Rapid Production of Pancreatic Carcinoma by Initiation With N-Nitroso-bis(2-oxopropyl)amine and Repeated Augmentation Pressure in Hamsters

Mizumoto, Kazuhiro; Tsutsumi, Masahiro; Denda, Ayumi; Konishi, Yoichi

doi:10.1093/jnci/80.19.1564

Cited by 52 publications

(48 citation statements)

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“…PDAs were induced in 12 animals according to the rapid production model (13)(14)(15). Briefly, BOP (30 mg/kg body weight) (Nakalai Tesque, Inc., Kyoto, Japan) was given subcutaneously at initiation, followed by two cycles of augmentation pressure, which consisted of choline-deficient diet administration and ethionine-methionine-BOP injection.…”

Section: Animals and Treatmentmentioning

confidence: 99%

“…However, at present, information on rate-limiting molecular events is exceedingly limited. Experimental models suitable for the investigation of human PDA development have been established in hamsters using the carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP), and related compounds (10)(11)(12), and we previously developed a rapid production approach to facilitate studies on the underlying mechanisms (13)(14)(15). We have reported several genetic changes in this model.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Shimizu

Kitahashi²,

Fujii³

et al. 2006

Oncol Rep

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Abstract. Alterations of the Smad4 gene, identified as a mediator of the transforming growth factor-ß pathway, were investigated in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 12 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/12, 8.3%) in the form of an ACC to ATC (Thr to IIe) transition at codon 73; none were detected in the three cell lines. No reduced or increased expression of the Smad4 gene was detected in any case using real-time quantitative RT-PCR. These results suggest that the Smad4 gene might play a role in limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.

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Section: Animals and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Shimizu

Kitahashi²,

Fujii³

et al. 2006

Oncol Rep

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“…For investigating the mechanisms of the development of pancreatic cancer, an experimental pancreatic ductal carcinogenesis model has been established with the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters (19)(20)(21)(22). This model provides unique characteristics that are similar to a sequence of well-characterized morphologic changes in the human pancreatic duct and frequently shows point mutations in codon 12 of the K-ras gene, in accordance with human findings (23,24).…”

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confidence: 94%

In Vivo SPECT Imaging with ¹¹¹In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model

Yoshimoto¹,

Hayakawa²,

Mutoh³

et al. 2012

J Nucl Med

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Early detection of pancreatic cancer is key to overcoming its poor prognosis. a v b 3 -integrin is often overexpressed in pancreatic tumor cells, whereas it is scarcely expressed in normal pancreatic cells. In this study, we investigated the usefulness of SPECT imaging with 111 In-1,4,7,10-tetraazacylododecane-N,N9,N$,N999-tetraacetic acidcyclo-(Arg-Gly-Asp-D-Phe-Lys) [ 111 In-DOTA-c(RGDfK)], an imaging probe of a v b 3 -integrin, for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. Methods: Hamsters were subcutaneously injected with the pancreatic duct carcinogen N-nitrosobis(2-oxopropyl)amine to induce pancreatic cancer. N-nitrosobis(2-oxopropyl)amine-treated hamsters underwent in vivo SPECT with 111 In-DOTA-c(RGDfK). After imaging, the tumorto-normal pancreatic tissue radioactivity ratios in excised pancreatic samples were measured with autoradiography (ARG) and compared with the immunopathologic findings for a v b 3 -integrin. In a mouse model in which inflammation was induced with turpentine, the uptake of 111 In-DOTA-c(RGDfK) in inflammatory regions was evaluated with ARG and compared with that of 18 F-FDG. Results: 111 In-DOTA-c(RGDfK) was clearly visualized in pancreatic cancer lesions as small as 3 mm in diameter. ARG analysis revealed high tumor-to-normal pancreatic tissue radioactivity ratios (4.6 6 1.0 [mean 6 SD] in adenocarcinoma and 3.3 6 1.4 in atypical hyperplasia). The uptake of 111 In-DOTA-c(RGDfK) strongly correlated with a v b 3 -integrin expression. In the inflammatory model, inflammation-to-muscle ratios for In-DOTA-c(RGDfK) were 8.37 6 4.37 and 1.98 6 0.60, respectively. These results imply that 111 In-DOTA-c(RGDfK) has a lower rate of false-positive tumor detection than 18 F-FDG. Conclusion: Our findings suggest that SPECT with 111 In-DOTA-c(RGDfK) has great potential for the early and accurate detection of pancreatic cancer.

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“…In order to control the disease, it is indispensable to detect tumors as early as possible and, in turn, to prevent their subsequent progression. An experimental model suitable for investigation of human PC development has been established in the hamster using the carcinogen, N-nitrosobis (2-oxopropyl)amine (BOP), and related compounds [1][2][3] . To facilitate studies of the underlying mechanisms, we have developed a rapid production model for PCs [4][5][6] , incorporating the principle of selection by resistance to cytotoxicity demonstrated earlier for liver carcinogenesis in rats 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pancreatic Carcinogenesis by Shark Cartilage Proteoglycan in Hamsters

et al. 2006

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Effects of shark cartilage proteoglycan (SCPG), which has heat-stable inhibitory activities against matrix metalloproteinase (MMP)-2 and -9 in vitro, on pancreatic carcinogenesis were studied in a rapid production model for pancreatic duct adenocarcinomas (PCs) in hamsters. Female Syrian golden hamsters received a diet containing 0% (group 1), 0.2% (group 2) or 0.4% (group 3) of SCPG for 50 days after initiation with N-nitrosobis(2-oxopropyl)amine followed by augmentation pressure. The number of PCs were 3.1 ± 2.0 in group 1 and 1.4 ± 0.9 in group 3, and total ductal lesions including hyperplasia, atypical hyperplasia and PCs were 9.7 ± 4.0 and 5.6 ± 2.7, respectively, the differences being significantly different (P < 0.05). These results were confirmed in a repeat experiment (P < 0.01). Gelatin zymography revealed that oral administration of SCPG did not affect the expression and activation of MMP-2 and MMP-9 in either serum or PC tissue. These results suggest that inhibition of pancreatic carcinogenesis by SCPG might involve a mechanism different from other synthetic

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Rapid Production of Pancreatic Carcinoma by Initiation With N-Nitroso-bis(2-oxopropyl)amine and Repeated Augmentation Pressure in Hamsters

Cited by 52 publications

References 0 publications

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

In Vivo SPECT Imaging with ¹¹¹In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model

Inhibition of Pancreatic Carcinogenesis by Shark Cartilage Proteoglycan in Hamsters

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Rapid Production of Pancreatic Carcinoma by Initiation With N-Nitroso-bis(2-oxopropyl)amine and Repeated Augmentation Pressure in Hamsters

Cited by 52 publications

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Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

In Vivo SPECT Imaging with 111In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model

Inhibition of Pancreatic Carcinogenesis by Shark Cartilage Proteoglycan in Hamsters

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In Vivo SPECT Imaging with ¹¹¹In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model