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https://www.readbyqxmd.com/read/29453386/anti-fibrotic-effects-of-cxcr4-targeting-i-body-ad-114-in-preclinical-models-of-pulmonary-fibrosis
#1
K Griffiths, D M Habiel, J Jaffar, U Binder, W G Darby, C G Hosking, A Skerra, G P Westall, C M Hogaboam, M Foley
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4 + fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449693/tumor-cell-intrinsic-tim-3-promotes-liver-cancer-via-nf-%C3%AE%C2%BAb-il-6-stat3-axis
#2
Hualin Zhang, Yang Song, Huimin Yang, Zhiyan Liu, Lifen Gao, Xiaohong Liang, Chunhong Ma
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449532/senescence-associated-secretory-factors-induced-by-cisplatin-in-melanoma-cells-promote-non-senescent-melanoma-cell-growth-through-activation-of-the-erk1-2-rsk1-pathway
#3
Xuerong Sun, Benyan Shi, Huiling Zheng, Ling Min, Jie Yang, Xiaoyi Li, Xiaoxin Liao, Weixing Huang, Mingmeng Zhang, Shun Xu, Zhe Zhu, Hongjing Cui, Xinguang Liu
Although targeted therapy and immunotherapy greatly improve the outcome of melanoma, drug resistance and low response rates still maintain the unsubstitutability of traditional chemotherapy. Cisplatin (CDDP) is widely used in different types of tumours with high response rates, but it generally has low efficiency in melanoma. The mechanisms underpinning the phenomena are not sufficiently understood. Here we demonstrated that various melanoma cell lines adopted senescence phenotype after CDDP treatment in contrast to the other types of tumour cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448617/microquantitation-of-prostate-speciflc-antigen-by-using-antibody-conjugated-magnetic-microsphere-beads
#4
Sang-Don Lee, Mijin Lee, So-Yeon Park, Yumin Ha, Sang-Chul Jung, Hangun Kim
Prostate-specific antigen (PSA) is a glycoprotein that is secreted by prostate gland epithelial cells, and elevation of PSA level in serum is often observed with prostate cancer or prostate disorders. Therefore, detection of PSA level in patient specimens is used as a diagnostic marker when screening of prostate cancer. In this study, we developed PSA antibody-conjugated microsphere beads that can be used for quantitation of PSA. We optimized the procedure for bead preparation and validated the detection analysis by using LNCaP and DU-145 prostate cancer cell lysates...
February 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29447335/condition-dependent-generation-of-aquaporin-4-antibodies-from-circulating-b-cells-in-neuromyelitis-optica
#5
Robert Wilson, Mateusz Makuch, Anne-Kathrin Kienzler, James Varley, Jennifer Taylor, Mark Woodhall, Jacqueline Palace, M Isabel Leite, Patrick Waters, Sarosh R Irani
Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro...
February 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29446213/osteopontin-is-essential-for-il-1%C3%AE-production-and-apoptosis-in-peri-implantitis
#6
Chengye Che, Jie Liu, Jianjun Yang, Lei Ma, Na Bai, Qian Zhang
BACKGROUND AND PURPOSE: Peri-implantitis is caused by a cascade of host and microbial factors leading to an oral inflammatory disease. The inflammation proliferates into supporting tissues surrounding implants and may finally lead to a complete loss of osseointegration. Being a phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) is involved in the differentiation of odontoblast-like cells during pulpal healing following tooth transplantation and the secretion of type I collagen in reparative dentin...
February 15, 2018: Clinical Implant Dentistry and related Research
https://www.readbyqxmd.com/read/29444980/circulating-t-fh-cells-serological-memory-and-tissue-compartmentalization-shape-human-influenza-specific-b-cell-immunity
#7
Marios Koutsakos, Adam K Wheatley, Liyen Loh, E Bridie Clemens, Sneha Sant, Simone Nüssing, Annette Fox, Amy W Chung, Karen L Laurie, Aeron C Hurt, Steve Rockman, Martha Lappas, Thomas Loudovaris, Stuart I Mannering, Glen P Westall, Michael Elliot, Stuart G Tangye, Linda M Wakim, Stephen J Kent, Thi H O Nguyen, Katherine Kedzierska
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T FH ) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5 - CXCR3 + antibody-secreting B cell population, CD21 hi CD27 + memory B cells, and CD21 lo CD27 + B cells...
