Publications by authors named "Yusuke Koike"

36 Publications

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

Jpn J Clin Oncol 2021 Jul 23. Epub 2021 Jul 23.

Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.

Background: Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable.

Methods: This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses.

Results: During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01).

Conclusions: The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.
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http://dx.doi.org/10.1093/jjco/hyab115DOI Listing
July 2021

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer.

Strahlenther Onkol 2021 Apr 28. Epub 2021 Apr 28.

Department of Urology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, 105-8461, Tokyo, Japan.

Purpose: To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria.

Methods: Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan-Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C‑indexes were used to assess model discrimination.

Results: Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5‑year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS.

Conclusion: While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.
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http://dx.doi.org/10.1007/s00066-021-01784-3DOI Listing
April 2021

A Case of Transplant Nephrectomy due to Chronic Graft Intolerance Syndrome.

Nephron 2020 26;144 Suppl 1:102-107. Epub 2020 Nov 26.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

We report a case of graft intolerance syndrome in which transplant nephrectomy was performed 11 years after kidney transplantation. A 46-year-old man was admitted to our hospital in February 2018 with a mild fever, left lower abdominal pain, and gross hematuria with enlargement of the transplanted kidney. Urinary tract infection was ruled out. Because the symptoms developed after the immunosuppressants had been stopped after kidney graft loss, graft intolerance syndrome was suspected. He had lost his graft in 2016 and had stopped all immunosuppressants since January of 2017. Immunosuppressive therapy was intensified, and steroid half-pulse therapy was added for 3 days. After the steroid pulse therapy, the C-reactive protein (CRP) decreased from 6.47 mg/dL to 0.76 mg/dL, but there was little improvement in the symptoms, and the CRP then increased to 4.44 mg/dL. Transplant nephrectomy was performed in March 2018. Postoperatively, the symptoms disappeared without the administration of immunosuppressants, and the CRP decreased. Pathologically, the resected kidney graft showed persistent active allograft rejection with severe endarteritis, transplant glomerulopathy, and diffuse interstitial fibrosis. Massive thrombi occluded the large arteries, and there was extensive hemorrhagic cortical necrosis. Transplant nephrectomy is uncommon in patients >6 months after transplantation. However, even if more time has passed since transplantation, as in this case, transplant nephrectomy may be a valid option in some cases of severe graft intolerance syndrome.
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http://dx.doi.org/10.1159/000511558DOI Listing
November 2020

Kidney Transplant Graftectomy by Severe Mixed-Type Rejection with Acute and Chronic Active Vascular Lesions at Entire Levels of the Renal Vasculature.

Nephron 2020 20;144 Suppl 1:59-64. Epub 2020 Nov 20.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Vascular lesions related to allograft rejection have a big impact on graft survival. As such, investigation of these lesions is important to understand the pathophysiology of rejection and its management. We report a case of kidney transplant graftectomy by severe mixed-type rejection with acute and chronic active vascular lesions caused by non-adherence to immunosuppressive treatment. The patient presented is a 29-year-old male who received a kidney transplantation in July 2011 (ABO compatible) from his father. He then did not come to the hospital for 3 months prior to his admission and also made his own decision to stop his medication regimen. On October 2013, the patient came to the hospital with dyspnea, nausea, and vomiting and had significant renal dysfunction (serum Cr 30.4 mg/dL, BUN 191 mg/dL). A kidney graft biopsy showed cortical necrosis with severe interstitial hemorrhage and thrombotic microangiopathy (TMA). Despite steroid pulse therapy, kidney graft function did not recover, and the patient underwent a subsequent graft resection. The resected kidney graft displayed various vascular lesions from the renal artery to the interlobular arteries and arterioles including endarteritis, TMA, fibrinoid necrosis, and transplant arteriopathy. This case shows the detailed pathological findings of the vascular lesions in the entire artery tree of kidney allograft, and the pathophysiology is discussed.
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http://dx.doi.org/10.1159/000512144DOI Listing
November 2020

Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation.

Front Immunol 2020 3;11:2068. Epub 2020 Sep 3.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.
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http://dx.doi.org/10.3389/fimmu.2020.02068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494805PMC
May 2021

Additive effects of intravenous and intravesical application of vibegron, a β-adrenoceptor agonist, on bladder function in rats with bladder overactivity.

Naunyn Schmiedebergs Arch Pharmacol 2020 11 18;393(11):2073-2080. Epub 2020 Jun 18.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

To examine the effects of intravenous and intravesical application of vibegron, a new β-adrenoceptor (β-AR) agonist, on bladder function in rats with oxotremorine methiodide (oxo-M: a nonselective muscarinic receptor agonist)-induced bladder overactivity. Cystometry was performed in conscious female rats with intravesical instillation of oxo-M (200 μM). In oxo-M-treated rats, vehicle or vibegron (1 and 10 mg/kg) was cumulatively applied intravenously at 30-min intervals. In other groups of rats, oxo-M + vehicle or oxo-M + vibegron (10, 100 μM, and 1 mM) was cumulatively instilled intravesically at 60-min intervals followed by intravenous application of vibegron (10 mg/kg). Expression of β-ARs in the bladder was also evaluated using immunohistochemical staining. Intravenous application of vibegron (10 mg/kg) significantly increased bladder capacity (1.3 times) and decreased baseline, threshold, and maximal voiding pressure compared with vehicle. Next, intravesical application of vibegron (1 mM) significantly increased threshold pressure and bladder capacity (1.2 times) compared with vehicle. Combined treatments of intravesical (1 mM) and intravenous (10 mg/kg) application of vibegron induced a significantly larger degree of increases in bladder capacity (1.4 times) compared with vehicle. In addition, β-ARs were expressed throughout the rat bladder, mainly in the urothelium. These results suggest that vibegron excreted in urine as an unchanged compound can induce the additive inhibitory effects on bladder overactivity possibly through urothelial β-AR activation, which inhibits the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressure and bladder capacity without affecting bladder contractile function after intravesical vibegron application.
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http://dx.doi.org/10.1007/s00210-020-01921-2DOI Listing
November 2020

Blood platelet volume predicts treatment-specific outcomes of metastatic castration-resistant prostate cancer.

