RESUMEN
Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (P<0.05). Carcinomas were smaller after saline (6+/-23 mm(2)) than after octreotide irrigation (70+/-120 mm(2), P<0.05). In conclusion this study showed that laparoscopic irrigation with taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.
Asunto(s)
Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Peroxidación de Lípido/efectos de los fármacos , Octreótido/farmacología , Taurina/análogos & derivados , Taurina/farmacología , Tiadiazinas/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Carcinoma Ductal Pancreático/inducido químicamente , División Celular/efectos de los fármacos , Cricetinae , Laparoscopía , Masculino , Mesocricetus , Octreótido/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Taurina/administración & dosificación , Irrigación Terapéutica , Tiadiazinas/administración & dosificación , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Resultado del TratamientoRESUMEN
Conventional linoleic acid (LA) is regarded as a promotor of carcinogenesis. However, the effect of its conjugated derivative on cancer is still unknown. Therefore we investigated the influence of conventional and conjugated LA on tumor growth and lipid peroxidation in a solid model of pancreatic adenocarcinoma in Syrian hamsters. 60 male hamsters were randomized in 4 groups (Gr.) (n=15). Gr. 1 and 2 received 0.5 ml 0.9% sodium chloride subcutaneously (s.c.) once a week while Gr. 3 and 4 were injected 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly for 12 weeks to induce pancreatic cancer. Gr. 1 and 3 received a diet containing conventional LA, Gr. 2 and 4 were fed a diet of conjugated LA. After 29 weeks all animals were sacrificed, pancreas was weighed and examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathion peroxidase and superoxide dismutase were determined in tumor-free as well as in pancreatic carcinoma tissue. Different diets did not influence the incidence of pancreatic carcinoma, however, pancreas weight was increased by conjugated LA compared to conventional LA. Furthermore both diets decreased the activity of glutathion peroxidase and increased the level of lipid peroxidation in pancreatic intratumoral tissue. The content of conjugated LA in dietary did not influence pancreatic tumor growth in a solid model of pancreatic adenocarcinoma in Syrian hamsters.
Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Ácido Linoleico/farmacología , Ácidos Linoleicos Conjugados/farmacología , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Adenocarcinoma/inducido químicamente , Animales , División Celular/efectos de los fármacos , Cricetinae , Grasas de la Dieta/farmacología , Glutatión Peroxidasa/metabolismo , Ácido Linoleico/administración & dosificación , Ácidos Linoleicos Conjugados/administración & dosificación , Masculino , Mesocricetus , Páncreas/enzimología , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/inducido químicamente , Neoplasias Pancreáticas/enzimología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
While conjugated linoleic acid (CLA) is regarded as an essential fatty acid with anticarcinogenic effects, conventional linoleic acid (LA) is reported to promote tumour growth in various experimental studies probably caused by high sensitivity to non-enzymatic lipid peroxidation. In order to evaluate the impact of dietary LA and CLA on liver metastasis and lipidperoxidation (LPO), 60 Syrian hamsters were injected with 10 mg N -nitrosobis-2-oxopropylamine (BOP)/kg body weight s.c. for 12 weeks. Animals were fed a special diet containing LA or CLA. The experiment was terminated after 24 weeks. Incidence, number and size of liver metastases were histologically determined. Furthermore, the activities of antioxidative enzymes and concentration of hepatic lipidperoxidation were measured intra- and extrametastatically. Incidence, number and size of liver metastases did not differ between the tumour groups. Otherwise, antioxidative enzyme activity of GSH-Px was higher in non-metastatic liver, while SOD activity and lipidperoxidation were increased in liver metastases. Conclusively there was no difference between the groups fed with LA and CLA according to the impact on liver metastasis in ductal pancreatic cancer.
Asunto(s)
Ácidos Linoleicos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas/secundario , Neoplasias Pancreáticas/patología , Animales , Cricetinae , Grasas Insaturadas en la Dieta/farmacología , Glutatión Peroxidasa/metabolismo , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/enzimología , Nitrosaminas , Neoplasias Pancreáticas/inducido químicamente , Superóxido Dismutasa/metabolismoRESUMEN
INTRODUCTION: In prospective clinical trials, octreotide improved quality of life and survival time in patients with pancreatic cancer. AIMS: To analyze whether octreotide modulates the hepatic oxygen radical metabolism and thus might decrease liver metastasis in an animal model of pancreatic cancer. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.
Asunto(s)
Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Octreótido/uso terapéutico , Neoplasias Pancreáticas/patología , Animales , Carcinógenos , Cricetinae , Grasas de la Dieta/administración & dosificación , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Neoplasias Hepáticas/patología , Masculino , Mesocricetus , Nitrosaminas , Octreótido/farmacología , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Neoplasias Pancreáticas/inducido químicamente , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas Experimentales/metabolismo , Octreótido/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Cricetinae , Glutatión Peroxidasa/metabolismo , Masculino , Mesocricetus , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Superóxido Dismutasa/metabolismoRESUMEN
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.