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https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#1
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#2
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108980/the-influence-of-macrophages-on-mesenchymal-stromal-cell-therapy-passive-or-aggressive-agents
#3
REVIEW
Fiona Carty, Bernard P Mahon, Karen English
Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date, however, recently a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to better design MSC therapies and clinical studies...
January 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28108813/relationship-between-il-27-and-coronary-arterial-lesions-in-children-with-kawasaki-disease
#4
Feifei Si, Yao Wu, Fang Gao, Siqi Feng, Ruixi Liu, Qijian Yi
Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy...
January 20, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28108611/reversal-of-diabetes-in-nod-mice-by-clinical-grade-proinsulin-and-il-10-secreting-lactococcus-lactis-in-combination-with-low-dose-anti-cd3-depends-on-the-induction-of-foxp3-positive-t-cells
#5
Tatiana Takiishi, Dana Paulina Cook, Hannelie Korf, Guido Sebastiani, Francesca Mancarella, João Paulo Monteiro Carvalho Mori Cunha, Clive Wasserfall, Noelia Casares, Juan José Lasarte, Lothar Steidler, Pieter Rottiers, Francesco Dotta, Conny Gysemans, Chantal Mathieu
The introduction of β-cell autoantigens via the gut through Lactococcus lactis (L. lactis) has been demonstrated to be a promising approach for diabetes reversal in NOD mice. Here we show that a combination therapy of low-dose anti-CD3 with a clinical-grade self-containing L. lactis, appropriate for human application, secreting human proinsulin and interleukin-10, cured 66% of mice with new-onset diabetes, which is comparable to therapy results with plasmid-driven L. lactis Initial blood glucose concentrations (<350 mg/dL) and insulin autoantibody positivity were predictors of the stable reversal of hyperglycemia, and decline in insulin autoantibody positivity was an immune biomarker of therapeutic outcome...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108590/human-immunity-against-ebv-lessons-from-the-clinic
#6
REVIEW
Stuart G Tangye, Umaimainthan Palendira, Emily S J Edwards
The mammalian immune system has evolved over many millennia to be best equipped to protect the host from pathogen infection. In many cases, host and pathogen have coevolved, each acquiring sophisticated ways of inducing or protecting from disease. Epstein-Barr virus (EBV) is a human herpes virus that infects >90% of individuals. Despite its ubiquity, infection by EBV is often subclinical; this invariably reflects the necessity of the virus to preserve its host, balanced with sophisticated host immune mechanisms that maintain viral latency...
January 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28107662/a-simple-and-powerful-co-delivery-system-based-on-ph-responsive-metal-organic-frameworks-for-enhanced-cancer-immunotherapy
#7
Fei Duan, Xiaochen Feng, Xinjian Yang, Wentong Sun, Yi Jin, Huifang Liu, Kun Ge, Zhenhua Li, Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8(+) cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28107607/epidemiology-update-for-hepatitis-c-virus-and-hepatitis-b-virus-in-end-stage-renal-disease-in-france-r%C3%A3-seau-epid%C3%A3-miologique-et-information-en-n%C3%A3-phrologie-registry
#8
Corinne Isnard Bagnis, Cécile Couchoud, Marc Bowens, Ayman Sarraj, Gilbert Deray, Jérôme Tourret, Patrice Cacoub, Sophie Tezenas du Montcel
BACKGROUND AND AIMS: Risk for HCV/HBV infection is increased in ESRD patients. We generate updated epidemiological data. METHODS: Based on the National French registry for ESRD, we extracted data for patients who started dialysis or preemptive transplantation between January, 2005 and December, 2013. A positive serum HBs Ag and/or a positive HCV RNA defined HBV and HCV infections, respectively. RESULTS: 72,948 patients were included among which 62...
January 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28107583/chronic-hepatitis-c-and-chronic-kidney-disease-advances-limitations-and-unchartered-territories
#9
Manuel Mendizabal, K Rajender Reddy
Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stage 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population...
January 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28107566/recent-advances-in-understanding-clonal-haematopoiesis-in-aplastic-anaemia
#10
REVIEW
Natasha Stanley, Timothy S Olson, Daria V Babushok
Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28107546/bone-marrow-stroma-protects-myeloma-cells-from-cytotoxic-damage-via-induction-of-the-oncoprotein-muc1
#11
Michal Bar-Natan, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Arie Apel, Hasan Rajabi, Athalia R Pyzer, Kristen Palmer, Michaela R Reagan, Myrna R Nahas, Rebecca Karp Leaf, Salvia Jain, Jon Arnason, Irene M Ghobrial, Kenneth C Anderson, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is a lethal haematological malignancy that arises in the context of a tumour microenvironment that promotes resistance to apoptosis and immune escape. In the present study, we demonstrate that co-culture of MM cells with stromal cells results in increased resistance to cytotoxic and biological agents as manifested by decreased rates of cell death following exposure to alkylating agents and the proteosome inhibitor, bortezomib. To identify the mechanism of increased resistance, we examined the effect of the co-culture of MM cells with stroma cells, on expression of the MUC1 oncogene, known to confer tumour cells with resistance to apoptosis and necrosis...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28107533/improvement-of-therapeutic-efficacy-of-oral-immunotherapy-in-combination-with-regulatory-t-cell-inducer-kakkonto-in-a-murine-food-allergy-model
#12
Yuka Nagata, Takeshi Yamamoto, Michie Hayashi, Shusaku Hayashi, Makoto Kadowaki
Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT...
