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Cancer Associated Fibroblast Colon

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https://www.readbyqxmd.com/read/30101717/novel-tetrahydrobenzo-b-thiophene-compounds-exhibit-anticancer-activity-through-enhancing-apoptosis-and-inhibiting-tyrosine-kinase
#1
Souad A El-Metwally, Ali K Khalil, Abeer M El-Naggar, Wael M El-Sayed
ackground: Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. OBJECTIVE: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. METHODS: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7-tetrahydrobenzo[b] thiophene (1)...
August 13, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/30083271/carcinoma-associated-fibroblasts-promote-the-stemness-and-chemoresistance-of-colorectal-cancer-by-transferring-exosomal-lncrna-h19
#2
Jing Ren, Liang Ding, Dongya Zhang, Guoping Shi, Qianyun Xu, Sunan Shen, Yaping Wang, Tingting Wang, Yayi Hou
Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). The crosstalk between carcinoma- associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment promotes tumor development and confers chemoresistance. In this study, we further investigated the underlying tumor-promoting roles of CAFs and the molecular mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed...
2018: Theranostics
https://www.readbyqxmd.com/read/29981368/mechanisms-of-action-of-vitamin-d-in-colon-cancer
#3
REVIEW
Gemma Ferrer-Mayorga, María Jesús Larriba, Piero Crespo, Alberto Muñoz
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC...
July 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29907957/laminin-%C3%AE-1-orchestrates-vegfa-functions-in-the-ecosystem-of-colorectal-carcinoma
#4
Elmina Mammadova-Bach, Tristan Rupp, Caroline Spenlé, Ivo Jivkov, Pattabhiraman Shankaranarayanan, Annick Klein, Laura Pisarsky, Agnès Méchine-Neuville, Gérard Cremel, Michèle Kedinger, Olivier De Wever, Noona Ambartsumian, Sylvie Robine, Erwan Pencreach, Dominique Guenot, Patricia Simon-Assmann, Jacky G Goetz, Gertraud Orend, Olivier Lefebvre
BACKGROUND INFORMATION: Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. RESULTS: By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth...
June 15, 2018: Biology of the Cell
https://www.readbyqxmd.com/read/29901199/fibroblast-growth-factor-18-promotes-the-growth-migration-and-invasion-of-mda%C3%A2-mb%C3%A2-231-cells
#5
Ziyi Yu, Longquan Lou, Yi Zhao
Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein has been associated with poor overall survival in cancer patients. However, its function has not been investigated in breast cancer. In the present study, we demonstrated that FGF18 promoted cell growth and metastasis in vitro and stimulated tumor growth in xenograft models in vivo. FGF18 mediated the proliferation of MDA‑MB‑231 cells via the ERK/c‑Myc signaling pathway and induced epithelial‑to‑mesenchymal transition (EMT) factors to promote cancer migration and invasion...
August 2018: Oncology Reports
https://www.readbyqxmd.com/read/29899872/hitting-two-oncogenic-machineries-in-cancer-cells-cooperative-effects-of-the-multi-kinase-inhibitor-ponatinib-and-the-bet-bromodomain-blockers-jq1-or-dbet1-on-human-carcinoma-cells
#6
Karin Bauer, Daniela Berger, Christoph C Zielinski, Peter Valent, Thomas W Grunt
In recent years, numerous new targeted drugs, including multi-kinase inhibitors and epigenetic modulators have been developed for cancer treatment. Ponatinib blocks a variety of tyrosine kinases including ABL and fibroblast growth factor receptor (FGFR), and the BET bromodomain (BRD) antagonists JQ1 and dBET1 impede MYC oncogene expression. Both drugs have demonstrated substantial anti-cancer efficacy against several hematological malignancies. Solid tumors, on the other hand, although frequently driven by FGFR and/or MYC, are often unresponsive to these drugs...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29888780/immunohistochemical-expression-of-fascin-1-in-colorectal-cancer-in-relation-to-clinical-and-pathological-parameters
#7
Barbara M Piskor, Anna Pryczynicz, Emilia Lubowicka, Katarzyna Miniewska, Justyna Zinczuk, Konrad Zareba, Katarzyna Guzinska-Ustymowicz
INTRODUCTION: Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 ex-pression and clinical-pathological parameters...
