A5028047618- Esophageal Cancer Research and Treatment
- Gastric Cancer Management and Outcomes
- Cancer Genomics and Diagnostics
- Gastrointestinal Tumor Research and Treatment
- Esophageal and GI Pathology
- Pancreatic and Hepatic Oncology Research
- Helicobacter pylori-related gastroenterology studies
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Gastroesophageal reflux and treatments
- Eosinophilic Esophagitis
- Cancer-related gene regulation
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Gastrointestinal disorders and treatments
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Tissue Engineering and Regenerative Medicine
- Ovarian cancer diagnosis and treatment
- Molecular Biology Techniques and Applications
- Microtubule and mitosis dynamics
- Advanced Biosensing Techniques and Applications
Brigham and Women's Hospital
2014-2024
Harvard University
2010-2024
Harvard University Press
2015
Boston Children's Hospital
2010
Sidney Kimmel Comprehensive Cancer Center
2005-2008
Johns Hopkins University
2005-2008
Abstract Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies that profiling results could commonly differ between primary and metastatic tumors. To evaluate heterogeneity, we sequenced paired GEA synchronous lesions across multiple cohorts, finding extensive differences in alterations, including discrepancies potentially clinically relevant...
The histologic changes associated with acute gastroesophageal reflux disease (GERD) have not been studied prospectively in humans. Recent studies animals challenged the traditional notion that esophagitis develops when esophageal surface epithelial cells are exposed to lethal chemical injury from refluxed acid.To evaluate features of inflammation GERD study its pathogenesis.Patients Dallas Veterans Affairs Medical Center who had successfully treated proton pump inhibitors (PPIs) began...
Ipilimumab is a monoclonal antibody that inhibits the CTLA4 receptor on cytotoxic T lymphocytes, resulting in immune-mediated tumor cell death. most often used treatment of metastatic melanoma, and rarely liver toxicity necessitating cessation occurs. The aim this study was to characterize histologic features clinical course ipilimumab-associated hepatitis. Eleven patients with suspicion ipilimumab-induced hepatitis, due development abnormal function tests (LFTs) while receiving treatment,...
Abstract Currently available human tumour cell line panels consist of a small number lines in each lineage that generally fail to retain the phenotype original patient tumour. Here we develop culture medium enables us routinely establish from diverse subtypes ovarian cancers with >95% efficiency. Importantly, 25 new described here genomic landscape, histopathology and molecular features tumours. Furthermore, profile drug response these correlate distinct groups primary tumours different...
Abstract Histone deacetylases (HDAC) play a critical role in chromatin modification and gene expression. Recent evidence indicates that HDACs can also regulate functions of nonhistone proteins by catalyzing the removal acetylated lysine residues. Here, we show HDAC inhibitor LBH589 down-regulates DNA methyltransferase 1 (DNMT1) protein expression nucleus human breast cancer cells. Cotreatment with proteasomal MG-132 abolishes ability to reduce DNMT1, suggesting pathway mediates DNMT1...
We report that DNA methyltransferase 1 (DNMT1) expression is dysregulated in breast cancer. The elevated protein levels are not a result of increased mRNA levels, but rather an increase half-life. found DNMT1 were cancer tissues and MCF-7 cells relative to normal human mammary epithelial (HMECs) without concomitant or proliferative fraction. Although properly S-phase-regulated both cell types, did follow S-phase fraction cells. Rather, stability was for HMECs, destruction domain mapped the...
Ag-specific T cell cytokine expression is dictated by the context in which TCR engagement occurs. Recently it has become clear that epigenetic changes play a role this process. DNA methyltransferase 3a (DNMT3a) de novo important to control of fate. We have determined DNMT3a increased following and costimulation mitigates protein expression. cells lacking simultaneously express IFN-gamma IL-4 after expansion under nonbiasing conditions. While global methylation from wild-type knockout...
