Efficacy and Safety of Tolvaptan for Patients With Autosomal Dominant Polycystic Kidney Disease in Real-world Practice: A Single Institution Retrospective Study.

BACKGROUND/AIM: We evaluated the efficacy and safety of tolvaptan for autosomal dominant polycystic kidney disease (ADPKD) in real-world practice. PATIENTS AND METHODS: We retrospectively reviewed the cases of 27 patients who had been diagnosed with ADPKD between January 2014 and December 2022. Among them, 14 patients received tolvaptan (60 mg/day; morning: 45 mg, night: 15 mg) after being admitted for 2 days. In the outpatient clinic, blood and urine samples were taken monthly. RESULTS: The mean age, pretreatment estimated glomerular filtration rate (eGFR), treatment duration, and total kidney volume were 60 years, 45.6 ml/min/1.73 m2, 2.8 years, and 2,390 ml, respectively. One month later, the patients' renal dysfunction had worsened slightly, and their serum sodium concentrations had significantly increased. After one year, the mean reduction in the eGFR was -5.5 ml/min/1.73 m2 Moreover, at 3 years the patients' renal function was stable. No hepatic dysfunction or electrolyte abnormalities were noted, although discontinuation occurred in two cases. Tolvaptan treatment is considered to be safe. CONCLUSION: Tolvaptan was effective against ADPKD in a real-world setting. Moreover, the safety of tolvaptan was confirmed.

Laparoscopic redo pyeloplasty with a buccal mucosal graft.

Introduction: Redo pyeloplasty can be difficult due to scar tissue or fibrosis. Ureteral reconstruction with a buccal mucosal graft is performed safely and successfully, but most reports of ureteral reconstruction using a buccal mucosal graft are of robot-assisted surgery, with few reports of laparoscopic-assisted surgery. A case of laparoscopic-assisted redo pyeloplasty using a buccal mucosal graft is presented. Case presentation: A 53-year-old woman was diagnosed with ureteropelvic junction obstruction, and a double-J stent was placed to relieve backache. She visited our hospital 6 months after double-J stent placement. Three months later, laparoscopic pyeloplasty was performed. At 2 months postoperatively, anatomic stenosis occurred. Holmium laser endoureterotomy and balloon dilation were performed; however, the anatomic stenosis recurred, and laparoscopic redo pyeloplasty with a buccal mucosal graft was performed. After redo pyeloplasty, obstruction was improved, and her symptoms disappeared. Conclusion: This is the first case of using a buccal mucosal graft for laparoscopic pyeloplasty in Japan.

Outcomes of dutasteride discontinuation in patients with benign prostatic hypertrophy.

To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression.

The choice of therapeutic agent in female overactive bladder patients in real-world practice.

OBJECTIVE: The reasons why anticholinergic drugs or ß3 adrenergic agonists are selected as treatments for overactive bladder (OAB) are unclear. The aim of this study was to investigate the background data of female OAB patients that were prescribed anticholinergic drugs or ß3 adrenergic agonists in a real-world setting. MATERIALS AND METHODS: Between January 2013 and December 2014, 75 patients who had been diagnosed with OAB were included in this study. Administered medications, age, the persistence on treatment rate at one-year, medical history, pretreatment total Overactive Bladder Symptom Score (OABSS), pretreatment score for each OABSS factor, body mass index (BMI), and various comorbidities were evaluated retrospectively. Since there were many types of anticholinergic drugs and few patients, we grouped the patients into those that were prescribed anticholinergic drugs (group A) and those that were prescribed ß3 adrenergic agonists (group B). RESULTS: 75 patients (29 in group A and 46 in group B) were included in this study. There were no significant differences in age, BMI, obesity, medical history, pretreatment total OABSS, or pretreatment score for each OABSS factor. There was a significant difference in the post-voiding residual urine volume (PVR) between the groups (group A: 22 ml, group B: 9 ml; p = 0.0252). The 1-year persistence on treatment rate was 28% in both groups. CONCLUSIONS: There were no significant differences in clinical characteristics of patients who were prescribed anticholinergics and ß3 adrenergic agonists for OAB treatment, but a marginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and ß3 adrenergic agonists were considered to be almost equivalent.