Int J Clin Oncol 2020 Sep 2;25(9):1695-1703. Epub 2020 Jun 2.

Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (mCRPC), it is unclear who benefits most from androgen receptor axis-targeted agents (ARATs) or docetaxel as the first-line treatment.

Methods: We conducted a retrospective study to explore new treatment-specific biomarkers in mCRPC. A total of 211 patients with mCRPC who received either ARAT or docetaxel as first-line treatment were included. Patients were compared for radiographic progression and prostate-specific antigen (PSA) progression. Multivariable Cox regression models were used to assess the association between pretreatment biomarkers and risk of events. The statistical interaction between biomarkers and clinical outcomes was also evaluated.

Results: Of all analyzed biomarkers, multivariable Cox regression models identified MPV [≤ median (9.7 fL)] as an independent prognostic factor of radiographic progression [hazard ratio (HR), 2.35; 95% confidence interval (CI), 1.15-4.80; P = 0.019] and PSA progression (HR, 1.96; 95% CI, 1.01-3.95; P = 0.048) in patients treated with ARAT, whereas such associations were not observed in those treated with docetaxel. Interaction analyses showed that those initially treated with docetaxel have lower risk of radiographic progression (HR, 0.33; 95% CI, 0.13-0.79; P = 0.014) and PSA progression (HR, 0.48; 95% CI, 0.23-0.98; P = 0.044) than ARAT when MPV was small.

Conclusions: The present study identified pretreatment MPV as a significant treatment-specific prognostic factor of PSA and radiographic progression in patients with mCRPC who received first-line treatment. Furthermore, our results suggested that those with small MPV may better be treated initially with docetaxel than ARAT.
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http://dx.doi.org/10.1007/s10147-020-01712-yDOI Listing
September 2020

Muir-Torre syndrome: sebaceous carcinoma concurrent with colon cancer in a kidney transplant recipient; a case report.

BMC Nephrol 2019 10 29;20(1):394. Epub 2019 Oct 29.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: Sebaceous carcinoma is a rare but progressive malignant skin cancer, and the incidence is approximately five times higher in post-transplant patients than in people who have not received kidney transplants. Sebaceous carcinoma is sometimes found concurrently with visceral cancers and a genetic abnormality, Muir-Torre syndrome. We report the case of a female kidney transplant recipient with sebaceous carcinoma concurrent with colon cancer 10 years after transplantation.

Case Presentation: A 43-year-old woman was admitted due to a rapidly progressive tumor on her head. Histologically, the tumor was diagnosed as sebaceous carcinoma. We diagnosed her with Muir-Torre syndrome based on the following evidence: 1) high prevalence of microsatellite instability in gene locus assay, 2) absence of mismatch repair proteins in the sebaceous carcinoma on immunohistochemical analysis, and 3) a genetic mutation of 1226_1227delAG in the MSH2 exon 7 in the lesion detected by DNA sequencing analysis. Several reports have shown an association between immunosuppressive agents and latent Muir-Torre syndrome progression. Therefore, the progression of colon cancer in this case originated from her genetic mutation for Muir-Torre syndrome and long-term use of immunosuppressive agents.

Conclusion: This case report not only highlights the importance of adequate diagnosis and therapy for Muir-Torre syndrome, but also suggests the further prevention of the development of malignant tumors in kidney transplant recipients. Physicians should be mindful that sebaceous carcinoma in kidney transplant recipients is highly concurrent with Muir-Torre syndrome.
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http://dx.doi.org/10.1186/s12882-019-1592-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819420PMC
October 2019

Interstitial fibroblasts in donor kidneys predict late posttransplant anemia.

Clin Kidney J 2021 Jan 24;14(1):132-138. Epub 2019 Sep 24.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Background: Posttransplant anemia (PTA) is associated with the progression of kidney disease and mortality in kidney transplant recipients. Although the main causes of PTA are recipient factors, donor factors have not been fully investigated. In this study we investigated the association of donor pathological findings with the incidence of PTA in kidney transplant recipients after 3 years of transplantation.

Methods: We conducted a retrospective cohort study at a single university hospital. A total of 50 consecutive adult recipients and donors were enrolled. To assess the structure of interstitial lesions, immunohistochemical staining of interstitial fibrosis and fibroblasts were assessed in 0-h biopsies for quantitative analysis.

Results: The incidence of PTA in this cohort was 30%. The mean hemoglobin (Hb) was 11.6 ± 0.8 g/dL in patients with PTA and 14.3 ± 1.5 g/dL in patients without PTA. An inverse association was observed in biopsies between interstitial fibrosis area and interstitial fibroblast area (P < 0.01) and each pathological finding was examined for its association with PTA incidence after multivariate adjustment. For the interstitial fibrosis area, the odds ratio (OR) was 1.94 [95% confidence interval (CI) 1.26-2.99; P < 0.01]. For the interstitial fibroblast area, the OR was 0.01 (95% CI 0.00-0.16; P < 0.01). Receiver operating characteristics curve analysis indicated that the interstitial fibroblast area had high predictive power for the incidence of PTA.

