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Báo cáo hóa học: " Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors | Woodrum et al. Journal of Translational Medicine 2010 8 14 http www.translational-medicine.eom content 8 1 14 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Comparison of three rapamycin dosing schedules in A J Tsc2 mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors Chelsey Woodrum Alison Nobil Sandra L Dabora Abstract Background Tuberous Sclerosis Complex TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney brain skin lungs and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC however tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2 - mice we compared kidney cystadenoma severity in A J and C57BL 6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A J Tsc2 - mice. In addition we used nude mice bearing Tsc2- - subcutaneous tumors to evaluate the therapeutic utility of sunitinib bevacizumab vincristine and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A J Tsc2 - mice compared with C57BL 6 Tsc2 -mice. Similar to kidney angiomyolipomas associated with TSC the severity of kidney cystadenomas increases with age in A J Tsc2 - mice. When rapamycin dosing schedules were compared in A J Tsc2 - cohorts we observed a 66 reduction in kidney tumor burden in mice treated daily for 4 weeks an 82 reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks and an 81 reduction in mice treated weekly for 12 weeks. In the Tsc2- - subcutaneous tumor mouse model vincristine is not effective but angiogenesis inhibitors sunitinib .