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https://www.readbyqxmd.com/read/29788332/constitutive-interferon-pathway-activation-in-tumors-as-an-efficacy-determinant-following-oncolytic-virotherapy
#1
Cheyne Kurokawa, Ianko D Iankov, S Keith Anderson, Ileana Aderca, Alexey A Leontovich, Matthew J Maurer, Ann L Oberg, Mark A Schroeder, Caterina Giannini, Suzanne M Greiner, Marc A Becker, E Aubrey Thompson, Paul Haluska, Mark E Jentoft, Ian F Parney, S John Weroha, Jin Jen, Jann N Sarkaria, Evanthia Galanis
Background: Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however. Methods: We performed RNA sequencing and gene set enrichment analysis to identify pathways differentially activated in MV-resistant (n = 3) and -permissive (n = 2) tumors derived from resected human glioblastoma (GBM) specimens and propagated as xenografts (PDX)...
May 16, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29787988/microrna-30e-promotes-hepatocyte-proliferation-and-inhibits-apoptosis-in-cecal-ligation-and-puncture-induced-sepsis-through-the-jak-stat-signaling-pathway-by-binding-to-fosl2
#2
Lan Ling, Shan-Hong Zhang, Li-Da Zhi, Hong Li, Qian-Kuan Wen, Gang Li, Wen-Jia Zhang
INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen-2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model...
May 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#3
Suliman Al-Fayoumi, Taishi Hashiguchi, Yuka Shirakata, John Mascarenhas, Jack W Singer
Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29778097/hyperprolactinemia-inducing-antipsychotics-increase-breast-cancer-risk-by-activating-jak-stat5-in-precancerous-lesions
#4
A N Johnston, W Bu, S Hein, S Garcia, L Camacho, L Xue, L Qin, C Nagi, S G Hilsenbeck, J Kapali, K Podsypanina, J Nangia, Y Li
BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1...
May 19, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#5
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29776962/shp-1-acts-as-a-tumor-suppressor-in-hepatocarcinogenesis-and-hcc-progression
#6
Liang-Zhi Wen, Kai Ding, Ze-Rui Wang, Chen-Hong Ding, Shu-Juan Lei, Jin-Pei Liu, Chuan Yin, Ping-Fang Hu, Jin Ding, Wan-Sheng Chen, Xin Zhang, Wei-Fen Xie
Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1, also known as PTPN6), is a nonreceptor protein tyrosine phosphatase that acts as a negative regulator of inflammation. Emerging evidence indicates that SHP-1 plays a role in inhibiting the progression of hepatocellular carcinoma (HCC). However, the role of SHP-1 in hepatocarcinogenesis remains unknown. Here we find that levels of SHP-1 are significantly downregulated in human HCC tissues compared with those in noncancerous tissues (P < 0...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29765118/ifn-%C3%AE-s-inhibit-hantaan-virus-infection-through-the-jak-stat-pathway-and-expression-of-mx2-protein
#7
Ning Li, Fan Luo, Qingzhou Chen, Ni Zhu, Hui Wang, Linlin Xie, Hairong Xiong, Ming Yue, Yun Zhang, Yong Feng, Wei Hou
Hantaan virus (HTNV), member of the newly defined Hantaviridae family, within the order Bunyavirales, can cause a hemorrhagic fever with renal syndrome with high fatality rates in humans. However, no specific antiviral agents are currently available for HTNV infection approved by the US Food and Drug Administration. Although interferon lambdas (IFN-λs) have been shown to induce an antiviral state against HTNV, the molecular mechanisms remain to be determined. In this study, we found that IFN-λs exerted its anti-HTNV effect by activating Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway-mediated antiviral immunity in A549 cells...
