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Effects Of Telomerase Inhibitor On Liver Cancer Xenograft In Rats

Posted on:2006-09-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:H J ZhangFull Text:PDF
GTID:1104360155450726Subject:Medical imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
Part 1 Establishment of Implanted Hepatic Cancer Model in Rats under the Guidence of B- ultrasoundObjective: The aim of this work was to develop a new method of establishing implanted hepatic cancer model in SD rats. Methods: 52 Adult SD rats were devided into 2 groups, 0.03ml concentrated cancerous suspension were injected into the rat liver guided by B ultrasound to create walker-256 tumor model. The success rate of implanted tumors, growth rapidity were evaluated and ultrasonic features, CT and MRI appearance were observed. Results: The success rate of implanted tumors was 98.1%(51/52), most tumors appeared as sharply marginated nodes. The maximum diameters of tumors 3, 6, 9, 12 days after implantation were 0.2 , 0.6, 0.9, 1.4 cm respectively and their corresponding tumor volumes were 0.004±0.001, 0.075±0.012, 0.288±0.037, 1.183±0.215cm~3. There was no significant difference between tumor volumes in 2 groups. Cancerous ascites could be observed in 3 rats, caused by tumor migrated to other abdominal organs or rat skin. Conclusion: It is a new way to establish implanted liver tumor models with easy and minimal traumatic manipulation and can be used widely.Part 2 Research on the Telomerase Activity in Ratswith Implanted Liver Cancer ModelsObjective: The aim of this study was to evaluate the role of telomerase activity in the development of implanted Walker-256 liver tumors in rats. Methods: The telomerase activity in 18 tumor tissues and their adjacent tissues, nomal liver tissues were detected by PCR-ELISA based TRAP(telomeric repeated sequences amplification protocol) 4,6,8days after implantation respectively. Results: We reported high telomerase activity in Walker-256 tumors compared to those in the adjacent tissues and normal liver tissues. The telomerase acitivity in tumor tissues were 0.767±0.117. 0.768±0.118. 0.774±0.111, while those in adjacent tissues were 0.389±0.263. 0.492±0.253. 0.584±0.239, and 0.231 ±0.022. 0.229±0.022. 0.233±0.021 in nomal tissues respectively. The level of telomerase activity in tumor tissue was significantly higher than that in adjacent tissue and normal liver tissue (p<0.05). The telomerase activity in tumor tissue has no significant correlation among tumor diameters (p>0.05). The level of telomerase activity in adjacent tissue was significantly increased in accordance with the growth of tumor. Conclusion: Telomerase activity is expressed in walker-256 tumors, the telomerase activity in malignant tumor tissues was significantly increased compared tothat of nomal tissue. Telomerase may play a critical role in the progression of tumor, the reactivation of telomerase is believed to be necessary for cell proliferation in tumors. The results presented here suggest that telomerase may be an important target for cancer therapy.Part 3 Effects of Telomerase Inhibitor onLiver Cancer Xenograft in RatsObjective: The aim of this paper was to evaluate the efficacy of telomerase inbitor for animal tumor in vivo as a potential therapeutic agent for malignant tumor. Methods: 42 SD rats with implanted Walker-256 tumors were devided into 2 groups. The telomerase inhibitor (azidothymidine, AZT) was injected into tumors to treat liver cancer (Walker-256) xenograft in SD rats in 1 group(AZT group). Equal volume of normal saline was injected into tumors in rats of another group (control group). The influence on telomerase activity, apoptotic indices(AI) and tumor volumes were detected and evaluated. Telomerase activity was examined by telomeric repeat amplification proctocol coupled with ELISA (TRAP-ELISA). The histological and ultrastructral changes in tumor tissure were observed under microscope and electronic microscope. AI and tumor volumes were calculated. The...
Keywords/Search Tags:Telomerase
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