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azoxymethane

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https://www.readbyqxmd.com/read/28522908/detection-and-characterization-of-murine-colitis-and-carcinogenesis-by-molecularly-targeted-contrast-enhanced-ultrasound
#1
Markus Brückner, Jan Heidemann, Tobias M Nowacki, Friederike Cordes, Jörg Stypmann, Philipp Lenz, Faekah Gohar, Andreas Lügering, Dominik Bettenworth
AIM: To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS: C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#2
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2(-/-)) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2(-/-) colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28494451/anthocyanins-prevent-colorectal-cancer-development-in-a-mouse-model
#3
Elisabeth Lippert, Petra Ruemmele, Florian Obermeier, Stefan Goelder, Claudia Kunst, Gerhard Rogler, Nadja Dunger, Helmut Messmann, Arndt Hartmann, Esther Endlicher
BACKGROUND: Colorectal cancer is the main leading cause of cancer-related deaths worldwide. Present data suggest that plant-derived anthocyanins have anti-inflammatory and chemopreventive properties. This study was aimed at evaluating the effect of an anthocyanin-rich extract from bilberries on colorectal tumour development and growth in the administration of azoxymethan (AOM)/dextran sodium sulfate (DSS) mouse model. METHODS: Colonic carcinogenesis was induced by AOM and DSS 3 or 5%, respectively, in 50 female Balb/c mice...
May 12, 2017: Digestion
https://www.readbyqxmd.com/read/28480409/biochemical-composition-and-nutritional-evaluation-of-barley-rihane-hordeum-vulgare-l
#4
Lamia Lahouar, Fatma Ghrairi, Amira El Arem, Sana Medimagh, Mouledi El Felah, Hichem Ben Salem, Lotfi Achour
BACKGROUND: Many experimental studies have suggested an important role for barley Rihane(BR)in the prevention of colon cancer and cardiovascular diseases. The objective of this study was to evaluate the physico-chemical properties and nutritional characterizations of BR compared to other varieties grown in Tunisia (Manel, Roho and Tej). MATERIAL AND METHODS: Total, insoluble and soluble dietary fiber(β-glucan), total protein, ash and some minerals of BR and Tunisian barley varieties were determined...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28478805/clostridium-butyricum-partially-regulates-the-development-of-colitis-associated-cancer-through-mir-200c
#5
Y Xiao, X Dai, K Li, G Gui, J Liu, H Yang
Colitis-associated cancer (CAC), one form of colorectal cancer (CRC),is an increasing concern worldwide. Both diagnosis and current therapy are challenging and bottlenecked. The aim of this study is to investigate novel mechanisms by which the therapeutic C. butyricum regulates colitis-induced oncogenesis. Mouse models of CAC were established with 2,4,6-Trinitrobenzenesulfonic acid (TNBS)and azoxymethane (AOM), following by biochemical, clinical and histological analysis. The integrity of epitheliumwas examined by electron microscopy (EM)...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28468928/sildenafil-suppresses-inflammation-driven-colorectal-cancer-in-mice
#6
Bianca N Islam, Sarah K Sharman, Yali Hou, Allison E Bridges, Nagendra Singh, Sangmi Kim, Ravindra Kolhe, Jimena Trillo-Tinoco, Paulo C Rodriguez, Franklin G Berger, Subbaramiah Sridhar, Darren D Browning
Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against DSS-induced barrier dysfunction...
May 3, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28455963/trkc-promotes-colorectal-cancer-growth-and-metastasis
#7
Min Soo Kim, Kwang Wook Suh, Suntaek Hong, Wook Jin
The current work reveals that TrkC receptor is crucial to many aspects of tumorigenicity and metastasis of cancer. However, with only a few exceptions, such as colorectal cancer (CRC), where suppressing tumorigenic and metastatic ability via expression of TrkC as tumor suppressor have been proposed. These diverse lines of evidence led us to investigate whether TrkC is involved in CRC progression. By using mouse models and molecular biology analyses, we demonstrate that TrkC acts as an activator in tumorigenicity and metastasis of colorectal cancer...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28434818/expression-of-a-kinase-anchor-protein-13-and-rho-associated-coiled-coil-containing-protein-kinase-in-restituted-and-regenerated-mucosal-epithelial-cells-following-mucosal-injury-and-colorectal-cancer-cells-in-mouse-models
#8
Yumi Kangawa, Toshinori Yoshida, Takeshi Tanaka, Akira Kataoka, Naomi Koyama, Tomoka Ohsumi, Shim-Mo Hayashi, Makoto Shibutani
We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled-coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during the healing stage of mouse colitis. BALB/c mice received an intraperitoneal injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran sulfate sodium (DSS) administered through their drinking water to induce colon cancer, or a 7-day administration of 4% DSS to induce colitis...
