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https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#1
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#2
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777913/the-tp53-induced-glycolysis-and-apoptosis-regulator-mediates-cooperation-between-htlv-1-p30-ii-and-the-retroviral-oncoproteins-tax-and-hbz-and-is-highly-expressed-in-an-in-vivo-xenograft-model-of-htlv-1-induced-lymphoma
#3
Tetiana Hutchison, Aditi Malu, Laçin Yapindi, Rachel Bergeson, Kendra Peck, Megan Romeo, Carolyn Harrod, Jordan Pope, Louisa Smitherman, Wesleigh Gwinn, Lee Ratner, Courtney Yates, Robert Harrod
The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ...
May 16, 2018: Virology
https://www.readbyqxmd.com/read/29777728/testosterone-induced-downregulation-of-migration-and-proliferation-in-human-umbilical-vein-endothelial-cells-by-androgen-receptor-dependent-and-independent-mechanisms
#4
Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova
Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools...
May 16, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29777573/quantiferon-cytomegalovirus-assay-a-potentially-useful-tool-in-the-evaluation-of-cmv-specific-cd8-t-cell-reconstitution-in-pediatric-hematopoietic-stem-cell-transplant-patients
#5
Bilio Paouri, Alexandra Soldatou, Eftihia Petrakou, Maria Theodosaki, Charalampos Tsentidis, Katerina Kaisari, Christina Oikonomopoulou, Minos Matsas, Eugenios Goussetis
Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV-specific T-cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV-specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon-CMV (QIAGEN® ) test was investigated prospectively. Thirty-seven pediatric allogeneic HSCT recipients were enrolled from 3/2010-6/2012. CMV viremia was detected via weekly real-time PCR...
May 18, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29777228/effects-of-clomiphene-citrate-on-male-obesity-associated-hypogonadism-a-randomized-double-blind-placebo-controlled-study
#6
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, Bruno Caramelli, Mariana Gomes Matheus, Alexandre Holthausen Campos, Luciana Cavalheiro Marti, Fernanda Agostini Rocha, Marcio C Mancini, Elaine Maria Frade Costa, Cintia Cercato
BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7...
May 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29777119/changes-in-t-cell-effector-functions-over-an-8-year-period-with-tnf-antagonists-in-patients-with-chronic-inflammatory-rheumatic-diseases
#7
Ilaria Sauzullo, Rossana Scrivo, Paola Sessa, Fabio Mengoni, Vincenzo Vullo, Guido Valesini, Claudio Maria Mastroianni
The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#8
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29776594/gearing-up-t-cell-immunotherapy-in-cervical-cancer
#9
REVIEW
Shilpa Raghuvanshi Chauhan, Mausumi Bharadwaj
The World Health Organization estimates more than 270,000 deaths annually by cervical cancer. Present vaccines are prophylactic in nature which cannot treat huge bulk of cervical cancer patients worldwide. Available therapies like radiotherapy, chemotherapy, or surgery are not effective in high-grade lesion, and hence, there is an unmet medical need for an effective form of therapy. T cells play a significant role in cervical cancer pathogenesis as human papilloma virus uses multiple mechanisms that dodge host T-cell immune-surveillance aiding in persistence of infection and establishment of cancer...
April 22, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#10
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#11
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29775441/-the-biological-function-and-significance-of-il-35-in-the-pathogenesis-of-atherosclerosis
#12
EDITORIAL
Mateusz Staciwa, Marlena Broncel
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29775163/methylprednisolone-inhibits-the-proliferation-of-endogenous-neural-stem-cells-in-nonhuman-primates-with-spinal-cord-injury
#13
Jichao Ye, Yi Qin, Yong Tang, Mengjun Ma, Peng Wang, Lin Huang, Rui Yang, Keng Chen, Chaopeng Chai, Yanfeng Wu, Huiyong Shen
OBJECTIVE The aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (ENSCs) in nonhuman primates with spinal cord injury (SCI). METHODS A total of 14 healthy cynomolgus monkeys ( Macaca fascicularis) (4-5 years of age) were randomly divided into 3 groups: the control group (n = 6), SCI group (n = 6), and methylprednisolone therapy group (n = 2). Only laminectomy was performed in the control animals at T-10. SCI was induced in monkeys using Allen's weight-drop method (50 mm × 50 g) to injure the posterior portion of the spinal cord at T-10...
May 18, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#14
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29774168/evaluating-the-potential-for-maximized-t-cell-redistribution-entropy-to-improve-abscopal-responses-to-radiotherapy
#15
Rachel Walker, Jonathan D Schoenfeld, Shari Pilon-Thomas, Jan Poleszczuk, Heiko Enderling
The potential for local radiation therapy to elicit systemic (abscopal) anti-tumor immune responses has been receiving a significant amount of attention over the last decade. We recently developed a mathematical framework designed to simulate the systemic dissemination of activated T cells among multiple metastatic sites. This framework allowed the identification of non-intuitive patterns of T cell redistribution after localized therapy, and offered suggestions as to the optimal site to irradiate in order to increase the magnitude of an immune-mediated abscopal response...
September 2017: Convergent Science Physical Oncology
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#16
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774027/clinical-remission-of-sight-threatening-non-infectious-uveitis-is-characterized-by-an-upregulation-of-peripheral-t-regulatory-cell-polarized-towards-t-bet-and-tigit
#17
Rose M Gilbert, Xiaozhe Zhang, Robert D Sampson, Michael R Ehrenstein, Dao X Nguyen, Mahid Chaudhry, Charles Mein, Nadiya Mahmud, Grazyna Galatowicz, Oren Tomkins-Netzer, Virginia L Calder, Sue Lightman
Background: Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+ CD25+ FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#18
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773592/investigating-chemoresistance-to-improve-sensitivity-of-childhood-t-cell-acute-lymphoblastic-leukemia-to-parthenolide
#19
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773281/-cutaneous-and-systemic-t-cell-lymphoma-treated-with-haploidentical-bone-marrow-transplantation
#20
M Méchineaud, M Mercier, Y Le Corre, A Croué, N Ifrah, L Martin
BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma...
May 14, 2018: Annales de Dermatologie et de Vénéréologie
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