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https://www.readbyqxmd.com/read/28713995/bioinformatic-analysis-of-computational-identified-differentially-expressed-genes-in-tumor-stoma-of-pregnancy%C3%A2-associated-breast-cancer
#1
Qian Zhou, Erhu Sun, Lijun Ling, Xiaofeng Liu, Min Zhang, Hong Yin, Cheng Lu
The present study aimed to screen the differentially expressed genes (DEGs) in tumor‑associated stroma of pregnancy‑associated breast cancer (PABC). By analyzing Affymetrix microarray data (GSE31192) from the Gene Expression Omnibus database, DEGs between tumor asso-ciated stromal cells and normal stromal cells in PABC were identified. Gene Ontology (GO) function and pathway enrichment analyses for the DEGs were then performed, followed by construction of a protein‑protein interaction (PPI) network. A total of 94 upregulated and 386 downregulated DEGs were identified between tumor associated stromal cells and normal stromal cells in patients with PABC...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28667193/pd-l1-protein-expression-in-tumour-cells-and-immune-cells-in-mismatch-repair-protein-deficient-and-proficient-colorectal-cancer-the-foundation-study-using-the-sp142-antibody-and-whole-section-immunohistochemistry
#2
Tony El Jabbour, Jeffrey S Ross, Christine E Sheehan, Kajsa E Affolter, Katherine B Geiersbach, Ann Boguniewicz, Sanaz Ainechi, Mary P Bronner, David M Jones, Hwajeong Lee
AIMS: Routine application of PD-L1 immunohistochemistry (IHC) in colorectal cancer (CRC) is limited due to lack of standardized scoring criteria, antibody clones, and intratumoral staining heterogeneity. We assessed PD-L1 protein expression on full face CRC tissue sections and applied two algorithms based on the published clinical trials that support the recent FDA approval for immune checkpoint inhibitors (ICPI) therapy in non-small cell lung cancer (NSCLC). METHODS: PD-L1/CD274 IHC (Roche/Ventana, clone SP142) was performed on representative tumour blocks from 52 mismatch repair-deficient (MMR-D) and 52 MMR-proficient (MMR-P) CRCs...
June 30, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28652380/immune-escape-in-breast-cancer-during-in-situ-to-invasive-carcinoma-transition
#3
Carlos R Gil Del Alcazar, Sung Jin Huh, Muhammad B Ekram, Anne Trinh, Lin L Liu, Francisco Beca, Xiaoyuan Zi, Minsuk Kwak, Helga Bergholtz, Ying Su, Lina Ding, Hege G Russnes, Andrea L Richardson, Kirsten Babski, Elizabeth Min Hui Kim, Charles McDonnell, Jon Wagner, Ron Rowberry, Gordon J Freeman, Deborah Dillon, Therese Sorlie, Lisa M Coussens, Judy E Garber, Rong Fan, Kristie Bobolis, D Craig Allred, Joon Jeong, So Yeon Park, Franziska Michor, Kornelia Polyak
To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS recurrent IDC...
June 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#4
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#5
Unmesh Jadhav, Madhurima Saxena, Nicholas K O'Neill, Assieh Saadatpour, Guo-Cheng Yuan, Zachary Herbert, Kazutaka Murata, Ramesh A Shivdasani
Replicating Lgr5(+) stem cells and quiescent Bmi1(+) cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5(+) ISCs triggers epithelial renewal from Bmi1(+) cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP(+) cells from Bmi1(GFP) mice are preterminal enteroendocrine cells and we identify CD69(+)CD274(+) cells as related goblet cell precursors. Upon loss of native Lgr5(+) ISCs, both populations revert toward an Lgr5(+) cell identity...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28633489/effects-of-early-pregnancy-on-uterine-lymphocytes-and-endometrial-expression-of-immune-regulatory-molecules-in-dairy-heifers1
#6
Sreelakshmi Vasudevan, Manasi M Kamat, Sadhat S Walusimbi, Joy L Pate, Troy L Ott
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested...
June 19, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#7
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28581487/emmprin-cd147-is-induced-by-c-ebp%C3%AE-and-is-differentially-expressed-in-alk-and-alk-anaplastic-large-cell-lymphoma
#8
Janine Schmidt, Irina Bonzheim, Julia Steinhilber, Ivonne A Montes-Mojarro, Carlos Ortiz-Hidalgo, Wolfram Klapper, Falko Fend, Leticia Quintanilla-Martínez
Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro...
June 5, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28579282/a-radiosensitivity-gene-signature-and-pd-l1-status-predict-clinical-outcome-of-patients-with-invasive-breast-carcinoma-in-the-cancer-genome-atlas-tcga-dataset
#9
Bum-Sup Jang, In Ah Kim
BACKGROUND AND PURPOSE: We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. MATERIAL AND METHODS: We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset...
