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Stroma cancer colon

Yi Zhong, Anne M Macgregor-Das, Tyler Saunders, Martin Whittle, Alvin Makohon-Moore, Zachary Kohutek, Justin Poling, Brian Herbst, Breanna Javier, Leslie Cope, Steven D Leach, Sunil R Hingorani, Christine A Iacobuzio-Donahue
PURPOSE: TP53 and the TGFβ pathway are major mediators of pancreatic cancer metastasis. The mechanisms by which they cause hematogenous metastasis have not been fully explored. EXPERIMENTAL DESIGN: KPC (LSL-KRASG12D/+;LSL-Trp53R172H/+; Ptf1aCre/+) mice were generated and the frequency and morphology of organ-specific hematogenous metastases compared to that seen in KPTC and KTC littermates (Tgfbr2+/-). Key findings were validated in primary cells from each genotype and samples of human pancreatic cancer liver metastases...
September 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Dana Simkova, Gvantsa Kharaishvili, Eva Slabakova, Paul G Murray, Jan Bouchal
BACKGROUND: Small leucine rich proteoglycans (SLRPs), major non-collagen components of the extracellular matrix (ECM), have multiple biological roles with diverse effects. Asporin, a member of the SLRPs class I, competes with other molecules in binding to collagen and affects its mineralization. Its role in cancer is only now being elucidated. METHODS: The PubMed online database was used to search relevant reviews and original articles. Furthermore, altered asporin expression was analysed in publicly available genome-wide expression data at the Gene Expression Omnibus database...
September 5, 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Camille Lehuédé, Fanny Dupuy, Rebecca Rabinovitch, Russell G Jones, Peter M Siegel
Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. Different stages of the metastatic cascade can also present distinct metabolic challenges to disseminating cancer cells. However, little is known regarding how changes in cellular metabolism, both within the cancer cell and the metastatic microenvironment, alter the ability of tumor cells to colonize and grow in distinct secondary sites...
September 15, 2016: Cancer Research
Jean Claude Reubi, Beatrice Waser, Helmut R Maecke, Jean E Rivier
: There is recent in vitro and in vivo evidence that somatostatin receptor sst2 antagonists are better tools to target neuroendocrine tumors (NET) than sst2 agonists. Indeed, antagonists bind to a greater number of sst2 sites than agonists. Whether sst2 antagonists could be used successfully to target non-NET tumors, expressing low sst2 density, is unknown. Here, we compare quantitatively (125)I-JR11 sst2 antagonist binding in vitro with that of the sst2 agonist (125)I-Tyr3-octreotide in large varieties of non-NET and NET...
August 25, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Sen-Wen Teng, Huann-Cheng Horng, Chi-Hong Ho, Ming-Shyen Yen, Hsiang-Tai Chao, Peng-Hui Wang
Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases...
August 20, 2016: Journal of the Chinese Medical Association: JCMA
Alzbeta Hulikova, Nicholas Black, Lin-Ting Hsia, Jennifer Wilding, Walter F Bodmer, Pawel Swietach
Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Marco Gerling, Nikè V J A Büller, Leonard M Kirn, Simon Joost, Oliver Frings, Benjamin Englert, Åsa Bergström, Raoul V Kuiper, Leander Blaas, Mattheus C B Wielenga, Sven Almer, Anja A Kühl, Erik Fredlund, Gijs R van den Brink, Rune Toftgård
A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature...
2016: Nature Communications
Tina J Hieken, Jun Chen, Tanya L Hoskin, Marina Walther-Antonio, Stephen Johnson, Sheri Ramaker, Jian Xiao, Derek C Radisky, Keith L Knutson, Krishna R Kalari, Janet Z Yao, Larry M Baddour, Nicholas Chia, Amy C Degnim
Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing...
2016: Scientific Reports
Jason M Knight, Eunji Kim, Ivan Ivanov, Laurie A Davidson, Jennifer S Goldsby, Meredith A J Hullar, Timothy W Randolph, Andrew M Kaz, Lisa Levy, Johanna W Lampe, Robert S Chapkin
The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs...
September 1, 2016: Physiological Genomics
Allen Mo, Stephen Jackson, Kamini Varma, Alan Carpino, Charles Giardina, Thomas J Devers, Daniel W Rosenberg
UNLABELLED: Although the progression of mutated colonic cells is dependent upon interactions between the initiated epithelium and surrounding stroma, the nature of these interactions is poorly understood. Here, the development of an ultrasensitive laser capture microdissection (LCM)/RNA-seq approach for studying the epithelial and stromal compartments of aberrant crypt foci (ACF) is described. ACF are the earliest identifiable preneoplastic lesion found within the human colon and are detected using high-definition endoscopy with contrast dye spray...
