Search results for "Rapamycin"
showing 4 items of 44 documents
Lipid Activates mTORC1 and mTORC2 in the Absorption of Dietary Triglycerides
2018
Mechanistic target of rapamycin (mTOR) senses amino acids; however, its role in lipid metabolism is less established. Organismal lipid requirements are largely met through dietary intake. How nutrient sensing mechanisms in gut interface with dietary fat remains unclear. Here we reveal fundamental and cooperative roles for mTOR complexes 1 and 2 (mTORC1/2) in absorption of dietary triglycerides. Dietary lipid activates mTORC1/2 signaling in gut. Hyperactivating mTORC1 by deleting Tsc1 is sufficient to promote triglyceride absorption and metabolic disease in high fat-fed mice. Conversely, blocking mTORC1/2 by deleting Raptor or Rictor each decreases triglyceride absorption. Loss of Raptor seq…
<p>Clinical Evaluation of Everolimus in the Treatment of Neuroendocrine Tumors of the Lung: Patient Selection and Special Considerations. A Sys…
2020
Abstract Neuroendocrine tumors (NETs) of the lung are well-differentiated neuroendocrine neoplasms (NENs) with a heterogeneous clinical behaviour. Unlike gastroenteropancreatic NENs where therapeutic armamentarium clearly increased over the last decade, everolimus represented the only clinical practical innovation for lung NET patients over the last years. Therefore, for lung NETs, a multidisciplinary discussion within a dedicated team remains critical for an adequate decision-making. Although the main regulatory authorities considered the everolimus-related evidence is enough to approve the drug in advanced lung NETs, several clinical features deserve to be discussed. In this review, we sy…
Efficacy of Rapamycin as Inducer of Hb F in Primary Erythroid Cultures from Sickle Cell Disease and β-Thalassemia Patients.
2015
Phenotypic improvement of hemoglobinopathies such as sickle cell disease and β-thalassemia (β-thal) has been shown in patients with high levels of Hb F. Among the drugs proposed to increase Hb F production, hydroxyurea (HU) is currently the only one proven to improve the clinical course of these diseases. However, Hb F increase and patient's response are highly variable, indicating that new pharmacological agents could be useful for patients not responding to HU or showing a reduction of response during long-term therapy. In this study we evaluated the efficacy of rapamycin, a lypophilic macrolide used for the prevention of acute rejection in renal transplant recipients, as an inducer of Hb…
MTOR inhibitor-based combination therapies for pancreatic cancer
2018
Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…