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https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#1
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#2
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T helper (Th1) cells and CD8(+) T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity towards CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108509/differential-pi3k%C3%AE-signaling-in-cd4-t-cell-subsets-enables-selective-targeting-of-t-regulatory-cells-to-enhance-cancer-immunotherapy
#3
Samir N Khleif, Shamim Ahmad, Rasha Abu Eid, Rajeev K Shrimali, Mason Webb, Vivek Verma, Atbin Doroodchi, Zuzana Berrong, Raed N Samara, Paulo C Rodriguez, Mikayel Mkrtichyan
To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108314/mirna-638-promotes-autophagy-and-malignant-phenotypes-of-cancer-cells-via-directly-suppressing-dact3
#4
Yanli Ren, Yujie Chen, Xue Liang, Yan Lu, Wenting Pan, Ming Yang
Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promote cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues...
January 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28108260/triple-negative-metastatic-breast-cancer-is-dependent-on-sphks-s1p-signaling-for-growth-and-survival
#5
Aparna Maiti, Kazuaki Takabe, Nitai C Hait
About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#6
Xiaohe Shen, Jizhao Yuan, Mengjie Zhang, Wenhua Li, Bing Ni, Yuzhang Wu, Li Jiang, Weiping Fan, Zhiqiang Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28106049/food-grade-tio2-impairs-intestinal-and-systemic-immune-homeostasis-initiates-preneoplastic-lesions-and-promotes-aberrant-crypt-development-in-the-rat-colon
#7
Sarah Bettini, Elisa Boutet-Robinet, Christel Cartier, Christine Coméra, Eric Gaultier, Jacques Dupuy, Nathalie Naud, Sylviane Taché, Patrick Grysan, Solenn Reguer, Nathalie Thieriet, Matthieu Réfrégiers, Dominique Thiaudière, Jean-Pierre Cravedi, Marie Carrière, Jean-Nicolas Audinot, Fabrice H Pierre, Laurence Guzylack-Piriou, Eric Houdeau
Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105958/dmirnet-inferring-direct-microrna-mrna-association-networks
#8
Minsu Lee, HyungJune Lee
BACKGROUND: MicroRNAs (miRNAs) play important regulatory roles in the wide range of biological processes by inducing target mRNA degradation or translational repression. Based on the correlation between expression profiles of a miRNA and its target mRNA, various computational methods have previously been proposed to identify miRNA-mRNA association networks by incorporating the matched miRNA and mRNA expression profiles. However, there remain three major issues to be resolved in the conventional computation approaches for inferring miRNA-mRNA association networks from expression profiles...
December 5, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28105931/regulatory-single-nucleotide-polymorphisms-rsnps-at-the-promoters-1a-and-1b-of-the-human-apc-gene
#9
Marina Yu Matveeva, Elena V Kashina, Vasily V Reshetnikov, Leonid O Bryzgalov, Elena V Antontseva, Natalia P Bondar, Tatiana I Merkulova
BACKGROUND: Germline mutations in the coding sequence of the tumour suppressor APC gene give rise to familial adenomatous polyposis (which leads to colorectal cancer) and are associated with many other oncopathologies. The loss of APC function because of deletion of putative promoter 1A or 1B also results in the development of colorectal cancer. Since the regions of promoters 1A and 1B contain many single nucleotide polymorphisms (SNPs), the aim of this study was to perform functional analysis of some of these SNPs by means of an electrophoretic mobility shift assay (EMSA) and a luciferase reporter assay...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28105157/prognostic-impact-of-the-tumor-infiltrating-regulatory-t-cell-foxp3-activated-cytotoxic-t-lymphocyte-granzyme-b-ratio-on-resected-left-sided-pancreatic-cancer
#10
Ho Kyoung Hwang, Hyoung-Il Kim, Se Hoon Kim, Junjeong Choi, Chang Moo Kang, Kyung Sik Kim, Woo Jung Lee
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B(+)) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)(+)] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105147/fgfr3-silencing-by-sirna-inhibits-invasion-of-a549-cells
#11
Yuhua Li, Xiguang Liu, Hongjun Zhang, Tao Jiang, Wenjing Xiao, Shufen Zhao, Xiaoyun Yu, Fanjie Han
The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104684/broad-and-conserved-immune-regulation-by-genetically-heterogeneous-melanoma-cells
#12
Natalie J Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to cytotoxic T lymphocyte (CTL)-based immunotherapy. Here we studied the reactions of malignant and benign melanocyte lines to CTL using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations and similar in benign and malignant cells...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28104391/na-h-exchanger-mediated-hydrogen-ion-extrusion-as-a-carcinogenic-signal-in-triple-negative-breast-cancer-etiopathogenesis-and-prospects-for-its-inhibition-in-therapeutics
#13
REVIEW
Schammim Ray Amith, Larry Fliegel
Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype...
