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https://www.readbyqxmd.com/read/29449694/interaction-between-stat3-and-gli1-tgli1-oncogenic-transcription-factors-promotes-the-aggressiveness-of-triple-negative-breast-cancers-and-her2-enriched-breast-cancer
#1
Sherona R Sirkisoon, Richard L Carpenter, Tadas Rimkus, Ashley Anderson, Alexandria Harrison, Allison M Lange, Guangxu Jin, Kounosuke Watabe, Hui-Wen Lo
Signal transducer and activator of transcription 3 (STAT3), glioma oncogene homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1 isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1 has not been explored. To address this knowledge gap, we analyzed 47 node-positive breast cancer specimens using immunohistochemical staining and found that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%) breast carcinomas, and in lymph node metastases (65%)...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449693/tumor-cell-intrinsic-tim-3-promotes-liver-cancer-via-nf-%C3%AE%C2%BAb-il-6-stat3-axis
#2
Hualin Zhang, Yang Song, Huimin Yang, Zhiyan Liu, Lifen Gao, Xiaohong Liang, Chunhong Ma
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449529/gambogenic-acid-inhibits-fibroblast-growth-factor-receptor-signaling-pathway-in-erlotinib-resistant-non-small-cell-lung-cancer-and-suppresses-patient-derived-xenograft-growth
#3
Linfeng Xu, Xiaoxiao Meng, Naihan Xu, Wenwei Fu, Hongsheng Tan, Li Zhang, Qianjun Zhou, Jianan Qian, Shiwei Tu, Xueting Li, Yuanzhi Lao, Hongxi Xu
Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449022/expression-patterns-of-claudin-5-and-its-related-signals-during-luteal-regression-in-pseudopregnant-rats-the-enhanced-effect-of-additional-pgf-treatment
#4
Lina Qi, Jingle Jiang, Pengjin Jin, Meiqian Kuang, Quanwei Wei, Fangxiong Shi, Dagan Mao
To study the expression patterns of claudin-5 and its related signals during luteal regression in rats, a sequential PMSG/hCG treatment paradigm was used to obtain a single, well-defined generation of corpus luteum (CL). A total of 35 rats were treated with one PGF or two PGF at an interval of 24 h from day 7 of pseudopregnancy to induce CL regression. Serum and ovaries were collected at 0, 2, 4, 8 or 24 h after one PGF injection (1 PGF), 2 or 24 h after two PGF injections (2 PGF). The serum progesterone level was detected by RIA; the ovarian expression of claudin-5, the phosphorylations of STAT3 (p-STAT3), Akt (p-Akt), ERK1/2 (p-ERK) and p38 MAPK (p-p38) were detected by western blot, real-time PCR and IHC...
February 12, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29448206/regulation-of-jak2-stat3-and-nf-%C3%AE%C2%BAb-signal-transduction-pathways-veronica-polita-alleviates-dextran-sulfate-sodium-induced-murine-colitis
#5
Md Rashedunnabi Akanda, Hyeon-Hwa Nam, Weishun Tian, Anowarul Islam, Byung-Kil Choo, Byung-Yong Park
Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) has become a worldwide emergent disease. Veronica polita (VP) is a medicinal herb that has strong antioxidant and anti-inflammatory properties. In the present study, we studied the protective effect of VP on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Phytochemical screening of VP extract demonstrated the presence of high total phenolic and flavonoid contents. Compared with the DSS group, VP significantly reduced clinical symptoms with less weight loss, bloody stool, shortening of the colon, and the severity of colitis was considerably inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in the colon and spleen...
February 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29448205/6-7-dimethoxy-1-2-3-4-tetrahydro-isoquinoline-3-carboxylic-acid-attenuates-colon-carcinogenesis-via-blockade-of-il-6-mediated-signals
#6
Priyanka Mishra, Vinit Raj, Archana S Bhadauria, Ashok K Singh, Amit Rai, Pranesh Kumar, Amit K Keshari, Arnab De, Amalesh Samanta, Umesh Kumar, Dinesh Kumar, Biswanath Maity, Sneha Nath, Anand Prakash, Kausar M Ansari, Sudipta Saha
In this study, we investigated the in vivo antiproliferative activity of 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15 days. Various physiological, oxidative parameters, histopathology, ELISA, gene and protein expression studies were conducted to evaluate the anti-CRC potential of M1. The histopathology and biochemical tests indicated the protective action of M1 in DMH-induced colon cancer...
