DOI： 10.1101/2022.08.08.502718

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

No head-to-head postmarket surveillance study has compared the differences in adverse events (AEs) between two combination therapies, axitinib (AXI) + pembrolizumab (PEMBRO) and lenvatinib (LEN) + PEMBRO, against metastatic renal cell carcinoma. This study aims to highlight the comprehensive differences in AEs between these two therapies based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. In total, 28 937 records were extracted from the FAERS database, and 139 AEs grouped into the System Organ Class according to the Medical Dictionary for Regulatory Activities were analysed. Logistic regression analyses were performed, and the reporting odds ratio with a 95% confidence interval was determined. We found that the incidences of cardiac and hepatobiliary disorders for AXI + PEMBRO, and blood and lymphatic system, metabolism and nutrition, and vascular disorders for LEN + PEMBRO, all of which were associated with serious AEs, were higher than those for LEN + PEMBRO and AXI + PEMBRO, respectively. The differences in the AEs between AXI + PEMBRO and LEN + PEMBRO were not derived merely from those between AXI and LEN monotherapies. Furthermore, remarkable AE potentiation was observed for AXI + PEMBRO. As FAERS is a spontaneous reporting system comprising partially limited information, analysing more detailed relationships between AEs and patient or treatment characteristics was challenging in this study. The present study is the first to show the overall real-world postmarketing differences in AEs between AXI + PEMBRO and LEN + PEMBRO. Our novel findings will substantially improve clinical practice; we recommend comparing patients' conditions associated with the above AEs when selecting between these two therapies. PATIENT SUMMARY: Herein, we highlight the differences in adverse events (AEs) between axitinib + pembrolizumab and lenvatinib + pembrolizumab therapies using data from the real-world Food and Drug Administration Adverse Event Reporting System database aimed at patients with metastatic renal cell carcinoma. We identified AEs that needed attention in each combination. We recommend the differences in AEs to be considered when selecting these two therapies.

DOI： 10.1016/j.euf.2022.07.003

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.

DOI： 10.1016/j.euf.2021.05.002

PubMed

researchmap

記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

我々が経験したロボット支援下前立腺全摘除術におけるインシデントを報告する.症例は70歳代男性.手術はda Vinci Xiで行われた.術中,1stポートのインストゥルメントを入れ替えた際に,モノポーラシザースよりチップカバーが外れ,紛失した.腹腔内や術野内外をX線透視も用いて探索するも見つからず,Computed tomographyを施行したところ,1stポート造設部の皮下に迷入していた.その後は手術を再開し,合併症なく終了.チップカバーは画像と同部位の皮下より摘出された.手術映像を見返したところ,チップカバーが適切に装着されておらず,インストゥルメント交換の際にトロッカーが皮下まで抜けていたことが判明した.本件のようなインシデントを予防するためには,チップカバーの適切な装着と,インストゥルメントの正しい手順での交換および交換時の確認が必要である.(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

TURBTは泌尿器科医にとって必須な手技であり,その良し悪しが患者の予後を規定するといっても過言ではない.加えて,TURBTは個体差によるバリエーションに富んでおり,初心者のみならず熟練者であってもその難しさを痛感する手術である.そのため,それぞれの症例に応じた戦略(根治的・姑息的・診断的切除の判断,切除の手順・方法等)をたてることが重要であり,加えて合併症対策をしっかりと行うこと,システム化された指導法を確立することが重要である.今回,初心に立ち返り当院における『合併症を回避するためのポイント』を整理した.術中合併症には穿孔や出血が挙げられる.高齢者,複数回のTUR歴やBCG治療歴などによる膀胱壁菲薄化が術中穿孔リスクとなる.出血は,術中の不十分な止血操作だけでなく,抗血小板薬・抗凝固薬の内服もリスクとなる.これらの薬剤継続による出血のみならず,休薬に伴う血栓症リスクを術前に評価することも重要である.術後合併症には前立腺肥大症などによる尿道カテーテル抜去後尿閉による穿孔がある.これらの合併症対策として,1.術前に画像検査で筋層浸潤の有無を判断し,症例に応じた戦略作成をたてること,2.抗血小板・抗凝固薬の継続,中止の取り扱いを検討すること,3.システム化された指導を行うこと,が重要である.これらのポイントについて,当科で実践している手技,術前戦略が功を奏した症例などを提示しながら解説する.(著者抄録)

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP). METHODS: We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term (<6 months) or long-term (≥6 months) neoadjuvant ADT before RP. RESULTS: Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93-1.51, p = 0.17), metastasis (OR 0.73, 95% CI, 0.45-1.19, p = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43-1.21, p = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39-0.80, p = 0.001, and OR 1.48, 95% CI 1.10-1.99, p = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00-3.93). CONCLUSION: Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.

DOI： 10.1080/21681805.2022.2034941

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

我々が経験したロボット支援下前立腺全摘除術におけるインシデントを報告する.症例は70歳代男性.手術はda Vinci Xiで行われた.術中,1stポートのインストゥルメントを入れ替えた際に,モノポーラシザースよりチップカバーが外れ,紛失した.腹腔内や術野内外をX線透視も用いて探索するも見つからず,Computed tomographyを施行したところ,1stポート造設部の皮下に迷入していた.その後は手術を再開し,合併症なく終了.チップカバーは画像と同部位の皮下より摘出された.手術映像を見返したところ,チップカバーが適切に装着されておらず,インストゥルメント交換の際にトロッカーが皮下まで抜けていたことが判明した.本件のようなインシデントを予防するためには,チップカバーの適切な装着と,インストゥルメントの正しい手順での交換および交換時の確認が必要である.(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J07650&link_issn=&doc_id=20220531400028&doc_link_id=%2Fcs5robot%2F2022%2F003501%2F032%2F0168-0172%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcs5robot%2F2022%2F003501%2F032%2F0168-0172%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本臨床腎移植学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.

DOI： 10.3390/genes13020285

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IVYSPRING INT PUBL  

Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME). Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2. Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities. Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC.

DOI： 10.7150/jca.66922

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

OBJECTIVES: To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. METHODS: In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. RESULTS: In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). CONCLUSIONS: The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.

DOI： 10.1111/iju.14679

PubMed

researchmap

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/iju.14679

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants.

DOI： 10.18926/AMO/62820

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

【目的】腹腔鏡下膀胱全摘除術(LRC)と開腹膀胱全摘除術(ORC)の長期制癌性を検討した本邦からの報告は少数である。当院におけるLRCとORCの周術期成績と長期治療成績を後方視的に比較検討した。【対象】2012年5月から2018年6月までに施行した膀胱全摘症例のうち78例(LRC48例,ORC30例)とした。【結果】観察期間中央値はLRC群30ヵ月,ORC群43.5ヵ月であった。LRC群で男性が多く,回腸導管の割合が高かった。手術時間はLRC群で長く(p=0.038),推定出血量と輸血症例が少なかった(ともにp<0.001)。術後病理結果はLRC群でG2症例が少なかった(p=0.008)が,断端陽性率を含む他の結果に差はなかった。リンパ節郭清領域はORCで内外腸骨動脈分岐部以下,LRCで総腸骨動脈分岐部以下を基本としたが,郭清リンパ節の数とリンパ節陽性症例の割合に差はなかった。LRC群とORC群の5年全生存率,癌特異生存率,無再発生存率は72.2%と54.4%(p=0.249),77.7%と63.4%(p=0.376),71.4%と55.0%(p=0.115)であった。【結語】当院におけるLRC群の周術期成績は出血量,輸血頻度においてORC群より優れていた。制癌性についてもORC群に比しLRC群が優れている傾向を認め,リンパ節郭清領域が制癌性に影響する報告を裏付ける結果となった。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

DOI： 10.18926/AMO/62810

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：英語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. METHODS: We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. RESULTS: From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. CONCLUSIONS: We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.