May 15, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29763909/cardiac-ablation-of-socs3-aggravates-doca-salt-induced-hypertrophic-remodeling-by-activation-of-gp130-dependent-signaling-in-mice
#8
Shuang Liu, Li-Xin Liu, Yun-Long Zhang, Song Lai, Yun-Peng Xie, Nan-Nan Li, Hong-Xia Wang, Yun-Long Xia, Ying Liu, Hui-Hua Li
BACKGROUND/AIMS: Cardiac remodeling is a critical pathogenetic process leading to heart failure. Suppressor of cytokine signaling-3 (SOCS3) is demonstrated as a key negative regulator of the gp130 receptor to inhibit cardiac hypertrophy. However, the role of SOCS3 in deoxycorticosterone-acetate (DOCA)-salt-induced cardiac remodeling remains unclear. METHODS: Cardiac-specific SOCS3 knockout (SOCS3cKO) and wild-type (WT) C57BL/6J mice were subjected to uninephrectomy and DOCA-salt for 3 weeks...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#9
Daniel G Stover, Carlos R Gil Del Alcazar, Jane Brock, Hao Guo, Beth Overmoyer, Justin Balko, Qiong Xu, Aditya Bardia, Sara M Tolaney, Rebecca Gelman, Maxwell Lloyd, Yu Wang, Yaomin Xu, Franziska Michor, Vivian Wang, Eric P Winer, Kornelia Polyak, Nancy U Lin
Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study enrolling patients with refractory, metastatic triple-negative breast cancer. The primary endpoint was objective response by RECIST 1.1. The study was designed to enroll patients whose archival tumor tissue was pSTAT3-positive ( T -score >5) by central immunohistochemistry...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29757976/fatty-acid-%C3%AE-oxidation-is-essential-in-leptin-mediated-oocytes-maturation-of-yellow-catfish-pelteobagrus-fulvidraco
#10
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755657/regulatory-effect-of-anti-gp130-functional-mab-on-il-6-mediated-rankl-and-wnt5a-expression-through-jak-stat3-signaling-pathway-in-fls
#11
Ping Miao, Xiao Wei Zhou, Ping Wang, Rong Zhao, Ninan Chen, Chao Ying Hu, Xue Hua Chen, Liu Qian, Qi Wen Yu, Ji Ying Zhang, Rong Xu, Dong Yi He, Lian Bo Xiao, Pu Li, Mason Lu, Dong Qing Zhang
We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined the interleukin 6 (IL-6), IL-6 receptor α (IL-6Rα), gp130, receptor activator of nuclear factor κB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Rα; WNT5A and RANKL levels were detected...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752314/ifnar1-controls-autocrine-type-i-ifn-regulation-of-pd-l1-expression-in-myeloid-derived-suppressor-cells
#12
Wei Xiao, John D Klement, Chunwan Lu, Mohammed L Ibrahim, Kebin Liu
Tumor cells respond to IFN-γ of activated T cells to upregulate programmed death-ligand 1 (PD-L1) in the tumor microenvironment as an adaptive immune resistance mechanism. Tumor cells also express oncogene-driven PD-L1. PD-L1 is also expressed on myeloid-derived suppressor cells (MDSCs). It is known that both type I and II IFNs upregulate PD-L1 expression in MDSCs. However, the molecular mechanism underlying PD-L1 expression in MDSCs is still largely unknown. We report in this article that MDSCs exhibit constitutive STAT1 phosphorylation in vitro without exogenous IFNs, indicating a constitutive active JAK-STAT signaling pathway in mouse MDSCs in vitro...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751177/activation-of-the-il-6-jak2-stat3-pathway-induces-plasma-cell-mastitis-in-mice
#13
Yang Liu, Jian Zhang, Yu-Hui Zhou, Hui-Min Zhang, Ke Wang, Yu Ren, Yi-Na Jiang, Shui-Ping Han, Jian-Jun He, Xiao-Jiang Tang
Plasma cell mastitis (PCM) is a chronic mastitis with limited treatment options and common recurrence. A histopathological hallmark of PCM is the infiltration of numerous plasma cells surrounding the mammary duct. Our previous study showed that the activity of the IL-6/STAT3 signaling pathway was elevated in patients with PCM. However, the etiology of PCM remains largely unclear. In this study, we sought to explore the effects of IL-6/JAK2/STAT3 signaling pathway in the pathogenesis of PCM. Histological analysis showed that the mammary glands of mice that received human breast tissue homogenates, followed by an injection of IL-6, exhibited features of PCM similar to human PCM...
