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Expression And Significance Of Beclinl And Caspase3 In Cervical Squamous Cancer Before Anf After Neoadjuvant Chemotherapy

Posted on:2011-06-06Degree:MasterType:Thesis
Country:ChinaCandidate:J LiFull Text:PDF
GTID:2154330332958685Subject:Obstetrics and gynecology
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Background and objectiveCervical cancer is the most common gynecological cancer. Although the surgery and radiation therapy of cervical cancer have achieved great success, after the initial treatment, there are still larger local tumor or sub-clinical micro-metastasis tumor which are uncontrollable, recurrent and metastases. To reduce the recurrence rate and increase the survival rate of these high-risk patients after treatment, Neoadjuvant chemotherapy(NACT) begin to be used in clinic currently. NACT is systemic adjuvant cytotoxic therapy taken before the local treatment, so it is also called preoperative chemotherapy or early chemotherapy. Many studies have supported the effectiveness of the NACT in local advanced cervical cancerPreoperative Drugs like Taxane and platinum are used commonly in cervical cancer. It has better tolerance and clinical response in patients with cervical cancer, however, not all patients respond as above. Patients who aren't sensitive to chemotherapy should do surgery, radiation therapy or other treatments in order to obtain better treatment. Therefore, we need to find the indicators to predict chemosensitivity to screening patients.Cancer is caused by imbalance between Cell proliferation, differentiation and cell death. Cell death particularly programmed cell death (PCD) is of great significance on tumor development and demise. Initially, people thought that the PCD was apoptosis, and now autophagic is also found in PCD. Many chemotherapeutic drugs achieve their cytotoxicity by inducing PCD. Therefore, the relationship between chemotherapy and the biological behavior of tumor markers becomes the research focus, and recently it showed that there was a very close relationship between chemotherapy and PCD. The relationship between NACT and PCD has also become the focus of current research, and now more and more attention is paid on neoadjuvant chemotherapy in treatment of cervical cancer. Furthermore, people began to consider using PCD to evaluate the potential value of cervical cancer treatment. Meanwhile, the relationship between apoptosis and autophagy in PCD can be analyzed by studying the pathway of tumor cell death after chemotherapy.Apoptosis is a basic biological phenomenon of cells, and it play an important role in removing unwanted or abnormal cells in multi-cellular organisms. Disorder of apoptosis may occur with many diseases directly or indirectly, such as cancer or autoimmune diseases. Caspase3 is one of the most important executors of apoptosis in Caspase family. It plays a key role in apoptosis and exists with inactive zymogen form in cells. Once activated, it enables many proteins or kinase relation with cell structure, cell cycle and DNA repair to be inactive.Autophagic cell death is different from apoptosis, and this PCD is not dependent on Caspase. Inhibition of autophagy has a relationship with tumorigenesis and has been a new target of tumor formation and tumor inhibition. Autophagy gene Beclinl is a mammal-specific gene involved in autophagy, located on chromosome 17q21, involved the formation of autophagosome and regulate cell growth through autophagy. As a suppressor gene, the absence of Beclinl may lead to the occurrence of many cancers.This study was to examine the expressions of Caspase3,Beclinl in carcinoma cervicis before and after neoadjuvant chemotherapy by immunohistochemistry and to evaluate the relationship between apoptosis and autophagy in the PCD process, and the relationship between neoadjuvant chemotherapy and Caspase3,Beclinl genes, In order to find a new target to guide therapy and predict efficacy of neoadjuvant chemotherapy.Subjects and MethodsUsed the way of immunohistochemical staining to detecte the expressions of Caspase3,Beclinl in cervical carcinoma tissue in 100 cases(50 pairs)with carcinoma cervicis before and after neoadjuvant chemotherapy. We explore the expression and relationship of the two kinds of gene. Furthermore, we explore the relationship between the expression of two kinds of gene and the clinical efficacy. Experimental procedure was executed according to reagent instructions.50 patients aged from 32 to 74 years, the average age of 51.6 years, of which 39 cases over 40 years old,11 cases less than 40 years old. Clinicopathological characteristics are as follows:I b2 of 18 cases,â…¡a1 of 15 cases,â…¡a2 of 11 cases andâ…¡b of 6 cases. Well differentiated and moderately differentiated in 43 cases and poorly differentiated in 7 cases. The 50 patients had no chemotherapy taboo. All specimens were confirmed by pathology.Statistical analysis software SPSS 10.0 was used to analyze the experimental data and clinical data, a= 0.05 was used as a standard test.Results1 46 cases of 50 patients responded to the NACT, of which 6 cases with clinical Complete remission,40 patients with clinical partially remission. The total effective rate was 92%; the remaining 4 patients showed a stable disease. There was no significant correlation among the efficacy of NACT in the patients with different clinical stage or pathological grade (P> 0.05).2 Both the expression of Beclinl and Caspase3 of Cervical Cancer mainly located in the cytoplasm, and the positive expression rates of Caspase3,Beclinl were obviously higher after neoadjuvant chemotherapy than that of before neoadjuvant chemotherapy (P< 0.05).3 The positive expression of Caspase3 before chemotherapy in NACT valid patients were higher than that of invalid ones, and the difference was significant (P <0.05). While the difference of the positive expression of Beclinl in this two group was not statistically significant (P>0.05).4 Correlation tests showed that there was no significant correlation between the expression of Caspase3 and Beclinl in cervical carcinoma tissue.Conclusion1 Paclitaxel-carboplatin chemotherapy is very effective for treating cervical cancer. Clinical and pathological features of cervical squamous cell carcinoma has nothing to do with the efficacy of NACT.2 Paclitaxel-carboplatin may play an anti-tumor role by increasing Caspase3 and Beclinl in the cytoplasm.3 The Caspase3 status can be used as a biological parameter to predict the efficacy of neoadjuvant chemotherapy.4 Apoptosis and autophagy can appear in the PCD process at the same time, but the two pathways do not influence each other.
Keywords/Search Tags:Cervical cancer, Neoadjuvant chemotherapy, Autophagy gene Beclin1, Apoptosis gene Caspase3
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