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https://www.readbyqxmd.com/read/27903674/atezolizumab-a-pd-l1-blocking-antibody-for-bladder-cancer
#1
Brant A Inman, Thomas A Longo, Sundhar Ramalingam, Michael R Harrison
Atezolizumab (Tecentriq™, MPDL3280A) is an FcγR-binding deficient, fully humanized, IgG1 monoclonal antibody designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironement and consequently increases T cell mediated immunity against the tumor. Atezolizumab has been FDA-approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase 2 trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27882694/fused-bicyclic-caspase-1-inhibitors-assembled-by-copper-free-strain-promoted-alkyne-azide-cycloaddition-spaac
#2
Linghui Qian, Chong-Jing Zhang, Ji'en Wu, Shao Q Yao
Challenges exist in the development of potent and selective small-molecule inhibitors against caspase-1. Herein, by making use of the copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) reaction between difluorinated cyclooctynes (DIFOs) and various azide-containing compounds, we showed for the first time that potential caspase-1 inhibitors could be rapidly synthesized. The resulting fused bicyclic compounds structurally resembled the central portion (P2 -P3 ) of Pralnacasan (a well-known small molecule caspase-1 inhibitor), with diversity at the P4 -position of the parental inhibitor conveniently installed from the azide component...
November 24, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27878564/the-role-of-b7-family-costimulatory-molecules-and-indoleamine-2-3-dioxygenase-in-primary-sj%C3%A3-gren-s-syndrome-and-systemic-sclerosis
#3
Nóra Legány, László Berta, László Kovács, Attila Balog, Gergely Toldi
B7 costimulatory molecules are present on antigen-presenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a molecule with important immunoregulatory functions. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2 molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28, CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults and 9 SSc and 15 pSS patients using flow cytometry...
November 23, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#4
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27821632/cytogenetic-and-molecular-characterization-of-b-genome-introgression-lines-of-brassica-napus-l
#5
Inderpreet Dhaliwal, Annaliese S Mason, Shashi Banga, Sakshi Bharti, Beerpal Kaur, Allison Mary Gurung, Phillip Anthony Salisbury, Jacqueline Batley, Surinder Singh Banga
Brassica napus introgression lines (ILs), having B-genome segments from B. carinata, were assessed genetically for extent of introgression and phenotypically for siliqua shatter resistance. Introgression lines had 7-9 % higher DNA content, were meiotically stable and had almost normal pollen fertility/seed set. Segment introgressions were confirmed by fl-GISH, SSR analyses and SNP studies. Genotyping with 48 B-genome specific SSRs detected substitutions from B3, B4, B6 and B7 chromosomes on 39 of the 69 introgression lines whereas SNP genotyping detected a total of 23 B-segments (≥ 3Mbp) from B4, B6, B7 introgressed into 10 of the 19 (C1, C2, C3, C5, C6, C8, C9, A3, A9, A10) chromosomes in 17 introgression lines...
November 7, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27820598/b7-h4-is-predictive-of-poor-prognosis-in-patients-with-gastric-cancer
#6
YongHui Cui, ZhiHan Li
BACKGROUND Recently, some studies were performed to evaluate the relevance of B7-H4 and gastric cancer (GC) prognosis. However, the results remained controversial. Therefore, we performed the present meta-analysis. MATERIAL AND METHODS We performed a systematic search in PubMed and Web of Science databases. All data were extracted and reviewed from each eligible study independently by 2 investigators. The strength of association between B7-H4 and GC prognosis was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI)...
November 7, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27816492/tremelimumab-in-combination-with-ablation-in-patients-with-advanced-hepatocellular-carcinoma
#7
Austin G Duffy, Susanna V Ulahannan, Oxana Makorova-Rusher, Osama Rahma, Heiner Wedemeyer, Drew Pratt, Jeremy L Davis, Marybeth S Hughes, Theo Heller, Mei ElGindi, Ashish Uppala, Firouzeh Korangy, David E Kleiner, William D Figg, David Venzon, Seth M Steinberg, Aradhana M Venkatesan, Venkatesh Krishnasamy, Nadine Abi-Jaoudeh, Elliot Levy, Brad J Wood, Tim F Greten
BACKGROUND: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 on the surface of activated T lymphocytes. Ablative therapies have been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced HCC. METHODS: Patients with HCC [Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1] were enrolled in a study of tremelimumab in combination with an ablative procedure performed during week 6...
November 2, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27801901/correlation-of-b7-h3-with-androgen-receptor-immune-pathways-and-poor-outcome-in-prostate-cancer-an-expression-based-analysis
#8
B Benzon, S G Zhao, M C Haffner, M Takhar, N Erho, K Yousefi, P Hurley, J L Bishop, J Tosoian, K Ghabili, M Alshalalfa, S Glavaris, B W Simons, P Tran, E Davicioni, R J Karnes, K Boudadi, E S Antonarakis, E M Schaeffer, C G Drake, F Feng, A E Ross
BACKGROUND: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer...