May 8, 2018: Cytokine
https://www.readbyqxmd.com/read/29750040/a-phase-ib-study-of-ruxolitinib-gemcitabine-%C3%A2-nab-paclitaxel-in-patients-with-advanced-solid-tumors
#14
Todd M Bauer, Manish R Patel, Andres Forero-Torres, Thomas J George, Albert Assad, Yining Du, Herbert Hurwitz
Purpose: Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients and methods: Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29749494/downregulation-of-rpn2-induces-apoptosis-and-inhibits-migration-and-invasion-in-colon-carcinoma
#15
Chongyao Bi, Baofei Jiang
The morbidity of colorectal cancer (CRC) increases annualy, which accounts to higher mortality worldwide. Therefore, it is important to study the pathogenesis of colon cancer. Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in CRC. In the present study, we investigated whether RPN2 can regulate apoptosis, migration and invasion by RNA interference in CRC and sought to clarify the molecular mechanism involved. Based on previous research, an abnormal high expression of RPN2 was observed in CRC tissues and cell lines by real-time (RT)-PCR, immunohistochemistry (IHC) and western blot analysis...
May 10, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29741263/the-2017-who-update-on-mature-t-and-natural-killer-nk-cell-neoplasms
#16
REVIEW
E Matutes
Over the last decade, there has been a significant body of information regarding the biology of the lymphoid neoplasms. This clearly supports the need for updating the 2008 WHO (World Health Organization) classification of haematopoietic and lymphoid tumours. The 2017 WHO classification is not a new edition but an update and revision of the 4th edition. New provisional entities but not new definitive entities are included, and novel molecular data in most of the entities and changes in the nomenclature in few of them have been incorporated...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29738371/apoa-1-mimetic-peptide-elk-2a2k2e-decreases-inflammatory-factor-levels-via-the-abca1-jak2-stat3-ttp-axis-in-thp-1-derived-macrophages
#17
Jia-Lin Wang, Duo Gong, Xin-Yan Hu, Su Wu, Xi-Long Zheng, Jie Wu, Xiao-Er Tang, Da-Wei Zhang, Chao-Ke Tang
OBJECTIVE: The aim of this study was to determine whether the apolipoprotein A-1 (apoA-1) mimetic peptide ELK-2A2K2E regulates inflammatory cytokine expression via activating the ATP-binding cassette transporter A1 (ABCA1)-janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3)- tristetraprolin (TTP) signaling pathway in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: The cells were treated with the apoA-1 mimetic peptide ELK-2A2K2E at different concentrations (0, 20, 40, 80 μg/ml) or incubated with ELK-2A2K2E (40 μg/ml) for different times (0, 6, 12, 24 h)...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29732039/jak-2-mutation-frequency-in-patients-with-thrombocytosis
#18
Osman Yokus, Habip Gedik
Background: We aimed to investigate the etiologic causes and the existence of Janus kinase 2 mutation (JAK2) in cases with thrombocytosis. Methods: In this retrospective study, patients who were admitted to hematology clinic with thrombocytosis between 2013 and 2015 were investigated in terms of the etiological causes of thrombocytosis and the existence of JAK2 mutation. Results: We retrospectively evaluated 136 cases that underwent JAK2 mutation analysis due to ET preliminary diagnosis in our hematology clinic...
2018: Caspian Journal of Internal Medicine
https://www.readbyqxmd.com/read/29728633/the-psoriasis-protective-tyk2-i684s-variant-impairs-il-12-stimulated-pstat4-response-in-skin-homing-cd4-and-cd8-memory-t-cells
#19
C Enerbäck, C Sandin, S Lambert, M Zawistowski, P E Stuart, D Verma, L C Tsoi, R P Nair, A Johnston, J T Elder
Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated TYK2 in psoriasis susceptibility. We performed an in-depth association analysis of TYK2 using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the TYK2 gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be deleterious based on its location in the pseudokinase domain...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29728434/focal-segmental-glomerulosclerosis-in-a-patient-with-prefibrotic-primary-myelofibrosis
#20
Gopal Krishana Bohra, Durga Shankar Meena, Nitin Bajpai, Abhishek Purohit
We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed thrombocytosis, leucocytosis and peripheral blood smear showed a leucoerythroblastic picture. JAK 2 mutation was positive. To confirm the diagnosis of myeloproliferative neoplasm, bone marrow biopsy was done, which was suggestive of primary myelofibrosis. The patient underwent kidney biopsy due to rapidly declining renal function and persistent proteinuria, which was suggestive of focal segmental glomerulosclerosis...
May 4, 2018: BMJ Case Reports
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