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Colorectal cancer marker

Stella Arelaki, Athanasios Arampatzioglou, Konstantinos Kambas, Efthimios Sivridis, Alexandra Giatromanolaki, Konstantinos Ritis
Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls...
2018: PloS One
Antonio Fadda, Davide Gentilini, Loredana Moi, Ludovic Barault, Vera Piera Leoni, Pia Sulas, Luigi Zorcolo, Angelo Restivo, Francesco Cabras, Federica Fortunato, Cesare Zavattari, Liliana Varesco, Viviana Gismondi, Maria Rosaria De Miglio, Antonio Mario Scanu, Federica Colombi, Pasquale Lombardi, Ivana Sarotto, Eleonora Loi, Francesco Leone, Silvia Giordano, Federica Di Nicolantonio, Amedeo Columbano, Patrizia Zavattari
Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment...
March 15, 2018: International Journal of Cancer. Journal International du Cancer
Jessada Thutkawkorapin, Hovsep Mahdessian, Tom Barber, Simone Picelli, Susanna von Holst, Johanna Lundin, Laura Valle, Vinaykumar Kontham, Tao Liu, Daniel Nilsson, Xiang Jiao, Annika Lindblom
Highly penetrant cancer syndromes account for less than 5% of all cases with familial colorectal cancer (CRC), and other genetic contribution explains the majority of the genetic contribution to CRC. A CRC susceptibility locus on chromosome 9q has been suggested. In this study, families where risk of CRC was linked to the region, were used to search for predisposing mutations in all genes in the region. No disease-causing mutation was found. Next, haplotype association studies were performed in the region, comparing Swedish CRC cases (2664) and controls (4782)...
February 16, 2018: Oncotarget
Xiao Sun, Tanxiao Huang, Fangsheng Cheng, Kaibing Huang, Ming Liu, Wan He, Mingwei Li, Xiaoni Zhang, Mingyan Xu, Shifu Chen, Ligang Xia
Postoperative monitoring for patients with colorectal cancer (CRC) requires sensitive biomarkers that are associated with medical response and adjuvant therapy following surgery. Conventional tumor biomarkers [including carcinoembryonic antigen (CEA), CA19-9 and CA125] are widely used, but none of the markers provide high sensitivity or specificity. Previous studies indicated that circulating tumor DNA (ctDNA) is useful for postoperative monitoring of patients with cancer. However, the majority of previous studies involved patients with lung cancer, and therefore further studies are required which investigate patients with CRC...
April 2018: Oncology Letters
Nengquan Sheng, Li Yan, Kai Wu, Weiqiang You, Jianfeng Gong, Landian Hu, Gewen Tan, Hongqi Chen, Zhigang Wang
Colorectal cancer (CRC) is one of the most common neoplasms worldwide. However, the mechanisms underlying its development are still poorly understood. Thyroid hormone Receptor Interactor 13 (TRIP13) is a key mitosis regulator, and recent evidence has shown that it is an oncogene. Here, we report that TRIP13, which is overexpressed in CRC, is correlated with the CEA (carcino-embryonic antigen), CA19-9 (carbohydrate antigen 19-9) and pTNM (pathologic primary tumor, lymph nodes, distant metastasis) classification...
March 14, 2018: Cell Death & Disease
Qingtao Meng, Shenshen Wu, Yajie Wang, Jin Xu, Hao Sun, Runze Lu, Na Gao, Hongbao Yang, Xiaobo Li, Boping Tang, Michael Aschner, Rui Chen
Myeloperoxidase (MPO) promoter single nucleotide polymorphisms (SNPs) rs2243828 (-764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 colorectal cancer (CRC) patients with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of CRC. The MPO rs2333227 TT genotype significantly increased the risk of CRC and decreased the overall survival time of patients...
