Neutrophil cathepsin G, but not elastase, induces aggregation of MCF-7 mammary carcinoma cells by a protease activity-dependent cell-oriented mechanism.

We previously found that a neutrophil serine protease, cathepsin G, weakens adherence to culture substrates and induces E-cadherin-dependent aggregation of MCF-7 human breast cancer cells through its protease activity. In this study, we examined whether aggregation is caused by degradation of adhesion molecules on the culture substrates or through an unidentified mechanism. We compared the effect of treatment with cathepsin G and other proteases, including neutrophil elastase against fibronectin- (FN-) coated substrates. Cathepsin G and elastase potently degraded FN on the substrates and induced aggregation of MCF-7 cells that had been subsequently seeded onto the substrate. However, substrate-bound cathepsin G and elastase may have caused cell aggregation. After inhibiting the proteases on the culture substrates using the irreversible inhibitor phenylmethylsulfonyl fluoride (PMSF), we examined whether aggregation of MCF-7 cells was suppressed. PMSF attenuated cell aggregation on cathepsin G-treated substrates, but the effect was weak in cells pretreated with high concentrations of cathepsin G. In contrast, PMSF did not suppress cell aggregation on elastase-treated FN. Moreover, cathepsin G, but not elastase, induced aggregation on poly-L-lysine substrates which are not decomposed by these enzymes, and the action of cathepsin G was nearly completely attenuated by PMSF. These results suggest that cathepsin G induces MCF-7 aggregation through a cell-oriented mechanism.

Preventive effect of daikenchuto, a traditional Japanese herbal medicine, on onset of ileus after gynecological surgery for malignant tumors.

BACKGROUND: Postoperative ileus is a major complication of abdominal surgical procedures. The purpose of this study was to investigate preventive effect of daikenchuto (DKT) on onset of ileus in patients who received gynecological surgery for malignant tumors. METHODS: A total of 904 patients who received gynecological surgery for malignant tumors by opening retroperitoneum along with retroperitoneal lymph node dissection during a period between 2004 and 2018 were included in this retrospective study. The retroperitoneum was not sutured in all patients. Comparisons were made for proportion of patients developing ileus (frequency of postoperative ileus onset), timing of ileus onset, and treatment types for ileus among following three groups: a group treated with enema or laxatives to release gas if they did not pass the intestinal gas for 3 days postoperatively (Group A, n = 152); a group treated with adhesion-inhibitory absorptive barrier at the opening to the retroperitoneum (Group B, n = 188); and a group treated with adhesion-inhibitory absorptive barrier and oral intake of DKT 7.5 g per day (Group C, n = 564). RESULTS: The frequency of ileus onset significantly decreased in both Groups B (4.8%) and C (3.5%) compared to Group A (16.4%). Furthermore, the frequency of ileus onset was significantly less in Group C compared to Group B. For the treatment types, frequency of ileus, which was successfully treated only with conservative therapy, was the same for Groups B and C. However, incidence of serious ileus that required surgery decreased by 45% in Group C (2/564) compared to Groups A (2/152) and B (3/188). CONCLUSIONS: Results suggest that DKT prevents development of serious ileus after gynecological surgery for malignant tumors and therefore contributes to improvement in patients' QOL.

A case of small cell carcinoma of the vagina.

Primary small cell carcinoma of the vagina is quite rare, and a standard treatment has not been established yet. Herein, we report a case of an 81-year-old woman who was diagnosed with a vaginal tumor without continuity with the uterine cervix. Histopathological diagnosis indicated alveolar solid growth of nuclear chromatin-rich atypical cells with a high N/C ratio and a partially recognized rosette-like structure, suggesting a differentiated neuroendocrine system. Chromogranin A and synaptophysin were positive. Stage I vaginal small cell carcinoma localized to the vagina was diagnosed. The tumor disappeared by radiation monotherapy with external beam irradiation and endocavitary irradiation. The patient remains alive without any disease 1 year and 8 months after the treatment, suggesting the efficacy of radiotherapy in small cell carcinoma of the vagina.