title: Molecular mechanisms in Barrett's metaplasia and its progression.
abstract: The dramatic increase in the incidence and poor overall survival rates of esophageal/gastroesophageal junction adenocarcinoma underscore the necessity to discover molecular markers that can be used for risk assessment, early diagnosis, and targeted therapeutic intervention. Barrett's esophagus (BE) is proposed to represent a precursor of esophageal/gastroesophageal junction adenocarcinoma. BE progression to invasive cancer is defined by a metaplasia-dysplasia-carcinoma progression characterized by an increasing accumulation of genetic changes associated with alterations in molecular gatekeepers of cell circuitries and tissue homeostasis. Using a combination of in situ tissue-based and high-throughput analyses, we investigated alterations of cell-cycle regulators and inflammation-associated molecular effectors. Our data suggest a potential synergistic effect of these alterations for the BE progression to cancer, and underscore the potential use of these markers: (1) in molecular panels assessing cancer risk in BE patients; and (2) as potential therapeutic targets for chemopreventive interventions and to enhance response to anti-neoplastic therapies.
authors: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jizzo@mdanderson.org
authors: Julie G
authors: JG
authors: Izzo
authors: Rajyalakshmi
authors: R
authors: Luthra
authors: Tseung-Teh
authors: TT
authors: Wu
authors: Arlene M
authors: AM
authors: Correa
authors: Madan
authors: M
authors: Luthra
authors: Sharmila
authors: S
authors: Anandasabapathy
authors: K S Clifford
authors: KS
authors: Chao
authors: Mien-Chie
authors: MC
authors: Hung
authors: Bharat
authors: B
authors: Aggarwal
authors: Walter N
authors: WN
authors: Hittelman
authors: Jaffer A
authors: JA
authors: Ajani
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D001471:Barrett Esophagus / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018890:Chemoprevention; D019938:Cyclin D1 / Q000502:physiology; D018450:Disease Progression; D042241:Early Diagnosis; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D008679:Metaplasia; D016328:NF-kappa B / Q000502:physiology; D011230:Precancerous Conditions / Q000473:pathology*; D018570:Risk Assessment; D015398:Signal Transduction / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D019938:Cyclin D1