Abstract The progression of precancerous lesions to malignancy is often accompanied by increasing complexity chromosomal alterations but how these arise poorly understood. Here we perform haplotype-specific analysis copy-number evolution in the Barrett’s esophagus (BE) esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data BE with dysplasia and microscopic EAC foci. We identify distinct patterns indicating multigenerational instability that initiated cell division...
In an earlier study wherein we induced acute reflux by interrupting proton pump inhibitor (PPI) therapy in patients with oesophagitis (RO) healed PPIs, refuted the traditional concept that RO develops as acid burn. The present explored our alternative hypothesis results from reflux-stimulated production of pro-inflammatory molecules mediated hypoxia-inducible factors (HIFs).Using oesophageal biopsies taken at baseline and 1 2 weeks off immunostained for HIF-1α, HIF-2α phospho-p65, measured...
Huang Q, Fan X, Agoston A T, Feng A, Yu H, Lauwers G, Zhang L & Odze R D (2011) Histopathology 59 , 188–197 Comparison of gastro‐oesophageal junction carcinomas in Chinese versus American patients Aims: To compare the clinical and pathological features (GEJ) patients. Methods results: Eighty consecutive with a GEJ carcinoma (43 from mainland China, 37 USA) were evaluated for association Barrett oesophagus (BO), chronic Helicobacter pylori gastritis, intestinal metaplasia, outcome....
A robotic implant for inducing tissue growth in tubular organs is demonstrated through esophageal lengthening swine.
SMAD4 (DPC4) is a tumour suppressor gene that dysregulated in various types, particularly pancreaticobiliary and gastrointestinal carcinomas. Corresponding loss of protein expression has been reported approximately 50% pancreatic 25% colonic adenocarcinomas. In the evaluation carcinoma unknown primary site, immunohistochemical often used to suggest origin, but there are limited data on spectrum carcinomas other sites. This study evaluates frequency large cohort from diverse anatomical...
Outcomes for pancreatic cancer (PC) patients remain strikingly poor with a 5-year survival of less than 8% due to the lack effective treatment modalities. Here, novel precision medicine approach PC is developed, which composed rationally designed tumor-targeting ICAM1 antibody-drug conjugate (ADC) optimized chemical linker and cytotoxic payload, complemented magnetic resonance imaging (MRI)-based molecular noninvasively evaluate efficiency ADC therapy. It shown that differentially...
Induction therapy followed by esophagectomy has become standard for treatment of intermediate-stage esophageal cancer in many centers. Herein we evaluate the feasibility and safety 3-hole minimally invasive (3HMIE) approach patients who received induction radiation chemotherapy. Between 2003 2012, records 119 consecutive with underwent 3HMIE were reviewed perioperative complications long-term outcomes. Comparison was made between procedures performed receiving neoadjuvant chemoradiation...
<h3>Background & Aims</h3> After esophagojejunostomy, rodents develop reflux esophagitis and a columnar-lined esophagus with features of Barrett's metaplasia. This rodent has been proposed to from cellular reprogramming progenitor cells, but studies on early development are lacking. We performed systematic, histologic, immunophenotypic analysis in rats after esophagojejunostomy. <h3>Methods</h3> At various times esophagojejunostomy 52 rats, the was removed tissue sections were evaluated for...
Complete response to neoadjuvant therapy, determined by pathologic examination of the resection specimen (pCR), is associated with a favorable outcome in esophageal adenocarcinomas (EAC), but there significant heterogeneity survival reported within this group. Our aim was determine predictors disease recurrence (DR) and EAC patients pCR therapy. A total 93 therapy were identified, predetermined set clinicopathologic variables examined, including patient age, sex, tumor location, pretreatment...
No consensus guideline has been established for microsatellite instability testing in upper gastrointestinal tract cancers. This study aims to determine whether targeted cancer next-generation sequencing can accurately detect cancers and screen patients with Lynch syndrome.In a cohort of 645 cancers, assessed by identifying characteristic insertion deletion mutations. Sequencing classification was compared mismatch repair protein IHC. Cancers were analyzed using protocol identify...