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Aaron P Thrift - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of barrett s esophagus and Esophageal Adenocarcinoma implications for screening and surveillance
Gastrointestinal Endoscopy Clinics of North America, 2021Co-Authors: Michael B Cook, Aaron P ThriftAbstract:In the United States, the incidence of Esophageal Adenocarcinoma increased markedly since the 1970s with a recent stabilization. Despite evolving screening and surveillance strategies to diagnose, risk triage, and intervene in Barrett's esophagus patients to prevent Esophageal Adenocarcinoma, most cases present with advanced disease and poor resultant survival. Epidemiologic studies have identified the main risk factors for these conditions, including increasing age, male sex, white race, gastroEsophageal reflux disease, abdominal obesity, cigarette smoking, and lack of infection with Helicobacter pylori. This review summarizes the current epidemiologic evidence with implications for screening and surveillance in Barrett's esophagus and Esophageal Adenocarcinoma.
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Determination of risk for Barrett's esophagus and Esophageal Adenocarcinoma.
Current Opinion in Gastroenterology, 2016Co-Authors: Aaron P ThriftAbstract:The incidence of Esophageal Adenocarcinoma and its precursor, Barrett's esophagus, have increased greatly over the past 40 years and continue to rise. This report summarizes the most recent data on the risk factors for Barrett's esophagus and Esophageal Adenocarcinoma.Other factors, highly correlated with increasing trends for obesity, are the dominant driver of the increase in incidence of Esophageal Adenocarcinoma, interacting with gastroEsophageal reflux disease symptoms. Abdominal obesity, independently of gastroEsophageal reflux disease symptoms, is associated with increased risk of Barrett's esophagus and this association is likely mediated by high levels of leptin and insulin. Use of aspirin, nonsteroidal anti-inflammatory drugs, statins, and proton pump inhibitors are associated with a reduced risk of Barrett's esophagus as well as lower risk of neoplastic progression in patients with Barrett's esophagus. An increasing number of genetic loci have been associated with risk of Barrett's esophagus and Esophageal Adenocarcinoma.Recent advances in identifying risk factors and reporting of more precise estimates of effect for the main risk factors will positively impact clinical risk stratification efforts for Barrett's esophagus and Esophageal Adenocarcinoma. Large pooling studies are underway to derive and validate reliable clinical risk models.
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Obesity in Relation to Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus
Current Nutrition Reports, 2016Co-Authors: Aaron P Thrift, Bradley J. KendallAbstract:The incidence of Esophageal Adenocarcinoma has increased rapidly in the USA and other western populations. Barrett’s esophagus, a metaplastic change in the distal esophagus, is the only known precursor for Esophageal Adenocarcinoma. Epidemiological studies strongly implicate gastroEsophageal reflux disease symptoms and obesity as the primary causal factors for Esophageal Adenocarcinoma and Barrett’s esophagus. Recent studies suggest that abdominal obesity, rather than overall obesity, is associated with Esophageal Adenocarcinoma and Barrett’s esophagus and that these associations are not entirely explained by gastroEsophageal reflux disease symptoms. Evidence from these studies indicates that abdominal obesity has both mechanical (for example, via disruption of the gastroEsophageal junction and resulting gastroEsophageal reflux symptoms) and nonmechanical metabolic and inflammatory effects on Esophageal Adenocarcinoma and Barrett’s esophagus. Overall, the current body of literature provides some insights into the potential biological mechanisms linking abdominal obesity with Esophageal Adenocarcinoma and Barrett’s esophagus.
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Determination of risk for Barrett's esophagus and Esophageal Adenocarcinoma.
Current opinion in gastroenterology, 2016Co-Authors: Aaron P ThriftAbstract:Purpose of review The incidence of Esophageal Adenocarcinoma and its precursor, Barrett's esophagus, have increased greatly over the past 40 years and continue to rise. This report summarizes the most recent data on the risk factors for Barrett's esophagus and Esophageal Adenocarcinoma. Recent findings Other factors, highly correlated with increasing trends for obesity, are the dominant driver of the increase in incidence of Esophageal Adenocarcinoma, interacting with gastroEsophageal reflux disease symptoms. Abdominal obesity, independently of gastroEsophageal reflux disease symptoms, is associated with increased risk of Barrett's esophagus and this association is likely mediated by high levels of leptin and insulin. Use of aspirin, nonsteroidal anti-inflammatory drugs, statins, and proton pump inhibitors are associated with a reduced risk of Barrett's esophagus as well as lower risk of neoplastic progression in patients with Barrett's esophagus. An increasing number of genetic loci have been associated with risk of Barrett's esophagus and Esophageal Adenocarcinoma. Summary Recent advances in identifying risk factors and reporting of more precise estimates of effect for the main risk factors will positively impact clinical risk stratification efforts for Barrett's esophagus and Esophageal Adenocarcinoma. Large pooling studies are underway to derive and validate reliable clinical risk models.
