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https://www.readbyqxmd.com/read/28235195/fasting-mimicking-diet-promotes-ngn3-driven-%C3%AE-cell-regeneration-to-reverse-diabetes
#1
Chia-Wei Cheng, Valentina Villani, Roberta Buono, Min Wei, Sanjeev Kumar, Omer H Yilmaz, Pinchas Cohen, Julie B Sneddon, Laura Perin, Valter D Longo
Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing β cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models...
February 23, 2017: Cell
https://www.readbyqxmd.com/read/28232835/mesenchymal-stem-cells-support-survival-and-proliferation-of-primary-human-acute-myeloid-leukemia-cells-through-heterogeneous-molecular-mechanisms
#2
Annette K Brenner, Ina Nepstad, Øystein Bruserud
Acute myeloid leukemia (AML) is a bone marrow malignancy, and various bone marrow stromal cells seem to support leukemogenesis, including osteoblasts and endothelial cells. We have investigated how normal bone marrow mesenchymal stem cells (MSCs) support the in vitro proliferation of primary human AML cells. Both MSCs and primary AML cells show constitutive release of several soluble mediators, and the mediator repertoires of the two cell types are partly overlapping. The two cell populations were cocultured on transwell plates, and MSC effects on AML cells mediated through the local cytokine/soluble mediator network could thus be evaluated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28232476/potential-targets-analysis-reveals-dual-pi3k-mtor-pathway-inhibition-as-a-promising-therapeutic-strategy-for-uterine-leiomyosarcomas-an-enitec-group-initiative
#3
Tine Cuppens, Daniela Annibali, An Coosemans, Jone Trovik, Natalja Ter Haar, Eva Colas, Angel Garcia-Jimenez, Koen Van de Vijver, Roy P M Kruitwagen, Mariël Brinkhuis, Michal Zikan, Pavel Dundr, Jutta Huvila, Olli Carpén, Johannes Haybaeck, Farid Moinfar, Helga B Salvesen, Maciej Stukan, Carole Mestdagh, Ronald P Zweemer, Leonardus F Massuger, Michael R Mallmann, Eva Wardelmann, Miriam Mints, Godelieve Verbist, Debby Thomas, Ellen Gommé, Els Hermans, Philippe Moerman, Tjalling Bosse, Frédéric Amant
Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment.Experimental Design: We investigated the expression of several druggable targets (phospho-S6(S240) ribosomal protein, PTEN, PDGFR-α, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues...
February 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28231748/aloe-emodin-enhances-tamoxifen-cytotoxicity-by-suppressing-ras-erk-and-pi3k-mtor-in-breast-cancer-cells
#4
Hsin-Shun Tseng, Yu-Fen Wang, Yew-Min Tzeng, Dar-Ren Chen, Ya-Fan Liao, Hui-Yu Chiu, Wen-Tsong Hsieh
Aloe-emodin (AE) is derived from Aloe vera and rhubarb (Rheum palmatum) and exhibits anticancer activities via multiple regulatory mechanisms in various cancers. AE can also enhance the anticancer efficacy of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil; however, its effects remain poorly characterized. MCF-7, MDA-MB-231, MDA-MB-468, BT-474, and HCC-1954 breast cancer cell lines were treated with the indicated conditions of AE, and cell viability assays were performed. The expression levels of signaling proteins were determined by western blot analysis, intracellular reactive oxygen species (ROS), cell cycle distributions, and rates of apoptosis as estimated by flow cytometry...
February 23, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28231742/stephania-tetrandra-and-ginseng-containing-chinese-herbal-formulation-nsenl-reverses-cisplatin-resistance-in-lung-cancer-xenografts
#5
Ling Jin, Meng Xu, Xue-Hua Luo, Xiao-Feng Zhu
Chinese Herbal Formulation, supplement energy and nourish lung (SENL), effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multi-drug resistance (MDR) in lung cancer cells in vitro. The present study is designed to assess the effect of a New SENL (NSENL, modification of SENL) formulation on resistance to chemotherapy of cisplatin (DDP)-resistant human lung cancer cell line (A549/DDP) xenografts in nude mice. We assessed six constituents in NSENL by high performance liquid chromatography (HPLC)...
February 23, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28231559/prostate-cancer-heterogeneity-discovering-novel-molecular-targets-for-therapy
#6
REVIEW
Chiara Ciccarese, Francesco Massari, Roberto Iacovelli, Michelangelo Fiorentino, Rodolfo Montironi, Vincenzo Di Nunno, Francesca Giunchi, Matteo Brunelli, Giampaolo Tortora
Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies...
February 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28230926/association-between-high-expression-of-phosphorylated-akt-and-mammalian-target-of-rapamycin-and-improved-survival-in-salivary-gland-adenoid-cystic-carcinoma
#7
Dai-Qiao Ouyang, Li-Zhong Liang, Zun-Fu Ke, Guang-Sen Zheng, De-Sheng Weng, Wei-Fa Yang, Yu-Xiong Su, Gui-Qing Liao
BACKGROUND: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. METHODS: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data...