June 1, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28577136/genome-wide-gene-expression-profiling-reveals-that-cd274-is-up-regulated-new-onset-type-1-diabetes-mellitus
#10
Chen Fang, Yun Huang, Yufang Pei, Hong-Hong Zhang, Xiaohong Chen, Heming Guo, Sicheng Li, Xiaoyan Ji, Ji Hu
AIMS: Early studies have identified type 1 diabetes mellitus (T1DM) as a disease that is caused by the autoimmune destruction of the insulin-producing pancreatic β-cells. Genetics, environment and the immune pathogenesis of T1DM are three major pillars of T1DM research. We try to understand the changes in the gene expression profile during the pathogenesis of T1DM. METHODS: We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray studies of T1DM with samples taken at or before the T1DM onset...
June 2, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28564607/specification-and-diversification-of-pericytes-and-smooth-muscle-cells-from-mesenchymoangioblasts
#11
Akhilesh Kumar, Saritha Sandra D'Souza, Oleg V Moskvin, Huishi Toh, Bowen Wang, Jue Zhang, Scott Swanson, Lian-Wang Guo, James A Thomson, Igor I Slukvin
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ(+)CD271(+)CD73(-) mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#12
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#13
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#14
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28503213/epigenetic-modifications-of-the-immune-checkpoint-genes-ctla4-and-pdcd1-in-non-small-cell-lung-cancer-results-in-increased-expression
#15
Sebastian Marwitz, Swetlana Scheufele, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics to predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order to overcome these limitations, we analyzed epigenetic modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39 patients. Results were correlated with transcriptome data...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28491094/immunoprofiling-of-adult-derived-human-liver-stem-progenitor-cells-impact-of-hepatogenic-differentiation-and-inflammation
#16
Hoda El-Kehdy, Camillo Sargiacomo, Mohammad Fayyad-Kazan, Hussein Fayyad-Kazan, Catherine Lombard, Laurence Lagneaux, Etienne Sokal, Mehdi Najar, Mustapha Najimi
Adult-derived human liver stem/progenitor cells (ADHLSCs) are, nowadays, developed as therapeutic medicinal product for the treatment of liver defects. In this study, the impact of hepatogenic differentiation and inflammation priming on the ADHLSCs' immune profile was assessed in vitro and compared to that of mature hepatocytes. The constitutive immunological profile of ADHLSCs was greatly different from that of hepatocytes. Differences in the expression of the stromal markers CD90 and CD105, adhesion molecules CD44 and CD49e, immunoregulatory molecules CD73 and HO-1, and NK ligands CD112 and CD155 were noted...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28433800/chromosomal-alterations-and-gene-expression-changes-associated-with-the-progression-of-leukoplakia-to-advanced-gingivobuccal-cancer
#17
Priyanka G Bhosale, Simona Cristea, Srikant Ambatipudi, Rajiv S Desai, Rajiv Kumar, Asawari Patil, Shubhada Kane, Anita M Borges, Alejandro A Schäffer, Niko Beerenwinkel, Manoj B Mahimkar
We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28423491/the-mir-25-93-106b-cluster-regulates-tumor-metastasis-and-immune-evasion-via-modulation-of-cxcl12-and-pd-l1
#18
Michele Cioffi, Sara M Trabulo, Mireia Vallespinos, Deepak Raj, Tony Bou Kheir, Meng-Lay Lin, Julfa Begum, Ann-Marie Baker, Ala Amgheib, Jaimy Saif, Manuel Perez, Joaquim Soriano, Manuel Desco, Maria Victoria Gomez-Gaviro, Lorena Cusso, Diego Megias, Alexandra Aicher, Christopher Heeschen
The stromal microenvironment controls response to injury and inflammation, and is also an important determinant of cancer cell behavior. However, our understanding of its modulation by miRNA (miR) and their respective targets is still sparse. Here, we identified the miR-25-93-106b cluster and two new target genes as critical drivers for metastasis and immune evasion of cancer cells. Using miR-25-93-106b knockout mice or antagomiRs, we demonstrated regulation of the production of the chemoattractant CXCL12 controlling bone marrow metastasis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409437/prognostic-significance-of-pd-l1-expression-on-tumor-cells-and-tumor-infiltrating-mononuclear-cells-in-upper-tract-urothelial-carcinoma
#19
Bo Zhang, Wei Yu, Xueru Feng, Zheng Zhao, Yu Fan, Yisen Meng, Shuai Hu, Yun Cui, Qun He, Hong Zhang, Dong Li, Zhisong He, Liqun Zhou, Jie Jin, Wenke Han
Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28406723/aspirin-use-and-colorectal-cancer-survival-according-to-tumor-cd274-programmed-cell-death-1-ligand-1-expression-status
#20
Tsuyoshi Hamada, Yin Cao, Zhi Rong Qian, Yohei Masugi, Jonathan A Nowak, Juhong Yang, Mingyang Song, Kosuke Mima, Keisuke Kosumi, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, NaNa Keum, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Edward L Giovannucci, Marios Giannakis, Scott J Rodig, Gordon J Freeman, Daniel Nevo, Molin Wang, Andrew T Chan, Charles S Fuchs, Reiko Nishihara, Shuji Ogino
Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway...
June 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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