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https://www.readbyqxmd.com/read/27913982/pharmacological-management-of-allergic-rhinitis-in-the-elderly
#1
REVIEW
Andrzej Bozek
Recent studies suggest that allergic rhinitis is highly prevalent in the elderly population, but is underdiagnosed and undertreated. This review article briefly introduces allergic rhinitis in the elderly (epidemiology and pathophysiology) and identifies the main goals of treatment in these patients with respect to age-related physiological factors, comorbid conditions and polypharmacy. The primary focus of the article is a narrative review of the literature concerning the different types of treatment options in elderly patients aged 60+ years (pharmacological therapy and allergen-specific immunotherapy)...
December 3, 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#2
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#3
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#4
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911948/tlr3-induced-maturation-of-murine-dendritic-cells-regulates-ctl-responses-by-modulating-pd-l1-trafficking
#5
Aditi Varthaman, Hélène D Moreau, Mathieu Maurin, Philippe Benaroch
Targeting TLR3 through formulations of polyI:C is widely studied as an adjuvant in cancer immunotherapy. The efficacy of such targeting has been shown to increase in combination with anti-PD-L1 treatment. Nevertheless, the mechanistic details of the effect of polyI:C on DC maturation and the impact on T-DC interactions upon PD-L1 blockade is largely unknown. Here we found that although DC treatment with polyI:C induced a potent inflammatory response including the production of type I interferon, polyI:C treatment of DCs impaired activation of peptide specific CD8+ T cells mainly due to PD-L1...
2016: PloS One
https://www.readbyqxmd.com/read/27911793/heterogeneous-yet-stable-v%C3%AE-2-t-cell-profiles-define-distinct-cytotoxic-effector-potentials-in-healthy-human-individuals
#6
Paul L Ryan, Nital Sumaria, Christopher J Holland, Claire M Bradford, Natalia Izotova, Capucine L Grandjean, Ali S Jawad, Lesley A Bergmeier, Daniel J Pennington
Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2((+))], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2((+)) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2((+)) T-cell biology...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#7
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#8
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#9
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#10
Hee Dong Han, Yeongseon Byeon, Jong-Hwa Jang, Hat Nim Jeon, Ga Hee Kim, Min Gi Kim, Chan-Gi Pack, Tae Heung Kang, In Duk Jung, Yong Taik Lim, Young Joo Lee, Jeong-Won Lee, Byung Cheol Shin, Hyung Jun Ahn, Anil K Sood, Yeong-Min Park
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#11
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27907966/getting-rid-of-weakness-in-the-icu-an-updated-approach-to-the-acute-management-of-myasthenia-gravis-and-guillain-barr%C3%A3-syndrome
#12
Alexis A Lizarraga, Karlo J Lizarraga, Michael Benatar
After prompt diagnosis, severe myasthenia gravis and Guillain-Barré syndrome (GBS) usually require management in the intensive care unit. In the myasthenic patient, recognition of precipitating factors is paramount, and frequent monitoring of bulbar, upper airway, and/or respiratory muscle strength is needed to identify impending myasthenic crisis. Noninvasive ventilation can be attempted prior to intubation and mechanical ventilation in the setting of respiratory failure. Cholinesterase inhibitors should be discontinued, but resumed prior to extubation, and steroid dosage could be increased once the airway is secured...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27905089/novel-paradigm-for-immunotherapy-of-ovarian-cancer-by-engaging-prophylactic-immunity-against-hepatitis-b-virus
#13
Marek Malecki, Emily Putzer, Caroline Quach, Chaitanya Dodivenaka, Xenia Tombokan
BACKGROUND: Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27904700/detection-of-gene-copy-number-alterations-in-dcis-and-invasive-breast-cancer-by-qm-fish
#14
Aifeng Pan, Yawei Zhou, Kun Mu, Yansong Liu, Feifei Sun, Peng Li, Li Li
The exact roles of copy number alteration (CNA) in initiation, progression and immunotherapy of breast cancer and the genomic alterations behind progression from ductal carcinoma in situ (DCIS) to invasive carcinoma remain unknown. Quantitative multi-gene fluorescence in situ hybridization (QM-FISH) opens a possibility of large scale genomic analysis of specific deletions and amplifications with high-resolution at one cell level. We detected CNAs of 30 genes using QM-FISH and analyzed their association with clinicopathological parameters and patients' outcomes in 66 breast cancers with synchronous invasive carcinoma and DCIS...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903969/targeting-tissue-factor-as-a-novel-therapeutic-oncotarget-for-eradication-of-cancer-stem-cells-isolated-from-tumor-cell-lines-tumor-xenografts-and-patients-of-breast-lung-and-ovarian-cancer
#15
Zhiwei Hu, Jie Xu, Jijun Cheng, Elizabeth McMichael, Lianbo Yu, William E Carson Iii
Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#16
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903432/antigen-presentation-for-priming-t-cellsin-central-system
#17
Shaoni Dasgupta, Subhajit Dasgupta
Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system...
November 26, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27902978/the-efficacy-of-sublingual-immunotherapy-for-allergic-rhinitis-may-vary-with-the-time-of-day
#18
Satoshi Igarashi, Keisuke Suzuki, Yuki Nakamura, Kayoko Ishimaru, Chiharu Fukano, Keisuke Masuyama, Katsuyo Ohashi-Doi, Atsuhito Nakao
BACKGROUND: Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR). However, many issues regarding SLIT remain to be resolved, including the optimal timing of administration. This study investigated the effect of time of day on SLIT efficacy with the goal of optimizing the therapeutic outcome. METHODS: We performed prophylactic SLIT at different times of day (10 a.m. or 10 p.m.) in 2 mouse models of AR: an ovalbumin (OVA)-induced AR model and Cry j 1-induced AR model, and compared the effects...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27900520/nuclear-medicine-imaging-of-multiple-myeloma-particularly-in-the-relapsed-setting
#19
REVIEW
Esther G M de Waal, Andor W J M Glaudemans, Carolien P Schröder, Edo Vellenga, Riemer H J A Slart
Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity...
November 29, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27900387/a-modification-specific-peptide-based-immunization-approach-using-crm197-carrier-protein-development-of-a-selective-vaccine-against-pyroglutamate-a%C3%AE-peptides
#20
Valérie Vingtdeux, Haitian Zhao, Pallavi Chandakkar, Christopher M Acker, Peter Davies, Philippe Marambaud
Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer's disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of Aβ...
November 28, 2016: Molecular Medicine
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