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https://www.readbyqxmd.com/read/28822855/tetrandrine-cardioprotection-in-ischemia-reperfusion-i-r-injury-via-jak3-stat3-hexokinase-ii
#1
Tie-Jun Zhang, Rui-Xia Guo, Xia Li, Yan-Wei Wang, Yong-Jun Li
Tetrandrine(TET), a bisbenzylisoquinoline alkaloid has been used for the treatment of cardiovascular diseases and hypertension. This study was to investigate whether tetrandrine exerts cardioprotection in ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of tetrandrine was evaluated by I/R injury cardiac cell model. Hexokinase II (HKII) is the critical regulators of mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28819126/targeted-blockade-of-tgf-%C3%AE-and-il-6-jak2-stat3-pathways-inhibits-lung-cancer-growth-promoted-by-bone-marrow-derived-myofibroblasts
#2
Jindong Shi, Jingjing Feng, Juan Xie, Zhoufang Mei, Tianyun Shi, Shengmei Wang, Yong Du, Gong Yang, Yougen Wu, Xiaojiao Cheng, Shanqun Li, Liming Zhu, Chung S Yang, Shuiping Tu, Zhijun Jie
To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) - lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor - SB431542 and/or JAK2/STAT3 inhibitor - JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814433/personalized-medicine-based-approach-to-model-patterns-of-chemoresistance-and-tumor-recurrence-using-ovarian-cancer-stem-cell-spheroids
#3
Shreya Raghavan, Pooja Mehta, Maria W Ward, Michael E Bregenzer, Elyse M A Fleck, Lijun Tan, Karen McLean, Ronald Buckanovich, Geeta Mehta
PURPOSE: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. In order to screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. EXPERIMENTAL DESIGN: We initiated spheroids with primary ALDH+ CD133+ ovarian cancer stem cells (OvCSCs) from different patient samples, and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor...
August 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28810537/cilostazol-protects-mice-against-myocardium-ischemic-reperfusion-injury-by-activating-a-ppar%C3%AE-jak2-stat3-pathway
#4
Jiangjin Li, Xiaoli Xiang, Xiaoxuan Gong, Yafei Shi, Jing Yang, Zuo Xu
Myocardial ischemia/reperfusion (MIR) injury causes severe arrhythmias and a high lethality. The present study is designed to investigate the effect of cilostazol on MIR injury and the underlying mechaism. We measured the effects of cilostazol on heart function parameters in a mouse model of MIR. Proinflammatory cytokines and apoptosis proteins in the myocardium were examined to investigate the anti-inflammatory and anti-apoptosis ability of cilostazol. The participation of PPARγ/JAK2/STAT3 pathway was investigated...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28800960/ets-transcription-factor-elf5-induces-lumen-formation-in-a-3d-model-of-mammary-morphogenesis-and-its-expression-is-inhibited-by-jak2-inhibitor-tg101348
#5
Jennifer Chean, Charng-Jui Chen, John E Shively
The loss of expression of a single gene can revert normal tissue to a malignant phenotype. For example, while normal breast has high lumenal expression of CEACAM1, the majority of breast cancers exhibit the early loss of this gene with the concurrent loss of their lumenal phenotype. MCF7 cells that lack CEACAM1 expression and fail to form lumena in 3D culture, regain the normal phenotype when transfected with CEACAM1. In order to probe the mechanism of this gain of function, we treated these cells with the clinically relevant Jak2 inhibitor TG101348 (TG), expecting that disruption of the prolactin receptor signaling pathway would interfere with the positive effects of transfection of MCF7 cells with CEACAM1...
August 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28798799/central-administration-of-1-deoxynojirimycin-attenuates-hypothalamic-endoplasmic-reticulum-stress-and-regulates-food-intake-and-body-weight-in-mice-with-high-fat-diet-induced-obesity
#6
Jongwan Kim, Eun-Young Yun, Fu-Shi Quan, Seung-Won Park, Tae-Won Goo
The α-glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#7
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28794380/tumor-lysis-syndrome-after-the-administration-of-ruxolitinib-in-a-patient-with-post-polycythemia-vera-myelofibrosis
#8
Megumi Koshiishi, Yuki Sueki, Ichiro Kawashima, Kei Nakajima, Toru Mitsumori, Keita Kirito
The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28791654/pharmacotherapy-of-myelofibrosis
#9
REVIEW
Douglas Tremblay, Bridget Marcellino, John Mascarenhas
Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors...
August 8, 2017: Drugs
https://www.readbyqxmd.com/read/28790099/gsk2586184-a-jak1-selective-inhibitor-in-two-patients-with-ulcerative-colitis
#10
Leonie C S De Vries, Valerie J Ludbrook, Kirsty J Hicks, Geert R D'Haens
Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus...
August 7, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28782829/the-participation-of-fibroblast-growth-factor-23-fgf23-in-the-progression-of-osteoporosis-via-jak-stat-pathway
#11
Lijun Xu, Lixia Zhang, Huijuan Zhang, Zaigang Yang, Lei Qi, Yurong Wang, Shuxin Ren
Osteoporosis (OP) is a major skeletal disorder for the old man. The fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by osteoblasts and osteocytes. However, the regulatory mechanisms of FGF23 in the progression of osteoporosis remain poorly understood. This study aims to explore the downstream regulating pathway of FGF23 in postmenopausal osteoporosis. The rat model of osteoporosis was established through ovariectomy (OVX). The investigation demonstrated that the serum levels of FGF23 and the phosphorylation levels of JAK2, STAT1 and STAT3 were up-regulated in the OVX + NVP-BGJ398 group while were down-regulated in the OVX + Anti-FGF23 group than that in the OVX group...
