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https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#1
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723632/potential-link-between-fusobacterium-enrichment-and-dna-methylation-accumulation-in-the-inflammatory-colonic-mucosa-in-ulcerative-colitis
#2
Tomomitsu Tahara, Ichiro Hirata, Naoko Nakano, Sayumi Tahara, Noriyuki Horiguchi, Tomohiko Kawamura, Masaaki Okubo, Takamitsu Ishizuka, Hyuga Yamada, Dai Yoshida, Takafumi Ohmori, Kohei Maeda, Naruomi Komura, Hirokazu Ikuno, Yasutaka Jodai, Toshiaki Kamano, Mitsuo Nagasaka, Yoshihito Nakagawa, Tetsuya Tuskamoto, Makoto Urano, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#3
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28707588/targeting-the-prokineticin-system-to-control-chronic-pain-and-inflammation
#4
Lucia Negri, Daniela Maftei
Prokineticin1 and prokineticin2 belong to a new family of chemokines identified in several species including mammals and characterized by the presence of five disulfide bridges. These proteins signal through two G-coupled receptors (prokineticin-receptor1 and prokineticin-receptor2) widely expressed in all tissues and involved in a large spectrum of biological activities, including angiogenesis, hematopoiesis, immune processes, inflammation and nociceptive transmission. Prokineticin2 is overexpressed in inflamed tissues and has a crucial role in neutrophil dependent inflammation and hypernociception...
July 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28706782/immunohistochemical-evaluation-of-podoplanin-in-odontogenic-tumours-cysts-using-anti-human-podoplanin-antibody
#5
Namrata Singhal, Nitin Khanduri, Deepak Kurup, Brijesh Gupta, Pranjan Mitra, Roshani Chawla
BACKGROUND: Odontogenic Cysts & tumors originate through some aberration from the normal pattern of odontogenesis. Ameloblastoma is one of the most frequent intraosseous odontogenic tumors. However it is no longer appropriate to use the diagnosis of ameloblastoma without specifying the type. Varied-clinical entities of ameloblastoma differ in their biologic behaviour. Odontogenic cysts like dentigerous and radicular cysts are less aggressive in nature than odontogenic tumors. Recently, podoplanin commonly used as a lymphatic endothelial marker in cancers has recently been found to play a possible role in odontogenic tumorigenesis also...
May 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/28706162/presence-of-salmonella-avra-in-colorectal-tumor-and-its-precursor-lesions-in-mouse-intestine-and-human-specimens
#6
Rong Lu, Maarten Bosland, Yinglin Xia, Yong-Guo Zhang, Ikuko Kato, Jun Sun
Evidence directly supporting an association between Salmonella infection and colorectal cancer in human subjects is sparse. It has been well recognized that Salmonella infection increases the risk of gallbladder cancer. AvrA, a bacterial protein from Salmonella enterica, plays a crucial role in establishing chronic infection. To our knowledge, the presence of the bacterial AvrA has never been studied in human samples. Here, we demonstrated the presence and cellular localization of AvrA in inflamed, colorectal tumor and its precursor lesions, using both animal experimental infection models and human clinical specimens...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700533/cd103-dendritic-cell-function-is-altered-in-the-colons-of-patients-with-ulcerative-colitis
#7
Hiroshi Matsuno, Hisako Kayama, Junichi Nishimura, Yuki Sekido, Hideki Osawa, Soumik Barman, Takayuki Ogino, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Motoi Uchino, Hiroki Ikeuchi, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Tsunekazu Mizushima
BACKGROUND: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). METHODS: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24)...
July 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28693133/overexpression-of-the-x-linked-ribosomal-protein-s4-predicts-poor-prognosis-in-patients-with-intrahepatic-cholangiocarcinoma
#8
Jie Kuang, Qin-Yu Li, Fei Fan, Ning-Jia Shen, Yong-Jie Zhan, Zhao-Hui Tang, Wen-Long Yu
X-linked ribosomal protein S4 (RPS4X) has previously been reported to be associated with cisplatin resistance and clinical outcome in bladder and ovarian cancer. However, the value of RPS4X as a diagnostic and prognostic marker in intrahepatic cholangiocarcinoma (ICC) has not yet been investigated. The present study evaluated the expression pattern, and diagnostic and prognostic value of RPS4X in patients with ICC. Retrospective analysis was performed for a total of 201 patients with intrahepatic cholangiocarcinoma, and 8 patients with inflammation of the bile duct...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28662970/molecular-dissection-of-cd8-t-cell-dysfunction
#9
REVIEW
Chao Wang, Meromit Singer, Ana C Anderson
Chronic viral infections and cancer often lead to the emergence of dysfunctional or 'exhausted' CD8(+) T cells, and the restoration of their functions is currently the focus of therapeutic interventions. In this review, we detail recent advances in the annotation of the gene modules and the epigenetic landscape associated with T-cell dysfunction. Together with analysis of single-cell transcriptomes, these findings have enabled a deeper and more precise understanding of the transcriptional mechanisms that induce and maintain the dysfunctional state and highlight the heterogeneity of CD8(+) T-cell phenotypes present in chronically inflamed tissue...
June 26, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28656348/pap-reg3a-favors-perineural-invasion-in-pancreatic-adenocarcinoma-and-serves-as-a-prognostic-marker
#10
Jérémy Nigri, Meritxell Gironella, Christian Bressy, Elena Vila-Navarro, Julie Roques, Sophie Lac, Caroline Bontemps, Coraline Kozaczyk, Jérôme Cros, Daniel Pietrasz, Raphaël Maréchal, Jean-Luc Van Laethem, Juan Iovanna, Jean-Baptiste Bachet, Emma Folch-Puy, Richard Tomasini
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer...