Conclusions: The presence of interstitial fibroblasts in donor kidneys may play an important role in predicting the incidence of PTA.
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http://dx.doi.org/10.1093/ckj/sfz122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857797PMC
January 2021

Short-term impact of androgen deprivation therapy on bone strength in castration-sensitive prostate cancer.

Int J Urol 2019 10 28;26(10):980-984. Epub 2019 Jul 28.

Department of Urology, Jikei University School of Medicine, Tokyo, Japan.

Objectives: To prospectively evaluate changes in bone quality and bone mineral density after androgen deprivation therapy in castration-sensitive prostate cancer.

Methods: A total of 32 patients with castration-sensitive prostate cancer who were scheduled for androgen deprivation therapy for >12 months were included. The bone mineral density of the femoral neck and lumbar spine was evaluated before, and 6 and 12 months after androgen deprivation therapy. Bone metabolic (serum undercarboxylated osteocalcin, tartrate-resistant acid phosphatase 5b and procollagen type I propeptides) and bone quality markers (plasma pentosidine and homocysteine) were measured before, and 3, 6 and 12 months after androgen deprivation therapy.

Results: The median patient age was 71 years. A total of 17 patients were treated primarily with androgen deprivation therapy, and 15 were treated with androgen deprivation therapy in combination with definitive radiotherapy. Bone quality markers did not change substantially after androgen deprivation therapy. Bone mineral density decreased significantly after 12 months of androgen deprivation therapy. Serum undercarboxylated osteocalcin and tartrate-resistant acid phosphatase 5b levels increased significantly 3 months after androgen deprivation therapy, but procollagen type I propeptides levels stayed unchanged.

Conclusions: Bone quality markers do not change substantially after androgen deprivation therapy, whereas bone mineral density decreases significantly. Bone turnover markers might play an important role in monitoring bone health during androgen deprivation therapy.
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http://dx.doi.org/10.1111/iju.14077DOI Listing
October 2019

Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome.

Int J Urol 2019 06;26 Suppl 1:35-40

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Objectives: To examine the correlation among bladder inflammation, angiogenesis, fibrosis and urothelial denudation in biopsied bladder specimens, and O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes and visual analog scale pain scores in interstitial cystitis/bladder pain syndrome patients with or without Hunner lesions (Hunner type interstitial cystitis or non-Hunner type interstitial cystitis).

Methods: Bladder biopsied tissues were collected from 12 Hunner type interstitial cystitis female patients, 12 non-Hunner type interstitial cystitis female patients and 12 age-matched non-interstitial cystitis female patients (controls). Immunohistochemical stainings of tissue necrotic factor-α, mast cell tryptase, vascular endothelial growth factor, CD31, transforming growth factor-β, SLUG associated with epithelial mesenchymal transition and E-cadherin as well as Masson trichrome staining were evaluated. The significant correlation between the expression of tissue necrotic factor-α, mast cell tryptase, vascular endothelial growth factor, CD31, transforming growth factor-β, collagen, SLUG or E-cadherin, and O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes or visual analog scale pain scores was then examined.

Results: The expression of tissue necrotic factor-α, vascular endothelial growth factor, CD31, transforming growth factor-β and SLUG was significantly increased in non-Hunner type interstitial cystitis and Hunner type interstitial cystitis patients compared with controls whereas the significant increases in the expression of mast cell tryptase and collagen were observed in Hunner type interstitial cystitis patients compared with controls and non-Hunner type interstitial cystitis patients. On the other hand, the expression of E-cadherin was significantly decreased in Hunner type interstitial cystitis patients compared with controls and non-Hunner type interstitial cystitis patients. In addition, the increased expression of CD31 in bladder tissues was strongly correlated with O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes and visual analog scale pain scores.

Conclusions: These results suggest that bladder angiogenesis evident as the increased expression of CD31 is strongly correlated with urinary frequency and bladder pain in patients with non-Hunner type interstitial cystitis and Hunner type interstitial cystitis.
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http://dx.doi.org/10.1111/iju.13972DOI Listing
June 2019

Differential expression of androgen receptor variants in hormone-sensitive prostate cancer xenografts, castration-resistant sublines, and patient specimens according to the treatment sequence.

Prostate 2019 06 18;79(9):1043-1052. Epub 2019 Apr 18.

Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.

Background: Androgen receptor variants (AR-vs), especially AR-v7 and AR-v 5, 6, and 7 exon-skipped (AR-v567es), are reportedly key players in the development of castration-resistant prostate cancer (CRPC). We previously established a mouse xenograft model (JDCaP) from a metastatic skin lesion from a Japanese patient with CRPC and that was revealed to exhibit androgen sensitivity. In the present study, we established multiple castration-resistant xenograft models from JDCaP mice to investigate the biological features of CRPC.

Methods: Tissue from JDCaP mice was transplanted into male and female nude mice, and after serial passaging, castration-resistant sublines (JDCaP-CR2M and JDCaP-CR4M in male mice, JDCaP-CR2F and JDCaP-CR4F in female mice) were established. We investigated anti-androgen and testosterone sensitivity and the messenger RNA expression pattern of full-length AR and AR-vs. In addition, we compared AR protein levels of patient specimens among primary, local-recurrent, and two skin-metastatic tumors.

