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https://www.readbyqxmd.com/read/29673141/subunit-specific-role-of-nf-%C3%AE%C2%BAb-in-cancer
#1
REVIEW
Barbara Kaltschmidt, Johannes F W Greiner, Hussamadin M Kadhim, Christian Kaltschmidt
The transcription factor NF-κB is a key player in inflammation, cancer development, and progression. NF-κB stimulates cell proliferation, prevents apoptosis, and could promote tumor angiogenesis as well as metastasis. Extending the commonly accepted role of NF-κB in cancer formation and progression, different NF-κB subunits have been shown to be active and of particular importance in distinct types of cancer. Here, we summarize overexpression data of the NF-κB subunits RELA, RELB, and c-REL (referring to the v-REL, which is the oncogene of Reticuloendotheliosis virus strain T) as well as of their upstream kinase inhibitor, namely inhibitor of κB kinases (IKK), in different human cancers, assessed by database mining...
April 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29672576/malnutrition-and-lipid-abnormalities-in-antiretroviral-na%C3%A3-ve-hiv-infected-adults-in-addis-ababa-a-cross-sectional-study
#2
Melaku Adal, Rawleigh Howe, Desta Kassa, Abraham Aseffa, Beyene Petros
BACKGROUND: Both under- and over-nutrition may occur among human immunodeficiency virus (HIV)-infected individuals and impact on the course of the acquired immune deficiency syndrome (AIDS) and its management due to the close interaction between immunity and nutrition. We investigated occurrence of undernutrition, excess weight and lipid abnormalities among antiretroviral naïve HIV-infected adults in Addis Ababa, Ethiopia. METHODS: A cross-sectional study on 594 antiretroviral therapy (ART) naïve HIV-infected adults was conducted in four hospitals in Addis Ababa from February to September 2013...
2018: PloS One
https://www.readbyqxmd.com/read/29671786/hiv-vaccination-a-roadmap-among-advancements-and-concerns
#3
REVIEW
Maria Trovato, Luciana D'Apice, Antonella Prisco, Piergiuseppe De Berardinis
Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been made to stop the AIDS pandemic. A major success of medical research has been the development of the highly active antiretroviral therapy and its availability to an increasing number of people worldwide, with a considerable effect on survival. However, a safe and effective vaccine able to prevent and eradicate the HIV pandemic is still lacking...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670617/restoration-of-decreased-t-helper-1-and-cd8-t-cell-subsets-is-associated-with-regression-of-lymphoproliferative-disorders-developed-during-methotrexate-treatment
#4
Shuntaro Saito, Katsuya Suzuki, Keiko Yoshimoto, Yuko Kaneko, Kunihiro Yamaoka, Takayuki Shimizu, Takehiko Mori, Shinichiro Okamoto, Kaori Kameyama, Koichi Amano, Jun-Ichi Tamaru, Michihide Tokuhira, Tsutomu Takeuchi
Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration ( n  = 35) and clinically matched controls ( n  = 35)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669885/the-heteroaryldihydropyrimidine-bay-38-7690-induces-hepatitis-b-virus-core-protein-aggregates-associated-with-promyelocytic-leukemia-nuclear-bodies-in-infected-cells
#5
Andrew D Huber, Jennifer J Wolf, Dandan Liu, Anna T Gres, Jing Tang, Kelsey N Boschert, Maritza N Puray-Chavez, Dallas L Pineda, Thomas G Laughlin, Emily M Coonrod, Qiongying Yang, Juan Ji, Karen A Kirby, Zhengqiang Wang, Stefan G Sarafianos
Heteroaryldihydropyrimidines (HAPs) are compounds that inhibit hepatitis B virus (HBV) replication by modulating viral capsid assembly. While their biophysical effects on capsid assembly in vitro have been previously studied, the effect of HAP treatment on capsid protein (Cp) in individual HBV-infected cells remains unknown. We report here that the HAP Bay 38-7690 promotes aggregation of recombinant Cp in vitro and causes a time- and dose-dependent decrease of Cp in infected cells, consistent with previously studied HAPs...
April 25, 2018: MSphere
https://www.readbyqxmd.com/read/29669806/targeting-merkel-cell-carcinoma-by-engineered-t-cells-specific-to-t-antigens-of-merkel-cell-polyomavirus
#6
Ioannis Gavvovidis, Matthias Leisegang, Gerald Willimsky, Natalie J Miller, Paul Nghiem, Thomas Blankenstein
PURPOSE: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials...
