Therapeutic Efficacy of YM155 to Regulate an Epigenetic Enzyme in Major Subtypes of RCC.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and includes more than 10 subtypes. Compared to the intensively investigated clear cell RCC (ccRCC), the underlying mechanisms and treatment options of other subtypes, including papillary RCC (pRCC) and chromogenic RCC (chRCC), are limited. In this study, we analyzed the public databases for ccRCC, pRCC, and chRCC and found that BIRC5 was commonly overexpressed in a large cohort of pRCC and chRCC patients as well as ccRCC and was closely related to the progression of RCCs. We investigated the potential of BIRC5 as a therapeutic target for these three types of RCCs. Loss and gain of function studies showed the critical role of BIRC5 in cancer growth. YM155, a BIRC5 inhibitor, induced a potent tumor-suppressive effect in the three types of RCC cells and xenograft models. To determine the mechanism underlying the anti-tumor effects of YM155, we examined epigenetic modifications in the BIRC5 promoter and found that histone H3 lysine 27 acetylation (H3K27Ac) was highly enriched on the promoter region of BIRC5. Chromatin-immunoprecipitation analysis revealed that H3K27Ac enrichment was significantly decreased by YM155. Immunohistochemistry of xenografted tissue showed that overexpression of BIRC5 plays an important role in malignancy in RCC. Furthermore, high expression of P300 was significantly associated with the progression of RCC. Our findings demonstrate the P300-H3K27Ac-BIRC5 cascade in three types of RCC and provide a therapeutic path for future research on RCC.

Predicting factor analysis of postoperative complications after robot-assisted radical cystectomy: Multicenter KORARC database study.

OBJECTIVES: To evaluate postoperative complications following robot-assisted radical cystectomy in patients diagnosed with bladder cancer and reveal if there are predictors for postoperative complications. METHODS: Prospectively collected medical records of 730 robot-assisted radical cystectomy patients between 2007/04 and 2019/05 in 13 tertiary referral centers were reviewed. Perioperative outcomes were compared between two groups by postoperative complications (complication vs non-complication). We assessed recurrence-free survival, cancer-specific survival, and overall survival between groups. Regression analyses were implemented to identify factors associated with postoperative complications. RESULTS: Any total and high-grade complication (Clavien-Dindo grade ≥3) rates were 57.8% and 21.1%, respectively. Patients in complication group had significantly higher proportion of diabetes mellitus (P = 0.048), chronic kidney disease (P = 0.011), dyslipidemia (P < 0.001), longer operation time (P = 0.001), more estimated blood loss (P = 0.001), and larger intraoperative fluid volume (P < 0.001). There was a significant difference in cancer-specific survival (log-rank P = 0.038, median cancer-specific survival: both groups not reached). Dyslipidemia (odds ratio 2.59, P = 0.002) and intraoperative fluid volume (odds ratio 1.0002, P = 0.040) were significantly associated with high-grade postoperative complications. Diabetes mellitus (odds ratio 1.97, P = 0.028), chronic kidney disease (odds ratio 1.89, P = 0.046), dyslipidemia (odds ratio 5.94, P = 0.007), and intraoperative fluid volume (odds ratio 1.0002, P = 0.009) were significantly associated with any postoperative complications. CONCLUSIONS: Patients with diabetes mellitus, chronic kidney disease, dyslipidemia, or a relatively large intraoperatively infused fluid volume are more likely to develop postoperative complications. Patients with postoperative complications might have a possibility of lower cancer-specific survival rate.

Oncological outcome according to attainment of pentafecta after robot-assisted radical cystectomy in patients with bladder cancer included in the multicentre KORARC database.

OBJECTIVES: To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS: Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS: Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS: Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.

Prospective assessment of urinary neutrophil gelatinase-associated lipoprotein in living kidney donors: toward understanding differences between chronic kidney diseases of surgical and medical origin.

OBJECTIVES: To evaluate the clinical implications of postoperative urinary neutrophil gelatinase-associated lipoprotein (NGAL) changes and the association between urinary NGAL (uNGAL) and renal function in living kidney donors. SUBJECTS, PATIENTS AND METHODS: We included 76 healthy adults who underwent donor nephrectomy between December 2013 and November 2014. Perioperative serum creatinine (sCr), uNGAL, serum NGAL (sNGAL), and urinary microalbumin were prospectively measured until 6 months postoperatively. Patients with chronic kidney disease (CKD) due to medical disorders who visited our outpatient clinic during the same period were included for comparison. RESULTS: The mean (SD) preoperative uNGAL of donors was 5 (5.17) ng/mL. uNGAL (corrected for urinary creatinine) was maximal at 1-2 days postoperatively, decreased on postoperative day 3, and stabilised by 7 days after surgery. Postoperative uNGAL was not associated with sex, age, or preoperative renal function. When corrected for sNGAL to compensate for the systemic increase in NGAL with major surgery, uNGAL on days 1-3 postoperatively was negatively correlated with sCr. Postoperatively, donor uNGAL remained higher than preoperatively for up to 6 months but was significantly lower than in patients with medical CKD with similar glomerular filtration rates. CONCLUSION: Acute kidney injury due to hyperfiltration of remnant kidney after donor nephrectomy was maximal within 1-2 days postoperatively. The rise in uNGAL during this period in donors was negatively correlated with postoperative sCr levels. Decreased renal function after nephrectomy differs from that of medical CKD.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

