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https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#1
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28092676/intracellular-il-37b-interacts-with-smad3-to-suppress-multiple-signaling-pathways-and-the-metastatic-phenotype-of-tumor-cells
#2
C Luo, Y Shu, J Luo, D Liu, D-S Huang, Y Han, C Chen, Y-C Li, J-M Zou, J Qin, Y Wang, D Li, S-S Wang, G-M Zhang, J Chen, Z-H Feng
Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092674/a-targetable-hb-egf-cited4-axis-controls-oncogenesis-in-lung-cancer
#3
C-H Hsieh, Y-T Chou, M-H Kuo, H-P Tsai, J-L Chang, C-W Wu
Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092042/alpha-based-multiplexed-assay-for-identifying-sh2-domain-antagonists
#4
Akira Asai, Kazuyuki Takakuma
Constitutive activation of STAT3/5b frequently occurs in various human malignancies. STAT3/5b activation involves dimerization via intermolecular pTyr-SH2 binding; therefore, antagonizing this interaction is a feasible approach to inhibit STAT3/5b activation for cancer therapy. We have developed a multiplexed assay to assess STAT3- and STAT5b-SH2 binding in a single well by combining AlphaLISA and AlphaScreen beads. In this chapter, we describe application of the method for the purpose of identifying new STAT3 and STAT5b antagonists...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28092032/expression-and-purification-of-soluble-stat5b-stat3-proteins-for-sh2-domain-binding-assay
#5
Akira Asai, Kazuyuki Takakuma
When a large hydrophobic full-length protein is expressed in bacteria, it is often challenging to obtain recombinant proteins in the soluble fraction. One way to overcome this challenge is expression of deletion mutants that have improved solubility while maintaining biological activity. In this chapter, we describe a protocol for expression of truncated forms of STAT5b and STAT3 proteins that are soluble and retain SH2-mediated activity for phospho-Tyr peptide recognition.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28090628/erk1-2-jnk-and-stat3-activation-and-correlation-with-tumor-differentiation-in-oral-scc
#6
I Gkouveris, N Nikitakis, D Avgoustidis, M Karanikou, G Rassidakis, A Sklavounou
Signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including ERK and JNK, have been implicated in oral squamous cell carcinoma (OSCC) development and progression. Our purpose was to evaluate the levels of activated STAT3, ERK1/2 and JNK by immunohistochemistry in OSCC and to investigate possible correlations of these molecules with each other as well as with the degree of tumor differentiation. Immunohistochemical assessment of the phosphorylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors...
January 16, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28089821/the-role-of-stat3-in-glioblastoma-progression-through-dual-influences-on-tumor-cells-and-the-immune-microenvironment
#7
Nakho Chang, Sun Hee Ahn, Doo-Sik Kong, Hye Won Lee, Do-Hyun Nam
Glioblastoma multiforme (GBM) is the most aggressive form of cancer that begins within the brain; generally, the patient has a dismal prognosis and limited therapeutic options. Signal transducer and activator of transcription 3 (STAT3) is a critical mediator of tumorigenesis, tumor progression, and suppression of anti-tumor immunity in GBM. In a high percentage of GBM cells and tumor microenvironments, persistent activation of STAT3 induces cell proliferation, anti-apoptosis, glioma stem cell maintenance, tumor invasion, angiogenesis, and immune evasion...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28089769/nuclear-translocation-of-stat3-and-nf-%C3%AE%C2%BAb-are-independent-of-each-other-but-nf-%C3%AE%C2%BAb-supports-expression-and-activation-of-stat3
#8
Antons Martincuks, Katarzyna Andryka, Andrea Küster, Hildegard Schmitz-Van de Leur, Michal Komorowski, Gerhard Müller-Newen
NF-κB and STAT3 are essential transcription factors in immunity and act at the interface of the transition from chronic inflammation to cancer. Different functional crosstalks between NF-κB and STAT3 have been recently described arguing for a direct interaction of both proteins. During a systematic analysis of NF-κB/STAT3 crosstalk we observed that appearance of the subcellular distribution of NF-κB and STAT3 in immunofluorescence heavily depends on the fixation procedure. Therefore, we established an optimized fixation protocol for the reliable simultaneous analysis of the subcellular distributions of both transcription factors...
January 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28089732/alox15-as-a-suppressor-of-inflammation-and-cancer-lost-in-the-link
#9
REVIEW
Rui Tian, Xiangsheng Zuo, Jonathan Jaoude, Fei Mao, Jennifer Colby, Imad Shureiqi
Mounting evidence supports a mechanistic link between inflammation and cancer, especially colon cancer. ALOX15 (15-lipoxygenase-1) plays an important role in the formation of key lipid mediators (e.g., lipoxins and resolvins) to terminate inflammation. ALOX15 expression is downregulated in colorectal cancer (CRC). Intestinally-targeted transgenic expression of ALOX15 in mice inhibited dextran sodium sulfate-induced colitis from promoting azoxymethane- induced colorectal tumorigenesis, demonstrating that ALOX15 can suppress inflammation-driven promotion of carcinogen-induced colorectal tumorigenesis and therefore ALOX15 downregulation during tumorigenesis is likely to enhance the link between colitis and colorectal tumorigenesis...