Reclassification prediction of first-year protocol biopsy on active surveillance of prostate cancer by p2PSA-related parameters: from PRIAS-JAPAN.

BACKGROUND: There is no useful predictive marker for reclassification on active surveillance. Thus, we aimed to investigate thresholds of [-2] proPSA (p2PSA)-related parameters to predict reclassification of the first-year protocol biopsy (1-year PBx) and evaluate the influence of clinical decision-making. METHODS: This was an observational, prospective cohort study conducted at 19 Japanese institutes. The inclusion criteria included clinical stage T1c/T2, prostate-specific antigen (PSA) levels ≤10 ng/mL, PSA density <0.2 ng/ml/cc, one or two positive biopsy cores, and Gleason score (GS) ≤6 (GS ≦7 for patients aged ≥70 years) at diagnostic biopsy. All participants were required to receive a blood-sampling test on a protocol visit at inclusion and at the 1-year PBx. PSA and PSA isoforms (free PSA, p2PSA) were measured, and parameters (%free PSA, %p2PSA, phi) were calculated. Multivariable logistic regression models were used to predict the reclassification risk. To assess the predictive power and thresholds for reclassification, we plotted Receiver Operating Characteristic (ROC) curves. Decision curve analysis (DCA) was used to evaluate the variables that yielded a net clinical benefit. RESULTS: A total of 135 patients were included, and 36 patients were reclassified on the 1-year PBx. Multivariate analyses showed that %p2PSA and phi at inclusion and p2PSA, %p2PSA, and phi before the 1-year PBx were significant predictors of reclassification at the 1-year PBx. The ROC analysis showed an optimal cutoff point, sensitivity, and specificity of %p2PSA and phi before the 1-year PBx of 1.64, 86%, 49% and 35.92, 89%, 47%, respectively. The DCA showed that phi before the 1-year PBx had the highest net benefit. The study limitation was its single-arm observational design. CONCLUSIONS: %p2PSA and phi before the 1-year PBx had a good prediction power. phi is the most useful indicator for clinical decision-making on active surveillance. TRIAL REGISTRATION: This study is registered atthe Japan Trial Register with ID UMIN000009876 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011573 ).

[Adult Prepubertal-Type Teratoma Diagnosed Using Fish Analysis : A Case Report].

A 34-year-old man visited our hospital complaining of a small painless left scrotal mass. His serum alpha-fetoprotein and human chorionic gonadotropin-beta levels were normal. Ultrasonography revealed a solitary 14 mm mass. Magnetic resonance imaging revealed a mass with high intensity on T2-weighted imaging. Computed tomography revealed a heterogeneous tumor in the left scrotum. Left high orchiectomy was performed. The histopathological diagnosis was a teratoma without germ cell neoplasia in situ (GCNIS). Fluorescence in situ hybridization analysis showed no appearance of i(12p). The patient was clinically diagnosed as having a prepubertal-type testicular teratoma. Adult teratomas contain GCNIS and are aggressively treated as malignant germ cell tumors. However, a prepubertal-type teratoma is benign and does not relapse. It is essential to validate the appearance of i(12p) to differentiate prepubertal and postpubertal-type teratoma.

The Association Between Hot Flashes and Renal Dysfunction After Androgen Deprivation Therapy With Radiotherapy in Japanese Patients With High-risk Prostate Cancer.

BACKGROUND/AIM: We investigated the changes in and characteristics of renal function in Japanese patients with high-risk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued. PATIENTS AND METHODS: Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months. RESULTS: The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months. CONCLUSION: Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and high-risk PCa patients prior to ADT.