April 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29668327/assessment-of-humoral-innate-and-t-cell-immune-responses-to-adeno-associated-virus-vectors
#7
Roberto Calcedo, Jessica A Chichester, James M Wilson
Adeno-associated virus (AAV)-based gene therapy is being applied to treat a wide array of diseases. Preexisting host immune responses to AAV and immune responses elicited by AAV vector administration remain a problem that needs to be further studied. Here we present a series of protocols to assess immune responses before and after AAV vector administration that are applicable to multiple animal models and phase 1 clinical trials. More specifically, they may be use to evaluate (1) the humoral immune response, through levels of AAV-neutralizing and binding antibodies; (2) the innate immune response, through the acute induction of inflammatory cytokines; and (3) the T-cell immune response, through the activation of transgene- and vector-specific CD8+ and CD4+ T cells...
April 2018: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29664712/chemokine-receptor-5-has-no-major-role-in-the-severity-of-hepatitis-c-virus-related-liver-damage
#8
Giuseppe Colucci, Roberta D'Ambrosio, Enrico Galmozzi, Marco Maggioni, Stella De Nicola, Alessio Aghemo, Massimo Colombo
Total or partial inactivation of the chemokine 5 (CC5) pathway, as caused by the CC5 receptor Δ32 deletion (CCR5Δ32), may result in a profound manipulation of immune surveillance with significant consequences on the course and response to therapy of diverse human infections, including HIV. It has been postulated that in chronic hepatitis C (CHC), such a deregulation of CC5 pathway may compromise T cell-dependent antiviral immune responses, which in turn may favor viral persistence. To test this hypothesis, we investigated a cohort of 100 patients with CHC in whom 12 heterozygous and 1 homozygous CCR5Δ32 mutations were detected compared to 8 and none in 98 healthy controls (13% vs...
April 17, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29661424/intravenous-immunoglobulin-and-rituximab-in-hla-highly-sensitized-kidney-transplant-recipients
#9
S Querido, A Weigert, T Adragão, J Henriques, R Birne, P Matias, C Jorge, C Nascimento, M Bruges, D Machado
INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney transplantation (KT) and, once transplanted, in the incidence of rejections and long-term allograft survival despite aggressive induction and maintenance therapy. METHODS: This study retrospectively evaluates the impact of combining T- and B-cell-depleting agents and intravenous immunoglobulin for induction therapy in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%, positive flow cytometry crossmatch or donor specific antibodies at the time of transplantation)...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29652795/counteracting-akt-activation-by-hiv-protease-inhibitors-in-monocytes-macrophages
#10
Sébastien Pasquereau, Amit Kumar, Wasim Abbas, Georges Herbein
Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells...
April 13, 2018: Viruses
https://www.readbyqxmd.com/read/29650491/fecal-microbiota-composition-drives-immune-activation-in-hiv-infected-individuals
#11
Charles Preston Neff, Owen Krueger, Kathy Xiong, Sabrina Arif, Nichole Nusbacher, Jennifer M Schneider, Annie W Cunningham, Abigail Armstrong, Sam Li, Martin D McCarter, Thomas B Campbell, Catherine A Lozupone, Brent E Palmer
The inflammatory properties of the enteric microbiota of Human Immunodeficiency Virus (HIV)-infected individuals are of considerable interest because of strong evidence that bacterial translocation contributes to chronic immune activation and disease progression. Altered enteric microbiota composition occurs with HIV infection but whether altered microbiota composition or increased intestinal permeability alone drives peripheral immune activation is controversial. To comprehensively assess the inflammatory properties of HIV-associated enteric microbiota and relate these to systemic immune activation, we developed methods to purify whole fecal bacterial communities (FBCs) from stool for use in in vitro immune stimulation assays with human cells...
March 26, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29649077/circulating-cxcr5-expressing-cd8-t-cells-are-major-producers-of-il-21-and-associate-with-limited-hiv-replication
#12
Federico Perdomo-Celis, Natalia A Taborda, Maria T Rugeles
BACKGROUND: Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29644994/autoimmune-hepatitis
#13
REVIEW
Giorgina Mieli-Vergani, Diego Vergani, Albert J Czaja, Michael P Manns, Edward L Krawitt, John M Vierling, Ansgar W Lohse, Aldo J Montano-Loza
Autoimmune hepatitis (AIH) is a severe liver disease that affects children and adults worldwide. The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology. AIH arises in genetically predisposed individuals when a trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune response directed against liver autoantigens; this immune response is permitted by inadequate regulatory immune control leading to a loss of tolerance...