Results: All JDCaP-CR sublines showed continuous growth following the administration of bicalutamide, although the effects of testosterone varied among sublines. Parental JDCaP and JDCaP-CR2M, JDCaP-CR4M, and JDCaP-CR4F sublines expressed AR-v7, whereas JDCaP-CR2F exhibited elevated AR-v567es expression resulting from genomic deletion, which was confirmed by DNA sequencing. Moreover, we confirmed AR-v7 expression in the tumor of the original patient after androgen-deprivation therapy.

Conclusions: Each JDCaP-CR subline showed different AR-v-expression patterns, with JDCaP-CR2F expressing AR-v567es due to genomic deletion. Our results indicated that AR-vs emerged after androgen-deprivation therapy and appeared essential for acquisition of castration resistance.
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http://dx.doi.org/10.1002/pros.23816DOI Listing
June 2019

[A Case of Metachronous Cancer Originating from Five Different Organs].

Hinyokika Kiyo 2018 May;64(5):231-234

The Department of Urology, The Jikei University Hospital.

Advances and improvements in the early detection, diagnosis, and treatment modalities have increased the opportunities to treat multiple primary malignancies. Herein, we report a male patient with five metachronous cancers. The patient had initially undergone partial tongue resection for tongue cancer in 2003 at the age of 57 years and was subsequently diagnosed with acute promyelocytic leukemia, duodenal cancer, prostate cancer, and bladder cancer, over a period of 13 years. The patient underwent androgen deprivation therapy and palliative radiation therapy for the management of metastatic prostate cancer in 2016. The poor prognosis of the patient was thought to be related to be the prostate cancer because the other cancers were either in remission or localized. The occurrence of five metachronous cancers is extremely rare, and this is the fourth case to be reported in the Japanese literature.
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http://dx.doi.org/10.14989/ActaUrolJap_64_5_231DOI Listing
May 2018

Clinicopathological features and outcomes of kidney allografts in plasma cell-rich acute rejection: A case series.

Nephrology (Carlton) 2018 Jul;23 Suppl 2:22-26

Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

Plasma cell-rich acute rejection (PCAR) is a rare type of acute rejection in renal transplantation. Despite aggressive immunotherapy, approximately 40-60% of patients develop graft loss within 1 year after an episode of PCAR. However, the reason for this outcome remains obscure. This study retrospectively identified six patients with PCAR diagnosed between 2009 and 2015 at a single university hospital. Clinicopathological data were collected. Five of the six patients were male, and mean age at the onset of PCAR was 49.0 ±14.5 years. None of the patients showed overall poor adherence to medication. Mean time to diagnosis was 302 ±234 days post-transplantation. All patients had preceding or concurrent viral infection. Four patients developed PCAR alone and two patients developed PCAR with antibody-mediated rejection. One of the six patients showed both severe tubulointerstitial and microvascular inflammation (total of Banff tubulitis 't' + interstitial inflammation 'i' + glomerulitis 'g' + peritubular capillaritis 'ptc' scores >10). This patient had progressive worsening of graft function and re-initiated dialysis at 74 months after a PCAR episode. In addition, three of the six patients had long-term recurrence of PCAR. With the recurrence of PCAR, patients with both moderate tubulointerstitial and microvascular inflammation (total of Banff 't' + 'i' + 'g' + 'ptc' scores >6) had progressive worsening of graft function. In summary, the present results suggest that concurrent moderate to severe tubulointerstitial and microvascular inflammation may lead to poor outcomes of graft function after a PCAR episode.
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http://dx.doi.org/10.1111/nep.13277DOI Listing
July 2018

Antibody-mediated rejection due to anti-HLA-DQ antibody after pregnancy and delivery in a female kidney transplant recipient.

Nephrology (Carlton) 2018 Jul;23 Suppl 2:81-84

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Herein, we report a case of antibody-mediated rejection (ABMR) due to anti-HLA-DQ antibody after pregnancy and delivery in a female kidney transplant recipient. A 34-year-old female recipient was admitted at 2 years after delivery for an examination of an elevated serum creatinine (S-Cr) level. The patient had received a living kidney transplantation from her mother at 22 years of age, and her kidney graft function was almost stable. The episode biopsy showed peritubular capillaritis and transplant capillaropathy with C4d immunoreactivity in the peritubular capillaries. Additional examination revealed expression of a donor-specific antibody (DSA) against HLA-DQ5, leading to the diagnosis of chronic active ABMR. Intravenous immunoglobulin, plasma exchange, and rituximab were administered, and her S-Cr level was maintained stable. This case demonstrates a possible relationship between pregnancy/delivery and development of ABMR due to a de novo DSA in a female kidney transplant recipient.
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http://dx.doi.org/10.1111/nep.13279DOI Listing
July 2018

Effects of combined treatment of tadalafil and tamsulosin on bladder dysfunction via the inhibition of afferent nerve activities in a rat model of bladder outlet obstruction.

Int Urol Nephrol 2018 May 8;50(5):839-844. Epub 2018 Mar 8.

Department of Urology, University of Pittsburgh School of Medicine, Suite 700, Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213-3221, USA.

Purpose: To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α-adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO).

Methods: Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied.

Results: In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures.

Conclusions: These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.
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http://dx.doi.org/10.1007/s11255-018-1835-8DOI Listing
May 2018

[CLINICAL PRESENTATION AND OUTCOMES OF PENILE FRACTURE: RETROSPECTIVE ANALYSIS OF 16 PATIENTS].

