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https://www.readbyqxmd.com/read/29228829/vanadium-pentoxide-increased-pten-and-decreased-shp1-expression-in-nk-92mi-cells-affecting-pi3k-akt-mtor-and-ras-mapk-pathways
#1
Francisco Gallardo-Vera, Miguel Tapia-Rodriguez, Daniel Diaz, Teresa Fortoul van der Goes, Luis F Montaño, Erika P Rendón-Huerta
Vanadium is an air pollutant that imparts immunosuppressive effects on NK cell immune responses, in part, by dysregulating interleukin (IL)-2/IL-2R-mediated JAK signaling pathways and inducing apoptosis. The aim of the present study was to evaluate effects of vanadium pentoxide (V2O5) on other IL-2 receptor-mediated signaling pathways, i.e. PI3K-AKT-mTOR and Ras-MAPK. Here, IL-2-independent NK-92MI cells were exposed to different V2O5 doses for 24 h periods. Expression of PI3K, Akt, mTOR, ERK1/2, MEK1, PTEN, SHP1, BAD and phosphorylated forms, as well as caspases-3, -8, -9, BAX and BAK in/on the cells were then determined by flow cytometry...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29228674/the-regulatory-role-of-aberrant-phosphatase-and-tensin-homologue-and-liver-kinase-b1-on-akt-mtor-c-myc-axis-in-pancreatic-neuroendocrine-tumors
#2
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
Pancreatic neuroendocrine tumor (pNET) is an uncommon type of pancreatic neoplasm. Low Phosphatase and Tensin Homologue (PTEN) expression and activation of the mechanistic target of rapamycin (mTOR) pathway have been noted in pNETs, and the former is associated with poor survival in pNET patients. Based on the results of the RADIANT-3 study, everolimus, an oral mTOR inhibitor, has been approved to treat advanced pNETs. However, the exact regulatory mechanism for the mTOR pathway in pNETs remains largely unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228561/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#3
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217266/auriculasin-induced-ros-causes-prostate-cancer-cell-death-via-induction-of-apoptosis
#4
Hyun-Dong Cho, Ju-Hye Lee, Kwang-Deog Moon, Ki-Hun Park, Mi-Kyung Lee, Kwon-Il Seo
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model...
December 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29208325/inhibitory-effects-of-compound-dmbt-on-hypoxia-induced-vasculogenic-mimicry-in-human-breast-cancer
#5
Shuixian Li, Qianyun Zhang, Lichun Zhou, Yanhui Guan, Shang Chen, Yu Zhang, Xiuzhen Han
Breast cancer is one of the most serious malignant tumors that harm to women's health. Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels, which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Prior antiangiogenic therapy just focused on vascular endothelial cells and did not significantly affect VM. DMBT, 6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-D-trehalose, has shown to have multiple anti-tumor invasion and metastasis activities; however the exact mechanism is not thoroughly elucidated...
