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https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#1
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29341436/a-novel-nir-fluorescent-probe-for-monitoring-cox-2-in-inflammation-and-tumor
#2
Qi Zhang, Zhihao Han, Ji Tao, Wancun Zhang, Ping Li, Liping Tang, Yueqing Gu
Targeting COX-2 for molecular imaging is an attractive approach applicable for its overexpression in inflammation and many malignancies. Herein, for monitoring COX-2, we synthesize a specific COX-2 probe CMP, based on celecoxib and a water-soluble near-infrared dye MPA. Its high affinity for binding to COX-2 is verified by molecular docking, dynamics simulation and inhibition assay. At cellular level, CMP selectively accumulates in cytoplasm of COX-2-positive cells. In vivo assays, probe guided-imaging in inflamed or cancerous tissues confirms that CMP can bind to the locally endogenic COX-2 and exhibit intense fluorescence...
January 17, 2018: Journal of Biophotonics
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#3
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29330435/beta-catenin-cleavage-enhances-transcriptional-activation
#4
Tatiana Goretsky, Emily M Bradford, Qing Ye, Olivia F Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C Keller, Preetika Sinh, Josep M Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A Barrett
Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29296835/mutation-load-and-an-effector-t-cell-gene-signature-may-distinguish-immunologically-distinct-and-clinically-relevant-lymphoma-subsets
#5
Christopher R Bolen, Ronald McCord, Sarah Huet, Garrett M Frampton, Richard Bourgon, Fabrice Jardin, Peggy Dartigues, Elizabeth A Punnoose, Edith Szafer-Glusman, Luc Xerri, Pierre Sujobert, Gilles Salles, Jeffrey M Venstrom
Identifying follicular lymphoma (FL) patients with preexisting antitumor immunity will inform precision medicine strategies for novel cancer immunotherapies. Using clinical and genomic data from 249 FL patients, we determined the clinical impact of mutation load and an effector T-cell (Teff) gene signature as proxies for the likelihood of a functional immune response. The FL mutation load estimate varied between 0 and 33 mutations per Mb (median, 6.6), and 92% of FL patients with a high mutation load had high Teff gene expression (P = ...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288743/the-good-and-bad-faces-of-the-cxcr4-chemokine-receptor
#6
REVIEW
Joaquin Teixidó, Mónica Martínez-Moreno, Marta Díaz-Martínez, Silvia Sevilla-Movilla
Chemokines are chemotactic cytokines that promote cell migration and activation under homeostatic and inflammatory conditions. Chemokines bind to seven transmembrane-spanning receptors that are coupled to heterotrimeric guanine nucleotide-binding (G) proteins, which are the responsible for intracellularly transmitting the activating signals for cell migration. Hematopoiesis, vascular development, lymphoid organ morphogenesis, cardiogenesis and neural differentiation are amongst the processes involving chemokine function...
December 27, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29285251/abnormally-glycosylated-muc1-establishes-a-positive-feedback-circuit-of-inflammatory-cytokines-mediated-by-nf-%C3%AE%C2%BAb-p65-and-ezh2-in-colitis-associated-cancer
#7
Sandra Cascio, Jacque L Faylo, Joshua C Sciurba, Jia Xue, Sarangarajan Ranganathan, Jason J Lohmueller, Pamela L Beatty, Olivera J Finn
The abnormal hypoglycosylated form of the epithelial mucin MUC1 is over-expressed in chronic inflammation and on human adenocarcinomas, suggesting its potential role in inflammation-driven tumorigenesis. The presence of human MUC1 aggravates colonic inflammation and increases tumor initiation and progression in an in vivo AOM/DSS mouse model of colitis-associated cancer (CAC). High expression levels of pro-inflammatory cytokines, including TNF-α and IL-6, were found in MUC1+ inflamed colon tissues. Exogenous TNF-α promoted the transcriptional activity of MUC1 as well as over-expression of its hypoglycosylated form in intestinal epithelial cells (IECs)...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285113/low-dose-irradiation-increases-adoptive-cytotoxic-t-lymphocyte-migration-in-gastric-cancer
#8
Juan Du, Shu Su, Hongyan Li, Jie Shao, Fanyan Meng, Mi Yang, Hanqing Qian, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic; however, the inefficient migration of adoptive immune cells to tumors is one of the rate-limiting factors of ACI. The present study investigated whether 2 Gy low dose irradiation (LDI) was able to increase the migration of adoptive lymphocytes to gastric cancer cells. Treatment with 2 Gy LDI resulted in marked chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 production from gastric cancer cell lines. A Transwell chamber migration assay demonstrated enhanced transmigration of cytotoxic T lymphocytes to gastric cancer cells following LDI treatment...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29275462/cancer-immunotherapy-targets-based-on-understanding-the-t-cell-inflamed-versus-non-t-cell-inflamed-tumor-microenvironment
#9
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29234718/a-case-of-multiple-squamous-cell-carcinomas-arising-from-red-tattoo-pigment
#10
E Maxim, H Higgins, L D'Souza
Ornamental tattooing involves the administration of exogenous pigments into the skin to create a permanent design. Our case focuses on a 62-year-old woman who presented with an inflamed enlarging nodule on her right proximal calf, which arose within the red pigment of an ornamental tattoo. The nodule was diagnosed as squamous cell carcinoma (SCC) and subsequently excised. Over the course of the following year, the patient was diagnosed with a total of five additional SCCs that also arose within the red pigment of the tattoo...
December 2017: International Journal of Women's Dermatology
https://www.readbyqxmd.com/read/29228057/n-acetylcysteine-nac-ameliorates-epstein-barr-virus-latent-membrane-protein-1-induced-chronic-inflammation
#11
Xiao Gao, Eirini-Maria Lampraki, Sarwah Al-Khalidi, Muhammad Asif Qureshi, Rhea Desai, Joanna Beatrice Wilson
Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions...
