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https://www.readbyqxmd.com/read/28719590/pericyte-expressed-tie2-controls-angiogenesis-and-vessel-maturation
#1
Martin Teichert, Laura Milde, Annegret Holm, Laura Stanicek, Nicolas Gengenbacher, Soniya Savant, Tina Ruckdeschel, Zulfiyya Hasanov, Kshitij Srivastava, Junhao Hu, Stella Hertel, Arne Bartol, Katharina Schlereth, Hellmut G Augustin
The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28719035/melatonin-inhibits-nucleus-pulposus-np-cell-proliferation-and-extracellular-matrix-ecm-remodeling-via-the-melatonin-membrane-receptors-mediated-pi3k-akt-pathway
#2
Zheng Li, Xingye Li, Chong Chen, Matthew T V Chan, William Ka Kei Wu, Jianxiong Shen
Pinealectomy in vertebrates accelerated intervertebral disc degeneration (IDD). However, the potential mechanisms, particularly, melatonin's role is still to be clarified. In this study, for first time, melatonin membrane receptors of MT1 and MT2 were found to be present in the human intervertebral disc tissues and nucleus pulposus (NP) cells, respectively. Melatonin treatment significantly inhibited NP cell proliferation in dose- dependent manner. Accordingly, melatonin down-regulated gene expression of cyclin D1, PCNA, matrix metallopeptidases-3 and -9 and upregulated gene expression of collagen type II alpha 1 chain and aggrecan in NP cells...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28718842/secreted-protein-acidic-and-rich-in-cysteine-sparc-enhances-cell-proliferation-migration-and-epithelial-mesenchymal-transition-and-sparc-expression-is-associated-with-tumor-grade-in-head-and-neck-cancer
#3
Chih-Hau Chang, Meng-Chi Yen, Ssu-Hui Liao, Yu-Ling Hsu, Chung-Sheng Lai, Kao-Ping Chang, Ya-Ling Hsu
Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718726/effects-of-the-notch1-signaling-pathway-on-human-lung-cancer-a549-cells
#4
Yun Zeng, Bijian Yin, Xinwei Wang, Guohao Xia, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
PURPOSE: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. MATERIALS AND METHODS: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. Apoptosis-related factors were detected by immunohistochemical assay. Caspase-8, caspase-3, caspase-9, PI3K, pAkt and pSTAT3 expressions were detected by Western blotting...
July 18, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28718684/role-of-gsk-3%C3%AE-in-regulation-of-canonical-wnt-%C3%AE-catenin-signaling-and-pi3-k-akt-oncogenic-pathway-in-colon-cancer
#5
Shelly Jain, Preety Ghanghas, Chandan Rana, S N Sanyal
Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway...
July 18, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28718669/fruit-peel-polyphenolic-extract-induced-apoptosis-in-human-breast-cancer-cells-is-associated-with-ros-production-and-modulation-of-p38mapk-erk1-2-and-the-akt-signaling-pathway
#6
Martin Kello, Lucia Kulikova, Janka Vaskova, Alexandra Nagyova, Jan Mojzis
Polyphenols represent a large group of natural substances with different biological properties. Currently, polyphenols are well studied due to their free radicals' scavenging and antioxidant activities. However, some studies indicate that polyphenols also exhibit pro-oxidant properties. In this study, the possible involvement of the pro-oxidant activities of fruit polyphenols was investigated in relation to apoptosis induction. To determine the type of cell death induced by fruit polyphenols (Flavine; F7), we assessed a series of assays, including measurements of caspase-7 activation, membrane mitochondrial potential changes, reactive oxygen (ROS) and nitrogen species production, lipid peroxidation, antioxidant enzymes activities, and PARP cleavage...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28718667/hydroxytyrosol-induces-apoptosis-and-cell-cycle-arrest-and-suppresses-multiple-oncogenic-signaling-pathways-in-prostate-cancer-cells
#7
Haseeb Zubair, Arun Bhardwaj, Aamir Ahmad, Sanjeev Kumar Srivastava, Mohammad Aslam Khan, Girijesh Kumar Patel, Seema Singh, Ajay Partap Singh
SCOPE: Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof. METHODS AND RESULTS: Treatment of LNCaP and C4-2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT's ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer-cell-specific effect...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28718419/targeting-pi3k-signaling-in-combination-cancer-therapy
#8
REVIEW
Elvire Pons-Tostivint, Benoît Thibault, Julie Guillermet-Guibert
Targeting upstream phosphatidylinositol-3-kinases (PI3Ks) in the PI3K/Akt/mTOR pathway appears to be a promising therapy in solid cancers; however, first early clinical trials with PI3K inhibitors in monotherapy have been disappointing. A massive array of preclinical and clinical trials are currently evaluating combinations of PI3K inhibitors in targeted therapies. These combinations include co-treatments with drugs directed against other intra-/extracellular signaling molecules, nuclear hormone receptors, DNA damage repair enzymes, and immune modulators...
June 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717943/a-pyrrole-based-natural-small-molecule-mitigates-hsp90-expression-in-mda-mb-231-cells-and-inhibits-tumor-angiogenesis-in-mice-by-inactivating-hsf-1
#9
K C Rashmi, H S Atreya, M Harsha Raj, Bharathi P Salimath, H S Aparna
Heat shock proteins (HSPs), molecular chaperones, are crucial for the cancer cells to facilitate proper functioning of various oncoproteins involved in cell survival, proliferation, migration, and tumor angiogenesis. Tumor cells are said to be "addicted" to HSPs. HSPs are overexpressed in many cancers due to upregulation of transcription factor Heat-shock factor 1 (HSF-1), the multifaceted master regulator of heat shock response. Therefore, pharmacological targeting of HSPs via HSF-1 is an effective strategy to treat malignant cancers like triple negative breast cancer...