November 1, 2016: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/27798164/programmed-death-ligand-1-plays-a-neuroprotective-role-in-experimental-autoimmune-neuritis-by-controlling-peripheral-nervous-system-inflammation-of-rats
#9
Yanan Ding, Ranran Han, Wei Jiang, Jinting Xiao, Haijie Liu, Xiuju Chen, Xiaowen Li, Junwei Hao
Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27785073/epidermal-growth-factor-receptor-and-b7-h3-expression-in-esophageal-squamous-tissues-correlate-to-patient-prognosis
#10
Jianxiang Song, Woda Shi, Yajun Zhang, Mingzhong Sun, Xiaodong Liang, Shiying Zheng
Biomarkers that can serve as diagnostic and prognostic indicators of esophageal squamous cell carcinoma (ESCC) are urgently needed to help improve patient outcomes. Here, the expression of epidermal growth factor receptor (EGFR) and costimulatory molecule B7-H3, both of which have been implicated in tumor onset and progression in certain tumors, was investigated in relation to the clinical characteristics and survival outcomes of patients with ESCC. ESCC tissue samples were analyzed for 100 patients. Tumor and patient characteristics were recorded...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27783810/construction-of-a-fusion-plasmid-containing-the-psca-gene-and-cytotoxic-t-lymphocyte-associated-antigen-4-ctla-4-and-its-anti-tumor-effect-in-an-animal-model-of-prostate-cancer
#11
T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27777774/5-fluorouracil-upregulates-cell-surface-b7-h1-pd-l1-expression-in-gastrointestinal-cancers
#12
Lauren Van Der Kraak, Gaurav Goel, Krishnaveni Ramanan, Christof Kaltenmeier, Lin Zhang, Daniel P Normolle, Gordon J Freeman, Daolin Tang, Katie S Nason, Jon M Davison, James D Luketich, Rajeev Dhupar, Michael T Lotze
BACKGROUND: Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed in several human cancers. Interaction of B7-H1 with programmed death 1 (PD-1) prevents T-cell activation and proliferation, sequestering the T-cell receptor from the cell membrane, inducing T-cell apoptosis, thereby leading to cancer immunoresistance. B7-H1 upregulation contributes to chemoresistance in several types of cancer, but little is known with respect to changes associated with 5-fluorouracil (5-FU) or gastrointestinal cancers...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27733175/increased-urinary-cd80-excretion-and-podocyturia-in-fabry-disease
#13
H Trimarchi, R Canzonieri, A Schiel, C Costales-Collaguazo, J Politei, A Stern, M Paulero, T Rengel, J Andrews, M Forrester, M Lombi, V Pomeranz, R Iriarte, A Muryan, E Zotta, M D Sanchez-Niño, A Ortiz
BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia...
October 13, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27731324/unique-b7-h1-expression-on-masticatory-mucosae-in-the-oral-cavity-and-trans-coinhibition-by-b7-h1-expressing-keratinocytes-regulating-cd4-t-cell-mediated-mucosal-tissue-inflammation
#14
S Kang, C Zhang, T Ohno, M Azuma
The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated...
October 12, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27721121/withdrawn-tumor-b7-h3-cd276-expression-and-smoking-history-in-relation-to-lung-adenocarcinoma-prognosis
#15
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Rie Sakakibara, Hironori Ninomiya, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
The Publisher regrets that this article is an accidental duplication of an article that has already been published in The Journal of Lung Cancer - http://dx.doi.org/10.1016/j.lungcan.2016.11.013. Please see online announcement for additional details. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
October 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27689750/prolongation-of-kidney-allograft-survival-regulated-by-indoleamine-2-3-dioxygenase-in-immature-dendritic-cells-generated-from-recipient-type-bone-marrow-progenitors
#16
Ning Na, Yun Luo, Daqiang Zhao, Shicong Yang, Liangqing Hong, Heng Li, Bin Miao, Jiang Qiu
Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance...
September 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27687589/immune-adjuvant-effect-of-a-toxoplasma-gondii-profilin-like-protein-in-autologous-whole-tumor-cell-vaccination-in-mice
#17
Kyoung-Ho Pyo, You-Won Lee, Sun Min Lim, Eun-Hee Shin
Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs)...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27671636/b7-h1-shapes-t-cell-mediated-brain-endothelial-cell-dysfunction-and-regional-encephalitogenicity-in-spontaneous-cns-autoimmunity
#18
Luisa Klotz, Ivan Kuzmanov, Stephanie Hucke, Catharina C Gross, Vilmos Posevitz, Angela Dreykluft, Andreas Schulte-Mecklenbeck, Claudia Janoschka, Maren Lindner, Martin Herold, Nicholas Schwab, Isis Ludwig-Portugall, Christian Kurts, Sven G Meuth, Tanja Kuhlmann, Heinz Wiendl
Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the blood-brain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27662596/immunosuppressive-effect-of-asp2408-a-novel-cd86-selective-variant-of-ctla4-ig-in-rats-and-cynomolgus-monkeys
#19
Shinsuke Oshima, Yasutomo Fujii, Erik E Karrer, Fujiko Takamura, Steven J Chapin, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi, Hidekazu Mizuhara
The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods...
September 19, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27632942/unstable-b7-h4-cell-surface-expression-and-t-cell-redirection-as-a-means-of-cancer-therapy
#20
Akira Iizuka, Ryota Kondou, Chizu Nonomura, Tadashi Ashizawa, Keiichi Ohshima, Masatoshi Kusuhara, Mitsuhiro Isaka, Yasuhisa Ohde, Ken Yamaguchi, Yasuto Akiyama
Tumor immune regulation has been demonstrated in clinical studies using antibodies targeted to the B7/CD28 family. B7 homolog 4 (B7-H4) negatively regulates immune responses and is overexpressed in many types of human cancer, indicating that B7-H4 may be a potential target of cancer therapy. B7-H4 expression is affected by the microenvironment, and its presence has been reported in cancer tissues and immune cells. We found an upregulation of B7-H4 expression using comprehensive whole exome sequencing and gene expression profiling (project HOPE) launched by the Shizuoka Cancer Center based on tumor tissue samples from 1,058 cancer patients...
September 12, 2016: Oncology Reports
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