الفهرس 
Pancreatic Cancer
Metformin and anti-diabetic tretatmentOnly 14 pages are availabe for public view
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Abstract
This study was designed to elucidate whether the biguanides metformin can act as treatment for induced pancreatic carcinogenicity in male Syrian golden hamsters induced by N-Nitrosobis (2- oxopropyl) amine (BOP), and to compare this results with those of standard drug used for treatment of pancreatic cancer, Gemcitabine. In this thesis, the study was performed; 26 weeks on Sixesty healthy, 6-week-old male Syrian Golden Hamsters have the same experimental designs as following; 6-week-old male Syrian Golden Hamsters divided into 6 groups. group 1 (G1) Hamsters were administered with BOP only by two consecutives s.c. injections of doses 60 and 30 mg/kg b.wt. at 0 and 1st week respectively. Control serving as positive control. group 2 (G2) Hamsters were administered with BOP then treated with Metformin at dose for 3 times in weeks (200 mg/kg b.wt./day). group 3 (G3) Hamsters were administered with BOP then treated with Gemcitabine for 2 times in weeks (25mg/kg b.wt). group 4 (G4) Hamsters were administered with the vehicle (0.09% saline) serving as negative control group. group 5 (G5) Hamsters were administered with 0.09% saline then Metformin. group 6 (G6) Hamsters were administered with 0.09% saline then Gemcitabine. Fifteen Hamsters were used in first 3 group and sex hamsters for the other 3 groups for the experimental design. Hamsters were amnestied to death by diethyl Ether after 26 weeks for study. In experimental study • Pancreas was grossly checked for tumors or abnormalities. • Blood were collected at sacrificed from dorsal vena cava for CBC determination. • Serum or Plasma were prepared for physiological analysis of o AST, ALT, total proteins, blood glucose levels, Albumin, triglycerides, cholesterol levels and creatinine levels. • Pancreas was collected, half will be fixed in 10% phosphate buffered formalin and the rest will be frozen in -80°C. • Histopathological analyses for generation of tumor incidence and multiplicities in pancreas and all collected organs from all groups. • Physiological analyses of liver o Levels of Catalase, SOD, GSH, MDA. • Molecular Semi quantitative reverse transcriptase (RT)-PCR analysis. • Statistical analysis. The results obtained can be summarized as follows qRT- PCR data analysis for Cu/Zn SOD gene expression Results showed that The qRT-PCR data analysis of cu/zn SOD gene relative to GAPDH housekeeping gene in pancreas showed that cu/zn SOD gene was up-regulated by 3.7 fold in metformin treated group (G2) and 86.6 fold in gemcitabine treated group (G3) when compared with normal untreated control group while it returned to nearly normal value in hamsters treated with BOP only (positive control). On the other hand, the qRT-PCR data analysis of cu/zn SOD gene relative to GAPDH housekeeping gene in liver show that cu/zn SOD gene returned to nearly normal value in all groups. Antioxidant enzymes activities and oxidative stress markers in liver tissues All of measured oxidative stress markers of SOD, CAT, GSH and MDA were significantly changed among all treated groups. Interestingly treatment with metformin and gemcitabine have significantly modulated all the parameters activities close to normal control levels without marked side effects, reflecting the safety profile this therapy. Complete blood count The biochemical analysis of the collected blood samples did not show any significant differences between the different animal groups changes except for the WBCs numbers of groups 1and 5 were significantly increased vs group 4 while in group 3 decreased vs group 1. Liver function parameters Several alterations were observed in the blood biochemistry parameters. ALT and AST levels were significantly increased in group 6 as compared with the –ve control in group 4 Again, the total protein level were significantly decreased in groups 5 versus the –ve control levels of group 4. The albumin levels were significantly decreased in groups 1 versus -ve control levels of group 4. Kidney function parameters The Creatinine levels were significantly decreased in group 1, 5 and 6 versus –ve control levels of group 4. Lipid profile levels Cholesterol and triglycerides levels were significantly decreased in group 1, 5 and 6 versus -ve control in group 4, while the triglycerides levels were significantly increased in groups 6 versus - ve control in group 4. On the other hand, the glucose levels of group 2 were found significantly increased as compared to +ve control ingroup1 and group6 as compared to -ve control in group4. Histological investigations Histological investigations of pancreas tissues in all groups showed that metformin treatment have the same effect of gemcitabine treatment that inhibited the numbers and area sizes of different types of pancreatic foci of cellular alterations caused by BOP induction. Conclusion and Recommendations The results of this study indicated that metformin treatment has protective effects on pancreatic cancer comparable to gemcitabine treatment (standard chemotherapy drug) but without side effects. Metformin exerts is anticancer effect through Cu/ZnSOD while gemcitabine increased its activity. However, more studies are required to explain its mechanism of action.