April 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28426873/high-fat-diet-induced-leptin-and-wnt-expression-rna-sequencing-and-pathway-analysis-of-mouse-colonic-tissue-and-tumors
#9
Harrison M Penrose, Sandra Heller, Chloe Cable, Hani Nakhoul, Melody Baddoo, Erik Flemington, Susan E Crawford, Suzana D Savkovic
Obesity, an immense epidemic affecting approximately half a billion adults, has doubled in prevalence in the last several decades. Epidemiological data support that obesity, due to intake of a high-fat, western diet, increases the risk of colon cancer; however, the mechanisms underlying this risk remain unclear. Here, utilizing next generation RNA sequencing, we aimed to determine the high-fat diet (HFD) mediated expression profile in mouse colon and the azoxymethane/dextran sulfate sodium model of colon cancer...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28416486/a-squalene-based-nanomedicine-for-oral-treatment-of-colon-cancer
#10
Larissa Kotelevets, Eric Chastre, Joachim Caron, Julie Mougin, Gerard Bastian, Alain Pineau, Francine Walker, Therese Lehy, Didier Desmaele, Patrick Couvreur
Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared to uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28410235/cysteinyl-leukotriene-receptor-1-facilitates-tumorigenesis-in-a-mouse-model-of-colitis-associated-colon-cancer
#11
Janina Osman, Sayeh Savari, Naveen Kumar Chandrashekar, Kishan Bellamkonda, Desiree Douglas, Anita Sjölander
Cysteinyl leukotriene receptor 1 (CysLT1R) has been shown to be up-regulated in the adenocarcinomas of colorectal cancer patients, which is associated with a poor prognosis. In a spontaneous model of colon cancer, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R in the induced azoxymethane/dextran sulfate sodium (AOM/DSS) model of colitis-associated colon cancer...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405523/histidine-decarboxylase-hdc-expressing-granulocytic-myeloid-cells-induce-and-recruit-foxp3-regulatory-t-cells-in-murine-colon-cancer
#12
Xiaowei Chen, Yoshihiro Takemoto, Huan Deng, Moritz Middelhoff, Richard A Friedman, Timothy H Chu, Michael J Churchill, Yan Ma, Karan K Nagar, Yagnesh H Tailor, Siddhartha Mukherjee, Timothy C Wang
The colorectal tumor microenvironment contains a diverse population of myeloid cells that are recruited and converted to immunosuppressive cells, thus facilitating tumor escape from immunoediting. We have identified a genetically and functionally distinct subset of dynamic bone marrow myeloid cells that are characterized by histidine decarboxylase (HDC) expression. Lineage tracing in Hdc-CreERT2;R26-LSL-tdTomato mice revealed that in homeostasis, there is a strong bias by HDC(+) myeloid cells toward the CD11b(+)Ly6G(hi) granulocytic lineage, which was accelerated during azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic carcinogenesis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400195/egfr-in-tumor-associated-myeloid-cells-promotes-development-of-colorectal-cancer-in-mice-and-associates-with-outcomes-of-patients
#13
Sriram Srivatsa, Mariel C Paul, Claudia Cardone, Martin Holcmann, Nicole Amberg, Paulina Pathria, Michaela A Diamanti, Markus Linder, Gerald Timelthaler, Hans P Dienes, Lukas Kenner, Fritz Wrba, Gerald W Prager, Stefan Rose-John, Robert Eferl, Giuseppina Liguori, Gerardo Botti, Erika Martinelli, Florian R Greten, Fortunato Ciardiello, Maria Sibilia
BACKGROUND & AIMS: Inhibitors of the epidermal growth factor receptor (EGFR) are the first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors are ineffective in these patients, and tumor level of EGFR does not associate with response to therapy. We screened human colorectal tumors for EGFR-positive myeloid cells and investigated their association with patient outcome. We also performed studies in mice to evaluate how EGFR expression in tumor cells and myeloid cells contributes to development of colitis-associated cancer and ApcMin-dependent intestinal tumorigenesis...
