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Virus T cell therapy

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https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#1
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28222623/interferon-%C3%AE-induced-cd100-on-na%C3%A3-ve-cd8-t-cells-enhances-antiviral-responses-to-hepatitis-c-infection-through-cd72-signal-transduction
#2
Bing Jie Li, Yu He, Ying Zhang, Yong Hong Guo, Yun Zhou, Pei Xin Zhang, Wei Wang, Jie Ru Zhao, Jin Ge Li, Wei Ze Zuo, Chao Fan, Zhan Sheng Jia
Objectives We investigated the effects of CD100 on naïve CD8(+) T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8(+) T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8(+) T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays...
February 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28222098/multicenter-study-of-skin-rashes-and-hepatotoxicity-in-antiretroviral-na%C3%A3-ve-hiv-positive-patients-receiving-non-nucleoside-reverse-transcriptase-inhibitor-plus-nucleoside-reverse-transcriptase-inhibitors-in-taiwan
#3
Pei-Ying Wu, Chien-Yu Cheng, Chun-Eng Liu, Yi-Chien Lee, Chia-Jui Yang, Mao-Song Tsai, Shu-Hsing Cheng, Shih-Ping Lin, De-Yu Lin, Ning-Chi Wang, Yi-Chieh Lee, Hsin-Yun Sun, Hung-Jen Tang, Chien-Ching Hung
OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study...
2017: PloS One
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#4
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28210784/novel-aids-therapies-based-on-gene-editing
#5
REVIEW
Kamel Khalili, Martyn K White, Jeffrey M Jacobson
HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV...
February 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28207896/rna-seq-analysis-of-chikungunya-virus-infection-and-identification-of-granzyme-a-as-a-major-promoter-of-arthritic-inflammation
#6
Jane A C Wilson, Natalie A Prow, Wayne A Schroder, Jonathan J Ellis, Helen E Cumming, Linden J Gearing, Yee Suan Poo, Adam Taylor, Paul J Hertzog, Francesca Di Giallonardo, Linda Hueston, Roger Le Grand, Bing Tang, Thuy T Le, Joy Gardner, Suresh Mahalingam, Pierre Roques, Phillip I Bird, Andreas Suhrbier
: Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28202614/virus-specific-cd8-t-cells-infiltrate-melanoma-lesions-and-retain-function-independently-of-pd-1-expression
#7
Dan A Erkes, Corinne J Smith, Nicole A Wilski, Sofia Caldeira-Dantas, Toktam Mohgbeli, Christopher M Snyder
It is well known that CD8(+) tumor-infiltrating lymphocytes (TILs) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. Although it is generally assumed that CD8(+) TILs will be tumor-associated Ag (TAA) specific, it is unknown whether CD8(+) T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. We compared TAA-specific and virus-specific CD8(+) T cells in the same tumors using murine CMV, a herpesvirus that causes a persistent/latent infection, and vaccinia virus, a poxvirus that is cleared by the host...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28197365/crispr-cas9-mediated-disruption-of-pd-1-on-human-t-cells-for-adoptive-cellular-therapies-of-ebv-positive-gastric-cancer
#8
Shu Su, Zhengyun Zou, Fangjun Chen, Naiqing Ding, Juan Du, Jie Shao, Lin Li, Yao Fu, Bian Hu, Yang Yang, Huizi Sha, Fanyan Meng, Jia Wei, Xingxu Huang, Baorui Liu
The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196487/anti-hsv-2-activity-of-terminalia-chebula-retz-extract-and-its-constituents-chebulagic-and-chebulinic-acids
#9
Ajay Kesharwani, Suja Kizhiyedath Polachira, Reshmi Nair, Aakanksha Agarwal, Nripendra Nath Mishra, Satish Kumar Gupta
BACKGROUND: Development of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV-2) infection is important from public health perspective. With an aim to identify natural products from medicinal plants, in the present study, the potential of Terminalia chebula Retz was investigated for its activity against HSV-2. METHODS: Fruits of Terminalia chebula Retz were used to prepare 50% ethanolic extract. In addition, chebulagic acid and chebulinic acid both purified from T...
February 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28194662/mmtv-pymt-and-derived-met-1-mouse-mammary-tumor-cells-as-models-for-studying-the-role-of-the-androgen-receptor-in-triple-negative-breast-cancer-progression
#10
Jessica L Christenson, Kiel T Butterfield, Nicole S Spoelstra, John D Norris, Jatinder S Josan, Julie A Pollock, Donald P McDonnell, Benita S Katzenellenbogen, John A Katzenellenbogen, Jennifer K Richer
Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study, we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression...
