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https://www.readbyqxmd.com/read/29785121/association-between-angiogenesis-and-cytotoxic-signatures-in-the-tumor-microenvironment-of-gastric-cancer
#1
Yi Feng, Ying Dai, Zhihua Gong, Jia-Nan Cheng, Longhui Zhang, Chengdu Sun, Xianghua Zeng, Qingzhu Jia, Bo Zhu
Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29779068/new-insights-into-the-inflamed-tumor-immune-microenvironment-of-gastric-cancer-with-lymphoid-stroma-from-morphology-and-digital-analysis-to-gene-expression
#2
Irene Gullo, Patrícia Oliveira, Maria Athelogou, Gilza Gonçalves, Marta L Pinto, Joana Carvalho, Ana Valente, Hugo Pinheiro, Sara Andrade, Gabriela M Almeida, Ralf Huss, Kakoli Das, Patrick Tan, José C Machado, Carla Oliveira, Fátima Carneiro
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations...
May 19, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#3
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777034/membrane-fluctuations-and-acidosis-regulate-cooperative-binding-of-marker-of-self-cd47-with-macrophage-checkpoint-receptor-sirp%C3%AE
#4
Jan Steinkühler, Bartosz Różycki, Cory Alvey, Reinhard Lipowsky, Thomas R Weikl, Rumiana Dimova, Dennis E Discher
Cell-cell interactions that result from membrane proteins binding weakly in trans can cause accumulations in cis that suggest cooperativity and thereby an acute sensitivity to environmental factors. The ubiquitous "marker of self" protein CD47 binds weakly to SIRPα on a macrophage, which leads to accumulation of SIRPα at a phagocytic synapse and ultimately to inhibition of engulfment of 'self' cells - including cancer cells. We reconstituted this macrophage checkpoint with CD47-GFP displayed on giant vesicles generated from plasma membranes and then imaged vesicles adhering to SIRPα immobilized on a surface...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29762526/hypoxia-metabolism-and-immune-cell-function
#5
REVIEW
Ewelina Krzywinska, Christian Stockmann
Hypoxia is a hallmark of inflamed, infected or damaged tissue, and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as inflammation, bacteriological infection or cancer. In addition, HIFs are central regulators of many innate and adaptive immunological functions, including migration, antigen presentation, production of cytokines and antimicrobial peptides, phagocytosis as well as cellular metabolic reprogramming...
May 15, 2018: Biomedicines
https://www.readbyqxmd.com/read/29757351/m10-a-novel-derivative-of-myricetin-prevents-ulcerative-colitis-and-colorectal-tumor-through-attenuating-robust-endoplasmic-reticulum-stress
#6
Feng Wang, Zhi-Yu Song, Xian-Jun Qu, Feng Li, Liang Zhang, Wen-Bao Li, Shu-Xiang Cui
Chronic gut inflammation disposes to an increased risk of colitis-associated cancer (CAC). Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis...
May 11, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29751600/inflamed-phylloides-tumour-in-a-girl-a-challenging-diagnosis-in-paediatric-breast-lesions
#7
Ilaria Testa, Cristina Salvatori, Marco Prestipino, Maria Elena Laurenti, Paolo Gerli, Giuseppe Di Cara, Nicola Principi, Susanna Esposito, Mirko Bertozzi
Introduction : Phylloides tumours (PTs) are rare fibroepithelial neoplasms that account for 0.3⁻0.9% of all breast tumours. These tumours typically occur in women aged 30⁻70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation : A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever...
May 11, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29745507/-comparison-of-early-response-to-combined-chemotherapy-gemcitabine-cisplatin-in-non-small-cell-lung-cancer-animal-model-between-using-18-f-fluorodeoxyglucose-and-18-f-fluorothymidine
#8
Yan Xing, Tiantian Wang, Lilei Guo, Na Sun, Jinhua Zhao
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer. Nowadays, gemcitabine and cisplatin in combination have been adopted as the first-line chemotherapy for patients with NSCLC. This study aimed to monitor early response to combined chemotherapy of gemcitabine plus cisplatin in a mouse model of NSCLC by using 18 F-fluorodeoxyglucose and 18 F-fluorothymidine small animal positron emission tomography (PET). Lewis lung carcinoma-bearing C57BL/6 mice were treated with gemcitabine-cisplatin or saline...