April 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28389570/bves-regulates-c-myc-stability-via-pp2a-and-suppresses-colitis-induced-tumourigenesis
#14
Bobak Parang, Andrew M Kaz, Caitlyn W Barrett, Sarah P Short, Wei Ning, Cody E Keating, Mukul K Mittal, Rishi D Naik, Mary K Washington, Frank L Revetta, J Joshua Smith, Xi Chen, Keith T Wilson, Thomas Brand, David M Bader, William P Tansey, Ru Chen, Teresa A Brentnall, William M Grady, Christopher S Williams
OBJECTIVE: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD. DESIGN: We determined BVES promoter methylation status using an Infinium HumanMethylation450 array screen of patients with UC with and without CAC...
May 2017: Gut
https://www.readbyqxmd.com/read/28381120/simultaneous-assessment-of-the-efficacy-and-toxicity-of-marine-mollusc-derived-brominated-indoles-in-an-in-vivo-model-for-early-stage-colon-cancer
#15
Babak Esmaeelian, Kirsten Benkendorff, Richard K Le Leu, Catherine A Abbott
The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita, while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later...
April 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28380450/the-g-protein-coupled-receptor-56-expressed-in-colonic-stem-and-cancer-cells-binds-progastrin-to-promote-proliferation-and-carcinogenesis
#16
Guangchun Jin, Kosuke Sakitani, Hongshan Wang, Ying Jin, Alexander Dubeykovskiy, Daniel L Worthley, Yagnesh Tailor, Timothy C Wang
Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28362171/effects-of-dietary-resistant-starch-on-the-wnt-signaling-pathway-and-preneoplastic-cells-in-the-colons-of-azoxymethane-treated-rats
#17
Nicole Cray, Yinsheng Zhao, Yinan Fang, Peng Liu, Linda Pollak, Susan Duvick, Diane F Birt, Elizabeth M Whitley
Dietary resistant starch (RS) has been suggested to reduce colonic neoplasia. To determine the effects of digestion-resistant cornstarch on colonic carcinogenesis and Wnt signaling in azoxymethane (AOM)-treated F344 rats, diets containing naturally occurring RS from corn lines derived partially from Guat209 (GUAT), AR16035 (AR), or a hybrid (ARxGUAT), containing 34.5 ± 2.0, 0.2 ± 0.1, and 1.9 ± 0.1% RS, respectively, were fed at 55% of the diet. GUAT-fed rats had increased cecal content and tissue weight and decreased cecal pH compared with AR- or ARxGUAT-fed rats...
March 31, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28360037/mitochondrial-dna-integrity-is-maintained-by-ape1-in-carcinogen-induced-colorectal-cancer
#18
Joan Ballista-Hernandez, Magaly Martinez-Ferrer, Roman Velez, Consuelo Climent, Maria M Sanchez-Vazquez, Ceidy Torres, Adlin Rodriguez-Munoz, Sylvette Ayala-Pena, Carlos A Torres-Ramos
Changes in mitochondrial DNA (mtDNA) integrity have been reported in many cancers, however, the contribution of mtDNA integrity to tumorigenesis is not well understood. We used a transgenic mouse model that is haploinsufficient for the apurinic/apyrimidinic endonuclease 1 (Apex1+/-) gene, which encodes the base excision repair (BER) enzyme APE1, to determine its role in protecting mtDNA from the effects of azoxymethane (AOM), a carcinogen used to induce colorectal cancer (CRC). Repair kinetics of AOM-induced mtDNA damage was evaluated using quantitative PCR after a single AOM dose and a significant induction in mtDNA lesions in colonic crypts from both wild type (WT) and Apex1+/-animals were observed...
March 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28357137/diet-induced-obesity-is-associated-with-an-impaired-nk-cell-function-and-an-increased-colon-cancer-incidence
#19
Ina Bähr, Vincent Goritz, Henriette Doberstein, Grit Gesine Ruth Hiller, Philip Rosenstock, Janine Jahn, Ole Pörtner, Tobias Berreis, Thomas Mueller, Julia Spielmann, Heike Kielstein
Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors...
2017: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/28350804/syndecan-1-deficiency-promotes-tumor-growth-in-a-murine-model-of-colitis-induced-colon-carcinoma
#20
Adi Binder Gallimidi, Gabriel Nussbaum, Esther Hermano, Barak Weizman, Amichay Meirovitz, Israel Vlodavsky, Martin Götte, Michael Elkin
Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated...
2017: PloS One
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