The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
A Polliack - One of the best experts on this subject based on the ideXlab platform.
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Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia
Bone Marrow Transplantation, 2003Co-Authors: L Weiss, R Or, G Amir, A Abdul-hai, A PolliackAbstract:Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the Purine Analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/c×C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabine-treated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals ( P =0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versus-leukemia appeared to be augmented in the same animals.
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The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models
Bone Marrow Transplantation, 2000Co-Authors: R Or, L Weiss, G Amir, S Tejman, A PolliackAbstract:Fludarabine phosphate, a Purine Analogue currently used in the therapy of hematological malignancies, is known to cause immunosuppression and long-lasting T cell lymphopenia. In this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across major and minor histocompatibility barriers was evaluated. Survival of (BALB/c × C57BL/6)F1 mice irradiated and transplanted across the major histocompatibility barrier with C57BL/6 spleen cells, and subsequently treated with fludarabine was significantly longer than that of the control animals ( P
John D. Schuetz - One of the best experts on this subject based on the ideXlab platform.
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Substrate Overlap between Mrp4 and Abcg2/Bcrp Affects Purine Analogue Drug Cytotoxicity and Tissue Distribution
Cancer research, 2007Co-Authors: Kazumasa Takenaka, Jessica A. Morgan, George L. Scheffer, Masashi Adachi, Clinton F. Stewart, Daxi Sun, Markos Leggas, Karin F.k. Ejendal, Christine A. Hrycyna, John D. SchuetzAbstract:The use of probe substrates and combinations of ATP-binding cassette (ABC) transporter knockout (KO) animals may facilitate the identification of common substrates between apparently unrelated ABC transporters. An unexpectedly low concentration of the Purine nucleotide Analogue, 9-(2-(phosphonomethoxy)ethyl)-adenine (PMEA), and up-regulation of Abcg2 in some tissues of the Mrp4 KO mouse prompted us to evaluate the possibility that Abcg2 might transport Purine-derived drugs. Abcg2 transported and conferred resistance to PMEA. Moreover, a specific Abcg2 inhibitor, fumitremorgin C, both increased PMEA accumulation and reversed Abcg2-mediated PMEA resistance. We developed Mrp4 and Abcg2 double KO mice and used both single KOs of Abcg2 and Mrp4 mice to assess the role of these transporters in vivo . Abcg2 contributed to PMEA accumulation in a variety of tissues, but in some tissues, this contribution was only revealed by the concurrent absence of Mrp4. Abcg2 also transported and conferred resistance to additional Purine Analogues, such as the antineoplastic, 2-chloro-2′-deoxyadenosine (cladribine) and puromycin, a protein synthesis inhibitor that is often used as a dominant selectable marker. Purine Analogues interact with ABCG2 by a site distinct from the prazosin binding site as shown by their inability to displace the substrate Analogue and photoaffinity tag [ 125 I]iodoarylazidoprazosin. These studies show that Abcg2, like Mrp4, transports and confers resistance to Purine nucleoside Analogues and suggest that these two transporters work in parallel to affect drug cytotoxicity and tissue distribution. This new knowledge will facilitate an understanding of how Abcg2 and Mrp4, separately and in combination, protect against Purine Analogue host toxicity as well as resistance to chemotherapy. [Cancer Res 2007;67(14):6965–72]
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substrate overlap between mrp4 and abcg2 bcrp affects Purine Analogue drug cytotoxicity and tissue distribution
Cancer Research, 2007Co-Authors: Kazumasa Takenaka, Jessica A. Morgan, George L. Scheffer, Masashi Adachi, Clinton F. Stewart, Daxi Sun, Markos Leggas, Karin F.k. Ejendal, Christine A. Hrycyna, John D. SchuetzAbstract:The use of probe substrates and combinations of ATP-binding cassette (ABC) transporter knockout (KO) animals may facilitate the identification of common substrates between apparently unrelated ABC transporters. An unexpectedly low concentration of the Purine nucleotide Analogue, 9-(2-(phosphonomethoxy)ethyl)-adenine (PMEA), and up-regulation of Abcg2 in some tissues of the Mrp4 KO mouse prompted us to evaluate the possibility that Abcg2 might transport Purine-derived drugs. Abcg2 transported and conferred resistance to PMEA. Moreover, a specific Abcg2 inhibitor, fumitremorgin C, both increased PMEA accumulation and reversed Abcg2-mediated PMEA resistance. We developed Mrp4 and Abcg2 double KO mice and used both single KOs of Abcg2 and Mrp4 mice to assess the role of these transporters in vivo . Abcg2 contributed to PMEA accumulation in a variety of tissues, but in some tissues, this contribution was only revealed by the concurrent absence of Mrp4. Abcg2 also transported and conferred resistance to additional Purine Analogues, such as the antineoplastic, 2-chloro-2′-deoxyadenosine (cladribine) and puromycin, a protein synthesis inhibitor that is often used as a dominant selectable marker. Purine Analogues interact with ABCG2 by a site distinct from the prazosin binding site as shown by their inability to displace the substrate Analogue and photoaffinity tag [ 125 I]iodoarylazidoprazosin. These studies show that Abcg2, like Mrp4, transports and confers resistance to Purine nucleoside Analogues and suggest that these two transporters work in parallel to affect drug cytotoxicity and tissue distribution. This new knowledge will facilitate an understanding of how Abcg2 and Mrp4, separately and in combination, protect against Purine Analogue host toxicity as well as resistance to chemotherapy. [Cancer Res 2007;67(14):6965–72]
L Weiss - One of the best experts on this subject based on the ideXlab platform.
