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Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Objective: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis‐assisted transurethral resection of bladder tumor with oral administration of 5‐aminolevulinic acid. We conducted a re‐analysis of perioperative hypotension in photodynamic diagnosis‐assisted transurethral resection of the bladder tumor with oral 5‐aminolevulinic acid to ascertain its safety. Methods: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. Results: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. Conclusions: Renal function impairment and the other adverse effects of 5‐aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case–control studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. Materials and Methods: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression‐free survival, and rehospitalization. Results: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression‐free survival (HR: 1.83, 95% CI: 1.12–3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99–3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). Conclusions: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. A retrospective analysis of 85 patients who underwent RARP at Kanazawa University Hospital between 2009 and 2019 and were selected for intermittent ADT for postoperative recurrence was analyzed. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed initial ADT was conducted to evaluate the rate of BCR following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. ADT may be applicable for BCR after RARP, and strong testosterone suppression could lead to better outcomes. Background: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. Methods: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. Results: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. Conclusions: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy. [ABSTRACT FROM AUTHOR]

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan–Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the postoperative urinary continence rate and incontinence types compared over time between conventional robot‐assisted radical prostatectomy (C‐RARP) and Retzius‐sparing RARP (RS‐RARP). Methods: All 61 cases were selected from the C‐RARP and RS‐RARP by propensity score matching, and the pad scale, 24‐h pad weight test, and International consultation on incontinence questionnaire‐short form (ICIQ‐SF) were followed‐up over time up to 12 months. Results: The probability of urinary continence per pad scale evaluation differed according to how it was defined: the continence rate 12 months after C‐RARP and RS‐RARP were 94% and 95% for 1 pad/day, 85% and 92% for 1 security pad/day, 61% and 85% for no pad use, respectively, which were all significantly better with RS‐RARP. The results of the 24‐h pad weight test were significantly better with RS‐RARP at both 3 and 12 months, with median C‐RARP versus RS‐RARP values of 5 versus 1 g and 2 versus 0 g, respectively. In terms of types of urinary incontinence, the rates of postoperative stress urinary incontinence (SUI) increased in both procedures but to a lesser extent in RS‐RARP. Other types of urinary incontinence, such as urge incontinence and terminal dribbling, did not differ significantly before and after surgery and between the two procedures. Conclusions: Postoperative urinary continence was better with RS‐RARP than with C‐RARP per all follow‐up parameters until 12 months postoperatively. Postoperative SUI was significantly lower with RS‐RARP than with C‐RARP, which was considered the main reason for better postoperative urinary continence with RS‐RARP. [ABSTRACT FROM AUTHOR]

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR‐controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C–C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4‐2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20‐treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C–C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti‐CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti‐CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration‐resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in diagnostic imaging have led to an increase in the diagnosis and treatment of small-diameter renal cell carcinomas in the elderly. Elderly patients may show impaired operative tolerance; thus, treatment should be more carefully chosen in them than in younger patients. In this study, a retrospective comparison of robot-assisted partial nephrectomy (RAPN) and percutaneous cryoablation (PCA) was conducted for small-diameter renal cell carcinomas in elderly patients. Both RAPN (with a slightly high complication rate but a low recurrence rate) and PCA (with a low complication rate but a slightly high recurrence rate) could be performed safely in elderly patients. RAPN proved to be a safe and effective method for treating small-diameter renal cell carcinomas in elderly patients, thereby being the first treatment of choice in such patients. PCA was also a safe and feasible alternative, especially in patients in whom general anesthesia poses a high risk. Advances in imaging technologies have increased the opportunities for treating small-diameter renal cell carcinomas (RCCs) in the elderly. This retrospective study based on real-world clinical practice compared perioperative complications, preoperative and postoperative renal function, recurrence-free survival, and overall survival in elderly patients with RCC who had undergone robot-assisted partial nephrectomy (RAPN) or percutaneous cryoablation (PCA). A total of 99 patients (aged ≥70 years), including 50 and 49 patients in the RAPN and PCA groups, respectively, were analyzed. In the entire cohort, Clavien–Dindo grade ≥3 complications occurred in only one patient who had undergone RAPN. Renal function was significantly lower in the postoperative period than in the preoperative period in both the RAPN and PCA groups. The recurrence-free survival and overall survival rates were worse in the PCA group than in the RAPN group, albeit not significantly. RAPN was considered a safe and effective method for treating RCCs in elderly patients. Moreover, although the recurrence rate was slightly higher in the PCA group than in the RAPN group, PCA was deemed to be a safe alternative, especially for treating patients in whom general anesthesia poses a high risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer. We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following transurethral resection of bladder tumor. Of the 109 patients with inchworm sign, 94 (86.2%) were non-muscle invasive bladder cancer. Non-papillary tumors and tumors located in the bladder neck were significant predictors of muscle invasive bladder cancer with inchworm sign. Additionally, inchworm sign was not a prognostic factor in patients with non-muscle invasive bladder cancer in this study. Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07–44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83–32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04–3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC. [ABSTRACT FROM AUTHOR]

Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2′s usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer. There is a need to identify prognostic factors for the appropriate choice of treatment for patients with hormone-naïve prostate cancer in Japanese men. Among the prostate cancer patients receiving treatment at our institution from 2000 to 2019, 198 patients with bone or visceral metastases at the initial diagnosis were included in the study. We retrospectively examined these factors of the overall survival, and identified Gleason pattern 5 content, bone scan index ≥ 1.5, and lactate dehydrogenase evels ≥ 300 IU/L as prognostic factors. Using these three factors, we developed a new prognostic model for overall survival that can more objectively predict the prognosis of patients simply and objectively. Background: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer (mHNPC). There is a need to identify prognostic factors for the appropriate choice of treatment for patients with mHNPC, and we retrospectively examined these factors. Methods: Patients with mHNPC treated at our institution from 2000 to 2019 were included in this study. Overall survival (OS) was estimated retrospectively using the Kaplan–Meier method, and factors associated with OS were identified using univariate and multivariate analyses. A prognostic model was then developed based on the factors identified. Follow-up was terminated on 24 October 2021. Results: The median follow-up duration was 44.2 months, whereas the median OS was 85.2 months, with 88 patients succumbing to their disease. Multivariate analysis identified Gleason pattern (GP) 5 content, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) levels ≥ 300 IU/L as prognostic factors associated with OS. We also developed a prognostic model that classified patients with mHNPC as low risk with no factor, intermediate risk with one factor, and high risk with two or three factors. Conclusions: Three prognostic factors for OS were identified in patients with mHNPC, namely GP5 inclusion, BSI ≥ 1.5, and LDH ≥ 300. Using these three factors, we developed a new prognostic model for OS that can more objectively predict patient prognosis. [ABSTRACT FROM AUTHOR]

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥ 7 and 273 had a GS of <7 or no malignancy. In this study, patients aged 75 years or older were classified as elderly patients. GS ≥ 7 was characterized by a prostate-specific antigen (PSA) of the maximum area under the curve of 12 ng ml−1 with a sensitivity of 76.2% and a specificity of 73.2%. For PSA levels between 4 ng ml−1 and 12 ng ml−1, based on the maximum area under the curve, patients with three or four of the following factors may present a GS of ≥ 7: percent free PSA >24, PSA density ≥ 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently. [ABSTRACT FROM AUTHOR]

Urachal cancer often presents at an advanced stage with poor prognosis due to the lack of an effective systematic therapeutic strategy. We experienced a case of metastatic urachal cancer treated effectively by combination chemotherapy and radiotherapy. A 55-year-old female presented to our department with right lower abdominal pain. A transurethral biopsy of an urachal tumor suggested urachal adenocarcinoma. The patient underwent chemotherapy with gemcitabine and cisplatin for metastatic urachal cancer. As tumor markers declined and the radiological findings indicated stability of disease, external beam radiotherapy was then administered to the primary site. Chemotherapy was then administered again in response to tumor markers gradually increasing and the progression of multiple peritoneal metastases. However, the patient did not complete chemotherapy due to hematological toxicity. The patient succumbed to primary disease 23 months after initial diagnosis. Previous studies have reported that the median time from the diagnosis of metastatic urachal cancer to mortality is just over 1 year. By contrast, in the present case the patient survived up to 2 years with combination chemotherapy and radiotherapy, a rare incidence worthy of reporting. [ABSTRACT FROM AUTHOR]