Renal Function Improves After the Discontinuation of Androgen Deprivation Therapy in Japanese Patients With Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. CONCLUSION: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.

High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy.

OBJECTIVES: To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. METHODS: One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. RESULTS: The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p < 0.0001). CONCLUSIONS: A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

Validation of the Effectiveness of Neutrophil-to-lymphocyte Ratio (NLR) as a Predictive Factor in Patients Undergoing Prostate Biopsy With Prostate Specific Antigen (PSA) Between 4.0 and 10.0 ng/ml.

BACKGROUND/AIM: This study aimed to access the effectiveness of serum neutrophil-to-lymphocyte ratio (NLR) in patients undergoing prostate needle biopsy with a prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. PATIENTS AND METHODS: A total of 633 cases were eligible. We evaluated several factors including age, PSA, PSA-density (PSAD), platelet-to-lymphocyte ratio (PLR) and NLR in the presence or absence of prostate cancer (PCa), retrospectively. We evaluated statistically the associations between each factor and pathological findings or Gleason score. RESULTS: A total of 201 were evaluated in this study. Regarding the presence or absence of prostate cancer, there were statistically significant differences in age, PSA levels, PSAD, the PLR and NLR. The mean NLR value of the patients with PCa was significantly lower compared to the entire cohort. Multivariate analysis showed that age, PSAD, and NLR were independent risk factors predicting PCa. CONCLUSION: For patients having a PSA between 4.0 and 10.0 ng/ml, NLR was a predicting factor of PCa prior to prostate needle biopsy and an effective biomarker and useful tool for avoiding unnecessary biopsies.

False-positive 123I-metaiodobenzylguanidine scan in a patient with renal cell carcinoma: A case of chromophobe renal cell carcinoma oncocytic variant with a complicated clinical course.

INTRODUCTION: 123I-metaiodobenzylguanidine scanning has high sensitivity and specificity for the diagnosis of tumors derived from sympathetic nerves or the adrenal medulla. We report the rare case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. CASE PRESENTATION: The patient was referred to our hospital with an incidental left renal mass during evaluation for hypertension. An ovarian tumor and prominent ascites were also observed. Serum and urine catecholamine levels were high to suspect a catecholamine-producing tumor of the kidney. 123I-metaiodobenzylguanidine scintigraphy showed increased 123I-metaiodobenzylguanidine intake in the tumor. Laparoscopic radical left nephrectomy was performed. The pathologic diagnosis was an oncocytic variant of chromophobe renal cell carcinoma. No pheochromocytoma features were found. CONCLUSION: We report the first case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. This case was diagnosed with primary aldosteronism and Meigs' syndrome, which made the clinical course more complicated.

Impact of Hypertension on Early Renal Dysfunction in Japanese Prostate Cancer Patients Treated With Androgen Deprivation Therapy.

Background/Aim: Recently, it was reported that the use of androgen deprivation therapy (ADT) is significantly associated with an increased risk of acute kidney injury (AKI) in patients with newly diagnosed non-metastatic prostate cancer. This study aimed to investigate the incidence of early renal dysfunction in Japanese prostate cancer patients receiving ADT and the factors associated with it. Patients and Methods: A total of 135 patients who had been pathologically diagnosed with prostate cancer and had received ADT for at least 6 months were eligible for study inclusion. The estimated glomerular filtration rate (eGFR) before treatment, and at 1, 3, and 6 months of ADT were evaluated retrospectively. We assessed renal function using eGFR and investigated the rate of change in the eGFR (ΔeGFR) during ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction after 6 months ADT. Results: A total of 110 cases were evaluated in this study. The incidence of renal dysfunction after 6 months ADT was 63% (69/110). The mean ΔeGFR after 1, 3, and 6 months of ADT were -0.6%, -3.1% and -1.7%, respectively (p<0.001). Multivariate analysis showed that renal dysfunction after 3 months of ADT and hypertension were independent risk factors for renal dysfunction after 6 months ADT. Conclusion: Renal dysfunction occurs from 1 month of ADT and hypertensive prostate cancer patients receiving ADT are at high risk of developing renal dysfunction, and that such patients should be treated very carefully. Therefore, patients that are started on ADT should undergo periodic prostate-specific antigen, renal function, and urinary salt intake examinations.