March 14, 2018: Cancer Research
Sun-Young Jun, Seung-Mo Hong, Young Kyung Bae, Hee Kyung Kim, Kyu Yun Jang, Dae Woon Eom
Heme oxygenase-1 (HO-1), a stress-response protein, is highly induced in various carcinomas. It is implicated in carcinogenesis and tumor progression. High HO-1 expression is associated with better prognosis of patients with colorectal and gastric cancers. Induction or inhibition of HO-1 can mediate chemo-sensitivity, therefore it might be a therapeutic target to develop anticancer agents. To define the clinicopathological and prognostic significance of HO-1 expression in small-intestinal adenocarcinomas (SIACs), immunohistochemical microarray analysis of HO-1 expression was performed for 191 surgically resected SIAC cases and results were compared with various clinicopathologic variables, including survival...
March 14, 2018: Pathology International
Wen Ye, Shaoping Ling, Ran-Yi Liu, Zhi-Zhong Pan, Gaoyuan Wang, Shijuan Gao, Jiangxue Wu, Lihua Cao, Lili Dong, Yingchang Li, Yi Zhou, Wuying Du, Xiangqi Meng, Jinna Chen, Xinyuan Guan, Yulong He, Changchuan Pan, X F Steven Zheng, Xuemei Lu, Shuai Chen, Wenlin Huang
Colorectal cancer (CRC) is the third most common cancer worldwide, with more than 1.3 million new cases and 690,000 deaths each year. In China, the incidence of CRC has increased dramatically due to dietary and lifestyle changes, to become the fifth leading cause of cancer-related death. Here, we performed whole-exome sequencing in 50rectal cancer cases among the Chinese population as part of the International Cancer Genome Consortium research project. Frequently-mutated genes and enriched pathways were identified...
March 14, 2018: Journal of Pathology
Sinead A Noonan, Maria E Morrissey, Petra Martin, Monika Biniecka, Shane Ó'Meachair, Aoife Maguire, Miriam Tosetto, Blathnaid Nolan, John Hyland, Kieran Sheahan, Diarmuid O'Donoghue, Hugh Mulcahy, David Fennelly, Jacintha O'Sullivan
Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA...
February 13, 2018: Oncotarget
Jiekai Yu, Yanqin Huang, Chen Lin, Xiaofen Li, Xuefeng Fang, Chenhan Zhong, Ying Yuan, Shu Zheng
The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85...
2018: Journal of Cancer
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Roslyn Dillon, Lisa J Croner, John Bucci, Stefanie N Kairs, Jia You, Sharon Beasley, Mark Blimline, Rochele B Carino, Vicky C Chan, Danissa Cuevas, Jeff Diggs, Megan Jennings, Jacob Levy, Ginger Mina, Alvin Yee, Bruce Wilcox
Early detection of colorectal cancer (CRC) is key to reducing associated mortality. Despite the importance of early detection, approximately 40% of individuals in the United States between the ages of 50-75 have never been screened for CRC. The low compliance with colonoscopy and fecal-based screening may be addressed with a non-invasive alternative such as a blood-based test. We describe here the analytical validation of a multiplexed blood-based assay that measures the plasma concentrations of 15 proteins to assess advanced adenoma (AA) and CRC risk in symptomatic patients...
February 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
Fu-Shu Jin, Hong-Mei Wang, Xiao-Yan Song
Long non-coding RNA (lnc)TCF7 has been reported to promote the self‑renewal of human cancer stem cells, and enhance the aggressiveness of human non‑small cell lung cancer and hepatocellular carcinoma cells. However, the effect of lncTCF7 on colorectal cancer (CRC) tumorigenesis and progression is currently unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction results demonstrated that lncTCF7 expression was higher in CRC tissues compared with adjacent normal tissues and was significantly associated with tumor size, differentiation degree, tumor‑node‑metastasis grade, lymph node metastasis and invasion depth...
March 9, 2018: Molecular Medicine Reports
Mehrdad Zeinalian, Morteza Hashemzadeh-Chaleshtori, Rasoul Salehi, Mohammad Hassan Emami
Microsatellite instability (MSI) is a molecular hallmark for some colorectal cancers (CRCs) in which short tandem repeats are prone to mutations along with DNA sequences. It is due to DNA-mismatch-repair system deficiency because of a germline/somatic mutation in mismatch-repair (MMR) genes. The germline mutations lead to Lynch syndrome (LS) while epigenetic gene silencing results in sporadic CRC tumors. We discuss in our paper the most important clinical aspects of MSI testing in CRCs. We reviewed the most reliable relevant studies and clinical trials according to their high-quality methods, particularly within two recent decades...
