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https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#1
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432476/immunological-mechanisms-of-adsorptive-cytapheresis-in-inflammatory-bowel-disease
#2
REVIEW
Esteban Sáez-González, Inés Moret, Diego Alvarez-Sotomayor, Francia Carolina Díaz-Jaime, Elena Cerrillo, Marisa Iborra, Pilar Nos, Belén Beltrán
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system...
April 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28432221/biological-considerations-of-plasma-derived-and-recombinant-factor-viii-immunogenicity
#3
Jesse Lai, Christine Hough, Julie Tarrant, David Lillicrap
In hemophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the formation of FVIII neutralizing antibodies, also known as inhibitors, in 25-30% of patients. This adverse event is associated with a significant increase in morbidity and economic burden, thus highlighting the need to identify methods to limit FVIII immunogenicity. Inhibitor development is regulated by a complex balance of genetic factors, such as FVIII genotype, and environmental variables, such as coexistent inflammation...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#4
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#5
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28428210/proton-chemical-shift-imaging-study-of-the-combined-antiretroviral-therapy-impact-on-neurometabolic-parameters-in-chronic-hiv-infection
#6
J Boban, D Kozic, V Turkulov, D Lendak, M Bjelan, M Semnic, S Brkic
BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy-na|fkve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28428185/investments-in-cancer-research-awarded-to-uk-institutions-and-the-global-burden-of-cancer-2000-2013-a-systematic-analysis
#7
Mahiben Maruthappu, Michael G Head, Charlie D Zhou, Barnabas J Gilbert, Majd A El-Harasis, Rosalind Raine, Joseph R Fitchett, Rifat Atun
OBJECTIVES: To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). DESIGN: Systematic analysis of all open-access data. SETTING AND PARTICIPANTS: Public and philanthropic funding to all UK cancer research institutions, 2000-2013...
April 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28428074/melittin-inhibits-tumor-growth-and-decreases-resistance-to-gemcitabine-by-downregulating-cholesterol-pathway-gene-clu-in-pancreatic-ductal-adenocarcinoma
#8
Xinjing Wang, Jing Xie, Xiongxiong Lu, Hongzhe Li, Chenlei Wen, Zhen Huo, Junjie Xie, Minmin Shi, Xiaomei Tang, Hao Chen, Chenghong Peng, Yuan Fang, Xiaxing Deng, Baiyong Shen
Melittin is a Chinese traditional medicine for treating chronic inflammation, immunological diseases and cancers, however, the efficacy of melittin and its mechanism for treating pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here we investigated the anti-cancer activity of melittin and its regulated mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by promoting cell apoptosis and cell-cycle arrest. Interestingly, the microarray analyses demonstrated that melittin significantly regulated cholesterol biosynthesis pathway during treatment...
April 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28428054/modified-nanoparticle-mediated-il-12-immunogene-therapy-for-colon-cancer
#9
Xiaoxiao Liu, Xiang Gao, Songping Zheng, Bilan Wang, Yanyan Li, Chanjuan Zhao, Yagmur Muftuoglu, Song Chen, Ying Li, Haiyan Yao, Hui Sun, Qing Mao, Chao You, Gang Guo, Yuquan Wei
For the past few years, immunotherapy has recently shown considerable clinical benefit in CRC therapy, and the application of immunologic therapies in cancer treatments continues to increase perennially. Interleukin-12, an ideal candidate for tumor immunotherapy, could activate both innate and adaptive immunities. In this study, we developed a novel gene delivery system with a self-assembly method by MPEG-PLA and DOTAP(DMP) with zeta-potential value of 38.5mV and size of 37.5nm. The supernatant of lymphocytes treated with supernatant from Ct26 transfected pIL12 with DMP could inhibit Ct26 cells growth ex vivo...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28426825/levels-of-hiv-1-persistence-on-antiretroviral-therapy-are-not-associated-with-markers-of-inflammation-or-activation
#10
Rajesh T Gandhi, Deborah K McMahon, Ronald J Bosch, Christina M Lalama, Joshua C Cyktor, Bernard J Macatangay, Charles R Rinaldo, Sharon A Riddler, Evelyn Hogg, Catherine Godfrey, Ann C Collier, Joseph J Eron, John W Mellors
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28425263/combination-therapy-with-dendritic-cell-based-vaccine-and-anti-cd69-antibody-enhances-antitumor-efficacy-in-renal-cell-carcinoma-bearing-mice
#11
Si-Ming Wei, Hang-Li Pan, Li Wang, Guo-Li Yin, Kai Zhong, Ya Zhou, Shu-Jiao Yang, Zhao-Liang Xin
BACKGROUND/AIM: Dendritic cell-based vaccine therapy for renal cell carcinoma is effective but requires improvement. Here we explored whether combination therapy with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor efficacy in renal cell carcinoma-bearing mice. MATERIALS AND METHODS: Balb/c mice were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated or were treated with Renca tumor lysate-pulsed dendritic cells (i...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424674/global-fecal-and-plasma-metabolic-dynamics-related-to-helicobacter-pylori-eradication
#12
Theresa Wan-Chen Yap, Alex Hwong-Ruey Leow, Ahmad Najib Azmi, Damien L Callahan, Guillermo I Perez-Perez, Mun-Fai Loke, Khean-Lee Goh, Jamuna Vadivelu
Background:Helicobacter pylori colonizes the gastric mucosa of more than half of the world's population. There is increasing evidence H. pylori protects against the development of obesity and childhood asthma/allergies in which the development of these diseases coincide with transient dysbiosis. However, the mechanism underlying the association of H. pylori eradication with human metabolic and immunological disorders is not well-established. In this study, we aimed to investigate the local and systemic effects of H...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28424453/comorbid-human-immunodeficiency-virus-hiv-and-muscle-specific-kinase-musk-myasthenia-gravis-a-case-report-and-literature-review
#13
Michael Sherpa, Ravi K Metai, Viki Kumar, Tinu Hirachan, Kawser U Ahmed, Sharon J Atkinson
BACKGROUND HIV infections with concomitant immunologically-mediated disorders have been frequently described but there has been little research on the association between HIV and myasthenia gravis. MuSK myasthenia gravis coexisting with HIV is an even a rarer entity and can occur as a part of immune restoration disease. We report the case of a patient with asymptomatic HIV infection who presented with new-onset MuSK myasthenia gravis. CASE REPORT A 44-year-old African-American woman with HIV since 2004 and on highly active antiretroviral therapy (HAART) presented to the ED with complains of double vision and difficulty swallowing for 2 weeks...
