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https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#1
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102026/piperine-a-pungent-alkaloid-from-black-pepper-inhibits-b-lymphocyte-activation-and-effector-functions
#2
David A Soutar, Carolyn D Doucette, Robert S Liwski, David W Hoskin
Piperine has several well-documented anti-inflammatory properties; however, little is known regarding its effect on humoral immunity. In this study, we describe the immunosuppressive effect of piperine on B lymphocytes, which are integral to the humoral immune response. Mouse B cells were cultured in the absence or presence of non-cytotoxic concentrations (25, 50, and 100 μM) of piperine during T-dependent or T-independent stimulation. Piperine inhibited B cell proliferation by causing G0/G1 phase cell cycle arrest in association with reduced expression of cyclin D2 and D3...
January 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28101222/frat1-expression-regulates-proliferation-in-colon-cancer-cells
#3
Kongxi Zhu, Jianqiang Guo, Hongjuan Wang, Weihua Yu
Colorectal cancer is one of the most common gastric malignancies worldwide. However, the underlying mechanism of colon cancer development and valuable indicators of the disease remain unclear. In this study, the expression of frequently rearranged in advanced T-cell lymphomas 1 (FRAT1) in colon cancer was investigated and the association between FRAT1 expression and biological properties of tumors was analyzed. A total of 147 colon cancer tissue samples and adjacent normal tissues were collected between January 2013 and June 2014...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101184/anti-inflammatory-effects-of-luteolin-on-experimental-autoimmune-thyroiditis-in-mice
#4
Nan Xia, Gang Chen, Min Liu, Xiaozhen Ye, Yahui Pan, Jiuyu Ge, Yanting Mao, Hongwei Wang, Jian Wang, Sijing Xie
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100745/disease-progression-dependent-effects-of-trem2-deficiency-in-a-mouse-model-of-alzheimer-s-disease
#5
Taylor R Jay, Anna M Hirsch, Margaret L Broihier, Crystal M Miller, Lee E Neilson, Richard M Ransohoff, Bruce T Lamb, Gary E Landreth
: Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#6
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100650/transforming-growth-factor-%C3%AE-suppresses-peroxisome-proliferator-activated-receptor-%C3%AE-expression-via-both-smad-binding-and-novel-tgf-%C3%AE-inhibitory-elements
#7
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ downregulation is prominent in fibrosis and mediated, via previously unknown mechanisms, by SMAD signaling. Here we show that TGF-β induces association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive corepressors E2F4 and p107...
January 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28100567/mecp2-regulated-glycogenes-contribute-to-proliferation-and-apoptosis-of-gastric-cancer-cells
#8
Yannan Qin, Lingyu Zhao, Xiaofei Wang, Dongdong Tong, Christopher Hoover, Fei Wu, Yingxun Liu, Lumin Wang, Liying Liu, Lei Ni, Tusheng Song, Chen Huang
Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis...
January 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28100386/-effect-of-extracellular-signal-regulated-kinas-1-2-expression-and-hpv16-infection-and-their-interaction-in-progression-of-cervical-cancerization
#9
S L Fan, L Ding, Z Y Ren, X Chen, X S Sun, C C Li, C L Liu, W L Jia, Q L Li, J T Wang
Objective: To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis. Methods: A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 57 cases with cervical intraepithelial neoplasm Ⅱ/Ⅲ (CIN Ⅱ/Ⅲ) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014...