February 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29444185/humoral-and-cell-mediated-immune-responses-after-a-booster-dose-of-hbv-vaccine-in-hiv-infected-children-adolescents-and-young-adults
#8
Vania Giacomet, Michela Masetti, Pilar Nannini, Federica Forlanini, Mario Clerici, Gian Vincenzo Zuccotti, Daria Trabattoni
OBJECTIVE: HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. DESIGN: 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. METHOD: All patients received a booster dose of HBV vaccine (HBVAXPRO 10 μg i...
2018: PloS One
https://www.readbyqxmd.com/read/29443417/chemokines-and-receptors-in-intestinal-b-lymphocytes
#9
REVIEW
Wang Zhiming, Wang Luman, Qian Tingting, Chu Yiwei
Recent studies indicate that chemoattractant cytokines (chemokines) and their receptors modulate intestinal B lymphocytes in different ways, including regulating their maturity and differentiation in the bone marrow and homing to intestinal target tissues. Here, we review several important chemokine/chemokine receptor axes that guide intestinal B cells, focusing on the homing and migration of IgA antibody-secreting cells (IgA-ASCs) to intestinal-associated lymphoid tissues. We describe the selective regulation of these chemokine axes in coordinating the IgA-ASC trafficking in intestinal diseases...
February 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29441788/expression-purification-and-biochemical-characterization-of-human-afamin
#10
Alessandra Altamirano, Andreas Naschberger, Barbara G Furnrohr, Radka Saldova, Weston B Struwe, Patrick M Jennings, Silvia Millán Martín, Suzana Malic, Immanuel Plangger, Stefan Lechner, Reina Pisano, Nicole Peretti, Bernd Linke, Mario M Aguiar, Friedrich Fresser, Andreas Ritsch, Tihana Lenac Rovis, Christina Goode, Pauline M Rudd, Klaus Scheffzek, Bernhard Rupp, Hans Dieplinger
Afamin is an 87 kDa glycoprotein with five predicted N-glycosylation sites. Afamin's glycan abundance contributes to conformational and chemical inhomogeneity presenting great challenges for molecular structure determination. For the purpose of studying the structure of afamin, various forms of recombinantly expressed human afamin (rhAFM) with different glycosylation patterns were thus created. Wild-type rhAFM and various hypo-glycosylated forms were expressed in CHO, CHO-Lec1 and HEK293T cells. Fully non-glycosylated rhAFM was obtained by transfection of point-mutated cDNA to delete all N-glycosylation sites of afamin...
February 14, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29437880/molecular-regulation-of-follicle-stimulating-hormone-synthesis-secretion-and-action
#11
Nandana Das, Rajendra Kumar
Follicle-stimulating hormone (FSH) plays fundamental roles in male and female fertility. FSH is a heterodimeric glycoprotein expressed by gonadotrophs in the anterior pituitary. The hormone-specific FSH-subunit is non-covalently associated with the common -subunit that is also present in the luteinizing hormone (LH), another gonadotrophic hormone secreted by gonadotropes and thyroid-stimulating hormone (TSH) secreted by thyrotrophs. Several decades of research led to the purification, structural characterization and physiological regulation of FSH in a variety of species including humans...
February 7, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29437789/targeted-bite-expression-by-an-oncolytic-vector-augments-therapeutic-efficacy-against-solid-tumors
#12
Tobias Speck, Johannes Pw Heidbuechel, Rūta Veinalde, Dirk Jaeger, Christof von Kalle, Claudia R Ball, Guy Ungerechts, Christine E Engeland
PURPOSE: Immunotherapy with bispecific T cell engagers has achieved striking success against hematological malignancies, but efficacy against solid tumors has been limited. We hypothesized that oncolytic measles viruses encoding bispecific T cell engagers (MV-BiTEs) represent a safe and effective treatment against solid tumors through local BiTE expression, direct tumor cell lysis and in situ tumor vaccination. EXPERIMENTAL DESIGN: To test this hypothesis, we generated MV-BiTEs from the Edmonston B vaccine strain to target two model antigens...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29437532/using-a-dihydrofolate-reductase-based-strategy-for-producing-the-biosimilar-version-of-pertuzumab-in-cho-s-cells
#13
Amin Ramezani, Abbas Ghaderi
Targeted therapy using monoclonal antibodies (mAbs) against epidermal growth factor receptor-2 (ErbB2) has been utilized for the treatment of breast cancer, recently. Pertuzumab, one of the anti-ErbB2 mAbs, was approved by FDA in 2012 for the treatment of metastatic breast cancer. The aim of this study was to produce biosimilar version of pertuzumab in Chinese hamster ovary (CHO)-S cell line, and compare its ErbB2-binding and biological activities, with commercial drug, Perjeta. To this end, a dihydrofolate reductase (DHFR)-based strategy was used to produce a CHO-S stable cell pool capable of producing high levels of pertuzumab...