Successful Response to Nivolumab Plus Ipilimumab Therapy in a Hemodialysis Patient With Metastatic Renal Cell Carcinoma.

Background/Aim: There are few reports about the administration of nivolumab plus ipilimumab to hemodialysis patients and their efficacy and safety have not been established yet. Case Report: A 74-year-old male, who was receiving hemodialysis, was presented with metastatic renal cell carcinoma (mRCC). Two years later, more metastases were found, hence, immunotherapy involving nivolumab plus ipilimumab was initiated. After two doses of immunotherapy, interstitial pneumonia was observed. Thus, steroid pulse therapy was administered immediately. Subsequently, computed tomography (CT) findings and symptoms improved markedly. One month later, a CT scan showed a nodular shadow and an air cavity. A fungal infection was strongly suspected, so an antifungal drug was administered. Conclusion: Combination immunotherapy with nivolumab plus ipilimumab was demonstrated to be effective in a hemodialysis patient with mRCC.

Replisome genes regulation by antitumor miR-101-5p in clear cell renal cell carcinoma.

Analysis of microRNA (miRNA) regulatory networks is useful for exploring novel biomarkers and therapeutic targets in cancer cells. The Cancer Genome Atlas dataset shows that low expression of both strands of pre-miR-101 (miR-101-5p and miR-101-3p) significantly predicted poor prognosis in clear cell renal cell carcinoma (ccRCC). The functional significance of miR-101-5p in cancer cells is poorly understood. Here, we focused on miR-101-5p to investigate the antitumor function and its regulatory networks in ccRCC cells. Ectopic expression of mature miRNAs or siRNAs was investigated in cancer cell lines to characterize cell function, ie, proliferation, apoptosis, migration, and invasion. Genome-wide gene expression and in silico database analyses were undertaken to predict miRNA regulatory networks. Expression of miR-101-5p caused cell cycle arrest and apoptosis in ccRCC cells. Downstream neighbor of son (DONSON) was directly regulated by miR-101-5p, and its aberrant expression was significantly associated with shorter survival in propensity score-matched analysis (P = .0001). Knockdown of DONSON attenuated ccRCC cell aggressiveness. Several replisome genes controlled by DONSON and their expression were closely associated with ccRCC pathogenesis. The antitumor miR-101-5p/DONSON axis and its modulated replisome genes might be a novel diagnostic and therapeutic target for ccRCC.

Role of pre-miR-532 (miR-532-5p and miR-532-3p) in regulation of gene expression and molecular pathogenesis in renal cell carcinoma.

Analyses of our previously determined microRNA (miRNA) expression signature of renal cell carcinoma (RCC) and The Cancer Genome Atlas (TCGA) database revealed that both strands of the pre-miR-532-duplex-miR-532-5p (the guide strand) and miR-532-3p (the passenger strand)- are closely associated with poor prognosis of RCC patients (P = 0.0411 and P = 0.022, respectively). In this study we investigated the functional significance of these miRNAs and identified gene targets involved in RCC pathogenesis. Ectopic expression of these miRNAs significantly attenuated the malignant phenotypes including proliferation, migration and invasion of two RCC cell lines, 786-O and A498. A combination of genome-wide gene expression and in silico database analyses revealed 36 and 34 genes as putative target oncogenes regulated by miR-532-5p and miR-532-3p, respectively, in RCC cells. Among these targets, expression of aquaporin9 (AQP9), a water channel protein, was directly regulated by both miR-532-5p and miR-532-3p, and high expression levels of AQP9 were significantly associated with poor prognosis of RCC patients (P = 2.03e-05). Multivariate analysis indicated that AQP9 expression is an independent prognostic factor for RCC patients. Aberrant AQP9 expression at both the gene and protein level was detected in RCC clinical specimens. siRNA-mediated knockdown of AQP9 by si-AQP9 inhibited the malignant phenotypes of RCC cells. Rescue assays of AQP9 overexpression showed that the miR-532/AQP9 axis was closely involved in RCC oncogenesis. The identification of antitumor miRNAs and their targets will contribute to an increased understanding of the molecular pathogenesis of RCC.

Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p.

OBJECTIVES: To identify oncogenes regulated by micro-ribonucleic acid, miR-199a/b-3p, in metastatic castration-resistant prostate cancer. METHODS: Advanced ribonucleic acid sequencing technologies were applied to construct a micro-ribonucleic acid expression signature using metastatic castration-resistant prostate cancer autopsy specimens. Ectopic expression of mature micro-ribonucleic acids or small-interfering ribonucleic acids were applied to functional assays for cancer cell lines. Genome-wide gene expression and in silico database analyses were carried out to predict micro-ribonucleic acid targets. RESULTS: Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for non-structural maintenance of chromosomes condensin I complex subunit H was directly regulated by miR-199a/b-3p. High expression of condensin I complex subunit H was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis (P < 0.0001). Overexpression of condensin I complex subunit H was detected in hormone-sensitive prostate cancer and castration-resistant prostate cancer specimens, and knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. CONCLUSIONS: Small ribonucleic acid sequencing of metastatic castration-resistant prostate cancer specimens showed the presence of several antitumor micro-ribonucleic acids whose targets are involved in hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer pathogenesis. Condensin I complex subunit H seems to be a promising diagnostic marker and therapeutic target for this disease. Our approach, based on the roles of anti-tumor micro-ribonucleic acids and their targets, will contribute to an improved understanding of the molecular pathogenesis of hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.

Pirin: a potential novel therapeutic target for castration-resistant prostate cancer regulated by miR-455-5p.

Androgen deprivation therapy is frequently used to treat prostate cancer (PCa), but resistance can occur, a condition known as castration-resistant prostate cancer (CRPC). Thus, novel approaches for identification of CRPC are important for designing effective PCa treatments. Analysis of microRNA (miRNA) expression signatures by RNA sequencing showed that both passenger and guide strands of the miR-455-duplex (miR-455-5p and miR-455-3p, respectively) acted as antitumor miRNAs in PCa cells. The involvement of miRNA passenger strands in cancer pathogenesis is a novel concept for miRNA functionality. Based on a large patient cohort in The Cancer Genome Atlas, expression of eight miR-455-5p/-3p target genes (PIR: P = 0.0137, LRP8: P = 0.0495, IGFBP3: P = 0.0172, DMBX1: P = 0.0175, CCDC64: P = 0.0446, TUBB1: P = 0.0149, KIF21B: P = 0.0336, and NFAM1: P = 0.0013) was significantly associated with poor prognosis of PCa patients. Here, we focused on PIR (pirin), a highly conserved member of the cupin superfamily. PIR expression was directly regulated by miR-455-5p, and PIR overexpression was detected in hormone-sensitive prostate cancer (HSPC) surgical specimens and CRPC autopsy specimens. Loss-of-function assays using siRNA or an inhibitor (bisamide) showed that downregulation of PIR expression blocked cancer cell migration and invasion. Moreover, the miR-455-5p/PIR axis contributed to cancer cell aggressiveness. These results suggest that PIR might be a promising diagnostic marker for HSPC and CRPC. Furthermore, CRPC treatment strategies targeting PIR may be possible in the future. Identification of antitumor miRNAs, including miRNA passenger strands, may contribute to the development of new diagnostic markers and therapeutic strategies for CRPC.

PSA response following the 'steroid switch' in patients with castration-resistant prostate cancer treated with abiraterone: A case report.