DOI： 10.1016/j.urolonc.2021.02.029

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To determine the impact of sarcopenia on erectile functional outcomes after a nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) using patient-reported validated questionnaires. MATERIALS AND METHODS: In this retrospective study, RARP was performed on 841 patients at Okayama University Hospital, of which 132 underwent NS RARP. Erectile functional outcomes were assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) and the Expanded Prostate Cancer Index Composite before and 1, 3, 6, and 12 months after surgery. Automated measurement of skeletal muscle at L3 was achieved using volume analyzer software and normalizing for height (cm²/m²) to calculate skeletal muscle index (SMI). Patients who had an IIEF-5≤4 comprised the group with erectile dysfunction (ED), and those with an IIEF-5≤5 made up the non-ED group. RESULTS: This study enrolled 95 patients of median age 65 years with a preoperative IIEF-5 of 16. There were no significant differences between patients with and without sarcopenia among those with preoperative IIEF-5. Postoperatively, in the ED group, SMI and preoperative IIEF-5 were significantly lower than in the non-ED group. Multiple linear regression analysis revealed that (1) both SMI and preoperative IIEF-5 were independent predictors of ED, and (2) sarcopenia and preoperative IIEF-5 were predictors of ED at 12 months after NS RARP. CONCLUSIONS: Patients with sarcopenia can have worse erectile functional outcomes after NS RARP. Sarcopenia and a lower preoperative IIEF-5 score may be predictive of postoperative ED.

DOI： 10.5534/wjmh.200036

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.

DOI： 10.1016/j.dmpk.2021.100407

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18926/AMO/62782

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To examine anti-adhesion and anti-biofilm effects of a diamond-like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube. METHODS: Diamond-like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond-like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein-expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony-forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond-like carbon-coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein-expressing Pseudomonas aeruginosa. RESULTS: The smooth and carbon-rich structure of the intraluminal diamond-like carbon film remained unchanged after the experiments. The numbers of colony-forming units suggested lower adherence of green fluorescent protein-expressing Pseudomonas aeruginosa and Escherichia coli in the diamond-like carbon-coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein-expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond-like carbon-coated samples. Finally, biofilm formation on the diamond-like carbon-coated samples was lower until at least day 14 compared with the uncoated samples. CONCLUSIONS: Intraluminal diamond-like carbon coating on a silicone tube has anti-adhesion and anti-biofilm effects. This technology can be applied to urinary catheters made from various materials.

DOI： 10.1111/iju.14675

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

岡山大学病院にて2018年1月より2020年9月までの期間に単一術者にて連続的に行われたロボット支援膀胱全摘(以下:RARC)46症例体腔外尿路変更(以下:ECUD)(23例),体腔内尿路変更(以下:ICUD)(23例)の比較検討を行った.検討項目は手術時間,推定出血量,輸血率,リンパ節郭清個数,入院日数,血液生化学データ,術後合併症とした.尿路変更に要した時間はICUD群の方が有意に長かったが,入院期間はICUD群が有意に短かった.他の周術期成績はECUDと同等であった.術者の視点では良好な拡大視野,尿管導管吻合の精緻性,同一視野で手術の流れが途切れることなく継続できることがICUDのメリットではないかと考える.(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

骨盤臓器脱に対する治療として,2010年に経腟メッシュ手術が,2014年に腹腔鏡下仙骨腟固定術が保険収載され,泌尿器科医が骨盤臓器脱に対する治療を行うことも一般的になってきている.2020年4月の診療報酬改定により,新たにロボット支援腹腔鏡下仙骨腟固定術が保険収載された.腹腔鏡下仙骨腟固定術は,正確な剥離操作を要し,深部での縫合結紮操作を多用する手術であることなど,良性疾患に対する手術でありながら手技の難易度が比較的高い術式であると考えられる.これに対して手術支援ロボットを用いることで,手術の難易度が低減されること,手術成績が向上することが期待される.当院でも2020年8月よりロボット支援下仙骨腟固定術を導入した.ロボット支援下仙骨腟固定術のメリットやデメリット,導入の意義などについて,手術導入に向けた取り組みについて述べる.(著者抄録)

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human RAD17, as an agonist of checkpoint signaling, plays an essential role in mediating DNA damage. This hospital-based case-control study aimed to explore the association between RAD17 rs1045051, a missense sin-gle nucleotide polymorphism (SNP), and prostate cancer risk. Subjects were 358 prostate cancer patients and 314 cancer-free urology patients undergoing treatment at the Zhujiang Hospital of Southern Medical University in China. RAD17 gene polymorphism rs1045051 was evaluated by the SNaPshot method. Compared with the RAD17 gene polymorphism rs1045051 AA genotype, there was a higher risk of prostate cancer for the CC gen-otype (adjusted odds ratio [AOR] = 1.731, 95% confidence interval [95%CI] = 1.031-2.908, p = 0.038). Compared with the A allele, the C allele was significantly associated with the disease status (AOR = 1.302, 95%CI = 1.037-1.634, p = 0.023). All these findings indicate that in the SNP rs1045051, both the CC genotype and C allele may have a substantial influence on the prostate cancer risk.

DOI： 10.18926/AMO/62379

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

近年,去勢抵抗性前立腺癌(castration-resistant prostate cancer:CRPC)に対する治療の選択肢は増えてきているが,分子標的薬の一種であるPoly ADP-ribose polymerase(PARP)阻害剤や免疫治療剤(Immuno-oncology drug:IO剤)もその有用性が報告され始めている。PARP阻害剤は,本邦でも2020年12月にBRCA遺伝子変異陽性の遠隔転移を有する去勢抵抗性前立腺癌に対するオラパリブの使用が承認された。これはPROfound試験の結果に基づくもので,BRCA1/2またはATM遺伝子変異陽性のmCRPC症例に対して,オラパリブ群とエンザルタミドまたはアビラテロン群を比較した結果,無増悪生存期間の有意な延長が確認されたものである。IO剤に関する試験も多数行われており,抗PD-1抗体であるペムブロリズマブは,がん化学療法後に増悪した進行・再発の高頻度マイクロサテライト不安定性(MSI-high)を有する固形癌への適応が承認された。さらに米国では腫瘍変異量の多い(TMB-h)進行固形癌に対する適応が追加承認された。遺伝子レベルで患者個別の特性に合わせた加療を行うプレシジョンメディシンとしてのPARP阻害剤やIO剤は今後のmCRPC治療において重要な役割を担うと考えられる。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

CASE PRESENTATION: A 49-year-old Asian male, who had undergone hemodialysis for >16 years, complained of a fever, dysgeusia and dysosmia, and was diagnosed with COVID-19 pneumonia based on severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS-CoV-2 PCR) and computed tomography (CT). Treatment was started with oral favipiravir and ciclesonide inhalation. On the 10th day of treatment, the patient had a persistent high fever and a chest CT showed exacerbation of pneumonia, so dexamethasone was intravenously started. He was discharged after confirming two consecutive negative SARS-CoV-2 PCR tests. Three months after COVID-19 treatment, a SARS-CoV-2 PCR test was negative and he underwent a deceased donor kidney transplantation. Basiliximab induction with triple drug immunosuppression consisting of extended-release tacrolimus, mycophenolate mofetil and prednisolone, which is our regular immunosuppression protocol, was used. He was discharged on postoperative day 18 without the need for postoperative hemodialysis or any complications. The serum creatinine level was 1.72 mg/dL 95 days postoperatively and he had a favorable clinical course that was similar to deceased donor kidney recipients without a history of SARS-CoV-2 infection. CONCLUSION: We report the first case of a kidney transplantation after COVID-19 treatment in Japan and the fourth case globally. We would like to provide information about our successful case due to the anticipated increase in similar candidates in the near future.

DOI： 10.1016/j.jiac.2021.03.018

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. METHODS: We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. RESULTS: The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. CONCLUSION: ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.

DOI： 10.1016/j.transproceed.2021.03.043

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4111/icu.20200450

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21873/anticanres.15029

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase (PDE) 5 inhibitor, tadalafil. METHODS: Wild-type (WT) and eNOS knockout (eNOS-KO) mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with bovine serum albumin. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37° warm ischemia for 45 min. RESULTS: Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and Infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both WT and eNOS-KO mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of VCAM-1 and KIM-1 was partially prevented by tadalafil. CONCLUSIONS: Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.Supplemental Visual Abstract; http://links.lww.com/TP/C223.

