Neoadjuvant Chemotherapy Based on Gemcitabine and FOLFIRINOX: Survival and Death of Cancer Cells in Patients with Adenocarcinoma of the Pancreatic Ducts
Introduction. The progression and response to systemic cancer treatment is largely dependent on the balance between death of cancer cells (apoptosis and necroptosis) and their survival (autophagy). Although this is well characterized in experiments, the status of cancer cell survival and cell death in adenocarcinoma of the human pancreatic ducts (hereinafter PDAC), especially in response to various types of chemotherapy, is poorly described. Materials and methods. Expression of cancer cell autophagy markers, apoptosis, and necroptosis were compared in pancreatic tissue samples from 51 patients. All patients were divided into the following 4 groups: group 1 consisted of patients after surgical resection of PDAC followed by folfirinox therapy (n11) group 2 consisted of patients after gemcitabine-based neoadjuvant therapy (n14) group 3 consisted of patients, who underwent PDAC resection without prior chemotherapy (n13) and group 4 13 samples of normal pancreas of 13 intact patients. Marker expression was carried out using a semi-automatic immunofluorescence assay similar to FACS, determining PDAC cells by CK-7 expression. In this paper, the final data are given in the form of tables. Results. The median (95 confidence interval) of patient survival was 31.6 (24.544.5) months after taking folfirinox, if compared to 15.8 (2.020.5) months after gemcitabine therapy (p0.039). Autophagy of PDAC tissue was reduced, if compared to normal pancreas based on decreased expression of BECLIN-1 and co-localization of LC3-Lamp-2, while necroptosis (RIP-1) was increased. Neoadjuvant therapy was associated with further reduction of autophagy based on accumulation of p62 / SQSTM-1, as well as the increased levels of necroptosis (RIP3 and pMLKL) and apoptosis (BAX, cleaved CASPASE-9 and CASPASE-3), increased nuclear p65 (NF-B ), and extracellular expression of HMGB1 with greater CD8 lymphocyte infiltration. Survival was associated with decreased autophagy and increased apoptosis. Markers of necroptosis (RIP-3, pMLKL) and apoptosis (BAX and cleaved CASPASE-9) were higher after the use of folfirinoks, if compared with the results of treatment based on gemcitabine.