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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of concomitant administration of a synthetic trypsin inhibitor (camostat) on pancreatic carcinogenesis in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Thirty-two female Syrian golden hamsters were given weekly 10 mg/kg s.c. injections of BOP for 5 weeks while simultaneously receiving a 500 ppm camostat diet (BOP + camostat group). Additional groups of 30 animals received either the s.c. injections of BOP (BOP group), or the 500 ppm camostat diet (camostat group) during the same 5-week period. Thirty weeks after the first BOP administration, the incidence of pancreatic adenocarcinomas in the BOP + camostat group was significantly lower than in the group administered BOP only (p < 0.05). Similarly, the total numbers of pancreatic adenocarcinomas or dysplastic lesions were significantly decreased in the BOP + camostat group as compared with the BOP group (p < 0.01). None of the animals receiving camostat alone developed any adenocarcinomas or dysplastic lesions of the pancreas. The results of the present experiments clearly show that camostat can inhibit induction of hamster pancreatic ductal neoplasms when administered simultaneously with BOP.
Pancreas 1994 Jan
PMID:Blocking effects of synthetic trypsin inhibitor (camostat) on pancreatic carcinogenesis in hamsters initiated with N-nitrosobis(2-oxopropyl)amine. 810 74

Cholecystokinin (CCK-A) and gastrin (CCK-B) receptors have been demonstrated in the azaserine-induced rat pancreatic carcinoma DSL-6. In order to determine at what stage in azaserine-induced pancreatic carcinogenesis gastrin (CCK-B) receptors are first expressed, we examined the binding of [125I]gastrin-I to normal rat pancreas, azaserine-induced premalignant pancreatic nodules, grossly normal internodular pancreas, and DSL-6 carcinoma. We observed that specific gastrin binding was absent in normal pancreas, premalignant nodules, and internodular pancreas, and also reconfirmed our previous report of marked overexpression of gastrin (CCK-B) receptors in the DSL-6 carcinoma. Specific cholecystokinin (CCK) binding was present in all pancreatic tissue types tested. Therefore, we conclude that the presence of gastrin (CCK-B) receptors in the azaserine-induced pancreatic carcinoma DSL-6, in contrast to their absence in premalignant nodules, suggests that the expression of the gastrin (CCK-B) receptor may be important in the transformation from premalignant nodules to pancreatic cancer.
Pancreas 1993 Sep
PMID:Temporal expression of the gastrin (CCK-B) receptor during azaserine-induced pancreatic carcinogenesis. 830 99

Sarcophytol A (SaA), a cembrane-type diterpene, inhibits pancreatic carcinogenesis induced by N-nitrosobis(2-oxypropyl)amine (BOP) in hamsters. The experimental groups received two injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were fed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with normal saline and fed the basal diet or the 0.05% SaA diet. All animals were killed 30 weeks after the start of the experiments. Seventeen BOP-treated hamsters fed the basal diet developed pancreatic tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 hamsters fed the 0.05% SaA diet (52.2%) developed pancreatic tumors. Pancreatic lesions included ductal hyperplasia, atypical ductal hyperplasia, and carcinoma in situ. Microscopic invasive carcinoma induced by BOP and the incidence of larger pancreatic tumors in hamsters were significantly higher in hamsters fed the basal diet than in hamsters fed the SaA diet (p < 0.05). The proliferating cell nuclear antigen (PCNA) labeling index of pancreatic carcinoma in BOP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 and 0.05% SaA diets yielded PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7.0%, respectively. k-ras mutation was detected in 40% of cancers in both groups. No pancreatic tumors developed in saline-treated groups, and no differences in body weights or histological findings in their organs, including the pancreas, were observed in either group. These findings suggest that SaA not only inhibits BOP-induced pancreatic carcinogenesis in hamsters, but also provides antipromotion and antiprogression effects on these tumors, even when SaA commences 1 week after the initiation of pancreatic carcinogenesis.
Pancreas 1996 Aug
PMID:Inhibitory effect of sarcophytol A on pancreatic carcinogenesis after initiation by N-nitrosobis(2-oxypropyl)amine in Syrian hamsters. 882 83

