Read by QxMD icon Read

Tejpar colon cancer

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
Philip D Dunne, Helen G Coleman, Peter Bankhead, Matthew Alderdice, Ronan T Gray, Stephen McQuaid, Victoria Bingham, Maurice B Loughrey, Jacqueline A James, Amy M B McCorry, Alan Gilmore, Caitriona Holohan, Dirk Klingbiel, Sabine Tejpar, Patrick G Johnston, Darragh G McArt, Federica Di Nicolantonio, Daniel B Longley, Mark Lawler
Purpose: BRAF mutation occurs in 8-15% of colon cancers (CC), and is associated with poor prognosis in metastatic disease. Compared to wild-type BRAF (BRAFWT) disease, stage II/III CC patients with BRAF mutant (BRAFMT) tumors have shorter overall survival after relapse; however, time-to-relapse is not significantly different. The aim of this investigation was to identify, and validate, novel predictors of relapse of stage II/III BRAFMT CC. Experimental design: We used gene expression data from a cohort of 460 patients (GSE39582) to perform a supervised classification analysis based on risk-of-relapse within BRAFMT stage II/III CC, to identify transcriptomic biomarkers associated with prognosis within this genotype...
March 2, 2018: Oncotarget
R Dienstmann, M J Mason, F A Sinicrope, A I Phipps, S Tejpar, A Nesbakken, S A Danielsen, A Sveen, D D Buchanan, M Clendenning, C Rosty, B Bot, S R Alberts, J Milburn Jessup, R A Lothe, M Delorenzi, P A Newcomb, D Sargent, J Guinney
Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
R Dienstmann, M J Mason, F A Sinicrope, A I Phipps, S Tejpar, A Nesbakken, S A Danielsen, A Sveen, D D Buchanan, M Clendenning, C Rosty, B Bot, S R Alberts, J Milburn Jessup, R A Lothe, M Delorenzi, P A Newcomb, D Sargent, J Guinney
No abstract text is available yet for this article.
February 9, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Albert Bosch-Vilaró, Bart Jacobs, Valentina Pomella, Layka Abbasi Asbagh, Richard Kirkland, Joe Michel, Sharat Singh, Xinjun Liu, Phillip Kim, Gregory Weitsman, Paul R Barber, Borivoj Vojnovic, Tony Ng, Sabine Tejpar
The EGFR inhibitor cetuximab is approved for the treatment of colorectal cancer. However, both innate and acquired resistance mechanisms, including compensatory feedback loops, limit its efficacy. Nevertheless, the emergence of these feedback loops has remained largely unexplored to date. Here, we showed feedback upregulation of HER3 and induction of HER3 phosphorylation after cetuximab treatment in colon cancer cells. We also showed that this upregulation occurs, at least partly, through AKT inhibition. Together with this, we observed increased HER2:HER3 dimerization upon cetuximab treatment...
January 17, 2017: Oncotarget
Sabine Tejpar, Sebastian Stintzing, Fortunato Ciardiello, Josep Tabernero, Eric Van Cutsem, Frank Beier, Regina Esser, Heinz-Josef Lenz, Volker Heinemann
Importance: Metastatic colorectal cancer (mCRC) is heterogeneous, and primary tumors arising from different regions of the colon are clinically and molecularly distinct. Objective: To examine the prognostic and predictive value of primary tumor location in patients with RAS wild-type (wt) mCRC treated with first-line fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab in the Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial and FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment For Patients With Metastatic Colorectal Cancer (FIRE-3) trial...
October 10, 2016: JAMA Oncology
Ida Kappel Buhl, Sarah Gerster, Mauro Delorenzi, Thomas Jensen, Peter Buhl Jensen, Fred Bosman, Sabine Tejpar, Arnaud Roth, Nils Brunner, Anker Hansen, Steen Knudsen
PURPOSE: This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. METHODS: To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial...
