Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Medicine and Health Sciences
Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani
Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani
Pharmaceutical Sciences Faculty Publications
Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, …
A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker
A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker
Pharmaceutical Sciences Faculty Publications
Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.