The peptide hormone cholecystokinin (CCK) has been shown to stimulate the growth of azaserine-induced preneoplastic nodules in the rat pancreas. Previously, our labortory demonstrated by classical binding studies that CCK receptors are overexpressed in azaserine-induced rat pancreatic neoplasms. In the present study, we utilized autoradiography to determine the temporal course of this increased receptor binding. Male Lewis rats were given azaserine or saline injections and sacrificed at 2, 4, 8, 12, and 18 months of age. Pancreatic tissue was harvested and autoradiography using 125l-labeled. CCK-8 was performed. Densitometry measurements of azaserine-induced pancreatic nodules, internodular pancreas, and normal pancreatic tissue (from saline-treated controls) of each age group were taken with an image analyzer. There was no statistically significant difference in CCK binding to internodular pancreas and normal pancreas at any age. At 2 months of age, there was no significant increase in CCK binding to azaserine-induced pancreatic nodules. However, at 4, 8, 12, and 18 months of age there was significantly greater CCK binding to azaserine-induced pancreatic nodules than to both internodular pancreas and normal pancreas (p < 0.001 for all groups). At 18 months of age, one azaserine-treated animal developed a pancreatic acinar cell carcinoma, which likewise exhibited significantly greater CCK binding than internodular pancreas or normal pancreas (p < 0.001 for both). These findings demonstrate increased CCK binding in azaserine-induced preneoplastic pancreatic nodules and pancreatic acinar cell carcinoma, compatible with our previous demonstration of receptor overexpression in these tissues. Increased CCK binding first becomes apparent by 4 months following exposure to azaserine. These result suggest that overexpression of CCK receptors, located specifically on preneoplastic and neoplastic pancreatic lesions, results in increased CCK binding and is involved in the mediation of CCK-stimulated growth during azaserine-induced pancreatic carcinogenesis.
Pancreas 1996 Nov
PMID:Autoradiographic localization of cholecystokinin (CCK) receptor expression during the development of azaserine-induced rat pancreatic carcinoma. 889 1

Epidemiologic studies have shown a lower risk of gastrointestinal cancer in green tea drinkers. In the present study, the inhibitory effect of green tea extract (GTE) on the process of pancreatic carcinogenesis induced by N-nitrosobis-(2-oxypropyl)amine (BOP) and on tumor promotion after transplantation of N-nitrosobis-(2-hydroxypropyl)amine (BHP)-induced pancreatic cancer were investigated in hamsters. In the first experiment, shortly after the initiation of pancreatic carcinogenesis by BOP, the animals in the GTE group were given GTE (0.5 mg/L) in their drinking water and the control group was given tap water. All animals were sacrificed 24 weeks later. There were no significant differences in body weight, water intake, or food consumption between the two groups during the experiments. GTE consumption was approximately 1.25 mg/day/100 g body weight during this experiment. Seven of the 13 hamsters (54%) in the control group were found to have pancreatic tumors, versus six of the 18 hamsters (33%) in the GTE group. The average number of tumors in the control group was 1.0/hamster, compared with 0.5/hamster in the GTE group. The overall incidence of macroscopic pancreatic tumors in the GTE group was about half that in the control group. The incidence of pancreatic cancer was 54% (12/13) in the control group and 44% (8/18) in the GTE group. The number of pancreatic cancers, including invasive carcinoma and carcinoma in situ, in the GTE group was 0.88/hamster, significantly lower than in the control group (1.68/hamster) (p < 0.05). The incidence of atypical ductal hyperplasia, which is thought to be an early pancreatic cancer, was also significantly lower in the GTE group than in the control group (1.50/hamster vs. 4.65/hamster) (p < 0.05). In the second experiment, 1-mm3 pieces of BHP-induced pancreatic cancer were transplanted into the back of hamsters. The control group (N = 16) was maintained on the basal diet and tap water throughout the experiment, and the GTE group (N = 16) was also maintained on the basal diet and tap water for the first 3 weeks after transplantation, when successful transplantation was confirmed and, thereafter, given tap water containing GTE (0.5 mg/L) for an additional 12 weeks. Tumor growth was similar in both groups until 11 weeks after transplantation, but inhibition of tumor growth became apparent after 11 weeks in the GTE group. At 13 weeks, the average tumor volume in the GTE group was 1.01 +/- 0.11 x 104 mm3, significantly smaller than that in the control group (1.98 +/- 0.37 x 104 mm3) (p < 0.05). The results demonstrated that GTE has an inhibitory effect on the process of pancreatic carcinogenesis and on tumor promotion of transplanted pancreatic cancer. These results suggest that GTE may come to serve as a chemopreventive and chemotherapeutic agent for pancreatic cancer.
Pancreas 1997 Oct
PMID:Inhibitory effect of green tea extract on the process of pancreatic carcinogenesis induced by N-nitrosobis-(2-oxypropyl)amine (BOP) and on tumor promotion after transplantation of N-nitrosobis-(2-hydroxypropyl)amine (BHP)-induced pancreatic cancer in Syrian hamsters. 933 91

This article summarizes the proceedings of the 1996 Comfort Symposium on Pancreatic Carcinogenesis that took place at the Mayo Clinic in Rochester, Minnesota, September 11-13, 1996. The annual series of Comfort lectures are aimed at discussing leading theories and advanced technological developments in the area of pancreatic research. The goals of this year's symposium were to summarize epidemiologic and experimental findings in the field of pancreatic cancer research, to foster communications among scientists studying this disease, and to identify areas of research that are likely to bridge the gaps between basic science and patient care. The topics discussed included (i) current algorithms for the diagnosis of early pancreatic cancer, (ii) animal and cellular models of pancreatic carcinogenesis, (iii) mechanisms of pain in pancreatic cancer, (iv) the role of signaling cascades and transcription factors in the regulation of pancreatic cell growth and differentiation, (v) methods to study genetic alterations associated with neoplastic diseases, and (vi) recent developments in gene-targeting techniques. The lectures and discussions during the symposium successfully achieved the goals outlined above and resulted in the identification of novel areas of research that may increase our understanding of the etiology and pathogenesis, and lead to early diagnosis and treatment of pancreatic cancer.
Pancreas 1998 Jan
PMID:1996 Comfort Symposium on Pancreatic Carcinogenesis. 943 55

