The expression of IL10RA in colorectal cancer and its correlation with the proliferation index and the clinical stage of the disease.

INTRODUCTION: Despite the widely described role of IL10 in immune response regulation during carcinogenesis, there is no established model describing the role of its receptor. The aim of this study is to elucidate the relationship between the subunit alpha of IL10 receptor (IL10RA) in the pathogenesis of colorectal cancer (CRC). METHODS: The study was conducted on archived paraffin blocks of 125 CRC patients, from which tissue microarrays (TMA) were made. These were subsequently used for immunohistochemistry to assess the expression of IL10RA, IL10, phosphorylated STAT3 (pSTAT3) and the Ki67 proliferation index. The intensity of both reactions was assessed by independent researchers using two approaches: digital image analysis and the Remmele and Stegner score (IRS). To assess the possible correlations between the two investigated markers and the clinical stage of CRC, the Pearson correlation coefficient was calculated. The expression of aforementioned proteins was assessed in tumor samples, healthy surgical margins and healthy control samples, obtained from cadavers during autopsy from the Department of Forensic Medicine. Statistical analysis was conducted using Statistica ver. 13.05 software. RESULTS: The final analysis included 105 CRC patients with complete clinical and pathological data, for whom the expressions of IL10RA, IL10, pSTAT3 and Ki67 were assessed using two independent methods. There was a positive correlation between the IL10RA expression and Ki-67 proliferation index (R = 0.63, p < 0.001) and a negative correlation between the IL10RA expression and the clinical stage of CRC (R = -0.21, p = 0.022). IL10RA correlated positively with pSTAT3 and IL10 in neoplastic tissue and tumor margin (with p < 0.01 for all correlations). We also observed a significantly higher expression of IL10RA in healthy surgical margins when compared to the actual tumor (p = 0.023, the paired t-test). The expression of IL10 was significantly higher in tumors than in healthy intestinal endothelium from control group. CONCLUSIONS: The correlations between the expression of IL10RA and the proliferation index or the clinical stage of CRC seem to confirm the importance of IL10RA in the pathogenesis of CRC. The higher expression of IL10RA in healthy surgical margins than in the tumor itself may suggest that IL10RA plays a role in regulating immune response to the neoplasm.

Nonfatal and fatal intoxications with pure caffeine - report of three different cases.

Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16 µg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64 µg/mL and 613.0 µg/mL. In case 2 the patient died 10 min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.