Publications by authors named "Hideki Sakai"

494 Publications

A case of early recurrent immunoglobulin A nephropathy and T-cell-mediated rejection in a transplant patient with Wiskott-Aldrich syndrome.

CEN Case Rep 2021 Jul 25. Epub 2021 Jul 25.

Department of Nephrology, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Wiskott-Aldrich syndrome (WAS) is an X-chromosome recessive immunodeficiency disease characterized by the triad of thrombocytopenia, eczema, and susceptibility to infection owing to WAS protein gene abnormalities. Kidney transplantation is rarely offered to WAS patients with end-stage renal disease because of concerns that thrombocytopenia and immune disorders may affect the clinical outcome. Here, we report the case of a 20-year-old kidney transplant patient who developed end-stage renal disease owing to immunoglobulin (Ig)A nephropathy caused by WAS. Despite recurrent IgA nephropathy and T-cell-mediated rejection 7 months after transplantation, two rounds of steroid pulse therapy attenuated his renal function and urinary abnormality. His serum creatinine level was maintained at approximately 1.5 mg/dL 1 year after transplantation. No other WAS-related complications were observed throughout the clinical course. Although WAS can cause poor prognosis in kidney transplant patients, careful follow-up may allow kidney transplantation to be performed.
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http://dx.doi.org/10.1007/s13730-021-00631-9DOI Listing
July 2021

Surveillance of urachal abscess in the Kyushu-Okinawa area of Japan.

Int J Urol 2021 Jul 21. Epub 2021 Jul 21.

Department of Urology, Faculty of Medicine, Saga University, Saga, Japan.

Objective: To report a multicenter experience with the management of urachal abscess treatment in Japan.

Methods: This was a retrospective study of 263 cases of urachal abscess managed at 12 university hospitals in the Kyushu-Okinawa region over a 10-year period. Age, sex, abscess size, clinical symptoms, type of urachal remnants, and treatment were collected and analyzed.

Results: The average age was 29.8 ± 18.1 years, with males accounting for approximately two-thirds of the study population. The average abscess size was 1.7 cm (range 0-11 cm). The most common presenting symptom was umbilical secretion (66%), followed by abdominal pain (46%). A total of 127 patients (48.3%) were treated with antibiotics alone, whereas 136 patients (51.7%) received surgical treatment. The surgical approach was laparotomy in 75 patients (61.0%) and laparoscopic surgery in 48 patients (39.0%). Regarding the type of urachal remnant, the urachus sinus (180 patients) accounted for 68.4% of the total.

Conclusions: To our knowledge, this study represents the first report on urachal abscess treatment in Japan. Our data show that the clinical symptoms might vary depending on the type of urachus remnant. It should be noted that gross hematuria, a characteristic symptom of urachal cancer, is rare in patients with urachal abscess.
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http://dx.doi.org/10.1111/iju.14637DOI Listing
July 2021

Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer.

Anticancer Res 2021 Aug;41(8):3815-3823

Department of Pharmacy Practice, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background/aim: A previous report showed that immune complex-ceruloplasmin (CP) in urine is associated with carcinogenesis and malignant behavior in bladder cancer (BC). We investigated the pathological significance and prognostic roles of urine and tissue levels of CP protein in BC patients.

Materials And Methods: Urine CP levels were measured using an enzyme-linked immunosorbent assay in 97 patients. CP expression in BC tissues was evaluated by immunohistochemical analysis in 176 patient samples.

Results: Urine CP levels were positively associated with tumor grade and pT stage in non-muscle invasive BC (NMIBC). CP expression in BC tissues was positively associated with tumor growth and progression. Multivariate analysis demonstrated that high urine CP levels was an independent predictor of recurrence in the urinary tract in NMIBC (hazard ratio=2.87, p=0.016).

Conclusion: CP-related markers, especially urine CP levels, are useful biomarkers of malignant potential and prognosis in NMIBC.
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http://dx.doi.org/10.21873/anticanres.15174DOI Listing
August 2021

Intravesical injection of onabotulinumtoxinA in neurogenic overactive bladder patients with human T-cell leukemia virus type 1-associated myelopathy: A single-institution case series.

IJU Case Rep 2021 Jul 5;4(4):251-254. Epub 2021 May 5.

Department of Urology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.

Introduction: Neurogenic overactive bladder is a main feature of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis. We successfully performed intravesical onabotulinumtoxinA therapy for refractory neurogenic overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.

