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Colorectal tumour

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...
April 10, 2018: Experimental and Molecular Pathology
Damiano Caputo, Alessandro Coppola, Vincenzo LA Vaccara, Silvia Angeletti, Gianluca Rizzo, Massimo Ciccozzi, Claudio Coco, Roberto Coppola
BACKGROUND: Risk of nodal involvement in T1 colorectal cancer is assessed by tumor histological features. In several tumours, the ratio between neutrophils and lymphocytes (NLR) or platelets and lymphocytes (PLR) have been applied to lymph-node metastases prediction. The aim of this study was to evaluate the role of NLR, derived NLR (dNLR) and PLR in predicting nodal involvement in T1 colorectal cancers. METHODS: NLR, derived NLR (dNLR) and PLR in surgical resected T1 colorectal cancers were retrospectively calculated and analysed in nodal positive and negative cases...
April 12, 2018: Minerva Chirurgica
Annemieke Cats, Edwin P M Jansen, Nicole C T van Grieken, Karolina Sikorska, Pehr Lind, Marianne Nordsmark, Elma Meershoek-Klein Kranenbarg, Henk Boot, Anouk K Trip, H A Maurits Swellengrebel, Hanneke W M van Laarhoven, Hein Putter, Johanna W van Sandick, Mark I van Berge Henegouwen, Henk H Hartgrink, Harm van Tinteren, Cornelis J H van de Velde, Marcel Verheij
BACKGROUND: Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. METHODS: In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function...
April 9, 2018: Lancet Oncology
Hans-Joachim Schmoll, Dirk Arnold, Aimery de Gramont, Michel Ducreux, Axel Grothey, Peter J O'Dwyer, Eric Van Cutsem, Frank Hermann, Ivan Bosanac, Belguendouz Bendahmane, Christoph Mancao, Josep Tabernero
PURPOSE: The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response. METHODS: MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study...
April 11, 2018: Journal of Cancer Research and Clinical Oncology
Sophie F Roerink, Nobuo Sasaki, Henry Lee-Six, Matthew D Young, Ludmil B Alexandrov, Sam Behjati, Thomas J Mitchell, Sebastian Grossmann, Howard Lightfoot, David A Egan, Apollo Pronk, Niels Smakman, Joost van Gorp, Elizabeth Anderson, Stephen J Gamble, Chris Alder, Marc van de Wetering, Peter J Campbell, Michael R Stratton, Hans Clevers
Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells...
April 11, 2018: Nature
Tiphanie Faïs, Julien Delmas, Nicolas Barnich, Richard Bonnet, Guillaume Dalmasso
Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae ) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections...
April 10, 2018: Toxins
Peter Falk, Andreas Jonsson, Torbjörn Swartling, Dan Asplund, Marie-Lois Ivarsson
Colorectal cancer is one of the most common forms of cancer. Spread of tumour to the peritoneal cavity may lead to seeding of cancer cells that adhere to and invade the peritoneal membrane causing peritoneal carcinomatosis. Matrix metalloproteinases (MMPs) play an essential role in cancer cell invasion and dissemination. The aim of this study was to evaluate the morphology and presence of matrix metalloproteinases in peritoneal carcinomatosis. Biopsy samples of the parietal peritoneum were taken from patients undergoing cytoreductive surgery for peritoneal carcinomatosis...
April 5, 2018: Medical Oncology
Chun Yue Mak, Helena Pui-Yee Sin, Vesta Cheuk-Ki Chan, Alvin Young
A 67-year-old Chinese man presented with acute loss of vision and pain in the left eye with hypopyon in the anterior chamber. The patient was afebrile with no systemic symptoms at presentation. Diagnosis of endogenous endophthalmitis was made with vitreous tap yielding Klebsiella pneumoniae Pars plana vitrectomy was performed twice to clear the infection. Thorough investigations showed no septic foci. Whole body positron emission tomography CT revealed a rectal tumour and biopsy showed adenocarcinoma. He was treated with neoadjuvant chemoirradiation followed by surgery to resect the tumour...
