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https://www.readbyqxmd.com/read/27903155/obesity-and-cancer-mechanisms-tumor-microenvironment-and-inflammation
#1
Neil M Iyengar, Ayca Gucalp, Andrew J Dannenberg, Clifford A Hudis
Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27897991/the-double-role-of-p53-in-cancer-and-autoimmunity-and-its-potential-as-therapeutic-target
#2
REVIEW
Alessandra Fierabracci, Marsha Pellegrino
p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27884517/endoscopic-morphological-features-of-ulcerative-colitis-associated-dysplasia-classified-according-to-the-scenic-consensus-statement
#3
Shinya Sugimoto, Makoto Naganuma, Yasushi Iwao, Katsuyoshi Matsuoka, Masayuki Shimoda, Shuji Mikami, Shinta Mizuno, Yoshihiro Nakazato, Kosaku Nanki, Nagamu Inoue, Haruhiko Ogata, Takanori Kanai
BACKGROUND AND AIMS: Recent advances in endoscopic equipment and diagnostic techniques have made possible the detection of early dysplasia in the inflamed mucosa of ulcerative colitis (UC). The SCENIC consensus statement recommends the use of unified terminology for the morphology of dysplasia. In this study, we investigated the endoscopic features of high-grade dysplasia (HGD) in a clinical setting. METHODS: We retrospectively identified 62 patients with UC who were diagnosed with colitis-associated cancer or HGD between 1997 and 2015...
November 21, 2016: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/27877245/imaging-nanotherapeutics-in-inflamed-vasculature-by-intravital-microscopy
#4
REVIEW
Zhenjia Wang
Intravital microscopy (IVM) is the application of light microscopy to real time study biology of live animal tissues in intact and physiological conditions with the high spatial and temporal resolution. Advances in imaging systems, genetic animal models and imaging probes, IVM has offered quantitative and dynamic insight into cell biology, immunology, neurobiology and cancer. In this review, we will focus on the targeting of nanotherapeutics to inflamed vasculature. We will introduce the basic concept and principle of IVM and demonstrate that IVM is a powerful tool used to quantitatively determine the molecular mechanisms of interactions between nanotherapeutics and neutrophils or endothelium in living mice...
2016: Theranostics
https://www.readbyqxmd.com/read/27869795/cd68-macrosialin-not-just-a-histochemical-marker
#5
Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells...
November 21, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27837027/association-of-pd-1-pd-l-axis-expression-with-cytolytic-activity-mutational-load-and-prognosis-in-melanoma-and-other-solid-tumors
#6
Ludmila Danilova, Hao Wang, Joel Sunshine, Genevieve J Kaunitz, Tricia R Cottrell, Haiying Xu, Jessica Esandrio, Robert A Anders, Leslie Cope, Drew M Pardoll, Charles G Drake, Janis M Taube
Programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade has led to remarkable and durable objective responses in a number of different tumor types. A better understanding of factors associated with the PD-1/PD-L axis expression is desirable, as it informs their potential role as prognostic and predictive biomarkers and may suggest rational treatment combinations. In the current study, we analyzed PD-L1, PD-L2, PD-1, and cytolytic activity (CYT) expression, as well as mutational density from melanoma and eight other solid tumor types using The Cancer Genome Atlas database...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27837020/density-of-immunogenic-antigens-does-not-explain-the-presence-or-absence-of-the-t-cell-inflamed-tumor-microenvironment-in-melanoma
#7
Stefani Spranger, Jason J Luke, Riyue Bao, Yuanyuan Zha, Kyle M Hernandez, Yan Li, Alexander P Gajewski, Jorge Andrade, Thomas F Gajewski
Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer-testis antigens. Therapies are being pursued to trigger immune infiltration into non-T-cell-inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27836246/emerging-role-of-immunotherapy-in-urothelial-carcinoma-immunobiology-biomarkers
#8
REVIEW
Randy F Sweis, Matthew D Galsky
Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement...
