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4EBP1

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https://www.readbyqxmd.com/read/28728363/effect-of-different-levels-of-protein-concentrates-supplementation-on-the-growth-performance-plasma-amino-acids-profile-and-mtor-cascade-genes-expression-in-early-weaned-yak-calves
#1
Quhani Peng, Nazir Ahmad Khan, B Xue, T H Yan, Z S Ahmad Wang
Objective: Yak is anone of the most important livestock species in the alpine-meadow grasslands of Qinghai-Tibetan plateau. WeThis study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to the changes occurring in the plasma- amino acids, and -insulin profile, and to the signaling activity of mammalian target of rapamycin (mTOR) cascade, in order to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks...
June 27, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28711648/alteration-of-pdgfr%C3%AE-akt-mtor-pathway-signaling-in-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#2
Yuka Hiraki-Hotokebuchi, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Makoto Endo, Nokitaka Setsu, Kuma Yuki, Takamichi Ito, Yukihide Iwamoto, Masutaka Furue, Yoshinao Oda
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by western blotting...
July 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28696243/inhibiting-4ebp1-in-glioblastoma
#3
Qi Wen Fan, Theodore P Nicolaides, William A Weiss
Glioblastoma is the most common and aggressive adult brain cancer. Tumors show frequent dysregulation of the phosphatidylinositol-3 kinase-mechanistic target of rapamycin pathway. While a number of small molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy has been limited. Reasons for treatment failure include poor penetration of agents into the brain, and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Clinical trials using allosteric mTOR inhibitors (rapamycin and rapalogs) to treat glioblastoma patients have also been unsuccessful or uncertain, in-part because rapamycin inefficiently blocks the mTORC1 target 4EBP1, and also feeds back to activate PI3K-AKT signaling...
July 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28664915/kinase-driven-metabolic-signalling-as-a-predictor-of-response-to-carboplatin-paclitaxel-adjuvant-treatment-in-advanced-ovarian-cancers
#4
Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K Alex Hodge, David S Alberts, Jose M Guillen-Rodriguez, Ting Dong, Maurizio Memo, Franco Odicino, Roberto Angioli, Lance A Liotta, Sergio L Pecorelli, Emanuel F Petricoin, Mariaelena Pierobon
BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection...
June 29, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28656204/effects-of-bufalin-on-the-mtor-p70s6k-pathway-and-apoptosis-in-esophageal-squamous-cell-carcinoma-in-nude-mice
#5
Yao Liu, Xu Wang, Ying Jia, Yueping Liu
The aim of this study was to investigate the effects of bufalin on the mammalian target of rapamycin (mTOR/p70S6 kinase (p70S6K) signaling pathway and cell apoptosis in orthotopically transplanted tumors in nude mice. The mice were inoculated with human esophageal squamous cell carcinoma (ESCC) ECA109 cells in order to establish a model of orthotopicall transplanted ESCC tumors. The mice are administered low, medium and high doses of bufalin (0.5, 1.0 and 1.5 mg/kg) or rapamycin, or a combination of both...
June 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28612529/-the-mechanism-of-combination-using-mtorc1-2-inhibitor-and-imatinib-to-suppress-cell-proliferation-of-ph-all-cell-line
#6
Jia-Hui Wu, Fang-Fang Shi, Yu-Ping Gong, Rui Shi
OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28594375/a-high-protein-diet-reduces-weight-gain-decreases-food-intake-decreases-liver-fat-deposition-and-improves-markers-of-muscle-metabolism-in-obese-zucker-rats
#7
William W French, Sami Dridi, Stephanie A Shouse, Hexirui Wu, Aubree Hawley, Sun-Ok Lee, Xuan Gu, Jamie I Baum
A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10)...
