Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α2 ß1 expression.

Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT1 receptor, which effectively inhibits integrin α2 ß1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.

A comparative study of transperineal software-assisted magnetic resonance/ultrasound fusion biopsy and transrectal cognitive fusion biopsy of the prostate.

BACKGROUND: The advantages and disadvantages of transperineal and transrectal biopsies remain controversial in the era of prostate targeted biopsy. In this study, we compared the cancer detection and complication rates of transperineal magnetic resonance/ultrasound (MR/US) fusion biopsy and transrectal cognitive fusion biopsy of the prostate. METHODS: This was a comparative study of two prospectively collected cohorts. Men with clinically suspected prostate cancer and prostate imaging reporting and data system (PI-RADS) score ≥ 3 lesions on multi-parametric magnetic resonance imaging (mpMRI) were enrolled. They underwent either transperineal software fusion biopsy or transrectal cognitive fusion biopsy and systematic biopsy. The detection rates of any prostate cancer and clinically significant prostate cancer (csPC, defined as Gleason score ≥ 3 + 4) and the complication rates between both groups were analysed. RESULTS: Ninety-two and 85 patients underwent transperineal software fusion and transrectal cognitive fusion biopsies, respectively. The detection rate for any prostate cancer was similar between both groups (60.8% vs. 56.4%, p = 0.659). In terms of csPC detection, transperineal fusion biopsy outperformed transrectal fusion biopsy (52.2% vs. 36.5%, p = 0.036). In multivariate regression analysis, age, PI-RADS score > 3, and transperineal route were significant predictors of csPC. Meanwhile, transperineal biopsy resulted in a higher rate of urinary retention than transrectal biopsy (18.5% vs. 4.7%, p = 0.009). No serious infectious complications were noted, although a patient developed sepsis after transrectal biopsy. CONCLUSIONS: Transperineal software fusion biopsy provided a higher csPC detection rate than transrectal cognitive fusion biopsy and carried minimal risk for infectious complications in patients with MRI-visible prostate lesions.

Combining prostate health index and multiparametric magnetic resonance imaging in estimating the histological diameter of prostate cancer.

BACKGROUND: Although multiparametric magnetic resonance imaging (mpMRI) is widely used to assess the volume of prostate cancer, it often underestimates the histological tumor boundary. The aim of this study was to evaluate the feasibility of combining prostate health index (PHI) and mpMRI to estimate the histological tumor diameter and determine the safety margin during treatment of prostate cancer. METHODS: We retrospectively enrolled 72 prostate cancer patients who underwent radical prostatectomy and had received PHI tests and mpMRI before surgery. We compared the discrepancy between histological and radiological tumor diameter stratified by Prostate Imaging-Reporting and Data System (PI-RADS) score, and then assessed the influence of PHI on the discrepancy between low PI-RADS (2 or 3) and high PI-RADS (4 or 5) groups. RESULTS: The mean radiological and histological tumor diameters were 1.60 cm and 2.13 cm, respectively. The median discrepancy between radiological and histological tumor diameter of PI-RADS 4 or 5 lesions was significantly greater than that of PI-RADS 2 or 3 lesions (0.50 cm, IQR (0.00-0.90) vs. 0.00 cm, IQR (-0.10-0.20), p = 0.02). In the low PI-RADS group, the upper limit of the discrepancy was 0.2 cm; so the safety margin could be set at 0.1 cm. In the high PI-RADS group, the upper limits of the discrepancy were 1.2, 1.6, and 2.2 cm in men with PHI < 30, 30-60, and > 60; so the safety margin could be set at 0.6, 0.8, and 1.1 cm, respectively. CONCLUSIONS: Radiological tumor diameter on mpMRI often underestimated the histological tumor diameter, especially for PI-RADS 4 or 5 lesions. Combining mpMRI and PHI may help to better estimate the histological tumor diameter.

Prostate cancer-secreted CCN3 uses the GSK3ß and ß-catenin pathways to enhance osteogenic factor levels in osteoblasts.

