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https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#1
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1)-which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma (Rb), adenomatous polyposis coli (APC), p53, p73, p21, p27, FOXO, STAT3, IKB, topoisomerase II and PAR-4-is the principal focus of SINE drug development...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28647611/autophagy-suppresses-isoprenaline-induced-m2-macrophage-polarization-via-the-ros-erk-and-mtor-signaling-pathway
#2
Meihua Shan, Junfang Qin, Fengjiao Jin, Xiao Han, Haitao Guan, Xiaoge Li, Jiahui Zhang, Hongyao Zhang, Yue Wang
The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1...
June 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#3
REVIEW
Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families...
June 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28647191/pyrrolidine-dithiocarbamate-alleviates-the-anti-tuberculosis-drug-induced-liver-injury-through-jak2-stat3-signaling-pathway-an-experimental-study
#4
Hong Zhang, Yang Liu, Li-Kun Wang, Na Wei
OBJECTIVE: To study the effect of pyrrolidine dithiocarbamate (PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. METHODS: Clean male SD rats were selected as experimental animals and randomly divided into normal group, model group, PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC, and AG490 group received intraperitoneal injection of AG490...
May 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28646856/the-imbalance-of-th17-treg-cells-is-involved-in-the-progression-of-nonalcoholic-fatty-liver-disease-in-mice
#5
Beihui He, Liyan Wu, Wei Xie, Yitong Shao, Jianping Jiang, Zhenzhong Zhao, Maoxiang Yan, Zhiyun Chen, Dawei Cui
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC)...
June 24, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#6
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#7
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646470/apobec3b-and-il-6-form-a-positive-feedback-loop-in-hepatocellular-carcinoma-cells
#8
Shuran Li, Xueyang Bao, Duowei Wang, Linjun You, Xianjing Li, Hongbao Yang, Jinsong Bian, Yun Wang, Yong Yang
APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3B and IL-6, and thereby promoted the prolonged non-resolving inflammation...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28646122/nintedanib-a-triple-tyrosine-kinase-inhibitor-attenuates-renal-fibrosis-in-chronic-kidney-disease
#9
Feng Liu, Li Wang, Hualin Qi, Jun Wang, Wei Jiang, Yi Wang, Liuqing Xu, Na Liu, Shougang Zhuang
<span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">Nintedanib (BIBF1120) is a triple kinase inhibitor</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> of </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">vascular endothelial growth factor receptor (VEGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> and Src family kinase, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">that has recently been approved by FDA to treat idiopathic pulmonary fibrosis...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#10
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28644966/an-immunosuppressive-function-of-interleukin-35-in-chronic-hepatitis-c-virus-infection
#11
Siqi Liu, Qian Zhang, Xue Shao, Wenrui Wang, Chuanhui Zhang, Zhenjing Jin
Interleukin (IL)-35, a newly identified member of the IL-12 cytokine family, has been reported to suppress inflammation and induce immunotolerance. However, little is known regarding the role of IL-35 during chronic hepatitis C virus (HCV) infection. Herein, we measured the serum IL-35 concentration of 73 patients with hepatitis C and 22 healthy individuals, as well as further investigated the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) and on hepatocytes infected with HCV in cell culture (HCVcc)...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28644441/micrornas-143-and-145-induce-epithelial-to-mesenchymal-transition-and-modulate-the-expression-of-junction-proteins
#12
Lidia Avalle, Danny Incarnato, Aurora Savino, Marta Gai, Francesca Marino, Sara Pensa, Isaia Barbieri, Michael B Stadler, Paolo Provero, Salvatore Oliviero, Valeria Poli
Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma's metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644106/viability-and-osteogenic-differentiation-of-human-periodontal-ligament-progenitor-cells-are-maintained-after-incubation-with-porphyromonas-gingivalis-protein-extract
#13
Mayra Laino Albiero, Rafael Nóbrega Stipp, Miki Taketomi Saito, Márcio Zaffalon Casati, Enilson Antonio Sallum, Francisco Humberto Nociti, Karina Gonzales Silvério
BACKGROUND: Porphyromonas gingivalis (Pg) is a major periodontal pathogen that contains immunostimulatory components. Periodontal ligament mesenchymal stem cells (PDLSCs) are responsible for regeneration of the periodontium that is lost due to periodontitis. Pathologic factors within the microenvironment that impair resident PDLSCs are not well understood. The present study investigated in vitro the effects of Pg protein extract (PgPE) on the biological properties of CD105-enriched PDL progenitor cell populations (PDL-CD105(+) cells)...