DOI： 10.1097/TP.0000000000003803

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/iju.14469

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/IJN.S301552

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

症例は19歳,男性。抗菌薬投与で改善しない排尿障害,排尿時痛を主訴に前医を受診。MRIで前立腺のT1強調像,T2強調像ともに低信号で,造影効果を伴う膀胱内に突出する腫瘤を指摘され当院紹介となった。血液,尿検査では特記事項なく,尿培養,尿細胞診は陰性であった。PSAを含め腫瘍マーカーの有意な上昇を認めなかった。膀胱鏡検査では前立腺部尿道に約35mmの非乳頭状広基性腫瘍を認めた。造影CTでは前立腺部にMRI同様の所見を認め,リンパ節腫大及び遠隔転移は認めなかった。排尿障害改善及び組織検査目的に経尿道的前立腺切除術(TUR-P)を施行した。切除組織は長紡錘形細胞の束状の増殖とリンパ球,形質細胞浸潤を認め,免疫染色でALK(anaplastic lymphoma kinase)陽性,α-smooth muscle actinが少数の細胞で陽性であり,前立腺炎症性偽腫瘍(inflammatory pseudtumor:IPT)と診断した。局所再発の可能性はあるものの,遠隔転移の可能性は低く,排尿状態の改善を得られたため経過観察の方針とした。術後10ヵ月現在で腫瘍の再燃を認めていない。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

症例は45歳,男性。X-1年9月に肉眼的血尿と右腰痛を主訴に当院を受診し,単純CTで右腎上極に長径5cm大の腫瘤を認めた。腹部造影CTでは動脈相で早期濃染,後期相でwashout patternを伴う内部不整な腫瘤を同部位に認めたが,明らかなリンパ節・他臓器転移を認めなかった。右腎癌cT1bN0M0 Stage Iと診断し,同年10月に腹腔鏡下右腎摘除術を施行した。病理所見は,腫瘍細胞は淡明細胞や好酸性細胞が乳頭状・管状の構造を取り,細胞質に好酸性の核小体および核周囲明庭を認めた。Fumarate hydratase(FH)免疫染色陰性でFH欠損腎細胞癌と診断した。術後2ヵ月で多発骨転移を認め,International Metastatic RCC Database Consortium(IMDC) intermediate riskと判断し,イピリムマブ・ニボルマブ併用療法を開始した。4コース施行後,CT上新規の転移巣や転移巣の増大を認めなかった。遺伝学的検査でFH遺伝子の病的バリアントを認め,腎細胞癌の家族歴と合わせ,遺伝性平滑筋腫症-腎細胞癌症候群(hereditary leiomyomatosis and renal cell carcinoma syndrome;HLRCC)関連腎細胞癌と診断した。現在ニボルマブ単剤投与を継続中で,骨転移増悪や新規遠隔転移は認めていない。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

1例目は27歳,女性。CTで8cm大の左腎腫瘍を認め,左腎癌cT2aN0M0と診断し,腹腔鏡下左腎摘除術を施行した。病理所見でTFE3免疫染色陽性で,Xp11.2転座型腎癌と考えられた。術後24ヵ月で傍大動脈リンパ節転移をきたし,sunitinib,axitinib投与後,現在nivolumabを投与中である。2例目は32歳,女性。CTで2cm大の緩徐に造影される左腎腫瘍を認めた。腹腔鏡下左腎部分切除術を施行し,病理所見でTFE3免疫染色陽性,Xp11.2転座型腎細胞癌と考えられた。術後50ヵ月で,再発転移を認めていない。3例目は31歳,女性。CTで右嚢胞性腎腫瘍と転移性肝腫瘍を指摘された。PET-CTで肝臓,骨,子宮に多発転移を認め,肝転移巣を生検し,未分化の尿路上皮癌と診断された。Gemcitabine+Cisplatin+Paclitaxelによる抗癌化学療法を2コース施行後,転移巣の増大,新たな転移巣(頭蓋骨,乳腺)の出現を認めた。新規転移巣を摘出し,病理所見でTFE3免疫染色陽性,最終的にXp11.2転座型腎細胞癌と考えられた。Temsirolimus投与するも,病状悪化し,第221病日に死亡した。Xp11.2転座型腎癌は若年者に多いとされる。確定診断には遺伝子検査またはFISHが求められるが,今回の3症例では施行していない。TFE3免疫染色はXp11.2転座型腎癌が疑われる際に有用である。(著者抄録)

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12894-021-00819-2

PubMed

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

症例は30代,女性。過去に左腋窩皮膚生検で神経線維腫と診断され,特徴的な皮膚所見や家族歴などから神経線維腫症1型(NF-1;von Recklinghausen病)を疑われていたが放置していた。20XX年2月に右大腿部痛,背部痛を主訴に近医を受診しMRI,造影CTで約13cm大の後腹膜腫瘤を指摘され,L2神経根からの発生と脊柱管内の浸潤も疑われ,神経線維腫の疑いとして手術目的に当科紹介された。合同での手術が必要と考えられたため,整形外科に紹介しMRIガイド下生検で悪性末梢神経鞘腫瘍の可能性を示唆された。同年6月に腫瘍の動脈塞栓術施行後に右後腹膜腫瘍摘出術を施行し,病理結果から悪性末梢神経鞘腫瘍と診断された。術後10ヵ月現在再発認めず,外来通院中である。後腹膜原発腫瘍において悪性末梢神経鞘腫瘍は極めて稀な症例であり,有効な治療法は確立されていない。今回,後腹膜原発の悪性末梢神経鞘腫瘍の1例を経験したので,若干の文献的考察を加えて報告する。(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.

DOI： 10.1093/molehr/gaaa085

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/molehr/gaaa085

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyaa132

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of this study was to compare the prognostic value of pretreatment inflammation-based scoring systems in terms of overall survival (OS) and progression-free survival (PFS) in patients with germ cell tumors (GCTs) receiving bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: We evaluated 63 patients with GCTs retrospectively. The Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio, prognostic index, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index, and albumin-to-globulin ratio (AGR) were measured in all patients before chemotherapy. To assess the predictive ability of each scoring system, areas under the receiver operating characteristic curve were calculated, and multivariate analysis was performed to identify associations between the predictive scores and OS. RESULTS: Of all the inflammation-based scoring systems, the GPS had the greatest area under the curve (0.847) for predicting OS, followed by the PNI (0.829) and AGR (0.810). Kaplan-Meier analyses revealed that the GPS, PNI, and AGR were significantly associated with OS, whereas the GPS, PLR, and PNI were significantly associated with PFS. In the multivariate analysis, the GPS was an independent predictor of OS and PFS. CONCLUSIONS: We demonstrated that the GPS was the most valuable biomarker of OS and PFS in patients with GCTs.

DOI： 10.4111/icu.20200103

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/iid3.470

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7150/ijbs.63125

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語  

Persistent Müllerian duct syndrome can cause an inguinal hernia, although this is a rare occurrence; recurrent inguinal hernias can, in turn, cause ongoing groin pain. Management of groin pain plays an important role in patients' quality of life. We present our experience with a 43-year-old man who had a 2-week history of left-sided groin pain. The patient underwent laparoscopic surgery for a left inguinal hernia via the transabdominal preperitoneal approach. Right-sided cryptorchidism was noted during surgery, with a solid structure-thought to be a uterus-extending into the left inguinal canal. The diagnosis was persistent Müllerian duct syndrome, and the groin pain was relieved after a laparoscopic right orchiectomy with a bilateral preperitoneal hernia repair using a mesh. Four years later, magnetic resonance imaging performed for new-onset left groin pain showed a left inguinal hernia caused by the uterine structure. We diagnosed the recurrent hernia as the cause of his pain. Prior to performing any invasive surgical procedures, an iliohypogastric nerve block was performed using 1% lidocaine. Short-term analgesia was provided by the block, improving his quality of life. He has been followed since then and has declined surgical neurectomy. An iliohypogastric nerve block can be an effective method of controlling groin pain caused by an inguinal hernia resulting from persistent Müllerian duct syndrome; the effectiveness of the nerve block will help determine whether surgical neurectomy is indicated for permanent pain control.

