Mesenchymal stem cells are more effective than captopril in reverting cisplatin-induced nephropathy

Cisplatin is a powerful anticancer drug but its nephrotoxic effects limit its clinical use.We aimed to evaluate the effect of mesenchymal stem cells(MSCs)injection or of captopril to counteract the cisplatin-induction of nephropathy.MSCs isolation,preparation and tracking,transforming growth factor-β(TGF-β)and interleukin-10(IL-10)expressions,kidney function tests,oxidative stress state,and histological examinations were done.Cisplatin-induced nephropathy was indicated biochemically and confirmed histopathologically.MSCs treatment showed normal kidney architecture and significantly decreased oxidative stress and TGF-β while increased IL-10 and improved kidney function tests.Rats treated with cisplatin+captopril showed noticeable kidney histopathological changes.Superior positive impact of MSCs in amelioration of cisplatin-induced nephropathy via their ability to motivate functional and structural renal repair is evidenced.

Associations between CD133,CK19 and G2/M in cirrhotic HCV(genotype-4)patients with or without accompanying tumor

Hepatitis C virus(HCV)-cirrhotic patients have the highest threat of developing hepatocellular carcinoma(HCC)and may be at risk of extra hepatic cancer.The present study was designed to investigate CD133 and CK19 in HCV(genotype-4)-cirrhotic patients with/without HCC or extra hepatic cancer,to assess the degree of their correlation with cell cycle abnormalities and finally to assess the role of their combination as diagnostic tool for discrimination of cirrhotic patients with HCC from those with extra hepatic cancer.The study included 77 HCV-cirrhotic patients and 20 healthy non-disease control group.Patients were categorized histo-pathologically into:24 have only liver cirrhosis,26 with HCC,and 27 patients with extra hepatic cancer.Cell cycle abnormalities,CD133 and CK19 were determined by flow cytometry technique.CD133 and CK19 showed marked elevation in HCC and extra hepatic cancer compared with liver cirrhosis and control subjects(p<0.0001).Positive associations were noted between CK19,CD133 and G2/M.They were gradually increased with progression from liver cirrhosis to HCC.Combination of the three showed the best AUC(0.978)and accuracy(92.5%)for discrimination of HCC from extra hepatic cancer.Combined CD133 with G2/M and CK19 comprises an excellent diagnostic panel for discrimination of HCV-cirrhotic patients with HCC from those with extra hepatic cancer.

Synergistic impacts of rifampicin and doxorubicin against thioacetamide-induced hepatocellular carcinoma in rats

Background and aims:Combination therapy is a promising new strategy that has been proposed to increase the efficacy of cancer treatment.We aimed to investigate the anti-cancer activity of rifampicin monotherapy and its combination with doxorubicin against hepatocellular carcinoma(HCC).Materials and methods:The in vitro half maximal inhibitory concentration(IC50)and selectivity index(SI)of the drugs under investigation against HepG2 and human lung fibroblast(WI38)cell lines were determined.For the in vivo experiment,male Sprague-Dawley albino rats were injected with thioacetamide at 200 mg/kg twice a week for 90 days;HCC development was confirmed histopathologically.Following HCC induction,the rats were treated with intraperitoneal doxorubicin,rifampicin,or their combination for 45 or 90 days.After sacrifice,the livers were examined histopathologically.The levels of aminotransferases,albumin,bilirubin,malondialdehyde,superoxide dismutase(SOD),catalase(CAT),total antioxidant capacity(TAC),and nitric oxide were measured by spectrophotometry.Alphafetoprotein,cancer antigen 19-9,tumor necrosis factor-alpha,interleukin-6,Bcl-2-associated X protein,caspase 3,caspase 8,and p53 were estimated using ELISA.Results:In vitro,the combination of doxorubicin and rifampicin showed the highest SI of 3.43.In vivo,among the measured markers,the levels of TAC,CAT,SOD,and p53 decreased(P<0.001)and the rest of the measured marker levels increased(P<0.001)in the HCC-bearing rats;after treatment in all groups,all these changes improved toward normal in a time-dependent manner.The combination of doxorubicin and rifampicin optimized the effects of the two individual drugs and exerted the best antioxidant effects.Conclusions:In general,compared with rifampicin or doxorubicin alone,combination therapy has favorable outcomes.Based on our results,the combination of rifampicin and doxorubicin might be applicable for HCC chemotherapy.