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mtor protein, human

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https://www.readbyqxmd.com/read/28528867/a-pan-cancer-proteogenomic-atlas-of-pi3k-akt-mtor-pathway-alterations
#1
Yiqun Zhang, Patrick Kwok-Shing Ng, Melanie Kucherlapati, Fengju Chen, Yuexin Liu, Yiu Huen Tsang, Guillermo de Velasco, Kang Jin Jeong, Rehan Akbani, Angela Hadjipanayis, Angeliki Pantazi, Christopher A Bristow, Eunjung Lee, Harshad S Mahadeshwar, Jiabin Tang, Jianhua Zhang, Lixing Yang, Sahil Seth, Semin Lee, Xiaojia Ren, Xingzhi Song, Huandong Sun, Jonathan Seidman, Lovelace J Luquette, Ruibin Xi, Lynda Chin, Alexei Protopopov, Thomas F Westbrook, Carl Simon Shelley, Toni K Choueiri, Michael Ittmann, Carter Van Waes, John N Weinstein, Han Liang, Elizabeth P Henske, Andrew K Godwin, Peter J Park, Raju Kucherlapati, Kenneth L Scott, Gordon B Mills, David J Kwiatkowski, Chad J Creighton
Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#2
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#3
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522343/exogenous-cathepsin-v-protein-protects-human-cardiomyocytes-hcm-from-angiotensin-%C3%A2-induced-hypertrophy
#4
Kun Huang, Lu Gao, Ming Yang, Jiliang Wang, Zheng Wang, Lin Wang, Guobin Wang, Huili Li
Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed...
May 15, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28520695/calreticulin-ameliorates-hypoxia-reoxygenation-induced-human-microvascular-endothelial-cell-injury-by-inhibiting-autophagy
#5
You Wang, Tian-Qi Tao, Dan-Dan Song, Xiu-Hua Liu
BACKGROUND: Autophagy has been found to be involved in myocardial ischemia/reperfusion injury. However, the underlying mechanism and significance of autophagy in reperfusion injury remain unclear. Herein, we evaluated the effects of exogenous calreticulin (CRT) on autophagy in hypoxia/reoxygenation (H/R)-treated human microvascular endothelial cells (MECs). METHODS: Human MECs were pretreated with CRT (25 pg/mL) for 30 min, followed by exposure in an incubator filled with a gas mixture of 90% N2, 5% O2, and 5% CO2 for 8-h hypoxia...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#6
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta Paola Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally-occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28508346/testosterone-insulin-like-effects-an-in-vitro-study-on-the-short-term-metabolic-effects-of-testosterone-in-human-skeletal-muscle-cells
#7
C Antinozzi, F Marampon, C Corinaldesi, E Vicini, P Sgrò, G B Vannelli, A Lenzi, C Crescioli, L Di Luigi
PURPOSE: Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery...
May 15, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#8
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#9
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28501615/the-changes-in-glucose-metabolism-and-cell-proliferation-in-the-kidneys-of-polycystic-kidney-disease-mini-pig-models
#10
Xiaoying Lian, Jing Zhao, Xiaoyuan Wu, Yingjie Zhang, Qinggang Li, Shupeng Lin, Xue-Yuan Bai, Xiangmei Chen
The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28498433/curcumin-induces-apoptotic-cell-death-and-protective-autophagy-in-human-gastric-cancer-cells
#11
Wei Li, Ying Zhou, Jin Yang, Haining Li, Huanhuan Zhang, Ping Zheng
Curcumin possesses an anticancer effect against a wide assortment of tumors with selective cytotoxicity for tumor cells. However, the mechanism involved in the curcumin‑induced anticancer effect remain unclear. In the present study, we investigated the efficacy of curcumin against human gastric cancer cell growth and the molecular mechanism involved. Our results demonstrated that curcumin inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN-28 in both a time- and dose-dependent manner...
May 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28488736/inhibition-of-mtor-pathway-decreases-the-expression-of-pre-meiotic-and-meiotic-markers-throughout-postnatal-development-and-in-adult-testes-in-mice
#12
P Sahin, N E Gungor-Ordueri, C Celik-Ozenci
Rapamycin (mTOR inhibitor) has been reported to have negative effect on human male gonadal function. Previously, we showed that mTOR signalling molecules are expressed during early spermatogenesis in mice. The objective of this study was to investigate the role of mTOR signalling in meiosis both during the first wave of spermatogenesis and also during adult spermatogenesis. Day 5 post-partum mice were administered rapamycin and retinoic acid (RA; a Stra8 activator), and expression of p-p70S6K and Stra8 proteins was evaluated...
May 10, 2017: Andrologia
https://www.readbyqxmd.com/read/28484006/uric-acid-priming-in-human-monocytes-is-driven-by-the-akt-pras40-autophagy-pathway
#13
Tania O Crişan, Maartje C P Cleophas, Boris Novakovic, Kathrin Erler, Frank L van de Veerdonk, Hendrik G Stunnenberg, Mihai G Netea, Charles A Dinarello, Leo A B Joosten
Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28481292/inhibition-of-human-lung-cancer-cell-proliferation-and-survival-by-post-exercise-serum-is-associated-with-the-inhibition-of-akt-mtor-p70-s6k-and-erk1-2
#14
Nigel Kurgan, Evelyn Tsakiridis, Rozalia Kouvelioti, Jessy Moore, Panagiota Klentrou, Evangelia Tsiani
Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and for the most cancer-related deaths. The survival pathway of Akt, its downstream effectors, the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70 S6K), and the Ras-extracellular signal-regulated kinase (Erk1/2) pathways are activated in cancer leading to cell survival and growth. Thus, approaches that inhibit these signaling molecules may prove useful in the fight against lung cancer. Exercise is associated with health benefits and a limited number of studies indicate that serum from physically active individuals inhibit mammary and prostate cancer cell growth...