2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29885857/from-epidemiology-to-treatment-aspirin-s-prevention-of-brain-and-breast-cancer-and-cardioprotection-may-associate-with-its-metabolite-gentisic-acid
#8
Meric A Altinoz, Ilhan Elmaci, Salih Cengiz, Ebru Emekli-Alturfan, Aysel Ozpinar
BACKGROUND: Epidemiological studies indicate that aspirin consumption reduces the risk of tumors, which is especially relevant for colonic adenoma and carcinoma. Similar observations were made for glial brain tumors and breast cancers, yet the results are inconsistent. Gentisic acid (GA) is a minor catabolite of aspirin; yet humans carrying CYP2C9-variants incapable to catabolize aspirin to GA do not benefit from aspirin in prevention against colonic adenoma. GA blocks binding of Fibroblastic Growth Factor to its receptor and its sulphonate metabolite dobesilic acid blocks growth of C6 glioblastoma in vivo...
August 1, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29872392/gpcromics-gpcr-expression-in-cancer-cells-and-tumors-identifies-new-potential-biomarkers-and-therapeutic-targets
#9
Paul A Insel, Krishna Sriram, Shu Z Wiley, Andrea Wilderman, Trishna Katakia, Thalia McCann, Hiroshi Yokouchi, Lingzhi Zhang, Ross Corriden, Dongling Liu, Michael E Feigin, Randall P French, Andrew M Lowy, Fiona Murray
G protein-coupled receptors (GPCRs), the largest family of targets for approved drugs, are rarely targeted for cancer treatment, except for certain endocrine and hormone-responsive tumors. Limited knowledge regarding GPCR expression in cancer cells likely has contributed to this lack of use of GPCR-targeted drugs as cancer therapeutics. We thus undertook GPCRomic studies to define the expression of endoGPCRs (which respond to endogenous molecules such as hormones, neurotransmitters and metabolites) in multiple types of cancer cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29747061/serrated-epithelial-colorectal-polyps-hyperplastic-polyps-sessile-serrated-adenomas-with-perineurial-stroma-clinicopathological-and-molecular-analysis-of-a-new-series
#10
Katharina Erlenbach-Wünsch, Michel Bihl, Arndt Hartmann, Gabriel M Groisman, Michael Vieth, Abbas Agaimy
Serrated colorectal fibroblastic polyps (FPs) are rare benign mucosal lesions composed of serrated epithelial crypts separated and distorted by intimately associated bland spindle cell proliferations with perineurial-like phenotype. We herein describe 21 new FPs affecting 10 females and 9 males aged 45 to 80 yrs. (mean, 62 yrs). Lesions originated in the sigmoid colon/rectosigmoid junction (n = 16), rectum (n = 2), and other parts of the colon (n = 3). Most patients had additional synchronous or metachronous polyps: classical adenomas (12 patients), sessile serrated adenoma/SSA (1 patient), hyperplastic polyps/HPs (7 patients), both HPs and adenomas (6 patients) and colorectal cancer (2 patients)...
