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Yanbo Sun, Weiming Li, Dali Sun, Shumin Li, Qingwen Xu, Yijun Li, Yueying Lin, Yuxing Qi, Ting Yang, Kun Su, Yunyun Cen, Xiongzhi Chen, Pengyuan Xu
Purpose: To investigate the role of percutaneous transhepatic cholangial drainage (PTCD) combined with percutaneous endoscopic jejunostomy (PEJ) in maintaining the nutrition state in patients with advanced ampullary neoplasms. Materials and Methods: Sixty patients who suffered from advanced ampullary neoplasms and could not tolerate internal drainage operation or biliary stent placement were enrolled. After PTCD, PEJ was implemented, and then the enteral nutrient solution + bile were instilled through PEJ tube for enteral nutrition support...
December 2018: Journal of Cancer Research and Therapeutics
Ruchika Saroa, Upma Bagai
Plasmodium berghei ANKA is known to be responsible for causing neurological complications in susceptible strain of mice. Despite the decades of research, pathogenesis of cerebral malaria is still unknown. Histopathological and immunofluorescent staining was performed on brain of P. berghei ANKA infected and artesunate-sulphadoxine-pyrimethamine (AS + SP) treated mice to understand the pathogenesis of experimental cerebral malaria in present study. Cerebral vessels were found to be congested with infected/non-infected RBCs and various leukocytes in infected mice...
December 2018: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Bahare Laribi, Mohammad Ali Sahraian, Mehdi Shekarabi, Rahimeh Emamnejad, Mohsen Marzban, Shokufeh Sadaghiani, Maryam Izad
Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively...
August 12, 2018: Iranian Journal of Allergy, Asthma, and Immunology
Tatiana N Sharapova, Elena A Romanova, Lidia P Sashchenko, Denis V Yashin
Tilorone hydrochloride, a low-molecular-weight synthetic compound, induces interferon production and has been reported to have both antiviral and antitumor activities. Here, we have demonstrated the ability of tilorone to activate NK cells and specific subpopulations of cytotoxic CD4+ and CD8+ T lymphocytes that recognize immune-evasive tumor cells and kill them via the FasL-Fas interaction. We have also performed a comparative analysis of characteristics between lymphocytes activated in the fraction of human peripheral blood mononuclear cells (PBMCs) upon treatment with different stimulants of the immune response: tilorone, innate immunity protein Tag7, and cytokine IL-2, a regulator of adaptive immunity...
December 11, 2018: IUBMB Life
Marta González Vicent, Blanca Molina, Jesús González de Pablo, Ana Castillo, Miguel Ángel Díaz
Ruxolitinib is a promising treatment for steroid refractory graft-versus-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively...
December 8, 2018: American Journal of Hematology
Anne S Dejean, Emeline Joulia, Thierry Walzer
Eomesodermin (Eomes) is a transcription factor (TF) of the T-box family closely related to T-bet known for its role in CD8 T cell and natural killer cell differentiation. However, the role of Eomes in CD4 T-cell differentiation is less well appreciated. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2019. 49: XXXX-XXXX] Mazzoni et al. and Gruarin et al. studied the role of Eomes in human CD4 T-cell differentiation. Mazzoni et al. showed that Eomes plays a key role in helper T cell (Th) plasticity by favoring the phenotype shift of Th17 cells towards non-classic Th1 cells; while Gruarin et al...
December 7, 2018: European Journal of Immunology
Alexander M Saucedo, Jorge De La Cerda, Hiroo Suami, Rita E Serda
Beyond heterogeneous cancer cells, the tumor microenvironment includes stromal and immune cells, blood vessels, extracellular matrix and biologically active molecules. Abnormal signaling, uncontrolled proliferation and high interstitial pressure all contribute to a chaotic, non-hierarchical vascular organization. Using an immune competent 4T1 breast adenocarcinoma murine model, this study fully characterizes the architecture and immunocyte milieu of the tumor microenvironment. Heterogeneous vessel distribution, chaotic connectivity, limited perfusion, cancer cell density, immune phenotype, and biological responses to immune therapy are presented...