May 8, 2017: Cancers
https://www.readbyqxmd.com/read/28478808/anticancer-activities-of-harmine-by-inducing-a-pro-death-autophagy-and-apoptosis-in-human-gastric-cancer-cells
#15
Chuan Li, Yihai Wang, Chunhua Wang, Xiaomin Yi, Mingya Li, Xiangjiu He
BACKGROUND: Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear. PURPOSE: To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells. METHODS/STUDY DESIGNS: The anti-proliferative activity of harmine in vitro was evaluated by MTT assay...
May 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28476678/anticancer-efficacy-of-the-ethyl-acetate-extract-from-the-traditional-chinese-medicine-herb-celastrus-orbiculatus-against-human-gastric-cancer
#16
Haibo Wang, Lide Tao, Tengyang Ni, Hao Gu, Feng Jin, Xiaojun Dai, Jun Feng, Yanbing Ding, Weiming Xiao, Shiyu Guo, Tadashi Hisamitsu, Yayun Qian, Yanqing Liu
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) herb Celastrus orbiculatus is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. The ethyl acetate extract of C. orbiculatus (C. orbiculatus extract, COE) was reported to show significant antitumor effects. However, no study in China or abroad has reported the effect and mechanism of COE in triggering apoptosis of gastric cancer (GC) cells...
May 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28476554/inhibition-of-autophagy-aggravated-4-nitrophenol-induced-oxidative-stress-and-apoptosis-in-nhpre1-human-normal-prostate-epithelial-progenitor-cells
#17
Yonghui Zhang, Chong Zhang, Fulu Dong, Miaomiao Chen, Jingchen Cao, Haiyan Wang, Ming Jiang
4-Nitrophenol (PNP), a well-established human carcinogen, has been proven to have detrimental effects on reproductive system of male rats in previous studies. The molecular mechanisms involved PNP-induced damage remain to be established. Autophagy can exert protective effects on various cytotoxic factors that induce injury. In the present study, we aim to investigate whether autophagy is induced by PNP and the function of autophagy in PNP-induced injury in NHPrE1, a normal human prostate epithelial progenitor cell line...
May 3, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28473727/cryptolepine-inhibits-melanoma-cell-growth-through-coordinated-changes-in-mitochondrial-biogenesis-dynamics-and-metabolic-tumor-suppressor-ampk%C3%AE-1-2-lkb1
#18
Harish C Pal, Ram Prasad, Santosh K Katiyar
Dysregulated mitochondrial dynamics and biogenesis have been associated with various pathological conditions including cancers. Here, we assessed the therapeutic effect of cryptolepine, a pharmacologically active alkaloid derived from the roots of Cryptolepis sanguinolenta, on melanoma cell growth. Treatment of human melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with cryptolepine (1.0, 2.5, 5.0 and 7.5 μM) for 24 and 48 h significantly (P < 0.001) inhibited the growth of melanoma cells but not normal melanocytes...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28473446/human-plasma-thioredoxin-80-increases-with-age-and-in-apoe-mice-induces-inflammation-angiogenesis-and-atherosclerosis
#19
Dominique Couchie, Boris Vaisman, Amna Abderrazak, Dler Faieeq Darweesh Mahmood, Magda M Hamza, Fanny Canesi, Vimala Diderot, Khadija El Hadri, Anne E Nègre-Salvayre, Aurélie Le Page, Tamas Fulop, Alan T Remaley, Mustapha Rouis
Background -Thioredoxin-1 (TRX1), a ubiquitous 12 kDa protein, exerts anti-oxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces up-regulation of pro-inflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a pro-inflammatory M1 phenotype. Methods -TRX1 and TRX80 plasma levels were determined using specific ELISA. ADAM-17 and ADAM-10 activities were measured using respectively SensoLyte® 520 ADAM10 Activity Assay Kit *Fluorimetric* and InnoZyme™ TACE Activity Kit...
May 4, 2017: Circulation
https://www.readbyqxmd.com/read/28468969/protein-kinase-ck2-controls-the-fate-between-th17-cell-and-regulatory-t-cell-differentiation
#20
Sara A Gibson, Wei Yang, Zhaoqi Yan, Yudong Liu, Amber L Rowse, Amy S Weinmann, Hongwei Qin, Etty N Benveniste
CK2 is a highly conserved and pleiotropic serine/threonine kinase that promotes many prosurvival and proinflammatory signaling pathways, including PI3K/Akt/mTOR and JAK/STAT. These pathways are essential for CD4(+) T cell activation and polarization, but little is known about how CK2 functions in T cells. In this article, we demonstrate that CK2 expression and kinase activity are induced upon CD4(+) T cell activation. Targeting the catalytic activity of CK2 using the next-generation small molecule inhibitor CX-4945 in vitro significantly and specifically inhibited mouse and human Th17 cell differentiation while promoting the generation of Foxp3(+) regulatory T cells (Tregs)...
May 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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