2018: Advanced Biomedical Research
Janette L Vardy, Haryana Mary Dhillon, Gregory R Pond, Corrinne Renton, Stephen J Clarke, Ian F Tannock
Background: Inflammation promotes the development of malignancy, while a variety of systemic markers of inflammation predict for worse cancer outcomes including recurrence and survival. Here, we evaluate the prognostic impact of cytokine concentrations, full blood count (FBC) differential ratios, cognitive function and fatigue on survival in patients with localised colorectal cancer (CRC). Patients and methods: Data are from a prospective longitudinal study comparing cognitive function and fatigue in patients with CRC who did (n=173) and did not (n=116) receive adjuvant/neoadjuvant chemotherapy...
2018: ESMO Open
C B Thomsen, T F Hansen, R F Andersen, J Lindebjerg, L H Jensen, A Jakobsen
BACKGROUND: Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). METHODS: The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR...
March 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
Allen Cohn, Michael A Morse, Bert O'Neil, Samuel Whiting, Claire Coeshott, John Ferraro, Donald Bellgrau, David Apelian, Timothy C Rodell
We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to identify the specific ras mutation and thereby to identify which GI-4000 product to administer...
April 2018: Journal of Immunotherapy
Marcel Wiesweg, Henning Reis, Tobias Köster, Moritz Goetz, Karl Worm, Thomas Herold, Andreas Paul, Alexander Dechêne, Brigitte Schumacher, Peter Markus, Isabel Virchow, Karina Kostbade, Nathalie Wolf, Gregor Zaun, Martin Metzenmacher, Kurt W Schmid, Martin Schuler, Stefan Kasper
BACKGROUND: Deregulation of signal transduction pathways plays a critical role in oncogenesis of colorectal cancer (CRC) and directly affects sensitivity to targeted therapies. Against this background we developed a comprehensive biomarker profiling program including markers of downstream signaling to study their association with clinical outcomes. PATIENTS AND METHODS: A prospectively studied cohort of 160 patients with metastatic CRC was included. Standard diagnostic workup included mutational analyses of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
February 17, 2018: Clinical Colorectal Cancer
Zhiming Shan, Na An, Jielin Qin, Junmei Yang, Hongqi Sun, Wei Yang
Substantial evidence has demonstrated the involvement of long non-coding RNAs (lncRNAs) in the development and progression of colorectal cancer (CRC) via their regulation on cancer cell proliferation, apoptosis, invasion and metastasis pathways. The current study aimed to understand the role of lncRNA Linc00675 in the progression and metastasis of CRC and to identify the potential lncRNA-miRNA interactions and signaling pathways underlying the mechanisms of action of Linc00675 in CRC. Our data firstly demonstrated the down-regulation of Linc00675 in both CRC cells and clinical CRC tissues...
March 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Marta Schirripa, Wu Zhang, Dongyun Yang, Shu Cao, Satoshi Okazaki, Fotios Loupakis, Martin D Berger, Yan Ning, Yuji Miyamoto, Mitsukuni Suenaga, Giulia Alberti, Jordan D West, Sara Lonardi, Taline Khoukaz, Francesca Bergamo, Francesca Battaglin, Carlotta Antoniotti, Alfredo Falcone, Sebastian Stintzing, Volker Heinemann, Heinz-Josef Lenz
BACKGROUND: Macrophages play a crucial role in the interaction between tumor and immune system, and iNOS is known as a surrogate marker of M1 macrophages activation. The goal of the study was to investigate the role of iNOS polymorphisms as prognostic marker in mCRC patients. MATERIALS AND METHODS: Functional significant polymorphisms in the promoter of INOS gene were analyzed by PCR-based and direct DNA sequencing in 4 cohorts of patients receiving bevacizumab based first-line chemotherapy: two evaluation cohorts (TRIBE ARM A and ARM B) and two validation cohorts (FIRE 3 arm A and MOMA)...
2018: PloS One
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