June 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28655914/igf1r-deficiency-attenuates-acute-inflammatory-response-in-a-bleomycin-induced-lung-injury-mouse-model
#11
Sergio Piñeiro-Hermida, Icíar P López, Elvira Alfaro-Arnedo, Raquel Torrens, María Iñiguez, Lydia Alvarez-Erviti, Carlos Ruíz-Martínez, José G Pichel
IGF1R (Insulin-like Growth Factor 1 Receptor) is a tyrosine kinase with pleiotropic cellular functions. IGF activity maintains human lung homeostasis and is implicated in pulmonary diseases such as cancer, ARDS, COPD, asthma and fibrosis. Here we report that lung transcriptome analysis in mice with a postnatally-induced Igf1r gene deletion showed differentially expressed genes with potentially protective roles related to epigenetics, redox and oxidative stress. After bleomycin-induced lung injury, IGF1R-deficient mice demonstrated improved survival within a week...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650441/neutrophil-mediated-anticancer-drug-delivery-for-suppression-of-postoperative-malignant-glioma-recurrence
#12
Jingwei Xue, Zekai Zhao, Lei Zhang, Lingjing Xue, Shiyang Shen, Yajing Wen, Zhuoyuan Wei, Lu Wang, Lingyi Kong, Hongbin Sun, Qineng Ping, Ran Mo, Can Zhang
Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain...
July 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#13
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28647616/photodynamic-therapy-in-dermatology-beyond-non-melanoma-cancer-an-update
#14
REVIEW
Xiang Wen, Yong Li, Michael R Hamblin
Photodynamic therapy (PDT) employs a photosensitizer (PS) and visible light in the presence of oxygen, leading to production of cytotoxic reactive oxygen species, which can damage the cellular organelles and cause cell death. In dermatology PDT has usually taken the form of topical application of a precursor in the heme biosynthesis pathway, called 5-aminolevulinic acid (or its methyl ester), so that an active PS, protoporphyrin IX accumulates in the skin. As PDT enhances dermal remodeling and resolves chronic inflamation, it has been used to treat cutaneous disorders include actinic keratoses, acne, viral warts, skin rejuvenation, psoriasis, localized scleroderma, some non-melanoma skin cancers and port-wine stains...
June 21, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28642759/biodistribution-and-efficacy-of-human-adipose-derived-mesenchymal-stem-cells-following-intranodal-administration-in-experimental-colitis
#15
Mercedes Lopez-Santalla, Pablo Mancheño-Corvo, Amelia Escolano, Ramon Menta, Olga DelaRosa, Jose Luis Abad, Dirk Büscher, Juan M Redondo, Juan A Bueren, Wilfried Dalemans, Eleuterio Lombardo, Marina I Garin
Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs). This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28627961/microsomal-prostaglandin-e2-synthase-1-inhibitors-a-patent-review
#16
Anastasia Psarra, Aikaterini Nikolaou, Maroula G Kokotou, Dimitris Limnios, George Kokotos
Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents. Areas covered: This review article summarizes the mPGES-1 inhibitors presented in patent literature from 2000 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo...
June 26, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28617757/looking-into-enteric-virome-in-patients-with-ibd-defining-guilty-or-innocence
#17
Susana Lopes, Patricia Andrade, Silvia Conde, Rodrigo Liberal, Cláudia C Dias, Salomão Fernandes, Jorge Pinheiro, Joana S Simões, Fátima Carneiro, Fernando Magro, Guilherme Macedo
BACKGROUND: Although there is some evidence suggesting that certain viruses may be involved in the onset of inflammatory bowel disease (IBD), data regarding viral prevalence and viral load in blood and mucosa of patients with IBD are scarce. The main aim of this study is to evaluate the prevalence and viral load of common Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 6 in blood and mucosa of adult patients with endoscopic active IBD. METHODS: From January to December 2014, ulcerative colitis and Crohn's disease patients with active endoscopic disease were consecutively enrolled...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#18
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609551/chronic-exposure-to-tetracyclines-and-subsequent-diagnosis-for-non-melanoma-skin-cancer-in-a-large-midwestern-u-s-patient-population
#19
P P Vakharia, B Nardone, B J Schlosser, D Lee, L Serrano, D P West
Tetracyclines (TCNs) are commonly used in the management of several chronic dermatological disorders, partly due to their affinity for inflamed skin tissue, as they are known to suppress cytokines including tumor necrosis factor-alpha and interleukin-6 that are typically involved in inflammatory skin disorders.(1) TCNs are known to be photoreactive following ultraviolet (UV) radiation exposure, a known risk factor for the development of nonmelanoma skin cancer (NMSC), notably basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)...
June 13, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28588582/nanoparticle-based-magnetic-resonance-imaging-on-tumor-associated-macrophages-and-inflammation
#20
REVIEW
Natalie J Serkova
The inflammatory response, mediated by tissue-resident or newly recruited macrophages, is an underlying pathophysiological condition for many diseases, including diabetes, obesity, neurodegeneration, atherosclerosis, and cancer. Paradoxically, inflammation is a double-edged sword in oncology. Macrophages are, generally speaking, the major drivers of inflammatory insult. For many solid tumors, high density of cells expressing macrophage-associated markers have generally been found in association with a poor clinical outcome, characterized by inflamed microenvironment, a high level of dissemination and resistance to conventional chemotherapies...
2017: Frontiers in Immunology
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