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https://www.readbyqxmd.com/read/29791864/lncrna-tug1-interacting-with-mir-144-contributes-to-proliferation-migration-and-tumorigenesis-through-activating-the-jak2-stat3-pathway-in-hepatocellular-carcinoma
#1
Jun Lv, Yongkui Kong, Zhiqiang Gao, Yanmin Liu, Pengfei Zhu, Zujiang Yu
Recently, it is reported that taurine upregulated gene 1 (TUG1) participates in the tumor progression by acting as a competing endogenous RNA (ceRNA) of miRNAs. Nonetheless, whether TUG1 could serve as a ceRNA of miR-144 in hepatocellular carcinoma (HCC) progression remains undefined. Here, our results indicated that there was a marked rise in TUG1 expression in HCC tissues and cells, and downregulation of TUG1 hindered proliferation and migration of HCC cells. Additionally, TUG1 was validated to act as a molecular sponge of miR-144...
May 20, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29789785/chronic-intake-of-commercial-sweeteners-induces-changes-in-feeding-behavior-and-signaling-pathways-related-to-the-control-of-appetite-in-balb-c-mice
#2
Alberto A Barrios-Correa, José A Estrada, Caroline Martel, Martin Olivier, Rubén López-Santiago, Irazú Contreras
Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29789628/targetable-vulnerabilities-in-t-and-nk-cell-lymphomas-identified-through-preclinical-models
#3
Samuel Y Ng, Noriaki Yoshida, Amanda L Christie, Mahmoud Ghandi, Neekesh V Dharia, Joshua Dempster, Mark Murakami, Kay Shigemori, Sara N Morrow, Alexandria Van Scoyk, Nicolas A Cordero, Kristen E Stevenson, Maneka Puligandla, Brian Haas, Christopher Lo, Robin Meyers, Galen Gao, Andrew Cherniack, Abner Louissaint, Valentina Nardi, Aaron R Thorner, Henry Long, Xintao Qiu, Elizabeth A Morgan, David M Dorfman, Danilo Fiore, Julie Jang, Alan L Epstein, Ahmet Dogan, Yanming Zhang, Steven M Horwitz, Eric D Jacobsen, Solimar Santiago, Jian-Guo Ren, Vincent Guerlavais, D Allen Annis, Manuel Aivado, Mansoor N Saleh, Amitkumar Mehta, Aviad Tsherniak, David Root, Francisca Vazquez, William C Hahn, Giorgio Inghirami, Jon C Aster, David M Weinstock, Raphael Koch
T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs)...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29786757/copy-number-abnormality-of-acute-lymphoblastic-leukemia-cell-lines-based-on-their-genetic-subtypes
#4
Chihiro Tomoyasu, Toshihiko Imamura, Toshihiro Tomii, Mio Yano, Daisuke Asai, Hiroaki Goto, Akira Shimada, Masashi Sanada, Shotaro Iwamoto, Junko Takita, Masayoshi Minegishi, Takeshi Inukai, Kanji Sugita, Hajime Hosoi
In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph- B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines...
May 21, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#5
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/29784961/sarcodon-imbricatus-polysaccharides-improve-mouse-hematopoietic-function-after-cyclophosphamide-induced-damage-via-g-csf-mediated-jak2-stat3-pathway
#6
Xue Wang, Qiubo Chu, Xue Jiang, Yue Yu, Libian Wang, Yaqi Cui, Jiahui Lu, Lirong Teng, Di Wang
Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines...
