Curriculum Vitaes
Profile Information
- Affiliation
- Joint Research Laboratory of Clinical Medicine , Fujita Health University
- Degree
- 医学博士(岐阜大学医学部医学系研究科)
- J-GLOBAL ID
- 201801019612715115
- researchmap Member ID
- B000294073
Research Interests
3Research Areas
1Research History
4-
Apr, 2022 - Present
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Jan, 2020 - Mar, 2022
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May, 2003 - Dec, 2019
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Dec, 2015 - Nov, 2017
Education
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Apr, 2009 - Mar, 2013
Committee Memberships
4Papers
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The Prostate, Sep 15, 2024BACKGROUND: Androgen receptor signaling inhibitors(ARSIs) have been used to treat patients with metastatic prostate cancer (PC) and castration-resistant prostate cancer (CRPC). In this study, we aimed to identify novel serum extracellular vesicle (EV)-based biomarkers to diagnose ARSI-resistance and therapeutic targets for ARSI-resistant CRPC. METHODS: Total RNA contained in serum EVs from 5 cases of CRPC before ARSI treatment and after acquiring ARSI-resistance was subjected to RNA-sequencing. The expression changes of selected RNAs contained in EVs were confirmed in 48 cases of benign prostatic hyperplasia (BPH) and 107 PC using reverse transcription-quantitative PCR (RT-qPCR) and compared with tissue RNA expression using public datasets. RESULTS: RNA-sequencing revealed that mitochondrial oxidative phosphorylation (OXPHOS)-related genes were increased in EVs after acquiring ARSI-resistance. Among them, RT-qPCR and datasets analysis demonstrated that SDHB mRNA was upregulated after acquiring ARSI-resistance in EVs and ARSI-exposed PC tissue compared to ARSI-naïve EVs and tissue, respectively. SDHB mRNA levels both in EVs and tissue were increased in localized PC compared with BPH and decreased in advanced PC. Tissue expression of SDHB mRNA was significantly correlated with those of other OXPHOS-related genes. SDHB mRNA in EVs (EV-SDHB) was elevated among 3 out of 7 ARSI-treating patients with stable PSA levels who later progressed to ARSI-resistant CRPC. CONCLUSIONS: The levels of OXPHOS-related mRNAs in EVs correlated with those in PC tissue, among which SDHB mRNA was found to be a novel biomarker to diagnose ARSI-resistance. EV-SDHB may be useful for early diagnosis of ARSI-resistance.
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Human cell, 37(5) 1559-1566, Sep, 2024Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.
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Non-coding RNA Research, 9(1) 76-83, Mar, 2024 Peer-reviewed
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Cancer Genomics - Proteomics, 20(5) 456-468, Aug 28, 2023
Misc.
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日本ミニマム創泌尿器内視鏡外科学会雑誌, 11(1) 91-94, Aug, 20192018年にロボット支援膀胱全摘除術が保険収載となったことにより、今後施行症例が増加すると思われる。しかし、膀胱全摘除術は、周術期合併症および死亡率とも未だ高い術式である。そのため、導入初期はプロクターによる指導や、適応の是非について慎重に検討する必要がある。一方尿変向術は、体腔内で尿路変向を行う。いわゆるICUDはあまり行われていない。ICUD普及のために、術式の標準化が必要と思われる。(著者抄録)
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JOURNAL OF UROLOGY, 197(4) E164-E164, Apr, 2017
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Emerging Infectious Diseases, 22(1) 142-144, Jan 1, 2016
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The Prostate, 75(14) 1568-78, Oct, 2015 Peer-reviewedBACKGROUND: The acquisition of drug resistance is one of the most malignant phenotypes of cancer and identification of its therapeutic target is a prerequisite for the development of novel therapy. MicroRNAs (miRNAs) have been implicated in various types of cancer and proposed as potential therapeutic targets for patients. In the present study, we aimed to identify miRNA that could serve as a therapeutic target for taxane-resistant prostate cancer. METHODS: In order to identify miRNAs related to taxane-resistance, miRNA profiling was performed using prostate cancer PC-3 cells and paclitaxel-resistant PC-3 cell lines established from PC-3 cells. Microarray analysis of mRNA expression was also conducted to search for potential target genes of miRNA. Luciferase reporter assay was performed to examine miRNA binding to the 3'-UTR of target genes. The effects of ectopic expression of miRNA on cell growth, tubulin polymerization, drug sensitivity, and apoptotic signaling pathway were investigated in a paclitaxel-resistant PC-3 cell line. RESULTS: The expression of miR-130a was down-regulated in all paclitaxel-resistant cell lines compared with parental PC-3 cells. Based on mRNA microarray analysis and luciferase reporter assay, we identified SLAIN1 as a direct target gene for miR-130a. Transfection of a miR-130a precursor into a paclitaxel-resistant cell line suppressed cell growth and increased the sensitivity to paclitaxel. Lastly, ectopic expression of miR-130a did not affect the polymerized tubulin level, but activated apoptotic signaling through activation of caspase-8. CONCLUSIONS: Our results suggested that reduced expression of miR-130a may be involved in the paclitaxel-resistance and that miR-130a could be a therapeutic target for taxane-resistant prostate cancer patients.
