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https://www.readbyqxmd.com/read/28742207/socs3-overexpression-enhances-adm-resistance-in-bladder-cancer-t24-cells
#1
M-Z Li, D-H Lai, H-B Zhao, Z Chen, Q-X Huang, J Situ
OBJECTIVE: JAK-STAT3 signaling pathway widely participates in cell proliferation and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast cancer and leukemia. However, its role in bladder cancer drug resistance is still unclear. This study established ADM resistant bladder cancer cell model to investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance. MATERIALS AND METHODS: ADM drug resistant cell line T24/ADM was established...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28739827/transcriptional-profiling-of-the-chicken-tracheal-response-to-virulent-mycoplasma-gallisepticum-strain-rlow
#2
J Beaudet, E R Tulman, K Pflaum, X Liao, G F Kutish, S M Szczepanek, L K Silbart, S J Geary
Mycoplasma gallisepticum, the primary etiologic agent of Chronic Respiratory Disease (CRD) in poultry, leads to prolonged recruitment and activation of inflammatory cells in the respiratory mucosa. This is consistent with the current model of immune dysregulation that ostensibly allows the organism to evade clearance mechanisms and establish chronic infection. To date, studies using qRT-PCR and microarrays have shown a significant transient up-regulation of cytokines and chemokines from tracheal epithelial cells (TECs) in vitro and tracheal tissue ex vivo in response to virulent strain Rlow, that contributes to the infiltration of inflammatory cells into the tracheal mucosa...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739485/hsp90-is-necessary-for-the-ack1-dependent-phosphorylation-of-stat1-and-stat3
#3
Nisintha Mahendrarajah, Marina E Borisova, Sigrid Reichardt, Maren Godmann, Andreas Sellmer, Siavosh Mahboobi, Andrea Haitel, Katharina Schmid, Lukas Kenner, Thorsten Heinzel, Petra Beli, Oliver H Krämer
Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells. These processes are associated with STAT1-dependent gene expression and an interaction between endogenous STAT1 and ACK1...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28739255/wp1066-a-small-molecule-inhibitor-of-the-jak-stat3-pathway-inhibits-ceramide-glucosyltransferase-activity
#4
Hirotaka Tsurumaki, Hikaru Katano, Kousuke Sato, Ryu Imai, Satomi Niino, Yoshio Hirabayashi, Shinichi Ichikawa
WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-cermide and UDP-glucose...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28738804/oncogenic-long-noncoding-rna-landscape-in-breast-cancer
#5
Shouping Xu, Dejia Kong, Qianlin Chen, Yanyan Ping, Da Pang
BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28737134/nephrotic-syndrome-in-primary-myelofibrosis-with-renal-extramedullary-hematopoiesis-and-glomerulopathy-in-the-jak-inhibitor-era
#6
Rachele Del Sordo, Rachele Brugnano, Carla Covarelli, Gioia Fiorucci, Franca Falzetti, Giorgio Barbatelli, Emidio Nunzi, Angelo Sidoni
Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure...
July 24, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#7
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729093/pim-kinases-1-2-and-3-in-intracellular-lif-signalling-proliferation-and-apoptosis-in-trophoblastic-cells
#8
Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M Morales-Prieto, Udo R Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3...
July 17, 2017: Experimental Cell Research
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
#9
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/28721333/pulmonary-cryptococcosis-in-a-ruxolitinib-treated-patient-with-primary-myelofibrosis
#10
Anna Hirano, Masahiro Yamasaki, Naomi Saito, Koji Iwato, Wakako Daido, Kunihiko Funaishi, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi
We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28716890/negative-regulation-of-cytokine-signaling-in-immunity
#11
Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko Nakatsukasa
Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28715864/in-vitro-and-in-vivo-anticancer-activity-of-2-acetyl-benzylamine-isolated-from-adhatoda-vasica-l-leaves
#12
C Balachandran, Y Arun, B Sangeetha, V Duraipandiyan, S Awale, N Emi, S Ignacimuthu, P T Perumal
One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28712096/myeloproliferative-neoplasms-translating-new-discoveries-into-better-outcomes-better-quality-of-life
#13
REVIEW
Leslie Padrnos, Ruben A Mesa
Despite the identification of JAK mutations and the development of targeted inhibitors, there remain significant unmet needs for patients with myeloproliferative neoplasms. Identification of the myeloproliferative neoplasm populations not currently benefiting from JAK inhibitor therapy highlights the therapeutic deficits still present in this heterogeneous stem cell malignancy. While JAK inhibition has provided significant benefits for patients with intermediate-2 or high-risk myelofibrosis and in patients with polycythemia vera in the second-line setting, JAK inhibitor monotherapy is not approved and not appropriate for all patients with myeloproliferative neoplasms...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28711084/herpes-zoster-in-psoriasis-patients-treated-with-tofacitinib
#14
Kevin L Winthrop, Mark Lebwohl, Arnon D Cohen, Jeffrey M Weinberg, Stephen K Tyring, Scott T Rottinghaus, Pankaj Gupta, Kaori Ito, Huaming Tan, Mandeep Kaur, Alexander Egeberg, Lotus Mallbris, Hernan Valdez
BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models...