A 69-year-old man presented initially with back pain and incomplete bilateral lower limb paralysis. The level of prostate-specific antigen (PSA) in the patient was elevated to 167.0 ng/ml, and multiple bone metastases were detected. Thoracic laminectomy was performed in an emergency due to spinal decompression. Subsequently, the patient was diagnosed with prostate cancer from an examination of resected bone specimens. Combined androgen blockade with degarelix and bicalutamide was initiated in October 2013. Consequently, the serum PSA level decreased to <1.0 ng/ml, but thereafter gradually increased. Subsequent bicalutamide withdrawal response was not observed, and switch of anti-androgen therapy to flutamide also resulted in a poor response. Then, abiraterone (1,000 mg daily) in combination with prednisolone (10 mg daily) was initiated when the level of PSA increased to 35.9 ng/ml in June 2015. The level of PSA decreased to the lowest point of 4 ng/ml; however, PSA level increased again to 21.7 ng/ml in April 2016. Consequently, a 'steroid switch' was attempted. Abiraterone therapy was continued, but concomitant corticosteroid was switched from prednisone to dexamethasone (1.0 mg per day). Fortunately, serum PSA level decreased promptly to the lowest point of 0.6 ng/ml. In the present case report, a review of recent literature was presented and potential explanations of the mechanism underlying the 'steroid switch' were described. Pharmacokinetic differences between dexamethasone and prednisolone may partially explain why the 'steroid switch' occurs. Other mechanisms may include the activation of the glucocorticoid receptor, mineralocorticoid receptor and/or mutant androgen receptor. Corticosteroids accelerate a number of transcription factors, cellular growth factors and cytokines, which may also be potential mechanisms. The 'steroid switch' at PSA progression might be a feasible option for therapy, which may delay the development of the disease. Although the underlying mechanisms require further study, clinicians should pay attention to this phenomenon.

Molecular pathogenesis of renal cell carcinoma: Impact of the anti-tumor miR-29 family on gene regulation.

OBJECTIVES: To identify key oncogenes and proteins that are controlled by the microRNA miR-29 family (miR-29a, miR-29b and miR-29c) in renal cell carcinoma pathogenesis. METHODS: Genome-wide gene expression and in silico database analyses were carried out. The Cancer Genome Atlas database was used to investigate the clinical significance of gene expression data in renal cell carcinoma patients. Loss-of-function assays were applied to investigate the function of target genes. RESULTS: We identified 47 possible target genes that might be regulated by the miR-29 family in renal cell carcinoma cells. Among the targets of the miR-29 family, high expression of 10 genes (ADAMTS14, TRIB13, SERPINH1, FCGR1B, COL1A1, LAIR2, WISP2, TREM1, TNKS1BP1 and GBP2) significantly predicted poor patient prognosis (P < 0.001). SERPINH1 was directly regulated by the miR-29 family, and its overexpression was detected in renal cell carcinoma surgical specimens and tyrosine kinase inhibitor failure autopsy specimens. High expression of SERPINH1 was significantly associated with tumor stage, pathological grade and poor prognosis (P < 0.0001). Knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. CONCLUSIONS: Genes regulated by the anti-tumor miR-29 family are closely involved in the molecular pathogenesis of renal cell carcinoma. Our approach based on anti-tumor microRNAs might contribute to the development of new diagnostic markers and therapeutic strategies.

Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance.

In the human genome, miR-451a, miR-144-5p (passenger strand), and miR-144-3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR-451a: P = .00305; miR-144-5p: P = .00128; miR-144-3p: P = 9.45 × 10-5 ). We previously reported that miR-451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR-144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR-144-5p and miR-144-3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR-144-5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2, TRIP13, ANKRD36, CENPF, NCAPG, CLEC2D, SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR-144-5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP, SDC3, SH2D1A, GZMH, KIF21B, TMC8, GAB3, HLA-DPB2, PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR-144-5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR-451a, miR-144-5p, and miR-144-3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis.