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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28324803/leishmania-donovani-resistant-to-ambisome-or-miltefosine-exacerbates-cd58-expression-on-nk-cells-and-promotes-trans-membrane-migration-in-association-with-cd2
#2
Pushkar Shivam, Sarita Kumari, Fauzia Jamal, Vikash Kumar, Manish Kumar, Sanjiva Bimal, Shyam Narayan, Vidya Nand Ravi Das, Krishna Pandey, Anil Kumar Gupta, Pradeep Das, Shubhankar Kumar Singh
Visceral leishmaniasis (VL) is a disease that is associated with compromised immunity and drug un-responsiveness as well as with the emergence of drug resistance in Leishmania donovani (Ld). Ld down-modulates cellular immunity by manipulating signaling agents, including a higher expression of the adhesion molecule CD58. The expression of CD58 and CD2 on natural killer (NK) cells facilitates intercellular adhesion and signaling. The influence of drug-resistant Ld on the expression of CD58 and CD2 was addressed in this study...
March 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28324760/trpv1-agonism-inhibits-endothelial-cell-inflammation-via-activation-of-enos-no-pathway
#3
Youping Wang, Lin Cui, Hui Xu, Suxiao Liu, Feiyun Zhu, Fengna Yan, Si Shen, Mingjun Zhu
BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca(2+)-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#4
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324619/identification-of-a-herv-k-env-surface-peptide-highly-recognized-in-ra-patients-a-cross-sectional-case-control-study
#5
G Mameli, G L Erre, E Caggiu, S Mura, D Cossu, Marco Bo, M L Cadoni, A Piras, N Mundula, E Colombo, G Buscetta, G Passiu, L A Sechi
Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19-37 , env-su 109-26 , env-su 164-186 , env-su 209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity...
March 21, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28324192/the-presence-of-human-papillomavirus-hpv-in-placenta-and-or-cord-blood-might-result-in-th2-polarization
#6
H-M Koskimaa, A Paaso, M J P Welters, S Grénman, K Syrjänen, S H van der Burg, S Syrjänen
The purpose of this study was to evaluate if an early exposure to human papillomavirus (HPV) during the prenatal period or infancy could result in HPV16-specific T helper (Th) responses resembling those of adults with HPV-induced lesions. We tested HPV16-specific cell-mediated immunity (CMI) in children born with HPV-positive umbilical cord blood and/or placenta or having persistent oral HPV infection and in constantly oral HPV-negative controls. Peripheral blood mononuclear cells from 33 children from the Finnish HPV Family Study cohort (mean age 14...
March 21, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#7
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323998/genes-outside-the-major-histocompatibility-complex-mhc-locus-are-linked-to-the-development-of-thyroid-autoantibodies-and-thyroiditis-in-nod-h2h4-mice
#8
Sandra M McLachlan, Sylvie Lesage, Roxanne Collin, Bianca Banuelos, Holly A Aliesky, Basil Rapoport
Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the Major Histocompatibility Class (MHC) molecule I-Ak from B10.A(4R) mice to non-obese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2 and the second generation backcross of F1 to NOD...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323750/humoral-responses-against-hiv-in-male-genital-tract-role-in-sexual-transmission-and-perspectives-for-preventive-strategies
#9
Amandine Gagneux-Brunon, Nicolas Rochereau, Elisabeth Botelho-Nevers, Frédéric Lucht, Bruno Pozzetto, Stéphane Paul, Thomas Bourlet
Most new HIV infections occur via sexual routes. The induction of protective anti-HIV antibodies in genital mucosa is an important step towards reducing HIV transmission. Mucosal anti-HIV antibodies may play a dual role by either protecting against HIV transmission or facilitating it. Protective properties against HIV of mucosal IgGs and IgAs exhibiting neutralizing or antibody dependent cell-mediated cytotoxicity (ADCC) activities have been described in highly exposed seronegative individuals (HESN). Conversely, some IgGs may facilitate the crossing of HIV free particles through epithelial barriers by transcytosis...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#10
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28323646/endothelial-cells-and-lymphatics-at-the-interface-between-the-immune-and-central-nervous-systems-implications-for-multiple-sclerosis
#11
Céline Meyer, Guillaume Martin-Blondel, Roland S Liblau
PURPOSE OF REVIEW: The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege. RECENT FINDINGS: T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS...
