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Colorectal tumour marker

Aires Martins, Alvaro Gonçalves, Teresa Almeida, Alberto Midões
Carcinoembryonic antigen (CEA) is still the most widely used tumour marker for gastrointestinal cancer. CEA was originally thought to be a specific marker for colorectal cancer, but it turned out to be a non-specific marker for further studies. CEA levels can be elevated in breast, lung and liver cancers, among others, including medullary thyroid cancer. The authors report a case of a 73-year-old woman who had a right hemicolectomy for an ascending colon adenocarcinoma and showed a persistent elevation in the CEA marker during follow-up...
June 11, 2018: BMJ Case Reports
R G Morgan, E Mortensson, A C Williams
Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-catenin signalling and is a marker of normal stem cells in several tissues, including the intestine. Consistent with stem cell potential, single isolated LGR5+ cells from the gut generate self-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target...
May 30, 2018: British Journal of Cancer
Päivi Sirniö, Anne Tuomisto, Taina Tervahartiala, Timo Sorsa, Kai Klintrup, Toni Karhu, Karl-Heinz Herzig, Jyrki Mäkelä, Tuomo J Karttunen, Tuula Salo, Markus J Mäkinen, Juha P Väyrynen
BACKGROUND: Matrix metalloproteinase-8 (MMP-8) is a protease mainly expressed by neutrophils that cleaves numerous substrates, including collagens and cytokines. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. However, short follow-up in our prospective cohort did not enable survival analyses at the time of the first publication. METHODS: Preoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival...
May 29, 2018: British Journal of Cancer
Dewen Tan, Yan Fu, Weidong Tong, Fan Li
PURPOSE: The lymphocyte to monocyte ratio, an inflammation-based score, has been used to predict the biological behavior of malignant tumors. However, the relationship between the lymphocyte to monocyte ratio and clinical outcomes in patients with colorectal cancer remains controversial. We conducted a meta-analysis to identify the association between the lymphocyte to monocyte ratio and the prognosis of patients with colorectal cancer. METHODS: Data were retrieved from PubMed, Embase, and Web of science, the hazard ratio and odds ratios with 95% confidence intervals were used to assess the prognostic value of the lymphocyte to monocyte ratio...
May 26, 2018: International Journal of Surgery
Erin L Symonds, Susanne K Pedersen, David H Murray, Maher Jedi, Susan E Byrne, Philippa Rabbitt, Rohan T Baker, Dawn Bastin, Graeme P Young
Background: Cell-free circulating tumour-derived DNA (ctDNA) can be detected by testing for methylated BCAT1 and IKZF1 DNA, which has proven sensitivity for colorectal cancer (CRC). A prospective correlative biomarker study between presence of methylated BCAT1 and IKZF1 in tissue and blood was conducted in cases with CRC to explore how detection of such ctDNA biomarkers relates to cancer characteristics, methylation in tissue and surgical resection of the primary cancer. Methods: Enrolled patients with invasive CRC had blood collected at diagnosis, prior to any treatment or surgery (peri-diagnostic sample)...
2018: Clinical Epigenetics
Mona Mohamed Watany, Nehal Mohamed Elmashad, Rehab Badawi, Nehad Hawash
PURPOSE: The aim of this work is to evaluate Fibulin-1 (FBLN1) and serine threonine kinase-31 (STK31) as colorectal cancer (CRC) tumour markers and their ability to differentiate it from colorectal benign lesions. MATERIAL AND METHODS: In this case-control study, FBLN1 and STK31 serum levels were measured in 120 participants; 49 CRC patients (group I), 26 patients with benign colorectal polyps (group II) and 45 healthy controls (group III). RESULTS: The means of serum FBLN1 were 1...
August 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Masaki Hashimoto, Fumihiro Tanaka, Kazue Yoneda, Teruhisa Takuwa, Ayumi Kuroda, Seiji Matsumoto, Yoshitomo Okumura, Nobuyuki Kondo, Tohru Tsujimura, Takashi Nakano, Seiki Hasegawa
Background: Circulating tumour cells (CTCs) are a potential surrogate for distant metastasis and are considered a useful clinical prognostic marker for metastatic colorectal cancer (mCRC). This prospective study evaluated the preoperative CTC count as a prognostic factor for pulmonary metastasectomy in mCRC patients. Methods: Seventy-nine mCRC patients who underwent curative-intent pulmonary metastasectomy were included. Preoperatively, 7.5 mL of peripheral blood from each patient was quantitatively evaluated for CTCs with the CellSearch® system...