Nihon Hinyokika Gakkai Zasshi 2018 ;109(4):204-207

Department of Urology, Jikei University School of Medicine.

(Background) Penile fracture as a result of sexual activity is exceedingly rare. Therefore, few studies have investigated it specifically in Japan. (Methods) We evaluated the clinical features and complications of all patients with penile fractures treated at Jikei University Hospital between 2005 and 2017. A total of 16 patients were identified and their etiologies, symptoms, treatment strategy, operative approach, and complications were reviewed. (Results) The median patient age was 41 years (range: 22-67). We were able to identify the etiology in 15 patients: 5 patients (31%) had suffered the fracture during sexual intercourse and 4 (25%) during masturbation. All patients were not suspected of having urethral injury. Eight patients underwent magnetic resonance imaging (MRI) prior to surgical repair. Disruption of tunica albuginea could be identified in all 7 patients with decent descriptions of the findings recorded for review. All patients underwent surgery, and the ruptured tunica albuginea was repaired. None of the patients developed erectile dysfunction (ED) but 1 patient (6%) had postoperative penile curvature. (Conclusions) Penile fracture most frequently occurred during sexual intercourse and masturbation. Our series had no ED, but longer follow-up is needed to draw definitive conclusions.
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http://dx.doi.org/10.5980/jpnjurol.109.204DOI Listing
January 2018

[SIGNIFICANT, TRANSIENT VISUAL DISTURBANCE AFTER LAPAROSCOPIC RADICAL PROSTATECTOMY].

Nihon Hinyokika Gakkai Zasshi 2018 ;109(3):156-159

Department of Urology, The Jikei University School of Medicine.

Visual disturbance following non-ophthalmologic surgery under general anesthesia is rare but can be devastating both socially and medicolegally. Immediate salvage intervention as well as prevention is of utmost importance since this can be a serious blow to patient's functional outcome postoperatively. We experienced a case of temporary but significant visual disturbance right after transperitoneal laparoscopic radical prostatectomy for localized prostate cancer. We need to raise our levels of vigilance to this condition since it can be avoided and prevented with immediate therapeutic intervention and decent clinical awareness.
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http://dx.doi.org/10.5980/jpnjurol.109.156DOI Listing
January 2018

Association Between GLCCI1 Promoter Polymorphism (Rs37972) and Post-Transplant Hypertension in Renal Transplant Recipients.

Kidney Blood Press Res 2017 8;42(6):1155-1163. Epub 2017 Dec 8.

Division of Nephrology and Hypertension, Department of Internal Medicine, Tokyo, Japan.

Background/aims: Post-transplant hypertension is highly prevalent in renal transplant recipients and is a risk factor for graft loss, cardiovascular disease and death. Glucocorticoid is used to prevent rejection, but simultaneously increases the risk of post-transplant hypertension. The glucocorticoid-induced transcript 1 (GLCCI1) promoter polymorphism (rs37972) has been reported to be associated with response to glucocorticoid therapy in asthma. We therefore examined the association between GLCCI1 promoter polymorphism and post-transplant hypertension in renal transplant recipients.

Methods: We conducted a retrospective cohort study of renal transplantation at a single university hospital from October 2003 to January 2014. Fifty consecutive adult recipients were analyzed, with clinical data retrieved from a prospectively collected database. Genotyping was carried out using genomic DNA derived from recipient's blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively analyzed by immunohistochemical staining of recipients' native kidney biopsy-specimens. The primary outcome measure was post-transplant hypertension.

Results: Post-transplant hypertension was observed in 14/17 (82%) of recipients with CC, 18/20 (90%) with CT, and 2/13 (15%) with TT genotype. CC/CT genotype was significantly associated with post-transplant hypertension, even after adjustment for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P = 0.026). In addition, we observed that GLCCI1 immunoreactivity in arteriolar endothelial cells was higher in kidney specimens obtained from recipients with a CC/CT genotype than a TT genotype (P = 0.021).

Conclusion: GLCCI1 promoter polymorphism rs37972 may be associated with post-transplant hypertension.
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http://dx.doi.org/10.1159/000485862DOI Listing
August 2018

A Novel Near-infrared Fluorescent Protein, iRFP720, Facilitates Transcriptional Profiling of Prostate Cancer Bone Metastasis in Mice.

Anticancer Res 2017 06;37(6):3009-3013

Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan

Background: Bone represents a frequent site of prostate cancer metastasis. As the molecular mechanism remains unclear, an accessible animal model is required.

Materials And Methods: We established a novel murine metastasis model using near-infrared fluorescent protein iRFP720-labelled prostate cancer (PC3) cells. To clarify transcriptional alterations during metastasis, iRFP720-PC3 cells were intracardially injected into male mice. mRNA expression profiles of metastasis in bone using marrow cancer cells extracted by centrifugal separation and cell sorting were compared with those of parental cells by microarray. Differentially expressed genes were analyzed by pathway analysis.

Results: We identified 327 and 197 genes being up- and down-regulated, respectively. Pathway analysis revealed that the p53 signaling pathway, extracellular matrix receptor interaction, Mammalian target of rapamycin signaling pathway, cancer-related pathways, small cell lung cancer, and Escherichia coli infection response were altered.