June 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29734330/sustained-activation-of-detoxification-pathways-promotes-liver-carcinogenesis-in-response-to-chronic-bile-acid-mediated-damage
#9
Agnese Collino, Alberto Termanini, Paola Nicoli, Giuseppe Diaferia, Sara Polletti, Camilla Recordati, Vittoria Castiglioni, Donatella Caruso, Nico Mitro, Gioacchino Natoli, Serena Ghisletti
Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers occurring in pediatric patients with genetic defects of hepatocyte phosphatidylcholine transporters and in the corresponding mouse model (Mdr2-/- mice), in which impaired bile salt emulsification leads to chronic hepatocyte damage and inflammation, eventually resulting in oncogenic transformation...
May 7, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29720595/cytoglobin-affects-tumorigenesis-and-the-expression-of-ulcerative-colitis-associated-genes-under-chemically-induced-colitis-in-mice
#10
Mohammad Yassin, Hannelouise Kissow, Ben Vainer, Philomeena Daphne Joseph, Anders Hay-Schmidt, Jørgen Olsen, Anders Elm Pedersen
Cytoglobin (Cygb) is a member of the hemoglobin family and is thought to protect against cellular hypoxia and oxidative stress. These functions may be particularly important in inflammation-induced cancer, e.g., in patients with ulcerative colitis (UC). In this study, we investigated the development of inflammation and tumors in a murine model of inflammation-induced colorectal cancer using a combined treatment of azoxymethane and dextran sulfate sodium. A bioinformatics analysis of genome-wide expression data revealed increased colonic inflammation at the molecular level accompanied by enhanced macroscopic tumor development in Cygb-deficient mice...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29717480/genetic-features-of-multicentric-multifocal-intramucosal-gastric-carcinoma
#11
Aya Mizuguchi, Atsushi Takai, Takahiro Shimizu, Tomonori Matsumoto, Ken Kumagai, Shin'ichi Miyamoto, Hiroshi Seno, Hiroyuki Marusawa
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection could lead to the development of gastric cancer. The finding that multiple gastric cancers can develop synchronously and/or metachronously suggests the development of field cancerization in chronically inflamed, H. pylori-infected gastric mucosa. The genetic basis of multiple tumorigenesis in the inflamed stomach, however, is not well understood. In this study, we analyzed the microsatellite instability (MSI) status and copy number aberrations (CNAs) of 41 multiple intramucosal early gastric cancers that synchronously or metachronously developed in 19 patients with H...
May 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29681426/tumor-inherent-interferons-impact-on-immune-reactivity-and-immunotherapy
#12
Natasha K Brockwell, Belinda S Parker
Immunotherapy has revolutionized cancer treatment, with sustained responses to immune checkpoint inhibitors reported in a number of malignancies. Such therapeutics are now being trialed in aggressive or advanced cancers that are heavily reliant on untargeted therapies, such as triple negative breast cancer. However, responses have been underwhelming to date and are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. The tumor immune microenvironment has been closely linked to immunotherapeutic response, with superior responses observed in patients with T cell-inflamed or 'hot' tumors...
April 19, 2018: Cytokine
https://www.readbyqxmd.com/read/29665677/a-nanoscale-metal-organic-framework-overcomes-hypoxia-for-photodynamic-therapy-primed-cancer-immunotherapy
#13
Guangxu Lan, Kaiyuan Ni, Ziwan Xu, Samuel S Veroneau, Yang Song, Wenbin Lin
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions...
April 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29662547/pd-l1-expression-testing-in-non-small-cell-lung-cancer
#14
REVIEW
Cristina Teixidó, Noelia Vilariño, Roxana Reyes, Noemí Reguart
In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29659925/tobacco-smoking-associated-alterations-in-the-immune-microenvironment-of-squamous-cell-carcinomas
#15
Alexis Desrichard, Fengshen Kuo, Diego Chowell, Ken-Wing Lee, Nadeem Riaz, Richard J Wong, Timothy A Chan, Luc G T Morris
Background: Tobacco smoking creates DNA damage, inducing mutations and potentially altering the tumor immune microenvironment. These types of genetic and immune microenvironment alterations are critical factors known to affect tumor response to immunotherapy. Here we analyze the association between the mutational signature of tobacco smoking, tumor mutational load, and metrics of immune activity in squamous cell carcinomas arising in the head and neck and lung. Methods: Using RNA and DNA sequencing data from The Cancer Genome Atlas head and neck (HNSC; n = 287) and lung (LUSC; n = 130) squamous cell carcinoma data sets and two independent gene expression data sets (HNSC, n = 136; LUSC, n = 75), we examined associations between the mutational smoking signature, mutation count, immune cell infiltration, cytolytic activity, and interferon-γ signaling...
