モルヒネは血管内皮増殖因子VEGFを抑制することによって、口腔癌細胞HSC-3細胞の活性および細胞増殖を阻害する

Purpose: Although many oral cancer patients require opioids, the effects of morphine and related drugs on oral cancer progression have not been well established. Thus, we examined the effects of morphine exposure on the viability of human oral squamous carcinoma HSC-3 cells and aimed to identify the underlying mechanism. Methods: We exposed HSC-3 cells to the various concentrations of morphine (0, 0.1, 1, 10, 100, or 1000 μmol/L) for 48 h and, subsequently, evaluated cell viability using the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and cytotoxicity using the lactate dehydrogenase (LDH) assay. To explore the effects of morphine on cell proliferation further, colony formation assay and cell cycle analysis were performed. Additionally, the intracellular expression of nuclear factor kappa B (NF-κB) was analyzed using flow cytometry, and vascular endothelial growth factor (VEGF)-A was evaluated using human VEGF assay. Results: Morphine exposure reduced cell viability and enhanced cytotoxicity in HSC-3 cells in a concentration-dependent manner. The number of colonies in the morphine-treated groups was significantly lower than that in the control group. Consistent with these results, morphine exposure significantly reduced the concentration of VEGF in the cell culture medium in a concentration-dependent manner. However, our data show that morphine at clinical concentrations (0.1-10 μmol/L) does not affect cell cycle and apoptosis. Conclusions: Our results suggest that in human oral cancer HSC-3 cells, morphine exposure inhibits cell viability and growth via suppression of VEGF in clinical conditions.博士（医学）・甲第727号・令和2年3月16日© Japanese Society of Anesthesiologists 2019This is a post-peer-review, pre-copyedit version of an article published in Journal of anesthesia. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00540-019-02645-1

心室中隔欠損症に対する小児心臓カテーテル検査における麻酔方法と重症合併症の関連

Pediatric cardiac catheterization requires unconsciousness and immobilization through general anesthesia or sedation. This study aimed to compare the occurrence of severe complications in pediatric diagnostic cardiac catheterization for ventricular septal defect between general anesthesia and sedation performed under similar institutional environments. Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients (aged <2 years) who underwent diagnostic cardiac catheterization for ventricular septal defect between July 2010 and March 2019. The composite outcome was the occurrence of severe complications, including catecholamine use and intensive care unit admission, within seven days after catheterization. Overlap weighting based on propensity scores was used to adjust for patient- and hospital-level confounding factors. We identified 3159 patients from 87 hospitals, including 930 under general anesthesia and 2229 under sedation. The patient- and hospital-level baseline characteristics differed between the groups. After adjustment, the proportion of patients with severe complications was significantly higher in the general anesthesia group than in the sedation group (2.4% vs. 0.6%; risk difference, 1.8% [95% confidence interval, 0.93–2.6%]). Severe complications occurred more frequently in the general anesthesia group than in the sedation group. Further research on anesthetic methods is necessary to assess the safety and accuracy of pediatric diagnostic cardiac catheterization.博士（医学）・甲第867号・令和5年3月15