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Esophageal Adenocarcinoma: The Influence of Medications Used to Treat Comorbidities on Cancer Prognosis
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2015Co-Authors: Aaron P ThriftAbstract:Esophageal Adenocarcinoma has undergone a continuous rise in incidence since the early 1970s and is the fastest rising cancer among white men in the United States. Epidemiologic studies have demonstrated that medications commonly used to treat multiple chronic conditions (for example, aspirin, non-aspirin nonsteroidal anti-inflammatory drugs, and statins) as well as powerful acid suppressants such as proton pump inhibitors are associated with a reduced risk of Esophageal Adenocarcinoma. The chemopreventive potential of these classes of medications appears to be especially applicable to persons with Barrett's esophagus, the only known premalignant condition for Esophageal Adenocarcinoma. However, it is not known whether these medications also influence cancer recurrence and cancer-specific mortality in persons diagnosed with Esophageal Adenocarcinoma. This is an important question because most patients with Esophageal Adenocarcinoma have 1 or more comorbid conditions at the time of their cancer diagnosis and are receiving medication to treat these conditions. This article summarizes the evidence on the associations between 4 commonly used classes of medications and (1) risk of developing Esophageal Adenocarcinoma and Barrett's esophagus and (2) risk of cancer recurrence and cancer-specific mortality in patients with Esophageal Adenocarcinoma.
Dennis Liang Fei - One of the best experts on this subject based on the ideXlab platform.
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Notch Signaling Drives Stemness and Tumorigenicity of Esophageal Adenocarcinoma
Cancer research, 2014Co-Authors: Zhiqiang Wang, Thiago G. Da Silva, Ke Jin, Xiaoqin Han, Prathibha Ranganathan, Xiaoxia Zhu, Avencia Sanchez-mejias, Feng Bai, Dennis Liang FeiAbstract:Esophageal Adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for Esophageal Adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating Esophageal Adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in Esophageal Adenocarcinoma treatment.
John R. Stroehlein - One of the best experts on this subject based on the ideXlab platform.
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Loss of TGF-β Adaptor β2SP Activates Notch Signaling and SOX9 Expression in Esophageal Adenocarcinoma
Cancer Research, 2013Co-Authors: Shumei Song, Chia Hsin Chan, Marta L. Davila, Dipen M Maru, Wayne L Hofstetter, Arlene M. Correa, Soichiro Honjo, Jaffer A Ajani, John R. StroehleinAbstract:TGF-β and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-β signaling components activates Notch signaling in Esophageal Adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-β adapter β2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or Esophageal Adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in Esophageal Adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in Esophageal Adenocarcinoma patients. Downregulation of β2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into Esophageal Adenocarcinoma cells of β2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in β2SP-silenced Esophageal Adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of Esophageal Adenocarcinoma cells with loss of β2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of β2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-β targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of β2SP switches TGF-β signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9.
Zhiqiang Wang - One of the best experts on this subject based on the ideXlab platform.
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Notch Signaling Drives Stemness and Tumorigenicity of Esophageal Adenocarcinoma
Cancer research, 2014Co-Authors: Zhiqiang Wang, Thiago G. Da Silva, Ke Jin, Xiaoqin Han, Prathibha Ranganathan, Xiaoxia Zhu, Avencia Sanchez-mejias, Feng Bai, Dennis Liang FeiAbstract:Esophageal Adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for Esophageal Adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating Esophageal Adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in Esophageal Adenocarcinoma treatment.
Alfred King-yin Lam - One of the best experts on this subject based on the ideXlab platform.
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Targeted Single Gene Mutation in Esophageal Adenocarcinoma.
