Influence of octreotide and tamoxifen on tumor growth and liver metastasis in N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian hamsters.

:In prospective clinical trials single octreotide therapy or combined therapy with tamoxifen has improved the quality of life and survival time in patients with pancreatic cancer. In this study we analyzed the influence of octreotide and tamoxifen on tumor growth and liver metastases in chemically induced pancreatic adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic carcinomas as well as the number and size of liver metastases. The combined therapy showed no superior effect to octreotide alone. Furthermore, there was no difference between the tamoxifen and the control group.

Wenger FA ，Kilian M ，Mautsch I ，Jacobi CA ，Schimke I ，Saul GJ ，Guski H ，Müller JM ... -  《hormone research》

Influence of octreotide on liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

In prospective clinical trials, octreotide improved quality of life and survival time in patients with pancreatic cancer. To analyze whether octreotide modulates the hepatic oxygen radical metabolism and thus might decrease liver metastasis in an animal model of pancreatic cancer. Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine (BOP) for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet (3.5% fat) or were fed a high-fat diet (21.4% fat). In the 25th week, the pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined intrahepatically. The number of liver metastases per animal and the size of liver metastases were increased by the high-fat diet, whereas they were decreased by octreotide. Octreotide increased activities of GSH-Px and SOD. The concentration of thiobarbituric acid reactive substances was increased by BOP and a high-fat diet and decreased by octreotide. Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. This is accompanied by high hepatic GSH-Px and SOD activity and a low level of lipid peroxidation.

Wenger FA ，Kilian M ，Mautsch I ，Jacobi CA ，Steiert A ，Peter FJ ，Guski H ，Schimke I ，Müller JM ... -  《-》

Effects of octreotide on liver metastasis and intrametastatic lipid peroxidation in experimental pancreatic cancer.

In prospective clinical trials, octreotide improved the quality of life and survival time in patients with pancreatic cancer. In this study, we analyzed whether octreotide modulates the intrametastatic oxygen radical metabolism and might decrease liver metastasis in a model of pancreatic cancer. Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet or were fed a high-fat diet. In the 25th week, pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and the activity of glutathione peroxidase and superoxide dismutase were determined intrahepatically and intrametastatically. The number and size of liver metastases per animal were increased by high-fat diet and decreased by octreotide. While high-fat diet increased intrahepatic extrametastatic lipid peroxidation, octreotide decreased intrahepatic extrametastatic lipid peroxidation and increased intrametastatic lipid peroxidation. Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. Possible mechanisms are the prevention of high lipid peroxidation in non-metastatic liver as well as the increase in intrametastatic lipid peroxidation, leading to loss of integrity of spread tumor cells.

Wenger FA ，Kilian M ，Jacobi CA ，Mautsch I ，Peter FJ ，Guski H ，Schimke I ，Müller JM ... -  《-》

Effects of octreotide, a somatostatin analogue, on initiation of pancreatic carcinogenesis in hamsters with N-nitrosobis(2-oxopropyl)amine.

The modifying effects of octreotide acetate, a somatostatin (SMS) analogue shown to inhibit secretion of digestive enzymes, bicarbonate and pancreatic juice, on the initiation phase of pancreatic carcinogenesis were investigated in hamsters simultaneously treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups 1-3, each consisting of 20 animals, were given BOP subcutaneously once a week three times at a dose of 10 mg/kg body weight during administration of octreotide acetate for 28 days via osmotic pumps implanted subcutaneously at doses of 6 microg/day (group 1), 3 microg/day (group 2) or 0 microg/day (saline) (group 3). Group 4-6 animals (each group ten animals) were similarly administered octreotide acetate for the same period with five subcutaneous injections of saline. At the termination of experimental week 40, the incidences and multiplicities of pancreatic ductal adenocarcinomas and dysplastic lesions did not significantly differ among groups 1-3. No neoplastic lesions were found in groups 4-6. Subcutaneous administration of octreotide acetate resulted in obviously increased plasma octreotide levels. Our results thus suggest that this SMS analogue may not modulate the initiation of BOP-induced pancreatic carcinogenesis, regardless of its pharmacological action.

Furukawa F ，Nishikawa A ，Nakamura H ，Miyauchi M ，Son H ，Hirose M ... -  《-》

Influence of different dietary fat intake on liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

Effects of polyunsaturated fatty acids (PUFA) on carcinogenesis are discussed controversially. Thus, tumor growth seems to be influenced by type and composition of fat dietary; however, the pathomechanism is still unknown. Therefore, we investigated the impact of different PUFAs on liver metastasis and hepatic lipid peroxidation in a solid model of ductal pancreatic cancer in Syrian hamsters. 90 male hamsters were randomized into 6 groups (n = 15). Accordingly groups 2, 4 and 6 received 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly by subcutaneous injection for 12 weeks in order to induce ductal pancreatic cancer, while groups 1, 3 and 5 were treated with 0.5 ml 0.9% sodium chloride. All hamsters received a standard fat diet (SFD) rich in n-6 PUFA for 16 weeks (2.9% fat). Afterwards, groups 1 and 2 had free access to SFD, while groups 3 and 4 were given a diet enriched with n-3, n-6 and n-9 PUFA (SMOF) and groups 5 and 6 were fed a diet high in n-3 PUFA (FISH-OIL). After 32 weeks all hamsters were sacrificed in order to determine incidence of pancreatic carcinoma and liver metastasis. Furthermore hepatic activities of glutathionperoxidase (GSH-Px) and superoxiddismutase (SOD) as well as levels of lipidperoxidation were analyzed intra- and extrametastatically. The incidence of liver metastasis was decreased in the FISH-OIL tumor group compared to the SFD and SMOF groups. However, GSH-Px activity was not influenced by different diets. Extrametastatic hepatic SOD activity did not differ between all groups, while intrametastatic hepatic SOD activity in the SFD-BOP group was increased. In the FISH-OIL-BOP and the SMOF-BOP group intrametastatic SOD activity was lower than in non-metastatic hepatic tissue. Furthermore levels of hepatic lipid peroxidation were decreased in the tumor groups treated with fish oil and SMOF compared to the SFD group. Comparing intra- and extrametastatic TBARS concentration there was no difference in the SFD-BOP and the SMOF-BOP groups, while in the FISH-OIL-BOP group intrametastatic TBARS concentration was increased. Conclusively, fish oil reduced the incidence of liver metastasis in experimental ductal pancreatic cancer. Maybe this effect is caused by an increase of intrametastatic hepatic lipid peroxidation.

Heukamp I ，Gregor JI ，Kilian M ，Kiewert C ，Jacobi CA ，Schimke I ，Walz MK ，Guski H ，Wenger FA ... -  《-》