August 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28782256/risk-factors-and-a-prognostic-model-for-post-splenectomy-survival-in-myelofibrosis
#12
Ayalew Tefferi, Mythri Mudireddy, Naseema Gangat, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, David M Nagorney
Palliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. In order to assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for post-splenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count <100 x 10(9)/L, 25% leukocyte count >25 x 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate-2, 21% intermediate-1 and 3% low...
August 7, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28771727/salvianolic-acids-enhance-cerebral-angiogenesis-and-neurological-recovery-by-activating-jak2-stat3-signaling-pathway-after-ischemic-stroke-in-mice
#13
Yaoru Li, Xiangjian Zhang, Lili Cui, Rong Chen, Ye Zhang, Cong Zhang, Xingyuan Zhu, Tingting He, Zuyuan Shen, Lipeng Dong, Jingru Zhao, Ya Wen, Xiufen Zheng, Pan Li
Post-stroke angiogenesis facilitates neurovascular remodeling process and promotes neurological recovery. Proangiogenic effects of Salvianolic acids (Sals) have been reported in various ischemic disorders. However, the underlying mechanisms are still poorly understood. Previous studies of our laboratory have demonstrated that activating Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the protection against cerebral ischemia/reperfusion injury. In the present study, we investigated the impacts of Sals on angiogenesis and long-term neurological recovery after ischemic stroke as well as the potential mechanisms...
August 3, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28770966/inhibition-of-mir-221-influences-bladder-cancer-cell-proliferation-and-apoptosis
#14
H Liu, J-K Chang, J-Q Hou, Z-H Zhao, L-D Zhang
OBJECTIVE: Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway participate in cell proliferation and apoptosis. Suppressors of cytokine signaling 3 (SOCS3) are negative regulators of JAK-STAT3. SOCS3 was found significantly declined, while microRNA-221 (miR-221) obviously up-regulated in bladder cancer tissue. Bioinformatics analysis revealed the complementary binding site between miR-221 and 3'-UTR of SOCS3. This study investigated the role of miR-221 in regulating SOCS3/JAK-STAT3 signaling pathway and bladder cancer cell proliferation and apoptosis...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28770707/pro-fibrotic-effect-of-il-6-via-aortic-adventitial-fibroblasts-indicates-il-6-as-a-treatment-target-in-takayasu-arteritis
#15
Xiufang Kong, Lili Ma, Zongfei Ji, Zhihui Dong, Zhigang Zhang, Jun Hou, Si Zhang, Lingying Ma, Lindi Jiang
OBJECTIVES: This study aimed to clarify potential mechanism of IL-6 involved in adventitial fibrosis via adventitial fibroblast in Takayasu arteritis (TAK). METHODS: Immunohistochemistry and double-labelled immunofluorescence were performed on vascular tissue from patients with TAK and controls. Human aorta adventitial fibroblast (AAF) was cultured and stimulated with interleukine 6 (IL-6)/IL-6 receptor (IL-6R). Real-time PCR, western blot, enzyme-linked immunosorbent assays, chromatin immunoprecipitation (ChIP) and reporter assay were conducted in vitro experiments to determine effect of IL-6/IL-6R on AAF...
July 6, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28765941/b7-h3-is-related-to-tumor-progression-in-ovarian-cancer
#16
Jingjing Zhang, Lu Liu, Sai Han, Yi Li, Qiuhong Qian, Qianqian Zhang, Hui Zhang, Ziyan Yang, Youzhong Zhang
B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but its role and mechanism is not clear. In this study, we further verified the expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues. Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as determined by immunofluorescence staining...
July 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28765891/non-coding-rna-886-promotes-renal-cell-carcinoma-growth-and-metastasis-through-the-janus-kinase-2-signal-transducer-and-activator-of-transcription-3-signaling-pathway
#17
Jun Lei, Ju-Hua Xiao, Shou-Hua Zhang, Zhi-Qiang Liu, Kai Huang, Zhi-Peng Luo, Xin-Lan Xiao, Zheng-Dong Hong
Non-coding RNA 886 (nc886) has been suggested to serve tumor-suppressing roles in several cancer cells. However, the expression pattern of nc886 and its function in renal cell carcinoma (RCC) has not been reported until now. The present study aimed to examine the expression of nc886 in human RCC tissues and to investigate the role of nc886 in RCC cell proliferation, apoptosis and invasion in vitro. Furthermore, whether nc886 exerts its function on RCC via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling was investigated...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28761070/homocysteine-induces-mitochondrial-dysfunction-involving-the-crosstalk-between-oxidative-stress-and-mitochondrial-pstat3-in-rat-ischemic-brain
#18
Shuang Chen, Zhiping Dong, Yaqian Zhao, Na Sai, Xuan Wang, Huan Liu, Guowei Huang, Xumei Zhang
Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cerebral ischemia. An elevated Hcy level was also accompanied by the significant inhibition of mitochondrial complex I-III enzymatic activities in addition to an increase in cytochrome c release...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#19
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28737134/nephrotic-syndrome-in-primary-myelofibrosis-with-renal-extramedullary-hematopoiesis-and-glomerulopathy-in-the-jak-inhibitor-era
#20
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
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