Case Presentation: We retrospectively reviewed four neurogenic overactive bladder patients with human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis who underwent bladder wall injections of onabotulinumtoxinA from April to October 2020. All patients were female. Their median age was 66 (range, 63-71) years. They were previously treated with β3-adrenergic receptor agonists or anticholinergic drugs alone or in combination for ≥12 weeks. However, insufficient results were obtained. After 4 weeks of intravesical onabotulinumtoxinA therapy, overactive bladder symptoms improved and maximum cystometric capacity increased in all cases.

Conclusion: Intravesical onabotulinumtoxinA therapy may be useful for treating refractory overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.
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http://dx.doi.org/10.1002/iju5.12301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255280PMC
July 2021

Impact of Doping a Phytosteryl Sulfate on the Properties of Liposomes Made of Saturated and Unsaturated Phosphatidylcholines.

J Oleo Sci 2021 Jul 9. Epub 2021 Jul 9.

Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science.

The size, dispersibility, and fluidity of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoy-2-oleoyl-sn-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) liposomes doped with β-sitosteryl sulfate (PSO) were comparatively studied. In all three types of liposomes, PSO reduced sizes and enhanced the negative values of the ζ-potential. However, the effect on sizes quantitatively differed in the three cases in a manner dependent on their phase behaviors. PSO rigidified each type of membrane in its liquid crystalline phase and fluidized the gel phase. It enhanced the glucose trapping efficiency (TE) of both DPPC and DOPC liposomes. The TE of DPPC first increased with the increasing concentration of PSO, then decreased gradually. On the other hand, in the case of DOPC, the TE increased significantly upon addition of PSO, then remained nearly constant. Though the exact dependence of TE on the PSO concentration differed in the two cases, its effect, in each case, was more than the effect of β-sitosterol (POH). The ability of PSO for reducing the size and enhancing dispersibility and TE of liposomes can be useful for preparing cosmetics and pharmaceutical formulations.
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http://dx.doi.org/10.5650/jos.ess21035DOI Listing
July 2021

Stage-specific Embryogenic Antigen-4 Expression in Castration-resistant Prostate Cancer and its Correlation With the Androgen Receptor.

Anticancer Res 2021 Jul;41(7):3327-3335

Department of Urology, University of the Ryukyus, Okinawa, Japan.

Background/aim: Stage-specific embryonic antigen (SSEA)-4 plays important roles in the malignant aggressiveness of various cancers. The aim of this study was to investigate the pathological characteristics of SSEA-4 in castration-resistant prostate cancer (CRPC).

Materials And Methods: SSEA-4 expression and its pathological roles were evaluated in five prostate cancer (PC) cell lines and 27 CRPC tissues. The relationship between SSEA-4 and the androgen receptor (AR) was also examined.

Results: SSEA-4 expression was detected in AR-negative cells (PC3, DU145, and AICaP1) but was not detected in AR-positive cells (LNCaP and AICaP2). SSEA-4 expression in human CRPC tissues was significantly higher than that in locally advanced or metastatic hormone sensitive PC (HSPC) tissues. A negative correlation was also detected between SSEA-4 and AR in CRPC tissues but not in HSPC tissues.

Conclusion: SSEA-4 was over-expressed in CRPC and the changes were mediated by complex mechanisms that related to the AR and hormonal therapy.
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http://dx.doi.org/10.21873/anticanres.15120DOI Listing
July 2021

Reliability and Validity of the Japanese Version of the Barthel Index Dyspnea Among Patients with Respiratory Diseases.

Int J Chron Obstruct Pulmon Dis 2021 21;16:1863-1871. Epub 2021 Jun 21.

Kobe University Graduate School of Health Sciences, Kobe, Hyogo, 654-0142, Japan.

Purpose: Japan has only a few respiratory disease-specific activity of daily living scales that are accepted outside of Japan, and they are not widely used. The Barthel Index dyspnea (BI-d), an improved version of the Barthel Index (BI), may be popular in Japan. The purpose of this study was to develop the Japanese version of BI-d (J-BI-d) and investigate its reliability and validity.

Patients And Methods: The J-BI-d was developed using the basic guidelines for scale translation. The study included patients with chronic respiratory disease, receiving outpatient care at two centers between January 2019 and February 2020. Scores on the J-BI-d, modified Medical Research Council scale (mMRC scale), BI, respiratory function tests, and 6-minute walk distance (6MWD) test were measured. To verify the test-retest reliability, the J-BI-d was re-administered, and the intraclass correlation coefficient (ICC) was obtained. Internal consistency was verified by Cronbach's alpha reliability coefficient, and criterion-related validity was verified through a correlation analysis of the J-BI-d with mMRC scale and 6MWD test. Divergent validity was verified through correlation analysis between the J-BI-d and BI.