December 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29207186/neuroglobin-promotes-the-proliferation-and-suppresses-the-apoptosis-of-glioma-cells-by-activating-the-pi3k-akt-pathway
#6
Bei Zhang, Yong Liu, Yajun Li, Xiao Zhe, Shijun Zhang, Lei Zhang
Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29190940/elevation-of-map17-enhances-the-malignant-behavior-of-cells-via-the-akt-mtor-pathway-in-hepatocellular-carcinoma
#7
Xinhuang Chen, Yan Liao, Yaqun Yu, Pengpeng Zhu, Jun Li, Liling Qin, Weijia Liao, Zhaoquan Huang
MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190547/low-folate-stress-reprograms-cancer-stem-cell-like-potentials-and-bioenergetics-metabolism-through-activation-of-mtor-signaling-pathway-to-promote-in-vitro-invasion-and-in-vivo-tumorigenicity-of-lung-cancers
#8
Wan-Jing Chen, Rwei-Fen S Huang
Low-folate (LF) nutritional status is associated with increased risks of lung cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and bioenergetics metabolism to increase metastasis potential of lung cancers. Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium enhanced CSC-like properties signified by increased expressions of the CSC surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted self-renewal ability of anchorage-independent oncospheroid formation...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29156676/uncoupling-torc2-from-agc-kinases-inhibits-tumour-growth
#9
Angus J M Cameron, Selvaraju Veeriah, Jacqueline J T Marshall, Elizabeth R Murray, Banafshé Larijani, Peter J Parker
Mammalian target of rapamycin (mTOR) is a central regulator of growth and metabolism. mTOR resides in two distinct multi-protein complexes - mTORC1 and mTORC2 - with distinct upstream regulators and downstream targets. While it is possible to specifically inhibit mTORC1 with rapamycin, or inhibit both mTOR complexes together with ATP pocket directed mTOR kinase inhibitors, it is not possible to assess the specific roles for mTORC2 pharmacologically. To overcome this, we have developed a novel, inducible, dominant negative system for disrupting substrate recruitment to mTORC2...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137348/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#10
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Siggillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133930/plc%C3%AE-dependent-mtor-signalling-controls-il-7-mediated-early-b-cell-development
#11
Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang
The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29080043/pi3k-akt-mtor-pathway-involvement-in-regulating-growth-hormone-secretion-in-a-rat-pituitary-adenoma-cell-line
#12
Carmelina Di Pasquale, Erica Gentilin, Simona Falletta, Mariaenrica Bellio, Mattia Buratto, Ettore Degli Uberti, Maria Chiara Zatelli
PURPOSE: Insulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion. METHODS: Cell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior...
October 27, 2017: Endocrine
https://www.readbyqxmd.com/read/29050229/ese-1-elf3-mrna-expression-associates-with-poor-survival-outcomes-in-her2-breast-cancer-patients-and-is-critical-for-tumorigenesis-in-her2-breast-cancer-cells
#13
Adwitiya Kar, Arthur Gutierrez-Hartmann
ESE-1/Elf3 and HER2 appear to establish a positive feedback regulatory loop, but the precise role of ESE-1 in HER2(+) breast tumorigenesis remains unknown. Analyzing public repositories, we found that luminal B and HER2 subtype patients with high ESE-1 mRNA levels displayed worse relapse free survival. We stably knocked down ESE-1 in HER2(+) luminal B BT474 cells and HER2 subtype SKBR3 cells, which resulted in decreased cell proliferation, colony formation, and anchorage-independent growth in vitro. Stable ESE-1 knockdown inhibited HER2-dependent signaling in BT474 cells and inhibited mTOR activation in SKBR3 cells, but reduced Akt signaling in both cell types...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046370/excessive-glucocorticoids-induced-muscle-murf1-overexpression-is-independent-of-akt-foxo1-pathway
#14
Xiao Juan Wang, Jing Jing Xiao, Lei Liu, Hong Chao Jiao, Hai Lin
The ubiquitin-proteasome system (UPS)-dependent proteolysis plays a major role in the muscle catabolic action of glucocorticoids (GCs). Atrogin-1 and muscle-specific RING finger protein 1 (MuRF1), two E3 ubiquitin ligases, are uniquely expressed in muscle. It has been previously demonstrated GCs treatment induced MuRF1 and atrogin-1 over expression. However, it is yet unclear whether the higher pharmacological dose of GCs induced muscle protein catabolism through MuRF1 and atrogin-1. In the present study, the role of atrogin-1 and MuRF1 in C2C12 cells protein metabolism during excessive dexamethasone (DEX) was studied...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28982149/the-interplay-of-cd150-and-cd180-receptor-pathways-contribute-to-the-pathobiology-of-chronic-lymphocytic-leukemia-b-cells-by-selective-inhibition-of-akt-and-mapk-signaling
#15
Inna Gordiienko, Larysa Shlapatska, Valeriia Kholodniuk, Lilia Sklyarenko, Daniel F Gluzman, Edward A Clark, Svetlana P Sidorenko
Cell surface expression of CD150 and CD180 receptors in chronic lymphocytic leukemia (CLL) associates with mutational IGHV status and favourable prognosis. Here we show a direct correlation between cell surface expression and colocalization of these receptors on CLL B cells. In the absence of CD150 and CD180 on the cell surface both receptors were expressed in the cytoplasm. The CD150 receptor was colocalized with markers of the endoplasmic reticulum, the Golgi apparatus and early endosomes. In contrast, CD180 was detected preferentially in early endosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28954551/heat-stress-induced-ligand-independent-met-and-egfr-signaling-in-hepatocellular-carcinoma
#16
Scott M Thompson, Danielle E Jondal, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Matthew P Stokes, Xiaoying Jia, Joseph P Grande, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
PURPOSE: The aims of the present study were two-fold: first, to test the hypothesis that heat stress induces MET and EGFR signaling in hepatocellular carcinoma (HCC) cells and inhibition of this signaling decreases HCC clonogenic survival; and second, to identify signaling pathways associated with heat-stress induced MET signaling. MATERIALS AND METHODS: MET(+) and EGFR(+) HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry...