July 17, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#10
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717222/fty720-induces-autophagy-associated-apoptosis-in-human-oral-squamous-carcinoma-cells-in-part-through-a-reactive-oxygen-species-mcl-1-dependent-mechanism
#11
Li-Yuan Bai, Chang-Fang Chiu, Shih-Jiuan Chiu, Po-Chen Chu, Jing-Ru Weng
In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC50 values of 6.1, 6.3, and 4.5 μM, respectively. This antiproliferative effect was attributable to the ability of FTY720 to induce caspase-dependent apoptosis. Mechanistic evidence suggests that FTY720-induced apoptosis was associated with its ability to inhibit Akt-NF-κB signaling, to facilitate the proteasomal degradation of the antiapoptotic protein Mcl-1, and to increase reactive oxygen species (ROS) generation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717171/the-aspirin-metabolite-salicylate-inhibits-lysine-acetyltransferases-and-muc1-induced-epithelial-to-mesenchymal-transition
#12
Harvey R Fernandez, Sara K Lindén
MUC1 is a transmembrane mucin that can promote cancer progression, and its upregulation correlates with a worse prognosis in colon cancer. We examined the effects of overexpression of MUC1 in colon cancer cells, finding that it induced epithelial to mesenchymal transition (EMT), including enhanced migration and invasion, and increased Akt phosphorylation. When the clones were treated with the aspirin metabolite salicylate, Akt phosphorylation was decreased and EMT inhibited. As the salicylate motif is necessary for the activity of the lysine acetyltransferase (KAT) inhibitor anacardic acid, we hypothesized these effects were associated with the inhibition of KAT activity...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717133/insulin-upregulates-betatrophin-expression-via-pi3k-akt-pathway
#13
Puhan Lu, Xi Chen, Zeqing Zhang, Jianhua Zhang, Yan Yang, Zhelong Liu, Junhui Xie, Shiying Shao, Xinrong Zhou, Shuhong Hu, Wentao He, Jiajun Zhao, Xuefeng Yu
Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716898/tbk1-provides-context-selective-support-of-the-activated-akt-mtor-pathway-in-lung-cancer
#14
Jonathan M Cooper, Yi-Hung Ou, Elizabeth McMillan, Rachel M Vaden, Aubhishek Zaman, Brian O Bodemann, Gurbani Makkar, Bruce A Posner, Michael White
Emerging observations link dysregulation of TANK-binding kinase 1 (TBK1) to developmental disorders, inflammatory disease, and cancer. Biochemical mechanisms accounting for direct participation of TBK1 in host defense signaling have been well described. However, the molecular underpinnings of the selective participation of TBK1 in a myriad of additional cell biological systems in normal and pathophysiological contexts remain poorly understood. To elucidate the context-selective role of TBK1 in cancer cell survival, we employed a combination of broad-scale chemogenomic and interactome discovery strategies to generate data-driven mechanism-of-action hypotheses...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716817/pi3k%C3%AE-%C3%AE-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#15
Evgeni Efimenko, Utpal P Davé, Irina V Lebedeva, Yao Shen, Maria J Sanchez-Quintero, Daniel Diolaiti, Andrew Kung, Brian J Lannutti, Jianchung Chen, Ronald Realubit, Zoya Niatsetskiya, Vadim Ten, Charles Karan, Xi Chen, Andrea Califano, Thomas G Diacovo
PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using a Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#16
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#17
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716056/the-inhibitory-effect-of-isoliquiritigenin-on-the-proliferation-of-human-arterial-smooth-muscle-cell
#18
Tianbao Chen, Shaoxiong Deng, Rong Lin
BACKGROUND: Isoliquiritigenin (ISL) has various biological activities including as antioxidant and an inhibitor of PI3K/AKT signaling pathway. However, both oxidative stress and activated PI3K/AKT signaling contribute to the aberrant proliferation of vascular smooth muscle cells (VSMCs). This study is aimed to explore the effect of ISL on the proliferation of human arterial smooth muscle cells (HASMCs) and to investigate the underlying mechanisms. METHODS: BrdU incorporation, cell cycle and reactive oxygen species (ROS) in normal or ISL treated HASMCs were analyzed by flow cytometry...
July 17, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28716053/ibrutinib-a-bruton-s-tyrosine-kinase-inhibitor-exhibits-antitumoral-activity-and-induces-autophagy-in-glioblastoma
#19
Jin Wang, Xiaoyang Liu, Yongzhi Hong, Songtao Wang, Pin Chen, Aihua Gu, Xiaoyuan Guo, Peng Zhao
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. METHODS: Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28715871/improvement-of-mitochondrial-function-by-celastrol-in-palmitate-treated-c2c12-myotubes-via-activation-of-pi3k-akt-signaling-pathway
#20
Mohamad Hafizi Abu Bakar, Joo Shun Tan
Compelling evidences posited that high level of saturated fatty acid gives rise to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. Celastrol is a pentacyclic triterpenoid derived from the root extracts of Tripterygium wilfordii that possesses potent anti-inflammatory properties in a number of animal models with metabolic diseases. However, the cellular mechanistic action of celastrol in alleviating obesity-induced insulin resistance in skeletal muscle remains largely unknown...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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