Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic ac...Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%;n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%;n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.展开更多
One of the main health problems with high and markedly increased complications is diabetes. Despite several projects with preventative strategies and armories of medication, the arrangement of diabetes remains grossly...One of the main health problems with high and markedly increased complications is diabetes. Despite several projects with preventative strategies and armories of medication, the arrangement of diabetes remains grossly unsatisfactory. Thus, it is vital to identify unfamiliar drugs or novel nutraceuticals for treating and preventing diabetes without side effects. The present study deals with scientific information on mushrooms with regards to its potential use as anti-diabetic active food. In addition to the anti-hyperglycemic action of mushrooms, the present study presents its effect on DNA damage, chromosome aberrations and sperm alternations in streptozotocin-induced diabetic rats. These animals have been treated, for 30 days, with amaryl (as control treatment) (0.03 mg/kg·b·wt/dl), low-dose mushroom (100 mg/kg·b·wt/dl) and high-dose mushroom (200 mg/ kg·b·wt/dl). The glucose level GL of streptozotocin-induced diabetic animals has been markedly improved by mushroom treatment;for example GL has decreases from 167.6 mg/dl down to 116.0 mg/dl for treatment with high-dose mushroom and 128.9 mg/dl for treatment with low-dose mushroom, comparing with amaryl treatment that decreases GL down to 92.6 mg/dl. But, the experimental results show that treatment with mushroom is better than treatment with amaryl in case of genetic changes (DNA fragmentation, disappear of some base pairs and chromosome aberrations. So, it is proposed that more close scientific attention be paid to precede more research of functional mushrooms for preventive and curative treatments for diabetes.展开更多
文摘Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%;n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%;n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.
文摘One of the main health problems with high and markedly increased complications is diabetes. Despite several projects with preventative strategies and armories of medication, the arrangement of diabetes remains grossly unsatisfactory. Thus, it is vital to identify unfamiliar drugs or novel nutraceuticals for treating and preventing diabetes without side effects. The present study deals with scientific information on mushrooms with regards to its potential use as anti-diabetic active food. In addition to the anti-hyperglycemic action of mushrooms, the present study presents its effect on DNA damage, chromosome aberrations and sperm alternations in streptozotocin-induced diabetic rats. These animals have been treated, for 30 days, with amaryl (as control treatment) (0.03 mg/kg·b·wt/dl), low-dose mushroom (100 mg/kg·b·wt/dl) and high-dose mushroom (200 mg/ kg·b·wt/dl). The glucose level GL of streptozotocin-induced diabetic animals has been markedly improved by mushroom treatment;for example GL has decreases from 167.6 mg/dl down to 116.0 mg/dl for treatment with high-dose mushroom and 128.9 mg/dl for treatment with low-dose mushroom, comparing with amaryl treatment that decreases GL down to 92.6 mg/dl. But, the experimental results show that treatment with mushroom is better than treatment with amaryl in case of genetic changes (DNA fragmentation, disappear of some base pairs and chromosome aberrations. So, it is proposed that more close scientific attention be paid to precede more research of functional mushrooms for preventive and curative treatments for diabetes.
