Interleukin-8 enhances the effect of colchicine on cell death.

Pro-inflammatory cytokines are known to be generated in tumors and play important roles in angiogenesis, mitosis, and tumor progression. However, few studies have investigated the synergistic effects of pro-inflammatory cytokines and anticancer drugs on cell death. In the present study, we examined the combined effects of pro-inflammatory cytokines and colchicine on cell death of cancer cells. Colchicine induces G2/M arrest in the cell cycle by binding to tubulin, one of the main constituents of microtubules. SUIT-2 human pancreatic cancer cell line cells overexpressing pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-8, and tumor necrosis factor (TNF)-α, were treated with colchicine. The effect of colchicine on cell death was enhanced in cells overexpressing IL-8. Moreover, the effect of colchicine on cell death was enhanced in cells overexpressing two IL-8 up-regulators, NF-κB and IL-6, but not in cells overexpressing an IL-8 down-regulator, splicing factor proline/glutamine-rich (SFPQ). Synergistic effects of IL-8 and colchicine were also observed in cells overexpressing IL-8 isoforms lacking the signal peptide. Therefore, IL-8 appeared to function as an enhancer of cell death in cancer cells treated with colchicine. The present results suggest a new role for IL-8 related to cell death of cancer cells.

The modified Altemeier procedure for a loop colostomy prolapse.

Loop colostomy prolapse is associated with an impaired quality of life. Surgical treatment may sometimes be required for cases that cannot be closed by colon colostomy because of high-risk morbidities or advanced disease. We applied the Altimeter operation for patients with transverse loop colostomy. The Altemeier operation is therefore indicated for rectal prolapse. This technique involves a simple operation, which includes a circumferential incision through the full thickness of the outer and inner cylinder of the prolapsed limb, without incising the abdominal wall, and anastomosis with sutures using absorbable thread. We performed the Altemeier operation for three cases of loop stomal prolapse. Those patients demonstrated no postoperative complications (including obstruction, prolapse recurrence, or hernia). Our findings suggest that this procedure is useful as an optional surgical treatment for cases of transverse loop colostomy prolapse as a permanent measure in patients with high-risk morbidities or advanced disease.

Laparoscopic Anatomical Liver Resection Using Liver Mapping of Incidental Indocyanine Green Fluorescence due to Cholestasis.

BACKGROUND/AIM: Indocyanine green (ICG) fluorescence is useful in laparoscopic hepatectomy (LH) for tumor identification and staining, as well as determination of resection margins. At our Institution, patient-specific, three-dimensional simulations and rehearsal of surgical strategies are carried out preoperatively. We describe cases in which ICG administered preoperatively became stagnated and fluoresced in an area similar to the preoperatively established resection area and the pathological findings in these cases. PATIENTS AND METHODS: Four patients who underwent LH at our hospital between 2020 and 2023 (due to hepatocellular carcinoma in two and colorectal liver metastasis in two) were enrolled in the present study. The ICG-fluorescing liver segments were resected laparoscopically and their pathological characteristics were examined using a fluorescence microscope. RESULTS: In four cases, the areas of ICG fluorescence seen intraoperatively were due to stasis of preoperatively administered ICG, which fortuitously was equivalent to the planned resection area in the preoperative patient-specific simulation. The fluorescent areas were resected; there were no cases of bile leakage or recurrence. Fluorescence microscopy revealed areas with diffuse ICG fluorescence in normal hepatocytes on the tumor's peripheral side. CONCLUSION: It was suggested that resection of the liver area that was fluorescent due to stagnation of preoperatively administered ICG was rational and justified both anatomically and oncologically. This resection may also contribute to the prevention of bile leakage and recurrence.

Alternative RNA splicing in expression of the glutathione synthetase gene in human cells.

Ubiquitous free radical production occurs continuously in cells and tissues. Glutathione is the most abundant mammalian antioxidant, and is synthesized by glutathione synthetase (GSS). Therefore, GSS plays an important role in defending the cell against reactive oxygen species. The expression of GSS has been studied in human cells; however, sequence information about alternative splicing variants of GSS mRNA has not been reported. In the present study, we identified a novel alternative splicing variant (ASV) of the GSS gene in 10 human normal tissues and five human cancer cell lines. The deleted transcript of GSS was characterized by an in-frame deletion of 333 bp, corresponding to the complete loss of exons 4 and 5. Thus this GSS ASV causes protein truncation. We quantified the mRNA of GSS ASV in human normal tissues using real-time PCR. The ASV was detected in colon, kidney, lung, liver, placenta, peripheral blood and uterus, but not in heart, skeletal muscle and spleen tissue. Our results provide a basis for more detailed studies on the regulation of GSS, and for further evaluation of this and other possible roles of GSS. Understanding the regulation of GSS expression is very important for the development of new strategies for controlling the development of GSH-based redox homeostasis.