Radiotherapy and high bilirubin may be metformin like effect on lung cancer via possible AMPK pathway modulation.

PURPOSE: Life expectancy of cancer patients determine the regimen of treatment. There is no feasible marker that determines the survival other than the stage of the disease or other patients related factors. Bilirubin can be a revealing marker for these. The effect of bilirubin may be due to the fact that the genetic and biochemical processes of bilirubin also modulate the tumour microenvironment. Radiotherapy and bilirubin can produce an effect similar to metformin via AMPK pathway. MATERIALS AND METHODS: This analysis was performed retrospectively in a cohort of 80 patients with a diagnosis of locoregional lung cancer with bilirubin levels in the accepted range. Receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cut-off points. Pre-treatment serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) levels and tumour volumes in the prognosis of the patients were investigated. RESULTS: The cut-off points for serum TBIL, DBIL and IBIL were 0.565 mg/dL, 0.105 mg/dL and 0.415 mg/dL,respectively. High TBIL 47.5 %, high DBIL and high IBIL were observed in 45 % of the entire patient population. The overall survival was three times longer in the high TBIL group than in the low TBIL group (OS; Hazard Ratio (HR), 0.33; 95% CI 0.16-0.70; p <0.001), locoregional free survival (LRFS; HR, 0.44; 95% CI 0.27-0.71; p <0.001) and distant metastasis-free survival (DMFS; HR, 0.44; 95% 0.25-0.80; p < 0.001). Similarly, high DBIL and high IBIL levels have been associated with longer OS, LRFS, and DMFS with significant differences. In addition, in the survival analysis of the cohort stratified with gross tumour volume (GTV) 128.5cc and TBIL 0.565 cut-off values; In the comparison of high TBIL and low TBIL groups, a significantly longer OS was observed in the high TBIL group in the patients with a GTV volume greater than128.5cc (p <0.001). CONCLUSION: Plasma bilirubin level at the time of diagnosis affects the survival of the patients independent of cancer stage and tumour volume. Possible additive interactions of radiotherapy and bilirubin are discussed with their pathophysiological mechanisms (Tab. 2, Fig. 7, Ref. 26).

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity.

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.