January 12, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#10
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088467/stat3-signaling-mediates-tumour-resistance-to-egfr-targeted-therapeutics
#11
Ahmad A Zulkifli, Fiona H Tan, Tracy L Putoczki, Stanley S Stylli, Rodney B Luwor
Several EGFR inhibitors are currently undergoing clinical assessment or are approved for the clinical management of patients with varying tumour types. However, treatment often results in a lack of response in many patients. The majority of patients that initially respond eventually present with tumours that display acquired resistance to the original therapy. A large number of receptor tyrosine and intracellular kinases have been implicated in driving signaling that mediates this tumour resistance to anti-EGFR targeted therapy, and in a few cases these discoveries have led to overall changes in prospective tumour screening and clinical practice (K-RAS in mCRC and EGFR T790M in NSCLC)...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28088463/stress-induced-egf-receptor-signaling-through-stat3-and-tumor-progression-in-triple-negative-breast-cancer
#12
Nikolas Balanis, Cathleen R Carlin
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28087906/-effect-and-its-molecular-mechanisms-of-curcumin-on-pulmonary-artery-smooth-muscle-cells-in-rat-model-with-chronic-obstructive-pulmonary-disease
#13
Xiangang Lin, Yenong Chen, Zhuqing Liu
Objective: To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD). Methods: A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087904/-protective-effect-of-diosgenin-on-chondrocytes-mediated-by-jak2-stat3-signaling-pathway-in-mice-with-osteoarthritis
#14
Jun Liu, Xiaole He, Ping Zhen, Shenghu Zhou, Xusheng Li
Objective: To investigate the effect of diosgenin (Dgn) on chondrocytes and its relation to JAK2/STAT3 signaling pathway in mice with osteoarthritis (OA).Methods: Fifteen male C57BL/6 mice were randomly divided into three groups:control group, OA group and OA+Dgn group. After 4 weeks of treatment, the histopathological changes of cartilage tissue were observed by toluidine blue staining under light microscopy and the ultrastructure of chondrocytes was observed under electron microscopy. The primarily cultured chondrocytes of OA mice were randomly divided into 4 groups:(1) OA group, (2) Dgn group, (3) Dgn+AG490 group, (4) AG490 group...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087888/simulated-microgravity-decreases-circulating-iron-in-rats-role-of-inflammation-induced-hepcidin-upregulation
#15
Thibault Cavey, Nicolas Pierre, Kévin Nay, Coralie Allain, Martine Ropert, Olivier Loréal, Frédéric Derbré
During spaceflight, humans exposed to microgravity exhibit an increase of iron storage and a reduction of circulating iron. Such perturbations could promote oxidative stress and anemia in astronauts. The mechanism by which microgravity modulates iron metabolism is still unknown. Herein, we hypothesized that microgravity up-regulates hepcidin, a hormone produced by the liver that is the main controller of iron homeostasis. To test this hypothesis, rats were submitted to hindlimb unloading (HU), the reference model to mimic the effects of microgravity in rodents...
January 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28087861/jolkinolide-a-and-jolkinolide-b-inhibit-proliferation-of-a549-cells-and-activity-of-human-umbilical-vein-endothelial-cells
#16
Lei Shen, Shan-Qiang Zhang, Lei Liu, Yu Sun, Yu-Xuan Wu, Li-Ping Xie, Ji-Cheng Liu
BACKGROUND Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. MATERIAL AND METHODS We used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers...
January 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28087671/induction-and-differentiation-of-il-10-producing-regulatory-b-cells-from-healthy-blood-donors-and-rheumatoid-arthritis-patients
#17
Zsuzsanna Bankó, Judit Pozsgay, Dániel Szili, Mária Tóth, Tamás Gáti, György Nagy, Bernadette Rojkovich, Gabriella Sármay
The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087469/tofacitinib-ameliorates-inflammation-in-a-rat-model-of-airway-neutrophilia-induced-by-inhaled-lps
#18
Elena Calama, Isabel Ramis, Anna Domènech, Cristina Carreño, Jorge De Alba, Neus Prats, Montserrat Miralpeix
BACKGROUND: and purpose: The Janus Kinase (JAK) family mediates the cytokine receptor-induced signalling pathways involved in inflammatory processes. The activation of the signal transducers and activators of transcription (STATs) by JAK kinases is a key point in these pathways. Four JAK proteins, JAK1, JAK2, JAK3 and tyrosine kinase 2 (Tyk2) associate with the intracellular domains of surface cytokine receptors are phosphorylating STATs and modulating gene expression. The aim of this study was to explore the role of JAK inhibition in an acute model of inhaled lipopolysaccharide (LPS)-induced airway inflammation in rats through evaluating the effects of tofacitinib, a marketed pan-JAK inhibitor...
January 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28081250/cutaneous-deficiency-of-filaggrin-and-stat3-exacerbates-vaccinia-disease-in-vivo
#19
Yong He, Ishrat Sultana, Kazuyo Takeda, Jennifer L Reed
RATIONALE: Defects in filaggrin and STAT3 are associated with atopic dermatitis (AD) and susceptibility to severe skin infection. METHODS: We evaluated skin infection with the current smallpox vaccine, ACAM-2000, in immunosuppressed mice with combined cutaneous deficiency in filaggrin and STAT3. In parallel, early events post-infection with ACAM-2000 were investigated in cultured keratinocytes in which filaggrin expression was knocked down via siRNA. RESULTS: Immunosuppressed, filaggrin-deficient mice, treated with the topical STAT3 inhibitor Stattic® prior to ACAM-2000 infection, demonstrated rapid weight loss, prolonged vaccinia burden in skin, and dermatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28079159/socs1-favors-the-epithelial-mesenchymal-transition-in-melanoma-promotes-tumor-progression-and-prevents-antitumor-immunity-by-pd-l1-expression
#20
R Berzaghi, V S C Maia, F V Pereira, F M Melo, M S Guedes, C S T Origassa, J B Scutti, A L Matsuo, N O S Câmara, E G Rodrigues, L R Travassos
Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development...
January 12, 2017: Scientific Reports
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