2017: PloS One
https://www.readbyqxmd.com/read/28107457/novel-analysis-of-immune-cells-from-nasal-microbiopsy-demonstrates-reliable-reproducible-data-for-immune-populations-and-superior-cytokine-detection-compared-to-nasal-wash
#13
Simon P Jochems, Katherine Piddock, Jamie Rylance, Hugh Adler, Beatriz F Carniel, Andrea Collins, Jenna F Gritzfeld, Carole Hancock, Helen Hill, Jesus Reiné, Alexandra Seddon, Carla Solórzano, Syba Sunny, Ashleigh Trimble, Angela D Wright, Seher Zaidi, Stephen B Gordon, Daniela M Ferreira
The morbidity and mortality related to respiratory tract diseases is enormous, with hundreds of millions of individuals afflicted and four million people dying each year. Understanding the immunological processes in the mucosa that govern outcome following pathogenic encounter could lead to novel therapies. There is a need to study responses at mucosal surfaces in humans for two reasons: (i) Immunological findings in mice, or other animals, often fail to translate to humans. (ii) Compartmentalization of the immune system dictates a need to study sites where pathogens reside...
2017: PloS One
https://www.readbyqxmd.com/read/28107430/discontinuation-from-antiretroviral-therapy-a-continuing-challenge-among-adults-in-hiv-care-in-ethiopia-a-systematic-review-and-meta-analysis
#14
Hailay Abrha Gesesew, Paul Ward, Kifle Woldemichael Hajito, Garumma Tolu Feyissa, Leila Mohammadi, Lillian Mwanri
BACKGROUND: Discontinuation of antiretroviral therapy (ART) reduces the immunological benefit of treatment and increases complications related to human immune-deficiency virus (HIV). However, the risk factors for ART discontinuation are poorly understood in developing countries particularly in Ethiopia. This review aimed to assess the best available evidence regarding risk factors for ART discontinuation in Ethiopia. METHODS: Quantitative studies conducted in Ethiopia between 2002 and 2015 that evaluated factors associated with ART discontinuation were sought across six major databases...
2017: PloS One
https://www.readbyqxmd.com/read/28106541/cell-membrane-and-intracellular-expression-of-toll-like-receptor-9-tlr9-in-colorectal-cancer-and-breast-cancer-cell-lines
#15
Shadab Shahriari, Somayeh Rezaeifard, Hamid Reza Moghimi, Mohammad Reza Khorramizadeh, Zahra Faghih
BACKGROUND: Toll-like receptor 9 (TLR9) is a DNA receptor of innate immune system which plays a pivotal role in inflammatory response. Recent evidence reveals over-expression and functionality of TLR9 in a wide variety of cancer cells and its contribution to tumor cell proliferation and survival. OBJECTIVE: In this study, we assessed the aberrant cell surface expression of TLR9 in cancer using cell-lines model. METHODS: Three breast cancer cell-lines (MDA-MB-231, MCF7 and SKBR3) and five colorectal adenocarcinoma cell-lines (HT29, HT29/219, SW480, SW48 and SW1116) in addition to one primary foreskin isolated fibroblast cell were analyzed for cell surface and intracellular expression of TLR9 by flow cytometry method...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106477/thymosin-alpha-1-and-hiv-1-recent-advances-and-future-perspectives
#16
Claudia Matteucci, Sandro Grelli, Emanuela Balestrieri, Antonella Minutolo, Ayele Argaw-Denboba, Beatrice Macchi, Paola Sinibaldi-Vallebona, Carlo Federico Perno, Antonio Mastino, Enrico Garaci
In spite of the consistent benefits for HIV-1 infected patients undergoing antiretroviral therapy, a complete immune reconstitution is usually not achieved. Actually, antiretroviral therapy may be frequently accompanied by immunological unresponsiveness, persistent inflammatory conditions and inefficient cytotoxic T-cell response. Thymosin alpha 1 is a thymic peptide that demonstrates a peculiar ability to restore immune system homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction...
January 20, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28106152/cancer-immunotherapy-immune-checkpoint-blockade-and-associated-endocrinopathies
#17
REVIEW
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra
Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28106067/multiple-sclerosis-in-2016-immune-directed-therapies-in-ms-efficacy-and-limitations
#18
Bernhard Hemmer, Mark Mühlau
No abstract text is available yet for this article.
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28105709/the-impact-of-co-existing-immune-mediated-on-phenotype-and-outcomes-in-inflammatory-bowel-diseases
#19
G Conway, G Velonias, E Andrews, J J Garber, V Yajnik, A N Ananthakrishnan
BACKGROUND: Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown. AIM: To determine the impact of concomitant immune-mediate disease on phenotypes and outcomes in IBD. METHODS: Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis...
January 20, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28105616/-interpretation-of-the-updates-of-nccn-2017-version-1-0-guideline-for-colorectal-cancer
#20
Gong Chen
The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting...
January 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
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