February 13, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28194010/intratumoral-modulation-of-the-inducible-co-stimulator-icos-by-recombinant-oncolytic-virus-promotes-systemic-anti-tumour-immunity
#11
Dmitriy Zamarin, Rikke B Holmgaard, Jacob Ricca, Tamar Plitt, Peter Palese, Padmanee Sharma, Taha Merghoub, Jedd D Wolchok, James P Allison
Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL)...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193996/a-case-report-of-primary-nasal-natural-killer-nk-t-cell-lymphoma-in-an-african-american-patient-presenting-with-hemophagocytic-syndrome
#12
Bowei Tan, Cherif Abdelmalek, James E O'Donnell, Thomas Toltaku, Rashid Chaudhry, Jen C Wang, Vladimir Gotlieb
BACKGROUND Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. CASE REPORT A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1...
February 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#13
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28181540/hiv-related-proteins-prolong-macrophage-survival-through-induction-of-triggering-receptor-expressed-on-myeloid-cells-1
#14
Zhihong Yuan, Xian Fan, Bashar Staitieh, Chetna Bedi, Paul Spearman, David M Guidot, Ruxana T Sadikot
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181505/parp-1-parp-2-double-deficiency-in-mouse-t-cells-results-in-faulty-immune-responses-and-t-lymphomas
#15
Judith Navarro, Beatriz Gozalbo-López, Andrea C Méndez, Françoise Dantzer, Valérie Schreiber, Carlos Martínez, David M Arana, Jordi Farrés, Beatriz Revilla-Nuin, María F Bueno, Coral Ampurdanés, Miguel A Galindo-Campos, Philip A Knobel, Sandra Segura-Bayona, Juan Martin-Caballero, Travis H Stracker, Pedro Aparicio, Margarita Del Val, José Yélamos
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179527/hiv-specific-granzyme-b-but-not-interferon-%C3%AE-secreting-t-cells-are-associated-with-reduced-viral-reservoirs-in-early-hiv-infection
#16
Feng Yun Yue, Jared C Cohen, Mu Ho, A K M Nur-Ur Rahman, Jun Liu, Shariq Mujib, Aamir Saiyed, Sabrina Hundal, Alexandra Khozin, Phil Bonner, Daheng Liu, Erika Benko, Colin Kovacs, Mario Ostrowski
A major barrier to an Human Immunodeficiency Virus Type 1 (HIV) infection cure is the establishment of a viral reservoir despite cART. It is unclear how HIV-specific CTLs influence the size of the reservoir in early HIV infection. 28 subjects with early HIV infection were recruited to receive cART and followed for 48 weeks. HIV reservoirs in peripheral CD4+ T cells measured by cell associated proviral DNA and viral outgrowth cultures were determined at baseline and 48 weeks of cART. At baseline, Granzyme B and IFN-γ ELISpot assays were performed with peptides spanning the HIV proteome...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28178658/prime-boost-immunization-by-both-dna-vaccine-and-oncolytic-adenovirus-expressing-gm-csf-and-shrna-of-tgf-%C3%AE-2-induces-anti-tumor-immune-activation
#17
So Young Kim, Dongxu Kang, Hye Jin Choi, Yeonsoo Joo, Joo-Hang Kim, Jae J Song
A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173821/identification-of-influenza-a-nucleoprotein-body-domain-residues-essential-for-viral-rna-expression-expose-antiviral-target
#18
Alicia M Davis, Jose Ramirez, Laura L Newcomb
BACKGROUND: Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions...
February 7, 2017: Virology Journal
https://www.readbyqxmd.com/read/28170421/comprehensive-mapping-of-antigen-specific-t-cell-responses-in-hepatitis-c-virus-infected-patients-with-or-without-spontaneous-viral-clearance
#19
Chao Zhang, Rui Hua, Yuanyuan Cui, Shasha Wang, Hongqing Yan, Dongmei Li, Yonghong Zhang, Zhengkun Tu, Pei Hao, Xinyue Chen, Jin Zhong, Junqi Niu, Xia Jin
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28169127/th17-treg-imbalance-is-an-indicator-of-liver-cirrhosis-process-and-a-risk-factor-for-hcc-occurrence-in-hbv-patients
#20
Kun Li, Huaie Liu, Tao Guo
OBJECTIVE: To determine the impact of T helper 17 cell (Th17)/regulatory T cell (Treg) ratio imbalance on the process and prognosis of hepatitis B virus (HBV)-related liver cirrhosis. METHODS: Patients with HBV who refused to accept any therapy from were recruited from 2009 to 2014 and followed-up to August 2016. Based on a liver stiffness measurement (LSM), the patients were divided into a low LSM group and a high LSM group. After propensity score matching, 150 patients were included...
February 3, 2017: Clinics and Research in Hepatology and Gastroenterology
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