Results: Data for 57 participants (mean age 74.4 ± 8.3 years) were analyzed, and reliability testing was performed with 42 of them. The mean time to retest was 8.1 ± 3.0 days, and the ICC (2, 1) was 0.76 (95% CI: 0.62-0.85), indicating high reliability. Cronbach's alpha reliability coefficient was 0.81, indicating high internal consistency. Correlation coefficients of the J-BI-d with 6MWD test (r = -0.46, p < 0.01) and mMRC scale ( = 0.76, p < 0.01) indicated high criterion-related validity. The J-BI-d and BI had a weak negative correlation (r = -0.29, p < 0.05), indicating high divergent validity.

Conclusion: The results of this study demonstrate high reliability and appropriate validity of the J-BI-d in patients with chronic respiratory disease.
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http://dx.doi.org/10.2147/COPD.S313583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232896PMC
June 2021

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study.

In Vivo 2021 Jul-Aug;35(4):2073-2080

Department of Pharmacy Practice, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background/aim: Little is known on urine biomarkers that are associated with malignant behavior in patients with bladder cancer (BC). Our aim was to identify BC-related factors in urine samples using our original method "immune complexome analysis", based on detecting the immune complex (IC).

Patients And Methods: Immune complexome analysis was performed using urine samples from 97 BC patients, including 67 with non-muscle invasive BC (NMIBC).

Results: Eight IC-antigens were recognized as candidates for BC-related factors from 20,165 proteins. IC-serum albumin, -fibrinogen γ chain, -hemoglobin subunit α, -hemoglobin subunit β, -ceruloplasmin, and fibrinogen β chain were significantly associated with either pathological features and/or outcome. IC-ceruloplasmin was most widely associated with pathological features in all BC patients and lamina propria invasion and urinary tract recurrence in NMIBC.

Conclusion: Based on detection of IC-antigens it was demonstrated that six IC-antigens, especially IC-ceruloplasmin, are potential urine biomarkers in BC.
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http://dx.doi.org/10.21873/invivo.12476DOI Listing
June 2021

Inhibition of gastric H,K-ATPase by new dihydropyrazole derivative KYY-008.

Biochem Biophys Res Commun 2021 Aug 21;567:177-182. Epub 2021 Jun 21.

Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.

The gastric proton pump (H,K-ATPase) responsible for the H secretion of gastric acid is an essential therapeutic target for acid-related diseases. H,K-ATPase belongs to a P-type ATPase family. Here, we examined the effects of a newly synthesized dihydropyrazole derivative KYY-008 on the H,K-ATPase. KYY-008 concentration-dependently inhibited the enzyme activity of the ATPase in the membrane fractions prepared from isolated hog gastric mucosa and from human kidney HEK293 cells in which gastric H,K-ATPase is exogenously expressed. The IC values in these samples were 3.4 μM and 3.7 μM, respectively. In addition, KYY-008 significantly inhibited the H,K-ATPase-derived H uptake into the tightly sealed vesicles prepared from the hog gastric mucosa. In contrast, KYY-008 has no effect on the activities of other P-type ATPases such as Na,K-ATPase and Ca-ATPase. KYY-008 did not change the ionic currents of voltage-dependent Ca channels, that were potential targets for some dihydropyrazole derivatives. Together, we discovered a new dihydropyrazole derivative which acts as a selective inhibitor of gastric H,K-ATPase.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.056DOI Listing
August 2021

Efficacy of propiverine hydrochloride for urinary incontinence after robot-assisted or laparoscopic radical prostatectomy.

Can J Urol 2021 Jun;28(3):10706-10712

Department of Urology and Renal Transplantation, Nagasaki University Hospital, Nagasaki, Japan.

Introduction: To clarify the efficacy and safety of propiverine hydrochloride for incontinence after robot-assisted laparoscopic prostatectomy (RALP)/laparoscopic radical prostatectomy (LRP), along with changes in the urethral pressure profile (UPP) and quality of life in patients treated with propiverine hydrochloride.

Materials And Methods: In this randomized, comparative study, 104 patients who were aware of urinary incontinence after RALP or LRP were assigned to receive propiverine hydrochloride (treatment group) or not (controls). Pad test results, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores, and UPP results [including maximum urethral closure pressure (MUCP) and functional urethral length (FUL)], were recorded immediately and at 6 months postoperatively.

