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https://www.readbyqxmd.com/read/28484017/structural-basis-for-cancer-immunotherapy-by-the-first-in-class-checkpoint-inhibitor-ipilimumab
#1
Udupi A Ramagopal, Weifeng Liu, Sarah C Garrett-Thomson, Jeffrey B Bonanno, Qingrong Yan, Mohan Srinivasan, Susan C Wong, Alasdair Bell, Shilpa Mankikar, Vangipuram S Rangan, Shrikant Deshpande, Alan J Korman, Steven C Almo
Rational modulation of the immune response with biologics represents one of the most promising and active areas for the realization of new therapeutic strategies. In particular, the use of function blocking monoclonal antibodies targeting checkpoint inhibitors such as CTLA-4 and PD-1 have proven to be highly effective for the systemic activation of the human immune system to treat a wide range of cancers. Ipilimumab is a fully human antibody targeting CTLA-4 that received FDA approval for the treatment of metastatic melanoma in 2011...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28481035/prb7-a-praseodymium-doped-boron-cluster-with-a-pr-ii-center-coordinated-by-a-doubly-aromatic-planar-%C3%AE-7-b7-3-ligand
#2
Teng-Teng Chen, Wan-Lu Li, Tian Jian, Xin Chen, Jun Li, Lai-Sheng Wang
The structure and bonding of a Pr-doped boron cluster (PrB7(-) ) are investigated using photoelectron spectroscopy and quantum chemistry. The adiabatic electron detachment energy of PrB7(-) is found to be low [1.47(8) eV]. A large energy gap is observed between the first and second detachment features, indicating a highly stable neutral PrB7 . Global minimum searches and comparison between experiment and theory show that PrB7(-) has a half-sandwich structure with C6v symmetry. Chemical bonding analyses show that PrB7(-) can be viewed as a Pr(II) [η(7) -B7(3-) ] complex with three unpaired electrons, corresponding to a Pr (4f(2) 6s(1) ) open-shell configuration...
May 8, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28479601/b7-dc-pd-l2-costimulation-of-cd4-t-helper-1-response-via-rgmb
#3
Xinxin Nie, Wenni Chen, Ying Zhu, Baozhu Huang, Weiwei Yu, Zhanshuai Wu, Sizheng Guo, Yiping Zhu, Liqun Luo, Shengdian Wang, Lieping Chen
The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo. In addition to interacting with the coinhibitory receptor PD-1, B7-DC has also been shown to bind repulsive guidance molecule b (RGMb). The functional consequences of the B7-DC/RGMb interaction, however, remain unclear. More than a decade ago, we reported that replacement of a murine B7-DC mutant lysine with serine (K113S) at positive 113 resulted in a loss of binding capacity to PD-1...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28479600/a-crucial-role-of-the-pd-1h-coinhibitory-receptor-in-suppressing-experimental-asthma
#4
Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28467047/electrophilic-halogenation-of-closo-1-2-c2b8h10
#5
Mario Bakardjiev, Aleš Růžička, Zdeňka Růžičková, Josef Holub, Oleg L Tok, Bohumil Štíbr
Initial studies on electrophilic halogenation of the dicarbaborane closo-1,2-C2B8H10 (1) have been carried out to reveal that the substitution takes place at B7 and B10 vertexes, which are the most removed from the CH positions. The course of the halogenation is strongly dependent on the nature of the halogenation agent and reaction conditions. Individual reactions led to the isolation of the monosubstituted compounds 1,2-C2B8H9-10-X (2) (where X = F, I) and 1,2-C2B8H9-7-X (3) (where X = Cl, I). Disubstituted carboranes 1,2-C2B8H8-7,10-X2 (4) (where X = Cl, Br, I) were obtained under more forcing conditions...