June 23, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28643230/crosstalk-between-m2-macrophages-and-glioma-stem-cells
#14
Leora M Nusblat, Molly J Carroll, Charles M Roth
PURPOSE: Given its extremely poor prognosis, there is a pressing need for an improved understanding of the biology of glioblastoma multiforme (GBM), including the roles of tumor subpopulations that may contribute to their growth rate and therapy resistance. The most malignant phenotypes of GBM have been ascribed to the presence of subpopulations of cancer stem cells (CSCs), which are resistant to chemotherapeutic drugs and ionizing radiation and which promote invasiveness and metastasis...
June 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28642874/combination-treatment-with-ppar%C3%AE-ligand-and-its-specific-inhibitor-gw9662-downregulates-bis-and-14-3-3-gamma-inhibiting-stem-like-properties-in-glioblastoma-cells
#15
Chang-Nim Im
PPARγ is a nuclear receptor that regulates differentiation and proliferation and is highly expressed in many cancer cells. Its synthetic ligands, such as rosiglitazone and ciglitazone, and its inhibitor GW9662, were shown to induce cellular differentiation, inhibit proliferation, and lead to apoptosis. Glioblastoma is a common brain tumor with poor survival prospects. Recently, glioblastoma stem cells (GSCs) have been examined as a potential target for anticancer therapy; however, little is known about the combined effect of various agents on GSCs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642362/regulation-of-rhoa-by-stat3-coordinates-glial-scar-formation
#16
Francois Renault-Mihara, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Kaori Yasutake, Seiji Okada, Masaya Nakamura, Hideyuki Okano
Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28642132/unphosphorylated-stat3-regulates-the-antiproliferative-antiviral-and-gene-inducing-actions-of-type-i-interferons
#17
Susan R Pfeffer, Meiyun Fan, Ziyun Du, Chuan He Yang, Lawrence M Pfeffer
Type I interferon (IFNα/β) induces antiviral and antiproliferative responses in cells through the induction of IFN-stimulated genes (ISGs). Although the roles of IFN-activated STAT1 and STAT2 in the IFN response are well described, the function of STAT3 is poorly characterized. We investigated the role of STAT3 in the biological response to IFNα/β in mouse embryonic fibroblasts (MEFs) with a germ line deletion of STAT3. These STAT3 knockout (STAT3-KO) MEFs were reconstituted with STAT3 or the F705-STAT3 mutant (unphosphorylated STAT3) where the canonical Y705 tyrosine phosphorylation site was mutated...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28641075/postconditioning-with-intralipid-emulsion-protects-against-reperfusion-injury-in-postinfarct-remodeled-rat-hearts-by-activation-of-ros-akt-erk-signaling
#18
Michael Zaugg, Phing-How Lou, Eliana Lucchinetti, Manoj Gandhi, Alexander S Clanachan
The clinically used lipid emulsion Intralipid (ILE) reduces ischemia reperfusion injury in healthy rodent hearts. We tested whether ILE is cardioprotective in postinfarct remodeled hearts. Postinfarct remodeled and sham Sprague-Dawley rat hearts were perfused in working mode and subjected to ischemia (15 minutes) and reperfusion (30 minutes). Left ventricular (LV) work was measured in hearts that were untreated or that received ILE (1%) postconditioning administered at the onset of reperfusion, or the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine (10 μM) alone or in combination with ILE...
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28640256/microrna-26a-cyclin-dependent-kinase-5-axis-controls-proliferation-apoptosis-and-in-vivo-tumor-growth-of-diffuse-large-b-cell-lymphoma-cell-lines
#19
Floriana Maria Farina, Alessandra Inguscio, Paolo Kunderfranco, Alice Cortesi, Leonardo Elia, Manuela Quintavalle
Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable therapeutic response to first-line chemo-immunotherapy, still 30-40% of patients is refractory, or relapse after this treatment. Thus, alternative strategies must be sought. Previous studies have indicated that cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is involved in tumor development and progression, and it may represent a potential therapeutic target. However, its role in modulating DLBCL growth and progression remains largely unexplored...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639178/effective-skin-cancer-treatment-by-topical-co-delivery-of-curcumin-and-stat3-sirna-using-cationic-liposomes
#20
Anup Jose, Suman Labala, Kunal Manoj Ninave, Sudeep Kumar Gade, Venkata Vamsi Krishna Venuganti
The aim of the present study was to evaluate the effectiveness of iontophoretic co-delivery of curcumin and anti-STAT3 siRNA using cationic liposomes against skin cancer. Curcumin was encapsulated in DOTAP-based cationic liposomes and then complexed with STAT3 siRNA. This nanocomplex was characterized for the average particle size, zeta-potential, and encapsulation efficiency. The cell viability studies in B16F10 mouse melanoma cells have shown that the co-delivery of curcumin and STAT3 siRNA significantly (p < 0...
June 21, 2017: AAPS PharmSciTech
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