April 11, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29642375/molecular-characterization-of-gastric-epithelial-cells-using-flow-cytometry
#16
Kevin A Bockerstett, Chun Fung Wong, Sherri Koehm, Eric L Ford, Richard J DiPaolo
The ability to analyze individual epithelial cells in the gastric mucosa would provide important insight into gastric disease, including chronic gastritis and progression to gastric cancer. However, the successful isolation of viable gastric epithelial cells (parietal cells, neck cells, chief cells, and foveolar cells) from gastric glands has been limited due to difficulties in tissue processing. Furthermore, analysis and interpretation of gastric epithelial cell flow cytometry data has been difficult due to the varying sizes and light scatter properties of the different epithelial cells, high levels of autofluorescence, and poor cell viability...
April 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29604293/immune-cell-production-of-interleukin-17-induces-stem-cell-features-of-pancreatic-intraepithelial-neoplasia-cells
#17
Yu Zhang, Michelle Zoltan, Erick Riquelme, Hanwen Xu, Ismet Sahin, Susana Castro-Pando, Maria Fernanda Montiel, Kyle Chang, Zhengyu Jiang, Jianhua Ling, Sonal Gupta, William Horne, Melissa Pruski, Huamin Wang, Shao-Cong Sun, Guillermina Lozano, Paul Chiao, Anirban Maitra, Steven D Leach, Jay K Kolls, Eduardo Vilar Sanchez, Timothy C Wang, Jennifer M Bailey, Florencia McAllister
BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17 A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to PanIN initiation and progression. We investigated the effects of IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KCiMist ;G) and Kras(G12D); Trp53(R172H); Pdx1-Cre (KPC) mice (which upon tamoxifen induction spontaneously develop pancreatic intraepithelial neoplasias, PanINs) and control littermates...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29577477/neutrophil-based-drug-delivery-systems
#18
REVIEW
Dafeng Chu, Xinyue Dong, Xutong Shi, Canyang Zhang, Zhenjia Wang
White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a central role in acute inflammation induced by pathogens. Adhesion to vasculature and tissue infiltration of neutrophils are key processes in acute inflammation. Many inflammatory/autoimmune disorders and cancer therapies have been found to be involved in activation and tissue infiltration of neutrophils. A promising strategy to develop novel targeted drug delivery systems is the targeting and exploitation of activated neutrophils...
March 26, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29574423/palliative-stenting-for-oesophagogastric-cancer-tumour-and-host-factors-and-prognosis
#19
James Hugh Park, Niall Woodley, Donald C McMillan, Paul Glen
OBJECTIVES: Palliative self-expandable metallic stent (SEMS) insertion is common in patients not suitable for resection of oesophagogastric (OG) cancer. Factors which may determine survival, however, are not clear. The present study examined the relationship between tumour and host factors, including the systemic inflammatory response and survival of patients undergoing palliative SEMS insertion. METHODS: Patients with a diagnosis of OG cancer who were considered suitable for palliative SEMS only without systemic therapy were identified...
March 23, 2018: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/29567384/chlorin-nanoparticles-for-tissue-diagnostics-and-photodynamic-therapy
#20
Claudia Scalfi-Happ, Zhenxin Zhu, Susanna Graefe, Arno Wiehe, Anastasia Ryabova, Victor Loschenov, Rainer Wittig, Rudolf W Steiner
BACKGROUND: Organic crystalline nanoparticles (NPs) are not fluorescent due to the crystalline structure of the flat molecules organized in layers. In earlier experiments with Aluminum Phthalocyanine (AlPc)-derived NPs, the preferential uptake and dissolution by macrophages was demonstrated [3]. Therefore, inflamed tissue or cancer tissue with accumulated macrophages may exhibit specific fluorescence in contrast to healthy tissue which does not fluoresce. The present study addresses the photobiological effects of NP generated from Temoporfin (mTHPC), a clinically utilized photosensitizer belonging to the chlorin family...
March 19, 2018: Photodiagnosis and Photodynamic Therapy
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