Prostate cancer osteoblastic bone metastases are incurable and associated with chronic bone pain and a high mortality rate. Osteoclast-targeting drugs intended to prevent skeletal-related events associated with prostate cancer bone metastases do not prolong overall survival. Improved understanding of the bone-derived factors that contribute to prostate cancer osteoblastic bone metastases is required to design treatments that will improve morbidities and overall survival. Activated osteoblasts stimulate prostate cancer growth in bone. In this study, we report that prostate cancer conditioned medium (CM) promoted bone morphogenetic protein (BMP)-2, -4 and -7 production and the expression of osteogenic transcription factors Runx2 and osterix in osteoblasts. Treating the prostate cancer CM with antibody against CCN3 (nephroblastoma-overexpressed), a cysteine-rich protein that belongs to the CCN family, reduced all of these increases. Incubation of osteoblasts with CCN3 facilitated phosphorylation of GSK3ß and ß-catenin. GSK3ß and ß-catenin inhibitors or siRNAs all abolished CCN3-induced promotion of BMPs, Runx2 and osterix expression in osteoblasts. Our results indicate that prostate cancer-secreted CCN3 enhances BMP, Runx2 and osterix expression in osteoblasts via the GSK3ß and ß-catenin signaling pathways. This understanding of the role played by CCN3 in osteoblastic prostate bone metastasis may lead to more efficient targeted therapies.

Combining prostate health index and multiparametric magnetic resonance imaging in the diagnosis of clinically significant prostate cancer in an Asian population.

OBJECTIVE: To evaluate the practicability of combining prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (csPC) in an Asian population. PATIENTS AND METHODS: We prospectively enrolled patients who underwent prostate biopsy due to elevated serum prostate-specific antigen (PSA > 4 ng/mL) and/or abnormal digital rectal examination in a tertiary referral center. Before prostate biopsy, the serum samples were tested for PSA, free PSA, and p2PSA to calculate PHI. Besides, mpMRI was performed using a 3-T scanner and reported in the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2). The diagnostic performance of PHI, mpMRI, and combination of both was assessed. RESULT: Among 102 subjects, 39 (38.2%) were diagnosed with PC, including 24 (23.5%) with csPC (Gleason ≥ 7). By the threshold of PI-RADS ≥ 3, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to predict csPC were 100%, 44.9%, 35.8%, and 100%, respectively. By the threshold of PHI ≥ 30, the sensitivity, specificity, PPV, and NPV to predict csPC were 91.7%, 43.6%, 33.3%, and 94.4%, respectively. The area under the receiver operator characteristic curve of combining PHI and mpMRI was greater than that of PHI alone (0.873 vs. 0.735, p = 0.002) and mpMRI alone (0.873 vs. 0.830, p = 0.035). If biopsy was restricted to patients with PI-RADS 5 as well as PI-RADS 3 or 4 and PHI ≥ 30, 50% of biopsy could be avoided with one csPC patient being missed. CONCLUSION: The combination of PHI and mpMRI had higher accuracy for detection of csPC compared with PHI or mpMRI alone in an Asian population.

External validation of the Simplified PADUA REnal (SPARE) nephrometry system in predicting surgical outcomes after partial nephrectomy.

BACKGROUND: Pentafecta is a major goal in the era of partial nephrectomy (PN). Simplified PADUA REnal (SPARE) nephrometry system was developed to evaluate the complexity of tumor. However, the predictive ability in pentafecta of SPARE system is yet to be determined. The aim of this study was to externally validate the applicability of SPARE nephrometry system in predicting pentafecta achievement after partial nephrectomy, and to examine inter-observer concordance. METHODS: We retrospectively reviewed data of 207 consecutive patients who underwent PN between January 2012 and August 2018 at a tertiary referral center. We obtained SPARE, R.E.N.A.L., and PADUA scores and evaluated correlations among the nephrometries and surgical outcomes including pentafecta by Spearman test. Logistic regression analysis was used to identify independent predictors of pentafecta outcomes. We compared the nephrometries to determine the predictive ability of achieving pentafecta using receiver operating characteristic curve analysis. Fleiss' generalized kappa was used to assessed interobserver variation in the SPARE system. RESULTS: Based on the SPARE system, 120, 74, and 13 patients were stratified into low-risk, intermediate-risk, and high-risk groups, respectively. Regarding the individual components of pentafecta, there were significant differences in the complication rate (p = 0.03), ischemia time (p < 0.001), and percent change of eGFR (p < 0.001) among the three risk groups. In addition, higher tumor complexity was significantly associated with a lower achievement rate of pentafecta (p = 0.01). In Spearman correlation tests, SPARE nephrometry was correlated with ischemia time (ρ:0.37, p < 0.001), operative time (ρ:0.28, p < 0.001), complication rate (ρ:0.34, p < 0.001), percent change of eGFR (ρ:0.34, p < 0.001), and progression of chronic kidney disease stage (ρ:0.17, p = 0.02). Multivariate analysis revealed that SPARE significantly affected pentafecta (OR: 0.67, p < 0.001). In ROC curve analysis, SPARE showed fair predictive ability in the achievement pentafecta (AUC: 0.71). The predictive ability of pentafecta was similar between nephrometries (SPARE vs. R.E.N.A.L., p = 0.78; SPARE vs. PADUA, p = 0.66). The interobserver concordance of SPARE was excellent (Kappa: 0.82, p = 0.03). CONCLUSIONS: SPARE system was a predictive factor of surgical outcomes after PN. This refined nephrometry had similar predictive abilities for pentafecta achievement compared with R.E.N.A.L. and PADUA.