Mutation of the p53 tumor suppressor gene is found in a large number of exocrine pancreatic tumors. The majority of these tumors is of the ductal cell phenotype. We examined 12 human acinar cell carcinomas and 42 transgenic mouse carcinomas (including 36 acinar cell tumors, four islet cell tumors, and two liver metastases of primary acinar cell tumors) for evidence of p53 mutation. Immunohistochemistry was used to identify p53 protein in tumor sections. To evaluate p53 exons 5-8, heteroduplex analysis was used on formalin-fixed, paraffin-embedded human tumor DNA, and single-strand conformation polymorphism analysis was used on frozen mouse tumor DNA. No molecular evidence of p53 mutation was found in any of the tumor DNAs and immunohistochemical data were regarded as negative. This study provides evidence that acinar cell carcinogenesis in both humans and transgenic mice is independent of p53 mutation.
Pancreas 1998 Jan
PMID:Evaluation of p53 mutation in pancreatic acinar cell carcinomas of humans and transgenic mice. 943 56

The effects of alpha-carotene, beta-carotene, palm carotene, and green tea polyphenols (GTP) on the progression stage of pancreatic carcinogenesis after rapid production of ductal lesions were studied in Syrian hamsters. Dose threshold inhibitory effects were noted for beta-carotene, 25 ppm, and palm carotene, 40 ppm, which includes 24 ppm beta-carotene reducing the numbers of putative preneoplastic lesions of duct epithelial hyperplasia and atypical hyperplasia, as well as carcinoma in situ and invasive carcinomas. GTP at doses of 500 and 5000 ppm, but not 100 ppm, also significantly decreased the numbers of hyperplasia and total duct lesions. Combined administration of 40 ppm palm carotene, and 50 ppm GTP similarly inhibited the lesion development. Alpha-carotene, however, did not affect pancreatic carcinogenesis. The results suggest that chemopreventive effects are exerted by beta-carotene and GTP above critical doses and that combined administration of palm carotene and GTP might be a candidate chemoprevention strategy for pancreatic cancer in humans.
Pancreas 1998 Jan
PMID:Inhibitory effects of beta-carotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by N-nitorsobis(2-oxopropyl)amine in Syrian golden hamsters. 943 57

Pancreatitis induced by ligation of the pancreatic duct produces morphologic similarities to human pancreatitis. This model is easily performed in big animals, but it is very difficult to perform pancreatic duct ligation in small animals. Many experimental studies of pharmaceutical treatments for pancreatitis used pancreatic duct-ligation models, but it is also difficult to evaluate the efficacy of the drugs used, because the animals used are of different species with individual differences. To overcome these problems, we ligated the main pancreatic duct of the splenic lobe by a 5.0 absorbable suture by using a surgical microscope and left the gastroduodenal lobe intact in the same rats. This model produced damaged pancreatic tissue in one part and normal pancreatic tissue in another part of the pancreas in the same animals, biochemically and histologically. We evaluated the effect of a new protease inhibitor (ONO-3404) on this preliminary model and found this new protease inhibitor demonstrated a hypertrophic effect on the damaged pancreatic tissue and the normal pancreatic tissue in the same animals. This model is also useful to study pharmaceutic treatment for pancreatic insufficiency and to study chemically induced pancreatic carcinogenesis in the damaged pancreatic tissue and the normal pancreatic tissue in the same animals.
Pancreas 1998 Apr
PMID:A new model for pancreatitis. 954 68

In this article, we introduce our rapid-production model for pancreatic duct adenocarcinomas and describe the mechanisms of pancreatic duct carcinogenesis so far elucidated in Syrian golden hamsters. It is evident that a series of histogenetic steps are involved, leading from hyperplasia through atypical hyperplasia to intraductal carcinoma and invasive carcinoma. As DNA alters, K-ras mutation appears to be an early event, whereas p53 mutations generally occur in the tumor-progression phase. The induced cancer cells may show autocrine growth, secreting TGF-alpha and vascular endothelial growth factor (VEGF), and are immortalized with a shortened TRF length and increased telomerase activity. The rapid-production model of pancreatic duct adenocarcinomas has not only provided a major stimulus to understanding induction mechanisms but should also serve as a bioassay to facilitate the identification of dietary risk factors and the search for appropriate chemopreventive or chemotherapeutic agents or both to help control this deadly disease.
Pancreas 1998 Apr
PMID:Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters. 954 70


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