Ornithine decarboxylase activity in Barrett's esophagus: A potential marker for dysplasia

Garewal, Harinder S.; Sampliner, Richard E.; Gerner, Eugene W.; Steinbronn, Karen; Alberts, David S.; Kendall, Dava

doi:10.1016/0016-5085(88)90259-4

Cited by 57 publications

(13 citation statements)

References 7 publications

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“…We found that a relatively low dose of DFMO (0.5 g/m 2 /d) suppressed mucosal polyamine content in dysplastic Barrett's epithelia. Specifically, significant reductions in the levels of putrescine and spermidine, but not spermine or histamine, were observed at 3 and 6 months compared with baseline biopsies consistent with the known mechanism of DFMO as an inhibitor of polyamine biosynthesis (6,42). Furthermore, the spermidine/spermine ratio was significantly suppressed at these same time points.…”

Section: Discussionsupporting

confidence: 65%

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Sinicrope

Broaddus

Joshi

et al. 2011

Cancer Prevention Research

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Patients with Barrett's esophagus (BE) and dysplasia are candidates for chemopreventive strategies to reduce cancer risk. We determined the effects of difluoromethylornithine (DMFO) on mucosal polyamines, gene expression, and histopathology in BE. Ten patients with BE and low-grade dysplasia participated in a single-arm study of DFMO (0.5 g/m 2 /d) given continuously for 6 months. Esophagoscopy with biopsies was conducted at baseline, 3, 6, and 12 months. Dysplasia was graded by a gastrointestinal pathologist. Audiology was assessed (at baseline and at 6 months). Mucosal polyamines were measured by high-performance liquid chromatography. Microarray-based gene expression was analyzed using a cDNA two-color chip. DFMO suppressed levels of the polyamines putrescine (P ¼ 0.02) and spermidine (P ¼ 0.02) and the spermidine/spermine ratio (P < 0.01) in dysplastic BE (6 months vs. baseline) that persisted at 6 months following drug cessation. Among the top 25 modulated genes, we found those regulating p53-mediated cell signaling (RPL11), cell-cycle regulation (cyclin E2), and cell adhesion and invasion (Plexin1). DFMO downregulated Kr€ uppellike factor 5 (KLF5), a transcription factor promoting cell proliferation, and suppressed RFC5 whose protein interacts with proliferating cell nuclear antigen. Histopathology showed regression of dysplasia (n ¼ 1), stable disease (n ¼ 8), and progression to high-grade dysplasia (n ¼ 1). Polyamines were suppressed in the responder to a greater extent than in stable cases. DFMO was well tolerated, and one patient had subclinical, unilateral ototoxicity. DFMO suppressed mucosal polyamines and modulated genes that may be mechanistically related to its chemopreventive effect. Further study of DFMO for the chemoprevention of esophageal cancer in BE patients is warranted.

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Section: Discussionsupporting

confidence: 65%

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Sinicrope

Broaddus

Joshi

et al. 2011

Cancer Prevention Research

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“…The surgical literature contrasts with this experience. Of 126 cases with high grade dysplasia alone by endoscopic biopsy, 41% had cancer at the time of esophagectomy (50,51). The majority of these cancers were early stage, with a more favorable patient survival.…”

Section: Ajg -July 1998mentioning

confidence: 99%

Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus

Sampliner

1998

The American Journal of Gastroenterology

105

110

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“…157,158 Moreover, expression of ODC has been found to increase significantly as dysplastic changes develop in the metaplastic mucosa. 157,159 In vitro, DFMO has been shown to reduce growth of metaplastic Barrett epithelial cells. 157 In clinical trials, treatment of patients with Barrett esophagus for 6 weeks with low dose DFMO (0.5 g/m 2 ) resulted in an approximately 60% decrease in polyamine content in metaplastic Barrett mucosa as well as in normal control epithelia.…”

Section: Inhibition Of Ornithine Decarboxylasementioning

confidence: 99%

Concepts in the Prevention of Adenocarcinoma of the Distal Esophagus and Proximal Stomach

Souza

Spechler

2005

CA: A Cancer Journal for Clinicians

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For decades, the incidence rates for squamous cell carcinoma of the esophagus and adenocarcinoma of the distal stomach have been declining while the rates for adenocarcinomas of the esophagus and gastric cardia have increased profoundly. Recent studies have shown that the gastroesophageal junction (GEJ) is regularly exposed to concentrated gastric acid and to a variety of nitrosating species, noxious agents that may contribute to carcinogenesis in this region. For adenocarcinomas that straddle the GEJ, it can be difficult to determine whether the tumor originated in the esophagus or in the gastric cardia. This classification problem hampers studies on the epidemiology and pathogenesis of GEJ tumors. Current concepts in the prevention of cancers of the distal esophagus and proximal stomach have emerged from advances in our understanding of the specific molecular events that occur during the evolution of these tumors. This report reviews those events and focuses on current concepts in the prevention of adenocarcinomas at the GEJ. The similarities and differences in risk factors, molecular pathogenesis, and in preventive strategies for adenocarcinomas of the esophagus and gastric cardia are highlighted. (CA Cancer J Clin 2005;55:334-351.)

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Ornithine decarboxylase activity in Barrett's esophagus: A potential marker for dysplasia

Cited by 57 publications

References 7 publications

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus

Concepts in the Prevention of Adenocarcinoma of the Distal Esophagus and Proximal Stomach

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