DOI： 10.1155/2021/7577632

PubMed

researchmap

記述言語：日本語   出版者・発行元：腎移植・血管外科研究会  

researchmap

記述言語：日本語   出版者・発行元：腎移植・血管外科研究会  

1.岡山大学の腎移植の背景・歴史 岡山大学泌尿器科は2009年に新しい腎移植プログラムを立ち上げ総計144例となった.成績も1年生存・生着率100%を維持している.2.人材確保 医局員の確保から始まる.3.育成 腎移植は幅広いテクニックが要求される.血管縫合糸は若手医師でも縫いやすく結紮もし易いGore-tex sutureを用いている.いい雰囲気でやることを心がけている.4.腎臓内科との連携 術前術後連携を取るため腎移植カンファレンスを月一回行い情報共有している.5.教室内での他の領域の医師との関係 腎移植チームのメンバーも腫瘍の手術やロボット手術を担当することによって腎移植のみに偏らない配慮をしている.6.働き方改革 移植前後の管理の簡略化に努めている.(著者抄録)

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

researchmap

記述言語：英語  

DOI： 10.18926/AMO/60806

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/iju.14382

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1089/hum.2020.156

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/luts.12312

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：日本語   出版者・発行元：(有)科学評論社  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7150/jca.47025

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00262-020-02498-8

PubMed

researchmap

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/iju.14210

researchmap

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/iju.14210

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study investigated the concordance between Gleason scores assigned to prostate biopsy specimens by outside pathologists and a urological pathology expert, and determined the risk of upgrading between opinion-matched Gleason grade group (GGG) 1 biopsy specimens and radical prostatectomy specimens. Between January 2012 and May 2018, 733 patients underwent robot-assisted radical prostatectomy. Patients whose original biopsy specimens from outside hospitals were reviewed by a urological pathology expert Okayama University Hospital were included. Patients who had received neoadjuvant hormonal therapy were excluded. Logistic regression analysis was used to identify predictors of upgrading among GGG 1 diagnoses. A total of 403 patients were included in the present study. Agreement in GGG between initial and second-opinion diagnoses was present in 256 cases (63.5%). Although opinion-matched cases improved concordance between biopsy and prostatectomy specimen GGG compared with single-opinion cases (initial, 35.2%; second-opinion, 36.5%; matched, 41.4%), 71% (56/79) of cases classified as GGG 1 were upgraded after prostatectomy. Multivariate analysis revealed that prostate-specific antigen density and Prostate Imaging Reporting and Data System version 2 score were significant predictors of upgrading (odds ratio, 1.10; P=0.01; and odds ratio, 1.88; P=0.03, respectively). In conclusion, the GGG concordance rate between needle-core biopsy and radical prostatectomy specimens was higher in opinion-matched cases; however, 71% of opinion-matched GGG1 cases were upgraded after robot-assisted radical prostatectomy. Urologists should propose treatment strategies or further biopsy rather than active surveillance for patients with GGG1 and a high PSAD and/or PI-RADS score.

DOI： 10.3892/mco.2020.1996

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Preemptive kidney transplantation (PEKT) is recognized as the best therapy to avoid dialysis. However, it is not clear whether PEKT recipients experience an improvement in quality of life (QoL) after kidney transplantation (KT) that exceeds that of non-PEKT recipients, since PEKT recipients have not experienced the heavy burden of dialysis. The aim of this study was to compare the changes in QoL for PEKT and non-PEKT recipients following transplantation. METHODS: Patients included in this study underwent living donor KT in our hospital. We excluded patients with incomplete SF-36 scores and with factors that could affect QoL, such as complications or rejection. QoL was assessed by the Short Form 36-Item Health Survey version 2.0 preoperatively and 3 and 12 months postoperatively. RESULTS: Eighty-eight patients underwent living donor KT in our hospital. Twelve PEKT and 20 non-PEKT recipients were enrolled in this retrospective study. In the non-PEKT group, both the physical and mental domain scores dramatically improved from baseline at 3 months, and remained at a similar level at 12 months. In contrast, in the PEKT group, only 1 domain of the physical and mental score improved at 3 months, and the social functioning score gradually improved at 12 months. Although the mental component score showed significant improvement in the non-PEKT group, it did not change in the PEKT group. CONCLUSIONS: The improvement of QoL after transplantation is more evident in the non-PEKT group. PEKT recipients have less mental satisfaction than non-PEKT recipients.

DOI： 10.1016/j.transproceed.2020.01.042

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2214/AJR.19.22074

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the feasibility of robotic renal autotransplantation (RAT) in a porcine model to reduce invasiveness of RAT. Five pigs underwent robotic RAT using the da Vinci® robotic system. A robotic left nephrectomy was performed in all cases. Robotic RAT was performed on the left side in all but one case. Four ports were used. In 3 cases, the kidney was taken out through the GelPort® and irrigated on ice with Ringer's solution. In 2 cases, a complete intracorporeal robotic RAT was performed. An end-to-side anastomosis was performed between the renal vein and the external iliac vein and between the renal artery and the external iliac artery. Ureteroneocystostomy was also performed in 2 cases. All cases were performed robotically without open conversion. The median (IQR) console time was 3.1 (0.7) h, and the operative time was 3.8 (1.1) h. The estimated blood loss was 30 (0) ml. The warm ischemia time was 4.0 (0.2) min, and the cold ischemia time was 97 (17) min. Intracorporeal transarterial hypothermic renal perfusion was feasible in the 2 complete intracorporeal robotic RAT cases by using a perfusion catheter through a laparoscopic port. Robotic RAT has the potential to be a new minimally invasive substitute for conventional open surgery.

DOI： 10.18926/AMO/57953

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11701-019-00975-6

PubMed

researchmap

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>症例は65歳男性。糖尿病性腎症による末期腎不全に対する腎移植術前CTにて右蝶形骨洞に真菌を疑う軟部影を認めたが、無症候性であった。しかしながら、移植後の免疫抑制状態で劇症型になる可能性を考慮し、移植3カ月前に内視鏡下副鼻腔手術ESSにて糸状菌塊を除去（粘膜への真菌浸潤なし）、追加治療することなく経過は安定していた。 生体腎移植については妻をドナーとしたABO不適合（術前減感作療法としてRituximab 200mg/body×1、DFPP×2、PE×1を実施、免疫抑制剤はTac-ER、MMF、PSL、Basiliximabを使用）、経過は良好でPOD18に退院となった（ Cr 1.28mg/dl ）。 移植後2カ月が経過し、右顔面痛・頭痛が出現、近医で副鼻腔洗浄や抗菌薬投与を受けるも改善せず。β-Dグルカン 53pg/mlと異常高値、副鼻腔MRIでは一部骨への浸潤を疑う軟部影を認め、再度ESSを施行、紙様板は腐骨化を認めたが真菌塊を可及的に除去した。VRCZも併用・継続し、術後1カ月でβ-Dグルカンも正常化、現在、再燃を認めていない。 浸潤性副鼻腔真菌症は副鼻腔から眼窩，海綿状静脈洞，頭蓋内へ浸潤し致死的となり、全生存率は概ね50%と、予後不良とされる。今回、予防的にESSを先行したが、腎移植後、急性浸潤性に再燃した症例を経験したので、若干の文献的考察を加えて報告する。 </p>

DOI： 10.11386/jst.55.Supplement_387_3

CiNii Article

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S2666-1683(20)33968-9

researchmap

記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

researchmap

掲載種別：研究論文（学術雑誌）  

Purpose: The purpose of this study was to analyze the outcome of patients with Birt–Hogg–Dubé (BHD) syndrome who underwent percutaneous thermal ablation of renal cell carcinoma (RCC). Materials and methods: Six patients with genetically proven BHD syndrome who underwent one or more sessions of percutaneous thermal ablation for the treatment of RCC were included. There were 4 men and 2 women, with a mean age of 57.3 ± 7.5 [SD] years (range: 44–67 years). A total of 29 RCCs (1–16 tumors per patient) were treated during 20 thermal ablation sessions (7 with radiofrequency ablation and 13 with cryoablation). Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function. Results: Technical success was achieved in all ablation sessions (success rate, 100%). No grade 4 or 5 adverse events were observed. All patients were alive with no distant metastasis during a median follow-up period of 54 months (range: 6–173 months). No local tumor progression was found. The mean decrease in estimated glomerular filtration rate during follow-up was 10.7 mL/min/1.73 m2. No patients required dialysis or renal transplantation. Conclusion: Radiofrequency ablation and cryoablation show promising results for the treatment of RCCs associated with BHD syndrome. Percutaneous thermal ablation may be a useful treatment option for this rare hereditary condition.

DOI： 10.1016/j.diii.2019.06.009

Scopus

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡・ロボティクス学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.urolonc.2019.05.019

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. RESULTS: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. CONCLUSIONS: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

DOI： 10.1016/j.jiac.2019.05.011

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. MATERIALS AND METHOD: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. RESULTS: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. CONCLUSIONS: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.