2016: PloS One
Loredana Vecchione, Valentina Gambino, Jonne Raaijmakers, Andreas Schlicker, Arianna Fumagalli, Mariangela Russo, Alberto Villanueva, Evelyne Beerling, Alice Bartolini, David G Mollevi, Nizar El-Murr, Marielle Chiron, Loreley Calvet, Céline Nicolazzi, Cécile Combeau, Christophe Henry, Iris M Simon, Sun Tian, Sjors in 't Veld, Giovanni D'ario, Sara Mainardi, Roderick L Beijersbergen, Cor Lieftink, Sabine Linn, Cornelia Rumpf-Kienzl, Mauro Delorenzi, Lodewyk Wessels, Ramon Salazar, Federica Di Nicolantonio, Alberto Bardelli, Jacco van Rheenen, René H Medema, Sabine Tejpar, René Bernards
BRAF(V600E) mutant colon cancers (CCs) have a characteristic gene expression signature that is also found in some tumors lacking this mutation. Collectively, they are referred to as "BRAF-like" tumors and represent some 20% of CCs. We used a shRNA-based genetic screen focused on genes upregulated in BRAF(V600E) CCs to identify vulnerabilities of this tumor subtype that might be exploited therapeutically. Here, we identify RANBP2 (also known as NUP358) as essential for survival of BRAF-like, but not for non-BRAF-like, CC cells...
April 7, 2016: Cell
Pu Yan, Dirk Klingbiel, Zenia Saridaki, Paola Ceppa, Monica Curto, Thomas Alexander McKee, Arnaud Roth, Sabine Tejpar, Mauro Delorenzi, Fredrik T Bosman, Roberto Fiocca
PURPOSE: SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival. EXPERIMENTAL DESIGN: We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Valérie Boige, Marc Vincent, Philippe Alexandre, Sabine Tejpar, Stefania Landolfi, Karine Le Malicot, Richard Greil, Pieter Jan Cuyle, Mette Yilmaz, Roger Faroux, Axel Matzdorff, Ramon Salazar, Côme Lepage, Julien Taieb, Pierre Laurent-Puig
Importance: Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on fluorouracil-related adverse events (fluorouracil AEs). However, conflicting results highlight the need for prospective validation in large, homogeneous patient populations uniformly treated with current standard combination therapies used in colon cancer (CC). Objective: To determine the impact of DPYD variants on fluorouracil AEs in patients with stage III CC treated with a fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) regimen...
January 21, 2016: JAMA Oncology
Sune Boris Nygård, Ben Vainer, Signe Lykke Nielsen, Fred Bosman, Sabine Tejpar, Arnaud Roth, Mauro Delorenzi, Nils Brünner, Eva Budinska
PURPOSE: Prospective-retrospective assessment of the TOP1 gene copy number and TOP1 mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan. TOP1 copy number status was analyzed by fluorescence in situ hybridization (FISH) using a TOP1/CEN20 dual-probe combination...
April 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nicky D'Haene, Marie Le Mercier, Nancy De Nève, Oriane Blanchard, Mélanie Delaunoy, Hakim El Housni, Barbara Dessars, Pierre Heimann, Myriam Remmelink, Pieter Demetter, Sabine Tejpar, Isabelle Salmon
OBJECTIVE: Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. METHODS: We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF)...
2015: PloS One
Jeroen Declercq, Bart Jacobs, Bart Biesmans, Arnaud Roth, Dirk Klingbiel, Sabine Tejpar, John W Creemers
High expression of the proprotein processing enzyme FURIN has been associated with tumor progression and metastasis. A SNP (rs4932178) in the promoter of FURIN has been reported to affect expression in liver, with the T allele resulting in higher expression than the C allele. In this study we have investigated the association of this SNP with prognostic and biological subgroups of colorectal cancer (CRC). In a panel of 1382 patients with CRC, this SNP had no impact on overall survival or on postoperative risk of relapse...
