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https://www.readbyqxmd.com/read/29352723/which-hiv-infected-adults-with-high-cd4-t-cell-counts-benefit-most-from-immediate-initiation-of-antiretroviral-therapy-a-post-hoc-subgroup-analysis-of-the-start-trial
#1
Jean-Michel Molina, Birgit Grund, Fred Gordin, Ian Williams, Mauro Schechter, Marcello Losso, Matthew Law, Ernest Ekong, Noluthando Mwelase, Athanasios Skoutelis, Martin J Wiselka, Linos Vandekerckhove, Thomas Benfield, David Munroe, Jens D Lundgren, James D Neaton
BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment. METHODS: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART. Participants with CD4 counts higher than 500 cells per μL were randomly assigned to receive immediate ART or to defer ART until CD4 counts were lower than 350 cells per μL...
January 15, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29352630/surgical-damage-to-the-lymphatic-system-promotes-tumor-growth-via-impaired-adaptive-immune-response
#2
Yoshiyuki Nakamura, Yasuhiro Fujisawa, Naoko Okiyama, Rei Watanabe, Ryota Tanaka, Yosuke Ishitsuka, Hideaki Tahara, Manabu Fujimoto
BACKGROUND: Both lymph nodes (LNs) and lymphatic channels from primary sites to regional LNs are critical for initiation of adaptive immunity. However, as LNs are common metastatic sites in skin cancers, LN biopsies or dissections are frequently performed. In addition, reconstructive skin flaps after tumor resection may damage lymphatic flow from primary sites to regional LNs. OBJECTIVE: This study was designed to investigate the effect on tumor progression by such surgeries...
December 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29352371/innate-and-adaptive-t-cells-in-influenza-disease
#3
REVIEW
Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H O Nguyen, Katherine Kedzierska
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized...
January 20, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29352109/role-of-b-and-t-lymphocyte-attenuator-in-renal-transplant-recipients-with-biopsy-proven-acute-rejection
#4
Zijie Wang, Haiwei Yang, Xuzhong Liu, Jingying Zhang, Zhijian Han, Jun Tao, Chunchun Zhao, Xiaobin Ju, Ruoyun Tan, Min Gu
BACKGROUND Acute rejection is a common predisposing cause of allograft dysfunction in kidney transplantation. Recently, the B and T lymphocyte attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160 pathway was found to be potentially involved in the regulation of T cell activation. This could mean that this pathway is involved in graft rejection in kidney transplantation; the present study aimed to explore this possibility. MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients with biopsy-proven acute rejection (BPAR) or stable allograft function, as well as in healthy volunteers...
January 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29352001/keap1-editing-using-crispr-cas9-for-therapeutic-nrf2-activation-in-primary-human-t-lymphocytes
#5
Sanjeev Noel, Sul A Lee, Mohanraj Sadasivam, Abdel R A Hamad, Hamid Rabb
Oxidant stress modifies T lymphocyte activation and function. Previous work demonstrated that murine T cell-specific kelch like-ECH-associated protein 1 (Keap1) deletion enhances antioxidant capacity and protects from experimental acute kidney injury. In this study, we used CRISPR technology to develop clinically translatable human T cell-specific KEAP1 deletion. Delivery of KEAP1 exon 2 specific Cas9:guide RNA in Jurkat T cells led to significant (∼70%) editing and upregulation of NRF2-regulated antioxidant genes NADPH dehydrogenase quinone 1 (NQO1) (up to 11-fold), heme oxygenase 1 (HO1) (up to 11-fold), and GCLM (up to 2-fold)...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#6
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29350748/protective-effect-of-chitosan-oligosaccharides-against-cyclophosphamide-induced-immunosuppression-and-irradiation-injury-in-mice
#7
Xingchen Zhai, Xin Yang, Pan Zou, Yong Shao, Shoujun Yuan, A M Abd El-Aty, Jing Wang
Chitosan oligosaccharides (COS), hydrolyzed products of chitosan, was found to display various biological activities. Herein, we assessed the immunostimulatory activity of COS both in in vitro and in vivo studies. In vitro cytotoxicity studies to murine macrophage RAW264.7 revealed that COS is safe even at the maximum tested concentration of 1000 μg/mL. It also stimulates the production of nitric oxide (NO) and tumor necrosis factor (TNF-α) and enhances the phagocytosis in COS-stimulated RAW264.7. We have shown that the COS could significantly (P < 0...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350470/specific-expression-of-pd-l1-in-rela-fusion-supratentorial-ependymoma-implications-for-pd-1-targeted-therapy
#8
Davis A Witt, Andrew M Donson, Vladimir Amani, Daniel C Moreira, Bridget Sanford, Lindsey M Hoffman, Michael H Handler, Jean M Mulcahy Levy, Kenneth L Jones, Anandani Nellan, Nicholas K Foreman, Andrea M Griesinger
BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#9
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#10
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348563/disruption-of-cxcr3-function-impedes-the-development-of-sj%C3%A3-gren-s-syndrome-like-xerostomia-in-non-obese-diabetic-mice
#11
Jing Zhou, Qing Yu
The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of patients with Sjögren's syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29345017/effects-of-nutritional-support-on-short-term-clinical-outcomes-and-immune-response-in-unresectable-locally-advanced-oesophageal-squamous-cell-carcinoma
#12
F Chen, J Fang, H Wang, T Song, W Zhu, M Wu, Y Wu
This retrospective study investigated the efficiency of nutritional support in unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC) patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil and cisplatin. In the routine care group, 63 patients served as historical controls and received nutrition support in a reactive manner. In addition, 57 patients in the nutritional support group received timely diet counselling, oral nutritional supplements, enteral nutrition and/or parenteral nutrition during CCRT...
