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https://www.readbyqxmd.com/read/28350860/uniquely-altered-transcripts-are-associated-with-immune-preservation-in-hiv-infection
#1
Michelle Zanoni, Ítalo Karmann Aventurato, James Hunter, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28350802/impact-of-lopinavir-ritonavir-exposure-in-hiv-1-infected-children-and-adolescents-in-madrid-spain-during-2000-2014
#2
Patricia Rojas Sánchez, Luis Prieto, Santiago Jiménez De Ory, Elisa Fernández Cooke, Maria Luisa Navarro, José Tomas Ramos, África Holguín
BACKGROUND: The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain. METHODOLOGY: Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28350664/human-adipose-derived-stem-cells-labeled-with-plasmonic-gold-nanostars-for-cellular-tracking-and-photothermal-cancer-cell-ablation
#3
Ronnie L Shammas, Andrew M Fales, Bridget M Crawford, Amy J Wisdom, Gayathri R Devi, David A Brown, Tuan Vo-Dinh, Scott T Hollenbeck
BACKGROUND: Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics. METHODS: To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy...
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28350521/clinical-activity-of-the-%C3%AE-secretase-inhibitor-pf-03084014-in-adults-with-desmoid-tumors-aggressive-fibromatosis
#4
Shivaani Kummar, Geraldine O'Sullivan Coyne, Khanh T Do, Baris Turkbey, Paul S Meltzer, Eric Polley, Peter L Choyke, Robert Meehan, Rasa Vilimas, Yvonne Horneffer, Lamin Juwara, Ann Lih, Amul Choudhary, Sandra A Mitchell, Lee J Helman, James H Doroshow, Alice P Chen
Purpose Desmoid tumors (aggressive fibromatosis) arise from connective tissue cells or fibroblasts. In general, they are slow growing and do not metastasize; however, locally aggressive desmoid tumors can cause severe morbidity and loss of function. Disease recurrence after surgery and/or radiation and diagnosis of multifocal desmoid tumors highlight the need to develop effective systemic treatments for this disease. In this study, we evaluate objective response rate after therapy with the γ-secretase inhibitor PF-03084014 in patients with recurrent, refractory, progressive desmoid tumors...
March 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28350440/identification-of-trypanosoma-brucei-adometdc-inhibitors-using-a-high-throughput-mass-spectrometry-based-assay
#5
Oleg A Volkov, Casey C Cosner, Anthony J Brockway, Martin Kramer, Michael Booker, Shihua Zhong, Ariel Ketcherside, Shuguang Wei, Jamie Longgood, Melissa K McCoy, Thomas E Richardson, Stephen A Wring, Michael Peel, Jeffrey D Klinger, Bruce A Posner, Jef K De Brabander, Margaret A Phillips
Human African trypanosomiasis (HAT) is a fatal infectious disease caused by the eukaryotic pathogen Trypanosoma brucei. Available treatments are difficult to administer and have significant safety issues. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the parasite polyamine biosynthetic pathway. Previous attempts to develop TbAdoMetDC inhibitors into anti-HAT therapies failed due to poor brain exposure. Here, we describe a large screening campaign of two small-molecule libraries (~400,000 compounds) employing a new high-throughput (~7 s per sample) mass spectrometry-based assay for AdoMetDC activity...
