A5087963651- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Colorectal Cancer Screening and Detection
- Pancreatic and Hepatic Oncology Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Inflammatory mediators and NSAID effects
- Colorectal and Anal Carcinomas
- Gastric Cancer Management and Outcomes
- Esophageal Cancer Research and Treatment
- Cancer-related Molecular Pathways
- Helicobacter pylori-related gastroenterology studies
- Estrogen and related hormone effects
- Digestive system and related health
- Synthesis of β-Lactam Compounds
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Colorectal Cancer Surgical Treatments
- Gastrointestinal disorders and treatments
- Cancer-related gene regulation
- Gastrointestinal Tumor Research and Treatment
- DNA Repair Mechanisms
- Cancer and Skin Lesions
- Eosinophilic Esophagitis
- Genomic variations and chromosomal abnormalities
Brigham and Women's Hospital
2008-2025
Harvard University
2005-2025
Dana-Farber Cancer Institute
2004-2025
Massachusetts General Hospital
2007-2024
Mass General Brigham
2024
Boston Children's Hospital
2022-2023
Victorian Comprehensive Cancer Centre
2018
The University of Melbourne
2018
National Cancer Institute
2006-2011
Duke Medical Center
2009-2011
Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor benefit adjuvant chemotherapy fluorouracil in stage II III colon cancer.
Colorectal cancer can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. We tested the hypothesis that colorectal cancers arising from microsatellite-instability pathway have distinctive clinical attributes affect outcome.
Studies showing that drugs inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest COX-2 inhibitors may also prevent sporadic neoplasia.We randomly assigned who had removed before study entry to receive placebo (679 patients) or 200 mg (685 400 (671 celecoxib twice daily. Randomization was stratified for use low-dose aspirin. Follow-up colonoscopies were performed at one three years after randomization. The...
Pancreatic ductal adenocarcinoma ranks among the most lethal of human malignancies. Here, we assess cooperative interactions two signature mutations in mice engineered to sustain pancreas-specific Cre-mediated activation a mutant Kras allele ( G12D ) and deletion conditional Ink4a/Arf tumor suppressor allele. The phenotypic impact alone was limited primarily development focal premalignant lesions, termed pancreatic intraepithelial neoplasias (PanINs), whereas sole inactivation failed produce...
PURPOSE: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. PATIENTS AND METHODS: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI IHC gene products. High-frequency (MSI-H) was defined as more than 30% at least five markers; low-level (MSI-L) 1% to 29% loci unstable. RESULTS: Of tumors tested, 818 showed intact expression hMSH2. these, 680 stable...
Activating KRAS mutations and p16(Ink4a) inactivation are near universal events in human pancreatic ductal adenocarcinoma (PDAC). In mouse models, Kras(G12D) initiates formation of premalignant lesions, loss either Ink4a/Arf (p16(Ink4a)/p19(Arf)) or p53 enables their malignant progression. As recent modeling studies have suggested a less prominent role for constraining progression, we sought to assess the pathological genomic impact p16(Ink4a), p19(Arf), and/or model. Rapidly progressive...
To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer.Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI IHC gene products. High-frequency (MSI-H) was defined as more than 30% at least five markers; low-level (MSI-L) 1% to 29% loci unstable.Of tumors tested, 818 showed intact expression hMSH2. Of these, 680 stable (MSS), 27 MSI-H, 111 MSI-L. In all, 228...
Abstract Several diverse genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These a spectrum pathologic changes; however, until now, there has no uniform nomenclature to characterize these changes. An international workshop, sponsored by The National Cancer Institute and the University Pennsylvania, was held from December 1 3, 2004 with goal establishing an internationally accepted for pathology neoplasia. in 12 existing reviewed at this standardized...
Abstract Purpose: Recent studies suggest that temozolomide has activity in neuroendocrine tumors. Low levels of the DNA repair enzyme, O6-methylguanine methyltransferase (MGMT), are associated with sensitivity to other tumor types. We evaluated prevalence MGMT deficiency tumors and correlated treatment response temozolomide-based regimens. Experimental Design: The deficiency, measured by immunohistochemistry, was assessed 97 archival specimens. Rates survival were next a cohort 101...
Purpose Colon cancers exhibiting DNA mismatch repair (MMR) defects demonstrate distinct clinical and pathologic features, including better prognosis reduced response to fluorouracil (FU) –based chemotherapy. This prospective study investigated adjuvant chemotherapy containing FU irinotecan in patients with MMR deficient (MMR-D) colon cancers. Patients Methods Cancer Leukemia Group B 89803 randomly assigned 1,264 stage III cancer postoperative weekly bolus FU/leucovorin (LV) or irinotecan,...
The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes tumor suppressor genes driving genesis progression this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform informatics tools have been used define copy number alterations in panel 24 cell lines 13 primary specimens. This high-resolution analysis has identified all known regional gains losses as well many previously...
Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in identification protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models cancer been shown to faithfully recapitulate molecular, biological, clinical features disease. Here, we sought exploit merits a well-characterized GEM model pancreatic determine whether proteomics technologies allow development such are relevant cancer. Methods...
The MutY human homologue (MYH) gene encodes a member of the base excision repair pathway that is involved in repairing oxidative damage to DNA. Two germline MYH mutations result Myh proteins containing amino acid substitutions Y165C and G382D (hereafter called mutations) are associated with adenomatous poly-posis colorectal cancer among patients from several European registries. We used population-based series 1238 1255 healthy control subjects Ontario, Canada, examine risk biallelic...
Inactivation of deoxyribonucleic acid (DNA) mismatch repair genes, most commonly human mutL homologue 1 (hMLH1) or mutS 2 (hMSH2), is a recently described alternate pathway in cancer development and progression. The resulting genetic instability characterized by widespread somatic mutations tumor DNA, termed high-frequency microsatellite (MSI-H). Although variety tumors, deficiency has been studied predominantly colorectal carcinoma. Most MSI-H carcinomas are sporadic, but some occur...
Abstract The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk cancer. trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or 400 daily. primary study analyses involved 3 years treatment. results showed significant antitumor effect but also indicated increased cardiovascular adverse events treated compared placebo. A...