DOI： 10.1016/j.urolonc.2019.05.021

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

S100A11, a member of the S100 family of proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in crosstalking between PDAC cells and surrounding fibroblasts in PDAC progression. An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation end products (RAGE) upon S100A11 binding and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinase kinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and its catalyzed production of prostaglandin E2 (PGE2), a strong chemoattractive fatty acid. The extracellularly released PGE2 from fibroblasts was required for the rise in cellular migration as well as infiltration of their adjacent PDAC cells in a coculture setting. Taken together, our data reveal a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway. The findings of this study will contribute to the establishment of a novel therapeutic antidote to PDACs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) through targeting the identified pathway.

DOI： 10.3727/096504019X15555408784978

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00345-019-02708-8

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/iju.14017

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jrr/rrz012

PubMed

researchmap

記述言語：英語  

DOI： 10.1002/iju5.12085

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)腎癌研究会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/luts.12245

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC.Methods Patients with symptomatic mCRPC, >= 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality.Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5).Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.

DOI： 10.1007/s10147-018-01389-4

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.urolonc.2019.01.018

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jiac.2018.11.013

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語  

DOI： 10.1111/iju.13907

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-018-1643-6

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.urology.2018.12.020

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyy166

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18926/AMO/56455

PubMed

researchmap

記述言語：英語   出版者・発行元：西日本泌尿器科学会  

Stage I期セミノーマの手術後には補助治療を行わず経過観察とするsurveillanceが現在の主流となっており、再発率は13〜20%と言われている。補助治療の有無によらず、再発の大半は手術後2年以内が占める。以降の再発は晩期再発と呼ばれ区別されているが、そのリスク因子は明確になっていない。手術後5年以降の再発は0.8%〜2.5%と報告されており、術後10年を超えての再発はさらに稀である。今回、我々は高位精巣摘除術14年後に発生したセミノーマ晩期再発を経験したので、若干の文献的考察を加え報告する。症例は40代、男性。右下腿浮腫、総腸骨リンパ節の腫大、骨盤内腫瘤を指摘され当科紹介受診した。患者は前医受診の14年前に右精巣腫瘍に対し高位精巣摘除術を行われており、セミノーマpT2N0M0 Stage IBとして術後6年間のフォローの後に終診となっていた。当科受診時にはLDH 667 U/l(120〜240U/l)、β-hCG 17.5mIU/l(&lt;0.5mIU/l)と高値を認め、骨盤内腫瘤生検によりセミノーマの再発と診断、救済化学療法としてBEP3コース、VeIP療法を3コース施行した。VeIP療法施行後、骨盤内残存腫瘤の切除を行った。摘出標本は壊死組織のみでviable cellは認めず、術後7ヵ月時点では局所再発、転移は認めていない。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01004&link_issn=&doc_id=20190222240009&doc_link_id=%2Fer9niuro%2F2019%2F008101%2F009%2F0045-0048%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2019%2F008101%2F009%2F0045-0048%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Programmed cell death protein 1 (PD-1) blockade is a promising therapeutic strategy against prostate cancer. Nitroxoline has been found to have effective anticancer properties in several cancer types. We investigated the efficacy of a combination therapy involving nitroxoline and PD-1 blockade in a prostate cancer mouse model. In our in vitro analysis, we found that nitroxoline inhibited the viability and proliferation of the mouse prostate cancer cell line RM9-Luc-PSA. Additionally, nitroxoline downregulated the expressions of phospho-PI3 kinase, phospho-Akt (Thr308), phospho-Akt (Ser473), phospho-GSK-3β, Bcl-2, and Bcl-xL. Nitroxoline also downregulated programmed death-ligand 1 (PD-L1) expression levels in prostate cancer cell line and tumor tissue. In our murine prostate cancer orthotopic model, nitroxoline plus PD-1 blockade synergistically suppressed tumor growth when compared with nitroxoline or PD-1 blockade alone, leading to reductions in tumor weight, bioluminescence tumor signals, and serum prostate-specific antigen levels. Furthermore, fluorescence-activated cell sorting analysis showed that the combination strategy significantly enhanced antitumor immunity by increasing CD44+CD62L+CD8+ memory T cell numbers and reducing myeloid-derived suppressor cell numbers in peripheral blood. In conclusion, our findings suggest that nitroxoline plus PD-1 blockade may be a promising treatment strategy in patients with prostate cancer.

DOI： 10.7150/ijbs.32259

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/mco.2019.1839

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18926/AMO/56380

PubMed

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

CiNii Article

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

Purpose: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. Methods: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. Results: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. Conclusions: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

DOI： 10.1007/s00345-018-2196-8

Scopus

researchmap

記述言語：英語   掲載種別：研究論文（大学，研究機関等紀要）  

DOI： 10.18926/AMO/56069

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/iju.13555

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index < 22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan-Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

DOI： 10.1007/s12032-018-1140-5

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-017-1176-0

Web of Science

researchmap

記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2018.36.6_suppl.214

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation experiment was performed to confirm the tumorigenicity. Furthermore, we used the model to assess conventional chemotherapeutic agent, docetaxel. The results showed that miPS-RM9CM cells exhibited increased resistance to docetaxel, however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608). Our current study demonstrates that CM from cultured RM9 cells play a crucial role in the determination of cell fate from miPSCs to cancer stem-like cells and provide a potentially valuable system for the study of CSCs.

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/mco.2018.1697

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

ObjectivesTo investigate the prevalence of fluoroquinolone-insusceptible and/or extended-spectrum beta-lactamase-producing Escherichia coli colonizing in the male rectum before transrectal prostate biopsy.
MethodsWe carried out a prospective cohort study of men undergoing transrectal prostate biopsy. CHROMagar Orientation originally supplemented with levofloxacin and CHROMagar Orientation/extended-spectrum beta-lactamase were used for detecting fluoroquinolone-insusceptible and extended-spectrum beta-lactamase-producing Escherichia coli. Rectal specimens were collected before prostate biopsy, and the results of cultures in the selective medium were compared with drug susceptibility measured by standard methods. Targeted prophylactic antimicrobials were administered to patients with drug-resistant Escherichia coli and the incidence of postoperative prostatitis was investigated. In the case of prostatitis, pathogens preoperatively isolated from the rectum and those from urine were compared using pulsed-field gel electrophoresis.
ResultsRectal colonization of fluoroquinolone-insusceptible or extended-spectrum beta-lactamase-producing Escherichia coli was detected in 217 of 694 (31.3%) and 85 of 640 (13.3%) participants, respectively. The sensitivity and specificity of fluoroquinolone-insusceptible selective media were 96.8% and 88.2%, respectively. A total of 618 participants underwent transrectal prostate biopsy, and postoperative acute prostatitis was observed in four of 618 (0.6%) participants. Escherichia coli strains isolated preoperatively from the rectum and postoperatively from urine were found to be identical.
ConclusionsThe present findings showed accuracy and performance of the selective media. Screening cultures before transrectal prostate biopsy using selective media seems to be helpful for guiding antibiotic prophylaxis and thus decreasing the rate of post-biopsy acute prostatitis.

DOI： 10.1111/iju.13447

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/beta-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)beta-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-beta-catenin (activated form of beta- catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/beta-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/beta-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/beta-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/beta-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-beta-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-beta-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-beta-catenin and inhibits Wnt/beta-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/beta-catenin signaling.

DOI： 10.3892/ol.2017.6833

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

We describe a 40-year-old living-donor renal-transplant recipient who underwent successful ureterolithotripsy. He had been on hemodialysis for &gt;15 years pre-transplant and underwent ureteroureterostomy along with the surgery. One year post-transplant, ultrasound examination demonstrated hydronephrosis, and CT showed a 6-mm ureteral calculus at the ureteroureterostomy site. No pain and no elevated serum creatinine were present. As the ureter was easily accessed, we performed a ureterolithotripsy, which would confirm whether a suture caused the calculus. Despite ureteral tortuosity, laser stone fragmentation succeeded. The calculus was completely removed with an antegrade guidewire. Mild postoperative ureteral stenosis resolved with a temporary ureteral stent without balloon dilation. Ureterolithotripsy is effective even in renal transplant recipients with ureteroureterostomy.