March 28, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28346697/car-t-cell-therapy-for-pancreatic-cancer
#6
REVIEW
Carl J DeSelm, Zachary E Tano, Anna M Varghese, Prasad S Adusumilli
Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a patient's own T cells to target cancer cells. The remarkable results in hematological malignancies prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#7
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28346521/hiv-1-gp120-envelope-glycoprotein-determinants-for-cytokine-burst-in-human-monocytes
#8
Benoît Levast, Lucie Barblu, Mathieu Coutu, Jérémie Prévost, Nathalie Brassard, Adam Peres, Camille Stegen, Joaquín Madrenas, Daniel E Kaufmann, Andrés Finzi
The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28346506/specific-expression-of-novel-long-non-coding-rnas-in-high-hyperdiploid-childhood-acute-lymphoblastic-leukemia
#9
Mathieu Lajoie, Simon Drouin, Maxime Caron, Pascal St-Onge, Manon Ouimet, Romain Gioia, Marie-Hélène Lafond, Ramon Vidal, Chantal Richer, Karim Oualkacha, Arnaud Droit, Daniel Sinnett
Pre-B cell childhood acute lymphoblastic leukemia (pre-B cALL) is a heterogeneous disease involving many subtypes typically stratified using a combination of cytogenetic and molecular-based assays. These methods, although widely used, rely on the presence of known chromosomal translocations, which is a limiting factor. There is therefore a need for robust, sensitive, and specific molecular biomarkers unaffected by such limitations that would allow better risk stratification and consequently better clinical outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28346490/effect-of-hiv-and-malaria-parasites-co-infection-on-immune-hematological-profiles-among-patients-attending-anti-retroviral-treatment-art-clinic-in-infectious-disease-hospital-kano-nigeria
#10
Feyisayo Ebenezer Jegede, Tinuade Ibijoke Oyeyi, Surajudeen Abiola Abdulrahman, Henry Akwen Mbah, Titilope Badru, Chinedu Agbakwuru, Oluwasanmi Adedokun
BACKGROUND: Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria. OBJECTIVE: To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement. METHODS: This was a cross sectional study conducted at Infectious Disease Hospital, Kano...
2017: PloS One
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#11
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#12
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346427/mir-21-is-required-for-anti-tumor-immune-response-in-mice-an-implication-for-its-bi-directional-roles
#13
W He, C Wang, R Mu, P Liang, Z Huang, J Zhang, L Dong
Here we show that miR-21, a microRNA known for its oncogenic activity, is also essential for mediating immune responses against tumor. Knockout of miR-21 in mice slowed the proliferation of both CD4(+) and CD8(+) cells, reduced their cytokine production and accelerated the grafted tumor growth. Further investigations indicated that miR-21 could activate CD4(+) and CD8(+) T cells via the PTEN/Akt pathway in response to stimulations. Taken together, these data suggest the key functions of miR-21 in mediating anti-tumor immune response and thereby uncover a bi-directional role of this traditionally known 'oncomiR' in tumorigenesis...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#14
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28346317/the-csf-immune-response-in-hiv-1-associated-cryptococcal-meningitis-macrophage-activation-correlates-of-disease-severity-and-effect-of-antiretroviral-therapy
#15
James E Scriven, Lisa M Graham, Charlotte Schutz, Thomas J Scriba, Katalin A Wilkinson, Robert J Wilkinson, David R Boulware, Britta C Urban, Graeme Meintjes, David G Lalloo
BACKGROUND: Immune modulation may improve outcome in HIV-associated cryptococcal meningitis. Animal studies suggest alternatively activated macrophages are detrimental but human studies are limited. We performed a detailed assessment of the cerebrospinal fluid (CSF) immune response and examined immune correlates of disease severity and poor outcome, and the effects of antiretroviral therapy (ART). METHODOLOGY: We enrolled persons ≥18 years with first episode of HIV-associated cryptococcal meningitis...
March 24, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#16
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345379/the-role-of-%C3%AE-%C3%AE-t-cells-in-pancreatic-cancer-what-could-this-mean-for-the-clinic
#17
Donnele Daley, George Miller
Pancreatic cancer is a devastating disease where the 5-year survival is less that 10%. Recent studies have shown that ?? T cells are a dominant lymphocyte subset in pancreatic cancer and they promote the progression of the disease. With the emerging use of T cell- based therapy for cancer, ?? T cells are an attractive target for novel immunotherapy in pancreatic cancer.
March 26, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#18
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#19
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28345022/ex%C3%A2-vivo-oncolytic-virotherapy-with-myxoma-virus-arms-multiple-allogeneic-bone-marrow-transplant-leukocytes-to-enhance-graft-versus-tumor
#20
Cameron L Lilly, Nancy Y Villa, Ana Lemos de Matos, Haider M Ali, Jess-Karan S Dhillon, Tom Hofland, Masmudur M Rahman, Winnie Chan, Bjarne Bogen, Christopher Cogle, Grant McFadden
Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice using an allogeneic mouse-mouse model...
March 17, 2017: Molecular Therapy Oncolytics
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