Conclusion: iRFP720 is useful for in vivo cell detection/isolation. The results of expression analysis may improve prostate cancer treatment strategies.
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http://dx.doi.org/10.21873/anticanres.11655DOI Listing
June 2017

Continence care with high QOL(quality of life) for the aged.

Nihon Rinsho 2017 04;75(4):636-640

At the time to select methods for continence care, doctors should consider not only scien- tific factors but also quality of life. Functions of lower urinary tract are storage and voiding. Urine is waste of human body, so it is essential to void urine perfectly in a view point of to keep homeostasis. All patients who have been using a indwelling urethral catheter for more than a few days have complicated urinary tract infection. A trick of increasing good points of urethral catheter is a use in a limited period. If patients who have lost voiding function can perform clean intermittent self-catheterization, they will be able to enjoy continence without infection.
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April 2017

Successful Treatment of Plasma Cell-Rich Acute Rejection Using Pulse Steroid Therapy Alone: A Case Report.

Case Rep Transplant 2017 10;2017:1347052. Epub 2017 Jan 10.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Despite the recent development of immunosuppressive agents, plasma cell-rich acute rejection (PCAR) has remained refractory to treatment. Herein, we report an unusual case of PCAR that responded well to pulse steroid therapy alone. A 47-year-old man was admitted for a protocol biopsy three months after kidney transplantation, with a stable serum creatinine level of 1.6 mg/dL. Histological examination showed focal aggressive tubulointerstitial inflammatory cell infiltration of predominantly polyclonal mature plasma cells, leading to our diagnosis of PCAR. Three months following three consecutive days of high-dose methylprednisolone (mPSL) therapy, an allograft biopsy performed for therapy evaluation showed persistent PCAR. We readministered mPSL therapy and successfully resolved the PCAR. Although PCAR generally develops more than six months after transplantation, we diagnosed this case early, at three months after transplantation, with focally infiltrated PCAR. This case demonstrates the importance of early diagnosis and prompt treatment of PCAR to manage the development and severity of allograft rejection.
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http://dx.doi.org/10.1155/2017/1347052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259612PMC
January 2017

Dual-Modality Imaging of Prostate Cancer with a Fluorescent and Radiogallium-Labeled Gastrin-Releasing Peptide Receptor Antagonist.

J Nucl Med 2017 Jan 11;58(1):29-35. Epub 2016 Aug 11.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York

Gastrin-releasing peptide (GRP) receptors (GRPr) are frequently overexpressed in human prostate cancer, and radiolabeled GRPr affinity ligands have shown promise for in vivo imaging of prostate cancer with PET. The goal of this study was to develop a dual-modality imaging probe that can be used for noninvasive PET imaging and optical imaging of prostate cancer.

Methods: We designed and synthesized an IRDye 650 and DOTA-conjugated GRPr antagonist, HZ220 (DOTA-Lys(IRDye 650)-PEG-[D-Phe, Sta]-BN(6-14)NH), by reacting DOTA-Lys-PEG-[D-Phe, Sta]-BN(6-14)NH (HZ219) with IRDye 650 N-hydroxysuccinimide (NHS) ester. Receptor-specific binding of gallium-labeled HZ220 was characterized in PC-3 prostate cancer cells (PC-3), and tumor uptake in mice was imaged with PET/CT and fluorescence imaging. Receptor binding affinity, in vivo tumor uptake, and biodistribution were compared with the GRPr antagonists HZ219, DOTA-PEG-[D-Phe, Sta]-BN(6-14)NH (DOTA-AR), and DOTA-(4-amino-1-carboxymethyl-piperidine)-[D-Phe, Sta]-BN(6-14)NH (DOTA-RM2).

Results: After hydrophilic-lipophilic balance cartridge purification, Ga-HZ220 was obtained with a radiochemical yield of 56% ± 8% (non-decay-corrected), and the radiochemical purity was greater than 95%. Ga-HZ220 had a lower affinity for GRPr (inhibitory concentration of 50% [IC], 21.4 ± 7.4 nM) than Ga-DOTA-AR (IC, 0.48 ± 0.18 nM) or Ga-HZ219 (IC, 0.69 ± 0.18 nM). Nevertheless, Ga-HZ220 had an in vivo tumor accumulation similar to Ga-DOTA-AR (4.63 ± 0.31 vs. 4.07 ± 0.29 percentage injected activity per mL [%IA/mL] at 1 h after injection) but lower than that of Ga-DOTA-RM2 (10.4 ± 0.4 %IA/mL). The tumor uptake of Ga-HZ220 was blocked significantly with an excessive amount of GRP antagonists. IVIS spectrum imaging also visualized PC-3 xenografts in vivo and ex vivo with a high-contrast ratio. Autoradiography and fluorescent-based microscopic imaging with Ga-HZ220 consistently colocated the expression of GRPr. Ga-HZ220 displayed a higher kidney uptake than both Ga-DOTA-AR and Ga-DOTA-RM2 (16.9 ± 6.5 vs. 4.48 ± 1.63 vs. 5.01 ± 2.29 %IA/mL).

Conclusion: Ga-HZ220 is a promising bimodal ligand for noninvasive PET imaging and intraoperative optical imaging of GRPr-expressing malignancies. Bimodal nuclear/fluorescence imaging may not only improve cancer detection and guide surgical resections, but also improve our understanding of the uptake of GRPr ligands on the cellular level.
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http://dx.doi.org/10.2967/jnumed.116.176099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209642PMC
January 2017

Successful treatment of recurrent Henoch-Schönlein purpura nephritis in a renal allograft with tonsillectomy and steroid pulse therapy.