February 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28230853/mesenchymal-stromal-cells-inhibit-cd25-expression-via-the-mtor-pathway-to-potentiate-t-cell-suppression
#8
Hyun Seung Yoo, Kyuheon Lee, Kwangmin Na, Yong Xu Zhang, Hyun-Ja Lim, TacGhee Yi, Sun U Song, Myung-Shin Jeon
Mesenchymal stromal cells (MSCs) are known to suppress T-cell activation and proliferation. Several studies have reported that MSCs suppress CD25 expression in T cells. However, the molecular mechanism underlying MSC-mediated suppression of CD25 expression has not been fully examined. Here, we investigated the mTOR pathway, which is involved in CD25 expression in T cells. We showed that MSCs inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase (iNOS) inhibitor...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#9
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230639/mammalian-target-of-rapamycin-inhibition-clinical-transplantation-liver
#10
Björn Nashan
The evidence base concerning use of mammalian target of rapamycin (mTOR) inhibitor therapy after liver transplantation is evolving rapidly, clarifying their benefits and disadvantages in different clinical scenarios. The H2304 trial showed that starting everolimus at 1 month posttransplant, with reduced tacrolimus, achieves a sustained improvement in renal function versus standard tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. Randomized studies evaluating early discontinuation of CNI therapy after introduction of an mTOR inhibitor consistently demonstrated a substantial improvement in renal function versus standard CNI therapy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230638/mtor-inhibition-cardiovascular-diseases-dyslipidemia-and-atherosclerosis
#11
Ammar Kurdi, Wim Martinet, Guido R Y De Meyer
Inhibitors of the mechanistic target of rapamycin (mTOR) have unique anti-atherosclerotic effects such as depletion of plaque macrophages, induction of autophagy and activation of cholesterol efflux. However, a common side effect of their use is dyslipidemia, a well-known risk factor for atherosclerosis. Indeed, mTOR inhibitors prevent lipid storage, increase LDL cholesterol levels and activate lipolysis. Although the net effect of mTOR inhibition seems favorable, the use of cholesterol lowering drugs to manage dyslipidemia remains the most recommended strategy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230637/mtor-inhibition-and-cardiovascular-diseases-cardiac-hypertrophy
#12
Ernesto Paoletti
Left ventricular hypertrophy (LVH) is highly prevalent in kidney transplant recipients, and is associated with poor clinical outcome. Immunosuppressive agents might affect LVH behavior after kidney transplantation. This review is an appraisal of available data regarding LVH in renal transplantation and especially of studies that evaluated LVH response to treatment. In particular, the role of mammalian target of rapamycin inhibitors adopted as immunosuppressive agents in kidney transplantation is reviewed in the light of recent studies that have shown LVH regression induced by this class of medications in kidney transplant recipients with posttransplant cardiomyopathy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230636/mtor-inhibition-clinical-transplantation-kidney
#13
Stuart M Flechner
No abstract text is available yet for this article.
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#14
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With an aim to evaluate anti-cancerous activities of 10-gingerol (10-G) against Hela cells, it was purified and identified from Tongling White Ginger by HSCCC, UPLC-TOF-MS/MS and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity and arrested cell cycle in G0/G1-phase. The most cell cycle related genes and proteins expression significantly decreased, followed by slight decrease in few and without affecting cyclin B1 and cyclin E1 (protein)...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28230287/therapeutic-potential-of-targeting-pi3k-akt-pathway-in-treatment-of-colorectal-cancer-rational-and-progress
#15
Afsane Bahrami, Majid Khazaei, Malihe Hasanzadeh, Soodabeh ShahidSales, Mona Joudi Mashhad, Marjaneh Farazestanian, Hamid Reza Sadeghnia, Majid Rezayi, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
PI3K/AKT/mTOR signaling pathway is one of the key dysregulated pathways in different tumor types, including colorectal cancer (CRC). Activation of this pathway is shown to be related with cellular transformation, tumor progression, cell survival and drug resistance. There is growing body of data evaluating the value of PI3K/AKT/mTOR inhibitors in CRC (e.g., BEZ235, NVP-BEZ235, OSI-027, everolimus, MK-2206, KRX-0401, BYL719 and BKM120). This report summarizes the current knowledge about PI3K/AKT pathway and its cross talk with ERK/MAPK and mTOR pathways with particular emphasis on the value of targeting this pathway as a potential therapeutic target in treatment of colorectal cancer...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230281/resveratrol-enhances-self-renewal-of-mouse-embryonic-stem-cells
#16
Na Li, Zhaoyu Du, Qiaoyan Shen, Qijing Lei, Ying Zhang, Mengfei Zhang, Jinlian Hua
Resveratrol (RSV) has been shown to affect the differentiation of several types of stem cells, while the detailed mechanism is elusive. Here, we aim to investigate the function of RSV in self-renewal of mouse embryonic stem cells (ESCs) and the related mechanisms. In contrast with its reported roles, we found unexpectedly that differentiated ESCs or iPSCs treated by RSV would not show further differentiation, but regained a naïve pluripotency state with higher expressions of core transcriptional factors and with the ability to differentiate into all three germ layers when transplanted in vivo...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229968/cytotoxic-and-toxicogenomic-effects-of-silibinin-in-bladder-cancer-cells-with-different-tp53-status
#17
Daiane Teixeira DE Oliveira, Andre Luiz Ventura Savio, Joao Paulo DE Castro Marcondes, Tatiane Martins Barros, Ludmila Correia Barbosa, Daisy Maria Favero Salvadori, Glenda Nicioli DA Silva
Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#18
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
February 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#19
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28229364/molecular-subtyping-in-diffuse-large-b-cell-lymphoma-closer-to-an-approach-of-precision-therapy
#20
REVIEW
Reem Karmali, Leo I Gordon
It has become clear that there is immense biological heterogeneity in diffuse large B cell lymphoma (DLBCL). Developing technology has allowed better characterization of patient subsets at a molecular level, allowing for a link of phenotype and clinical outcomes to oncogenic mechanisms and biologic signatures. Cell of origin and double hit status are able to identify aggressive subsets, with molecular profiling allowing for a clearer understanding of biologic pathways that contribute to cellular resistance to conventional treatment in these subsets...
February 2017: Current Treatment Options in Oncology
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