February 13, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29434831/cxcl5-secreted-from-adipose-tissue-derived-stem-cells-promotes-cancer-cell-proliferation
#14
Yuying Zhao, Xiaosan Zhang, Hong Zhao, Jingxuan Wang, Qingyuan Zhang
Accumulating data suggest that adipose tissue facilitates breast tumor initiation and progression through paracrine and endocrine pathways, and that adipose tissue-derived stem cell (ASC) is likely the major cell type responsible for tumorigenesis and tumor development. However, it remains unknown how ASCs exert their effects. In the present study, in cultured breast cancer cell lines, including estrogen receptor (ER)-positive MCF-7 cells and ER-negative MDA-MB-231 cells, the effects on tumor proliferation of isolated ASCs from human breasts were examined...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434811/regulatory-effects-of-four-ginsenoside-monomers-in-humoral-immunity-of-systemic-lupus-erythematosus
#15
Xin Yu, Na Zhang, Wanfu Lin, Chen Wang, Wei Gu, Changquan Ling, Yinglu Feng, Yonghua Su
Ginsenosides Rb1, Rh1, Rg1 and Rg3 are known as the main active components extracted from the roots of the Panax ginseng C.A. Meyer, and were reported to have immunoregulatory effects. Disruption of B-cell immune regulation during the pathogenesis of systemic lupus erythematosus (SLE) may lead to the production of large amounts of antibodies. The present study investigated the effects of the four ginsenoside monomers on B-cell immune regulation and observed that they inhibited the proliferation and secretion of B cells induced by LPS, caused an upregulation of the expression of apoptosis-associated proteins Fas/Fas ligand and caspase-3, the expression of FcγRIIB (CD32) as well as the proportion of inactive B cells (CD19+CD27-)...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434775/il-25-promotes-th2-bias-by-upregulating-il-4-and-il-10-expression-of-decidual-%C3%AE-%C3%AE-t-cells-in-early-pregnancy
#16
Yuan Zhang, Ying Wang, Ming-Qing Li, Jie Duan, Deng-Xuan Fan, Li-Ping Jin
Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434607/the-role-of-the-endothelium-during-antibody-mediated-rejection-from-victim-to-accomplice
#17
REVIEW
Amy Rachael Cross, Denis Glotz, Nuala Mooney
Antibody-mediated rejection (AMR) of solid organ transplants is characterized by the activation and injury of the allograft endothelium. Histological and transcriptomic studies have associated microvascular inflammation and endothelial lesions with the severity of rejection and poor graft outcomes. The allograft endothelium forms the physical barrier between the donor organ and the recipient; this position directly exposes the endothelium to alloimmune responses. However, endothelial cells are not just victims and can actively participate in the pathogenesis of rejection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#18
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29430664/blimp-1-is-insufficient-to-induce-antibody-secretion-in-the-absence-of-irf4-in-dt40-cells
#19
Paulina M Budzyńska, Minna K Kyläniemi, Olli Lassila, Kalle-Pekka Nera, Jukka Alinikula
Differentiation of B cells into antibody secreting cells (ASCs), plasmablasts and plasma cells, is regulated by a network of transcription factors. Within this network factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial...
February 11, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29429467/-effects-of-toll-like-receptor-blockers-on-intestinal-mucosal-injury-in-mice-with-endotoxemia
#20
Chang Liu, Ke Jing
OBJECTIVE: To investigate the effects of Toll-like receptor blockers TLR2-Ab and TLR4-Ab on the tight junction protein ZO-1 in intestinal epithelial cells in mice, as well as their effects on nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). METHODS: A total of 32 BALB/C mice were divided into control group, model group, TLR4 treatment group, and TLR2 treatment group, with 8 mice in each group. A mouse model of endotoxemia was established by intraperitoneal injection of lipopolysaccharide...
February 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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