Nephrology (Carlton) 2016 Jul;21 Suppl 1:53-6

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

We report a case of recurrent Henoch-Schönlein purpura nephritis (HSPN) treated successfully with a tonsillectomy and steroid pulse therapy in a kidney transplant patient. A 29-year-old woman was admitted to our hospital for an episode biopsy; she had a serum creatinine (S-Cr) of 1.0 mg/dL and 1.34 g/day proteinuria 26 months after kidney transplantation. Histological examination revealed increased amounts of mesangial matrix and mesangial hypercellularity with IgA deposition. Of note, one glomerulus showed focal endocapillary proliferation and tuft necrosis. We diagnosed active recurrent HSPN. Considering both the histological findings and refractory clinical course of the native kidney, she was treated for 3 consecutive days with steroid pulse therapy and a tonsillectomy. The patient's proteinuria decreased gradually to less than 150 mg/day 6 months later. A second biopsy 6 years after kidney transplantation showed an excellent response to treatment and revealed a marked reduction in both the mesangial matrix and mesangial hypercellularity, with trace IgA deposition. We conclude that a tonsillectomy and steroid pulse therapy appeared to be useful in this patient with active recurrent HSPN. This paper is the first to report a tonsillectomy and steroid pulse therapy as a therapeutic option for active recurrent HSPN. Further studies are needed to elucidate the efficacy and mechanisms of tonsillectomy with recurrent HSPN in kidney transplant patients.
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http://dx.doi.org/10.1111/nep.12770DOI Listing
July 2016

Rare case of nephrocalcinosis in the distal tubules caused by hereditary renal hypouricaemia 3 months after kidney transplantation.

Nephrology (Carlton) 2016 Jul;21 Suppl 1:67-71

Division of Nephrology and Hypertension, Department of Internal Medicine.

We report a rare case of nephrocalcinosis caused by hereditary renal hypouricaemia 3 months after kidney transplantation. A 41-year-old man who underwent living-related kidney transplantation from his father was admitted to our hospital for a protocol biopsy; he had a serum creatinine (S-Cr) of 1.37 mg/dL and no proteinuria. Histologically, there was no evidence of rejection or calcineurin inhibitor toxicity, although scattered nephrocalcinosis was observed in the distal tubules. Perioperatively, the patient had a serum uric acid (S-UA) of 1.9 mg/dL with a fractional excretion of uric acid (FEUA) of 29% (normal, <10%) and UA clearance of 26.8 mL/min (normal, 7.3-14.7 mL/min) 3 days after kidney transplantation. The donor also had a relatively low S-UA of 2.4 mg/dL and high FEUA of 10.3%. Subsequent DNA direct sequencing followed by restriction fragment length polymorphism revealed that both the recipient's and donor's urate transporter 1 (URAT1) gene had a heterozygous nonsense mutation in exon 5 (C889T). Further, the immunoreactivity of antibodies for the C terminus of URAT1 revealed a partial deletion. De Galantha and von Kossa staining revealed that the nephrocalcinosis was due to urate crystals and calcium stones. Therefore, we diagnosed hereditary renal hypouricaemia. We directed the patient to avoid hard exercise, drink plenty of water, and alkalize the urine. The 1-year follow-up allograft biopsy showed no evidence of nephrocalcinosis in the distal tubules. This is the first report of nephrocalcinosis in the distal tubules as a diagnostic clue to hereditary renal hypouricaemia. We also review the related literature.
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http://dx.doi.org/10.1111/nep.12774DOI Listing
July 2016

Combination therapy with β3 -adrenoceptor agonists and muscarinic acetylcholine receptor antagonists: Efficacy in rats with bladder overactivity.

Int J Urol 2016 05 18;23(5):425-30. Epub 2016 Feb 18.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Objective: To investigate the efficacy of combination therapy of a selective β3 -adrenoceptor agonist (mirabegron) and muscarinic acetylcholine receptor antagonists (a selective muscarinic acetylcholine receptor2 antagonist: methoctramine hemihydrate or a selective muscarinic acetylcholine receptor3 antagonist; 4-DAMP) compared with monotherapy of either agent in rats with oxotremorine methiodide (a non-selective muscarinic acetylcholine receptor agonist)-induced bladder overactivity.

Methods: Cystometry was carried out in conscious female rats with intravesical instillation of oxotremorine methiodide (200 μmol/L). Either mirabegron (0.3-3 mg/kg), methoctramine (0.1-1 mg/kg) or 4-DAMP (0.03-0.3 mg/kg) was cumulatively applied intravenously. Also, the effects of combined application of mirabegron (3 mg/kg) plus methoctramine (1 mg/kg) or 4-DAMP (0.3 mg/kg) on cystometric parameters were compared with those of single-agent monotherapy.

Results: Intravesical instillation of oxotremorine methiodide induced bladder overactivity, as evidenced by decreases in threshold pressure and bladder capacity. In oxotremorine methiodide-treated rats, single application of mirabegron (1, 3 mg/kg), methoctramine (0.3, 1 mg/kg) or 4-DAMP (0.1, 0.3 mg/kg) decreased baseline pressure and increased bladder capacity. In addition, reductions in threshold pressure and maximal voiding pressure were also seen after the administration of 4-DAMP (0.3 mg/kg). The combined treatment of mirabegron plus 4-DAMP induced a larger increase in bladder capacity compared with monotherapy of either drug, whereas there were no significant changes in cystometric parameters between the combination therapy of mirabegron plus methoctramine and monotherapy of either drug.