May 3, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28465443/phase-i-and-preliminary-phase-ii-study-of-trc105-in-combination-with-sorafenib-in-hepatocellular-carcinoma
#6
Austin Duffy, Chi Ma, Susanna Ulahannan, Osama E Rahma, Oxana Makarova-Rusher, Liang Cao, Yunkai Yu, David Kleiner, Jane Trepel, Min-Jung Lee, Yusuke Tomita, Seth M Steinberg, Theo Heller, Baris Turkbey, Peter L Choyke, Cody J Peer, William D Figg, Bradford J Wood, Tim F Greten
Endoglin (CD105) is an endothelial membrane receptor expressed on tumor vasculature. Endoglin expression is induced by VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 monoclonal antibody that inhibits angiogenesis, causes antibody-dependent cellular cytotoxicity (ADCC) and apoptosis of proliferating endothelium. <br /><br />Experimental Design: Patients with HCC (Childs Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, 15mg/kg q 2wks given with sorafenib 400mg bid...
May 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28461179/immune-characterization-of-the-programmed-death-receptor-pathway-in-high-risk-prostate%C3%A2-cancer
#7
Wesley Baas, Svetlana Gershburg, Danuta Dynda, Kristin Delfino, Kathy Robinson, Daotai Nie, Jennifer Holmes Yearley, Shaheen Alanee
BACKGROUND: Programmed cell death-1 (PD-1), a T-cell inhibitory receptor, and its ligand, PD-L1, have been reported to be expressed in many tumor types, and this expression has led to the development of many drugs targeting the PD-1 pathway. The objective of this study was to determine the expression of PD-1 and PD-L1 in high-grade prostate cancer tissues, and correlate the expression with disease and patient characteristics. MATERIALS AND METHODS: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed and scored from 0 to 5 on prostatectomy/biopsy tissue samples taken from 25 men with high-grade prostate cancer...
April 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28454382/increased-b7-h4-expression-during-esophageal-squamous-cell-carcinogenesis-is-associated-with-il-6-stat3-signaling-pathway-activation-in-mice
#8
Xinran Chen, Wei Wang, Hongwei Man, Pengfei Li, Baoen Shan
B7-homolog 4 (B7-H4), one of the costimulatory molecules of the B7 family, has been reported to be widely expressed in multiple types of cancer tissues, and to be important in tumor progression and poor prognosis. However, the role of B7-H4 in esophageal precancerous lesions has not been elucidated yet. In the present study, a model of esophageal squamous cell carcinogenesis was established in 208 C57BL/6 mice by 4-nitroquinoline-1-oxide (4NQO) drinking water of mice, and the changes in the expression of B7-H4 during the whole pathological process were investigated...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#9
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#10
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28427226/microrna-152-regulates-immune-response-via-targeting-b7-h1-in-gastric-carcinoma
#11
Yaxin Wang, Di Wang, Gengchen Xie, Yuping Yin, Ende Zhao, Kaixiong Tao, Ruidong Li
MiR-152 has been reported may be involved in carcinogenesis in gastric cancer. However, its role has not been comprehensively investigated in gastric cancer. We found miR-152 in human gastric cancer tissues were significantly lower than that in matched adjacent normal tissues. Meanwhile, lower miR-152 was also found in gastric cancer cell lines. The stage, tumor size and lymph node metastasis rate were significant higher in low-miR-152 group in clinical patients. Furthermore, there was a marked correlation between the levels of miR-152 and B7-H1 mRNA in gastric cancer tissues...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412649/proinflammatory-effects-of-diesel-exhaust-particles-from-moderate-blend-concentrations-of-1st-and-2nd-generation-biodiesel-in-beas-2b-bronchial-epithelial-cells-the-fuelhealth-project
#12
Tonje S Skuland, Magne Refsnes, Pål Magnusson, Michał Oczkowski, Joanna Gromadzka-Ostrowska, Marcin Kruszewski, Remigiusz Mruk, Oddvar Myhre, Anna Lankoff, Johan Øvrevik
Biodiesel fuel fuels are introduced at an increasing extent as a more carbon-neutral alternative to reduce CO2-emissions, compared to conventional diesel fuel. In the present study we have investigated the impact of increasing the use of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend (B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro system...