February 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29448029/microrna-874-inhibits-tnf-%C3%AE-induced-remodeling-in-human-fetal-airway-smooth-muscle-cells-by-targeting-stat3
#7
Meihua Sun, Yuanyuan Huang, Feng Li, Haibo Li, Bo Zhang, Lianhua Jin
Pro-inflammatory cytokines-induced airway remodeling was a significant feature of asthma disease. The aim of the present study was to explore the functional significance of miR-874 in tumor necrosis factor (TNF)-α-treated human fetal airway smooth muscle (fASM) cells. Here, we found that TNF-α treatment significantly down-regulated the expression of miR-874 in fASM cells. MiR-874 overexpression markedly inhibited cell viability and migration, suppressed the expression of PCNA and Ki67, reduced the expression of collagen I and collagen III, decreased the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and induced an obvious elevation of tissue inhibitors of metalloproteinases (TIMPs)...
February 12, 2018: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29445990/time-dependent-lxr-rxr-pathway-modulation-characterizes-capillary-remodeling-in-inflammatory-corneal-neovascularization
#8
Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Pierfrancesco Mirabelli, Mieszko Lachota, Lasse Jensen, Beatrice Peebo, Neil Lagali
Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency...
February 14, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29445144/lenalidomide-regulates-cns-autoimmunity-by-promoting-m2-macrophages-polarization
#9
Qinjie Weng, Jiaying Wang, Jiajia Wang, Jing Wang, Fahmida Sattar, Zhikang Zhang, Jiahuan Zheng, Zijie Xu, Mengting Zhao, Xuan Liu, Lijun Yang, Guifeng Hao, Liang Fang, Q Richard Lu, Bo Yang, Qiaojun He
Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445008/blockade-of-host-%C3%AE-2-adrenergic-receptor-enhances-graft-versus-tumor-effect-through-modulating-apcs
#10
Hemn Mohammadpour, Rachel O'Neil, Jingxin Qiu, Philip L McCarthy, Elizabeth A Repasky, Xuefang Cao
Allogeneic hematopoietic cell transplantation is a potential curative therapy for hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor (GVT) effect. Recent studies have shown that β2-adrenergic receptor (β2AR) signaling can have an important impact on immune cell function, including dendritic cells (DCs). In this article, we demonstrate that pretreatment of host mice with a β2AR blocker significantly increases the GVT effect of donor CD8 + T cells by decreasing tumor burden without increasing graft-versus-host disease...
February 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29444468/a-major-component-of-vitamin-e-%C3%AE-tocopherol-inhibits-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-eml4-alk
#11
Yuki Uchihara, Takayuki Kidokoro, Kenji Tago, Tadahiko Mashino, Hiroomi Tamura, Megumi Funakoshi-Tago
Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. α-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29443378/hepatitis-c-virus-e2-envelope-glycoprotein-induces-an-immunoregulatory-phenotype-in-macrophages
#12
Young-Chan Kwon, Keith Meyer, Guangyong Peng, Soumya Chatterjee, Daniel F Hoft, Ranjit Ray
A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29441884/mir-204-14-3-3%C3%AE-axis-regulates-osteosarcoma-cell-proliferation-through-sata3-pathway
#13
Ruibo Zhao, Hongbo He, Yong Zhu, Jun Wan, Yusheng Li, Shuguang Gao, Can Zhang
Hyperproliferation of cells is a major problem is osteosarcoma (OS). So, further elucidation of the molecular mechanisms underlying hyperproliferation of OS is needed. Western blots results showed that 14-3-3ζ protein was upregulated in OS cell lines; 14-3-3ζ knockdown significantly suppressed OS cell proliferation, as well as the protein levels of p-STAT3, c-Myc and Cyclin D1. MicroRNA-204 (miR-204) has been regarded as an essential regulator in cancer carcinogenesis, including OS. Here, we revealed that miR-204 directly targets the 3'UTR of 14-3-3ζ to inhibit its expression, thus to suppress 14-3-3ζ -induced OS cell hyperproliferation...