January 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28104022/-immune-checkpoint-inhibitor-therapy-in-advanced-head-and-neck-cancer
#14
W Hang, Z X Xu, Q Zhang, X Lu, G Liu
Immune checkpoint inhibitor therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, improves the life quality of cancer patients and has joined the ranks of surgery, radiation, and chemotherapy to become a major choice for cancer therapy. Over the past few years, multiple exciting results have been obtained on checkpoint inhibitor therapy in advanced head and neck cancer. However, questions such as patient selection and biomarkers for assessing the therapy are largely unsolved...
January 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28103502/tim3-gal9-interactions-between-t-cells-and-monocytes-result-in-an-immunosuppressive-feedback-loop-that-inhibits-th1-responses-in-osteosarcoma-patients
#15
Xiuzhong Li, Yanqing Chen, Xu Liu, Jin Zhang, Xu He, Guodong Teng, Dazhi Yu
The Tim3/Gal9 pathway is associated with immunosuppression and worse clinical outcome in multiple cancers. To illustrate the specific mechanism of Tim3/Gal9 interaction in osteosarcoma, we examined expression, function, and regulation of Tim3/Gal9 in various cells from osteosarcoma patients. Data showed that CD4(+) T cells, CD8(+) T cells, and monocytes from both peripheral blood and tumor of osteosarcoma patients contained high frequencies of Tim3(+) cells, while the Gal9 expression was primarily found in regulatory T cells (Tregs) from osteosarcoma patients and was elevated compared to that in non-cancer controls...
January 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28103241/contextual-refinement-of-regulatory-targets-reveals-effects-on-breast-cancer-prognosis-of-the-regulome
#16
Erik Andrews, Yue Wang, Tian Xia, Wenqing Cheng, Chao Cheng
Gene expression regulators, such as transcription factors (TFs) and microRNAs (miRNAs), have varying regulatory targets based on the tissue and physiological state (context) within which they are expressed. While the emergence of regulator-characterizing experiments has inferred the target genes of many regulators across many contexts, methods for transferring regulator target genes across contexts are lacking. Further, regulator target gene lists frequently are not curated or have permissive inclusion criteria, impairing their use...
January 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28102867/a-systems-approach-for-the-elucidation-of-crucial-genes-and-network-constituents-of-cervical-intraepithelial-neoplasia-1-cin1
#17
Shikha Suman, Ashutosh Mishra, Anurag Kulshrestha
Cervical intra-epithelial neoplasia 1 (CIN1) is a pre-cancerous cervical cancer condition characterized by changes in the squamous cells of the cervix. Early detection may facilitate treatment as CIN1 may increase the risk of developing cervical cancer. An extensive system level analysis has been carried out to detect crucial network components of CIN1. Differential expression analysis was performed to identify genes that are differentially expressed in CIN1 in comparison to normal cells. Gene Ontology (GO) and pathway enrichment analyses of DEGs were followed by the construction of a protein-protein interaction (PPI) network...
January 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28102845/h19-let-7-lin28-reciprocal-negative-regulatory-circuit-promotes-breast-cancer-stem-cell-maintenance
#18
Fei Peng, Ting-Ting Li, Kai-Li Wang, Guo-Qing Xiao, Ju-Hong Wang, Hai-Dong Zhao, Zhi-Jie Kang, Wen-Jun Fan, Li-Li Zhu, Mei Li, Bai Cui, Fei-Meng Zheng, Hong-Jiang Wang, Eric W-F Lam, Bo Wang, Jie Xu, Quentin Liu
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102353/cofilin-regulates-nuclear-architecture-through-a-myosin-ii-dependent-mechanotransduction-module
#19
O'Neil Wiggan, Bryce Schroder, Diego Krapf, James R Bamburg, Jennifer G DeLuca
Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#20
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
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