April 5, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28404927/prognostic-role-of-b7-h4-in-patients-with-non-small-cell-lung-cancer-a-meta-analysis
#13
Zhibo Tan, Weixi Shen
B7 homolog 4 (B7-H4) has been recently reported to be a prognostic marker in non-small cell lung cancer (NSCLC) in some studies. However, the results remained conflicting. Thus, we aimed to comprehensively assess the association between B7-H4 expression and prognosis of NSCLC patients by performing a meta-analysis. Relevant publications were thoroughly searched of PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate the effects...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28351777/enhance-the-anti-renca-carcinoma-effect-of-a-dna-vaccine-targeting-g250-gene-by-co-expression-with-cytotoxic-t-lymphocyte-associated-antigen-4-ctla-4
#14
Youguang Zhao, Zhitao Wei, Hang Yang, Xiaowei Li, Qiwu Wang, Liang Wang, Shadan Li
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 with a greater affinity. Co-expression specific antigens and extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for its enhancement on G250/MN/CA IX (G250)-specific immune responses and its anti-tumor effects in renal carcinoma mice model. Consequently, we constructed a DNA vaccine containing the G250 and the CTLA-4 gene...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28347512/characterization-of-immune-regulatory-molecules-b7-h4-and-pd-l1-in-low-and-high-grade-endometrial-tumors
#15
Amy Bregar, Amit Deshpande, Chris Grange, Tong Zi, Jennifer Stall, Heather Hirsch, Jason Reeves, Sriram Sathyanarayanan, Whitfield B Growdon, Bo R Rueda
BACKGROUND: The objective of this investigation was to characterize the expression landscape of immune regulatory molecules programmed death-ligand-1 (PD-L1, B7-H1) and B7-H4 in a cohort of endometrial tumors across the spectrum of grade and histology. MATERIALS AND METHODS: With institutional review board approval, 70 endometrial tumors from patients with known clinical outcomes were identified representing a spectrum of grade and histology. Immunohistochemistry (IHC) was performed for PD-L1 and B7-H4 and scored...
March 24, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28340813/comparison-of-anti-hla-antibody-production-according-to-gestational-periods-in-pregnant-women
#16
COMPARATIVE STUDY
B Cerci Gurbuz, M Soyoz, D Ozkale Okyay, T Kilicaslan Ayna, I Pirim
BACKGROUND: To evaluate paternal anti-HLA antibody profiles, sera samples were collected from pregnant women in different trimesters and the panel-reactive antibody (PRA) specificities were identified. METHODS: From 2013 to 2015, serum samples were obtained from 41 pregnant women who had registered at the Izmir Tepecik Education and Research Hospital Gynecology Clinic. Anti-HLA antibodies were screened by using the panel reactive antibody screening and identification tests...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28338007/human-immunodeficiency-virus-type-1-myeloid-derived-suppressor-cells-inhibit-cytomegalovirus-inflammation-through-interleukin-27-and-b7-h4
#17
Ankita Garg, Rodney Trout, Stephen A Spector
HIV/CMV co-infected persons despite prolonged viral suppression often experience persistent immune activation, have an increased frequency of myeloid derived suppressor cells (MDSC) and are at increased risk for cardiovascular disease. We examined how HIV MDSC control CD4(+) T cell IFNγ response to a CMVpp65 peptide pool (CMVpp65). We show that HIV/CMV co-infected persons with virologic suppression and recovered CD4(+) T cells compared to HIV(-)/CMV(+) controls exhibit an increase in CD4(+)CX3CR1(+)IFNγ(+) cells in response to CMVpp65; MDSC depletion further augmented CD4(+)CX3CR1(+)IFNγ(+) cells and IFNγ production...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#18
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
June 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28333016/predictors-of-liver-toxicity-following-stereotactic-body-radiation-therapy-for-hepatocellular-carcinoma
#19
Michael Velec, Carol R Haddad, Tim Craig, Lisa Wang, Patricia Lindsay, James Brierley, Anthony Brade, Jolie Ringash, Rebecca Wong, John Kim, Laura A Dawson
PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28325750/molecular-pathways-evaluating-the-potential-for-b7-h4-as-an-immunoregulatory-target
#20
Heather L MacGregor, Pamela S Ohashi
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment anti-tumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies...
March 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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