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https://www.readbyqxmd.com/read/28440295/kdm3-epigenetically-controls-tumorigenic-potentials-of-human-colorectal-cancer-stem-cells-through-wnt-%C3%AE-catenin-signalling
#1
Jiong Li, Bo Yu, Peng Deng, Yingduan Cheng, Yongxin Yu, Kareena Kevork, Sivakumar Ramadoss, Xiangming Ding, Xinmin Li, Cun-Yu Wang
Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription...
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28438427/systematic-review-of-perioperative-and-survival-outcomes-of-liver-resections-with-and-without-preoperative-portal-vein-embolization-for-colorectal-metastases
#2
REVIEW
Natasha Ironside, Richard Bell, Adam Bartlett, John McCall, James Powell, Sanjay Pandanaboyana
BACKGROUND: The aim of this systematic review was to evaluate perioperative and long term outcomes in patients who underwent PVE prior to liver resection for colorectal liver metastases. METHODS: A systematic search of PubMed, MEDLINE, Embase and the Cochrane library was performed in accordance with PRISMA guidelines. Studies including patients who underwent liver resection with and without PVE (N-PVE) were included. RESULTS: Thirteen studies including 1345 were included of which 539 patients had PVE and 806 had N-PVE...
April 21, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28433252/nrasq61r-immunohistochemistry-detects-both-nrasq61r-and-krasq61r-mutations-in-colorectal-cancer
#3
Jie-Yang Jhuang, Chang-Tsu Yuan, Yu-Lin Lin, Mei-Ling Cheng, Jau-Yu Liau, Jia-Huei Tsai
The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody that is increasingly being used to detect the NRAS(Q61R) mutation in melanomas. This antibody has been reported to be highly correlated with the NRAS(Q61R) mutation status in melanomas and follicular neoplasms of the thyroid gland. However, its utility in colorectal carcinoma (CRC) has remained largely unknown. In this study, we assessed the sensitivity, specificity, and diagnostic utility of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113 CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations...
April 19, 2017: Pathology
https://www.readbyqxmd.com/read/28433044/-laparoscopic-diverting-ileostomy-in-rectal-cancer-surgery
#4
P Ihnát, P Vávra, P Guňková, A Zatloukal, S Czudek, P Zonča
INTRODUCTION: Low anterior resection (LAR) with total mesorectal excision (TME) represents the gold standard for patients with low rectal carcinoma. Protective ileostomy (PI) is commonly performed during LAR in an effort to protect low rectal anastomosis. The aim of this study is to analyse outcomes in our own patient population, focusing on morbidity associated with PI. METHOD: A retrospective clinical study of patients operated on between 2013 and 2015 was conducted in University Hospital Ostrava...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/28432443/progastrin-a-potential-predictive-marker-of-liver-metastasis-in-colorectal-cancer
#5
David A Westwood, Oneel Patel, Christopher Christophi, Arthur Shulkes, Graham S Baldwin
BACKGROUND AND AIMS: Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer. METHODS: Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included...
April 21, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28427281/the-servier-oncology-pipeline-in-2017
#6
Patrick Therasse, Beatrice Perron, Sarah A Novack, Jean-Pierre Abastado
Cancer is a complex, multifactorial disease that for years has been the focus of intensive research efforts to explore both the molecular and biological mechanisms involved and the development of novel agents to target these pathways. Servier is an independent French pharmaceutical company with a focus on oncology. Currently, Servier's commercial portfolio includes agents used to treat non-Hodgkin's lymphoma and metastatic colorectal cancer; Servier's oncology pipeline involves agents for the treatment of both solid and hematological tumors...
April 21, 2017: Future Oncology
https://www.readbyqxmd.com/read/28427085/tumour-invasiveness-the-local-and-systemic-environment-and-the-basis-of-staging-systems-in-colorectal-cancer
#7
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/28424871/final-analysis-of-the-randomised-peak-trial-overall-survival-and-tumour-responses-during-first-line-treatment-with-mfolfox6-plus-either-panitumumab-or-bevacizumab-in-patients-with-metastatic-colorectal-carcinoma
#8
Fernando Rivera, Meinolf Karthaus, J Randolph Hecht, Isabel Sevilla, Frédéric Forget, Gianpiero Fasola, Jean-Luc Canon, Xuesong Guan, Gaston Demonty, Lee S Schwartzberg
PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective...
