Search

Background/aim: Ferroptosis is a nonapoptotic type of cell death that is dependent on iron and involves the accumulation of reactive oxygen species. Ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) are ferroptosis regulators that inhibit ferroptosis through independent pathways. This study assessed the prognostic value of GPX4 and FSP1 expression in colorectal cancer (CRC). We also examined the effects of FSP1 and GPX4 inhibition on cell survival of CRC cells., Materials and Methods: This study included 206 surgical specimens from Stage II or III CRC patients. FSP1 and GPX4 expression was analyzed immunohistochemically, and the association of their expression levels with clinical outcome was evaluated. We also examined the effects of FSP1 and GPX4 inhibitors on the cell proliferative capacity of CRC cell lines., Results: Overall survival and recurrence-free survival were reduced in patients with high expression of FSP1 or GPX4, and those with both GPX4 and FSP1 expression showed worse prognosis. Positivity of both FSP1 and GPX4 was an independent poor prognostic factor for CRC patients. In CRC cells, the combination of GPX4 and FSP1 inhibitors led to more effective cell death than either inhibitor alone., Conclusion: High expression of both GPX4 and FSP1 is a significant poor prognostic factor for CRC. Simultaneous inhibition of GPX4 and FSP1 to induce ferroptosis may be a novel therapeutic strategy in CRC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to evaluate the clinical impact of the level of inferior mesenteric artery (IMA) ligation in patients with advanced low rectal cancer., Patients and Methods: All enrolled patients (n=350) underwent curative resection of rectal cancer with D3 lymph node dissection, with either IMA (high-tie) or superior rectal artery (SRA) (low-tie) ligation., Results: There were 27 and 65 patients in the high-tie and low-tie groups, respectively. There was no significant difference in the postoperative complication rate. Postoperative anastomotic leakage developed in five patients in the low-tie group and none in the high-tie group. The overall recurrence rates were 37.0% (n=10) and 40.0% (n=26) in the high-tie and low-tie groups, respectively, with no significant difference between the two groups (p=0.748). Local recurrences and lymph node metastases developed in five and no patients in the high-tie group and in 13 and one patient in the low-tie group, respectively. In the multivariate analysis, pathological T4 and pathological N2 and N3 were independent poor prognostic factors for overall survival (OS), whereas left colic artery (LCA) preservation was not significant., Conclusion: No significant difference in oncological outcomes was observed in advanced low rectal cancer surgery with respect to the level of the IMA ligation. Thus, the less complicated high-tie procedure should be adopted as a standard procedure., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Glutathione peroxidase 4 (GPX4) is a glutathione-dependent antioxidant enzyme known to regulate ferroptosis, which is a non-apoptotic form of cell death accompanied by iron-dependent accumulation of reactive oxygen species (ROS). This study evaluated the expression and function of GPX4 in GC., Materials and Methods: The expression of GPX4 was examined in five human GC cell lines (KATO-III, MKN-1, MKN-28, MKN-45, and MKN-74) using real-time quantitative PCR and western blotting. The role of GPX4 in GC was examined using small interference RNA and cell proliferation and ROS assays. Finally, we analyzed GPX4 expression in tumor tissues from 106 patients who underwent GC surgery using immunohistochemistry and evaluated the relationship between GPX4 levels and clinical outcomes of GC., Results: GPX4 was expressed in all GC cell lines at various levels. GPX4 silencing and inhibition significantly reduced cell proliferation and increased ROS generation. Furthermore, the mRNA levels of prostaglandin-endoperoxide synthase 2, a known biomarker of ferroptosis, were increased after GPX4 silencing. GPX4 expression was found to be an independent prognostic factor for overall and disease-specific survival in GC patients., Conclusion: GPX4 can regulate cancer cell death via ferroptosis in GC cell lines and represents a significant risk factor for survival in patients with GC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Nutritional status is strongly associated with cancer prognosis. The aim of this study was to identify the most useful combination of nutrition-related serum markers for predicting prognosis of patients with colorectal cancer (CRC)., Patients and Methods: A total of 523 patients who underwent proctocolectomies for CRC at our hospital were enrolled in this study. Serum concentrations of albumin, cholinesterase and total cholesterol, and total peripheral lymphocyte count (TLC) were used as nutrition-related markers., Results: In multivariate analysis of nutrition-related markers, serum albumin and cholinesterase levels were found to be independent prognostic indicators. Cut-off values from receiver operating characteristic analyses were used to sort patients as ChE High or ChE Low (serum cholinesterase level ≥ or <221.5), and as Alb High or Alb Low (serum albumin level ≥ or <3.85). We then sorted them into three groups: ChE High /Alb High (Group A); ChE High /Alb Low or ChE Low /Alb High (Group B); and ChE Low /Alb Low (Group C). Their 5-year overall survival rates differed significantly (Group A: 81.6%, Group B: 62.1%, Group C: 42.7%, p<0.0001); as did their 5-year disease-specific survival rates (Group A: 90.1%, Group B: 73.8%, Group C: 62.2%, p<0.0001)., Conclusion: The combination of serum cholinesterase and albumin levels is useful for predicting the prognosis of patients with CRC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Therapeutic strategies for positive peritoneal lavage cytology [CY(+)] findings have not yet been established. The aim of the present study was to compare the effects of neoadjuvant systemic chemotherapy and surgery followed by S-1 adjuvant chemotherapy for treating gastric carcinoma in patients with CY(+) status without peritoneal metastasis., Patients and Methods: Twenty-three patients with CY(+) status without peritoneal metastasis who underwent curative surgery for gastric carcinoma between October 1999 and December 2014 were included in the study. Ten patients received neoadjuvant systemic chemotherapy followed by surgery, whereas 13 patients underwent surgery, in nine cases followed by S-1 adjuvant chemotherapy., Results: The 5-year survival in both groups was 15%, and no significant difference was observed. However, the prognosis for patients with CY(-) status after neoadjuvant systemic chemotherapy was significantly better than that of patients who were still CY(+) after neoadjuvant systemic chemotherapy (p<0.01). Among all patients, the prognosis of those with less than clinical N2 disease was significantly better than that of patients with clinical N3 (p<0.01). In multivariate analysis, clinical lymph node metastasis was the only independent prognostic factor for CY(+) patients without peritoneal metastasis (p<0.05)., Conclusion: The prognosis of gastric carcinoma with CY(+) without peritoneal metastasis is still stage IV disease and is dependent on the degree of clinical lymph node metastasis, in spite of therapeutic treatment., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Unlabelled: THE AIM of this study was to compare the efficacy and toxicity of S-1 to an oral combination regimen of tegafur and uracil (UFT) with leucovorin (LV) in metastatic colorectal carcinoma (CRC) patients., Patients and Methods: Fifty-two patients were treated with either S-1 (80 mg/m2/d), administered for 28 days every 42 days, or UFT (300 mg/m2/d) and LV (90 mg/d), administered for 28 days every 35 days. The clinical results were compared retrospectively., Results: There were no statistically significant differences in overall response between the two patient groups. The overall response rate was 11.8% in the S-1 group, and 11.1% in the UFT/LV group. No statistically significant difference in-time- to progression (TTP) or survival time was observed between the treatments. The median survival time was 29 months with S-1 and 12 months with UFT/LV., Conclusion: The oral S-1 provided similar safety and efficacy, compared to UFT/LV for metastatic CRC.