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https://www.readbyqxmd.com/read/28645104/b7-h4-as-an-independent-prognostic-indicator-of-cancer-patients-a-meta-analysis
#1
Zibo Meng, Feiyang Wang, Yushun Zhang, Shoukang Li, Heshui Wu
The expression of B7-H4 was observed in a variety of tumors, however the prognostic value in cancer was still controversial. Therefore, we conducted this meta-analysis to explore the potential role of B7-H4 in cancer prognostic prediction. Twenty-seven studies including 3771 patients were brought into the analysis according to the inclusion and exclusion criteria. The pooled results demonstrated that elevated B7-H4 predicted a poor OS (HR = 1.93, 95% CI 1.71-2.18, P < 0.001) and DFS (HR = 1.84, 95% CI 1...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#2
REVIEW
Maja Matic, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly...
June 21, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28613437/t-cell-subsets-predicting-belatacept-resistant-rejection-finding-the-root-where-the-trouble-starts
#3
EDITORIAL
T Wekerle
The potential of costimulation blockade to revolutionize post-transplant immunosuppression has remained largely unfulfilled to date. Belatacept, the only costimulation blocker approved in organ transplant recipients, has not replaced the 30-plus-year-old CNIs as the mainstay of immunosuppression and is currently used infrequently. Modulating pathogenic immune responses through the interruption of costimulatory signals, which a naïve T cell requires for its full activation, has captivated immunologists since the demonstration that such costimulation blockade leads to antigen-specific immunomodulation (at least in vitro)...
June 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28608180/montelukast-improves-the-changes-of-cytoskeletal-and-adaptor-proteins-of-human-podocytes-by-interleukin-13
#4
Tae-Sun Ha, Ja Ae Nam, Su-Bin Seong, Moin A Saleem, Se Jin Park, Jae Il Shin
OBJECTIVE AND DESIGN: Interleukin-13 (IL-13) has recently been reported to be a potential cytokine in the pathogenesis of minimal-change nephrotic syndrome (MCNS). However, the mechanistic insights associated with podocyte dysfunction mediated by IL-13-induced changes in various slit diaphragm (SD) and cytoskeletal molecules have not yet been shown in cultured human podocytes in vitro. MATERIALS: Human conditionally immortalized podocytes were used. TREATMENT: Podocytes were incubated with various concentrations of IL-13 during the indicated time periods (6, 12, and 24 h) and montelukast was administered with the dose of 0...
June 12, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28599283/remarkably-similar-ctla-4-binding-properties-of-therapeutic-ipilimumab-and-tremelimumab-antibodies
#5
Mengnan He, Yan Chai, Jianxun Qi, Catherine W H Zhang, Zhou Tong, Yi Shi, Jinghua Yan, Shuguang Tan, George F Gao
Monoclonal antibody based immune checkpoint blockade therapies have achieved clinical successes in management of malignant tumors. As the first monoclonal antibody targeting immune checkpoint molecules entered into clinics, the molecular basis of ipilimumab-based anti-CTLA-4 blockade has not yet been fully understood. In the present study, we report the complex structure of ipilimumab and CTLA-4. The complex structure showed similar contributions from VH and VL of ipilimumab in binding to CTLA-4 front β-sheet strands...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591700/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpesvirus-infected-cells-by-lenalidomide-and-pomalidomide
#6
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583712/structural-influences-on-the-activity-of-bismuth-iii-indole-carboxylato-complexes-towards-helicobacter-pylori-and-leishmania
#7
Amita Pathak, Victoria L Blair, Richard L Ferrero, Lukasz Kedzierski, Philip C Andrews
Seven new bismuth(III) complexes derived from indole-carboxylic acids have been synthesised: five are homoleptic; [Bi(IAA)3] B1, [Bi(IPA)3] B2, [Bi(IBA)3] B3, [Bi(MICA)3] B4, [Bi(IGA)3] B6, and two are heteroleptic [BiPh(MICA)2] B5 (where IAA-H=2-(1H-indol-3-yl)acetic acid, IPA-H=3-(1H-indol-3-yl)propanoic acid, IBA-H=4-(1H-indol-3-yl)butanoic acid, IGA-H=2-(1H-indol-3-yl)-2-oxoacetic acid, and MICA-H=1-methyl-1H-indole-3-carboxylic acid). All complexes were fully characterised by elemental analysis, infrared and mass-spectroscopy, and nuclear magnetic resonance ((1)H, (13)C) spectroscopy...
May 31, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28564646/constitutive-activation-of-smoothened-in-the-renal-collecting-ducts-leads-to-renal-hypoplasia-hydronephrosis-and-hydroureter
#8
Deepak Prasad Gupta, Jae-Won Hwang, Eui-Sic Cho, Won Kim, Chang Ho Song, Ok Hee Chai
Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development...
June 1, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28539467/b7-h3-expression-in-nsclc-and-its-association-with-b7-h4-pd-l1-and-tumor-infiltrating-lymphocytes
#9
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
#10
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/28484017/structural-basis-for-cancer-immunotherapy-by-the-first-in-class-checkpoint-inhibitor-ipilimumab
#11
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 23, 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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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