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Effective Of Growth Inhibition And Apoptosis Induction By Retinoic Acid Combined With Adriamycin Or Interferon On Transitional Cell Carcinoma Of Bladder

Posted on:2005-01-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:L X QianFull Text:PDF
GTID:1104360125951685Subject:Surgery
Abstract/Summary:PDF Full Text Request
Bladder cancer is a kind of commonly encountered malignant tumour in genitourinary tract. Its incidence rate is the highest among the malignant tumors in domestic urological surgery. Among bladder cancers, more than 90% is BTCC (Bladder Transitional Cell Cancer). Over 70% of BTCC may recrudesce postoperative. Among the recrudescing BTCC, 30% worsen. Therefore, BTCC threatens human health severely. The preferred treatment for BTCC is surgery. It is necessary for any patient treated by transurethral resection of bladder cancer, partial excision of bladder or other operation remaining bladder to receive regularly intravesical irrigation chemotherapy and cystoscope recheck after the operation. The chemoprophylaxis after surgery is very important for decreasing the recurrence rate of BTCC. Currently, the Pharmaceuticals in common use are BCG vaccine, mitomycin, adriamycin, hydroxyl camptothecine (HCPT), cytokines and etc. It is necessary for any invasive or superficial BTCC patient recrudescing after operation to receive general chemotherapy. Most bladder cancer patients suffer obvious toxic side-effects caused by chemotherapy,including dysfunctional of heart, liver or kidney, arrest of bone marrow and disorders of alimentary tract. At present, bladder tumour isn't very sensitive to radiation therapy, so it isn't applied commonly in clinical treatment of bladder cancer. Retinoic acid can regulate the growth and differentiation of normal and malignant epithelial cells inside or outside of body. Retinoic acid and its analogs have been used in the animal models and clinical trials for treating human malignant tumour.Considering looking for long-term effective Pharmaceuticals for chemoprophylaxis,general chemotherapy and radiotherapeutic sensitivity increasing, we have observed the growth inhibition and apoptosis induced by 4-HRP (one ramification of retinoic acid), hydrochloric adriamycin and the simultaneous or successive combination of them on bladder cancer cell strain T24 through a series of experiments including cell culture experiments, molecular biology experiments and animal model, moreover, we have establish Wistar rat bladder cancer Model by intravesicular administration of N-methyl-N-nitrosourea (MNU) in order to investigate the morphological changes of the bladder mucosa, and compare the influences caused by 4-HRP, hydrochloric adriamycin and the simultaneous or successive combination of them on the formation of rat bladder cancer and histopathological changes. Compare the results of growth inhibition and apoptosis induced by separate or combined administration of all-trans-retinoic acid (ATRA) or 9-cis retinoic acid (9cRA) and interferon a-2a (IFNa-2a) on four kinds of human bladder cancer cell strain to investigate the related possible molecular mechanism.1 Growth inhibition and apoptosis induced by the combination of 4-HPR and adriamycin on bladder transitional cell cancer line T24Bladder transitional cancer cell line T24 was cultured in vitrowith 10-6 5X10-6 10-5mol/L concentrations of 4-HPR and 0.05mg/L ADM. The cellular toxicity effects were evaluated by the method of MTT. Flow cytometry was used to determine the effects of cellular growth inhibition by the 4-HPR,adriamycin or the combination of the two agents. The results revealed that the apoptosis rate induced by 5u mol/L 4-HPR and 0.05mg/L adriamycin reached 5% and 22% on T24 cell and the apoptosis rate was 63% (P<0.05) after combination these two agents. Apoptosis rate induced by 0.5mg/L adriamycin was 21.3% and then raised to 99% (P<0.05) after acted together with 5 u mol/L 4-HPR. The results demonstrate that 4-HPR had a dose-and time-dependant induction of apoptosis. With the combination of ADM,4-HPR can show stronger growth inhibition than it does by itself, meanwhile it can shorten the prophase time and deduce the dosage of ADM.2, The establishment of animal model of the bladder cancer in Wistar rats induced by N-methyl-N-nitrosourea (MNU) and the efficacy of intravesical irrigation of 4-HPR for the rat bladder cancerOne...
Keywords/Search Tags:bladder transitional cell carcinoma, apoptosis, growth inhibition, retinoid
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