Simultaneous pancreas-kidney transplantation initial experience

Linhares, Marcelo Moura; Gonzalez, A. Medina; Triviño, Tarcísio; Melaragno, Cláudio S.; Moura, Ricardo P.; Garcez, MF; Sa, Jazaeri; Aguiar, Wilson; Succi, T; Barbosa, Cassiano; Pestana, José Osmar Medina

doi:10.1016/s0041-1345(03)00328-2

Cited by 6 publications

(4 citation statements)

References 5 publications

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“…Rapamycin was first isolated from the bacterium Streptomyces hygroscopicus , which was found in a soil sample taken from Easter Island, as a fungicide and subsequently discovered to have potent immunosuppressive and anti-tumour properties [173–175]. As an immunosuppressive drug, rapamycin (rapamune, sirolimus) was approved by FDA (USA Food and Drug Administration) in 1999 for prevention of renal allograft rejection [176].…”

Section: Mtor Pathway Inhibitors In Cancer Therapymentioning

confidence: 99%

The mTOR Signalling Pathway in Human Cancer

Pópulo

Lopes

Soares

2012

IJMS

690

596

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The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. It is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals, and essential signalling pathways, such as PI3K, MAPK and AMPK, in order to control cell growth, proliferation and survival. mTORC2 is considered resistant to rapamycin and is generally insensitive to nutrients and energy signals. It activates PKC-α and AKT and regulates the actin cytoskeleton. Deregulation of multiple elements of the mTOR pathway (PI3K amplification/mutation, PTEN loss of function, AKT overexpression, and S6K1, 4EBP1 and eIF4E overexpression) has been reported in many types of cancers, particularly in melanoma, where alterations in major components of the mTOR pathway were reported to have significant effects on tumour progression. Therefore, mTOR is an appealing therapeutic target and mTOR inhibitors, including the rapamycin analogues deforolimus, everolimus and temsirolimus, are submitted to clinical trials for treating multiple cancers, alone or in combination with inhibitors of other pathways. Importantly, temsirolimus and everolimus were recently approved by the FDA for the treatment of renal cell carcinoma, PNET and giant cell astrocytoma. Small molecules that inhibit mTOR kinase activity and dual PI3K-mTOR inhibitors are also being developed. In this review, we aim to survey relevant research, the molecular mechanisms of signalling, including upstream activation and downstream effectors, and the role of mTOR in cancer, mainly in melanoma.

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Section: Mtor Pathway Inhibitors In Cancer Therapymentioning

confidence: 99%

The mTOR Signalling Pathway in Human Cancer

Pópulo

Lopes

Soares

2012

IJMS

690

596

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“…It is a macrocyclic lactone produced by Streptomyces hygroscopicus and was first found from a soil sample of Easter Island (Rapa Nui) during a discovery program for anti-microbial agents in 1975 [57,58]. Rapamycin was initially developed as an anti-fungal agent and subsequently discovered to have equally potent immunosuppressive properties [57,59-61]. The preclinical studies on the immunosuppressive effect of rapamycin has been extensively reviewed [62].…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Updates of mTOR Inhibitors

Zhou¹,

Luo²,

Huang

2010

ACAMC

159

116

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Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.

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“…It was initially developed as an anti-fungal agent and subsequently discovered to have equally potent immunosuppressive and anti-tumor properties (Vezina et al, 1975; Douros and Suffness, 1981; Eng et al, 1984; Linhares et al, 2003). In 1999, rapamycin (Rapamune, Sirolimus), as an immunosuppresive drug, was approved by the Food and Drug Administration (FDA) in USA (Huang and Houghton, 2001).…”

Section: Mtor Regulation Of Cell Motilitymentioning

confidence: 99%

mTOR Signaling in Cancer Cell Motility and Tumor Metastasis

Zhou

Huang

2010

Crit Rev Eukar Gene Expr

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Tumor cell migration is a key step for formation of cancer metastasis. The mammalian target of rapamycin (mTOR), a highly conserved and ubiquitously expressed serine-threonine kinase, has been intensely studied for over a decade as a central regulator of cell growth, proliferation, differentiation and survival. Recent data have shown that mTOR also plays a critical role in the regulation of tumor cell motility and cancer metastasis. Here we briefly review recent advances about mTOR signaling in tumor cell motility. We also discuss recent findings about the mechanism by which rapamycin, a specific inhibitor of mTOR, inhibits cell motility in vitro and metastasis in vivo.

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Simultaneous pancreas-kidney transplantation initial experience

Cited by 6 publications

References 5 publications

The mTOR Signalling Pathway in Human Cancer

The mTOR Signalling Pathway in Human Cancer

Updates of mTOR Inhibitors

mTOR Signaling in Cancer Cell Motility and Tumor Metastasis

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