Results: No serious intraoperative complications or adverse events were caused by propiverine hydrochloride. The pad-test negative rate was significantly greater in the treatment group than in controls (89.1% vs. 73.2%, p = 0.044). Changes in ICIQ-SF scores and MUCP were significantly greater in the treatment group than in controls [-6.5 vs. -4.5 points (p = 0.021), and +49.5 vs. +28.7 mmHg (p = 0.038), respectively]. FUL change did not significantly differ between groups [+4.5 vs. +3.8 mm (p = 0.091)]. In univariate logistic regression analyses, body mass index (BMI), MUCP, and treatment with propiverine hydrochloride were significantly associated with continence status. In multivariate analyses, BMI and MUCP were independently associated with continence status [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.047-1.530 (p = 0.015), and OR, 0.986; 95% CI, 0.973-0.999 (p = 0.042), respectively].

Conclusions: Treatment with propiverine hydrochloride alleviated urinary incontinence while improving patient symptoms and quality of life after RALP or LRP.
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June 2021

Age-associated bladder and urethral coordination impairment and changes in urethral oxidative stress in rats.

Life Sci 2021 Aug 7;279:119690. Epub 2021 Jun 7.

Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Aims: We examined age-associated changes in bladder and urethral coordination involving the nitric oxide (NO)/soluble guanylyl cyclase (sGC) system, which induces urethral smooth muscle relaxation, and urethral ischemic/oxidative stress changes in rats.

Main Methods: Sixteen female Sprague-Dawley rats were divided into young (3 months old) and middle-aged (12-15 months old) groups. Urethral activity was evaluated by simultaneously recording intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia. Sodium nitroprusside (SNP, 0.1 mg/kg), an NO donor, and BAY 41-2272, a novel NO-independent stimulator of sGC (0.1 mg/kg), were administered intravenously to both groups. N-nitro-l-arginine methyl ester hydrochloride (l-NAME, 100 mg/kg) was also injected intravenously, to inhibit NO synthase activity in both groups. Staining for the ischemic marker, hypoxia-inducible factor-1α (HIF-1α), and the oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), was performed on tissue sections of the urethra, in both groups.

Key Findings: Baseline UPP and UPP changes were significantly lower in middle-aged rats than in young rats. After administration of SNP and BAY 41-2272, baseline UPP and UPP nadir were significantly decreased in both groups. After administration of l-NAME, UPP change/bladder contraction amplitude in young rats was still lower than at baseline but was completely restored to control levels in middle-aged rats. Immunoreactivity of HIF-1α, 8-OHdG, and MDA was higher in middle-aged rats than in young rats.

Significance: Age-associated ischemic and oxidative stress in the urethra might be correlated with impairment of the NO/sGC system and with coordination of the bladder and urethra.
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http://dx.doi.org/10.1016/j.lfs.2021.119690DOI Listing
August 2021

Spontaneous intraperitoneal renal rupture with urinoma formation in the fetus.

Urol Case Rep 2021 Jul 5;37:101697. Epub 2021 May 5.

Department of Urology and Renal Transplantation, Nagasaki University Hospital, Nagasaki, Japan.

Spontaneous intraperitoneal renal rupture with urinoma formation in fetuses is an unusual condition that is caused by upper or lower urinary tract obstruction. We report the case of a neonatal male infant who presented with a spontaneous intraperitoneal right renal rupture accompanying ipsilateral ureterovesical junction obstruction (UVJO). Fetuses with UVJO accompanying contralateral multicystic dysplastic kidney should be observed carefully because of the risk of spontaneous renal rupture.
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http://dx.doi.org/10.1016/j.eucr.2021.101697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167486PMC
July 2021

Rheology of α-Gel Formed by Amino Acid-Based Surfactant with Long-Chain Alcohol: Effects of Inorganic Salt Concentration.

Langmuir 2021 06 3;37(23):7032-7038. Epub 2021 Jun 3.

Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Mixtures of surfactants, long-chain alcohols, and water sometimes yield lamellar gels with hexagonally packed alkyl chains. This assembly is called "α-gel" or "α-form hydrated crystal." In this study, we characterized the rheological properties of α-gel prepared using disodium -dodecanoylglutamate (C12Glu-2Na), 1-hexadecanol (C16OH), and water at different NaCl concentrations. The α-gel structure was assessed using small- and wide-angle X-ray scattering (SWAXS). The SWAXS measurements revealed that an increased NaCl concentration (0-200 mmol dm) resulted in a decreased -spacing caused by the screening of electrostatic repulsion between lamellar bilayers. This led to an increased amount of excess water (i.e., the water present between the α-gel domains), and hence, the viscosity of the α-gel decreased in the range of the NaCl concentration. A further increase in the NaCl concentration (200-1000 mmol dm) resulted in decreased electrostatic repulsion between the α-gel domains and/or an increased number of α-gel domains (multilamellar vesicles). These effects increased the domain-to-domain interactions, leading to increased viscosity. Therefore, we concluded that the viscosity of the α-gel was controlled by the amount of excess water and the domain-to-domain interactions. Once the network structure collapsed under the strain, it was difficult to recover the original network structure. The low recoverability resulted from increased cohesion between the domains at high NaCl concentrations.
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http://dx.doi.org/10.1021/acs.langmuir.1c00626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280742PMC
June 2021

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study.

Int J Clin Oncol 2021 Aug 26;26(8):1553-1560. Epub 2021 May 26.

Department of Medical Oncology, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan.

Background: Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols.

Methods: Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate.

Results: Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1-6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively.

Conclusion: This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.
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http://dx.doi.org/10.1007/s10147-021-01935-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286943PMC
August 2021

Rapid controlled release by photo-irradiation using morphological changes in micelles formed by amphiphilic lophine dimers.

Sci Rep 2021 May 24;11(1):10754. Epub 2021 May 24.

Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.

Photo-induced rapid control of molecular assemblies, such as micelles and vesicles, enables effective and on-demand release of drugs or active components, with applications such as drug delivery systems (DDS) and cosmetics. Thus far, no attempts to optimize the responsiveness of photoresponsive molecular assemblies have been published. We previously reported photoresponsive surfactants bearing a lophine dimer moiety that exhibit fast photochromism in confined spaces, such as inside a molecular assembly. However, rapid control of the micelle structures and solubilization capacity have not yet been demonstrated. In the present work, photo-induced morphological changes in micelles were monitored using in-situ small-angle neutron scattering (SANS) and UV/Vis absorption spectroscopy. An amphiphilic lophine dimer (3TEG-LPD) formed elliptical micelles. These were rapidly elongated by ultraviolet light irradiation, which could be reversed by dark treatment, both within 60 s. For a solution of 3TEG-LPD micelles solubilizing calcein as a model drug molecule, fluorescence and SANS measurements indicated rapid release of the incorporated calcein into the bulk solvent under UV irradiation. Building on these results, we investigated rapid controlled release via hierarchical chemical processes: photoisomerization, morphological changes in the micelles, and drug release. This rapid controlled release system allows for effective and on-demand DDS.
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http://dx.doi.org/10.1038/s41598-021-90097-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144387PMC
May 2021

Editorial Comment to Green-light laser en bloc resection versus conventional transurethral resection for initial non-muscle-invasive bladder cancer: A randomized controlled trial.

Int J Urol 2021 May 19. Epub 2021 May 19.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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http://dx.doi.org/10.1111/iju.14607DOI Listing
May 2021

Survival of detached cancer cells is regulated by movement of intracellular Na,K-ATPase.

iScience 2021 May 15;24(5):102412. Epub 2021 Apr 15.

Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.

Beginning of metastasis, cancer cells detach from the primary tumor and they can survive even under loss of anchorage; however, the detachment-elicited mechanisms have remained unknown. Here, we found that Na,K-ATPase α3-isoform (α3NaK) in human cancer cells is dynamically translocated from intracellular vesicles to the plasma membrane when the attached cells are detached and that this mechanism contributes to the survival of the detached (floating) cancer cells. α3NaK was detected in the plasma membrane of floating cancer cells in peritoneal fluids of patients, while it was in the cytoplasm of the cells in primary tumor tissues. On cancer cell detachment, we also found the focal-adhesion-kinase-dependent Ca response that induces the α3NaK translocation via nicotinic acid adenine dinucleotide phosphate pathway. Activation of AMP-activated protein kinase was associated with the translocated α3NaK in the plasma membrane. Collectively, our study identifies a unique mechanism for survival of detached cancer cells, opening up new opportunities for development of cancer medicines.
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http://dx.doi.org/10.1016/j.isci.2021.102412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099779PMC
May 2021

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer.

In Vivo 2021 May-Jun;35(3):1693-1701

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background/aim: The pathological significance of thrombospondin (TSP)-1 and -2 in bladder cancer (BC) is well-known whereas that of TSP-3, 4 and 5 remains unclear. Our aim is to clarify the pathological significance and prognostic roles of TSP-3 to 5 expression in BC patients.