May 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29782975/roles-of-germline-jak2-activation-mutation-jak2-v625f-in-the-pathology-of-myeloproliferative-neoplasms
#7
Qing-Yun Wu, Meng-Meng Ma, Lin Fu, Yuan-Yuan Zhu, Yang Liu, Jiang Cao, Ping Zhou, Zhen-Yu Li, Ling-Yu Zeng, Feng Li, Xiao-Yun Wang, Kai-Lin Xu
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29778097/hyperprolactinemia-inducing-antipsychotics-increase-breast-cancer-risk-by-activating-jak-stat5-in-precancerous-lesions
#8
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/29773603/clinical-efficacy-of-ruxolitinib-and-chemotherapy-in-a-child-with-philadelphia-chromosome-like-acute-lymphoblastic-leukemia-with-golga5-jak2-fusion-and-induction-failure
#9
Yang Y Ding, Julie W Stern, Tracey F Jubelirer, Gerald B Wertheim, Fumin Li, Fengqi Chang, Zhaohui Gu, Charles G Mullighan, Yong Li, Richard C Harvey, I-Ming Chen, Cheryl L Willman, Stephen P Hunger, Marilyn M Li, Sarah K Tasian
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773105/-protective-role-of-green-tea-polyphenols-in-intestinal-mucosal-barrier-function-of-mice-with-colitis-induced-by-tnbs-through-inhibiting-jak2-stat3-pathway
#10
Jin Xi, Sitang Ge, Lugen Zuo, Yuke Zhu, Lian Wang, Qiaoli Xie
Objective To analyze the therapeutic effect of green tea polyphenols (GTP) in mice with colitis induced by TNBS and its possible mechanism. Methods Colitis was induced by TNBS in BALB/C mice. The mice were randomly divided into GTP group (n=10) and TNBS model group (n=10). Mice in the GTP group were given GTP [0.2 mL at a dose level of 100 mg/(kg.d)] by oral gavage, and mice in the model group were given normal saline [0.2 ml/d] by gavage. Four weeks later, the mice were sacrificed. Disease activity index (DAI) and inflammatory score were evaluated by HE staining...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29771430/senp3-protects-h9c2-cells-from-apoptosis-triggered-by-h-r-via-stat3-pathway
#11
Y Zhang, L-M Zheng, C-X Wang, J-M Gu, S Xue
OBJECTIVE: To investigate whether SENP3 protects H9C2 cells from apoptosis triggered by H/R through the signal transducer and activator of transcription 3 (STAT3) pathway. MATERIALS AND METHODS: Male C57BL mice were cultured and mouse models of myocardial I/RI were established. At the same time, cardiomyoblast H9C2 cell line of rat embryo was cultured. Reactive oxygen species (ROS) level was detected during H/R using 2',7'-dichlorofluorescein diacetate (DCFH) kit...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29767839/jak2-v617f-positive-acute-myeloid-leukaemia-aml-a-comparison-between-de-novo-aml-and-secondary-aml-transformed-from-an-underlying-myeloproliferative-neoplasm-a-study-from-the-bone-marrow-pathology-group
#12
Jason Aynardi, Rashmi Manur, Paul R Hess, Seble Chekol, Jennifer J D Morrissette, Daria Babushok, Elizabeth Hexner, Heesun J Rogers, Eric D Hsi, Elizabeth Margolskee, Attilio Orazi, Robert Hasserjian, Adam Bagg
The JAK2 V617F mutation is characteristic of most Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and occurs rarely in de novo acute myeloid leukaemia (AML). We sought to characterize AMLs that harbour this mutation and distinguish those that arise de novo (AML-DN) from those that reflect transformation of an underlying MPN (AML-MPN). Forty-five patients with JAK2 V617F-mutated AML were identified; 15 were AML-DN and 30 were AML-MPN. AML-MPN cases were more likely to have splenomegaly (P = 0·02), MPN-like megakaryocytes and higher mean JAK2 V617F VAF at diagnosis (P = 0·04)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765446/inhibitory-effect-of-pdgf-bb-and-serum-stimulated-responses-in-vascular-smooth-muscle-cell-proliferation-by-hinokitiol-via-up-regulation-of-p21-and-p53
#13
Jiun-Yi Li, Chun-Ping Liu, Wei-Cheng Shiao, Thanasekaran Jayakumar, Yi-Shin Li, Nen-Chung Chang, Shih-Yi Huang, Cheng-Ying Hsieh
Introduction: Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis , Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Material and methods: Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum)...
