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https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#1
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28685773/inhibition-of-the-b7-h3-immune-checkpoint-limits-tumor-growth-by-enhancing-cytotoxic-lymphocyte-function
#2
Young-Hee Lee, Natalia Martin-Orozco, Peilin Zheng, Jing Li, Peng Zhang, Haidong Tan, Hyun Jung Park, Mira Jeong, Seon Hee Chang, Byung-Seok Kim, Wei Xiong, Wenjuan Zang, Li Guo, Yang Liu, Zhong-Jun Dong, Willem W Overwijk, Patrick Hwu, Qing Yi, Larry Kwak, Zhiying Yang, Tak W Mak, Wei Li, Laszlo G Radvanyi, Ling Ni, Dongfang Liu, Chen Dong
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity...
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28679835/new-b7-family-checkpoints-in-human-cancers
#3
REVIEW
Ling Ni, Chen Dong
T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and CTL antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently, five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7, were identified...
July 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28676400/inhibition-of-b7-h3-reverses-oxaliplatin-resistance-in-human-colorectal-cancer-cells
#4
Pengfei Zhang, Zhen Chen, Kuan Ning, Jian Jin, Xiaofeng Han
B7-H3, an immunoregulatory protein, has been found highly expressed in several cancer types, and involved in cancer cell migration and invasion. Here, we investigated the role of B7-H3 in oxaliplatin resistance in colorectal cancer (CRC) cells. Transient silencing of B7-H3 enhanced oxaliplatin sensitivity by increasing oxaliplatin-induced DNA damage. The overexpression of B7-H3 increased oxaliplatin resistance reducing the formation of phosphorylated histone H2AX (γH2AX) loci. The silencing of X-ray repair cross complementing group 1 (XRCC1), upregulated in B7-H3 overexpressing cells, induced an increase in cell death following oxaliplatin treatment...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28627681/b7-h3-promotes-the-proliferation-migration-and-invasiveness-of-cervical-cancer-cells-and-is-an-indicator-of-poor-prognosis
#5
Yi Li, Jingjing Zhang, Sai Han, Qiuhong Qian, Qian Chen, Lu Liu, Youzhong Zhang
B7-H3 is an immune regulatory molecule whose aberrant expression in tumors is associated with adverse outcomes. Upregulation of B7-H3 may promote tumor cell proliferation and metastasis in vitro, but the role of B7-H3 in cervical cancer has not yet been investigated. We measured B7-H3 expression in 90 cervical cancer patient and 20 non‑cervical lesion patient tissues using immunohistochemistry and in 30 cervical cancer patient and 30 healthy donor blood samples using ELISA. The association of B7-H3 expression and the prognosis of cervical cancer patients was investigated...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28562360/b7-h3-promotes-gastric-cancer-cell-migration-and-invasion
#6
Yecheng Li, Xiaodong Yang, Yong Wu, Kui Zhao, Zhenyu Ye, Junjia Zhu, Xiaohui Xu, Xin Zhao, Chungen Xing
B7-H3 (B7 homologue 3, CD276) is a member of the B7 immunoregulatory family and promotes tumor progression. The present study demonstrated that B7-H3 promotes gastric cancer cell migration and invasion. shRNA-mediated B7-H3 silencing in the N87 gastric cancer cell line suppressed cell migration and invasion in vitro and in vivo; downregulated metastasis-associated CXCR4; and inhibited AKT, ERK, and Jak2/Stat3 phosphorylation. B7-H3-silenced cells injected into the tail veins of 4-week-old female BALB/c nude mice produced fewer metastases than control cells, and resulted in longer survival times...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539467/b7-h3-expression-in-nsclc-and-its-association-with-b7-h4-pd-l1-and-tumor-infiltrating-lymphocytes
#7
Mehmet Altan, Vasiliki Pelekanou, Kurt A Schalper, Maria I Toki, Patricia Gaule, Konstantinos N Syrigos, Roy S Herbst, David L Rimm
Background and Purpose: <p>The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members.  Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor infiltrating lymphocytes (TILs), PD-L1, B7-H4 and major clinico-pathological characteristics is in 3 NSCLC cohorts.</p> <p>Experimental design:</p> <p>We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4 and TILs in 634 NSCLC cases with validated antibodies...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#8
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/28529630/spectroscopic-photoacoustic-molecular-imaging-of-breast-cancer-using-a-b7-h3-targeted-icg-contrast-agent
#9
Katheryne E Wilson, Sunitha V Bachawal, Lotfi Abou-Elkacem, Kristen Jensen, Steven Machtaler, Lu Tian, Jürgen K Willmann
Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target...
