The Experts below are selected from a list of 109842 Experts worldwide ranked by ideXlab platform
Sandra L Dabora - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:BackgroundSkin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors.Methods0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.ResultsTreatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin.ConclusionTopical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
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topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors. 0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts. Treatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin. Topical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
Aubrey Rauktys - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:BackgroundSkin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors.Methods0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.ResultsTreatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin.ConclusionTopical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
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topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors. 0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts. Treatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin. Topical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
J Clardy - One of the best experts on this subject based on the ideXlab platform.
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Refined structure of the FKBP12-Rapamycin-FRB ternary complex at 2.2 A resolution.
Acta Crystallographica Section D Biological Crystallography, 1999Co-Authors: J Liang, J Choi, J ClardyAbstract:The structure of the FKBP12–Rapamycin–FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent Rapamycin binds FK506-binding protein (FKBP12) and the FKBP12–Rapamycin binding (FRB) domain of FKBP12–Rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for Rapamycin's biological activity. The conformation of Rapamycin in the ternary complex is very similar to that observed in the FKBP12–Rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9°) rotation repositions the FRB-binding face of Rapamycin in the ternary complex. There are extensive Rapamycin–protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and α1 and α4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.
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Refined structure of the FKBP12-Rapamycin-FRB ternary complex at 2.2 A resolution.
Acta crystallographica. Section D Biological crystallography, 1999Co-Authors: J Liang, J Choi, J ClardyAbstract:The structure of the FKBP12-Rapamycin-FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent Rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-Rapamycin binding (FRB) domain of FKBP12-Rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for Rapamycin's biological activity. The conformation of Rapamycin in the ternary complex is very similar to that observed in the FKBP12-Rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of Rapamycin in the ternary complex. There are extensive Rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.
Ichiro Katayama - One of the best experts on this subject based on the ideXlab platform.
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a topical combination of Rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex tsc a pilot study of nine japanese patients with tsc of different disease severity
British Journal of Dermatology, 2011Co-Authors: Mari Watayakaneda, Mari Tanaka, Ayumi Nakamura, Shoji Matsumoto, Ichiro KatayamaAbstract:Summary Background Dysregulation of mTOR signalling by mutations in tuberin and/or hamartin leads to the formation of tuberous sclerosis complex (TSC). Trials to treat TSC using mTOR inhibitors, including Rapamycin, have been performed. Although Rapamycin improves many TSC lesions, significant side-effects appear after systemic administration. Topical administration has been recommended. Objectives The efficacy of Rapamycin–tacrolimus ointment was examined for TSC-related angiofibroma. Methods Left–right comparisons of the tacrolimus ointments with/without 0·2% Rapamycin was conducted in symmetrical facial angiofibromas in nine patients with definitive TSC. After the 3-month treatment, a cumulative score for redness, flatness and papule size was used to evaluate the efficacy of the treatment. Blood Rapamycin levels were analysed by liquid chromatography-electrospray mass spectrometry (LC-ESI/MS). Results At the end of the treatment, all of the scores significantly improved for Rapamycin–tacrolimus treatment compared with tacrolimus alone. No adverse reactions were noted and blood levels of Rapamycin were below the detection limit in all cases. Conclusions Topical application of Rapamycin–tacrolimus ointment is a safe and useful treatment for TSC-related angiofibroma.
Nancy Lee - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:BackgroundSkin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors.Methods0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.ResultsTreatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin.ConclusionTopical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
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topical Rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
BMC Dermatology, 2008Co-Authors: Aubrey Rauktys, Nancy Lee, Laifong Lee, Sandra L DaboraAbstract:Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with Rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical Rapamycin in a mouse model for TSC-related tumors. 0.4% and 0.8% Rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected Rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts. Treatment with topical Rapamycin improved survival and reduced tumor growth. Topical Rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected Rapamycin. Topical Rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