Emotional sensitivity predicts internship performance of medical students enrolled under different admission screening protocols.

BACKGROUND AND PURPOSE: People with heightened emotional sensitivity can perceive better how others feel. Students admitted to medical school by interviews for assessing pre-set personal qualities, such as emotional sensitivity, may be more likely to meet patients' satisfaction in the future. We tested whether a student enrolled by passing the interview would have more emotional sensitivity than those by taking an exam. We also investigated what impact the enrolment protocols might have on students' internship performance. METHODS: Participants were first- and second-year medical students and assigned into the interviewed group or examined group according to the entrance protocols. Two emotion-related tasks and one control task were adopted. Subsequently, the performance evaluation of clinical work from students' advisors about these two groups of participants were collected after they finished the internship training at the hospital. CONCLUSIONS: Students selected through the pre-programmed interview which is based on personal qualities showed greater emotional sensitivity than those selected by the exam. Those students with better emotional sensitivity also performed better when they were in the internship training. Emotional sensitivity is a valid index to predict students' future performance and could be used in the selection protocol for medical students.

Danshen (Salvia miltiorhiza) inhibits Leu27 IGF-II-induced hypertrophy in H9c2 cells.

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.

The role of genotype/phenotype at apurinic/apyrimidinic endonuclease Rs1130409 in renal cell carcinoma.

The DNA repair capacity plays a critical role in maintaining the genomic stability and gatekeeping for individual cancer risk. In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein expressions by real-time quantitative reverse transcription method and Western blotting. The results showed that compared with the wild-type TT genotype, the people with TG and GG genotypes of apurinic/APE Asp148Glu had 0.88- and 1.09-fold risk of RCC, respectively. We have also examined the in vivo transcriptional (RNA) and translational (protein) levels with renal tissues of various apurinic/APE Asp148Glu genotypes, revealing that the apurinic/APE mRNA and protein were of similar levels among people of TT, TG, or GG genotypes. There was no joint gene-environment effect of apurinic/APE Asp148Glu genotype and smoking habit on RCC risk. The evidence indicated that apurinic/APE Asp148Glu genotypic variants did not alter its mRNA and protein expression among RCC patients. The genotype of apurinic/APE Asp148Glu may not serve as a proper predictive marker for RCC risk in Taiwan.

Osajin displays potential antiprostate cancer efficacy via impairment of fatty acid synthase and androgen receptor expression.

BACKGROUND: Currently, antiprostate cancer (PCa) drugs, including androgen deprivation therapy (ADT), are initially effective; however, most patients with PCa who receive ADT eventually progress to deadly aggressiveness. There is an urgent need to seek alternative strategies to cure this lethal disease. Activation of lipogenesis has been demonstrated to lead to PCa progression. Therefore, targeting the aberrant lipogenic activity could be developed therapeutically in PCa. The aim of this study is to investigate the molecular basis and efficacy of osajin, a bioactive prenylated isoflavonoid, in PCa. METHODS: PCa cells, LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant), were used in this study. Proliferation, migration, and invasion analyses were conducted by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, a wound healing assay, and the transwell method. Lipogenesis was determined by a Fatty Acid Quantification Kit and oil red O staining. Apoptosis was assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, caspase enzymatic activity, and Western blot analyses. RESULTS: Osajin inhibited fatty acid synthase (FASN) expression, a key enzyme for lipogenesis, in PCa cells. By inhibiting FASN, osajin decreased the fatty-acid levels and lipid accumulation. Significantly, osajin downregulated androgen receptor (AR) and prostate-specific antigen (PSA) in PCa cells. Moreover, osajin suppressed PCa cell growth, migration, and invasion. Through activation of the caspase-dependent pathway, osajin induced apoptosis in PCa cells. CONCLUSIONS: These data provide a novel molecular basis of osajin in PCa cells, and cotargeting lipogenesis and the AR axis via impairment of FASN and AR expression by osajin could be applied as a new and promising approach for the treatment of malignant PCa.

The role of RENAL, PADUA, C-index, CSA nephrometry systems in predicting ipsilateral renal function after partial nephrectomy.