Patients And Methods: TSP-3 to 5 expression, proliferation index (PI), apoptotic index (AI) and microvessel density (MVD) were evaluated in 206 BC patients by immunohistochemical techniques.

Results: TSP-5 expression was positively associated with grade, T stage, metastasis, and worse prognosis. PI in TSP-5-positive tissues was significantly higher compared to negative tissues. In contrast, AI in TSP-5-positive tissues was significantly lower compared to negative tissues. Expressions of TSP-3 and 4 were not associated with any clinicopathological features, survival, PI, or AI.

Conclusion: TSP-5 plays important roles in malignant behavior via cell survival regulation whereas the pathological significance of TSP-3 and TSP-4 in BC might be minimal.
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http://dx.doi.org/10.21873/invivo.12429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193323PMC
June 2021

Anion-π interaction at the solid/water interfaces.

Chem Commun (Camb) 2021 May;57(38):4650-4653

Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan and Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Anion-π interaction has been found to play a key role in interfacial phenomena. In this study, we evaluated the anion-π interactions at the solid/water interface. Anion adsorption originating from anion-π interaction at the interfaces followed the hydration energy and the presence of conjugated systems of the anions by the QCM measurements. Force curve measurements revealed that the single-molecule force of anion-π interaction between an NDI unit and the negatively charged surface of the cantilever was ∼40 pN. To the best of our knowledge, this is the first example of obtaining a single-molecule force for anion-π interactions.
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http://dx.doi.org/10.1039/d1cc01186cDOI Listing
May 2021

Efficacy of salt reduction for managing overactive bladder symptoms: a prospective study in patients with excessive daily salt intake.

Sci Rep 2021 Feb 18;11(1):4046. Epub 2021 Feb 18.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

This study aimed to investigate the efficacy of salt intake restriction on overactive bladder (OAB) symptoms in patients with excessive salt intake. Patients received a brochure on nutritional guidance regarding salt intake reduction and received health education every 4 weeks for 12 weeks. Data from overactive bladder symptom score (OABSS) questionnaires and frequency volume charts (FVCs) were evaluated. The daily salt intake was estimated by determining the urinary sodium and creatinine concentrations using spot urine samples. Of the 98 patients included, 71 (72.4%) successfully restricted their daily salt intake after 12 weeks (salt restricted [R] group), while 27 (27.6%) did not (salt non-restricted [N-R] group). The scores to each OABSS question and the resulting total score improved significantly in the R group; however, the individual scores remained unchanged and the total score increased in the N-R group. The FVC data indicated improved voided volumes in the R group as compared to in the N-R group. Ultimately, 17 (23.9%) patients in the R group no longer fulfilled the OAB diagnostic criteria after salt intake reduction. Thus, salt intake reduction improved urinary symptoms in patients with OAB and may be a therapeutic option for OAB in patients with excessive daily salt intakes.
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http://dx.doi.org/10.1038/s41598-021-83725-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893030PMC
February 2021

Adsorption of Hydrophilic Amine-Based Protic Ionic Liquids on Iron-Based Substrates.

J Oleo Sci 2021 Mar 12;70(3):333-339. Epub 2021 Feb 12.

Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science.

We synthesized hydrophilic amine-based protic ionic liquids (PILs) with hydroxy groups in their cations and anions, and characterized their adsorption at a solid (iron-based substrate) / aqueous solution interface. The IL samples employed in this study were triethanolamine lactate, diethanolamine lactate, and monoethanolamine lactate. Quartz crystal microbalance with dissipation monitoring (QCM-D) measurements revealed that the adsorption mass of the hydrophilic PILs was larger than that of the comparative materials, including a non-IL sample (1,2,6-hexanetriol) and an OH-free sample in the cations (triethylamine lactate). Additionally, an increase in the number of hydroxy groups in the cations resulted in an increased adsorption mass. Force curve measurements by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) measurements proved the high adsorption density of the hydrophilic PILs on the iron-based substrate. A decreased kinetic friction coefficient was also observed in the hydrophilic PIL systems. Moreover, hydrophilic PILs are expected to have potential applications as water-soluble lubricants and additives for metal surface treatments.
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http://dx.doi.org/10.5650/jos.ess20279DOI Listing
March 2021

Presurgical bladder wall thickness is a useful marker to predict the postsurgical improvement of symptoms in patients with pelvic organ prolapse-related overactive bladder.

