7 results on '"J Mark Farrant"'
Search Results
2. Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells.
- Author
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Amani Al-Adsani, Zoë D Burke, Daniel Eberhard, Katherine L Lawrence, Chia-Ning Shen, Anil K Rustgi, Hiroshi Sakaue, J Mark Farrant, and David Tosh
- Subjects
Medicine ,Science - Abstract
BACKGROUND:The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. METHODOLOGY/PRINCIPAL FINDINGS:AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype. CONCLUSIONS/SIGNIFICANCE:These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ.
- Published
- 2010
- Full Text
- View/download PDF
3. Barrett's esophagus: cancer and molecular biology
- Author
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Arashinder S. Dhaliwal, Daniel Tong, Nicholas J. Clemons, J. Mark Farrant, Benjamin J. Colleypriest, Kaushal Parikh, Mark J. Krasna, Kausilia K. Krishnadath, Kiron M. Das, Leonard P. Griffiths, E. Daniel Pirchi, Katerina Dvorak, Yu Chen, David Tosh, Michael K. Gibson, Simon Law, Manisha Bajpai, Jari Räsänen, and Wayne A. Phillips
- Subjects
Oncology ,medicine.medical_specialty ,Surgical approach ,business.industry ,General Neuroscience ,medicine.medical_treatment ,Esophageal adenocarcinoma ,Cancer ,medicine.disease ,Molecular biology ,humanities ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,medicine.anatomical_structure ,History and Philosophy of Science ,Esophagectomy ,Internal medicine ,Barrett's esophagus ,medicine ,Esophagus ,CDX2 ,business ,Chemoradiotherapy - Abstract
The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.
- Published
- 2013
- Full Text
- View/download PDF
4. Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium
- Author
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Jonathan M. Quinlan, Zoë D. Burke, Yu Chen, Ramiro Jover, Leonard P. Griffiths, David Tosh, Stephen G. Ward, J. Mark Farrant, M Bock, Jonathan M.W. Slack, Leigh Biddlestone, Wei-Yuan Yu, and Benjamin J. Colleypriest
- Subjects
0301 basic medicine ,Male ,Pathology ,Cancer Research ,Esophageal Neoplasms ,Biopsy ,Epithelium ,Mice ,0302 clinical medicine ,Metaplasia ,CDX2 Transcription Factor ,CDX2 ,Càncer ,Oesophageal cancer ,Anatomy ,Neoplasm Proteins ,Barrett's oesophagus ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Hepatocyte Nuclear Factor 4 ,Loricrin ,030211 gastroenterology & hepatology ,medicine.symptom ,Villin ,Hepatocyte nuclear factor 4-alpha ,Adult ,medicine.medical_specialty ,Stratified squamous epithelium ,Biology ,Adenocarcinoma ,Organ culture ,Article ,03 medical and health sciences ,Barrett Esophagus ,Esophagus ,Organ Culture Techniques ,SDG 3 - Good Health and Well-being ,medicine ,Animals ,Humans ,Molecular Biology ,HNF4α ,Histologia ,Cell Biology ,digestive system diseases ,030104 developmental biology ,biology.protein ,Ectopic expression ,Developmental Biology - Abstract
Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium.
- Published
- 2017
- Full Text
- View/download PDF
5. The role of Cdx2 in Barrett's metaplasia
- Author
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Jonathan M.W. Slack, J. Mark Farrant, David Tosh, and Benjamin J. Colleypriest
- Subjects
Esophageal Neoplasms ,Adenocarcinoma ,Biology ,Models, Biological ,Biochemistry ,Barrett Esophagus ,Esophagus ,Metaplasia ,medicine ,Animals ,Humans ,CDX2 Transcription Factor ,CDX2 ,Homeodomain Proteins ,Transdifferentiation ,Cancer ,Intestinal metaplasia ,Anatomy ,medicine.disease ,Phenotype ,digestive system diseases ,Epithelium ,medicine.anatomical_structure ,embryonic structures ,Cancer research ,Homeobox ,medicine.symptom - Abstract
Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In addition, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia.
- Published
- 2010
- Full Text
- View/download PDF
6. Barrett's esophagus: cancer and molecular biology
- Author
-
Michael K, Gibson, Arashinder S, Dhaliwal, Nicholas J, Clemons, Wayne A, Phillips, Katerina, Dvorak, Daniel, Tong, Simon, Law, E Daniel, Pirchi, Jari, Räsänen, Mark J, Krasna, Kaushal, Parikh, Kausilia K, Krishnadath, Yu, Chen, Leonard, Griffiths, Benjamin J, Colleypriest, J Mark, Farrant, David, Tosh, Kiron M, Das, and Manisha, Bajpai
- Subjects
Esophagectomy ,Barrett Esophagus ,Cell Transformation, Neoplastic ,Esophagus ,Esophageal Neoplasms ,Interleukin-6 ,NF-kappa B ,Humans ,Adenocarcinoma - Abstract
The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.
- Published
- 2013
7. Dexamethasone Treatment Induces the Reprogramming of Pancreatic Acinar Cells to Hepatocytes and Ductal Ce
- Author
-
Chia-Ning Shen, Daniel Eberhard, J. Mark Farrant, Kate Lawrence, Anil K. Rustgi, David Tosh, Amani Al-Adsani, Hiroshi Sakaue, and Zoë D. Burke
- Subjects
Peanut agglutinin ,medicine.medical_specialty ,Ductal cells ,Blotting, Western ,Gastroenterology and Hepatology/Pancreas ,lcsh:Medicine ,Gastroenterology and Hepatology ,Biology ,Dexamethasone ,Gastroenterology and Hepatology/Hepatology ,03 medical and health sciences ,Cytokeratin ,0302 clinical medicine ,Epidermal growth factor ,Internal medicine ,medicine ,Animals ,lcsh:Science ,Pancreas ,030304 developmental biology ,Cell Line, Transformed ,0303 health sciences ,Multidisciplinary ,Epidermal Growth Factor ,Reverse Transcriptase Polymerase Chain Reaction ,CCAAT-Enhancer-Binding Protein-beta ,Transdifferentiation ,lcsh:R ,Correction ,Cell Differentiation ,Flow Cytometry ,Immunohistochemistry ,3. Good health ,Rats ,Microscopy, Electron ,Endocrinology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocyte ,Cancer research ,biology.protein ,Hepatocytes ,Ectopic expression ,lcsh:Q ,Reprogramming ,Research Article - Abstract
Background: The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. Methodology/Principal Findings: AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBP beta (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBP beta in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBP beta, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype. Conclusions/Significance: These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBP beta.
- Published
- 2010
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