BACKGROUND: Functional outcome is an important issue in nephron-sparing surgery. Various nephrometries have been developed to predict renal function preservation. The aim of this study was to examine the applicability of R.E.N.A.L., PADUA, C-index, and mathematical tumor contact surface area (CSA) in predicting ipsilateral renal function after partial nephrectomy using radio-isotope scans. METHODS: We performed this retrospective study in patients who underwent partial nephrectomy between May 2013 and April 2017, and used abdominopelvic computerized tomography or magnetic resonance imaging to obtain R.E.N.A.L., C-index, and CSA. Renal function was measured by 99mTc mercaptoacetyltriglycine (MAG3). We evaluated correlations between nephrometries and perioperative parameters, and comparatively analyzed different nephrometries to determine the predictive ability in the percent change of effective renal plasma flow of the affected kidney. RESULTS: Three, two, and 35 patients received partial nephrectomy in open, laparoscopic, and robotic approaches, respectively. The median (IQR) tumor size was 3.13 (2.4) cm. The median (IQR) R.E.N.A.L., PADUA, C-index, and CSA scores were 7 (3), 8 (2), 2.01 (1.87), and 14.14 (19.25) cm2, respectively. Spearman correlation analysis showed that four nephrometries were correlated with each other. The strongest correlations were between CSA and C-index (coefficient: - 0.885, p < 0.001), followed by R.E.N.A.L. and PADUA (coefficient: 0.778, p < 0.001). Ischemia time was significantly correlated with R.EN.A.L. (coefficient: 0.35, p = 0.025), PADUA (coefficient: 0.42, p = 0.007), C-index (coefficient: - 0.45, p = 0.004), and CSA (coefficient: 0.41, p = 0.009). In multivariate analysis, PADUA significantly affected ischemia time (p = 0.04). The percent change in effective renal plasma flow (PCE) of the operated kidney was correlated with PADUA (coefficient: 0.48 p = 0.002), C-index (coefficient: - 0.74, p < 0.001), and CSA (coefficient: 0.75, p < 0.001). Only CSA and C-index independently affected PCE (both p < 0.05) in multivariate analysis. In ROC curve analysis, both C-index and CSA could predict 20% change in effective renal plasma flow (AUC: 0.91 vs 0.86, p = 0.2) of the affected kidney. CONCLUSIONS: We suggest using PADUA to evaluate surgical complexity and ischemia time. Regarding the accuracy of the prediction of post-operative ipsilateral renal function, both CSA and C-index outperformed R.E.N.A.L. and PADUA nephrometries.

Contribution of Inflammatory Cytokine Interleukin-18 Genotypes to Renal Cell Carcinoma.

Interleukin-18 (IL-18) is a multi-functional immuno-mediator in the development and progression of many types of infectious and inflammatory diseases. In this study, we evaluated the contribution of IL-18 genotypes to renal cell carcinoma (RCC) in Taiwan via the genotyping of IL-18 -656 (A/C), -607 (A/C), and -137 (G/C). Moreover, we analyzed their interactions with smoking, alcohol drinking, hypertension, and diabetes status. The results showed an association of the AC and CC genotypes of IL-18 -607 with a significant decrease in the risk of RCC compared with the AA genotype (odds ratio (OR) = 0.44 and 0.35, 95% confidence interval (CI) = 0.27⁻0.72 and 0.18⁻0.66, p = 0.0008 and 0.0010, respectively). Furthermore, a significantly lower frequency of the C allele at -607 was observed in the RCC group (35.3% vs. 49.8%; OR = 0.53; 95% CI = 0.35⁻0.71, p = 0.0003). However, IL-18 -656 and -137 did not exhibit a likewise differential distribution of these genotypes between the control and case groups. Stratifying the population according to smoking, alcohol drinking, hypertension, and diabetes status revealed a different distribution of IL-18 -607 genotypes among non-smokers, non-drinkers, and patients without diabetes, but not among smokers, drinkers, or patients with diabetes. These findings suggest that IL-18 -607 genotypes may play a role in the etiology and progression of RCC in Taiwan and may serve as a useful biomarker for early detection.

Ganoderma tsugae Inhibits the SREBP-1/AR Axis Leading to Suppression of Cell Growth and Activation of Apoptosis in Prostate Cancer Cells.