Low Urin Tract Symptoms 2021 Jul 12;13(3):347-355. Epub 2021 Feb 12.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Objectives: Pelvic organ prolapse (POP) is a cause of overactive bladder (OAB), and transvaginal mesh (TVM) surgery can improve the symptoms. Bladder wall thickness (BWT) is a useful and safe marker to evaluate bladder function in urinary disorders. The main purpose of this study is to clarify the relationship between BWT and changes in the OAB symptom score (OABSS) after TVM operation in patients with POP.

Methods: BWT was measured by ultrasonography before and 6 months after surgery at three sites in the bladder: the anterior wall, trigone, and dome. Similarly, the OABSS was evaluated at the time of BWT measurement. Changes induced in BWT at each site and the mean BWT at all sites after TVM surgery were analyzed. Similarly, the relationship between presurgical BWT and the decrease in OABSS was investigated.

Results: TVM surgery improved OABSS in 30 patients (responders; 73.2%), while 11 patients were judged as nonresponders (26.8%). BWT at the anterior bladder wall and dome as well as the mean BWT at all three sites were significantly decreased by TVM surgery (P < .001). Similar trends were identified in OABSS responders; however, all markers showed no significant changes in OABSS nonresponders. All the BWT-related markers before surgery were significantly lower in OABSS responders than in OABSS nonresponders.

Conclusions: BWT at the bladder anterior wall and dome, but not the trigone, were decreased by TVM surgery. We conclude that presurgical BWT may be a useful marker to predict the improvement in OAB symptoms by TVM surgery in patients with POP-related OAB.
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http://dx.doi.org/10.1111/luts.12374DOI Listing
July 2021

Editorial Comment to Does cognitive behavioral therapy using a self-check sheet improve night-time frequency in patients with nocturia? Results of a multicenter randomized controlled trial.

Int J Urol 2021 04 31;28(4):449. Epub 2021 Jan 31.

Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

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http://dx.doi.org/10.1111/iju.14516DOI Listing
April 2021

Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia.

Molecules 2021 Jan 16;26(2). Epub 2021 Jan 16.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.
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http://dx.doi.org/10.3390/molecules26020450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829696PMC
January 2021

Rare case of penile fracture caused by an injury to the crus penis: Delayed repair using the transperineal approach.

IJU Case Rep 2021 Jan 17;4(1):36-38. Epub 2020 Nov 17.

Department of Urology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.

Introduction: Penile fracture is a rare urologic emergency, and its surgical treatment is selected based on the damaged site of the penile corpus cavernosum. Penile fractures at the site of the crus penis are quite rare, and there is controversy regarding the preferred method of surgical repair.

Case Presentation: A 25-year-old Asian man was injured when rolling over in bed. Magnetic resonance imaging showed a tear in the left crus of the penis with a hematoma. Delayed surgery was successfully performed using the transperineal approach. He did not experience pain, dysuria, or erectile dysfunction postoperatively.

Conclusion: Delayed surgical repair using transperineal approach may be useful for penile fractures associated with penile crus injuries.
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http://dx.doi.org/10.1002/iju5.12232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784756PMC
January 2021

Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature.

Sci Rep 2021 01 8;11(1):31. Epub 2021 Jan 8.

Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.

A biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biomembranes into cells (cytolysis) without perturbating cell viability and expected to be a promising drug delivery vector. Examples of CPP include peptides with multiple arginine units with strong cationic properties, which is the key to cytolysis. Here we show the conclusive evidence to support the mechanism of CPP's cytolysis and way to control it. The mechanism we proposed is attributed to biomembrane's physicochemical nature as lamellar liquid crystal (Lα). Cytolysis occurs as the temporal and local dynamic phase transitions from Lα to an undulated lamellar with pores called Mesh. We have shown this phase transfer of Lα composed of dioleoyl-phosphatidylcholine (DOPC) with water by adding oligo-arginine (Rx) as CPP at the equilibrium. Using giant unilamellar vesicle composed of DOPC as a single cell model, we could control the level of cytolysis of CPP (FITC-R8) by changing the curvature of the membrane through osmotic pressure modulation. The cytolysis of CPP utilizes biomembrane's inherent topological and functional flexibility corresponding to the stimuli.
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http://dx.doi.org/10.1038/s41598-020-79518-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794472PMC
January 2021

Excessive accumulation of visceral fat is associated with lower urinary symptoms including overactive bladder in female patients.

Int J Urol 2021 Apr 29;28(4):397-403. Epub 2020 Dec 29.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Objective: To assess the relationship between visceral fat accumulation and lower urinary tract symptoms in female patients.