2015: BioMed Research International
L De Smedt, J Lemahieu, S Palmans, O Govaere, T Tousseyn, E Van Cutsem, H Prenen, S Tejpar, M Spaepen, G Matthijs, C Decaestecker, X Moles Lopez, P Demetter, I Salmon, X Sagaert
BACKGROUND: Microsatellite instability (MSI) accounts for 15% of all colorectal tumours. Several specific clinicopathologicals (e.g., preference for the proximal colon over the distal colon, improved prognosis and altered response to chemotherapeutics) are described for this subset of tumours. This study aimed to analyse morphological, inflammatory and angiogenic features of MSI vs microsatellite stable (MSS) tumours. METHODS: Twenty-seven MSS and 29 MSI, TNM stage matched, colorectal tumours were selected from the archive of the Department of Pathology, UZ Leuven...
July 28, 2015: British Journal of Cancer
D Klingbiel, Z Saridaki, A D Roth, F T Bosman, M Delorenzi, S Tejpar
BACKGROUND: Although colon cancer (CC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CC, the impact varies according to clinicopathological parameters. We studied how MSI status affects prognosis in a trial-based cohort of stage II and III CC patients treated with 5-fluorouracil (5-FU)/leucovorin or FOLFIRI. MATERIALS AND METHODS: Tissue specimens of 1254 patients were tested for 10 different loci and were classified as MSI-high (MSI-H) when three or more loci were unstable and MSS otherwise...
January 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Frank A Sinicrope, Qian Shi, Thomas C Smyrk, Stephen N Thibodeau, Rodrigo Dienstmann, Justin Guinney, Brian M Bot, Sabine Tejpar, Mauro Delorenzi, Richard M Goldberg, Michelle Mahoney, Daniel J Sargent, Steven R Alberts
BACKGROUND & AIMS: Categorization of colon cancers into distinct subtypes using a combination of pathway-based biomarkers could provide insight into stage-independent variability in outcomes. METHODS: We used a polymerase chain reaction-based assay to detect mutations in BRAF (V600E) and in KRAS in 2720 stage III cancer samples, collected prospectively from patients participating in an adjuvant chemotherapy trial (NCCTG N0147). Tumors deficient or proficient in DNA mismatch repair (MMR) were identified based on detection of MLH1, MSH2, and MSH6 proteins and methylation of the MLH1 promoter...
January 2015: Gastroenterology
Layka Abbasi Asbagh, Iria Vazquez, Loredana Vecchione, Eva Budinska, Veerle De Vriendt, Maria Francesca Baietti, Mikhail Steklov, Bart Jacobs, Nicholas Hoe, Sharat Singh, Naga-Sailaja Imjeti, Pascale Zimmermann, Anna Sablina, Sabine Tejpar
Inappropriate activation of epidermal growth factor receptor (EGFR) plays a causal role in many cancers including colon cancer. The activation of EGFR by phosphorylation is balanced by receptor kinase and protein tyrosine phosphatase activities. However, the mechanisms of negative EGFR regulation by tyrosine phosphatases remain largely unexplored. Our previous results indicate that protein tyrosine phosphatase receptor type O (PTPRO) is down-regulated in a subset of colorectal cancer (CRC) patients with a poor prognosis...
October 30, 2014: Oncotarget
Antonio F Di Narzo, Sabine Tejpar, Simona Rossi, Pu Yan, Vlad Popovici, Pratyaksha Wirapati, Eva Budinska, Tao Xie, Heather Estrella, Adam Pavlicek, Mao Mao, Eric Martin, Weinrich Scott, Fred T Bosman, Arnaud Roth, Mauro Delorenzi
BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis...
October 2014: Journal of the National Cancer Institute
Zenia Saridaki, Joanne B Weidhaas, Heinz-Josef Lenz, Pierre Laurent-Puig, Bart Jacobs, Jef De Schutter, Wendy De Roock, David W Salzman, Wu Zhang, Dongyun Yang, Camilla Pilati, Olivier Bouché, Hubert Piessevaux, Sabine Tejpar
PURPOSE: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer. EXPERIMENTAL DESIGN: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome...
September 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
E Missiaglia, B Jacobs, G D'Ario, A F Di Narzo, C Soneson, E Budinska, V Popovici, L Vecchione, S Gerster, P Yan, A D Roth, D Klingbiel, F T Bosman, M Delorenzi, S Tejpar
BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis...
October 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"