DOI： 10.18926/AMO/55445

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

DOI： 10.1111/jgh.13757

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1089/bio.2017.0076

PubMed

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

DOI： 10.3892/ol.2017.6548

Web of Science

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

A 38-year-old woman with a 2.7-cm left ureteral stenosis requiring chronic ureteral stent exchange elected to undergo robotic renal autotransplantation. Left ureteropelvic junction obstruction (UPJO) was also suspected. Robotic donor nephrectomy contributed to the fine dissection for desmoplastic changes. The kidney was removed through a Gelport and examined on ice. UPJO was not seen. An end-to-side robotic anastomosis was created between the renal and external iliac vessels. The console time was 507 min, and the warm ischemia time was 4 min 5 sec. She became stent-free. Robotic renal autotransplantation is a new, minimally invasive approach to renal preservation.

DOI： 10.18926/AMO/55313

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

We developed and validated a novel hTERT/CMV promoter element-driven gene expression cassette that can robustly enhance cancer-specific gene expression. The following gene expressional elements were located in tandem within the plasmid construct: [hTERT core promoter, cytomegalovirus (CMV) minimized promoter, RU5' sequence, an inserted gene, BGH polyA, hTERT enhancer]; this is hereafter referred to as the hT/Cm-R-hT construct. Using various human cancer cell lines and normal cells, the cancer-specific transcription of the green fluorescent protein (GFP) gene was examined by western blotting and fluorescence microscopy. Cancer-specific gene expression was robustly achieved in the hT/Cm-R-hT plasmid in comparison to the other control hT/Cm-driven construct. Notably, the expression level of GFP observed in the hT/Cm-RhT-driven construct was superior to that of the control plasmid with the conventional CMV promoter in HEK293 cells, which are known to possess higher hTERT activity than normal cells. We next examined the availability of hT/Cm-R-hT in detecting the target GFP expressing cancer cells from human peripheral blood mononuclear cells (PBMCs). The hT/Cm-R-hT plasmid successfully induced cancer-specific gene expression; the robust expression of GFP was observed in target HeLa cancer cells, whereas GFP was not visibly expressed in normal PBMCs. The plasmid allowed for the selective visualization of viable HeLa cancer cells in mixed cell cultures containing up to 10000-fold more PBMCs. These findings indicate that the hT/Cm-R-hT expressional system is a valuable tool for detecting viable cancer cells mixed with normal cells. The current system can therefore be applied to the in vitro detection of cancer cells that are disseminated in the blood and other types of body fluid in vivo. Since the current system can also be applied to other types of vectors, including virus vectors, this approach using the hTERT promoter-based construct is expected to become a valuable tool for enhancing cancer specific gene expression.

DOI： 10.3892/or.2017.5710

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objectives: Sexually transmitted infections due to Chlamydia trachomatis (C. trachomatis) are a worldwide public health problem. The aim of this study was to investigate the drug susceptibilities of C. trachomatis strains isolated from the urethra and pharynx of Japanese males.
Methods: Urethral and pharyngeal swabs were collected between 2013 and 2014 from Japanese males with urethritis. Using a McCoy cell line, 18 chlamydial strains were isolated from urethra in 18 patients and 7 from the pharynx in 7 of the 18 patients. The minimum inhibitory concentrations (MICs) of levofloxacin (LVFX) and azithromycin (AZM) were measured using the standard method of the Japanese Society of Chemotherapy.
Results: The MICs of LVFX and AZM against urethral chlamydial strains were 0.125-0.5 mu g/mL and 0.125-0.25 mu g/mL, respectively. In pharyngeal strains, the MICs of LVFX and AZM were 0.125-0.25 mu g/mL and 0.125-0.25 mu g/mL, respectively. In 7 patients with chlamydial strains isolated from both the urethra and pharynx, the MICs of LVFX between these strains were identical in 3 of 6 patients (no growth was observed for one pharyngeal strain), while the MICs of AZM between these strains were identical in all 6 patients (not performed for one patient).
Conclusions: Our data suggest that C. trachomatis strains isolated from the urethra and pharynx of Japanese males are susceptible to LVFX and AZM. Although measuring the MICs of chlamydial strains is labor intensive, it is a significant surveillance tool for treating chlamydial infections and preventing the spread of STIs. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.04.005

Web of Science

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3) overexpression, induced using an adenovirus (Ad)-REIC, has been revealed to have a dramatic therapeutic effect on multiple types of cancer. To achieve an improved therapeutic effect from Ad-REIC on cancer, our group previously developed an enhanced gene expression system, the C-TSC cassette [cytomegalovirus (CMV)-RU5' located upstream (C); another promoter unit composed of triple tandem promoters, human telomerase reverse transcriptase (hTERT), simian virus 40 and CMV, located downstream of the cDNA (TSC); plus a polyadenylation (polyA) signal]. When applied to the conventional Ad-REIC, this novel system induced the development of an enhanced product, Ad-C-TSC-REIC, which exhibited a noticeable anticancer effect. However, there were difficulties in terms of Ad-C-TSC-REIC productivity in HEK293 cells, which are a widely used donor cell line for viral production. Productivity of Ad-C-TSC-REIC was significantly reduced compared with the conventional Ad-REIC, as the Ad-C-TSC-REIC had a significantly higher ability to induce apoptotic cell death of not only various types of cancer cell, but also HEK293 cells. The present study aimed to overcome this problem by modifying the C-TSC structure, resulting in an improved candidate: A C-T cassette (C: CMV-RU5' located upstream; T: another promoter unit composed of a single hTERT promoter, located downstream of the cDNA plus a polyA signal), which demonstrated gene expression comparable to that of the C-TSC system. The improved adenovirus REIC/Dkk-3 product with the C-T cassette, named Ad-C-T-REIC, exhibited a higher expression level of REIC/Dkk3, similar to that of Ad-C-TSC-REIC. Notably, the vector mitigated the cell death of donor HEK293 cells, resulting in a higher rate of production of its adenovirus. These results indicated that Ad-C-T-REIC has the potential to be a useful tool for application in cancer gene therapy.

DOI： 10.3892/ol.2017.6201

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jvs.2016.09.039

PubMed

researchmap

記述言語：英語   出版者・発行元：CELL PRESS  

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147.

DOI： 10.18926/AMO/54982

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

We report the case of a 58-year-old Japanese man with bilateral synchronous renal cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69 mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic embolization was performed for the left tumor, and 1 month later, a right open partial nephrectomy was performed. No recurrence was observed during a 16-month follow-up, and the serum creatinine level has been stable. The prognosis of bilateral synchronous RCC is better than that of dialysis patients. The novel approach of combining cryoablation and partial nephrectomy can achieve good cancer control and renal function in bilateral RCC.

DOI： 10.18926/AMO/54989

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objectives: This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue.
Methods: The penetration of levofloxacin (LVFX) 500 mg or sitafloxacin (STFX) 100 mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500 mg (n = 9) or STFX 100 mg (n = 9) was administered orally 1 h before orchiectomy, and 0.5 g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed.
Results: The mean ratio of the epididymal concentration to the serum concentration was 1.48 +/- 0.45 for LVFX and 1.54 +/- 0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84 mu g/ml in serum and 14.1 mu g/g in epididymal tissue and area under the concentration-time curve for 24 h (AUC(24)) of 68.5 mu g h/ml in serum and 108.9 mu g h/g in epididymal tissue. For STFX, the Cmax was 1.22 mu g/ml in serum and 1.66 mu g/g in epididymal tissue, and the AUC24 was 9.58 mu g h/ml in serum and 13.1 mu g h/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed.
Conclusions: The results of this study suggest that oral administration of LVFX 500 mg or STFX 100 mg achieves effective epididymal concentrations for treatment of epididymitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.12.010

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（大学，研究機関等紀要）  

DOI： 10.18926/AMO/54976

PubMed

researchmap

掲載種別：研究論文（学術雑誌）  

© 2017 S. Karger AG, Basel. Introduction: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). Materials and Methods: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra-A nd perioperative complications were collected. Results: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. Conclusions: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

DOI： 10.1159/000460304

Scopus

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本インターベンショナルラジオロジー学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

researchmap

記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

DOI： 10.18632/oncotarget.15505

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/iju.13281

Scopus

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.111.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and nonADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

DOI： 10.18926/AMO/54823

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Background: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, beta-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria.
Objectives: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment.
Methods: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study.
Results: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 59 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial.
Conclusions: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

DOI： 10.1093/jac/dkw424

Web of Science

PubMed

researchmap

記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

Urethral diverticular clear cell adenocarcinoma in a female patient is extremely rare. This tumor sometimes displays a characteristic image on magnetic resonance imaging, surrounding the urethra like the prostate does in men. We report a patient with this tumor who underwent cystourethrectomy and ileal conduit diversion. We think that imaging studies could be useful to make the appropriate diagnosis. UROLOGY 99: e25-e26, 2017. (C) 2016 Elsevier Inc.