Methods: In this single-center study, we enrolled all women who underwent screening abdominal computed tomography 3 months before the study, irrespective of whether they experienced lower urinary tract symptoms. The Overactive Bladder Symptom Score was used to assess subjective symptoms. Uroflowmetry and ultrasound assessment of post-void residual urine were carried out to assess objective signs. We analyzed the relationship between lower urinary tract symptoms and various body fat accumulation parameters, including visceral fat area, visceral fat volume and total abdominal fat volume, assessed using computed tomography scans.

Results: A total of 182 patients were divided into the overactive bladder (n = 71, 39.0%) and the non-overactive bladder (n = 111, 61.0%) groups. The visceral fat area, visceral fat volume and visceral fat volume/total abdominal fat volume values were all significantly higher in the overactive bladder group than in the non-overactive bladder group (P < 0.001). Of these parameters, the visceral fat volume/total abdominal fat volume ratio showed the strongest correlation with the total Overactive Bladder Symptom Score (r = 0.394, P < 0.001). The maximum urine flow rate correlated negatively with the visceral fat volume/total abdominal fat volume value (visceral fat volume/total abdominal fat volume r = -0.289, P < 0.001). Subsequent multivariate analysis showed that a high visceral fat volume/total abdominal fat volume value, age and metabolic syndrome-related diseases were independent risk factors for the presence of overactive bladder.

Conclusions: Excessive accumulation of visceral fat is independently associated with overactive bladder in females.
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http://dx.doi.org/10.1111/iju.14476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048866PMC
April 2021

Present Status, Limitations and Future Directions of Treatment Strategies Using Fucoidan-Based Therapies in Bladder Cancer.

Cancers (Basel) 2020 Dec 15;12(12). Epub 2020 Dec 15.

Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan.

Bladder cancer (BC) is a common urological cancer, with poor prognosis for advanced/metastatic stages. Various intensive treatments, including radical cystectomy, chemotherapy, immune therapy, and radiotherapy are commonly used for these patients. However, these treatments often cause complications and adverse events. Therefore, researchers are exploring the efficacy of natural product-based treatment strategies in BC patients. Fucoidan, derived from marine brown algae, is recognized as a multi-functional and safe substrate, and has been reported to have anti-cancer effects in various types of malignancies. Additionally, in vivo and in vitro studies have reported the protective effects of fucoidan against cancer-related cachexia and chemotherapeutic agent-induced adverse events. In this review, we have introduced the anti-cancer effects of fucoidan extracts in BC and highlighted its molecular mechanisms. We have also shown the anti-cancer effects of fucoidan therapy with conventional chemotherapeutic agents and new treatment strategies using fucoidan-based nanoparticles in various malignancies. Moreover, apart from the improvement of anti-cancer effects by fucoidan, its protective effects against cancer-related disorders and cisplatin-induced toxicities have been introduced. However, the available information is insufficient to conclude the clinical usefulness of fucoidan-based treatments in BC patients. Therefore, we have indicated the aspects that need to be considered regarding fucoidan-based treatments and future directions for the treatment of BC.
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http://dx.doi.org/10.3390/cancers12123776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765304PMC
December 2020

Correction: Oral Intake of Royal Jelly Has Protective Effects against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial. , 2019, , 2.

Medicines (Basel) 2020 Nov 19;7(11). Epub 2020 Nov 19.

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki 852-8501, Japan.

We, the authors, wish to make the following correction to our published paper [...].
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http://dx.doi.org/10.3390/medicines7110071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699318PMC
November 2020

The Relationship Between Actin Cytoskeleton and Membrane Transporters in Cisplatin Resistance of Cancer Cells.

Front Cell Dev Biol 2020 27;8:597835. Epub 2020 Oct 27.

Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

Cisplatin [-diamminedichloroplatinum (II)] is a platinum-based anticancer drug widely used for the treatment of various cancers. It forms interstrand and intrastrand cross-linking with DNA and block DNA replication, resulting in apoptosis. On the other hand, intrinsic and acquired cisplatin resistance restricts its therapeutic effects. Although some studies suggest that dramatic epigenetic alternations are involved in the resistance triggered by cisplatin, the mechanism is complicated and remains poorly understood. Recent studies reported that cytoskeletal structures regulate cisplatin sensitivity and that activities of membrane transporters contribute to the development of resistance to cisplatin. Therefore, we focus on the roles of actin filaments and membrane transporters in cisplatin-induced apoptosis. In this review, we summarize the relationship between actin cytoskeleton and membrane transporters in the cisplatin resistance of cancer cells.
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http://dx.doi.org/10.3389/fcell.2020.597835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655133PMC
October 2020
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