OBJECTIVES: To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. METHODS: A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. RESULTS: The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). CONCLUSION: We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered.

Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma.

Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised.

Usefulness of the diameter-axial-polar nephrometry score for predicting perioperative parameters in robotic partial nephrectomy.

PURPOSE: The present study aimed to verify the association between diameter-axial-polar (DAP) nephrometry and surgical outcomes, postoperative renal function, and perioperative complications in patients undergoing robotic partial nephrectomy (RPN). METHODS: Diameter-axial-polar nephrometry was assessed using computed tomography or magnetic resonance imaging on 158 patients who received RPN between July 2007 and February 2013. Demographic data, surgical data, and perioperative complications were recorded, and percent change between the preoperative and last estimated glomerular filtration rate (eGFR) was determined. Linear regression analysis was conducted to assess the relationship between the DAP sum score and warm ischemia time (WIT), estimated blood loss (EBL), and percent decrease in eGFR. Multivariable linear regression analysis was conducted to determine the relationship between each DAP scoring parameter and surgical outcomes. RESULTS: The median patient age was 50.5 years and median DAP sum score was 6. On linear regression, the DAP sum score was associated with WIT and EBL. On multivariable regression, all DAP parameters were associated with WIT, but the polar distance was not associated with EBL. Patients with a higher DAP sum score showed greater decrease in eGFR after RPN. Patients with a DAP sum score of 6 or higher had a higher risk of major complications than those with a DAP sum score below 6. CONCLUSIONS: Diameter-axial-polar nephrometry predicted WIT and EBL in patients who underwent RPN. It was also associated with the decrease in eGFR and rate of major perioperative complications, and thus can be useful for surgical planning or patient counseling before RPN.

Prospective measurement of urinary microalbumin in living kidney donor nephrectomy: toward understanding the renal functional recovery period.

PURPOSE: We determined the clinical implications of perioperative urinary microalbumin excretion in relation to renal function after living donor nephrectomy. MATERIALS AND METHODS: Between August 2010 and January 2013, 259 donors undergoing live donor nephrectomy were enrolled in the study. The donor urinary albumin-to-creatinine ratio was measured perioperatively, and changes in perioperative urinary albumin-to-creatinine ratio and the implications of preoperative microalbuminuria (urinary albumin-to-creatinine ratio 30 mg/gm or greater) were investigated. The relationships between perioperative urinary albumin-to-creatinine ratio and recovery of renal function and implantation biopsy histology were also analyzed. RESULTS: Mean ± SD preoperative urinary albumin-to-creatinine ratio was 7.1±12.7 mg/gm. The urinary albumin-to-creatinine ratio was increased after 1 day (24.7±18.9 mg/gm, p <0.001) and stabilized after 1 month (10.3±10.7 mg/gm, p <0.001). Preoperative microalbuminuria was not associated with perioperative estimated glomerular filtration rate during a followup period of 6 months but was associated with histological abnormalities. Donors with a higher urinary albumin-to-creatinine ratio before donation, even in the normal range, consistently had an increased postoperative urinary albumin-to-creatinine ratio. A ROC curve analysis showed that age, preoperative estimated glomerular filtration rate and 1-month postoperative urinary albumin-to-creatinine ratio were highly predictive of delayed recovery of renal function (AUC 0.884, p <0.001). The 1-month postoperative urinary albumin-to-creatinine ratio was associated with delayed recovery of renal function (OR 1.05 for each 0.1 mg/gm increase, p=0.021). CONCLUSIONS: Donors with higher preoperative urinary albumin-to-creatinine ratio levels require close observation because there is a greater possibility of microalbuminuria developing after donation even if the ratio is within the normal range. A higher urinary albumin-to-creatinine ratio was also associated with delayed recovery of renal function and histological abnormalities.

Robot-assisted radical prostatectomy in the Korean population: a 5-year propensity-score matched comparative analysis versus open radical prostatectomy.