DOI： 10.1016/j.urology.2016.10.021

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. Materials and Methods: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. Results: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. Conclusion: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

DOI： 10.21873/anticanres.11321

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

We elucidate the fate of cases clinically suspected of carcinoma in situ (Cis) of the upper tract with serial ureteroscopy. Of 143 patients who underwent ureteroscopy for suspected upper tract urothelial carcinoma (UTUC) between January 2008 and February 2016, 12 cases with consistently positive urine cytology and poorly detectable upper-tract malignancies by imaging were reviewed. In these 12 patients, 19 ureteroscopy procedures (25 renal units) were performed. Vesical random biopsy was performed before the 1st ureteroscopy to exclude malignancy of the bladder in all 12 cases. Median follow-up was 42 (13-67) months. Positive biopsy results at the 1st ureteroscopy were obtained in 3 (25%) patients and all were diagnosed wth Cis of the upper tract. Two (17%) of 9 patients who were negative or inconclusive at the 1st ureteroscopy were finally diagnosed as UTUC, but plural ureteroscopy procedures were needed for the diagnoses in both. Carcinoma of the bladder appeared in 5 (42%) patients during follow-up, despite the earlier ruling out of vesical malignancy. Four (33%) of those 5 patients never developed upper-tract urothelial carcinoma during follow-up. Caution is required before undertaking radical surgery for cases clinically suspected of Cis of the upper tract. In our experience, only 42% of such patients developed UTUC; another 33% eventually developed carcinoma of the bladder without UTUC.

DOI： 10.18926/AMO/55205

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Purpose: To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment.
Material and methods: Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared.
Results: After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p =.01).
Conclusions: Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

DOI： 10.1080/13645706.2016.1249889

Web of Science

PubMed

researchmap

記述言語：英語  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10157-017-1454-1

PubMed

researchmap

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-017-1203-1

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

DOI： 10.1038/cgt.2016.53

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive.
In this study, we examined the roles of dynamin at the invadopodia of bladder cancer cells. Although all three dynamin isoforms (dynamin1, 2 and 3) are expressed in human bladder cancer cell line T24, only dynamin2 localizes to the invadopodia. Inhibition of dynamin2 function, using either RNA interference (RNAi) or the dynamin specific inhibitor Dynasore, caused defects in invadopodia formation and suppressed invasive activity of 124 bladder cancer cells. Structure-function analysis using dynamin2 deletion fragments identified the proline/arginine-rich domain (PRD) of dynamin2 as indispensable for invadopodia formation and invasiveness of 124 cells. Thus, dynamin2 contributes to bladder cancer invasion by controlling invadopodia formation in bladder cancer cells and may prove a valuable therapeutic target. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2016.10.063

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants.

DOI： 10.18926/AMO/54508

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pantreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied, Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

DOI： 10.1038/cgt.2016.31

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients.

DOI： 10.18926/AMO/54507

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10585-016-9801-2

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jiac.2016.04.004

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We compared the implant quality of intraoperatively built custom-linked (IBCL) seeds with loose seeds in permanent prostate brachytherapy. Between June 2012 and January 2015, 64 consecutive prostate cancer patients underwent brachytherapy with IBCL seeds (n = 32) or loose seeds (n = 32). All the patients were treated with 144 Gy of brachytherapy alone. Brachytherapy was performed using a dynamic dose calculation technique. Computed tomography/magnetic resonance imaging fusion-based dosimetry was performed 1 month after brachytherapy. Post-implant dose-volume histogram (DVH) parameters, prostate sector dosimetry, operation time, seed migration, and toxicities were compared between the IBCL seed group and the loose seed group. A sector analysis tool was used to divide the prostate into six sectors (anterior and posterior sectors at the base, mid-gland, and apex). V100 (95.3% vs 89.7%; P = 0.014) and D90 (169.7 Gy vs 152.6 Gy; P = 0.013) in the anterior base sector were significantly higher in the IBCL seed group than in the loose seed group. The seed migration rate was significantly lower in the IBCL seed group than in the loose seed group (6% vs 66%; P < 0.001). Operation time per seed was significantly longer in the IBCL seed group than in the loose seed group (1.31 min vs 1.13 min; P = 0.003). Other post-implant DVH parameters and toxicities did not differ significantly between the two groups. Our study showed more dose coverage post-operatively in the anterior base prostate sector and less seed migration in IBCL seed implantation compared with loose seed implantation.

DOI： 10.1093/jrr/rrw018

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

DOI： 10.1111/jgh.13259

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Upper urinary tract calculi are common; however, there is no recommended treatment selection for elderly patients. Ureteroscopic holmium laser lithotripsy (URS lithotripsy) is minimally invasive, and it provides a high stone-free rate (SFR) treatment for upper urinary tract calculi. Here, we retrospectively evaluated the surgical outcomes of URS lithotripsy after dividing the 189 cases into 3 groups by patient age: the '&lt; 65 group' (&lt; 65 years old, n=108), the '65-74 group' (65-74 years old, n=42), and the '&gt;= 75 group' (&gt;= 75 years old, n=39). The patients 'characteristics, stone status, and perioperative outcomes were assessed. The 65-74 group and the &gt;= 75 group had a significantly higher prevalence of hypertension compared to the &lt; 65 group. Compared to the &lt; 65 group, the 65-74 group had a significantly higher prevalence of hyperlipidemia, and the &gt;= 75 group had significantly higher the American Society of Anesthesiologists (ASA) scores. Despite these preoperative risk factors, SFR and postoperative pyelonephritis in the 65-74 group and the &gt;= 75 group were similar to those of the &lt; 65 group. In conclusion, URS lithotripsy is the preferred treatment for upper urinary tract calculi, even for elderly patients who have multiple preoperative risk factors.

DOI： 10.18926/AMO/54414

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m(2)) on day 1, 8, cisplatin (70mg/m(2)) on day 1, and paclitaxel (80mg/m(2)) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystoure-threctomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component.

DOI： 10.18926/AMO/54423

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

DOI： 10.1038/gt.2016.7

Web of Science

PubMed

researchmap

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

In minimally invasive partial nephrectomy (MIPN), it is important to preoperatively predict the degree of difficulty of tumor resection. When severe adhesions occur between the renal capsule and perinephric adipose tissue, detachment can be difficult. Preoperative prediction of adhesion is thought to be useful in the selection of surgical procedure. Subjects were 63 patients of a single surgeon who had received MIPN between April 2008 and August 2013 at Okayama University Hospital. Of these patients, this study followed 47 in whom the presence or absence of adhesions between the renal capsule and perinephric adipose tissue was confirmed using intraoperative videos. Data collected included: sex, BMI, CT finding (presence of fibroids in perinephric adipose tissue), comorbidities and lifestyle. Adhesion was observed in 7 patients (14.9). The mean operative time was 291.6min in the adhesion group, and 226.3min in the group without. The increased time in the adhesions group was significant (p&lt;0.05). Predictive factors were a positive CT finding for fibroid structure and comorbidity of hypertension (p&lt;0.05). In MIPN, difficulty of surgery can be affected by the presence of adhesion of the perinephric adipose tissue. Predicting such adhesion from preoperative CT is thus important.