December 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27827303/an-hdac6-inhibitor-confers-protection-and-selectively-inhibits-b-cell-infiltration-in-dss-induced-colitis-in-mice
#9
Anh Do, Robert C Reid, Rink-Jan Lohman, Matthew J Sweet, David P Fairlie, Abishek Iyer
Small molecule histone deacetylase (HDAC) inhibitors with anti-inflammatory activity may be candidates for targeting intestinal inflammatory pathways in inflammatory bowel disease (IBD). This study investigated whether treatment with a potent HDAC6 inhibitor, BML-281, could protect against colonic inflammation and prevent inflammatory cell infiltration into the colon to drive disease pathology in a mouse model of acute DSS-colitis. Control and acute DSS-colitis mice were treated with BML-281 (1mg/kg/day s.c...
November 8, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27826372/vascular-inflammation-a-novel-access-route-for-nanomedicine
#10
Roberto Molinaro, Christian Boada, Guillermo Medrano Del Rosal, Kelly A Hartman, Claudia Corbo, Elizabeth D Andrews, Naama E Toledano-Furman, John P Cooke, Ennio Tasciotti
Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD...
September 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/27821498/established-t-cell-inflamed-tumors-rejected-after-adaptive-resistance-was-reversed-by-combination-sting-activation-and-pd-1-pathway-blockade
#11
Ellen Moore, Paul E Clavijo, Ruth Davis, Harrison Cash, Carter Van Waes, Young Kim, Clint Allen
Patients with head and neck squamous cell carcinoma harbor T cell-inflamed and non-T cell-inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell-inflamed (MOC1), but not non-T cell-inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27789270/topical-5-fluorouracil-is-a-novel-targeted-therapy-for-the-keratocystic-odontogenic-tumor
#12
Nicholas J Ledderhof, Marco F Caminiti, Grace Bradley, David K Lam
PURPOSE: The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis. MATERIALS AND METHODS: An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014...
September 30, 2016: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/27752256/understanding-immune-cells-in-tertiary-lymphoid-organ-development-it-is-all-starting-to-come-together
#13
Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27717961/malignant-inflammation-in-cutaneous-t-cell-lymphoma-a-hostile-takeover
#14
Thorbjørn Krejsgaard, Lise M Lindahl, Nigel P Mongan, Mariusz A Wasik, Ivan V Litvinov, Lars Iversen, Erik Langhoff, Anders Woetmann, Niels Odum
Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome...
October 7, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27716626/secretory-leukoprotease-inhibitor-is-required-for-efficient-quercetin-mediated-suppression-of-tnf%C3%AE-secretion
#15
Stefania De Santis, Dale Kunde, Grazia Serino, Vanessa Galleggiante, Maria Lucia Caruso, Mauro Mastronardi, Elisabetta Cavalcanti, Nicole Ranson, Aldo Pinto, Pietro Campiglia, Angelo Santino, Rajaraman Eri, Marcello Chieppa
Dendritic cells (DCs) are professional antigen presenting cells (APCs) that in response to microbial infections generate long-lasting adaptive immune response. Following microbial uptake, DCs undergo a cascade of cellular differentiation that ultimately leads to "mature" DCs. Mature DCs produce a variety of inflammatory cytokines, including tumor necrosis factor-α (TNFβ) a key cytokine for the inflammatory cascade. In numerous studies, polyphenols, including quercetin, demonstrated their ability to suppress TNFα secretion and protect from the onset of chronic inflammatory disorders...
October 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27706546/a-liver-nodule-in-a-patient-transplanted-for-primary-sclerosing-cholangitis-an-interdisciplinary-diagnostic-approach
#16
S H Loosen, M Schmeding, C Roderburg, M Binnebösel, I Temizel, F M Mottaghy, J J W Tischendorf, F Tacke, N T Gaisa, K Hussein, U Lehmann, C Trautwein, U P Neumann, T Luedde
We report the case of a 53-year-old female patient who was transplanted with the liver of a 71-year-old male donor for advanced primary sclerosing cholangitis (PSC) and who additionally was diagnosed with a histologically non-classifiable colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4 months after transplantation, a liver lesion measuring 16 × 23 mm was detected in the transplanted liver. This lesion had not been noticed immediately after transplantation and showed a pattern suspicious for malignancy in contrast-enhanced ultrasound...
