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https://www.readbyqxmd.com/read/28938599/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#1
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938529/defining-a-therapeutic-window-for-kinase-inhibitors-in-leukemia-to-avoid-neutropenia
#2
Kate McArthur, Akshay A D'Cruz, David Segal, Kurt Lackovic, Andrew F Wilks, Joanne A O'Donnell, Cameron J Nowell, Motti Gerlic, David C S Huang, Christopher J Burns, Ben A Croker
Neutropenia represents one of the major dose-limiting toxicities of many current cancer therapies. To circumvent the off-target effects of cytotoxic chemotherapeutics, kinase inhibitors are increasingly being used as an adjunct therapy to target leukemia. In this study, we conducted a screen of leukemic cell lines in parallel with primary neutrophils to identify kinase inhibitors with the capacity to induce apoptosis of myeloid and lymphoid cell lines whilst sparing primary mouse and human neutrophils. We have utilized a high-throughput live cell imaging platform to demonstrate that cytotoxic drugs have limited effects on neutrophil viability but are toxic to hematopoietic progenitor cells, with the exception of the topoisomerase I inhibitor SN-38...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936833/-mechanism-of-salvianolate-injection-combined-with-aspirin-in-treatment-of-stable-angina-pectoris-based-on-biomolecules-network
#3
Yuan Li, Lian-Xin Wang, Yan-Ming Xie
Biomolecular network analysis was used to predict the mechanism of Salvianolate injection combined with aspirin for the treatment of stable angina pectoris(SAP). Related genes of Salvianolate injection, aspirin and SAP were obtained from Genecards, STITCH and DisGeNET databases. Agilent literature search software was used to construct biomolecular network; modules were identified by AP, MCODE and MCL methods. DAVID software was used for identification of related KEGG pathways. Results showed that Salvianolate injection and aspirin had a coverage rate of 45...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28931061/binding-of-a-c-type-lectin-s-coiled-coil-domain-to-the-domeless-receptor-directly-activates-the-jak-stat-pathway-in-the-shrimp-immune-response-to-bacterial-infection
#4
Jie-Jie Sun, Jiang-Feng Lan, Xiao-Fan Zhao, Gerardo R Vasta, Jin-Xing Wang
C-type lectins (CTLs) are characterized by the presence of a C-type carbohydrate recognition domain (CTLD) that by recognizing microbial glycans, is responsible for their roles as pattern recognition receptors in the immune response to bacterial infection. In addition to the CTLD, however, some CTLs display additional domains that can carry out effector functions, such as the collagenous domain of the mannose-binding lectin. While in vertebrates, the mechanisms involved in these effector functions have been characterized in considerable detail, in invertebrates they remain poorly understood...
September 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28929088/microbial-invasion-vs-tick-immune-regulation
#5
REVIEW
Daniel E Sonenshine, Kevin R Macaluso
Ticks transmit a greater variety of pathogenic agents that cause disease in humans and animals than any other haematophagous arthropod, including Lyme disease, Rocky Mountain spotted fever, human granulocytic anaplasmosis, babesiosis, tick-borne encephalitis, Crimean Congo haemorhagic fever, and many others (Gulia-Nuss et al., 2016). Although diverse explanations have been proposed to explain their remarkable vectorial capacity, among the most important are their blood feeding habit, their long term off-host survival, the diverse array of bioactive molecules that disrupt the host's natural hemostatic mechanisms, facilitate blood flow, pain inhibitors, and minimize inflammation to prevent immune rejection (Hajdušek et al...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28920589/neuroimmunology-jak-in-the-itch
#6
Yvonne Bordon
No abstract text is available yet for this article.