DOI： 10.18926/AMO/54185

Web of Science

PubMed

researchmap

記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

0

DOI： 10.1016/S0016-5085(16)31025-3

Web of Science

researchmap

記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

DOI： 10.1016/S0016-5085(16)33891-4

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objectives: The aim of this study is to characterize the potential differences between male and female patients with acute pyelonephritis (AP) and to predict the severity of AP based on the length of hospital stay.
Methods: We conducted a retrospective medical chart review of 172 consecutive adult patients who were hospitalized in Tsuyama Central Hospital due to AP from January 2007 through June 2012. We analyzed the length of hospital stay by the proportional hazard model.
Results: A total of 172 patients were identified who were admitted to our hospital with a diagnosis of AP. Of them, 62% (106/172) were female. Except for urological malignancy, there was no significant difference between men and women in underlying disease. Out of 26 variables, univariate analysis in male showed that only urolithiasis (OR 1.75, p = 0.0294) was significantly associated with longer hospital stay, while septic shock (OR 3.18, P = 0.003), urological malignancy (OR 2.94, P = 0.002), age over 65 (OR 1.66, p = 0.018) and neurogenic bladder (OR 1.92, p = 0.014) were all associated with longer hospital stay in female patients.
Conclusions: This is the first report to identify the risk factors for prolonged hospital stay for the patients who were admitted with AP in the Japanese population. The risk factors causing prolonged hospital stay were totally different between males and females. Reviewing the medical history based on sex gender might enable a clinician to predict the severity of acute pyelonephritis during the initial evaluation. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2015.11.007

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein a (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.
Experimental Design: In this randomized, open-label, phase II study, patients ages &gt;= 18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1: 1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary end-points were overall survival (OS), immune response, and toxicity.
Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.
Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. (C) 2015 AACR.

DOI： 10.1158/1078-0432.CCR-15-1265

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

This multi-institutional retrospective analysis examined learning curves for dosimetric parameters and operation time after introduction of intraoperatively built custom-linked (IBCL) seeds. Data from consecutive patients treated with seed implantation before and after introduction of IBCL seeds (loose seed, n = 428; IBCL seed, n = 426) were collected from 13 centers. Dose-volume histogram parameters, operation times, and seed migration rates were compared before and after introduction of IBCL seeds. At the 1-month CT analysis, no significant differences were seen in dose to 90% of prostate volume between before and after IBCL seed introduction. No learning curve for dosimetry was seen. Prostate and rectal volume receiving at least 150% of prescription dose (V150 and RV150) were higher in the loose-seed group than in the IBCL-seed group. Operation time was extended by up to 10 min when IBCL seeds were used, although there was a short learning curve of about five patients. The percentage of patients with seed migration in the IBCL-seed group was one-tenth that in the loose-seed group. Our study revealed no dosimetric demerits, no learning curve for dosimetry, and a slightly extended operation time for IBCL seeds. A significant reduction in the rate of seed migration was identified in the IBCL-seed group.

DOI： 10.1093/jrr/rrv065

Web of Science

Scopus

PubMed

researchmap

掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japanese Society of Interventional Radiology  

DOI： 10.22575/interventionalradiology.1.1_1

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11), and 1.0 x 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 x 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199)

DOI： 10.1111/cts.12362

Web of Science

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

researchmap

記述言語：日本語   出版者・発行元：(株)日本医学館  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本性機能学会  

researchmap

記述言語：日本語   出版者・発行元：医学図書出版(株)  

researchmap

記述言語：英語  

DOI： 10.3892/or.2015.3770

researchmap

記述言語：英語  

DOI： 10.4137/CMO.S23252

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/gt.2014.100

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本泌尿器内視鏡学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The Wnt signaling pathway plays a crucial role in human cancer development, and axis inhibition protein 2 (Axin2) is a master scaffold protein involved in Wnt signaling. Axin2 negatively regulates Wnt signaling and acts as a tumor suppressor protein. The present study evaluated the association between the Axin2 single nucleotide polymorphism (SNP) rs2240308 [guanine (G)/adenine (A)] and the incidence of prostate cancer. In total, 103 patients with prostate cancer and 100 cancer-free control males were included in this case-control study, and were genotyped using the genomic DNA extracted from peripheral blood samples. The results revealed a higher incidence of prostate cancer in the subjects with the homozygous GG genotype and a reduced cancer incidence in the patients with the GA genotype of the rs2240308 SNP (G/A) in the Axin2 gene. T-he adjusted odds ratio for carriers with the GA genotype was 0.377 (95% CI, 0.206-0.688; P=0.001) and that for the AA genotype was 0.830 (95% CI, 0.309-2.232; P=0.712) compared with the GG genotype. Therefore, the GA genotype was found to exhibit a protective effect that decreased the risk of prostate cancer. To the best of our knowledge, this is the first study to demonstrate the significant association between this SNP (rs2240308, G/A) and the risk of prostate cancer. This association indicates the possibility that the variations in the Axin2 gene in this position may play a significant role in promoting the development of cancer in the prostate. We believe that the Axin2 SNP (rs2240308) could be a useful biomarker for the predisposition and early diagnosis of the disease.

DOI： 10.3892/ol.2014.2177

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HUMANA PRESS INC  

For expression of genes in mammalian cells, various vectors have been developed using promoters including CMV, EF-1 alpha, and CAG promoters and have been widely used. However, such expression vectors sometimes fail to attain sufficient expression levels depending on the nature of cargo genes and/or on host cell types. In the present study, we aimed to develop a potent promoter system that enables high expression levels of cargo genes ubiquitously in many different cell types. We found that insertion of an additional promoter downstream of a cargo gene greatly enhanced the expression levels. Among the constructs we tested, C-TSC cassette (C: CMV-RU5' located upstream; TSC: another promoter unit composed of triple tandem promoters, hTERT, SV40, and CMV, located downstream of the cDNA plus a polyadenylation signal) had the most potent capability, showing far higher efficiency than that of potent conventional vector systems. The results indicate that the new expression system is useful for production of recombinant proteins in mammalian cells and for application as a gene therapeutic measure.

DOI： 10.1007/s12033-014-9738-0

Web of Science

PubMed

researchmap

記述言語：英語  

DOI： 10.1038/hr.2014.38

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

DOI： 10.1111/jgh.12501

Web of Science

PubMed

researchmap

記述言語：日本語   出版者・発行元：(一社)日本移植学会  

researchmap

記述言語：日本語   出版者・発行元：医学図書出版(株)  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I-IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.

DOI： 10.3892/ol.2013.1777

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Gene expression systems with various promoters, including the cytomegalovirus (CMV) promoter, have been developed to increase the gene expression in a variety of normal and cancer cells. In particular, in the clinical trials of cancer gene therapy, a more efficient and robust gene expression system is required to achieve sufficient therapeutic outcomes. By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. We termed this novel gene expression cassette the super gene expression (SGE) system, and herein verify the utility of the SGE cassette for a replication-deficient adenoviral vector. We newly developed an adenoviral vector expressing the tumor suppressor, reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), based on the CMV promoter-driven SGE system (Ad-SGE-REIC) and compared the therapeutic utility of Ad-SGE-REIC with that of the conventional adenoviral vectors (Ad-CMV-REIC or Ad-CAG-REIC). The results demonstrated that the CMV promoter-SGE system allows for more potent gene expression, and that the Ad-SGE-REIC is superior to conventional adenoviral systems in terms of the REIC protein expression and therapeutic effects. Since the SGE cassette can be applied for the expression of various therapeutic genes using various vector systems, we believe that this novel system will become an innovative tool in the field of gene expression and gene therapy.

DOI： 10.3892/or.2013.2958

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

We report 3 patients with the rare complication of an indwelling urethral catheter misdirected into the ureter. This is the largest series to date. Patients were referred to us for a variety of reasons following exchange of their chronic indwelling urinary catheters. CT in all cases demonstrated the urinary catheters residing in the left ureter. The ages of the patients were 37, 67 and 81 years old. All patients suffered from neurogenic bladder. Two patients were female, one was male, and 2 of the 3 had a sensory disorder inhibiting their pain response. The catheters were replaced with open-end Foley catheters. Extensive follow-up CT scans were obtained in one case, demonstrating improvement of hydronephrosis and no evidence of ureteral stenosis. Cystoscopy in this patient demonstrated normally positioned and functioning ureteral orifices. Although the placement of an indwelling urethral catheter is a comparatively safe procedure, one must keep in mind that this complication can occur, particularly in female patients with neurogenic bladder. CT without contrast is a noninvasive, definitive diagnostic tool.

DOI： 10.18926/AMO/52144

Web of Science

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n = 217), focusing on a comparison of those undergoing conventional (n = 113) and modified ultradissection (n = 104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and D'Amico prognostic criteria distributions. The mean operative time was shorter (p &lt; 0.001) and the estimated blood loss was less (p &lt; 0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p &lt; 0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck.

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Objectives: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC).
Materials and Methods: We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines in vitro and A549 cells in vivo. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines.
Results: Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a nonmalignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells in vivo. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells.
Conclusion: Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC.

DOI： 10.1371/journal.pone.0087900