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Effect Of Oxaliplatin Combined With Five Fluorouracil Preoperative Short Course Chemotherapy On The Expression Of Survivin Gene In Colorectal Adenocarcinoma

Posted on:2015-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y ShenFull Text:PDF
GTID:2254330428999661Subject:Surgery
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Background and purpose:Colorectal cancer is one of the most common malignant tumor and isgreat harm to human life. In recent years, the incidence and mortality ofcolorectal cancer are significantly increased, along with the changes ofdiet structure and other reasons. Now Its incidence is approximately inthird malignant tumor with younger trend. Among cases of colorectalcancer, approximately30-50%of patients will occur metastaticrecurrence, and colorectal cancer becomes the leading cause of death inpatients with cancer.Operation is the most important means of treatment of rectal cancer, butthe recurrence rate is still high in advanced colorectal cancer. In recentyears, new adjuvant chemotherapy as a method of comprehensive therapyin colorectal cancer has received more and more attention. Neoadjuvantchemotherapy is a systemic chemotherapy before operation orradiotherapy. its purpose is to make the primary tumors or metastaticlesions reduce, to decrease tumor staging, to make unresectable tumors beremoved, to improve the curative operation resection rate, to reduce therecurrence rate, to control the very small cancer and sub clinical fociexisted before operation, to make inhibition of tumor proliferation induced by the operation, to control iatrogenic metastasis, to easy reacheffective concentration of chemotherapy and the killing effect of highdose in local tumor before the blood supply and lymph tube damage, tohelp the postoperative chemotherapy regimens and to provide the basis ofpostoperative judgment or choice of anticancer drugs, to assist theevaluation of prognosis, and to prevent distant metastasis. Despite thelack of randomized data confirms its efficacy, the application ofpreoperative radiotherapy and chemotherapy in patients with colorectalcancer are more and more popular.However, preoperative chemotherapy is not without its drawbacks. Theside effects of chemotherapy drugs may affect the patients preoperativepreparation adjusted to the best condition. adjuvant chemotherapy withhigh dose and multiple courses even makes some patients to delay theoperation due to bone marrow suppression. for some patients with cancernot be sensitive to chemotherapy, there is the risk of delay in treatmentand disease progression. Li et al. performed a series of studies aboutpostoperative wound healing on96cases of rectal cancer undergoingneoadjuvant chemotherapy, experiments show the incidence of delayedhealing of incision (32.3%) in patients with neoadjuvant chemotherapywas significantly higher than the control group (15.8%), postoperativeincision infection rate is also significantly elevated (21.9%vs12.6%). Soit is not uniform provisions for the preoperative neoadjuvantchemotherapy scheme and course.Preoperative short course chemotherapy can reduce the effect of highdose chemotherapy on operation, does not delay the operative treatmentin cases of colorectal cancer with incomplete obstruction or slow bleeding,and to improve the safety of the operation. Liu et al. report, the efficacy of radical operation in group of preoperative short course chemotherapywas significantly higher than that of control group, the side reaction islittle, and the radical operation can be normally performed in the end of acourse of preoperative short-range impact chemotherapy.Oxaliplatin as the third generation platinum drug, has strong anticanceractivity, a synergistic effect with5-FU, efficacy on many kinds of cancer,low toxic and side effect, and been widely applied. Recently, researchersshowed that oxaliplatin chemotherapy can reduce colon cancer cellsapoptosis inhibiting gene (survivin) activity by changing the p38mitogen-activating protein(MAP) and proteasome, then can induce theapoptosis of tumor cells be changed.Survivin is a new member of the family of inhibitor of apoptosis protein(IAP), also is currently the strongest apoptosis inhibiting factor. Thecomplex Survivin function includes inhibition of cell apoptosis,promoting cell transformation and involved in cell mitosis, formation ofblood vessels and produce of tumor drug resistance etc.. Sohn et al.researchers found that oxaliplatin could inhibit the expression of Survivintumor cells in HCT116human colon cancer cells.Through the investigation of colorectal cancer patients beforechemotherapy of oxaliplatin combined with five fluorouracil short-rangeimpact after the operation, the resected tumor tissues were detectedapoptosis inhibiting gene expression of Survivin, further evaluation ofshort-range chemotherapy for colorectal cancer patients on the value ofpreoperative.Methods:99cases of colorectal cancer were randomly divided into two groups. In with five fluorouracil short-range impact chemotherapy was underwent,then the operation was performed three days later. In control groupincluding49cases, routine operation was received after preoperativepreparation.1.To observe and record the data of two groups of patients, including sex,age and body weight. After admission, before and after operation, ofperipheral blood was examined for routine blood test, liver and kidneyfunction. Close observation and record of adverse reactions afteroperation was done, then comparative analysis was made.2. Immunohistochemical detection of survivinImmunohistochemical staining of survivin was performed on tumor tissuespecimens of operative excision by a horseradish-peroxidase techniqueaccording to the manufacturer’s recommendation.3. detection of survivin mRNA expressionDetection of survivin mRNA expression was performed on tumor tissuespecimens of operative excision by RT-PCR technology. The Ct valuewas gotten by continuous collection of fluorescence signal with theSequence Detection Software V1.2analysis software. Based on the Ctvalue and the standard concentration, we draw the standard curve,calculate the amplification efficiency and calculation relativequantification of Survivin mRNA.4Statistical analysisdata were processed by statistical software SARS6.12, all variables areused to describe the X±s, between the two groups were compared usingt test group designed for data analysis, comparison of count data using x2test. Results:1. adverse effect of a preoperative oxaliplatin combined with fivefluorouracil short-range impact chemotherapy on operationAdverse reactions of patients in experimental group after operation,including abdominal infection, anastomotic fistula, diarrhea, intestinalobstruction, pulmonary infection, urinary tract infection, incisioninfection rate, all similar to that in the control group (P>0.05), there wasno statistical significance. The rusult shows that preoperative oxaliplatincombined with five fluorouracil short range impact chemotherapy is safeand no adverse effect on operation.2. Expression of survivin on colorectal cancer tissues detected byimmunohistochemical techniquethe rates of expression of survivin on tumor specimens in theexperimental group and in the control group were respectively88%and95.90%, there was significant difference between the two groups(P<0.05). In the patients with lymph node metastasis, the expression rateof Survivin in neoadjuvant chemotherapy experimental group was lowerthan that in operation control group, the difference was significant(P<0.05).3. Expression of Survivin mRNA on colorectal cancer tissues detectedby RT-PCR techniqueaverage level of survivin mRNA expression in experimental group is18.1356±16.3216, significantly lower than that in control group32.3904±18.6915, there was significant difference (P=0.0041). Conclusion:1Survivin expression on tumor tissue of colorectal cancer inexperimental group with preoperative oxaliplatin combined with fivefluorouracil short-range impact chemotherapy is lower than that incontrol group with simple operation.2preoperative oxaliplatin combined with five fluorouracil short-rangeimpact chemotherapy can induce apoptosis in tumor tissues of colorectalcancer.3preoperative oxaliplatin combined with five fluorouracil short-rangeimpact chemotherapy is safe, does not cause adverse reaction onoperation.
Keywords/Search Tags:oxaliplatin, neoadjuvant chemotherapy, survivinfive fluorouracil, colorectal cancer
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