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immunocompetent cell

Sarah Löw, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas...
February 2018: Seminars in Neurology
Caroline K Søgaard, Siver A Moestue, Morten B Rye, Jana Kim, Anala Nepal, Nina-Beate Liabakk, Siri Bachke, Tone F Bathen, Marit Otterlei, Deborah K Hill
Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth in vivo in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP)...
February 20, 2018: Oncotarget
Gairu Li, Yang Xiang, Jin Zhao, Junmin Chang
The in vitro immune activities of Saccharum Alhagi polysaccharides (SAP) have been previously studied. The present study aimed to investigate the effects of SAP-1 and SAP-2 on the activity of RAW264.7 mouse macrophages. RAW264.7 cells were treated with 150, 300 and 600 mg/l concentrations of SAP-1 (a 50% alcohol precipitation) and SAP-2 (an 80% alcohol precipitation) or with 10 mg/l lipopolysaccharide. Untreated cells were used as a negative control. An MTT assay was used to detect the proliferation of the cells, and Hoechst 33528 staining was conducted in order to visualize the cell nuclei...
April 2018: Experimental and Therapeutic Medicine
Aleta Pupovac, Berna Senturk, Chiara Griffoni, Katharina Maniura-Weber, Markus Rottmar, Sally L McArthur
3D human skin models provide a platform for toxicity testing, biomaterials evaluation, and investigation of fundamental biological processes. However, the majority of current in vitro models lack an inflammatory system, vasculature, and other characteristics of native skin, indicating scope for more physiologically complex models. Looking at the immune system, there are a variety of cells that could be integrated to create novel skin models, but to do this effectively it is also necessary to understand the interface between skin biology and tissue engineering as well as the different roles the immune system plays in specific health and disease states...
March 15, 2018: Advanced Healthcare Materials
Jessica Wagner, C Leah Kline, Lanlan Zhou, Kerry S Campbell, Alexander W MacFarlane, Anthony J Olszanski, Kathy Q Cai, Harvey H Hensley, Eric A Ross, Marie D Ralff, Andrew Zloza, Charles B Chesson, Jenna H Newman, Howard Kaufman, Joseph R Bertino, Mark N Stein, Wafik El-Deiry
ONC201 is a first-in-class, orally active anti-tumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. ONC201 has demonstrated safety and preliminary efficacy in the first-in-human trial where patients were dosed every 3 weeks. We hypothesized that dose-intensification of ONC201 may impact anti-tumor efficacy. We discovered that ONC201 exerts dose- and schedule-dependent effects on tumor progression and cell-death signaling in vivo. With dose intensification, we note a potent anti-metastasis effect and inhibition of cancer cell migration and invasion...
March 13, 2018: Journal of Clinical Investigation
Masami Yamamoto, Sachiyo Nomura, Akihiro Hosoi, Koji Nagaoka, Tamaki Iino, Tomohiko Yasuda, Tomoko Saito, Hirokazu Matsushita, Eiji Uchida, Yasuyuki Seto, James R Goldenring, Kazuhiko Kakimi, Masae Tatematsu, Tetsuya Tsukamoto
Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies.MNU was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only one tumor from a p53 knockout mouse could be cultured and the cells are subcutaneously transplantable into a C57BL/6 mouse. We cultured this subcutaneous tumor, and sub-cloned it. The mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and FGFR4 in YTN16 cells was knocked-out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931...
March 13, 2018: Cancer Science
Rea Lo Dico, Annemilai Tijeras-Raballand, Philippe Bonnin, Jean Marie Launay, Rachid Kaci, Cynthia Pimpie, Brice Malgras, Anthony Dohan, Gianluigi Maria Lo Dico, Marc Pocard
BACKGROUND: Curative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis...
January 31, 2018: European Journal of Surgical Oncology
Buigues A, Ferrero H, Martínez J, Pellicer N, Pellicer A, Gómez R
To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows non-invasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for two weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group)...
March 6, 2018: Biology of Reproduction
Priscila Marques de Macedo, Rodrigo Almeida-Paes, Marcos de Abreu Almeida, Rowena Alves Coelho, Marcio Amaral de Oliveira Filho, Denise Machado Medeiros, Adriano Gomes-Silva, Jéssica Ribeiro de Lima, Alda Maria Da-Cruz, Rosely Maria Zancopé-Oliveira, Antonio Carlos Francesconi do Valle
The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process...
January 2018: Revista da Sociedade Brasileira de Medicina Tropical
Binghao Li, Yang Zeng, Patrick M Reeves, Chongzhao Ran, Qiuyan Liu, Xiying Qu, Yingying Liang, Zhao Liu, Jianping Yuan, Pierre R Leblanc, Zhaoming Ye, Ann E Sluder, Jeffrey A Gelfand, Timothy A Brauns, Huabiao Chen, Mark C Poznansky
AMD3100 (plerixafor), a CXCR4 antagonist, has been demonstrated to suppress tumor growth and modulate intratumoral T-cell trafficking. However, the effect of AMD3100 on immunomodulation remains elusive. Here, we explored immunomodulation and antitumor efficacy of AMD3100 in combination with a previously developed mesothelin-targeted, immune-activating fusion protein, VIC-008, in two syngeneic, orthotopic models of malignant mesothelioma (MM) in immunocompetent mice. We showed that combination therapy significantly suppressed tumor growth and prolonged animal survival in two mouse models...
March 6, 2018: Cancer Immunology Research
Hiroshi Nakashima, Tran Nguyen, Kazue Kasai, Carmela Passaro, Hirotaka Ito, William F Goins, Imran Shaikh, Ronald Erdelyi, Reiko Nishihara, Ichiro Nakano, David A Reardon, Ana C Anderson, Vijay Kuchroo, E Antonio Chiocca
PURPOSE: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives. EXPERIMENTAL DESIGN: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34...