Aims: To evaluate urinary incontinence using the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), daily pad use, and 24‐h pad weight test before and after radical prostatectomy (RP) chronologically, and the correlation between them. Methods: ICIQ‐SF and questions on daily pad use provided subjective, and 24‐h pad weight test for objective evaluation. Results: In total, 258 cases were recruited. The continence rate at 12 months after RP was 67% for no pad use, 87% for security 1 pad/day, and 94% for 1 pad/day. The median ICIQ‐SF total score before and at 1, 3, 6, and 12 months after RP was 0, 10, 7, 5, and 4, respectively. Incontinence patterns differed when comparing ICIQ‐SF results pre‐ and post‐RP. Significant correlation existed between the ICIQ‐SF total score, 24‐h pad weight test, and daily pad use; however, point distribution on each scatter plot varied widely. Comparing results before and at 12 months after RP revealed complete recovery for 35% of patients from the ICIQ‐SF total score, 67% from daily pad use, and 64% from the 24‐h pad weight test. A combination of all 3 showed a recovery of preoperative levels in 29% of patients. Conclusions: ICIQ‐SF was effective and convenient for evaluating UI, including the pattern of UI, after RP. Significant correlation, but wide variations, among ICIQ‐SF, daily pad use, and the 24‐h pad weight test existed. The best evaluation method would be the one that can compare UI status pre‐ and post‐RP using the ICIQ‐SF and 24‐h pad weight test. [ABSTRACT FROM AUTHOR]

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel‐resistant and castration‐resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C‐C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel‐resistant cell line, DU145‐TxR/CxR, from a previously established paclitaxel‐resistant cell line, DU145‐TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145‐TxR and DU145‐TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145‐TxR and DU145‐TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145‐TxR and DU145‐TxR/CxR cells under treatments of cabazitaxel. The CCL2‐CCR2 axis decreased apoptosis through the inhibition of caspase‐3 and poly(ADP‐ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2‐CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel. Cabazitaxel‐resistant cell line DU145‐TxR/CxR cells secreted CCL2, and CCL2 induces resistance to the antiproliferative effect of cabazitaxel in DU145‐TxR/CxR cells in an autocrine manner. Inhibition of the CCL2‐CCR2 axis may be a potential treatment candidate in combination with cabazitaxel. [ABSTRACT FROM AUTHOR]

Objective: To assess the chronological changes in urinary incontinence and urethral function before and after radical prostatectomy (RP), and to compare the findings of pelvic magnetic resonance imaging (MRI) before and after RP to evaluate the anatomical changes. Patients and Methods: In total, 185 patients were evaluated with regard to the position of the distal end of the membranous urethra (DMU) on a mid‐sagittal MRI slice and urethral sphincter function using the urethral pressure profilometry. The patients also underwent an abdominal leak point pressure test before RP and at 10 days and 12 months after RP. The results were then compared with the chronological changes in urinary incontinence. Results: The MRI results showed that the DMU shifted proximally to an average distance of 4 mm at 10 days after RP and returned to the preoperative position at 12 months after RP. Urethral sphincter function also worsened 10 days after RP, with recovery after 12 months. The residual length of the urethral stump and urinary incontinence were significantly associated with the migration length of the DMU at 10 days after RP. The residual length of the urethral stump was a significant predictor of urinary incontinence after RP. Conclusion: This is the first study to elucidate that the slight vertical repositioning of the membranous urethra after RP causes chronological changes in urinary incontinence. A long urethral residual stump reduces urinary incontinence after RP. [ABSTRACT FROM AUTHOR]

Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C-C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor-a (TNF-α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF-α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF-α and CCR7. Second, low concentrations of TNF-α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF-α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis. [ABSTRACT FROM AUTHOR]

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co‐cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration‐dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C‐C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. [ABSTRACT FROM AUTHOR]

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins. [ABSTRACT FROM AUTHOR]

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial–mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial–mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial–mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial–mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma. [ABSTRACT FROM AUTHOR]