March 18, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323545/creation-of-a-bioengineered-skin-flap-scaffold-with-a-perfusable-vascular-pedicle
#12
Bernhard J Jank, Jeremy Goverman, Jacques P Guyette, Jon M Charest, Mark A Randolph, Glenn R Gaudette, Joshua R Gershlak, Martin Purschke, Emilia Javorsky, Rosalynn M Nazarian, David A Leonard, Curtis L Cetrulo, William G Austen, Harald Christian Ott
Full thickness skin loss is a challenging problem due to limited reconstructive options, demanding 75 million surgical procedures annually in the United States. Autologous skin grafting is the gold standard treatment, but results in donor site morbidity and poor aesthetics. Numerous skin substitutes are available on the market to date, however, none truly function as full thickness skin due to their lack of a vascular network. The creation of an autologous full thickness skin analogue with a vascular pedicle would result in a paradigm shift in the management of wounds and in reconstruction of full thickness skin defects...
March 21, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28323529/altered-expression-of-a-chloroplast-protein-affects-the-outcome-of-virus-and-nematode-infection
#13
Elena Ganusova, J Hollis Rice, Timothy Scott Carlew, Akshita Patel, Emmanuel Perrodin-Njoku, Tarek Hewezi, Tessa M Burch-Smith
The chloroplast-resident RNA helicase ISE2 (INCREASED SIZE EXCLUSION LIMIT 2) can modulate the formation and distribution of plasmodesmata and intercellular trafficking. We have determined that ISE2 expression is induced by viral infection. Therefore the responses of Nicotiana benthamiana plants with varying levels of ISE2 expression to infection by Tobacco mosaic virus (TMV) and Turnip mosaic virus (TuMV) were examined. Surprisingly, increased or decreased ISE2 expression led to faster viral systemic spread and is some cases enhanced systemic necrosis...
March 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28323528/plant-immunity-inducer-development-and-application
#14
Dewen Qiu, Yijie Dong, Yi Zhang, Shupeng Li, Fachao Shi
Plant immunity inducers represent a new and rapidly developing field in plant protection research. In this paper, we discuss recent research on plant immunity inducers and their development and applications in China. Plant immunity inducers include plant immunity-inducing proteins, chitosan oligosaccharides, and microbial inducers. These compounds and microorganisms can trigger defense responses and confer disease resistance in plants. We also describe the mechanisms of plant immunity inducers and how they promote plant health...
March 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#15
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28323492/regulatory-and-exhausted-t-cell-responses-to-aav-capsid
#16
Gwladys Gernoux, James M Wilson, Christian Mueller
Recombinant adeno-associated viruses are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting Hemophilia B patients 10 years ago, immune responses to AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells which have correlated with a decline in AAV transduced tissue in some patients...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#17
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28320170/evaluating-the-association-of-allergies-with-multiple-sclerosis-susceptibility-risk-and-disease-activity-in-a-pediatric-population
#18
Theresa Bourne, Michael Waltz, T C Casper, K Kavak, G Aaen, A Belman, L Benson, M Candee, T Chitnis, J Graves, B Greenberg, M Gorman, Y Harris, L Krupp, T Lotze, S Mar, J Ness, C Olsen, S Roalstad, M Rodriguez, J Rose, J Rubin, T Schreiner, J M Tillema, I Kahn, A Waldman, L Barcellos, E Waubant, B Weinstock-Guttman
BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320058/regional-differences-between-perisynovial-and-infrapatellar-adipose-tissue-depots-and-their-response-to-class-ii-and-iii-obesity-in-patients-with-oa
#19
Natalia S Harasymowicz, Nick D Clement, Asim Azfer, Richard Burnett, Donald M Salter, A Hamish W R Simpson
OBJECTIVE: Obesity is associated with an increased risk of developing Osteoarthritis (OA), which is postulated to be secondary to inflammation from adipose tissue (AT). There are peri-articular adipose depots in synovial joints, the association of this tissue with OA has not been extensively explored. The aim of this study was to investigate differences in local AT depots in knees with OA and changes related to class II and III obesity. METHODS: Synovium and the infrapatellar fat pad (IPFP) were collected during total knee replacement from 69 patients with end-stage OA...
March 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28319849/the-association-between-three-major-physiological-stress-systems-and-oxidative-dna-and-lipid-damage
#20
Catherine N Black, Mariska Bot, Dóra Révész, Peter G Scheffer, Brenda Penninx
BACKGROUND: Increased activity of the three major physiological stress systems (immune-inflammatory system, hypothalamic-pituitary-adrenal-axis [HPA-axis], and autonomic nervous system [ANS]) is part of the pathophysiology of various somatic and psychiatric diseases. Oxidative damage is a key mechanism in both ageing and disease. Elucidating the relationship between these stress systems and oxidative damage would contribute to the understanding of the role of physiological stress in disease...
March 6, 2017: Psychoneuroendocrinology
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