September 2016: Molecular Cancer Research: MCR
Anna O Abacjew-Chmyłk, Łukasz Chmyłko, Dariusz Grzegorz Wydra, Hanna Olszewska, Paulina Kobiela, Katarzyna Ciach
BACKGROUND: Nulliparity is one of the most important reproductive risk factors for endometrial cancer. It is still discussed whether multiparity implies a more favorable course of the disease and higher overall survival rates. The aim of the study was to analyze the effect of parity on the overall survival of endometrial cancer patients in Poland. MATERIAL AND METHOD: A retrospective analysis of parity on survival rates was performed in 810 women treated surgically for endometrial cancer in a single referential center of gynecological oncology...
2016: Ginekologia Polska
Sarah Nietzer, Florentin Baur, Stefan Sieber, Jan Hansmann, Thomas Schwarz, Carolin Stoffer, Heide Häfner, Martin Gasser, Ana Maria Waaga-Gasser, Heike Walles, Gudrun Dandekar
Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts...
July 2016: Tissue Engineering. Part C, Methods
Gemma Ferrer-Mayorga, Gonzalo Gómez-López, Antonio Barbáchano, Asunción Fernández-Barral, Cristina Peña, David G Pisano, Ramón Cantero, Federico Rojo, Alberto Muñoz, María Jesús Larriba
OBJECTIVE: Colorectal cancer (CRC) is a major health concern. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this disease. Given the strong influence of tumour stroma on cancer progression, we investigated the potential effects of the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on CRC stroma. DESIGN: Expression of vitamin D receptor (VDR) and two 1,25(OH)2D3 target genes was analysed in 658 patients with CRC with prolonged clinical follow-up...
April 6, 2016: Gut
T T Vellinga, S den Uil, I H B Rinkes, D Marvin, B Ponsioen, A Alvarez-Varela, S Fatrai, C Scheele, D A Zwijnenburg, H Snippert, L Vermeulen, J P Medema, H B Stockmann, J Koster, R J A Fijneman, J de Rooij, O Kranenburg
Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to-mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive colon tumors, challenging the notion of tumor EMT. To separately study the neoplastic and stromal compartments of colon tumors, we have generated a stroma gene filter (SGF). Comparative analysis of stroma(high) and stroma(low) tumors shows that the neoplastic cells in stroma(high) tumors express specific EMT drivers (ZEB2, TWIST1, TWIST2) and that 98% of differentially expressed genes are strongly correlated with them...
March 21, 2016: Oncogene
Nicole C Panarelli, Thusitha Somarathna, Wade S Samowitz, Susan Kornacki, Scott A Sanders, Marco R Novelli, Neil A Shepherd, Rhonda K Yantiss
Endoscopic mucosal biopsy may misplace mucosal elements into the submucosa of colonic adenomas, mimicking invasive adenocarcinoma. Biopsy-related misplacement can be more challenging to recognize than typical misplaced epithelium (pseudoinvasion) in pedunculated polyps. We compared the features of 16 polyps with biopsy-related misplaced epithelium with those of 10 adenomas with pseudoinvasion and 10 adenomas with invasive adenocarcinoma and performed Ki67 and p53 immunostaining on all cases. Features of misplaced epithelium in polyps referred to the Bowel Cancer Screening Program Expert Board in the United Kingdom were also evaluated for the same morphologic features...
August 2016: American Journal of Surgical Pathology
Togo Ikuta, Masafumi Kurosumi, Toshimasa Yatsuoka, Yoji Nishimura
Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles...
May 1, 2016: Experimental Cell Research
Valentina Doldi, Marzia Pennati, Barbara Forte, Paolo Gandellini, Nadia Zaffaroni
Metastatic prostate cancer is a lethal disease that remains incurable despite the recent approval of new drugs, thus making the development of alternative treatment approaches urgently needed. A more precise understanding of the molecular mechanisms underlying prostate cancer dissemination could lead to the identification of novel therapeutic targets for the design of efficient anti-metastatic strategies. MicroRNA (miRNAs) are endogenous, small non-coding RNA molecules acting as key regulators of gene expression at post-transcriptional level...
July 2016: Cellular and Molecular Life Sciences: CMLS
Hidehiko Takigawa, Yasuhiko Kitadai, Kei Shinagawa, Ryo Yuge, Yukihito Higashi, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma-associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor-β (PDGFR-β) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-β, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF)...
May 2016: Cancer Science
Ohad Tarcic, Ioannis S Pateras, Tomer Cooks, Efrat Shema, Julia Kanterman, Hadas Ashkenazi, Hana Boocholez, Ayala Hubert, Ron Rotkopf, Michal Baniyash, Eli Pikarsky, Vassilis G Gorgoulis, Moshe Oren
Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription...
February 16, 2016: Cell Reports
Minmin Li, Mei Li, Tao Yin, Huashan Shi, Yuan Wen, Binglan Zhang, Meihua Chen, Guangchao Xu, Kexin Ren, Yuquan Wei
Cancer‑associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small‑molecule dipeptidyl peptidase inhibitor PT‑100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT‑100 alone...
March 2016: Molecular Medicine Reports
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