Purpose: We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. Materials and Methods: DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs’ function. Results: Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. Conclusions We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.

Purpose: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. Materials and Methods: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. Results: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). Conclusion Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Purpose: To find out the incidence and predictors for late high-grade genitourinary (GU) toxicity following salvage radiotherapy (SRT), we investigated the consecutive patients who were treated with SRT after radical prostatectomy. Materials and Methods: Patients who underwent SRT for biochemical recurrence after radical prostatectomy were reviewed. The incidence of GU toxicity was assessed and risk factors for grade ≥2 and ≥3 GU toxicity were evaluated. The STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guided the reporting of this study. Results: Among the total of 217 patients, 88 patients (40.5%) showed late grade ≥2 GU toxicity. The incidence of late grade ≥3 GU toxicity was 11.5%. The presence of grade ≥2 baseline GU dysfunction (hazard ratio [HR], 6.097; 95% confidence interval [CI], 3.280–11.333; p<0.001) and short interval (<1 year) from surgery to SRT (HR, 1.994; 95% CI, 1.182–3.365; p=0.01) were associated with late grade ≥2 GU toxicity. A short interval from surgery to SRT was an independent predictor of late grade ≥3 GU toxicity (HR, 2.975; 95% CI, 1.135–7.794; p=0.027). Conclusions The incidence of late high-grade GU toxicity was not uncommon after SRT. Thus, care should be taken when we consider SRT in patients with baseline urinary dysfunction and a short interval from surgery to SRT, to determine an optimal treatment strategy with balancing quality of life and oncologic outcome of patients.

Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods: and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10 6 cells), renal artery moderate dose (RA-MD) (1.0×10 6 cells), renal artery high dose (RA-HD) (2.0×10 6 cells), tail vein low dose (TV-LD) (0.5×10 6 cells), tail vein moderate dose (TV-MD) (1.0×10 6 cells), and tail vein high dose (TV-HD) (2.0×10 6 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p＜0.01), 16 weeks (p＜0.05), and 24 weeks (p＜0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p＜0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p＜0.01, p＜0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions Our findings confirm the efficacy and safety of high dose (2×10 6 cells) injection of hBMSC via the tail vein.

To become skilled in singing, one needs the ability to accurately perceive music and the capacity to vocalize it. Recognition of music can be distinguished by the perception of pitch and rhythm. Pitch perception is often determined by genetics and neurological differences, whereas rhythm perception is influenced more by environmental factors than genetics. Tone deafness, or amusia, can stem from difficulties in perceiving pitch or from an inability to sing despite accurate pitch perception, known specifically as “purely vocal tone deafness.” This condition involves a disconnect between perception and the act of singing. And this can also arise from problems in the memory of perceived musical notes. Tone deafness not only affects musical abilities but also impacts language processing and communication.

Glottic closure is essential for vocalization and airway protection. Several pathological conditions cause glottic insufficiency, such as vocal fold paralysis and presbylarynx, which is the age-related atrophy of laryngeal muscle. Injection laryngoplasty is common technique to treat glottic insufficiency, because it can be easily and inexpensively performed in an outpatient setting. Different injection material should be selected according to the purpose and patient condition before the procedure. Ideal material for injection laryngoplasty must be biocompatible, and the injected volume should be maintained for the desired duration without migration. Further, it will be better if it could be easily injected and removed. In this article, we reviewed the published research related to material for the injection laryngoplasty and tried to think about the limitations of current studies and the future direction of treatment.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects* ; Exanthema/chemically induced* ; Far East ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Thiohydantoins/adverse effects*

Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Purpose: This study aimed to evaluate the impact of serum testosterone level before enzalutamide treatment in metastatic castration-resistant prostate cancer (mCRPC) for antitumor outcomes. Materials and Methods: Single-center, retrospective study including patients that treated with enzalutamide for mCRPC before and after docetaxel chemotherapy. Clinicopathological parameters including serum testosterone at initial enzalutamide use were examined. Prostate-specific antigen (PSA) response, progression-free survival (PFS), and cancer-specific survival (CSS) were the outcomes of interest. Logistic-regression analysis was done for discovering odds for PSA response. Cox-proportional model was applied for risk stratification for progression and cancer-specific death. Results: A total of 228 patients with mCRPC, treated with enzalutamide, both prechemotherapy and postchemotherapy, between 2011 and 2019 were included. One hundred sixty-two of patients (71.1%) experienced PSA decline over 50%. Median PFS and CSS were 5.4 and 13.2 months, respectively. Serum testosterone at initial enzalutamide use was the noble predictor for progression (hazard ratio [HR], 0.409; p=0.020) and cancer-specific death (HR, 0.454; p=0.033) in postchemotherapy group. No significant effect of serum testosterone in prechemotherapy group was detected. Time to CRPC, high-metastatic burden revealed as risk factors for PSA response, PFS, and CSS, both in prechemotherapy and postchemotherapy group. Conclusions High testosterone level at commencement of enzalutamide treatment was associated with a good prognosis in postdocetaxel setting, but not related to oncological outcomes in chemotherapy-naïve patients.

We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9%vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs <4; hazard ratio: 4.386; P = 0.0004) was the only significant predictor of BCR in the PSM cohort. Periurethral frozen sections had a sensitivity of 83.3% and a specificity of 84.2% in detecting PSM with Gleason pattern ≥4. Multivariate analysis showed that membranous urethra length (odds ratio [OR]: 0.79, P = 0.0376) and extracapsular extension of the apex (OR: 4.58, P = 0.0226) on magnetic resonance imaging (MRI) and positive periurethral tissue (OR: 17.85, P < 0.0001) were associated with PSM of the apex. PSM with Gleason pattern ≥4 is significantly predictive of BCR. Intraoperative frozen sections of periurethral tissue can independently predict PSM, whereas sections of the bladder neck and dorsal vein could not. Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes.