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https://www.readbyqxmd.com/read/28427085/tumour-invasiveness-the-local-and-systemic-environment-and-the-basis-of-staging-systems-in-colorectal-cancer
#1
J H Park, H van Wyk, C S D Roxburgh, P G Horgan, J Edwards, D C McMillan
BACKGROUND: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. METHODS: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR)...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28424337/physical-and-chemical-gradients-in-the-tumor-microenvironment-regulate-tumor-cell-invasion-migration-and-metastasis
#2
Madeleine J Oudin, Valerie M Weaver
Cancer metastasis requires the invasion of tumor cells into the stroma and the directed migration of tumor cells through the stroma toward the vasculature and lymphatics where they can disseminate and colonize secondary organs. Physical and biochemical gradients that form within the primary tumor tissue promote tumor cell invasion and drive persistent migration toward blood vessels and the lymphatics to facilitate tumor cell dissemination. These microenvironment cues include hypoxia and pH gradients, gradients of soluble cues that induce chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to the concentration, organization, and stiffness of the extracellular matrix that produce haptotactic, alignotactic, and durotactic gradients...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28407462/overexpression-of-postn-in-tumor-stroma-is-a-poor-prognostic-indicator-of-colorectal-cancer
#3
Hyeon Jeong Oh, Jeong Mo Bae, Xian-Yu Wen, Nam-Yun Cho, Jung Ho Kim, Gyeong Hoon Kang
Background: Tumor microenvironment has recently drawn attention in that it is related with tumor prognosis. Cancer-associated fibroblast also plays a critical role in cancer invasiveness and progression in colorectal cancers. Periostin (POSTN), originally identified to be expressed in osteoblasts and osteoblast-derived cells, is expressed in cancer-associated fibroblasts in several tissue types of cancer. Recent studies suggest an association between stromal overexpression of POSTN and poor prognosis of cancer patients...
April 12, 2017: Journal of Pathology and Translational Medicine
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
#4
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/28392501/non-coding-rnas-the-trojan-horse-in-two-way-communication-between-tumor-and-stroma-in-colorectal-and-hepatocellular-carcinoma
#5
Cristina- Sorina Cătană, Martin Pichler, Gianluigi Giannelli, Robert M Mader, Ioana Berindan-Neagoe
In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382517/doublecortin-and-cam-kinase-like-1-expression-in-pathological-stage-i-non-small-cell-lung-cancer
#6
Hiroyuki Tao, Toshiki Tanaka, Kazunori Okabe
PURPOSE: Doublecortin and CaM kinase-like-1 (DCLK1) regulates microtubule polymerization in migrating neurons. Recently, DCLK1 has been reported to act as an intestinal tumor stem cell marker and has been shown to be expressed in cancer cells and in the stroma of breast, colon, pancreatic, and prostate cancers. Here, we studied DCLK1 expression in non-small cell lung cancer (NSCLC) by immunohistochemistry in association with clinicopathological factors and patient prognosis. METHODS: DCLK1 expression was analyzed by immunohistochemical staining of surgical specimens from 232 patients with pathological stage I NSCLC, including 187 adenocarcinomas...
April 5, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28379958/il-15-regulates-migration-invasion-angiogenesis-and-genes-associated-with-lipid-metabolism-and-inflammation-in-prostate-cancer
#7
Krizia Rohena-Rivera, María M Sánchez-Vázquez, Diana A Aponte-Colón, Ingrid S Forestier-Román, Mario E Quintero-Aguiló, Magaly Martínez-Ferrer
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical prostatectomy (RP). However, 15-30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28133201/-long-term-survival-in-response-to-multimodality-therapy-in-a-patient-with-invasive-pancreatic-cancer-with-cyst-formation
#8
Hironobu Makino, Hisashi Kametaka, Tadaomi Fukada, Kazuhiro Seike, Akio Hasegawa, Masaru Isozaki
The patient was a 61-year-old man. Computed tomography(CT)in April 2007 revealed a pancreatic cyst in the tail of the pancreas. Rapid enlargement was noted in November 2007, and the patient was referred to the surgery department. CT showed a cystic lesion containing a nodular shadow in the pancreatic tail. Tumor marker measurements yielded normal carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels, but the duke pancreatic monoclonal antigen type 2(DUPAN-2)level was elevated. A diagnosis of mucinous cystic neoplasm(MCN)of the pancreas was made in December 2007, and distal pancreatectomy and partial colectomy were performed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28130225/cellular-model-of-colon-cancer-progression-reveals-signatures-of-mrnas-mirna-lncrnas-and-epigenetic-modifications-associated-with-metastasis
#9
Matjaz Rokavec, David Horst, Heiko Hermeking
Here, we developed and comprehensively characterized a cellular model of colon cancer progression consisting of four defined derivatives of a colon cancer cell line that resulted from consecutive epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) and phenotypically recapitulate the metastatic cascade. Initial EMT was induced by prolonged exposure to IL6, a cytokine also generated by the tumor-stroma. Genome-wide characterization of transcriptional (mRNA, miRNA, and lncRNA) and epigenetic (DNA methylation, H3K4me3, H3K79me3, and H3K27me3 histone modifications) profiles of the cell derivatives, combined with correlative analyses of expression, methylation, and clinical data from the TCGA-COAD database gave insights into the molecular basis of their phenotypic changes...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28041973/prognostic-significance-of-stromal-grem1-expression-in-colorectal-cancer
#10
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Hyeon Jeong Oh, Xianyu Wen, Seorin Jeong, Nam Yun Cho, Woo Ho Kim, Gyeong Hoon Kang
Cancer-associated fibroblasts are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by cancer-associated fibroblasts in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall, GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4...
April 2017: Human Pathology
https://www.readbyqxmd.com/read/28034806/targeting-the-extracellular-matrix-of-ovarian-cancer-using-functionalized-drug-loaded-lyophilisomes
#11
Sophieke C H A van der Steen, René Raavé, Sjoerd Langerak, Laurens van Houdt, Sander M J van Duijnhoven, Sanne A M van Lith, Leon F A G Massuger, Willeke F Daamen, William P Leenders, Toin H van Kuppevelt
Epithelial ovarian cancer is characterized by a high mortality rate and is in need for novel therapeutic avenues to improve patient outcome. The tumor's extracellular matrix ("stroma") offers new possibilities for targeted drug-delivery. Recently we identified highly sulfated chondroitin sulfate (CS-E) as a component abundantly present in the ovarian cancer extracellular matrix, and as a novel target for anti-cancer therapy. Here, we report on the functionalization of drug-loaded lyophilisomes (albumin-based biocapsules) to specifically target the stroma of ovarian carcinomas with the potential to eliminate cancer cells...
April 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#12
Leandro N Güttlein, Lorena G Benedetti, Cristóbal Fresno, Raúl G Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A Fernández, Vanesa Gottifredi, Norberto W Zwirner, Andrea S Llera, Osvaldo L Podhajcer
Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28013338/colon-cancer-cell-derived-12-s-hete-induces-the-retraction-of-cancer-associated-fibroblast-via-mlc2-rho-rock-and-ca-2-signalling
#13
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
May 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27991924/cooperation-among-heterogeneous-prostate-cancer-cells-in-the-bone-metastatic-niche
#14
K Shahriari, F Shen, A Worrede-Mahdi, Q Liu, Y Gong, F U Garcia, A Fatatis
The growth of disseminated tumor cells into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the interleukin (IL)-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells exposed in vitro to medium conditioned by IL-1β-expressing cancer cells responded by upregulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27942988/investigation-of-malignant-transformation-of-sporadic-adenomas-of-colon-by-fluorimetry
#15
Yu S Korneva, A E Dorosevich, V S Maryakhina
In this work, biochemical changes in sporadic adenoma during progression to colon cancer have been detected by spectral techniques. It is shown that spectra of all types of adenomas as well as adenocarcinoma have two maxima at 265 ÷ 270 nm and at 330 ÷ 340 nm. The first maximum is primarily defined by tryptophan containing peptides. The second maximum of the spectra is in the main defined by collagen presence in stroma of tumors and normal mucosa. Progression of precancer lesions to advanced cancer leads to increase of NADH concentration impacting on the second maximum of spectra...
February 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/27925182/proteomics-analysis-of-differential-protein-expression-identifies-heat-shock-protein-47-as-a-predictive-marker-for-lymph-node-metastasis-in-patients-with-colorectal-cancer
#16
Koichiro Mori, Yuji Toiyama, Kohei Otake, Hiroyuki Fujikawa, Susumu Saigusa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Yuhko Kobayashi, Issei Kobayashi, Yasuhiko Mohri, Ajay Goel, Masato Kusunoki
The discovery of biomarkers to predict the potential for lymph node (LN) metastasis in patients with colorectal cancer (CRC) is essential for developing improved strategies for treating CRC. In the present study, they used isobaric tags for relative and absolute quantitation to conduct a proteomic analysis designed to identify novel biomarkers for predicting LN metastasis in patients with CRC. They identified 60 differentially expressed proteins specifically associated with LN metastasis in CRC patients and classified the molecular and functional characteristics of these proteins by bioinformatic approaches...
March 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27853865/adequately-defining-tumor-cell-proportion-in-tissue-samples-for-molecular-testing-improves-interobserver-reproducibility-of-its-assessment
#17
Benoît Lhermitte, Caroline Egele, Noëlle Weingertner, Damien Ambrosetti, Bérengère Dadone, Valérie Kubiniek, Fanny Burel-Vandenbos, John Coyne, Jean-François Michiels, Marie-Pierre Chenard, Etienne Rouleau, Jean-Christophe Sabourin, Jean-Pierre Bellocq
Gene mutation status assessment of tumors has become standard practice in diagnostic pathology. This is done using samples comprising tumor cells but also non-tumor cells, which may dramatically dilute the proportion of tumor DNA and induce false negative results. Increasing sensitivity of molecular tests presently allows detection of a targeted mutation in a sample with a small percentage of tumor cells, but assessment of tumor cellularity remains essential to adequately interpret the results of molecular tests...
January 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27826041/smc1a-recruits-tumor-associated-fibroblasts-tafs-and-promotes-colorectal-cancer-metastasis
#18
Pengyang Zhou, Nan Xiao, Jian Wang, Zhanhuai Wang, Shuchun Zheng, Siyang Shan, Jianping Wang, Jinlin Du, Jianwei Wang
Tumor-associated-fibroblasts (TAFs) are the most important host cells in the stroma and take part in extracellular matrix construction and cancer colony development. During cancer colonization, seed cells from primary tumor can reconstruct the microenvironment by recruiting circulating cancer cells and TAFs to the metastasis site. Previous studies have established that SMC1A, a subunit of cohesin, is an important trigger signal for liver metastasis in colorectal cancer. We investigated the particular effects as well as the underlying mechanism of SMC1A on TAFs recruitment during liver metastasis of colorectal cancer...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27805003/image-analysis-derived-metrics-of-histomorphological-complexity-predicts-prognosis-and-treatment-response-in-stage-ii-iii-colon-cancer
#19
Artur Mezheyeuski, Ina Hrynchyk, Mia Karlberg, Anna Portyanko, Lars Egevad, Peter Ragnhammar, David Edler, Bengt Glimelius, Arne Östman
The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27804849/when-neighbors-talk-colon-cancer-cell-invasion-and-tumor-microenvironment-myofibroblasts
#20
Jolien Bridelance, Zuzanna Drebert, Olivier De Wever, Marc Bracke, Ilse M Beck
Historically, the word cancer is derived from the Latin cancer, as the red swollen arteries near a tumor reminded the physician Galenus and his fellow Romans of a red crab. Currently, cancer remains the disease to beat as it remains a leading cause of death worldwide (WHO). Tumors do not simply consist out of cancer cells, as they can recruit normal cells, which will form the tumor-associated stroma. These stromal cells together with the extracellular matrix, constitute the tumor microenvironment. Reciprocal communication between tumor-associated stromal cells and cancer cells is important for the induction of epithelial-to-mesenchymal transition and invasion...
October 28, 2016: Current Drug Targets
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