Methods in Molecular Biology, 2018Co-Authors: Katherine Ting-wei Lee, Robert A. Smith, Vinod Gopalan, Alfred King-yin LamAbstract:Esophageal Adenocarcinoma is heterogeneous and studies have reviewed many important mutations that contribute to the pathogenesis of the cancer. These discoveries have helped paved the way into identifying new gene markers or gene targets to develop novel molecular directed therapy for better patient outcomes in Esophageal Adenocarcinoma. Despite the recent bloom in next-generation sequencing, Sanger sequencing still represents the gold standard method for the study of the driver genes in Esophageal Adenocarcinoma. This chapter focuses on the sequencing techniques in identification of single gene mutations.
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Epigenetics: DNA Methylation Analysis in Esophageal Adenocarcinoma
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Farhadul Islam, Vinod Gopalan, Johnny Cheuk On Tang, Alfred King-yin LamAbstract:The aberrant DNA methylation has been noted to occur at promoter of tumor suppressor, cell adhesion, DNA repair, and other growth regulating genes during the progression of nonneoplastic Esophageal mucosa to Barrett esophagus to Esophageal Adenocarcinoma. Methylation-mediated silencing of individual gene or concurrent loss of a number of genes plays crucial roles in dysplasia-metaplasia-neoplasia sequence of Esophageal Adenocarcinoma. In addition, promoter methylation of genes had shown significant prognostic potential in patients with Esophageal Adenocarcinoma. Thus, determination of methylation status of genes of interest can be used as a molecular marker for risk stratification and/or better prognosis of patients with Esophageal Adenocarcinoma. There are a number of methods including bead array, PCR and sequencing, pyrosequencing, methylation-specific PCR, and PCR with high-resolution melt curve available to determine the methylation status of particular gene of interest. Herein, we describe the polymerase chain reaction followed by sequencing-based protocol for identifying DNA methylation status in Esophageal Adenocarcinoma.
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DNA Genome Sequencing in Esophageal Adenocarcinoma.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Suja Pillai, Vinod Gopalan, Alfred King-yin LamAbstract:Next-generation sequencing refers to the high-throughput DNA sequencing technologies, which are capable of sequencing large numbers of different DNA sequences in a single/parallel reaction. It is a powerful tool to identify inherited and acquired genetic alterations associated with the development of Esophageal Adenocarcinoma. Whole-genome sequencing is the most comprehensive but expensive, whereas whole-exome sequencing is cost-effective but it only works for the known genes. Thus, second-generation sequencing methods can provide a complete picture of the Esophageal Adenocarcinoma genome by detecting and discovering different type of alterations in the cancer. This would help in diagnostics and will further help in developing personalized medicine in Esophageal Adenocarcinoma.
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Histopathological Assessment for Esophageal Adenocarcinoma
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Alfred King-yin LamAbstract:In the World Health Organization (WHO) classification, Adenocarcinoma of esophagus comprises preinvasive type (dysplasia), Adenocarcinoma, adenoid cystic carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. For Adenocarcinoma, it is important to determine the grading of the cancer and histological variants such as signet ring Adenocarcinoma. In the current day management of Esophageal Adenocarcinoma by neoadjuvant therapy, the histology of the cancer and the lymph nodal status may change after the therapy. Tumor regression grading systems could be used to assess the response to the neoadjuvant therapy in Esophageal Adenocarcinoma.
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Detection and Quantification of MicroRNAs in Esophageal Adenocarcinoma.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Moein Amin, Vinod Gopalan, Farhadul Islam, Alfred King-yin LamAbstract:MicroRNAs (miRNAs) are a class of small, noncoding RNAs that have been emerging as novel regulators in Esophageal Adenocarcinoma. Their role has been established in various aspects of Esophageal Adenocarcinoma including carcinogenesis, progression, treatment, and prognosis. Therefore, miRNA detection, profiling, and quantification have become extremely important for scientists and clinicians. As miRNAs are small, their detection can be challenging. There have been various methods developed to detect and/or quantify miRNAs. This chapter aims to introduce the fundamentals and methods of the most commonly used approaches including miRNA microarrays and quantitative real-time polymerase chain reaction (RT-qPCR) to detect and quantify miRNAs in Esophageal Adenocarcinoma.