Conclusion: These results suggest that the combination therapy of β3 -adrenoceptor agonists plus muscarinic acetylcholine receptor3 antagonists is more effective compared with monotherapy for the treatment of bladder overactivity. In contrast, the efficacy of β3 -adrenoceptor agonists might not be increased by the addition of muscarinic acetylcholine receptor2 antagonists.
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http://dx.doi.org/10.1111/iju.13066DOI Listing
May 2016

Mitochondrial protein-derived cryptides: Are endogenous N-formylated peptides including mitocryptide-2 components of mitochondrial damage-associated molecular patterns?

Biopolymers 2016 Nov;106(4):580-7

Laboratory of Peptide Science, Graduate School of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan.

Recently, much attention has been paid to "nonclassical" bioactive peptides, which are fragmented peptides simultaneously produced during maturation and degradation of various functional proteins. We identified many fragmented peptides derived from various mitochondrial proteins including mitocryptide-1 and mitocryptide-2 that efficiently activate neutrophils. These endogenous, functionally active, fragmented peptides are referred to as "cryptides." Among them, mitocryptide-2 is an N-formylated cryptide cleaved from mitochondrial cytochrome b that is encoded in mitochondrial DNA (mtDNA). It is known that 13 proteins encoded in mtDNA are translated in mitochondria as N-formylated forms, suggesting the existence of endogenous N-formylated peptides other than mitocryptide-2. Here, we investigated the effects of N-formylated peptides presumably cleaved from mtDNA-encoded proteins other than cytochrome b on the functions of neutrophilic cells to elucidate possible regulation by endogenous N-formylated cryptides. Four N-formylated cryptides derived from cytochrome c oxidase subunit I and NADH dehydrogenase subunits 4, 5, and 6 among 12 peptides from mtDNA-encoded proteins efficiently induced not only migration but also β-hexosaminidase release, which is an indicator of neutrophilic phagocytosis, in HL-60 cells differentiated into neutrophilic cells. These activities were comparable to or higher than those induced by mitocryptide-2. Although endogenous N-formylated peptides that are contained in mitochondrial damage-associated molecular patterns (DAMPs) have yet to be molecularly identified, they have been implicated in innate immunity. Thus, N-formylated cryptides including mitocryptide-2 are first-line candidates for the contents of mitochondrial DAMPs to promote innate immune responses. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 580-587, 2016.
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http://dx.doi.org/10.1002/bip.22788DOI Listing
November 2016

Salvage I seed implantation for prostate cancer with postradiation local recurrence.

Urol Int 2013 6;90(3):294-300. Epub 2013 Mar 6.

Department of Urology, Tochigi Cancer Center, Utsunomiya, Japan.

Introduction: Although radiotherapy has been important in the therapy for localized prostate cancer, prostate-specific antigen failure may occur. This study evaluated the effects and side effects of (125)I low-dose-rate brachytherapy for patients with postradiation local failure.

Patients And Methods: 15 patients who received salvage brachytherapy were analyzed. A prescribed dose of 144 Gy was selected. Median follow-up calculated from the date of salvage brachytherapy was 33.0 months (range 6-51).

Results: 5 patients (33.3%) developed prostate-specific antigen failure. The biochemical relapse-free survival rate was 100% at 1 year, 91.7% at 2 years, and 60.2% at 3 years. All acute genitourinary and gastrointestinal adverse events were in grade 1-2 according to Common Terminology Criteria for Adverse Events version 3. As for late adverse events, 1 patient (6.7%) developed grade 3 hematuria at 17 months postsalvage.

Conclusions: Although careful patient selection is needed, salvage (125)I prostate brachytherapy appears to provide good prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after initial radiotherapy.
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http://dx.doi.org/10.1159/000346322DOI Listing
November 2013

Pathophysiology of urinary incontinence in murine models.

Int J Urol 2013 Jan 6;20(1):64-71. Epub 2012 Nov 6.

Department of Urology, Jikei University School of Medicine, Tokyo, Japan.

Urethral closure mechanisms under stress conditions consist of passive urethral closure involving connective tissues, fascia and/or ligaments in the pelvis and active urethral closure mediated by hypogastric, pelvic and pudendal nerves. Furthermore, we have previously reported that the active urethral closure mechanism might be divided into two categories: (i) the central nervous control passing onto Onuf's nucleus under sneezing or coughing; and (ii) the bladder-to-urethral spinal reflex under Valsalva-like stress conditions, such as laughing, exercise or lifting heavy objects. There are over 200 million people worldwide with urinary incontinence, a condition that is associated with a significant social impact and reduced quality of life. Therefore, basic research for urinary continence mechanisms in response to different stress conditions can play an essential role in developing treatments for stress urinary incontinence. It has been clinically shown that the etiology of stress urinary incontinence is divided into urethral hypermobility and intrinsic sphincter deficiency, which could respectively correspond to passive and active urethral closure dysfunction. In this review, we summarize the representative stress urinary incontinence animal models and the methods to measure leak point pressures under stress conditions, and then highlight stress-induced urinary continence mechanisms mediated by active urethral closure mechanisms, as well as future pharmacological treatments of stress urinary incontinence. In addition, we introduce our previous reports including sex differences in urethral closure mechanisms under stress conditions and urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury in female rats.
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http://dx.doi.org/10.1111/j.1442-2042.2012.03225.xDOI Listing
January 2013
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