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https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#1
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346417/xylose-donor-transport-is-critical-for-fungal-virulence
#2
Lucy X Li, Carsten Rautengarten, Joshua L Heazlewood, Tamara L Doering
Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading cause of fungal meningitis worldwide and is responsible for hundreds of thousands of deaths annually. Cryptococcal glycans are required for fungal survival in the host and for pathogenesis. Most glycans are made in the secretory pathway, although the activated precursors for their synthesis, nucleotide sugars, are made primarily in the cytosol. Nucleotide sugar transporters are membrane proteins that solve this topological problem, by exchanging nucleotide sugars for the corresponding nucleoside phosphates...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346407/relaxin-reverses-inflammatory-and-immune-signals-in-aged-hearts
#3
Brian Martin, Beth Ann Gabris-Weber, Rajiv Reddy, Guillermo Romero, Ansuman Chattopadhyay, Guy Salama
BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF...
2018: PloS One
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#4
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346185/higher-art-adherence-is-associated-with-lower-systemic-inflammation-in-treatment-na%C3%A3-ve-ugandans-who-achieve-virologic-suppression
#5
Jose R Castillo-Mancilla, Mary Morrow, Yap Boum, Helen Byakwaga, Jessica E Haberer, Jeffrey N Martin, David Bangsberg, Samantha Mawhinney, Nicholas Musinguzi, Yong Huang, Russell P Tracy, Tricia H Burdo, Kenneth Williams, Conrad Muzoora, Peter W Hunt, Mark J Siedner
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, the kynurenine/tryptophan (K/T) ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naïve adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit...
January 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29345842/pd-l1-is-a-promising-blood-marker-for-predicting-tumor-progression-and-prognosis-in-patients-with-gastric-cancer
#6
Masahiko Amatatsu, Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Sumiya Ishigami, Shoji Natsugoe
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. On the other hand, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345737/present-status-and-future-perspective-of-peptide-based-vaccine-therapy-for-urological-cancer
#7
REVIEW
Wataru Obara, Mitsugu Kanehira, Toyomasa Katagiri, Renpei Kato, Yoichiro Kato, Ryo Takata
The use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and the lack of significant side effects when administered in-vivo. Peptide-based vaccine therapy against several cancers including urological cancers had made progress for several decades, but there is no approval peptide vaccine all over the world. Peptides vaccines were also shown to induce a high frequency of immune response in patients who were accompanied by clinical efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345571/targeting-cytosolic-phospholipase-a2%C3%AE-for-novel-anti-inflammatory-agents
#8
Jalal Soubhye, Pierre van Antwerpen, Francois Dufrasne
Group IV cytosolic phospholipase A2 (cPLA2α) plays a critical role in inflammatory processes. It produces arachidonic acid which is the main source of the pro-inflammatory eicosanoids mediators that are important in innate immune system. In some cases, these pro-inflammatory mediators cause damages to the host tissues and therefore promote autoimmune diseases. Consequently, development of potent inhibitors against cPLA2α could improve the therapy of inflammatory diseases. In the last two decades, intense efforts have been done to find potent cPLA2α inhibitors...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345374/ship-negatively-regulates-type-ii-immune-responses-in-mast-cells-and-macrophages
#9
REVIEW
Peter Dobranowski, Laura M Sly
SHIP is a hematopoietic-specific lipid phosphatase that dephosphorylates PI3K-generated PI(3,4,5)-trisphosphate. SHIP removes this second messenger from the cell membrane blunting PI3K activity in immune cells. Thus, SHIP negatively regulates mast cell activation downstream of multiple receptors. SHIP has been referred to as the "gatekeeper" of mast cell degranulation as loss of SHIP dramatically increases degranulation or permits degranulation in response to normally inert stimuli. SHIP also negatively regulates Mϕ activation, including both pro-inflammatory cytokine production downstream of pattern recognition receptors, and alternative Mϕ activation by the type II cytokines, IL-4, and IL-13...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345371/therapeutic-manipulation-of-host-cell-death-pathways-to-facilitate-clearance-of-persistent-viral-infections
#10
REVIEW
James Cooney, Cody Allison, Simon Preston, Marc Pellegrini
Most persistent viral infections can be controlled, but not cured, by current therapies. Abrogated antiviral immunity and stable latently infected cells represent major barriers to cure. This necessitates life-long suppressive antiviral therapy. Achieving a cure for HIV, hepatitis B virus, Epstein Barr-virus, and others, requires novel approaches to facilitate the clearance of infected cells from the host. One such approach is to target host cell death pathways, rather than the virus itself. Here, we summarize recent findings from studies that have utilized therapeutics to manipulate host cell death pathways as a means to treat and cure persistent viral infections...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345362/innate-lymphoid-cells-in-antitumor-immunity
#11
REVIEW
Bérengère Salomé, Camilla Jandus
Innate lymphoid cells (ILCs) are the most recently characterized subset of innate lymphocytes. Based on their specific transcriptional regulation, cytokine secretion pattern and effector functions ILCs mirror the different CD4 T helper cell subsets, with the unique attributes of acting locally in early phases of immune responses, in an antigen-independent manner. In this review, we discuss how ILCs have been implicated in tumorigenesis. Their presence might favor or inhibit tumor growth, depending on the cytokines released and the specific tumor microenvironment...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345343/mycobacterium-tuberculosis-rewiring-host-cell-signaling-to-promote-infection
#12
REVIEW
Michael D Stutz, Michelle P Clark, Marcel Doerflinger, Marc Pellegrini
The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345255/pure-mechanistic-analysis-of-additive-neuroprotective-effects-between-baicalin-and-jasminoidin-in-ischemic-stroke-mice
#13
Peng-Qian Wang, Qiong Liu, Wen-Juan Xu, Ya-Nan Yu, Ying-Ying Zhang, Bing Li, Jun Liu, Zhong Wang
Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM)...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29345251/cancer-associated-cachexia
#14
REVIEW
Vickie E Baracos, Lisa Martin, Murray Korc, Denis C Guttridge, Kenneth C H Fearon
Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells...
