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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
#1
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
#2
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
#3
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...
June 6, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28574820/differentiation-capacities-of-skeletal-muscle-satellite-cells-in-lantang-and-landrace-piglets
#4
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...
May 15, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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-pik3-akt-mtor-pathway-activation-in-hepatic-metastases-from-breast-cancer
#13
Mariaelena Pierobon, Corrine Ramos, Shukmei Wong, K Alex Hodge, Jessica Aldrich, Sara A Byron, Stephen P Anthony, Nicholas J Robert, Donald W Northfelt, Mohammad Jahanzeb, Linda Vocila, Julia D Wulfkuhle, Guido Gambara, Rosa Isela Gallagher, Bryant Dunetz, Nicholas Hoke, Ting Dong, David W Craig, Massimo Cristofanilli, Brian Leyland Jones, Lance 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. <p>Experimental Design: NGS-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
#14
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
#15
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...
April 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440448/modified-panax-ginseng-extract-regulates-autophagy-by-ampk-signaling-in-a549-human-lung-cancer-cells
#16
Hwa-Seung Yoo, Jung Min Kim, Eunbi Jo, Chong-Kwan Cho, Seung-Yeul Lee, Hwan Su Kang, Min-Goo Lee, Pei-Ying Yang, Ik-Soon Jang
Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells...
June 2017: Oncology Reports
https://www.readbyqxmd.com/read/28422725/mir-199a-3p-enhances-cisplatin-sensitivity-of-cholangiocarcinoma-cells-by-inhibiting-mtor-signaling-pathway-and-expression-of-mdr1
#17
Qiang Li, Xuefeng Xia, Jie Ji, Jianghui Ma, Liang Tao, Linjun Mo, Wei Chen
Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different human malignancies, however, little is known about miR-199a-3p in cholangiocarcinoma cells. In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406985/metformin-inhibited-esophageal-squamous-cell-carcinoma-proliferation-in-vitro-and-in-vivo-and-enhanced-the-anti-cancer-effect-of-cisplatin
#18
Feng Wang, Xianfei Ding, Tao Wang, Zhengzheng Shan, Jun Wang, Shaoxuan Wu, Yanyan Chi, Yana Zhang, Zhuan Lv, Liuxing Wang, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied...
2017: PloS One
https://www.readbyqxmd.com/read/28402274/magnesium-isoglycyrrhizinate-shows-hepatoprotective-effects-in-a-cyclophosphamide-induced-model-of-hepatic-injury
#19
Wenjiao Jiang, Jingyan Liu, Peijin Li, Qianfeng Lu, Xue Pei, Yilin Sun, Guangji Wang, Kun Hao
The purpose of the current study was to investigate the effect of Magnesium Isoglycyrrhizinate (GM) on cyclophosphamide (CP)-induced hepatic injury in vivo and in vitro. The results demonstrated that GM exerted a protective effect on CP-induced acute liver injury, as evidenced by the alleviations of hepatic pathological damage and serum transaminase activities. Meantime, GM attenuated serum and HepG2 cell supernatant levels of TNF-α, IL-6, IL-1β, SOD and MDA. Western blot results presented that GM down-regulated the expressions of the microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6 kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), p- inhibitor of NF-κB(IκB)α and p-nuclear factor kappa B(NF-κB)p65 in CP-stimulated hepatic tissue and HepG2 cells...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395726/-over-expressions-of-p-eif4e-and-p-4ebp1-are-associated-with-poor-prognosis-in-nasopharyngeal-carcinoma
#20
Jun Zheng, Chunyan Zhang, Yiqiang Zhang, Jinhong Pei, Songqing Fan
Objective To observe the expressions of phosphorylated eukaryotic translation initiation factor 4E (p-eIF4E) and phospho-eIF4E-binding protein 1 (p-4EBP1) and investigate their associations with clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). Methods We detected the expressions of p-eIF4E and p-4EBP1 proteins by immunohistochemistry in NPC tissues (n=314 cases), and analyzed the associations between the expressions of p-eIF4E and p-4EBP1 proteins and clinicopathological features and prognosis in NPC by SPSS16...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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