OBJECTIVES: To compare the oncological outcomes of robot-assisted laparoscopic radical prostatectomy with those of open radical prostatectomy in contemporary Korean prostate cancer patients. METHODS: From a group of 1172 patients consisting of 592 (50.5%) robot-assisted laparoscopic radical prostatectomy and 580 (49.5%) open radical prostatectomy cases carried out between 1992 and 2008, 175 robot-assisted laparoscopic radical prostatectomy cases were matched with an equal number of open radical prostatectomy cases by propensity scoring based on patient age, preoperative prostate-specific antigen, biopsy Gleason score and clinical tumor stage. Competing-risks survival analyses were used to evaluate oncological outcomes, including rates of positive surgical margin, biochemical-recurrence, adjuvant therapy, cancer-specific survival, overall survival and metastasis-free survival during the mean follow up of 58.4 months. RESULTS: Positive surgical margin rates were comparable between robot-assisted laparoscopic radical prostatectomy and open radical prostatectomy cohorts (19.4% vs 21.8%), with comparable rates for all pathological stages and risk subgroups. Positive surgical margin rates according to location were comparable, with the apical margin being the most common location. Robot-assisted laparoscopic radical prostatectomy recovered higher lymph node yields compared with open radical prostatectomy (12.5 vs 3.8; P < 0.001). The robot-assisted laparoscopic radical prostatectomy and the open radical prostatectomy groups showed equal oncological outcomes regarding 5-year biochemical recurrence-free survival (log-rank P = 0.651), metastasis-free survival (log-rank P = 0.876), cancer-specific survival (log-rank P = 0.076) and overall survival (log-rank P = 0.648), respectively. Between groups, there was no difference in the rate of adjuvant therapy, time to first adjuvant therapy failure or in the rate of subsequent secondary treatment. CONCLUSIONS: Robot-assisted laparoscopic radical prostatectomy represents an effective surgical approach for the treatment of prostate cancer in the Korean population, as it provides equivalent oncological outcomes to open radical prostatectomy.

Kidney, ureter, and urinary bladder segmentation based on non-contrast enhanced computed tomography images using modified U-Net.

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Variation of Saponarin Content in Barley Sprouts (Hordeum vulgare L.) by Natural Light Shielding: Implication of the Importance of Light Intensity.

Saponarin is a functional metabolite produced by barley sprouts, and the mass production of saponarin by this crop is attractive for dietary supplement manufacturing. Light is the most important environmental factor determining plant growth, survival, and the production of secondary metabolites including flavonoids. This study was conducted to investigate the importance of light intensity for saponarin production in barley sprouts using a hydroponic growth system. Light intensity was manipulated by using shielding treatments to 100, 80, 70, and 50% natural sunlight (NS), and crop cultivation was performed on a monthly cycle. We found that the growth rate and biomass of barley sprouts did not differ in response to the shield treatments, whereas the saponarin content did. The highest saponarin content (i.e., from 1329 to 1673 mg 100 g-1) was observed in the 100% NS treatment, and it gradually decreased as light intensity also decreased. Statistical analysis revealed a significant polynomial relationship of saponarin content with cumulative PPFD (R2 = 76%), implying that the absolute total amount of light exposure over the growth period has a large effect on saponarin productivity in a hydroponic facility. Taken together, our results showed that shielding conditions, which are often unintentionally created by the design of cultivation facilities, can adversely affect saponarin production in barley sprouts. In addition, it was confirmed through our findings that light conditions with at least 70% NS in the cultivation facility enable the production of an amount corresponding to the saponarin content of the sprouts (>1000 mg 100 g-1) produced in the open field. Further studies are needed to investigate the underlying physiological and molecular mechanisms responsible for the relationship of saponarin content with light quantity and quality in barley sprouts.

Effect of α1D-adrenoceptor blocker for the reduction of ureteral contractions.

PURPOSE: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (α1-ARs) are abundant in ureteral smooth muscle, distributed with different α1-AR subtypes. α1D-AR is the most widely distributed in the ureter. However, the effect of α1D-AR blockade on ureteric contraction remains unknown. MATERIALS AND METHODS: We dissected smooth muscle tissues (3 mm×3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. RESULTS: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro , we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. CONCLUSIONS: We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones.

Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1.

The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.

Saponarin, a Di-glycosyl Flavone from Barley (Hordeum vulgare L.): An Effective Compound for Plant Defense and Therapeutic Application.