April 5, 2018: BMJ Case Reports
Terri Patricia McVeigh, Raghav Sundar, Nikolaos Diamantis, Stan B Kaye, Udai Banerji, Juanita S Lopez, Johann de Bono, Winette T A van der Graaf, Angela J George
INTRODUCTION: Adolescents and young adults (AYAs) diagnosed with cancer between ages 15-39 years may harbour germline variants associated with cancer predisposition. Such variants represent putative therapeutic targets, as may somatic variants in the tumour. Germline and tumour molecular profiling is increasingly utilised to facilitate personalisation of cancer treatment in such individuals. AIM: Considering AYAs with advanced solid tumours managed in a specialist drug development unit (DDU), the aims of this study were to investigate the use and impact of: 1...
March 31, 2018: European Journal of Cancer
Julia Bergheim, Alexander Semaan, Heidrun Gevensleben, Susanne Groening, Andreas Knoblich, Jörn Dietrich, Julia Weber, Jörg C Kalff, Friedrich Bootz, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) methylation in circulating cell-free DNA (ccfDNA) are powerful biomarkers for colorectal cancer (CRC) screening, as well as head and neck squamous cell carcinoma staging and monitoring. In the present study, we investigated SEPT9 and SHOX2 ccfDNA methylation as auxiliary pre and post-therapeutic staging parameters in CRC patients. METHODS: ccfDNA methylation was quantified in 184 prospectively enrolled patients prior to and 3-10 days after surgery, and biomarker levels were associated with clinico-pathological parameters...
April 3, 2018: British Journal of Cancer
Guoda Han, Zhijiang Wei, Haibin Cui, Wei Zhang, Xiaonan Wei, Zhiliang Lu, Xiyong Bai
Colorectal cancer (CRC) is one of the most common cause of cancer-related death in both female and male patients, with a high capacity for tumour migration and invasion. Recently, aberrant nucleolar and spindle-associated protein 1 (NUSAP1) expression has been reported in several cancers. However, the biological function and molecular mechanism of NUSAP1 in CRC have not been reported. Here, we demonstrated that NUSAP1 gene expression was notably upregulated in CRC tissues and cell lines (Caco2, LS174T, SW480, and LoVo)...
March 30, 2018: Experimental Cell Research
Sadiya Khwaja, Kaneez Fatima, Hassanain, Chittaranjan Behera, Avneet Kour, Arjun Singh, Suaib Luqman, Jayanta Sarkar, Debabrata Chanda, Karuna Shanker, A K Gupta, D M Mondhe, Arvind S Negi
Curcumin possesses an attractive chemical structure with highly conjugated diferuloylmethane core. Curcumin mimics have been designed and prepared with an additional bridged phenyl ring in conjugation. Fourteen diverse analogues were evaluated against a panel of human cancer cell lines. The best analogue of the series i.e. compound 6a exhibited potent cytotoxicity against A431, epidermoid carcinoma cell line (IC50  = 1.5 μM) and DLD1, colorectal adenocarcinoma cell line (IC50  = 6.9 μM). In tubulin kinetics experiment, compound 6a destabilized polymerisation process (IC50  = 4...
March 26, 2018: European Journal of Medicinal Chemistry
Cecilia Menna, Giammauro Berardi, Simone Maria Tierno, Claudio Andreetti, Giulio Maurizi, Anna Maria Ciccone, Antonio D'Andrilli, Francesco Cassiano, Camilla Poggi, Daniele Diso, Federico Venuta, Erino Angelo Rendina, Mohsen Ibrahim
BACKGROUND: Lung metastases occur in 10-20% of patients with colorectal cancer (CRC). Lung metastatic pathways of CRC is poorly known and the optimal management for recurrent lung metastases remains uncertain. METHODS: Long-term oncological outcomes of 203 patients with CRC lung metastases who underwent metastasectomy were investigated in this multicentre retrospective study. Ninety-two (45.3%) patients with tumour relapse underwent repeated metastasectomy and 11 (5...