September 27, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28937244/cardiac-at1-receptor-dependent-and-igf1-receptor-independent-signaling-is-activated-by-a-single-bout-of-resistance-exercise
#17
S Fs Melo, V G Barauna, T Fernandes, E C Carmo, C Ro Carvalho, E M Oliveira
AT1 receptor (AT1R) blockade prevents physiological cardiac hypertrophy induced by resistance training. Also, our group showed that a single bout of resistance exercise (RE) activates the AKT/mTOR which was also inhibited by AT1R blocker. Here, we investigated whether IGF1-receptor (IGF1-R) and MAPKs were also activated after a single bout of RE. Wistar rats were divided into Sedentary (SED); Sedentary treated with losartan (SED+LOS); Exercise (EX); and Exercise treated with losartan (EX+LOS). Cardiac tissue was obtained 5 and 30 minutes after 4 sets of 12 repetitions of squat exercise (80%1RM)...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#18
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
December 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28912474/rhus-coriaria-increases-protein-ubiquitination-proteasomal-degradation-and-triggers-non-canonical-beclin-1-independent-autophagy-and-apoptotic-cell-death-in-colon-cancer-cells
#19
Khawlah Athamneh, Hussain El Hasasna, Halima Al Samri, Samir Attoub, Kholoud Arafat, Nehla Benhalilou, Asma Al Rashedi, Yusra Al Dhaheri, Synan AbuQamar, Ali Eid, Rabah Iratni
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect of Rhus coriaria extract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the viability and colony growth of colon cancer cells. Moreover, RCE induced Beclin-1-independent autophagy and subsequent caspase-7-dependent apoptosis. Blocking of autophagy by chloroquine significantly reduced RCE-induced cell death, while blocking of apoptosis had no effect on RCE-induced cell death...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911141/glucagon-decreases-igf-1-bioactivity-in-humans-independently-of-insulin-by-modulating-its-binding-proteins
#20
RANDOMIZED CONTROLLED TRIAL
Zeinab Sarem, Christiane Bumke-Vogt, Ayman M Mahmoud, Biruhalem Assefa, Martin O Weickert, Aikatarini Adamidou, Volker Bähr, Jan Frystyk, Matthias Möhlig, Joachim Spranger, Stefanie Lieske, Andreas L Birkenfeld, Andreas F H Pfeiffer, Ayman M Arafat
Context: Depending on its lipolytic activity, glucagon plays a promising role in obesity treatment. Glucagon-induced growth hormone (GH) release can promote its effect on lipid metabolism, although the underlying mechanisms have not been well-defined. Objective: The present study highlights the glucagon effect on the GH/insulinlike growth factor 1 (IGF-1)/IGF-binding protein (IGFBP) axis in vivo and in vitro, taking into consideration insulin as a confounding factor...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
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