January 18, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29344269/early-and-partial-reduction-in-cd4-foxp3-regulatory-t-cells-during-colitis-associated-colon-cancer-induces-cd4-and-cd8-t-cell-activation-inhibiting-tumorigenesis
#13
Jonadab E Olguín, Itzel Medina-Andrade, Emmanuel Molina, Armando Vázquez, Thalia Pacheco-Fernández, Rafael Saavedra, Carlos Pérez-Plasencia, Yolanda I Chirino, Felipe Vaca-Paniagua, Luis E Arias-Romero, Emma B Gutierrez-Cirlos, Sonia A León-Cabrera, Miriam Rodriguez-Sosa, Luis I Terrazas
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men in North America and Europe. CRC is associated with inflammatory responses in which intestinal pathology is caused by different cell populations including a T cell dysregulation that concludes in an imbalance between activated T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that actively suppress pathological and physiological immune responses, contributing to the maintenance of immune homeostasis...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344157/expression-and-clinical-significance-of-programmed-death-1-on-lymphocytes-and-programmed-death-ligand-1-on-monocytes-in-the-peripheral-blood-of-patients-with-cervical-cancer
#14
Ying Zhang, Weipei Zhu, Xueguang Zhang, Qiuxia Qu, Liyuan Zhang
The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343554/biased-generation-and-in-situ-activation-of-lung-tissue-resident-memory-cd4-t-cells-in-the-pathogenesis-of-allergic-asthma
#15
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343525/lack-of-remuscularization-following-transplantation-of-human-embryonic-stem-cell-derived-cardiovascular-progenitor-cells-in-infarcted-nonhuman-primates
#16
Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian'an Wang
Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myo-cardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cy-closporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and Simulect in cynomolgous monkeys that had received intramyocardial injections of 1×107 EGFP-expressing hPSC-CVPCs after MI...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29343453/polygonatum-sibiricum-polysaccharides-play-anti-cancer-effect-through-tlr4-mapk-nf-%C3%AE%C2%BAb-signaling-pathways
#17
Tingting Long, Zijing Liu, Jingchuan Shang, Xing Zhou, Shuang Yu, Hui Tian, Yixi Bao
OBJECTIVE: To investigate the anti-cancer effect of Polygonatum sibiricum polysaccharides (PSP) and the underlying mechanism. METHODS: Tumor-bearing mice were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot were performed to detect the mRNA and protein expressions, respectively...
January 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29342998/-x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia-report-of-a-family-and-literature-review
#18
T Y He, Y Xia, C G Li, C R Li, Z X Qi, J Yang
Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29342501/selective-activation-of-tumor-necrosis-factor-receptor-2-induces-anti-inflammatory-responses-and-alleviates-experimental-arthritis
#19
Roman Fischer, Marcel Proske, Maëlle Duffey, Hubert Stangl, George F Martinez, Nathalie Peters, Alexandra Kraske, Rainer H Straub, John R Bethea, Roland E Kontermann, Klaus Pfizenmaier
OBJECTIVES: Regulatory T cells (Tregs) modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor 2 (TNFR2) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Tregs. Here, we investigated the therapeutic activity of a novel TNFR2 agonist in experimental arthritis and the role of different Treg subsets. METHODS: A novel mouse TNFR2-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic engineering...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29341972/ocular-surface-and-tear-film-characteristics-in-a-sclerodermatous-chronic-graft-versus-host-disease-mouse-model
#20
Jingliang He, Mio Yamane, Shinsuke Shibata, Masaki Fukui, Eisuke Shimizu, Tetsuya Yano, Shin Mukai, Yutaka Kawakami, Shaowei Li, Kazuo Tsubota, Yoko Ogawa
PURPOSE: To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model. METHODS: The ocular surface features and tear film parameters of the mouse model were assessed by histopathology, immunohistochemistry, electron microscopy, quantitative polymerase chain reaction, and flow cytometry. RESULTS: The mice exhibited loss of body weight and decreased tear secretion (P < 0...
January 16, 2018: Cornea
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