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Urology case reports, 3(5) 138-40, Sep, 2015 Peer-reviewedA 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).
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Hinyokika kiyo. Acta urologica Japonica, 60(12) 615-20, Dec, 2014 Peer-reviewedThe management of urinoma after blunt renal trauma is still controversial, ranging from percutaneous drainage or ureteral stent placement for the symptomatic urinoma and waiting for spontaneous vanishment of the asymptomatic urinoma. We present two cases of symptomatic urinoma and a case of asymptomatic urinoma after renal laceration. All patients underwent selective renal arterial embolization for vascular complications, including active bleeding, pseudoaneurysm and arteriovenous fistula. Urinomas, which had been observed in all cases gradually reduced and vanished 1-24 months later. All cases were successfully managed without catheterization or percutaneous drainage for urinoma.
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Anticancer research, 34(7) 3419-23, Jul, 2014 Peer-reviewedBACKGROUND/AIM: Exosomes have been demonstrated to be useful non-invasive biomarkers for several cancers including prostate cancer. Since normal cells also secrete exosomes, isolation of cancer-derived exosomes from blood is a prerequisite for their better understanding. The aim of this study is to establish the method for isolation of prostate cancer-related exosomes from blood. MATERIALS AND METHODS: Exosomes were collected from prostate cancer LNCaP and PC-3 cell lines by ultracentrifugation and by using magnetic beads conjugated with anti-CD9 antibody and anti-prostate-specific membrane antigen (PSMA) antibody. Prostate cancer-related exosomes were also isolated from the plasma of prostate cancer patients by anti-PSMA beads. Isolated exosomes were analyzed by western blotting. RESULTS: Exosomes were isolated from LNCaP cells by ultracentrifugation, contained PSMA and androgen receptor (AR). AR was also detected in exosomes isolated from LNCaP cells by anti-PSMA and anti-CD9 beads, showing that AR is present in prostate cancer-related exosomes. The amount of CD9 in isolated exosomes was much higher in advanced and chemo-resistant prostate cancer patients than in prostate cancer patients without metastasis and healthy volunteers, indicating that patients with aggressive prostate cancer exhibit higher levels of prostate cancer-related exosomes in blood. CONCLUSION: The immunoaffinity-based method we developed is capable of isolating prostate cancer-related exosomes from blood, the use of which will enhance investigation processes on exosomes in prostate cancer.
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Hinyokika kiyo. Acta urologica Japonica, 57(7) 363-6, Jul, 2011 Peer-reviewedWe retrospectively reviewed the records of 35 patients with penile cancer, who had been treated at Gifu University Hospital and its affiliated hospitals between July 1994 and January 2009. The mean values of follow-up periods, ages, serum squamous cell carcinoma levels and maximum diameters of the tumor were 23.7±28.0 months, 72.3±10.5 year-old, 4.5±4.3 ng/ml, and 4.0±2.6 cm, respectively. Systemic chemotherapy and local radiotherapy were performed in six, and three cases, respectively. Ten patients died of penile cancer. By univariate analyses, maximum tumor diameter (<- 4.3 cmvs >4.3 cm), T factor (<T3 vs >- T3) and N factor (<N2 vs >- N2) were significantly associated with cancer-specific survival. The five-year survival of stage N2 cases (28.6%) were significantly lower than that of stage N0 and N1 cases (68.4%) (p=0.0003). By multivariate analyses N factor (<N2 vs >- N2) was significantly associated with cancer specific survival (p=0.020). We concluded that the development of effective systemic chemotherapy might be crucial to improve the prognosis of patients with metastatic diseases.
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Hinyokika kiyo. Acta urologica Japonica, 53(2) 117-9, Feb, 2007 Peer-reviewedA 56-year-old Japanese man consulted a urologist because of urethral bleeding. He had been undergoing hemodialysis for the past 15 years due to polycystic kidney disease. Computed tomography revealed an irregular cyst wall in the left kidney. Since a neoplasm could not be ruled out, we removed the left kidney, by laparoscopic radical nephrectomy after obtaining the patient's consent. Histopathologic diagnosis was renal cell carcinoma. Fourteen months after the operation, urethral bleeding recurred. Further examination of the bladder and the urethra revealed no significant abnormalities. The patient insisted on right nephrectomy. Therefore, laparoscopic radical nephrectomy was performed. Histopathologic diagnosis was also renal cell carcinoma. Renal cell carcinoma in patients with end-stage renal disease is fairly common and is associated with acquired cystic kidney disease. However, renal cell carcinoma associated with polycystic kidney disease is extremely rare.
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Acta urologica Japonica, 51(9) 631-633, Sep, 2005
Research Projects
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2024 - Mar, 2027
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2023 - Mar, 2026
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科学研究費助成事業 基盤研究(C), 日本学術振興会, Apr, 2021 - Mar, 2024
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科学研究費助成事業 基盤研究(C), 日本学術振興会, Apr, 2021 - Mar, 2024
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Japan Society for the Promotion of Science, Apr, 2016 - Mar, 2019