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https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#1
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28720093/solanum-nigrum-unripe-fruit-fraction-attenuates-adriamycin-resistance-by-down-regulating-multi-drug-resistance-protein-mdr-1-through-jak-stat-pathway
#2
Sankar Jagadeeshan, Diana David, S Jisha, S Manjula, S Asha Nair
BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S...
July 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28719732/genome-wide-association-meta-analysis-reveals-novel-juvenile-idiopathic-arthritis-susceptibility-loci
#3
Laura A McIntosh, Miranda C Marion, Marc Sudman, Mary E Comeau, Mara L Becker, John F Bohnsack, Tasha E Fingerlin, Thomas A Griffin, J Peter Haas, Daniel J Lovell, Lisa A Maier, Peter A Nigrovic, Sampath Prahalad, Marilynn Punaro, Carlos D Rosé, Carol A Wallace, Carol A Wise, Halima Moncrieffe, Timothy D Howard, Carl D Langefeld, Susan D Thompson
OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. This study focuses on identifying new associations among oligoarticular and polyarticular rheumatoid factor negative (RF(-) ) JIA, which are clinically similar and the most prevalent JIA disease subtypes. METHODS: Three cohorts totaling 2,751 oligoarticular and polyarticular RF(-) JIA cases were genotyped on the Affymetrix Genome-Wide SNP Array 6...
July 18, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#4
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28708884/a-jak1-2-inhibitor-baricitinib-inhibits-osteoclastogenesis-by-suppressing-rankl-expression-in-osteoblasts-in-vitro
#5
Kohei Murakami, Yasuhiro Kobayashi, Shunsuke Uehara, Takako Suzuki, Masanori Koide, Teruhito Yamashita, Midori Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, Yukio Nakamura
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28704535/interferon-related-genetic-markers-of-necroinflammatory-activity-in-chronic-hepatitis-c
#6
Rosario López-Rodríguez, Ángel Hernández-Bartolomé, María Jesús Borque, Yolanda Rodríguez-Muñoz, Samuel Martín-Vílchez, Luisa García-Buey, Leticia González-Moreno, Yolanda Real-Martínez, Paloma Muñoz de Rueda, Javier Salmerón, José Ramón Vidal-Castiñeira, Carlos López-Larrea, Luis Rodrigo, Ricardo Moreno-Otero, Paloma Sanz-Cameno
INTRODUCTION: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients...
2017: PloS One
https://www.readbyqxmd.com/read/28684419/versican-g1-domain-enhances-adenoviral-mediated-transgene-expression-and-can-be-modulated-by-inhibitors-of-the-janus-kinase-jak-stat-and-src-family-kinase-pathways
#7
Patricia Y Akinfenwa, Wesley S Bond, Cristhian J Ildefonso, Mary Y Hurwitz, Richard L Hurwitz
To examine the biochemical influences that may contribute to the success of gene therapy for ocular disorders, the role of versican, a vitreous component, in adenoviral-mediated transgene expression was examined. Versican is a large chondroitin sulfate-containing, hyaluronic acid-binding proteoglycan present in the extracellular matrix and in ocular vitreous body. Y79 retinoblastoma cells and CD44-negative SK-N-DZ neuroblastoma cells transduced with adenoviral vectors in the presence of versican respond with an activation of transgene expression...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28677798/microrna-448-suppresses-metastasis-of-pancreatic-ductal-adenocarcinoma-through-targeting-jak1-stat3-pathway
#8
Dan-Li Yu, Tao Zhang, Kun Wu, Yan Li, Juan Wang, Jun Chen, Xiao-Quan Li, Xing-Guo Peng, Jia-Ning Wang, Li-Guo Tan
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients...