April 20, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28424287/protective-efficacy-of-formaldehyde-inactivated-whole-virus-vaccine-and-antivirals-in-a-murine-model-of-coxsackievirus-a10-infection
#14
Zhenjie Zhang, Zhaopeng Dong, Juan Li, Michael J Carr, Dongming Zhuang, Jianxing Wang, Yawei Zhang, Shujun Ding, Yigang Tong, Dong Li, Weifeng Shi
Coxsackievirus A10 (CVA10) is one of the major pathogens associated with hand, foot and mouth disease (HFMD). CVA10 infection can cause herpangina and viral pneumonia, which can be complicated by severe neurological sequelae. Morbidity and mortality of CVA10-associated HFMD has been increasing in recent years, particularly in the pan-Pacific region. There are limited studies however on the pathogenesis and immunology of CVA10-associated HFMD infections, and few antiviral drugs or vaccines have been reported...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28421634/vagus-nerve-stimulation-a-new-promising-therapeutic-tool-in-inflammatory-bowel-disease
#15
B Bonaz, V Sinniger, S Pellissier
Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe. The pathophysiology of IBD involves immunological, genetic and environmental factors. The treatment is medico-surgical but suspensive. Anti-TNFα agents have revolutionized the treatment of IBD but have side effects. In addition, a non-negligible percentage of patients with IBD stop or take episodically their treatment. Consequently, a nondrug therapy targeting TNFα through a physiological pathway, devoid of major side effects and with a good cost-effectiveness ratio, would be of interest...
April 18, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28421005/autoimmune-aspects-of-neurodegenerative-and-psychiatric-diseases-a-template-for-innovative-therapy
#16
REVIEW
Peter de Haan, Hans C Klein, Bert A 't Hart
Neurodegenerative and psychiatric diseases (NPDs) are today's most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe debilitating character, remarkably few effective interventions have become available. The current treatments, if available, comprise the lifelong intake of general immunosuppressants to delay disease progression or neurotransmitter antagonists/agonists to dampen undesired behaviors...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28417469/oesophageal-involvement-in-26-consecutive-patients-with-mucous-membrane-pemphigoid
#17
O Zehou, J-J Raynaud, C Le Roux-Villet, M Alexandre, G Airinei, F Pascal, M Heller, N Lièvre, L Laroche, F Caux, R Benamouzig, C Prost-Squarcioni
BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not yet been thoroughly described. OBJECTIVES: This study was undertaken to systematically characterise the endoscopic lesions of a series of patients with oesophageal symptoms seen in a referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic and immunological findings of consecutively referred MMP patients with oesophageal involvement, systemic and endoscopic treatments and follow-up, are described...
April 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28416698/selective-in-vivo-removal-of-pathogenic-anti-mag-autoantibodies-an-antigen-specific-treatment-option-for-anti-mag-neuropathy
#18
Ruben Herrendorff, Pascal Hänggi, Hélène Pfister, Fan Yang, Delphine Demeestere, Fabienne Hunziker, Samuel Frey, Nicole Schaeren-Wiemers, Andreas J Steck, Beat Ernst
Anti-MAG (myelin-associated glycoprotein) neuropathy is a disabling autoimmune peripheral neuropathy caused by monoclonal IgM autoantibodies that recognize the carbohydrate epitope HNK-1 (human natural killer-1). This glycoepitope is highly expressed on adhesion molecules, such as MAG, present in myelinated nerve fibers. Because the pathogenicity and demyelinating properties of anti-MAG autoantibodies are well established, current treatments are aimed at reducing autoantibody levels. However, current therapies are primarily immunosuppressive and lack selectivity and efficacy...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416614/modeling-combined-immunosuppressive-and-anti-inflammatory-effects-of-dexamethasone-and-naproxen-in-rats-predicts-the-steroid-sparing-potential-of-naproxen
#19
Xiaonan Li, Debra C DuBois, Dawei Song, Richard R Almon, William J Jusko, Xijing Chen
Dexamethasone (DEX), a widely prescribed corticosteroid (CS), has long been the cornerstone for the treatment of inflammation and immunological dysfunctions in Rheumatoid Arthritis (RA). The CS are frequently used in combination with other anti-rheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) to mitigate disease symptoms and minimize unwanted effects. The steroid dose-sparing potential of the NSAID naproxen (NPX) was explored with in vitro and in vivo studies...
April 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28416454/e1a-is-an-exogenous-in-vivo-tumour-suppressor
#20
F J Cimas, J L Callejas-Valera, D C García-Olmo, J Hernández-Losa, P Melgar-Rojas, M J Ruiz-Hidalgo, R Pascual-Serra, M Ortega-Muelas, O Roche, P Marcos, E Garcia-Gil, D M Fernandez-Aroca, S Ramón Y Cajal, J S Gutkind, R Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent)...
April 14, 2017: Cancer Letters
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