The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
Malcolm S Mitchell - One of the best experts on this subject based on the ideXlab platform.
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phase ii trial of Carbetimer in metastatic melanoma
Investigational New Drugs, 1993Co-Authors: Walter D Y Quan, Malcolm S MitchellAbstract:A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v. daily for five days every 21-day cycle was conducted in patients with metastatic melanoma. No responses were seen in 18 evaluable patients. Two patients had stable disease for five months. Toxicity was generally manageable and included mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site, and nausea. Carbetimer is inactive in metastatic melanoma at this dose and schedule.
Walter D Y Quan - One of the best experts on this subject based on the ideXlab platform.
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phase ii trial of Carbetimer in metastatic melanoma
Investigational New Drugs, 1993Co-Authors: Walter D Y Quan, Malcolm S MitchellAbstract:A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v. daily for five days every 21-day cycle was conducted in patients with metastatic melanoma. No responses were seen in 18 evaluable patients. Two patients had stable disease for five months. Toxicity was generally manageable and included mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site, and nausea. Carbetimer is inactive in metastatic melanoma at this dose and schedule.
G Obryantear - One of the best experts on this subject based on the ideXlab platform.
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effects of Carbetimer a new antineoplastic drug on bone metabolism
Bone, 1991Co-Authors: Jeanjacques Body, S Nejai, Gabriela Cristina Fernandez, F Glibert, G ObryantearAbstract:Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.
Jeanjacques Body - One of the best experts on this subject based on the ideXlab platform.
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effects of Carbetimer a new antineoplastic drug on bone metabolism
Bone, 1991Co-Authors: Jeanjacques Body, S Nejai, Gabriela Cristina Fernandez, F Glibert, G ObryantearAbstract:Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.
S Nejai - One of the best experts on this subject based on the ideXlab platform.
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effects of Carbetimer a new antineoplastic drug on bone metabolism
Bone, 1991Co-Authors: Jeanjacques Body, S Nejai, Gabriela Cristina Fernandez, F Glibert, G ObryantearAbstract:Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.