January 18, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29345000/cell-death-under-epithelial-mesenchymal-transition-control-in-prostate-cancer-therapeutic-response
#15
REVIEW
Diane Begemann, Harry Anastos, Natasha Kyprianou
Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits...
January 17, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29344894/systems-biology-approaches-in-cancer-pathology
#16
Aaron DeWard, Rebecca J Critchley-Thorne
The complex network of the tissue system, in both pre-neoplastic tissues and tumors, demonstrates the need for a systems biology approach to cancer pathology, in which quantification of key tissue system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. A systems biology approach to cancer pathology enables integration of key system features that are relevant to diagnoses, patient outcomes, and responses to therapies. Key tissue system features relevant to cancer pathology include molecular and morphologic abnormalities in epithelia, cellular changes in the stroma such as immune infiltrates, and relationships between components of the system, such as interactions and spatial relationships between epithelial and stromal components, and also between specific immune cell subsets...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344893/profiling-tumor-infiltrating-immune-cells-with-cibersort
#17
Binbin Chen, Michael S Khodadoust, Chih Long Liu, Aaron M Newman, Ash A Alizadeh
Tumor infiltrating leukocytes (TILs) are an integral component of the tumor microenvironment and have been found to correlate with prognosis and response to therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow cytometry suffer from limitations in phenotypic markers and can be challenging to practically implement and standardize. An alternative approach is to acquire aggregative high dimensional data from cellular mixtures and to subsequently infer the cellular components computationally...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344676/application-of-genome-editing-techniques-in-immunology
#18
REVIEW
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29344434/rare-multidrug-resistant-pulmonary-nocardiosis-in-aids
#19
Cherry O Onaiwu, Manasa Velagapudi, Luay Sarsam, Lindsay Utley, Lauren Bricker, Venkata Sunil Bendi, Renuga Vivekanandan
Nocardiosis is an opportunistic infection in patients with depressed cell-mediated immunity. Inhalation is the primary route for exposure via dust particles. Patients with acquired immune deficiency syndrome (AIDS) are at increased risk of disseminated disease. A challenge in the diagnosis of pulmonary nocardiosis is that it can mimic other pulmonary diseases. Nocardia farcinica tends to be a more virulent, multidrug-resistant strain with an increased tendency to disseminate. This report describes a 64-year-old man with AIDS found to have pulmonary nocardiosis that did not respond to standard antibiotic therapy...
November 11, 2017: Curēus
https://www.readbyqxmd.com/read/29344407/tpf-induction-chemotherapy-increases-pd-l1-expression-in-tumour-cells-and-immune-cells-in-head-and-neck-squamous-cell-carcinoma
#20
Charlotte Leduc, Julien Adam, Emilie Louvet, Tony Sourisseau, Nicolas Dorvault, Marine Bernard, Elodie Maingot, Laura Faivre, Mei-Shiue Cassin-Kuo, Emilie Boissier, Marie-Charlotte Dessoliers, Angélique Robin, Odile Casiraghi, Caroline Even, Stéphane Temam, Ken A Olaussen, Jean-Charles Soria, Sophie Postel-Vinay
Background: Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) therapies have demonstrated promising activity in advanced head and neck squamous cell carcinoma (HNSCC), with overall response rates of approximately 20% in unselected populations and survival benefit. Whether induction docetaxel, platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune infiltrates is unknown. Patients and methods: Patients with locally advanced HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by induction TPF followed by surgery were retrospectively considered...
2018: ESMO Open
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