January 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28100035/stromal-cells-act-as-guardians-for-endothelial-progenitors-by-reducing-their-immunogenicity-after-co-transplantation
#10
Naima Souidi, Meaghan Stolk, Juliane Rudeck, Dirk Strunk, Katharina Schallmoser, Hans-Dieter Volk, Martina Seifert
Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal strem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28099945/in-vivo-and-in-vitro-effects-of-microrna-27a-on-proliferation-migration-and-invasion-of-breast-cancer-cells-through-targeting-of-sfrp1-gene-via-wnt-%C3%AE-catenin-signaling-pathway
#11
Ling-Yu Kong, Mei Xue, Qing-Cai Zhang, Chuan-Fu Su
This study aims to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/β-catenin signaling pathway. BC and normal breast tissues were obtained from 396 female BC patients and 308 female patients with benign breast lesions respectively. Human normal mammary epithelial (MCF-10A) and BC cell lines (BT-20, MCF-7, T-47D and MDA-MB-231) were cultured. After cell transfection, BC cells were assigned to six groups: control, miR-27a mimics, miR-27a inhibitors, negative control (NC), si-SFRP1 and si-SFRP1 + miR-27a inhibitors groups...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099934/tolfenamic-acid-induced-alterations-in-genes-and-pathways-in-pancreatic-cancer-cells
#12
Umesh T Sankpal, Steve Goodison, Michelle Jones-Pauley, Myrna Hurtado, Fan Zhang, Riyaz Basha
Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#13
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099498/oral-tolerance-induced-by-ova-intake-ameliorates-tnbs-induced-colitis-in-mice
#14
Lisiery N Paiatto, Fernanda G D Silva, Julia Bier, Márcia R Brochetto-Braga, Áureo T Yamada, Wirla M S C Tamashiro, Patricia U Simioni
INTRODUCTION: Literature data have shown that the consumption of dietary proteins may cause modulatory effects on the host immune system, process denominated oral tolerance by bystander suppression. It has been shown that the bystander suppression induced by dietary proteins can improve inflammatory diseases such as experimental arthritis. Here, we evaluated the effects of oral tolerance induced by ingestion of ovalbumin (OVA) on TNBS-induced colitis in mice, an experimental model for human Crohn's disease...
2017: PloS One
https://www.readbyqxmd.com/read/28099492/priming-cross-protective-bovine-viral-diarrhea-virus-specific-immunity-using-live-vectored-mosaic-antigens
#15
Shehnaz Lokhandwala, Xin Fang, Suryakant D Waghela, Jocelyn Bray, Leo M Njongmeta, Andy Herring, Karim W Abdelsalam, Christopher Chase, Waithaka Mwangi
Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28099487/metabolic-imaging-of-head-and-neck-cancer-organoids
#16
Amy T Shah, Tiffany M Heaster, Melissa C Skala
Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model...
2017: PloS One
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#17
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096669/nanocoating-with-plant-derived-pectins-activates-osteoblast-response-in-vitro
#18
J Folkert, A Meresta, T Gaber, K Miksch, F Buttgereit, J Detert, N Pischon, K Gurzawska
A new strategy to improve osseointegration of implants is to stimulate adhesion of bone cells, bone matrix formation, and mineralization at the implant surface by modifying surface coating on the nanoscale level. Plant-derived pectins have been proposed as potential candidates for surface nanocoating of orthopedic and dental titanium implants due to 1) their osteogenic stimulation of osteoblasts to mineralize and 2) their ability to control pectin structural changes. The aim of this study was to evaluate in vitro the impact of the nanoscale plant-derived pectin Rhamnogalacturonan-I (RG-I) from potato on the osteogenic response of murine osteoblasts...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28096525/toll-like-receptor-4-signaling-in-high-mobility-group-box-1-protein-1-mediated-the-suppression-of-regulatory-t-cells
#19
Chunyan Luo, Huiting Liu, Hu Wang, Jiajun Wang
BACKGROUND Treg cells play a central role in the suppression of immune response, and their suppressive capacity can be modulated by toll-like receptor (TLR) ligands. However, the detailed pathway of TLR ligand modulation is still unknown. The present study aimed to evaluate the effect of the high mobility group box-1 protein 1 (HMGB1) and lipopolysaccharide (LPS) on Treg cells through TLR4 signaling. MATERIAL AND METHODS Treg cells were purified from healthy human peripheral blood mononuclear cells (PBMCs) by magnetic-bead activity cell sorting (MACS), blocked by anti-TLR4 monoclonal antibody, and then incubated with different concentration of LPS or HMGB1...
January 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28096513/targeting-tnfr2-with-antagonistic-antibodies-inhibits-proliferation-of-ovarian-cancer-cells-and-tumor-associated-tregs
#20
Heather Torrey, John Butterworth, Toshiyuki Mera, Yoshiaki Okubo, Limei Wang, Danielle Baum, Audrey Defusco, Sara Plager, Sarah Warden, Daniel Huang, Eva Vanamee, Rosemary Foster, Denise L Faustman
Major barriers to cancer therapy include the lack of selective inhibitors of regulatory T cells (Tregs) and the lack of broadly applicable ways to directly target tumors through frequently expressed surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is an attractive target protein because of its restricted abundance to highly immunosuppressive Tregs and oncogenic presence on human tumors. We characterized the effect of TNFR2 inhibition using antagonistic antibodies. In culture-based assays, we found that two TNFR2 antagonists inhibited Treg proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion...
January 17, 2017: Science Signaling
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