August 2017: Oncology Reports
https://www.readbyqxmd.com/read/28674362/the-amelioration-of-myelofibrosis-with-thrombocytopenia-by-a-jak1-2-inhibitor-ruxolitinib-in-a-post-polycythemia-vera-myelofibrosis-patient-with-a-jak2-exon-12-mutation
#9
Kazuhiko Ikeda, Koki Ueda, Takahiro Sano, Kazuei Ogawa, Takayuki Ikezoe, Yuko Hashimoto, Soji Morishita, Norio Komatsu, Hitoshi Ohto, Yasuchika Takeishi
Less than 5% of patients with polycythemia vera (PV) show JAK2 exon 12 mutations. Although PV patients with JAK2 exon 12 mutations are known to develop post-PV myelofibrosis (MF) as well as PV with JAK2V617F, the role of JAK inhibitors in post-PV MF patients with JAK2 exon 12 mutations remains unknown. We describe how treatment with a JAK1/2 inhibitor, ruxolitinib, led to the rapid amelioration of marrow fibrosis, erythrocytosis and thrombocytopenia in a 77-year-old man with post-PV MF who carried a JAK2 exon 12 mutation (JAK2H538QK539L)...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28673391/the-development-and-use-of-janus-kinase-2-inhibitors-for-the-treatment-of-myeloproliferative-neoplasms
#10
REVIEW
Gabriela S Hobbs, Sarah Rozelle, Ann Mullally
Following the discovery of the JAK2V617F mutation, Janus kinase (JAK) 2 inhibitors were developed as rationally designed therapy in myeloproliferative neoplasms (MPNs). Although JAK2 inhibitors have clinical efficacy in MPN, they are not clonally selective for the JAK2V617F-mutant cells. Because activated JAK-signal transducer and activator of transcription (STAT) signaling is a common feature of MPN, JAK2 inhibitors are efficacious regardless of the specific MPN phenotypic driver mutation. The Food and Drug Administration approved the JAK1/JAK2 inhibitor, ruxolitinib, for the treatment of myelofibrosis and polycythemia vera...
August 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28668884/loss-of-tyrosine-kinase-2-does-not-affect-the-severity-of-jak2v617f-induced-murine-myeloproliferative-neoplasm
#11
Takumi Yamaji, Kotaro Shide, Takuro Kameda, Masaaki Sekine, Ayako Kamiunten, Tomonori Hidaka, Yoko Kubuki, Haruko Shimoda, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Shojiro Yamamoto, Satoru Hasuike, Kenji Nagata, Kazuya Shimoda
BACKGROUND/AIM: In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. MATERIALS AND METHODS: We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28665449/high-expression-of-il-4r-enhances-proliferation-and-invasion-of-hepatocellular-carcinoma-cells
#12
Changkuo Guo, Yuming Ouyang, Jing Cai, Le Xiong, Yajie Chen, Xiaoli Zeng, Anwen Liu
OBJECTIVE: In this study, we aimed to investigate the expression and function of interleukin-4 receptor (IL-4R) in hepatocellular carcinoma (HCC). METHODS: We collected 40 pairs of human HCC and adjacent normal tissue specimens and examined the expression levels of IL-4R. After IL-4R knockdown in HCC cell lines, cell proliferation and invasion ability were examined. Cell cycle and apoptosis were analyzed by flow cytometry. The activity of multiple signaling pathways was examined by Western blot...
June 15, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28664526/inhibitory-effect-and-mechanism-of-mesenchymal-stem-cells-cultured-in-3d-system-on-hepatoma-cells-hepg2
#13
Diandian Zhao, Lingling Hou, Mengwu Pan, Jilei Hua, Ziling Wang, Jinsheng He, Honggang Hu
Mesenchymal stem cells (MSCs) exhibit the feature of homing to tumor site and being immunosuppressive, which have broad prospects in tumor therapy. However, MSCs are commonly cultured in a two-dimensional (2D) condition, which would gradually loss some in vivo important properties. In this study, we built a three-dimensional (3D) system with collagen/Matrigel scaffolds to culture MSCs. The results indicated that MSCs in 3D scaffolds showed higher proliferation ability than that of in 2D cells. In vitro, 3D-cultured MSC-conditioned media (CM) significantly inhibited the proliferation of hepatoma cells HepG2 than that of in 2D-cultured MSC-CM and control groups...
June 29, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28656237/matrine-increases-the-inhibitory-effects-of-afatinib-on-h1975-cells-via-the-il%C3%A2-6-jak1-stat3-signaling-pathway
#14
Shui-Fang Chen, Ze-Ying Zhang, Jian-Li Zhang
Resistance to epidermal growth factor receptor (EGFR) inhibitors is of primary concern in the treatment of non‑small‑cell lung cancer (NSCLC) with EGFR mutations. To investigate the effects of matrine on H1975 cells and to examine a novel, potential treatment option for NSCLC, the present study measured cell viability, apoptotic rate, interleukin 6 (IL‑6) expression and activation of the janus kinase (JAK) 1/signal transducer and activator of transcription (STAT)3 signaling pathway in cells treated with or without matrine, in the presence or absence of afatinib...