March 2018: Journal of Thoracic Disease
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
Teresa P Raposo, Mireia Sueca Comes, Adeyemi Idowu, Bora Agit, James Hassall, Wakkas Fadhil, Robert Nica, Rupert Ecker, Takashi Yao, Mohammad Ilyas
INTRODUCTION: CD10 is a cell membrane-bound endopeptidase which is expressed in normal small bowel but not in normal colon. It is aberrantly expressed in a small proportion of colorectal cancers (CRC) and this has been associated with liver metastasis and poor prognosis. We sought to investigate the mechanism of CD10 activity and its association with clinicopathological features. MATERIAL AND METHODS: CD10 was stably knocked down by lentiviral shRNA transduction in the CRC cell lines SW480 and SW620 which are derived from a primary tumour and its corresponding metastasis respectively...
June 2018: Experimental and Molecular Pathology
Robert R J Coebergh van den Braak, Anieta M Sieuwerts, Zarina S Lalmahomed, Marcel Smid, Saskia M Wilting, Sandra I Bril, Shanshan Xiang, Michelle van der Vlugt-Daane, Vanja de Weerd, Anne van Galen, Katharina Biermann, J Han J M van Krieken, Wigard P Kloosterman, John A Foekens, John W M Martens, Jan N M IJzermans
The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (let-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment...
March 27, 2018: Scientific Reports
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
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
Mona Alibolandi, Khalil Abnous, Sajjad Anvari, Marzieh Mohammadi, Mohammad Ramezani, Seyed Mohammad Taghdisi
Poor aqueous solubility of chemotherapeutics such as SN38 (7-ethyl-10-hydroxycamptothecin) and the associated systemic adverse effects are serious limitations of their clinical use. To improve the drug delivery efficiency of such compounds, they were covalently conjugated to hydrophilic macromolecular carriers that specifically deliver the drug moiety to the tumour cells. In the current study, we developed a PEGylated acetylated carboxymethylcellulose conjugate of SN38 which was covalently attached to an aptamer against a cancer stem cell marker, CD133...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Shelize Khakoo, Alexandros Georgiou, Marco Gerlinger, David Cunningham, Naureen Starling
Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations that are present in the corresponding tumour, thereby allowing for quantitative and qualitative real-time evaluation in body fluids as an alternative to onerous repeat biopsies. Improvements in the sensitivity of techniques used to identify ctDNA has led to a surge of research investigating its role in the detection of: early disease, relapse, response to therapy and emerging drug resistance mechanisms. Following curative surgery, ctDNA detection is a promising marker of minimal residual disease and could better select patients for adjuvant chemotherapy...
February 2018: Critical Reviews in Oncology/hematology
Kosmas Daskalakis, Olov Norlén, Andreas Karakatsanis, Per Hellman, Rolf Larsson, Peter Nygren, Peter Stålberg
Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers...
April 2018: Endocrine-related Cancer
Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues...
February 6, 2018: Gut
Andreas Kleppe, Fritz Albregtsen, Ljiljana Vlatkovic, Manohar Pradhan, Birgitte Nielsen, Tarjei S Hveem, Hanne A Askautrud, Gunnar B Kristensen, Arild Nesbakken, Jone Trovik, Håkon Wæhre, Ian Tomlinson, Neil A Shepherd, Marco Novelli, David J Kerr, Håvard E Danielsen
BACKGROUND: Chromatin organisation affects gene expression and regional mutation frequencies and contributes to carcinogenesis. Aberrant organisation of DNA has been correlated with cancer prognosis in analyses of the chromatin component of tumour cell nuclei using image texture analysis. As yet, the methodology has not been sufficiently validated to permit its clinical application. We aimed to define and validate a novel prognostic biomarker for the automatic detection of heterogeneous chromatin organisation...
March 2018: Lancet Oncology
David S Williams, Dmitri Mouradov, Robert N Jorissen, Marsali R Newman, Elham Amini, David K Nickless, Julie A Teague, Catherine G Fang, Michelle Palmieri, Marie J Parsons, Anuratha Sakthianandeswaren, Shan Li, Robyn L Ward, Nicholas J Hawkins, Ian Faragher, Ian T Jones, Peter Gibbs, Oliver M Sieber
OBJECTIVE: Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear. DESIGN: A prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF / KRAS mutations...
January 30, 2018: Gut
Reetta Peltonen, Pia Österlund, Marko Lempinen, Arno Nordin, Ulf-Håkan Stenman, Helena Isoniemi
Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Steven Carberry, Beatrice D'Orsi, Naser Monsefi, Manuela Salvucci, Orna Bacon, Joanna Fay, Markus Rehm, Deborah McNamara, Elaine W Kay, Jochen H M Prehn
The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members of the BCL-2 protein family. Activation of this death pathway plays a crucial role in cancer progression and chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that stage II and III colorectal cancer patients possessed decreased levels of BOK protein in their tumours compared to matched normal tissue...
January 26, 2018: Cell Death & Disease
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