2017: Theranostics
https://www.readbyqxmd.com/read/28513992/immunoregulatory-protein-b7-h3-promotes-growth-and-decreases-sensitivity-to-therapy-in-metastatic-melanoma-cells
#10
Karine Flem-Karlsen, Christina Tekle, Yvonne Andersson, Kjersti Flatmark, Øystein Fodstad, Caroline E Nunes-Xavier
B7-H3 (CD276) belongs to the B7-family of immunoregulatory proteins, and has been implicated in cancer progression and metastasis. In this study, we found that metastatic melanoma cells with knockdown expression of B7-H3 showed modest decrease in proliferation and glycolytic capacity, and were more sensitive to dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP kinase (MAPK)- and AKT/mTOR-pathways: vemurafenib (PLX4032; BRAF inhibitor), binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor) and triciribidine (API-2; AKT inhibitor)...
May 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28495553/the-expanding-repertoire-of-targets-for-immune-checkpoint-inhibition-in-bladder-cancer-what-lies-beneath-the-tip-of-the-iceberg-pd-l1
#11
REVIEW
Alexander Sankin, Deepa Narasimhulu, Peter John, Benjamin Gartrell, Mark Schoenberg, Xingxing Zang
Over the last decade, a new understanding of tumor-immune system interplay has been ushered in, lead in large part by the discovery of immune checkpoints mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1 immune checkpoint pathway has already shown great success as a cancer immunotherapy for advanced urothelial carcinoma, leading to durable clinical remissions in an otherwise incurable disease. There are newly described members of the B7-CD28 family including B7-H3, B7x, and HHLA2...
May 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28416840/-b7-h3-silencing-inhibits-human-hematological-malignancy-xenograft-tumor-tumorigenesis-and-metastasis-in-nude-mice
#12
X X Yan, W Zhang, J Wang, X Y Ke
OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene silencing on the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR (qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13 strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in U937, Maver and Z138 was performed by lentivirus transduction and the effect of B7-H3 silencing in stable cell lines was tested by qPCR and FCM...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28401653/selective-blockade-of-b7-h3-enhances-antitumour-immune-activity-by-reducing-immature-myeloid-cells-in-head-and-neck-squamous-cell-carcinoma
#13
Liang Mao, Teng-Fei Fan, Lei Wu, Guang-Tao Yu, Wei-Wei Deng, Lei Chen, Lin-Lin Bu, Si-Rui Ma, Bing Liu, Yansong Bian, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa...
April 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28399408/eradication-of-tumors-through-simultaneous-ablation-of-cd276-b7-h3-positive-tumor-cells-and-tumor-vasculature
#14
Steven Seaman, Zhongyu Zhu, Saurabh Saha, Xiaoyan M Zhang, Mi Young Yang, Mary Beth Hilton, Karen Morris, Christopher Szot, Holly Morris, Deborah A Swing, Lino Tessarollo, Sean W Smith, Sylvia Degrado, Dmitry Borkin, Nareshkumar Jain, Julia Scheiermann, Yang Feng, Yanping Wang, Jinyu Li, Dean Welsch, Gary DeCrescenzo, Amit Chaudhary, Enrique Zudaire, Kimberly D Klarmann, Jonathan R Keller, Dimiter S Dimitrov, Brad St Croix
Targeting the tumor vasculature with antibody-drug conjugates (ADCs) is a promising anti-cancer strategy that in order to be realized must overcome several obstacles, including identification of suitable targets and optimal warheads. Here, we demonstrate that the cell-surface protein CD276/B7-H3 is broadly overexpressed by multiple tumor types on both cancer cells and tumor-infiltrating blood vessels, making it a potentially ideal dual-compartment therapeutic target. In preclinical studies CD276 ADCs armed with a conventional MMAE warhead destroyed CD276-positive cancer cells, but were ineffective against tumor vasculature...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28386362/b7-h3-regulates-migration-and-invasion-in-salivary-gland-adenoid-cystic-carcinoma-via-the-jak2-stat3-signaling-pathway
#15
Teng-Fei Fan, Wei-Wei Deng, Lin-Lin Bu, Tian-Fu Wu, Wen-Feng Zhang, Zhi-Jun Sun
B7 Homolog 3 (B7-H3), a newly identified member of the B7 family, is over-expressed in various human cancers and plays a vital role in tumor progression. To identify the expression pattern of B7-H3 in human salivary adenoid cystic carcinoma (AdCC) and its underlying mechanisms, we characterized B7-H3 expression in AdCC tissue microarrays using immunohistochemical staining, and analyzed potentially associated molecules. The results showed that B7-H3 was highly expressed in salivary AdCC, compared with normal salivary glands...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28382144/b7-h3-promotes-the-migration-and-invasion-of-human-bladder-cancer-cells-via-the-pi3k-akt-stat3-signaling-pathway