June 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28655832/an-unbiased-high-throughput-screen-to-identify-novel-effectors-that-impact-on-cardiomyocyte-aggregate-levels
#15
Patrick M McLendon, Gregory Davis, James Gulick, Sonia R Singh, Na Xu, Nathan Salomonis, Jeffery D Molkentin, Jeffrey Robbins
Rationale: Post-mitotic cells such as cardiomyocytes appear to be particularly susceptible to proteotoxic stimuli, and large, proteinaceous deposits are characteristic of the Desmin Related Cardiomyopathies and crystallin cardiomyopathic diseases. Increased activity of protein clearance pathways in the cardiomyocyte such as proteasomal degradation and autophagy have proven to be beneficial in maintaining cellular and cardiac function in the face of multiple proteotoxic insults, holding open the possibility of targeting these processes for the development of effective therapeutics...
June 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/28649004/macc1-regulates-fas-mediated-apoptosis-through-stat1-3-mcl-1-signaling-in-solid-cancers
#16
Harikrishnan Radhakrishnan, Katharina Ilm, Wolfgang Walther, Senji Shirasawa, Takehiko Sasazuki, Peter T Daniel, Bernhard Gillissen, Ulrike Stein
MACC1 was identified as a novel player in cancer progression and metastasis, but its role in death receptor-mediated apoptosis is still unexplored. We show that MACC1 knockdown sensitizes cancer cells to death receptor-mediated apoptosis. For the first time, we provide evidence for STAT signaling as a MACC1 target. MACC1 knockdown drastically reduced STAT1/3 activating phosphorylation, thereby regulating the expression of its apoptosis targets Mcl-1 and Fas. STAT signaling inhibition by the JAK1/2 inhibitor ruxolitinib mimicked MACC1 knockdown-mediated molecular signatures and apoptosis sensitization to Fas activation...
June 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28646470/apobec3b-and-il-6-form-a-positive-feedback-loop-in-hepatocellular-carcinoma-cells
#17
Shuran Li, Xueyang Bao, Duowei Wang, Linjun You, Xianjing Li, Hongbao Yang, Jinsong Bian, Yun Wang, Yong Yang
APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3B and IL-6, and thereby promoted the prolonged non-resolving inflammation...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28645562/anti-myeloma-effects-of-ruxolitinib-combined-with-bortezomib-and-lenalidomide-a-rationale-for-jak-stat-pathway-inhibition-in-myeloma-patients
#18
Mariana B de Oliveira, Veruska L Fook-Alves, Angela I P Eugenio, Rodrigo C Fernando, Luiz Felipe G Sanson, Mariana F de Carvalho, Walter M T Braga, Faith E Davies, Gisele W B Colleoni
JAK proteins have been linked with survival and proliferation of multiple myeloma (MM) cells; therefore, JAK inhibition could be a therapeutic strategy for MM. We evaluated JAK1 and JAK2 expression in MM patients and the effects of JAK/STAT pathway inhibition on apoptosis, cell cycle, gene and protein expression in RPMI-8226 and U266 MM cell lines. 57% of patients presented overexpression of JAK2 and 27%, of JAK1. After treatment with ruxolitinib and bortezomib, RPMI-8226 and U266 presented 50% of cells in late apoptosis, reduction of anti-apoptotic genes expression and higher number of cells in SubG0 phase...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645489/effects-of-hypnotic-bromovalerylurea-on-microglial-bv2-cells
#19
Shun Kawasaki, Naoki Abe, Fumito Ohtake, Afsana Islam, Mohammed Emamussalehin Choudhury, Ryo Utsunomiya, Satoshi Kikuchi, Tasuku Nishihara, Jun Kuwabara, Hajime Yano, Yuji Watanabe, Mayuki Aibiki, Toshihiro Yorozuya, Junya Tanaka
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1)...
June 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#20
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
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