June 8, 2017: Nutrients
https://www.readbyqxmd.com/read/28584287/rescue-of-impaired-sociability-and-anxiety-like-behavior-in-adult-cacna1c-deficient-mice-by-pharmacologically-targeting-eif2%C3%AE
#8
Z D Kabir, A Che, D K Fischer, R C Rice, B K Rizzo, M Byrne, M J Glass, N V De Marco Garcia, A M Rajadhyaksha
CACNA1C, encoding the Cav1.2 subunit of L-type Ca(2+) channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28574820/differentiation-capacities-of-skeletal-muscle-satellite-cells-in-lantang-and-landrace-piglets
#9
Chun-Qi Gao, Yin-Long Xu, Cheng-Long Jin, Xiao-Chao Hu, Hai-Chang Li, Guang-Xu Xing, Hui-Chao Yan, Xiu-Qi Wang
We isolated and cultured satellite cells (SCs) from the longissimus dorsi muscles of 1-day-old male Landrace and Lantang piglets to compare the SC differentiation capacity in the two breeds. Lantang piglets yielded more (P < 0.05) SCs per gram of muscle than Landrace piglets (5.2 ± 0.9×104 vs. 2.4 ± 0.2×104). Transcription of the differentiation markers myogenin and myosin heavy chain I (MyHC I) in the longissimus dorsi muscle was higher in Lantang than Landrace piglets (P < 0.05). Protein levels of myogenin (P < 0...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571990/optimal-ratios-of-essential-amino-acids-stimulate-%C3%AE-casein-synthesis-via-activation-of-the-mammalian-target-of-rapamycin-signaling-pathway-in-mac-t-cells-and-bovine-mammary-tissue-explants
#10
S S Li, J J Loor, H Y Liu, L Liu, A Hosseini, W S Zhao, J X Liu
Amino acids are the building blocks of proteins and serve as key molecular components upstream of the signaling pathways that regulate protein synthesis. The objective of this study was to systematically investigate the effect of essential AA ratios on milk protein synthesis in vitro and to elucidate some of the underlying mechanisms. Triplicate cultures of MAC-T cells and bovine mammary tissue explants (MTE) were incubated with the optimal AA ratio (OPAA; Lys:Met, 2.9:1; Thr:Phe, 1.05:1; Lys:Thr, 1.8:1; Lys:His, 2...
May 29, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28554144/muscle-specific-deletion-of-socs3-does-not-reduce-the-anabolic-response-to-leucine-in-a-mouse-model-of-acute-inflammation
#11
M K Caldow, D J Ham, A Chee, J Trieu, T Naim, D I Stapleton, K Swiderski, G S Lynch, R Koopman
Excessive inflammation reduces skeletal muscle protein synthesis leading to wasting and weakness. The janus kinase/signal transducers and activators of transcription-3 (JAK/STAT3) pathway is important for the regulation of inflammatory signaling. As such, suppressor of cytokine signaling-3 (SOCS3), the negative regulator of JAK/STAT signaling, is thought to be important in the control of muscle homeostasis. We hypothesized that muscle-specific deletion of SOCS3 would impair the anabolic response to leucine during an inflammatory insult...
May 25, 2017: Cytokine
https://www.readbyqxmd.com/read/28549345/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#12
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544394/muscle-metabolic-alterations-induced-by-genetic-ablation-of-4e-bp1-and-4e-bp2-in-response-to-diet-induced-obesity
#13
Olivier Le Bacquer, Kristell Combe, Christophe Montaurier, Jérôme Salles, Christophe Giraudet, Véronique Patrac, Carla Domingues-Faria, Christelle Guillet, Katie Louche, Yves Boirie, Nahum Sonenberg, Cédric Moro, Stéphane Walrand
SCOPE: In recent years, several studies reported the role of eIF4E-binding proteins (4E-BPs) on the development of diet-induced obesity and insulin resistance. Our aim was to investigate the effect of 4E-BP protein deletion on lipid accumulation and metabolism in skeletal muscle in response to a high fat diet-induced obesity in 4E-BP1/2 DKO mice. METHODS AND RESULTS: Diet-induced obesity engendered increased ectopic accumulation of lipotoxic species in skeletal muscle of 4E-BP1 and 4E-BP2 double-knockout mice (4E-BP1/2 DKO), namely diacylglycerols and ceramides...
May 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#14
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499984/systemic-pten-akt1-mtor-pathway-activity-in-patients-with-normal-tension-glaucoma-and-ocular-hypertension-a-case-series
#15
Gerassimos Lascaratos, Kai-Yin Chau, Haogang Zhu, Despoina Gkotsi, Deborah Kamal, Ivan Gout, Philip J Luthert, Anthony H V Schapira, David F Garway-Heath
Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients...
