筋層浸潤性膀胱癌における壁浸潤長は予後予測因子であり、血清cell-free DNAと関連する

Background: We investigated the potential of the depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC). Moreover, we examined the association between the preoperative levels of circulating cell-free DNA and DOI.博士（医学）・甲第876号・令和5年3月15

無症候性腎機能障害が結腸癌術後の臨床経過に及ぼす影響

Purpose: To evaluate the effect of mild renal dysfunction on the clinical course after colectomy in patients with colon cancer. Methods: The subjects of this retrospective study were 263 patients who underwent surgical resection for colon cancer at our hospital between 2011 and 2015. Renal function was assessed based on preoperative estimated glomerular filtration rate (eGFR) values. Patients were divided into groups based on their eGFR value of 55 ml/min/1.73 m2. The Mann-Whitney U test, chi-square or Fisher exact test, and log-rank test were used in the data analysis. Results: There were 59 patients (22.4%) in the low eGFR group and 204 patients in the normal eGFR group. There were differences between the groups in age, comorbidities, and the levels of hemoglobin, albumin, and serum creatinine. The overall postoperative complication rate, frequency of severe complications, and length of stay were significantly higher in the low eGFR group than in the normal eGFR group. Multivariate analysis revealed that low eGFR was the only independent risk factor for severe complications (Clavien-Dindo classification III/IV). There were no differences in survival between the groups. Conclusion: Preoperative asymptomatic renal dysfunction may be correlated with the development of postoperative complications and a possible significant risk factor for severe complications after colon cancer surgery.博士（医学）・甲第804号・令和3年12月21日© 2021. Springer Nature Singapore Pte Ltd.The version of record of this article, first published in Surgery Today, is available online at Publisher’s website: http://dx.doi.org/10.1007/s00595-021-02363-w.発行元が定める登録猶予期間終了の後、本文を登録予定（2021.01

膀胱癌細胞株において、ヘパラナーゼを阻害することにより、細胞浸潤、遊走、接着能を抑制する

Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer.博士（医学）・乙第1506号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Syndecan-1を介したmicroRNA-126および149は前立腺癌における細胞増殖を制御する

MicroRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by miR-126 and miR-149 is essential for syndecan-1-mediated development of androgen-refractory prostate cancer.博士（医学）・乙第1358号・平成27年5月28日Copyright © 2014 Elsevier Inc