Prolongation Of Renal Allograft Survival In A Large Animal Model By Oral Rapamycin Monotherapy

Granger, Darla K.; Cromwell, John W.; Chen, Sally C.; Goswitz, Joseph J.; Morrow, David T.; Beierle, Floyd A.; Sehgal, Suren N.; Canafax, Daniel M.; Matas, Arthur J.

doi:10.1097/00007890-199501270-00005

Cited by 10 publications

(10 citation statements)

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“…For example, in pharmacokinetic studies performed to support the current experiments (S.R. Magari and F. Cerasoli, unpublished observations), the absolute oral bioavailability of rapamycin was measured as 15% which corroborates previous animal and clinical studies (21)(22)(23)(24). This degree of oral bioavailability and resultant circulating and/or tissue rapamycin concentrations, to which the HT26-1 cells are exposed, explains why intravenous rapamycin yields an ED 50 that is 16.3% of the oral ED 50 ‫ف(‬ 1.3 and 8.0 mg/kg, respectively; Fig.…”

Section: Discussionsupporting

confidence: 90%

Pharmacologic control of a humanized gene therapy system implanted into nude mice.

Magari¹,

Rivera²,

Iuliucci³

et al. 1997

J. Clin. Invest.

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Systemic delivery of specific therapeutic proteins by a parenteral route of administration is a recognized practice in the management of several gene defects and acquired diseases. As an alternative to repetitive parenteral administration, gene therapy may provide a novel means for systemic delivery of therapeutic proteins while improving patient compliance and therapeutic efficacy. However, for gene therapy to be an efficacious and safe approach to the clinical management of such diseases, gene expression must be tightly regulated. These investigations demonstrate precise in vivo control of protein expression from cells that are engineered to secrete human growth hormone (hGH) in response to stimulation by rapamycin. The cells were implanted intramuscularly into nu / nu mice and stimulated by intravenous or oral administration of rapamycin. In vivo experiments demonstrate that the activity and pharmacokinetics of rapamycin determine the level of serum hGH that result from the engineered cells. In addition, responsiveness of the cells to rapamycin, number of cells implanted, hGH expression kinetics, and the pharmacokinetics of hGH itself, also influence the circulating levels of hGH after rapamycin stimulation. Controlled manipulation of several of these parameters, either independently or in combination, allows for precise regulation of circulating hGH concentration in vivo. ( J. Clin. Invest. 1997. 100:2865-2872.)

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Section: Discussionsupporting

confidence: 90%

Pharmacologic control of a humanized gene therapy system implanted into nude mice.

Magari¹,

Rivera²,

Iuliucci³

et al. 1997

J. Clin. Invest.

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“…47 Sirolimus was also effective in preventing acute allograft rejection in rat models of pancreas and small-bowel transplantation [49][50][51][52] and showed efficacy in the treatment of ongoing heart, kidney, and pancreas rejection. 53,54 In addition, sirolimus showed efficacy in transplant models of different large animal models [55][56][57][58][59][60][61] and nonhuman primates. 35,36,62 Like sirolimus, RAD showed high efficacy in preventing and treating allograft rejections in rat models of heart, 46 kidney, 63 and lung transplantation [64][65][66] and in transplant models of nonhuman primates.…”

Section: Preclinical Animal Studiesmentioning

confidence: 99%

mTOR inhibitors: An overview

Neuhaus

Klupp

Langrehr

2001

Liver Transplantation

181

142

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“…Rapamycyna została po raz pierwszy zidentyfikowana jako lek przeciwgrzybiczny [21,22]. Identyfikacja właściwości immunosupresyjnych Rapamycyny [23] umożliwiła wykorzystanie leku w procedurach allogenicznych transplantacji nerki [24]. Immunosupresyjny wpływ Rapamycyny na układ immunologiczny polega na zmniejszeniu odpowiedzi limfocytów T na sygnały proproliferacyjne, indukowanej przez IL-1, Il-2, IL-3, IL-4, IL-6.…”

Section: Wiktoria Maria Suchorska Mikołaj Nowak / Zeszyty Naukowe Wcunclassified

Ocena potencjału terapeutycznego Temsirolimusu w zaawansowanym stadium renal cell carcinoma

Suchorska

Nowak²

2017

los

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Prolongation Of Renal Allograft Survival In A Large Animal Model By Oral Rapamycin Monotherapy

Cited by 10 publications

References 0 publications

Pharmacologic control of a humanized gene therapy system implanted into nude mice.

Pharmacologic control of a humanized gene therapy system implanted into nude mice.

mTOR inhibitors: An overview

Ocena potencjału terapeutycznego Temsirolimusu w zaawansowanym stadium renal cell carcinoma

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