#16
Yuchao Li, Guoning Guo, Jie Song, Zhiping Cai, Jin Yang, Zhiwen Chen, Yun Wang, Yaqin Huang, Qiangguo Gao
Bladder cancer is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human bladder cancer tissues, the exact role and molecular mechanism of B7-H3 in bladder cancer remain unknown. In this study, we first detected the expression of B7-H3 in human bladder cancer samples and cell lines, and analyzed its correlations with clinicopathological pathological parameters. Next, siRNAs or overexpression plasmids of B7-H3 were transfected into T24 or 5637 cells, and cell proliferation, apoptosis, migration and invasion were analyzed via CCK-8, colony formation, flow cytometry and transwell assays, protein expression levels were determined by western blotting...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28376772/different-expression-of-b7-h3-in-the-caput-corpus-and-cauda-of-the-epididymis-in-mouse
#17
Kai Li, Xuedong Wei, Guangbo Zhang, Miao Li, Xuefeng Zhang, Chenhao Zhou, Jianquan Hou, Hexing Yuan
BACKGROUND: B7-H3, a member of the B7 family of the Ig superfamily of proteins, has been detected in the epididymis, which is a storage organ related to sperm maturation. However, the characteristics of its expression in different regions of the epididymis remain unknown. Our aim was to investigate the expression of B7-H3 in the caput, corpus, and cauda of the epididymis. METHODS: We extracted epididymis specimens from adult male C57BL/6 mice. The expression of B7-H3 was then measured with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and western blotting...
April 4, 2017: BMC Urology
https://www.readbyqxmd.com/read/28373465/evaluation-of-prognostic-immune-signatures-in-patients-with-breast-colorectal-and-pancreatic-cancer-receiving-chemotherapy
#18
Ursula M Vogl, Leopold Öhler, Masa Rasic, Josa M Frischer, Madhura Modak, Johannes Stöckl
BACKGROUND: CD97 is a member of the epidermal growth factor-seven transmembrane (EGF-TM7) receptor family and is dominantly expressed on immune cells and in a variety of malignant diseases. B7-H1 and B7-H3 are transmembrane proteins that are involved in suppression of the immune system. The aim of this study was to evaluate if these molecules are up-regulated in patients with cancer and change during chemotherapy. MATERIALS AND METHODS: We analyzed cluster of differentiation (CD) protein expression levels on tumor cell lines and in blood samples of 37 patients with solid tumors at baseline and during chemotherapy; we correlated the serum levels of CD proteins with survival outcome...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28293664/the-expression-of-b7-h3-molecule-in-periodontal-disease
#19
Saumya John, Arun Kurumathur, Avaneendra Talwar, Keerthana Kumar, Teenu Abraham, Ananthi Alagiri, Gnanasagar Walaja, Jasmine Clements
STATEMENT OF THE PROBLEM: T cells have been shown to play a role in the etiopathogenesis of periodontal disease. B7-H3, a costimulatory molecule, is found to be associated with regulation of T cell function in some tumoral tissues, as well as autoimmune and inflammatory diseases. PURPOSE: The aim of this study was to investigate the expression of B7-H3 molecule in healthy and diseased gingival tissue samples. MATERIALS AND METHOD: Gingival samples were taken from 2 groups (A and B) representing periodontal health and periodontal disease, respectively...
March 2017: Journal of Dentistry
https://www.readbyqxmd.com/read/28271685/the-expression-of-b7-h3-in-circulating-cd4-cd25high-t-cells-circulating-cd14-monocytes-and-plasma-during-hepatitis-b-virus-infection-progression
#20
Jun-Chi Xu, Ming Li, Yuan Ma, Cui-Lin Shi, Xiao-Yan Zhu, Hua-Feng Song, Hui Chen, Chuan-Wu Zhu, Ping Xu
BACKGROUND: B7-H3 is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, the role of B7-H3 which express in CD14+ monocytes and CD4+CD25high T cells had not been investigated. METHODS: Cytometry and ELISA were used in this study. RESULTS: The study showed that B7-H3 expression in CD14+ monocytes, CD4+CD25high T cells, and plasma was significantly increased in AHB, CHB, HBV-LC, and HBV-HCC group...
March 1, 2017: Clinical Laboratory
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