2017: PloS One
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#12
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29203393/pyrin-inflammasome-regulates-tight-junction-integrity-to-restrict-colitis-and-tumorigenesis
#13
Deepika Sharma, Ankit Malik, Clifford S Guy, Rajendra Karki, Peter Vogel, Thirumala-Devi Kanneganti
BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) increase risk for colorectal cancer. Mutations in the Mediterranean fever gene (MEFV or pyrin) are associated with hereditary autoinflammatory disease and severe IBD. Expression of MEFV, a sensor protein that the initiates assembly of the inflammasome complex, is increased in colon biopsies from patients with IBD. We investigated the role of pyrin in intestinal homeostasis in mice. METHODS: Mefv-/- mice and C57/BL6 mice (controls) were given azoxymethane followed by multiple rounds of dextran sodium sulfate (DSS) to induce colitis and tumorigenesis...
December 1, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29193895/inflammatory-cytokines-stabilize-soxc-transcription-factors-to-mediate-the-transformation-of-fibroblast-like-synoviocytes-in-arthritic-disease
#14
Pallavi Bhattaram, George Muschler, Viktor Wixler, Véronique Lefebvre
OBJECTIVES: Fibroblast-like synoviocytes (FLS) produce key synovial fluid and tissue components to ensure joint integrity under healthy conditions, whereas they become cancer-like and aggressively contribute to joint degeneration in inflammatory arthritis. Here we asked whether the SOXC transcription factors SOX4 and SOX11, whose functions are critical in joint development and many cancer types, contribute to FLS activities under normal and inflammatory conditions. METHODS: We inactivated the SOXC genes in FLS of adult mice and studied consequences on joint homeostasis and tumor necrosis factor-alpha (TNFα)-induced arthritis...
November 28, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29191507/viscoelastic-properties-of-human-pancreatic-tumors-and-in-vitro-constructs-to-mimic-mechanical-properties
#15
Andres Rubiano, Daniel Delitto, Song Han, Michael Gerber, Carly Galitz, Jose Trevino, Ryan M Thomas, Steven J Hughes, Chelsey S Simmons
Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue...
November 27, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29157287/safety-in-treatment-of-hepatocellular-carcinoma-with-immune-checkpoint-inhibitors-as-compared-to-melanoma-and-non-small-cell-lung-cancer
#16
Zachary J Brown, Bernd Heinrich, Seth M Steinberg, Su Jong Yu, Tim F Greten
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29090383/patients-with-advanced-periodontal-disease-before-intensity-modulated-radiation-therapy-are-prone-to-develop-bone-healing-problems-a-2-year-prospective-follow-up-study
#17
Jennifer M Schuurhuis, Monique A Stokman, Max J H Witjes, Harry Reintsema, Johannes A Langendijk, Arjan Vissink, Frederik K L Spijkervet
PURPOSE: Intensity-modulated radiation therapy (IMRT) has changed radiation treatment of head and neck cancer (HNC). However, it is still unclear if and how IMRT changes oral morbidity outcomes. In this prospective study, we assessed the outcome of reducing post-IMRT sequelae by means of pre-radiation dental screening and eliminating oral foci. METHODS: All consecutive dentate patients > 18 years, diagnosed with primary oral or oropharyngeal carcinoma, referred for pre-treatment dental screening between May 2011 and May 2013, were included and followed for 2 years...
October 31, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29083935/tri-nucleotide-consortium-of-androgen-receptor-is-associated-with-low-serum-fsh-and-testosterone-in-asthenospermic-men
#18
Haroon Latif Khan, Shahzad Bhatti, Sana Abbas, Yousaf Latif Khan, Muhammad Aslamkhan, Rosa Maria Marquez Gonzalez, Gerardo Rodriguez Gonzalez, Hikmet Hakan Aydin, Magali Segundo Trinidad
Androgen mediating signaling is implicated in regulating the expression of reproductive related genes. Any deviation in the gene expression might be the ignitable precursor for genomic instability that inflames the genomic rearrangements and a leading cause of cancer. The main goal of this study was to determine the relationships between trinucleotide repeats of androgen receptor (AR), sex steroids, and sexual function in men presenting with reduced sperm motility. We investigated the singleton or combinatorial effects of the length of trinucleotide repeats of AR on reproductive hormones, clinical parameters, semen analyses, as well as sexual assessment function of 210 asthenospermic outpatients along with 125 normal subjects...
October 30, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29081776/innate-lymphoid-cells-in-intestinal-inflammation
#19
REVIEW
Alessandra Geremia, Carolina V Arancibia-Cárcamo
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn's disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29079529/mri-visualization-of-neuroinflammation-using-vcam-1-targeted-paramagnetic-micelles
#20
Francesca Garello, Amerigo Pagoto, Francesca Arena, Annalisa Buffo, Francesco Blasi, Diego Alberti, Enzo Terreno
The detection of neuroinflammatory processes using innovative and non-invasive imaging techniques is of great help to deeply investigate the onset and progression of neurodegenerative diseases. Since Vascular Cell Adhesion Molecule (VCAM-1) is over expressed at the blood brain barrier in the event of neuroinflammation, the goal of this work was the testing of MRI detectable micelles targeted towards VCAM-1 to visualize inflamed regions in a mouse model of acute neuroinflammation. The developed probe allowed for the early detection of the disease, with higher T1 signal enhancement and more precise localization in comparison to untargeted micelles or to the clinically approved contrast agent MultiHance...
November 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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