Saponarin (SA) is a major di-C-glycosyl-O-glycosyl flavone, which is predominantly accumulated in the young green leaves of barley (Hordeum vulgare L.), with numerous biological functions in plants, such as protection against environmental stresses. Generally, SA synthesis and its localization in the mesophyll vacuole or leaf epidermis are largely stimulated in response to biotic and abiotic stresses to participate in a plant's defense response. In addition, SA is also credited for its pharmacological properties, such as the regulation of signaling pathways associated with antioxidant and anti-inflammatory responses. In recent years, many researchers have shown the potential of SA to treat oxidative and inflammatory disorders, such as in protection against liver diseases, and reducing blood glucose, along with antiobesity effects. This review aims to highlight natural variations of SA in plants, biosynthesis pathway, and SA's role in response to environmental stress and implications in various therapeutic applications. In addition, we also discuss the challenges and knowledge gaps concerning SA use and commercialization.

Biostimulatory Effects of Chlorella fusca CHK0059 on Plant Growth and Fruit Quality of Strawberry.

Green algae have been receiving widespread attention for their use as biofertilizers for agricultural production, but more studies are required to increase the efficiency of their use. This study aimed to investigate the effects of different levels of Chlorella fusca CHK0059 application on strawberry plant growth and fruit quality. A total of 800 strawberry seedlings were planted in a greenhouse and were grown for seven months under different Chlorella application rates: 0 (control), 0.1, 0.2, and 0.4% of the optimal cell density (OCD; 1.0 × 107 cells mL-1). The Chlorella application was conducted weekly via an irrigation system, and the characteristics of fruit samples were monitored monthly over a period of five months. The growth (e.g., phenotype, dry weight, and nutrition) and physiological (e.g., Fv/Fm and chlorophylls) parameters of strawberry plants appeared to be enhanced by Chlorella application over time, an enhancement which became greater as the application rate increased. Likewise, the hardness and P content of strawberry fruits had a similar trend. Meanwhile, 0.2% OCD treatment induced the highest values of soluble solid content (9.3-12 °Brix) and sucrose content (2.06-2.97 g 100 g-1) in the fruits as well as fruit flavor quality indices (e.g., sugars:acids ratio and sweetness index) during the monitoring, whilst control treatment represented the lowest values. In addition, the highest anthocyanin content in fruits was observed in 0.4% OCD treatment, which induced the lowest incidence of grey mold disease (Botrytis cinerea) on postharvest fruits for 45 days. Moreover, a high correlation between plants' nutrients and photosynthetic variables and fruits' sucrose and anthocyanin contents was identified through the results of principal component analysis. Overall, C. fusca CHK0059 application was found to promote the overall growth and performance of strawberry plants, contributing to the improvement of strawberry quality and yield, especially in 0.2% OCD treatment.

TNM-Based Head-to-Head Comparison of Urachal Carcinoma and Urothelial Bladder Cancer: Stage-Matched Analysis of a Large Multicenter National Cohort.

PURPOSE: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. MATERIALS AND METHODS: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. RESULTS: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. CONCLUSION: Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Korean Society of Endourology and Robotics (KSER) recommendation on the diagnosis, treatment, and prevention of urolithiasis.

This article provides evidence-based recommendations and expert opinions to aid urologists in making optimal decisions regarding managing urolithiasis in various clinical scenarios. The most frequently asked questions by urologists in their clinical practice have been collected and answered in the form of FAQs; based on the latest evidence and expert opinions. The natural history of urolithiasis is divided into active treatment and silent phases, with the active treatment stage divided into typical and special situations and peri-treatment management. The authors address 28 key questions, offering practical guidance for the proper diagnosis, treatment, and prevention of urolithiasis in clinical practice. This article is expected to be served as a valuable resource for urologists.

Ginsenoside Rh2 sensitizes the anti-cancer effects of sunitinib by inducing cell cycle arrest in renal cell carcinoma.

Sunitinib, a VEGF blockade, is used to treat clear cell renal cell carcinoma (ccRCC). However, the anti-cancer treatment effects of sunitinib do not last long in ccRCC patients. Ginsenoside, a natural medicine extracted from ginseng, has been studied in cancer treatment and shown to have anti-tumor effects and low toxicity. We assessed cell viability and cell cycle analysis in ccRCC cell lines after treatment with ginsenoside and sunitinib. DNA damage was evaluated by measuring 8-OHdG levels and comet assay. ROS levels, reflecting the cause of oxidative stress, were also measured. Ginsenoside significantly enhanced the inhibition of cell viability by sunitinib, a result that was also confirmed in the xenograft model. In cell cycle analysis, combination treatment of ginsenoside and sunitinib enhanced G2M arrest in comparison with single-treatment groups. In addition, DNA damage was increased by ginsenoside and sunitinib according to the comet assay, and the level of 8-OHdG, which reflects oxidative DNA damage, also increased. We verified that ginsenoside enhances the efficacy of sunitinib to inhibit the proliferation of ccRCC cells via induction of oxidative DNA damage. The combination therapy of sunitinib and ginsenoside suggested the possibility of effectively treating ccRCC patients.