The literature on apoptosis has grown tremendously in recent years, and the mechanisms that are involved in this programmed cell death pathway have been enlightened. It is now known that apoptosis takes place starting from early development to adult stage for the homeostasis of multicellular organisms, during disease development and in response to different stimuli in many different systems. In this review, we attempted to summarize the current knowledge on the circumstances and the mechanisms that lead to induction of apoptosis, while going over the molecular details of the modulator and mediators of apoptosis as well as drawing the lines between programmed and non-programmed cell death pathways. The review will particularly focus on Bcl-2 family proteins, the role of different caspases in the process of apoptosis, and their inhibitors as well as the importance of apoptosis during different disease states. Understanding the molecular mechanisms involved in apoptosis better will make a big impact on human diseases, particularly cancer, and its management in the clinics.

AIM:To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS:A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (n = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS:Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION:Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

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Melatonin, in rats, reduced the level of MDA, which is elevated by radiotherapy and increased the levels of SOD and GPX, which are involved in the antioxidant system.

The M30-monoclonal antibody recognizes a neo-epitope of cytokeratin 18 which is formed after caspase-cleavage during apoptosis. Caspase-cleaved cytokeratin 18 is released from apoptotic cells into circulation. The aim of this study was to evaluate the relationship between M30-antigen level and chemotherapy response in neoadjuvant treatment of breast cancer. Forty-two patients with invasive breast carcinoma received 4 cycles of anthracycline based neoadjuvant chemotherapy. Serum samples were obtained for assessment of M30-antigen levels before the administration of first chemotherapy cycle (baseline), and then after 24 and 48 hours for determination of chemotherapy induced apoptosis. M30-antigen levels at 24 and 48 hours were found to be significantly higher than baseline (p < 0.001, p = 0.003, respectively). M30-antigen levels in responders showed statistically significant increases at 24 and 48 hours (p < 0.001; p = 0.004, respectively), while statistically significant increases were not observed in nonresponders. Percentage change of M30-antigen levels was significantly higher in responders than nonresponders at 24 hours (p = 0.020). In conclusion, our study revealed a significant relationship between increases of M30-antigen levels in serum and overall response to therapy.

Background: One of the major goals of oncology is to predict the response of patients with cancer to chemotherapeutic agents by employing laboratory methods variously called ‘tumor chemosensitivity assays’, ‘drug response assays’, or ‘drug sensitivity assays’, in vitro. The MTT assay is one of the methods used to predict the drug response in malignancies. However, it may suffer from interference by the anticancer drugs with the MTT assay. Methods: The MTT assay, a colorimetric viability assay, was checked in a cell-free system in terms of its possible chemical interactions with 22 different anticancer drugs. Results: It was found that epirubicine, paclitaxel, doxetaxel, and cisplatin caused a relatively significant increase in absorbance values, resulting in the MTT assay giving rise to false results (untrue increase in viability) although most of the drugs tested did not seem to cause any significant change. Conclusion: It was concluded that before employing the MTT assay, drugs (or any kind of substances) to be included in the assay should be checked first in terms of possible chemical interactions with MTT, otherwise it may be impossible to evaluate the MTT viability assay results correctly.