoadjuvant chemotherapy, but the two ways may don't influence each other. |
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