April 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28424486/meta-analysis-reveals-the-prognostic-value-of-circulating-tumour-cells-detected-in-the-peripheral-blood-in-patients-with-non-metastatic-colorectal-cancer
#9
Yan-Jun Lu, Peng Wang, Jing Peng, Xiong Wang, Yao-Wu Zhu, Na Shen
Detecting circulating tumour cells (CTCs) is considered as effective and minimally invasive technique to predict the prognosis of patients with metastatic colorectal cancer (CRC), but its clinical validity is still conflicting in patients without metastasis. We performed this meta-analysis to evaluate whether detection of CTCs in the peripheral blood can be used as a prognostic marker for patients with non-metastatic CRC. We performed a comprehensive search of the EMBASE, PubMed, and Web of Science databases (up to September 2016)...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#10
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28419692/associating-liver-partition-and-portal-vein-ligation-for-staged-hepatectomy-after-pre-operative-chemotherapy
#11
Florian W R Vondran, Felix Oldhafer, Kristina I Ringe, Thomas C Wirth, Moritz Kleine, Mark D Jäger, Juergen Klempnauer, Hueseyin Bektas
BACKGROUND: Recently a procedure termed 'Associating Liver Partition and Portal vein ligation for Staged hepatectomy' (ALPPS) was developed to increase the resectability of marginally resectable or locally unresectable liver tumours. This study focused on the application of ALPPS in patients with advanced colorectal liver metastases (CRLM) and pre-operative chemotherapy, with the aim to investigate whether the latter still allows for sufficient hypertrophy of the future liver remnant (FLR) following the first step of ALPPS...
April 16, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28416736/nomo-1-gene-is-deleted-in-early-onset-colorectal-cancer
#12
José Perea, Juan Luis García, Jessica Pérez, Daniel Rueda, María Arriba, Yolanda Rodríguez, Miguel Urioste, Rogelio González-Sarmiento
To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess the status of NOMO1, a gene located in that region, we analyzed differential clinicopathological, familial and molecular features of CRC subsets with and without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We confirmed the region by fluorescence in-situ hybridization, and Quantitative Real-Time PCR analyzed the status of NOMO1 in different age-of-onset and Microsatellite Instability (MSI)-status CRC subsets...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413670/glasgow-prognostic-score-predicts-prognosis-of-intrahepatic-cholangiocarcinoma
#13
Qun-Xiong Pan, Zi-Jian Su, Jian-Hua Zhang, Chong-Ren Wang, Shao-Ying Ke
High Glasgow Prognostic Score (GPS) has been associated with poor prognosis in patients with lung, ovarian, colorectal and renal cancer, as well as hepatocellular carcinoma. The aim of this study was to investigate the prognostic value of GPS in patients with intrahepatic cholangiocarcinoma (ICC) undergoing partial hepatectomy. A total of 72 patients with pathologically confirmed ICC were classified according to their GPS scores assigned based on the preoperative levels of C-reactive protein (CRP) and albumin...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28412738/reduced-nov-expression-correlates-with-disease-progression-in-colorectal-cancer-and-is-associated-with-survival-invasion-and-chemoresistance-of-cancer-cells
#14
Jun Li, Lin Ye, Ping-Hui Sun, Fei Zheng, Fiona Ruge, Lucy K Satherley, Yi Feng, Huishan Zhao, Guifang Du, Tingting Wang, Yao Yang, Xuemei Ma, Shan Cheng, Xiaomei Yang, Hefen Yu, Xu Teng, Yang Si, Zhongtao Zhang, Wen G Jiang
Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in certain malignancies. In the current study, we aim to investigate the role played by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of 359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was investigated using in vitro NOV knockdown and overexpression models. NOV transcripts were reduced in the CRC tumours compared with the paired adjacent normal colorectal tissues (p < 0.01) and was associated with distant metastases...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407529/resection-of-colorectal-liver-metastases-after-second-line-chemotherapy-is-it-worthwhile-a-livermetsurvey-analysis-of-6415-patients
#15
René Adam, Bin Yi, Pasquale F Innominato, Eduardo Barroso, Christophe Laurent, Felice Giuliante, Lorenzo Capussotti, Réal Lapointe, Jean-Marc Regimbeau, Santiago Lopez-Ben, Helena Isoniemi, Catherine Hubert, Jen-Kou Lin, Thomas Gruenberger, Dominique Elias, Oleg G Skipenko, Alfredo Guglielmi
PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively)...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407110/prognostic-and-predictive-value-of-primary-tumour-side-in-patients-with-ras-wild-type-metastatic-colorectal-cancer-treated-with-chemotherapy-and-egfr-directed-antibodies-in-six-randomised-trials
#16
D Arnold, B Lueza, J-Y Douillard, M Peeters, H-J Lenz, A Venook, V Heinemann, E Van Cutsem, J-P Pignon, J Tabernero, A Cervantes, F Ciardiello
Background: There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome. Methods: This retrospective analysis investigated the prognostic and predictive influence of the localisation of the primary tumour in patients with unresectable RAS wt mCRC included in six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus EGFR antibody therapy (experimental arm) with chemotherapy or chemotherapy and bevacizumab (control arms)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28404198/molecular-fluorescence-guided-surgery-of-peritoneal-carcinomatosis-of-colorectal-origin-a-single-centre-feasibility-study
#17
Niels J Harlaar, Marjory Koller, Steven J de Jongh, Barbara L van Leeuwen, Patrick H Hemmer, Schelto Kruijff, Robert J van Ginkel, Lukas B Been, Johannes S de Jong, Gursah Kats-Ugurlu, Matthijs D Linssen, Annelies Jorritsma-Smit, Marleen van Oosten, Wouter B Nagengast, Vasilis Ntziachristos, Gooitzen M van Dam
BACKGROUND: Optimum cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is essential for the curative treatment of peritoneal carcinomatosis of colorectal origin. At present, surgeons depend on visual inspection and palpation for tumour detection. Improved detection of tumour tissue using molecular fluorescence-guided surgery could not only help attain a complete cytoreduction of metastatic lesions, but might also prevent overtreatment by avoiding resection of benign lesions...
December 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28404093/somatic-pole-proofreading-domain-mutation-immune-response-and-prognosis-in-colorectal-cancer-a-retrospective-pooled-biomarker-study
#18
Enric Domingo, Luke Freeman-Mills, Emily Rayner, Mark Glaire, Sarah Briggs, Louis Vermeulen, Evelyn Fessler, Jan Paul Medema, Arnoud Boot, Hans Morreau, Tom van Wezel, Gerrit-Jan Liefers, Ragnhild A Lothe, Stine A Danielsen, Anita Sveen, Arild Nesbakken, Inti Zlobec, Alessandro Lugli, Viktor H Koelzer, Martin D Berger, Sergi Castellví-Bel, Jenifer Muñoz, Marco de Bruyn, Hans W Nijman, Marco Novelli, Kay Lawson, Dahmane Oukrif, Eleni Frangou, Peter Dutton, Sabine Tejpar, Mauro Delorenzi, Rachel Kerr, David Kerr, Ian Tomlinson, David N Church
BACKGROUND: Precision cancer medicine depends on defining distinct tumour subgroups using biomarkers that may occur at very modest frequencies. One such subgroup comprises patients with exceptionally mutated (ultramutated) cancers caused by mutations that impair DNA polymerase epsilon (POLE) proofreading. METHODS: We examined the association of POLE proofreading domain mutation with clinicopathological variables and immune response in colorectal cancers from clinical trials (VICTOR, QUASAR2, and PETACC-3) and colorectal cancer cohorts (Leiden University Medical Centre 1 and 2, Oslo 1 and 2, Bern, AMC-AJCC-II, and Epicolon-1)...
November 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28401350/peritoneal-fluid-biomarkers-in-the-detection-of-colorectal-anastomotic-leaks-a-systematic-review
#19
REVIEW
Emma C Wright, Patricia Connolly, Mark Vella, Susan Moug
PURPOSE: Anastomotic leak (AL) in colorectal surgery leads to significant morbidity, mortality and poorer oncological outcomes. Diagnosis of AL is frequently delayed as current methods of detection are not 100% sensitive or specific. 'Biomarkers', such as cytokines and markers of ischaemia, from the milieu of the anastomosis may aid early detection. This paper aims to review the evidence for their role in AL detection, allowing identification of targets for future research. METHODS: A systematic review was performed using PubMed, MEDLINE and Cochrane Library databases...
April 12, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28399112/cetuximab-in-treatment-of-metastatic-colorectal-cancer-final-survival-analyses-and-extended-ras-data-from-the-nordic-vii-study
#20
Tormod Kyrre Guren, Maria Thomsen, Elin H Kure, Halfdan Sorbye, Bengt Glimelius, Per Pfeiffer, Pia Österlund, Fridbjörn Sigurdsson, Inger Marie Bowitz Lothe, Astrid Marie Dalsgaard, Eva Skovlund, Thoralf Christoffersen, Kjell Magne Tveit
BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis. METHODS: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study...
April 11, 2017: British Journal of Cancer
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