December 3, 2018: Biomedical Microdevices
Michael P Dubé, Ellen S Chan, Jordan E Lake, Brett Williams, Jennifer Kinslow, Alan Landay, Robert W Coombs, Michelle Floris-Moore, Heather J Ribaudo, Kevin E Yarasheski
Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to their glucoregulatory actions. We evaluated inflammation and immune markers in suppressed HIV infection during treatment with the DPP-4 inhibitor sitagliptin. Methods: Virologically suppressed adults with HIV without diabetes mellitus on stable ART with ≥100/mm 3 CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/d vs. placebo in a multicenter trial...
December 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Laurence C Menard, Paul Fischer, Bijal Kakrecha, Peter S Linsley, Erik Wambre, Maochang C Liu, Blake J Rust, Deborah Lee, Becky Penhallow, Nataly Manjarrez Orduno, Steven G Nadler
Checkpoint inhibitors target the inhibitory receptors expressed by tumor-infiltrating T cells in order to reinvigorate an anti-tumor immune response. Therefore, understanding T cell composition and phenotype in human tumors is crucial. We analyzed by flow cytometry tumor-infiltrating lymphocytes (TILs) from two independent cohorts of patients with different cancer types, including RCC, lung, and colon cancer. In healthy donors, peripheral T cells are usually either CD4+ or CD8+ with a small percentage of CD4+ CD8+ DP cells (<5%)...
2018: Frontiers in Immunology
Suzanne Furlong, Melanie R Power Coombs, Javad Ghassemi-Rad, David W Hoskin
Thy-1 (CD90) is a glycosylphosphatidylinositol-anchored protein (GPI-AP) with signaling properties that is abundant on mouse T cells. Upon antibody-mediated crosslinking, Thy-1 provides a T cell receptor (TcR)-like signal that is sufficient to drive CD4+ T cell proliferation and differentiation into effector cells when costimulatory signals are provided by syngeneic lipopolysaccharide-matured bone marrow-derived dendritic cells. In this study, we investigated the impact of Thy-1 signaling on the production of the T helper (Th) cell subset-associated cytokines, interferon (IFN) γ, interleukin (IL)-4 and IL-17A, as well as the in vitro polarization of highly purified resting CD4+ T cells into Th1, Th2, and Th17 cells...
2018: Frontiers in Cell and Developmental Biology
Raju Sunagar, Sudeep Kumar, Prachi Namjoshi, Sarah J Rosa, Karsten R O Hazlett, Edmund J Gosselin
Francisella tularensis (Ft) is a biothreat agent for which there is no FDA-approved human vaccine. Currently, there are substantial efforts underway to develop both vaccines and the tools to assess these vaccines. Tularemia laboratory research has historically relied primarily upon a small number of inbred mouse strains, but the utility of such findings to outbred animals may be limited. Specifically, C57BL/6 mice are more susceptible than BALB/c mice to Ft infection and less easily protected against challenge with highly virulent type A Ft...
2018: PloS One
Attilio Bondanza, Loredana Ruggeri, Maddalena Noviello, Dirk-Jan Eikema, Chiara Bonini, Christian Chabannon, Steffie van der Werf, Anja van Biezen, Liesbeth C de Wreede, Lara Crucitti, Luca Vago, Mara Merluzzi, Maria Speranza Massei, Hendrik Veelken, Yener Koc, Peter Bader, Bernd Gruhn, Franco Locatelli, Fabio Ciceri, Antoine Toubert, Andrea Velardi
HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM)...
December 7, 2018: Bone Marrow Transplantation
Luuk Gras, Margaret May, Lars Peter Ryder, Adam Trickey, Marie Helleberg, Niels Obel, Rodolphe Thiebaut, Jodie Guest, John Gill, Heidi Crane, Viviane Dias Lima, Antonella dʼArminio Monforte, Timothy R Sterling, Jose Miro, Santiago Moreno, Christoph Stephan, Colette Smith, Janet Tate, Leah Shepherd, Mike Saag, Armin Rieger, Daniel Gillor, Matthias Cavassini, Marta Montero, Suzanne M Ingle, Peter Reiss, Dominique Costagliola, Ferdinand W N M Wit, Jonathan Sterne, Frank de Wolf, Ronald Geskus
BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV uninfected individuals more likely and whether restoration depends on gender, age and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell count and their ratio using cross-sectional data from 2,309 HIV-negative individuals...