April 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29764839/lineage-restriction-analyses-in-chip-indicate-myeloid-bias-for-tet2-and-multipotent-stem-cell-origin-for-dnmt3a
#14
Manuel Buscarlet, Sylvie Provost, Yassamin Feroz Zada, Vincent Bourgoin, Luigina Mollica, Marie-Pierre Dubé, Lambert Busque
We analyzed DNA from PMN (granulocytes), CD14+ (monocytes), CD19+ (B-cells) and CD3+ (T-cells) of 107 individuals with clonal hematopoiesis of indeterminate potential (CHIP) to perform lineage restriction analysis of different gene mutations. Individuals were aged 55 to 96 (mean age: 70.0). Three lineage categories were defined: myeloid (PMN±monocytes), myelolympho-B (myeloid and B-cells), multipotent (myeloid, B and T-cells). Six individuals with aberrant patterns were excluded from analysis. Fifty-six had a single DNMT3A mutation, 24 had a single TET2 mutation, 7 had a single mutation in other genes (JAK2, ASXL1, CBL or TP53), and 14 had multiple mutations...
May 15, 2018: Blood
https://www.readbyqxmd.com/read/29763638/effects-of-sc99-on-cerebral-ischemia-perfusion-injury-in-rats-selective-modulation-of-microglia-polarization-to-m2-phenotype-via-inhibiting-jak2-stat3-pathway
#15
Yiping Ding, Jinhong Qian, Haiying Li, Haitao Shen, Xiang Li, Yan Kong, Zhuan Xu, Gang Chen
Inhibition of Janus kinases 2-Signal transducers and activators of transcription3 (JAK2-STAT3) pathway has been shown to exert anti-inflammatory actions. SC99, a novel specific inhibitor targeting JAK2-STAT3 pathway, has been verified to negatively modulate platelet activation and aggregation in vitro. In current study, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in Sprague Dawley rats and primary cultured microglia was exposed to oxygen and glucose deprivation (OGD/R) in vitro...
May 12, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#16
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/29755699/sequential-immunotherapy-in-a-patient-with-primary-refractory-hodgkin-lymphoma-and-novel-mutations
#17
Richard Greil, Lisa Pleyer, Bettina Jansko, Carmen Feierabend, Lukas Rettenbacher, Olga Stiefel, Christoph Rass, Patrick Morre, Daniel Neureiter, Sigrun Greil-Ressler
Primary resistant Hodgkin lymphoma is an aggressive disease with few treatment options and short survival. Neoplastic cells of classical Hodgkin lymphoma are heavily dependent on microenvironmental stimuli, regularly express PD-L1, and a relevant proportion of relapsed patients is sensitive to blocking of the PD1/PD-L1 axis. However, response duration is limited and further treatment options are unknown but urgently needed. We report a case of a patient without relevant response to five subsequent chemotherapy regimens who immediately and dramatically responded to an anti-PD1 mab...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752723/mimetics-of-suppressor-of-cytokine-signalling-3-novel-potential-therapeutics-in-triple-breast-cancer
#18
Sara La Manna, Eunmi Lee, Maria Ouzounova, Concetta Di Natale, Ettore Novellino, Antonello Merlino, Hasan Korkaya, Daniela Marasco
Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumour growth and metastasis...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29751177/activation-of-the-il-6-jak2-stat3-pathway-induces-plasma-cell-mastitis-in-mice
#19
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/29749443/trim24-sirna-induced-cell-apoptosis-and-reduced-cell-viability-in-human-nasopharyngeal-carcinoma-cells
#20
Peng Wang, Na Shen, Danzheng Liu, Xianhui Ning, Daquan Wu, Xinsheng Huang
Nasopharyngeal carcinoma (NPC) is a common cancer occurring primarily in East Asia and Africa. The high rate of recurrence and metastasis of NPC continuously endangers the health of patients. The present study aimed to identify the underlying mechanisms involved in the progression of NPC and provide experimental basis to develop a novel and efficient agent against NPC. The present study measured the expression level of tripartite motif containing 24 (TRIM24) in tumor tissues from NPC patients using reverse transcription quantitative polymerase chain reaction...
May 2, 2018: Molecular Medicine Reports
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