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Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia
Bone Marrow Transplantation, 2003Co-Authors: L Weiss, R Or, G Amir, A Abdul-hai, A PolliackAbstract:Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the Purine Analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/c×C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabine-treated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals ( P =0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versus-leukemia appeared to be augmented in the same animals.
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The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models
Bone Marrow Transplantation, 2000Co-Authors: R Or, L Weiss, G Amir, S Tejman, A PolliackAbstract:Fludarabine phosphate, a Purine Analogue currently used in the therapy of hematological malignancies, is known to cause immunosuppression and long-lasting T cell lymphopenia. In this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across major and minor histocompatibility barriers was evaluated. Survival of (BALB/c × C57BL/6)F1 mice irradiated and transplanted across the major histocompatibility barrier with C57BL/6 spleen cells, and subsequently treated with fludarabine was significantly longer than that of the control animals ( P
Farhad Ravandi - One of the best experts on this subject based on the ideXlab platform.
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treatment of hairy cell leukemia during pregnancy are Purine Analogues and rituximab viable therapeutic options
Clinical Lymphoma Myeloma & Leukemia, 2013Co-Authors: Naval Daver, Hagop M Kantarjian, Aziz Nazha, Rodney Haltom, Farhad RavandiAbstract:Approximately 1 in 1000 pregnancies in the United States are plagued by concurrent neoplastic diseases. These account for the second leading cause of maternal mortality in the United States.1 The majority of these cases are related to solid tumors with only 25% of the cases related to hematologic malignancies.2 Hairy cell leukemia (HCL) is a relatively uncommon lymphoproliferative disorder.3 The outcome of patients with HCL has significantly improved with the introduction of Purine nucleoside Analogues including cladribine and monoclonal antibodies including rituximab. Remission rates of > 90% have been documented after just 1 course of therapy.4,5 The management of the pregnant patient with hematologic malignancies represents a diagnostic, therapeutic, and social challenge, requiring a multidisciplinary team approach. There is scant published literature regarding treatment of HCL in pregnancy. The therapeutic efficacy, teratogenicity, and maternal toxicities of Purine Analogues and rituximab in pregnancy are poorly defined.6,7 Orlowski published the first report of successful pregnancy outcome after treatment of HCL with cladribine, suggesting that fertility may be preserved in some female patients exposed to Purine Analogues.8 However, to our knowledge this is the first report of a favorable outcome in a pregnant HCL patient treated sequentially with a monoclonal antibody (rituximab) followed by a Purine Analogue (cladribine).
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Purine Analogue combinations for indolent lymphomas
Seminars in Hematology, 2006Co-Authors: Nicholas Di Bella, Farhad RavandiAbstract:Indolent lymphomas are a group of lymphoid malignancies with differing patterns of behavior and responses to treatment. The progress in treating patients with hairy cell leukemia (HCL) using nucleoside Analogues can be used as a model for other indolent B-lymphoproliferative disorders, such as follicular lymphoma. Recent advancements in therapeutic options available for these patients include combination therapy with agents that have differing mechanisms of action and non-overlapping toxicity. It has been shown that patients who are candidates for aggressive therapy might receive benefit, including disease-free survival and overall survival, from combination Purine Analogue therapy. Using these more aggressive therapeutic approaches earlier in the disease course and as maintenance therapy may further enhance outcomes. With the advent of these new therapies along with the molecular evaluation of these regimens, we may be nearing the time where the goal for more advanced indolent lymphoma will be to achieve a cure.
R Or - One of the best experts on this subject based on the ideXlab platform.
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Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia
Bone Marrow Transplantation, 2003Co-Authors: L Weiss, R Or, G Amir, A Abdul-hai, A PolliackAbstract:Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the Purine Analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/c×C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabine-treated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals ( P =0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versus-leukemia appeared to be augmented in the same animals.
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The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models
Bone Marrow Transplantation, 2000Co-Authors: R Or, L Weiss, G Amir, S Tejman, A PolliackAbstract:Fludarabine phosphate, a Purine Analogue currently used in the therapy of hematological malignancies, is known to cause immunosuppression and long-lasting T cell lymphopenia. In this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across major and minor histocompatibility barriers was evaluated. Survival of (BALB/c × C57BL/6)F1 mice irradiated and transplanted across the major histocompatibility barrier with C57BL/6 spleen cells, and subsequently treated with fludarabine was significantly longer than that of the control animals ( P