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28710306/ruxolitinib-treatment-in-an-infant-with-jak2-polycythaemia-vera-associated-budd-chiari-syndrome
#15
Mehmet Enes Coskun, Sue Height, Anil Dhawan, Nedim Hadzic
Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction commonly seen with myeloproliferative neoplasms (MPNs). Polycythaemia vera (PV) is a very rare MPN in childhood. This is the youngest reported patient diagnosed with PV and BCS secondary to JAK V617F mutation.A 26-month-old girl was admitted with a 5-month history of abdominal distension, hepatosplenomegaly and ascites. Imaging studies revealed occlusion of the right hepatic vein and marked attenuation of the middle and left hepatic veins...
July 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28708884/a-jak1-2-inhibitor-baricitinib-inhibits-osteoclastogenesis-by-suppressing-rankl-expression-in-osteoblasts-in-vitro
#16
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
#17
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/28700333/onc201-selectively-induces-apoptosis-in-cutaneous-t-cell-lymphoma-cells-via-activating-pro-apoptotic-integrated-stress-response-and-inactivating-jak-stat-and-nf-%C3%AE%C2%BAb-pathways
#18
Xiao Ni, Xiang Zhang, Cheng-Hui Hu, Timothy Langridge, Rohinton S Tarapore, Joshua E Allen, Wolfgang Oster, Madeleine Duvic
Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4+ malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698206/expression-of-pim-kinases-in-reed-sternberg-cells-fosters-immune-privilege-and-tumor-cell-survival-in-hodgkin-lymphoma
#19
Maciej Szydłowski, Monika Prochorec-Sobieszek, Anna Szumera-Cieckiewicz, Edyta Derezinska, Grazyna Hoser, Danuta Wasilewska, Olga Szymanska-Giemza, Ewa Jabłonska, Emilia Białopiotrowicz, Tomasz Sewastianik, Anna Polak, Wojciech Czardybon, Michał Gałezowski, Renata Windak, Jan Maciej Zaucha, Krzysztof Warzocha, Krzysztof Brzózka, Przemysław Juszczynski
Reed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) express multiple immunoregulatory proteins that shape the cHL microenvironment and allow tumor cells to evade immune surveillance. Expression of certain immunoregulatory proteins is modulated by pro-survival transcription factors, such as NFκB and STATs. Since these factors also induce expression of the oncogenic PIM1/2/3 serine/threonine kinases, and since PIMs modulate transcriptional activity of NFκB and STATs, we hypothesized that these kinases support RS cell survival and foster their immune privilege...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28686728/regulation-of-platelet-activating-factor-mediated-protein-tyrosine-phosphatase-1b-activation-by-a-janus-kinase-2-calpain-pathway
#20
Geneviève Hamel-Côté, Daniel Gendron, Marek Rola-Pleszczynski, Jana Stankova
Atherosclerosis is a pro-inflammatory condition underlying many cardiovascular diseases. Platelet-activating factor (PAF) and interleukin 6 (IL-6) are actively involved in the onset and progression of atherosclerotic plaques. The involvement of monocyte-derived macrophages is well characterized in the installation of inflammatory conditions in the plaque, but less is known about the contribution of monocyte-derived dendritic cells (Mo-DCs). In the same way, the involvement of calcium, phospholipase C and A2 in PAF-induced IL-6 production, in different cells types, has been shown; however, the importance of the Jak/STAT pathway and its regulation by protein-tyrosine phosphatases in this response have not been addressed...
2017: PloS One
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