October 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441069/interleukin-6-and-interferon-%C3%AE-signaling-via-jak1-stat-differentially-regulate-oncolytic-versus-cytoprotective-antiviral-states
#14
Oded Danziger, Tal Pupko, Eran Bacharach, Marcelo Ehrlich
Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK-STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK-STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440639/the-small-gtpase-rhou-lays-downstream-of-jak-stat-signaling-and-mediates-cell-migration-in-multiple-myeloma
#15
Sara Canovas Nunes, Martina Manzoni, Marco Pizzi, Elisa Mandato, Marilena Carrino, Laura Quotti Tubi, Renato Zambello, Fausto Adami, Andrea Visentin, Gregorio Barilà, Livio Trentin, Sabrina Manni, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29440449/impact-of-the-anti-cancer-drug-nt157-on-tyrosine-kinase-signalling-networks
#16
Shih-Ping Su, Efrat Flashner-Abramson, Shoshana Klein, Mor Gal, Rachel S Lee, Jianmin Wu, Alexander Levitzki, Roger J Daly
The small molecule drug NT157 has demonstrated promising efficacy in pre-clinical models of a number of different cancer types, reflecting activity against both cancer cells and the tumour microenvironment. Two known mechanisms of action are degradation of insulin-receptor substrates (IRS)-1/2, and reduced Stat3 activation, although it is possible that others exist. In order to interrogate the effects of this drug on cell signalling pathways in an unbiased manner, we have undertaken mass spectrometry-based global tyrosine phosphorylation profiling of NT157-treated A375 melanoma cells...
February 12, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29439310/lncrna-ab073614-induces-epithelial-mesenchymal-transition-of-colorectal-cancer-cells-via-regulating-the-jak-stat3-pathway
#17
Jinfang Xue, Liya Liao, Fang Yin, Haoyu Kuang, Xiaojun Zhou, Yanan Wang
BACKGROUND: LncRNAs are involved in the metastasis and recurrence of human tumors, including colorectal cancer (CRC). We previously reported that lncRNA AB073614 promotes tumor proliferation and metastasis and predicted a poor clinical outcome of CRC patients. Herein, we investigated the underlying mechanism of lncRNA AB073614-related metastasis in CRC. MATERIAL AND METHODS: The expression of lncRNA AB073614 in CRC tissues were evaluated by quantitative real-time PCR (qRT-PCR)...
January 26, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29439293/-status-of-stat3-in-psoriatic-arthritis
#18
EDITORIAL
John D Mountz
Joint disease and enthesopathy are seen in about one-third of patients with psoriasis and are usually preceded by the cutaneous manifestations of psoriasis. The relationships between the pathogenesis of psoriatic skin disease and the pathogenesis of psoriatic arthritis have not been defined, however, and the central question as to whether psoriatic skin disease initiates development of joint disease remains unresolved. This article is protected by copyright. All rights reserved.
February 13, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29438885/the-positive-effects-of-secreting-cytokines-il-17-and-ifn-%C3%AE-on-the-early-stage-differentiation-and-negative-effects-on-the-calcification-of-primary-osteoblasts-in-vitro
#19
Zhongxiu Wang, Jingyi Tan, Lihong Lei, Weilian Sun, Yanmin Wu, Peihui Ding, Lili Chen
OBJECTIVE: Interleukin-17 (IL-17) and interferon-gamma (IFN-γ) are all pro-inflammatory cytokines produced by specific subsets of T-cells and are also considered crucial regulators in bone remodeling, but their effects on osteogenesis have not been carefully studied. So, this study aimed to investigate the effects of secreting cytokines IL-17 and IFN-γ on the osteogenesis of primary osteoblasts and to clarify the potential roles of the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway in bone remodeling...
February 10, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29438179/a-novel-small-molecular-stat3-inhibitor-5br-6b-induces-apoptosis-and-inhibits-migration-in-colorectal-cancer-cells
#20
Zhe Liu, Huan Wang, Lingnan Guan, Siyi Chen, Maode Lai
Signal transducers and activators of transcription 3 (STAT3) represent a transcription factor that is constitutively activated in various cancers. Numerous studies have shown that STAT3 plays crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. In this study, we investigated a novel inhibitor, called -6b, to target STAT3 in colorectal cancer cells. The influence of 5Br-6b on the proliferation of colorectal cell lines SW480 and HCT116 was evaluated using an 3-(4, 5-dimethylthiazolyl)-2 and 5-diphenyltetrazolium bromide assay...
February 12, 2018: Anti-cancer Drugs
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