Recent research suggests that the activation of lipid biosynthesis (lipogenesis) is linked with prostate cancer (PCa) malignancy. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcriptional regulator controlling lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an important role in lethal PCa aggressiveness from androgen-responsive to castration-resistant status. In this study, we showed that the quality-assured Ganoderma tsugae ethanol extract (GTEE), a Chinese natural and herbal product, significantly inhibited expression of SREBP-1 and its downstream genes associated with lipogenesis in PCa cells. Through inhibiting SREBP-1, GTEE reduced the levels of intracellular fatty acids and lipids in PCa cells. Importantly, GTEE also downregulated the expression of AR and prostate-specific antigen (PSA) in both androgen-responsive and castration-resistant PCa cells. By blocking the SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well as activating the caspase-dependent apoptotic pathway in PCa cells. These data provide a new molecular basis of GTEE for the development of a potential therapeutic approach to treat PCa malignancy.

Zanthoxylum avicennae extract enhances GSK-3ß to attenuate ß-catenin via phosphatase 2A to block metastatic effects of HA22T cells and hepatocellular carcinoma xenografted nude mice.

Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/ß-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on ß-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft nude mice were used to confirm the assessed cellular effects. Mice treated with YBBEs showed a strong increasing trend in PP2Acα, GSK-3ß, APC, and ß-TrCP/HOS levels, however the expression of ß-catenin, p-GSK-3ß, TBX 3, and IL8 proteins showed a decreasing trend. YBBE significantly downregulated the nuclear and cytosolic ß-catenin levels by facilitating the proteosomal degradation of ß-catenin. Moreover, as observed by co-immunoprecipitation assay, YBBE directly promoted the protein interactions between GSK-3ß, ß-TrCP, APC, PP2A, and ß-catenin. In conclusion, both in vitro and in vivo models clearly demonstrated that YBBE inhibits ß-catenin involved metastatic signaling in highly metastatic HA22T cells through PP2A activation.

The percentage of resected and ischemic volume determined by a geometric model is a significant predictor of renal functional change after partial nephrectomy.

PURPOSE: The percentage of parenchyma preserved plays a predominant role in predicting renal function after partial nephrectomy (PN). Currently there is no standard method to estimate preserved renal parenchyma. In this study we propose a formula of the percentage of resected and ischemic volume (PRAIV) determined by a geometric model and evaluate the relationships between renal functional change and PRAIV as well as other clinical parameters. MATERIALS AND METHODS: We identified 71 patients who underwent open PN between January 2004 and April 2014. Assuming the kidney to be an ellipsoid with bilaterally equal volume and tumor to be a sphere, we calculated PRAIV by integral calculus. Nadir estimated glomerular filtration rate (eGFR) between postoperative 3 and 12 months were recorded. The correlation between percent eGFR reduction, PRAIV, and other clinical parameters were examined. RESULTS: On univariate analysis, age (p=0.03), depth of tumor invasion (p=0.004), C index (p=0.003), RAIV (p=0.04), and PRAIV (p<0.001) were correlated with percent reduction of eGFR. However, only age (p=0.007) and PRAIV (p<0.001) were significantly correlated with percent reduction of eGFR on multivariate analysis. Depicting these values along the regression line, we found R2 was 0.194 and 0.073 for PRAIV and age, respectively. CONCLUSIONS: PRAIV determined by a geometric model is a significant predictor of renal functional change after PN. Using PRAIV, we can estimate percent eGFR reduction preoperatively for better patient consultation and surgical planning.

A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

PURPOSE: We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. MATERIALS AND METHODS: We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. RESULTS: Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). CONCLUSIONS: Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy.

Chemiluminescence analysis of antioxidant capacity for serum albumin isolated from healthy or uremic volunteers.

Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end-stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD-ALB) or healthy volunteers (N-ALB). From high-performance liquid chromatography spectra, we observed that one uremic solute binds to HD-ALB via the formation of disulfide bonds between HD-ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N-ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD-ALB. Our results suggest that protein-bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD-ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd.

Mitotic arrest induced in human DU145 prostate cancer cells in response to KHC-4 treatment.

In this study, the antitumor activity of KHC-4 was analyzed using human prostate cancer (CaP) cells and the underlining anticancer mechanisms of KHC-4 were identified. KHC-4 inhibited cell proliferation and induced cytotoxicity in the castration-resistant CaP DU145 cell line. The most effective concentration of KHC-4 was 0.1 µM. Cell cycle analysis demonstrated that KHC-4 treatment caused G2/M arrest and a subsequent increase in the sub-G1 population. Furthermore, KHC-4 is up-regulated p21, p27, and p53 in a time- and concentration-dependent manner. The exposure of cells to KHC-4 induced Cdk1/cyclin B1 complex activity, which led to cell cycle arrest. Moreover, KHC-4 inhibited the activities of MMP-2 and MMP-9 to inhibit tumor cell metastasis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1879-1887, 2016.