PURPOSE To clarify the role of ABCB1, ABCG2, and CYP3A in blood and brain exposure of everolimus using knockout mouse models. EXPERIMENTAL DESIGN We used wild-type, Abcb1a/1b(-/-), Abcg2(-/-), Abcb1a/1b;Abcg2(-/-), and Cyp3a(-/-) mice to study everolimus oral bioavailability and brain accumulation. RESULTS Following everolimus administration, brain concentrations and brain-to-liver ratios w...

BACKGROUND The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. METHODS In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with ...

Pancreatic neuroendocrine tumors (PanNETs) are frequently diagnosed at unresectable stage and remain a medical challenge. Everolimus (RAD001, Afinitor(®), Novartis, Basel, Switzerland), an orally administered inhibitor of mammalian target of rapamycin (mTOR), was recently approved by the Food and Drug Administration to treat patients with advanced PanNETs. This review will examine the mechanism...

Modern radiation therapy strives to minimize injury to organs while increasing the anticancer effects. The present study aimed to investigate the radiosensitizing effects of everolimus and to examine the molecular mechanisms responsible for everolimus‑mediated radiosensitization. Radiation in combination with everolimus (30 nM) sensitized Ras-transformed cells to radiation in vitro. Radiation i...

BACKGROUND Sorafenib-everolimus combination therapy may be more effective than sorafenib monotherapy for hepatocellular carcinoma (HCC). To better understand this effect, we comparatively profiled the metabolite composition of HepG2 cells treated with sorafenib, everolimus, and sorafenib-everolimus combination therapy. MATERIAL AND METHODS A 2D HRMAS 1H-NMR metabolomic approach was applied to...

OBJECTIVES Therapeutic monitoring of sirolimus and everolimus is necessary in order to minimize adverse side-effects and to ensure effective immunosuppression. A sirolimus-dosing model using the concentration/dose ratio has been previously proposed for kidney transplant patients, and the aim of our study was the evaluation of this single model for the prediction of trough sirolimus and everolim...

Everolimus inhibits mTOR kinase activity and its downstream targets by acting on mTORC1 and has anti-tumorigenic activity in ovarian cancer. Clinical and epidemiologic data find that obesity is associated with worse outcomes in ovarian cancer. In addition, obesity leads to hyperactivation of the mTOR pathway in epithelial tissues, suggesting that mTOR inhibitors may be a logical choice for trea...

BACKGROUND Everolimus has been approved for second-line treatment of patients with metastatic renal cell carcinoma (mRCC) after failure of sorafenib or sunitinib. The purpose of this retrospective study was to assess the efficacy and safety of everolimus in Taiwanese patients with mRCC. METHODS Between March 2009 and August 2011, 24 mRCC patients treated with everolimus were analyzed. Prior t...

BACKGROUND Rapamycin (sirolimus)-eluting stents are associated with reduced restenosis rates in animal studies and initial human trials. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) inhibits in-stent neointimal growth in rabbit iliac arteries. METHODS AND RESULTS New Zealand white rabbits were randomized to everolimus 1.5 mg/...

Everolimus is used as an immunosuppressant in renal allograft transplant rejection and in metastatic breast cancer treatment. One side effect of everolimus is stomatitis, referred to as mammalian target of rapamycin inhibitor-associated stomatitis. This side effect can affect treatment course and contribute to discontinuation of therapy or dose reduction, previously reported in the treatment of...