December 3, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Ariel Isser, Jonathan P Schneck
Adoptive cell transfer (ACT) of engineered T cell receptors (TCRs) for cancer immunotherapy has evolved from simple gene transfer of isolated TCRs to various affinity enhancement techniques that overcome limitations imposed by central and peripheral tolerance on TCR affinity. In the current issue of the JCI, Poncette et al. used mice with human TCRαβ and HLA gene loci to discover CD4+ TCRs of optimal affinity for cancer testis antigen (CTA) NY-ESO-1. They combined this TCR with a previously discovered NY-ESO-1-specific CD8+ TCR in an ACT fibrosarcoma tumor model to demonstrate the importance of T cell help in mediating antitumor responses...
December 10, 2018: Journal of Clinical Investigation
Chien-Chun Steven Pai, Donald M Simons, Xiaoqing Lu, Michael Evans, Junnian Wei, Yung-Hua Wang, Mingyi Chen, John Huang, Chanhyuk Park, Anthony Chang, Jiaxi Wang, Susan Westmoreland, Christine Beam, Dave Banach, Diana Bowley, Feng Dong, Jane Seagal, Wendy Ritacco, Paul L Richardson, Soumya Mitra, Grace Lynch, Pete Bousquet, John Mankovich, Gillian Kingsbury, Lawrence Fong
While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte-associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4-binding domain...
December 10, 2018: Journal of Clinical Investigation
Lucia Poncette, Xiaojing Chen, Felix Km Lorenz, Thomas Blankenstein
Adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy...
December 10, 2018: Journal of Clinical Investigation
Melanie Boxberg, Lena Leising, Katja Steiger, Moritz Jesinghaus, Aezlat Alkhamas, Marion Mielke, Nicole Pfarr, Carolin Götz, Klaus Dietrich Wolff, Wilko Weichert, Andreas Kolk
Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial-mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3+ /CD4+ /CD8+ /CD4+ FOXP3+ /IL-17A+ ) were quantified, and ratios were calculated...
December 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Dibyendu Dutta, In Park, Hiwot Guililat, Samuel Sang, Arpita Talapatra, Laura Hanson, Nathaniel Crain Mills
Sperm granuloma may develop in the epididymis following vasectomy or chemical insults. Inflammation due to sperm granuloma causes abdominal and scrotal pain. Prolonged and persistent inflammation in the epididymis due to sperm granuloma may lead to infertility. Extravasation of germ cells into the interstitium of epididymis following damage of the epididymal epithelium is one of the primary reasons for sperm granuloma-associated pathology. Since testosterone is vital for the maintenance of epididymal epithelium, we investigated the pathology of sperm granuloma and its relationship with testosterone...
December 5, 2018: Reproductive Biology
Gregory T Wolf, William Winter, Emily Bellile, Ariane Nguyen, C R Donnelly, Jonathan B McHugh, Dafydd Thomas, Lahin Amlani, Laura Rozek, Yu L Lei
INTRODUCTION: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed...
December 2018: Oral Oncology
Shamir Geller, Patricia L Myskowski, Melissa Pulitzer, Steven M Horwitz, Alison J Moskowitz
The vast majority of cutaneous T-cell lymphomas (CTCL) are encompassed by mycosis fungoides and CD30+ lymphoproliferative disorder (LPD), however rare distinct CTCLs have been defined. The current edition of the World Health Organization (WHO) includes 12 CTCL subtypes with discrete diagnosable clinical, histologic and phenotypic features. The rarest subtypes, i.e. those that comprise <1% to 2%, include indolent entities, such as primary cutaneous CD4+ small/medium T-cell LPD (SMPTC-LPD), primary cutaneous acral CD8+ T-cell lymphoma (acral CD8+ TCL) and subcutaneous panniculitis-like TCL (SPTCL) and aggressive entities, such as primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) and primary cutaneous gamma /delta T-cell lymphoma (PCGDTCL)...
November 21, 2018: Chinese Clinical Oncology
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