March 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elena Blanco, Martín Pérez-Andrés, Sonia Arriba-Méndez, Teresa Contreras-Sanfeliciano, Ignacio Criado, Ondrej Pelak, Ana Serra-Caetano, Alfonso Romero, Noemí Puig, Ana Remesal, Juan Torres Canizales, Eduardo López-Granados, Tomas Kalina, Ana E Sousa, Menno Van Zelm, Mirjam Van der Burg, Jacques J M van Dongen, Alberto Orfao
BACKGROUND: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity and neoplasia. Immunoglobulin heavy chain (IgH)-isotype serum levels can partly explain such age-related differences, but their relationship with the IgH-isotype distribution within memory B-cell (MBCs) and plasma cell (PCs) compartments remains to be investigated. OBJECTIVE: We studied the age-related distribution of MBCs and PCs expressing different IgH-isotypes, in addition to the immature/transitional and naive B-cell compartments...
March 2, 2018: Journal of Allergy and Clinical Immunology
Katarzyna C Pituch, Jason Miska, Giedre Krenciute, Wojciech K Panek, Gina Li, Tania Rodriguez-Cruz, Meijing Wu, Yu Han, Maciej S Lesniak, Stephen Gottschalk, Irina V Balyasnikova
In order to fully harness the potential of immunotherapy with chimeric antigen receptor (CAR)-modified T cells, pre-clinical studies must be conducted in immunocompetent animal models that closely mimic the immunosuppressive malignant glioma (MG) microenvironment. Thus, the goal of this project was to study the in vivo fate of T cells expressing CARs specific for the MG antigen IL13Rα2 (IL13Rα2-CARs) in immunocompetent MG models. Murine T cells expressing IL13Rα2-CARs with a CD28.ζ (IL13Rα2-CAR.CD28...
February 8, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Aglaia Domouchtsidou, Vahé Barsegian, Stefan P Mueller, Jan Best, Judith Ertle, Sotiria Bedreli, Peter A Horn, Andreas Bockisch, Monika Lindemann
The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
Erik Ladomersky, Lijie Zhai, Alicia Lenzen, Kristen L Lauing, Jun Qian, Denise M Scholtens, Galina Gritsina, Xuebing Sun, Ye Liu, Fenglong Yu, Wenfeng Gong, Yong Liu, Beibei Jiang, Zhiyu Tang, Ricky Patel, Leonidas C Platanias, C David James, Roger Stupp, Rimas V Lukas, David C Binder, Derek A Wainwright
PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents...
March 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Andreas Habertheuer, Laxminarayana Korutla, Susan Rostami, Sanjana Reddy, Priti Lal, Ali Naji, Prashanth Vallabhajosyula
OBJECTIVE: In heart transplantation, there is a critical need for development of biomarkers to noninvasively monitor cardiac allografts for immunologic rejection or injury. Exosomes are tissue-specific nanovesicles released into circulation by many cell types. Their profiles are dynamic, reflecting conditional changes imposed on their tissue counterparts. We proposed that a transplanted heart releases donor-specific exosomes into the recipient's circulation that are conditionally altered during immunologic rejection...
February 1, 2018: Journal of Thoracic and Cardiovascular Surgery
Bo G Lindberg, Xiongzhuo Tang, Widad Dantoft, Priya Gohel, Shiva Seyedoleslami Esfahani, Jessica M Lindvall, Ylva Engström
Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub) encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila...
March 2, 2018: PLoS Pathogens
Konstantin A Rogovin, Anastasiya M Khrushchova, Olga N Shekarova, Nina A Vasilieva, Nina Yu Vasilieva
Androgen-dependent male sexual traits (STs) as well as immunocompetence are theoretically assumed to be key indicators of a male's quality for the mate-choosing female. We studied mate choice by sexually motivated (SM) females of Campbell's dwarf hamsters. Females chose between 2 tethered male siblings that differed in expression of STs. Males were unrelated to the female and able to contact and copulate with her. In both males, we measured sex-related morphology of body mass, mid-ventral specific skin gland, ano-genital distance, and external testicular diameter...
October 2017: Current Zoology
M Antonieta Núñez, Karla Contreras, M Soledad Depix, Enrique Geoffroy, Nicolás Villagra, Sandra Mellado, Ana M Salinas
BACKGROUND: Bartonella henselae is the causal agent of cat scratch disease in immunocompetent persons and bacterial angiomatosis in immunocompromised patients. In Chile, the prevalence of antibodies against B. henselae in healthy children and adolescents is 13.3%, in persons with occupational risk 60.5%, and in cats 85.6%. There are no published data regarding the seroprevalence in blood donors in our country, so determining if B. henselae is present in the blood of donors at the time of donation is very important, since this microorganism can survive up to 35 days in the red blood cells stored in a blood bank at 4 °C...
December 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
L-L Yang, L Wu, G-T Yu, W-F Zhang, B Liu, Z-J Sun
Targeted therapy using monoclonal antibodies (mAbs) has emerged as a widely used form of immunotherapy in head and neck squamous cell carcinoma (HNSCC). Membrane-associated glycoprotein CD317 has been preferentially overexpressed by multiple myeloma cells, and its humanized mAb has been previously used in clinical trials. However, overexpression of CD317 in HNSCC and its correlation with tumor immunity is still uncertain. Here, the immunoreactivity of CD317 was detected in human HNSCC tissue microarrays, which contained 43 oral mucosa samples, 48 dysplasia samples, and 165 primary HNSCC...
February 1, 2018: Journal of Dental Research
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