May 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28497545/milk-protein-synthesis-is-regulated-by-t1r1-t1r3-a-g-protein-coupled-taste-receptor-through-the-mtor-pathway-in-the-mouse-mammary-gland
#16
Junqiang Liu, Yanhong Wang, Dewei Li, Yanhuan Wang, Menglu Li, Caifa Chen, Xingtang Fang, Hong Chen, Chunlei Zhang
SCOPE: Understanding the regulatory mechanism of milk protein synthesis is important to develop strategies to improve milk protein and enhance lactation performance. mTOR pathway is a crucial modulator of protein synthesis. In this study, we want to investigate if T1R1/T1R3 can regulate milk protein synthesis and mediate the mTOR pathway in the mice mammary gland in vivo. METHODS AND RESULTS: T1R1 knockout mice, WT mice, and mammary explants were used. The weigh-suckle-weigh method was used to quantify the milk yield...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28455969/bmp2-promotes-proliferation-and-invasion-of-nasopharyngeal-carcinoma-cells-via-mtorc1-pathway
#17
Meng-He Wang, Xiao-Min Zhou, Mei-Yin Zhang, Lu Shi, Ruo-Wen Xiao, Li-Si Zeng, Xian-Zi Yang, X F Steven Zheng, Hui-Yun Wang, Shi-Juan Mai
Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples...
April 2017: Aging
https://www.readbyqxmd.com/read/28446508/enrichment-of-pi3k-akt-mtor-pathway-activation-in-hepatic-metastases-from-breast-cancer
#18
Mariaelena Pierobon, Corinne Ramos, Shukmei Wong, K Alex Hodge, Jessica Aldrich, Sara Byron, Stephen P Anthony, Nicholas J Robert, Donald W Northfelt, Mohammad Jahanzeb, Linda Vocila, Julia Wulfkuhle, Guido Gambara, Rosa I Gallagher, Bryant Dunetz, Nicholas Hoke, Ting Dong, David W Craig, Massimo Cristofanilli, Brian Leyland-Jones, Lance A Liotta, Joyce A O'Shaughnessy, John D Carpten, Emanuel F Petricoin
Purpose: Little is known about the molecular signatures associated with specific metastatic sites in breast cancer. Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis.Experimental Design: Next-generation sequencing-based whole-exome sequencing was coupled with reverse-phase protein microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28442534/oncogenic-%C3%AE-catenin-and-pik3ca-instruct-network-states-and-cancer-phenotypes-in-intestinal-organoids
#19
Pamela Riemer, Mattias Rydenfelt, Matthias Marks, Karen van Eunen, Kathrin Thedieck, Bernhard G Herrmann, Nils Blüthgen, Christine Sers, Markus Morkel
Colorectal cancer is driven by cooperating oncogenic mutations. In this study, we use organotypic cultures derived from transgenic mice inducibly expressing oncogenic β-catenin and/or PIK3CA(H1047R) to follow sequential changes in cancer-related signaling networks, intestinal cell metabolism, and physiology in a three-dimensional environment mimicking tissue architecture. Activation of β-catenin alone results in the formation of highly clonogenic cells that are nonmotile and prone to undergo apoptosis. In contrast, coexpression of stabilized β-catenin and PIK3CA(H1047R) gives rise to intestinal cells that are apoptosis-resistant, proliferative, stem cell-like, and motile...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28442344/mir-221-regulates-cd44-in-hepatocellular-carcinoma-through-the-pi3k-akt-mtor-pathway
#20
Jihye Kim, Jinmai Jiang, Mohamed Badawi, Thomas D Schmittgen
CD44 and miR-221 are upregulated in hepatocellular carcinoma (HCC) cell lines and tumors, however a connection between the two has not been identified. As the expression of miR-221 directly correlated with CD44 in HCC cells, we hypothesized that miR-221 may directly or indirectly regulate CD44 expression. Inhibition of miR-221 with antisense in Sk-Hep-1 or SNU-449 cell lines reduced CD44 protein expression while miR-221 mimic increased CD44 protein levels. miR-221 antisense did not alter the CD44 mRNA levels in Sk-Hep-1 or SNU-449 cells suggesting that regulation of CD44 protein occurs post transcriptionally...
June 3, 2017: Biochemical and Biophysical Research Communications
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