April 12, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29643841/mouse-models-that-enhanced-our-understanding-of-adult-t-cell-leukemia
#14
REVIEW
Sara Moodad, Abdou Akkouche, Rita Hleihel, Nadine Darwiche, Marwan El-Sabban, Ali Bazarbachi, Hiba El Hajj
Adult T cell Leukemia (ATL) is an aggressive lymphoproliferative malignancy secondary to infection by the human T-cell leukemia virus type I (HTLV-I) and is associated with a dismal prognosis. ATL leukemogenesis remains enigmatic. In the era of precision medicine in oncology, mouse models offer one of the most efficient in vivo tools for the understanding of the disease biology and developing novel targeted therapies. This review provides an up-to-date and comprehensive account of mouse models developed in the context of ATL and HTLV-I infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29643247/the-pathway-to-establishing-hiv-latency-is-critical-to-how-latency-is-maintained-and-reversed
#15
Simin D Rezaei, Hao K Lu, J Judy Chang, Ajantha Rhodes, Sharon R Lewin, Paul U Cameron
HIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4+ T cells. Induction of viral expression from latently infected cells occurs following T cell receptor (TCR) activation but not all latently infected cells respond to TCR stimulation. We compared two models of latently infected cells using an enhanced green fluorescent protein (EGFP) reporter virus to infect CCL19 treated resting CD4+ (rCD4) T cells (pre-activation latency) or activated CD4+ T cells that returned to a resting state (post-activation latency)...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643243/inefficient-hiv-1-trans-infection-of-cd4-t-cells-by-macrophages-from-hiv-1-nonprogressors-is-associated-with-altered-membrane-cholesterol-and-dc-sign
#16
Diana C DeLucia, Charles R Rinaldo, Giovanna Rappocciolo
Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29621877/the-prognostic-role-of-circulating-epstein-barr-virus-dna-copy-number-in-angioimmunoblastic-t-cell-lymphoma-treated-with-dose-adjusted-epoch
#17
Jin-Hua Liang, Luo Lu, Hua-Yuan Zhu, Wang Li, Lei Fan, Jian-Yong Li, Wei Xu
Purpose: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. Materials and Methods: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. Results: Twenty-two subjects (36...
April 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29620933/dynamics-of-lymphocyte-reconstitution-following-hematopoietic-transplantation-during-chronic-lcmv-infection
#18
Mitra Bhattacharyya, Pablo Penaloza-MacMaster
Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of cured a HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus (LCMV), and performed bone marrow transplantation to assess lymphocyte reconstitution...
March 18, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29619416/early-and-late-changes-in-natural-killer-cells-in-response-to-ledipasvir-sofosbuvir-treatment
#19
Lucy Golden-Mason, Rachel H McMahan, Michael S Kriss, Alexandra L Kilgore, Linling Cheng, Rachael J Dran, Amanda Wieland, Hugo R Rosen
Chronic hepatitis C virus (HCV) infection is characterized by dysregulated natural killer (NK) cell responses. NKs play a critical role in achieving sustained responses to interferon (IFN)-α-based therapy. Rapid sustained HCV-RNA clearance is now achieved with direct-acting antivirals (DAAs). Studies of patients receiving first-wave DAAs suggest NK functional restoration. Here, we investigate the effect of mainstream DAA treatment on NKs. We collected a prospective cohort of male HCV genotype 1-infected patients treated with ledipasvir/sofosbuvir (n = 22)...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29618655/il-27-gene-therapy-induces-depletion-of-tregs-and-enhances-the-efficacy-of-cancer-immunotherapy
#20
Jianmin Zhu, Jin-Qing Liu, Min Shi, Xinhua Cheng, Miao Ding, Jianchao C Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Lanchun Lu, Xueliang Pan, Pan Zheng, Yang Liu, Xue-Feng Bai
Tumor-induced expansion of Tregs is a significant obstacle to cancer immunotherapy. However, traditional approaches to deplete Tregs are often inefficient, provoking autoimmunity. We show here that administration of IL-27-expressing recombinant adeno-associated virus (AAV-IL-27) significantly inhibits tumor growth and enhances T cell responses in tumors. Strikingly, we found that AAV-IL-27 treatment causes rapid depletion of Tregs in peripheral blood, lymphoid organs, and - most pronouncedly - tumor microenvironment...
April 5, 2018: JCI Insight
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