October 5, 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27706097/anti-inflammatory-effects-of-aspalathus-linearis-and-cyclopia-spp-extracts-in-a-uvb-keratinocyte-hacat-model-utilising-interleukin-1%C3%AE-accumulation-as-biomarker
#17
Tandeka Magcwebeba, Pieter Swart, Sonja Swanevelder, Elizabeth Joubert, Wentzel Gelderblom
Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have been demonstrated in skin cancer models in vivo. In the current study, the anti-inflammatory effects of methanol and aqueous extracts of these herbal teas were investigated in a UVB/HaCaT keratinocyte model with intracellular interleukin-1α (icIL-1α) accumulation as a biomarker...
October 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27692729/midkine-is-up-regulated-in-both-cancerous-and-inflamed-bowel-reflecting-lymph-node-metastasis-in-colorectal-cancer-and-clinical-activity-of-ulcerative-colitis
#18
Malgorzata Krzystek-Korpacka, Sabina Gorska, Dorota Diakowska, Bartosz Kapturkiewicz, Magdalena Podkowik, Andrzej Gamian, Iwona Bednarz-Misa
Midkine is a multifunctional cytokine and growth factor displaying proinflammatory and pro-tumorigenic activity. Its association with bowel diseases has not been fully elucidated. Our purpose was to delineate midkine expression pattern by RT-qPCR in inflamed/cancerous bowel (n=208) and whole blood (n=150) in colorectal cancer (CRC), Crohn's disease (CD), and ulcerative colitis (UC) and to evaluate midkine dynamics in early postoperative period following colorectal surgery. The expression of midkine was significantly up-regulated in stage III CRC and independently associated with lymph node metastasis...
September 28, 2016: Cytokine
https://www.readbyqxmd.com/read/27679575/vam3-a-compound-derived-from-vitis-amurensis-rupr-attenuated-colitis-related-tumorigenesis-by-inhibiting-nf-%C3%AE%C2%BAb-signaling-pathway
#19
Lingling Xuan, Rentao Jiang, Zhiyuan Wu, Honggan Yi, Chunsuo Yao, Qi Hou, Chunfeng Qu
BACKGROUND: Chronic inflammation is one of the important mediators of colitis-related colon cancer (CRC). Abundant mast cells (MCs) were observed in the tumor microenvironment and mediators released upon MC activation play an important role in the process of chronic inflammation. Previously, we found that activation of intestine mucosal MCs recruited and modulated the inflammatory CD11b(+)Gr1(+) cells to promote the CRC development. In the current study we investigated the effects of Vam3, a resveratrol dimer with potent anti-inflammatory effects, on CRC development...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27661668/colonic-lamina-propria-inflammatory-cells-from-patients-with-ibd-induce-the-nuclear-factor-e2-related-factor-2-thereby-leading-to-greater-proteasome-activity-and-apoptosis-protection-in-human-colonocytes
#20
Marie-Luise Kruse, Martin Friedrich, Alexander Arlt, Christoph Röcken, Jan-Hendrik Egberts, Susanne Sebens, Heiner Schäfer
BACKGROUND: The antioxidant transcription factor Nrf2 confers broad cytoprotection and has a dual role in tumorigenesis. Enhancing proteasome activity is one mechanism by which Nrf2 can promote cancer development, e.g., colorectal cancer. This study investigated whether this potential oncogenic effect of Nrf2 emerges already from the epithelial adaptation to persistent oxidative stress during inflammatory bowel disease (IBD). METHODS: Reactive oxygen species (ROS)-producing inflammatory myeloid cells (IMCs) from colon tissue of patients with IBD were cocultured with human NCM460 colonocytes...
September 21, 2016: Inflammatory Bowel Diseases
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