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28919782/inhibitory-effects-of-a-selective-jak2-inhibitor-on-adrenocorticotropic-hormone-production-and-proliferation-of-corticotroph-tumor-att20-cells
#7
Yuko Asari, Kazunori Kageyama, Yuki Nakada, Mizuki Tasso, Shinobu Takayasu, Kanako Niioka, Noriko Ishigame, Makoto Daimon
PURPOSE: The primary cause of Cushing's disease is adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak-STAT pathway is located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28918255/microglia-mediated-baff-baffr-ligation-promotes-neuronal-survival-in-brain-ischemia-injury
#8
Kai Li, Wei Yu, Rangjuan Cao, Zhihua Zhu, Guoqing Zhao
The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. We found that under ischemic condition, the B-cell activating factor (BAFF) was vastly upregulated in microglia and this upregulation could at least be attributed to JAK-STAT signaling pathway activated by IFN-γ and IL-10, which were spatio-temporally enriched in I/R injured brain as well...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28914550/socs3-participates-in-cholinergic-pathway-regulation-of-synovitis-in-rheumatoid-arthritis
#9
Tong Li, Shiyao Wu, Sha Li, Xuelian Bai, Hui Luo, Xiaoxia Zuo
Stimulation of the cholinergic inflammatory pathway can promote collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 signaling. Suppressor of cytokine signaling (SOCS) protein can also regulate inflammatory processes and activate JAK/STAT signal transduction, but its involvement in rheumatoid arthritis (RA) has not been demonstrated. This study investigated the effect of SOCS on cholinergic pathway regulation of synovitis in the fibroblast-like synoviocytes (FLSs) of RA and CIA mice...
September 15, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28911610/myrciaria-cauliflora-extract-improves-diabetic-nephropathy-via-suppression-of-oxidative-stress-and-inflammation-in-streptozotocin-nicotinamide-mice
#10
Jeng-Dong Hsu, Chia-Chun Wu, Chi-Nan Hung, Chau-Jong Wang, Hui-Pei Huang
Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28906039/novel-role-of-the-nociceptin-system-as-a-regulator-of-glutamate-transporter-expression-in-developing-astrocytes
#11
Logan C Meyer, Caitlin E Paisley, Esraa Mohamed, John W Bigbee, Tomasz Kordula, Hope Richard, Kabirullah Lutfy, Carmen Sato-Bigbee
Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1 in both human and rodent brain astrocytes. This nociceptin-mediated response takes place during a critical developmental window that coincides with the early stages of astrocyte maturation...
September 14, 2017: Glia
https://www.readbyqxmd.com/read/28904065/angptl1-interacts-with-integrin-%C3%AE-1%C3%AE-1-to-suppress-hcc-angiogenesis-and-metastasis-by-inhibiting-jak2-stat3-signaling
#12
Qian Yan, Lingxi Jiang, Ming Liu, Dandan Yu, Yu Zhang, Yan Li, Shuo Fang, Yan Li, Ying-Hui Zhu, Yunfei Yuan, Xin Yuan Guan
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2 mediated anti-apoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903034/piwi-is-required-to-limit-exhaustion-of-aging-somatic-stem-cells
#13
Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T Madden, Victoria V Lunyak, Heinrich Jasper
Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs), yet little is known about mechanisms regulating genome maintenance in these cells. Here, we show that intestinal stem cells (ISCs) induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28902351/anoctamin5-regulates-cell-migration-and-invasion-in-thyroid-cancer
#14
Zhengyan Chang, Chunmiao Cai, Dongyan Han, Yaohui Gao, Qianyu Li, Lijin Feng, Wei Zhang, Jiayi Zheng, Jiaoying Jin, Huizhen Zhang, Qing Wei
Anoctamin/TMEM16 family members have recently been identified as novel calcium-activated chloride channels, and dysregulation of many family members participates in tumorigenesis and progression. However, the exact role of anoctamin5 (ANO5), one member of this family, in thyroid cancer is still not clarified. In this study, we firstly found that the expression levels of ANO5 was significantly downregulated in thyroid cancer compared to adjacent normal tissue by mining the public GEO database. Subsequently, we further demonstrated that the expression levels of ANO5 was significantly downregulated in 69...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901399/downregulated-socs1-expression-activates-the-jak1-stat1-pathway-and-promotes-polarization-of-macrophages-into-m1-type