March 29, 2018: Annals of Thoracic Surgery
Daniel Temko, Inge C Van Gool, Emily Rayner, Mark Glaire, Seiko Makino, Matthew Brown, Laura Chegwidden, Claire Palles, Jeroen Depreeuw, Andrew Beggs, Chaido Stathopoulou, John Mason, Ann-Marie Baker, Marc Williams, Vincenzo Cerundolo, Margarida Rei, Jenny C Taylor, Anna Schuh, Ahmed Ahmed, Frédéric Amant, Diether Lambrechts, Vincent Thbm Smit, Tjalling Bosse, Trevor A Graham, David N Church, Ian Tomlinson
Genomic instability, a hallmark of cancer, is generally thought to occur in the mid to late stages of tumorigenesis, following the acquisition of permissive molecular aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their mutation burden is among the highest in human cancer), distinct mutational signature, lymphocytic infiltrate and excellent prognosis. To what extent these characteristics are determined by the timing of POLE mutations in oncogenesis is unknown...
March 31, 2018: Journal of Pathology
Jon Zabaleta, Tomohiko Iida, Pierre E Falcoz, Samer Salah, José R Jarabo, Arlene M Correa, Maria G Zampino, Takashi Matsui, Sukki Cho, Francesco Ardissone, Kazuhiro Watanabe, Michel Gonzalez, Pascal Gervaz, Jose I Emparanza, Víctor Abraira
OBJECTIVES: To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. METHODS: We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014...
March 21, 2018: European Journal of Surgical Oncology
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
Kun Wang, Da Xu, Xiao-Luan Yan, Graeme Poston, Bao-Cai Xing
BACKGROUND: Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. METHODS: We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015...
March 2, 2018: European Journal of Surgical Oncology
S Yamashita, Y S Chun, S E Kopetz, J-N Vauthey
BACKGROUND: Despite a 5-year overall survival rate of 58 per cent after liver resection for colorectal liver metastases (CLMs), more than half of patients develop recurrence, highlighting the need for accurate risk stratification and prognostication. Traditional prognostic factors have been superseded by newer outcome predictors, including those defined by the molecular origin of the primary tumour. METHODS: This review synthesized findings in the literature using the PubMed database of articles in the English language published between 1998 and 2017 on prognostic and predictive biomarkers in patients undergoing resection of CLMs...
March 26, 2018: British Journal of Surgery
Stephen Bell, Joseph C Kong, Roger Wale, Margaret Staples, Karen Oliva, Simon Wilkins, Paul Mc Murrick, Satish K Warrier
BACKGROUND: Obesity is common in Western countries and its prevalence is increasing. Colorectal cancer is common, and surgery for colorectal cancer is technically more challenging in obese patients. Laparoscopic surgery for colon cancer has been shown to be oncologically equivalent, with improved short- term outcomes. Laparoscopic surgery for rectal cancer has proven technically challenging, and recent results have raised concerns about oncologic equivalence. OBJECTIVE: To evaluate the effect of body mass index (BMI) on the clinical and oncological outcomes of surgery for colorectal cancer, including the rate at which laparoscopic surgery is attempted and the rate at which laparoscopic surgery is converted to open surgery...
March 25, 2018: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
Keller Deborah S, Steele Scott R
Colorectal cancer is the 3rd most commonly diagnosed cancer, with rectal cancer specifically accounting for 1/3 of new cases. Despite advances in care, there is still a lack of standardization in diagnosis, staging, and treatment, with associated high rates of positive margins, recurrence, and mortality. The gold standard for curative resection remains a total mesorectal excision(TME), and the quality of the TME is one of the most important prognostic factors for local recurrence. The proper TME specimen with negative resection margins is inherently challenging due to patient and tumour-related factors...
March 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
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