Prompt coronary reperfusion is the gold standard for minimizing injury following acute myocardial infarction. Rapamycin, mammalian target of Rapamycin (mTOR) inhibitor, exerts preconditioning-like cardioprotective effects against ischemia/reperfusion (I/R) injury. We hypothesized that Rapamycin, given at the onset of reperfusion, reduces myocardial infarct size through modulation of mTOR comple...

PC is a rare, debilitating disease with lifelong limited mobility caused by mutations in KRT6, 16, or 17. There are no approved therapies. mTOR regulates expression of KRT6 and its binding partners KRT16 We completed Ph. 2/3 3b trials QTORIN rapamycin for PC. identified cohort subjects, gradual responders, who accrued higher response between 12 24 weeks therapy. The trial was randomized withdra...

Rapamycin and its analogues are being tested as new antitumor agents. Rapamycin binds to FKBP-12 and this complex inhibits the activity of FRAP/mammalian target of rapamycin, which leads to dephosphorylation of 4EBP1 and p70 S6 kinase, resulting in blockade of translation initiation. We have found that RAP inhibits the growth of HER-2-overexpressing breast cancer cells. The phosphorylation of m...

Rapamycin) signaling controls growth and metabolism from yeast to mammals [1]. Mammalian or mechanistic TOR (mTOR) plays the key role in aging and age-related disease [2]. Rapamycin, a drug used clinically for organ transplants, coronary stent coating and certain forms of cancer treatments, is an inhibitor for mTOR. In the first robust demonstration of pharmacologically-induced life extension i...

Mammalian target of rapamycin (mTOR) regulates cell growth, cell differentiation and protein synthesis. Rapamycin, an inhibitor of mTOR, has been widely used as an immunosuppressant and anti-cancer drug. Recently, mTOR inhibitors have also been reported to be a potential anti-epileptic drug, which may be effective when used in young patients with genetic epilepsy. Thus, a suitable dose of rapam...

It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed th...

Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing Program (PPTP). Here we have evaluated rapamycin combined with agents used frequently in the treatment of childhood malignancies. Rapamycin was tested in vitro against 23 cell lines alone or in combination with melphalan, cisplatin, vinc...

PURPOSE Rapamycin has been shown to have antitumor effects in various tumor models. To study the effect of rapamycin at different stages of breast cancer development, we used two unique mouse models of breast cancer with activated phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive and metastatic, and mammary intraepithelial neoplasia-outgrowths (MIN-O), a model for h...

Rapamycin is a canonical allosteric inhibitor of the mammalian tarpet of rapamycin (mTOR) kinase with immunosuppressive and proapoptotic activities. We found that in vitro rapamycin also regulates the proteasome, which is an essential intracellular protease of the ubiquitin-proteasome pathway. Rapamycin inhibits proteinase and selected peptidase activities of the catalytic core proteasome at lo...

PURPOSE The mammalian target of rapamycin (mTOR) kinase acts downstream of phosphoinositide 3-kinase/Akt to regulate cellular growth, metabolism, and cytoskeleton. Because approximately 60% of sporadic colorectal cancers (CRC) exhibit high levels of activated Akt, we determined whether downstream mTOR signaling pathway components are overexpressed and activated in CRCs. EXPERIMENTAL DESIGN HC...