August 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29731961/macrophages-induce-budding-in-aggressive-human-colon-cancer-subtypes-by-protease-mediated-disruption-of-tight-junctions
#11
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720595/cytoglobin-affects-tumorigenesis-and-the-expression-of-ulcerative-colitis-associated-genes-under-chemically-induced-colitis-in-mice
#12
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/29626120/a-new-method-for-tumor-imaging-by-targeting-cancer-associated-fibroblasts
#13
Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand, Uwe Haberkorn
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts (CAFs), which are present in more than 90% of epithelial carcinomas including pancreatic, colon and breast cancer. CAFs feature a high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but associated with a poor prognosis in cancer patients...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29560130/stromal-mir-20a-controls-paracrine-cxcl8-secretion-in-colitis-and-colon-cancer
#14
Steven A Signs, Robert C Fisher, Uyen Tran, Susmita Chakrabarti, Samaneh K Sarvestani, Shao Xiang, David Liska, Veronique Roche, Wei Lai, Haley R Gittleman, Oliver Wessely, Emina H Huang
Inflammatory bowel disease (IBD) affects one million people in the US. Ulcerative colitis (UC) is a subtype of IBD that can lead to colitis-associated cancer (CAC). In UC, the rate of CAC is 3-5-fold greater than the rate of sporadic colorectal cancer (CRC). The pathogenesis of UC and CAC are due to aberrant interactions between host immune system and microenvironment, but precise mechanisms are still unknown. In colitis and CAC, microenvironmental fibroblasts exhibit an activated, inflammatory phenotype that contributes to tumorigenesis accompanied by excessive secretion of the chemokine CXCL8...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29507676/dimethyl-fumarate-is-highly-cytotoxic-in-kras-mutated-cancer-cells-but-spares-non-tumorigenic-cells
#15
Nathaniel Edward Bennett Saidu, Marie Bretagne, Audrey Lupo Mansuet, Pierre-Alexandre Just, Karen Leroy, Olivier Cerles, Sandrine Chouzenoux, Carole Nicco, Diane Damotte, Marco Alifano, Bruno Borghese, François Goldwasser, Frédéric Batteux, Jérôme Alexandre
KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29507627/cancer-associated-fibroblasts-enhance-tumor-18-f-fdg-uptake-and-contribute-to-the-intratumor-heterogeneity-of-pet-ct
#16
Chengfang Shangguan, Guifang Gan, Jieying Zhang, Jinliang Wu, Ying Miao, Miao Zhang, Biao Li, Jun Mi
Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent 18 F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low)...
2018: Theranostics
https://www.readbyqxmd.com/read/29498307/kr%C3%A3-ppel-like-factor-4-mediates-cellular-migration-and-invasion-by-altering-rhoa-activity
#17
Philip R Brauer, Jee Hun Kim, Humberto J Ochoa, Elizabeth R Stratton, Kathryn M Black, William Rosencrans, Eliza Stacey, Engda G Hagos
Kru¨ppel like factor 4 (KLF4) is a transcription factor that regulates genes related to differentiation and proliferation. KLF4 also plays a role in metastasis via epithelial to mesenchymal transition. Here, we investigate the function of Klf4 in migration and invasion using mouse embryonic fibroblasts and the RKO human colon cancer cell line. Compared to wild-type, cells lacking Klf4 exhibited increased migration-associated phenotypes. In addition, overexpression of Klf4 in Klf4-/- MEFs attenuated the presence of stress fibers to wild-type levels...
December 2018: Cell Communication & Adhesion
https://www.readbyqxmd.com/read/29496994/fascin1-suppresses-rig-i-like-receptor-signaling-and-interferon-%C3%AE-production-by-associating-with-i%C3%AE%C2%BAb-kinase-%C3%AF%C2%B5-ikk%C3%AF%C2%B5-in-colon-cancer
#18
Tomio Matsumura, Shigeaki Hida, Masato Kitazawa, Chifumi Fujii, Akira Kobayashi, Michiko Takeoka, Shun-Ichiro Taniguchi, Shin-Ichi Miyagawa
Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce interferon-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein RIG-I (retinoic acid-inducible gene I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29435153/heterotypic-breast-cancer-model-based-on-a-silk-fibroin-scaffold-to-study-the-tumor-microenvironment
#19
Ewelina Dondajewska, Wojciech Juzwa, Andrzej Mackiewicz, Hanna Dams-Kozlowska
An intensive investigation of the development of in vitro models to study tumor biology has led to the generation of various three-dimensional (3D) culture methods that better mimic in vivo conditions. The tumor microenvironment (TME) is shaped by direct interactions among cancer cells, cancer-associated cells and the extracellular matrix (ECM). Recognizing the need to incorporate both tissue dimensionality and the heterogeneity of cells, we have developed a 3D breast cancer model. NIH3T3 fibroblasts and EMT6 breast cancer cell lines were seeded in various ratios onto a silk fibroin scaffold...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29358871/-fusobacterium-s-link-to-colorectal-neoplasia-sequenced-a-systematic-review-and-future-insights
#20
Hisham Hussan, Steven K Clinton, Kristen Roberts, Michael T Bailey
AIM: To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development. METHODS: Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer (CRC) were included in the analysis...
December 28, 2017: World Journal of Gastroenterology: WJG
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