#15
Yan-Bing Liang, Hao Tang, Zhi-Bin Chen, Li-Jin Zeng, Jing-Guo Wu, Wen Yang, Zhen-Yu Li, Zhong-Fu Ma
Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh)RNA into mouse macrophage cells, reverse transcription‑quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK)1 and signal transducer and activator of transcription (STAT)1 increased significantly...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900038/socs1-is-an-inducible-negative-regulator-of-ifn-lambda-induced-gene-expression-in-vivo
#16
Tanja Blumer, Mairene Coto-Llerena, Francois H T Duong, Markus H Heim
Type I (α and β) and type III (λ) interferons (IFNs) are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor κB. Secreted IFNs induce autocrine and paracrine signalling through the JAK-Stat pathway leading to the transcriptional induction of hundreds of IFN stimulated genes (ISGs), amongst them sensory pathway components such as cGAS, STING, RIG-I, MDA5 and the transcription factor IRF7 that enhance the induction of IFNαs and IFNλss...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28894040/the-role-of-vitamin-d-in-the-development-of-autoimmune-diseases
#17
Katarzyna A Lisowska, Ewa Bryl
Witamina D, poza istotną rolą w utrzymaniu homeostazy wapnia i metabolizmie kostnym, odgrywa ważną rolę w funkcjonowaniu układu odpornościowego. Niedobór witaminy D wiąże się z wieloma niekorzystnymi dla zdrowia skutkami, włączając w to m.in. osłabienie odporności, czego skutkiem jest zwiększona podatność na zakażenia wirusowe, bakteryjne oraz grzybicze. W artykule opisano podstawy metabolizmu witaminy D oraz jej rolę fizjologiczną, ze szczególnym uwzględnieniem wpływu na komórki układu odpornościowego...
August 28, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28893346/overexpression-of-microrna-34a-5p-inhibits-proliferation-and-promotes-apoptosis-of-human-cervical-cancer-cells-by-downregulation-of-bcl-2
#18
Xiufen Wang, Yucui Xie, Jing Wang
Aberrant expressions of microRNAs (miRNAs) are involved in the development and progression of various types of cancers.In this study, we investigated the roles of miR-34a-5p in proliferation, migration, invasion and apoptosis of cervical cancer cells (HeLa cells). We found that overexpression of miR-34a-5p significantly inhibited the viabilities, migration, and invasion of HeLa cells, but promoted cell apoptosis. Suppression of miR-34a-5p showed opposite effects. The expression levels of Bcl-2 in HeLa cells were increased by miR-34a-5p suppression but decreased by miR-34a-5p overexpression...
August 30, 2017: Oncology Research
https://www.readbyqxmd.com/read/28893190/canonical-and-non-canonical-jak-stat-transcriptional-targets-may-be-involved-in-distinct-and-overlapping-cellular-processes
#19
Amy Tsurumi, Connie Zhao, Willis X Li
BACKGROUND: The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway has been well-characterized as a crucial signal transduction cascade that regulates vital biological responses including development, immunity and oncogenesis. Additionally to its canonical pathway that uses the phosphorylated form of the STAT transcription factor, recently the non-canonical pathway involving heterochromatin formation by unphosphorylated STAT was recently uncovered. Considering the significant role of the JAK/STAT pathway, we used the simple Drosophila system in which the non-canonical pathway was initially characterized, to compare putative canonical versus non-canonical transcriptional targets across the genome...
September 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28891341/small-molecule-therapy-for-managing-moderate-to-severe-psoriatic-arthritis
#20
Luisa Costa, Antonio Del Puente, Rosario Peluso, Marco Tasso, Paolo Caso, Maria Sole Chimenti, Vincenzo Sabbatino, Nicolò Girolimetto, Carolina Benigno, Nicoletta Bertolini, Aurora Del Puente, Roberto Perricone, Raffaele Scarpa, Francesco Caso
The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases...
September 11, 2017: Expert Opinion on Pharmacotherapy
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