Urinary tract infection after radiation therapy or radical prostatectomy on the prognosis of patients with prostate cancer: a population-based study.

BACKGROUND: We aimed to assess the trends in urinary tract infections (UTIs) and prognosis of patients with prostate cancer after radical prostatectomy (RP) and radiation therapy (RT) as definitive treatment options. METHODS: The data of patients diagnosed with prostate cancer between 2007 and 2016 were collected from the National Health Insurance Service database. The incidence of UTIs was evaluated in patients treated with RT, open/laparoscopic RP, and robot-assisted RP. The proportional hazard assumption test was performed using the scaled Schoenfeld residuals based on a multivariable Cox proportional hazard model. Kaplan-Meier analysis were performed to assess survival. RESULTS: A total of 28,887 patients were treated with definitive treatment. In the acute phase (< 3 months), UTIs were more frequent in RP than in RT; in the chronic phase (> 12 months), UTIs were more frequent in RT than in RP. In the early follow-up period, the risk of UTIs was higher in the open/laparoscopic RP group (aHR, 1.63; 95% CI, 1.44-1.83; p < 0.001) and the robot-assisted RP group (aHR, 1.26; 95% CI, 1.11-1.43; p < 0.001), compared to the RT group. The robot-assisted RP group had a lower risk of UTIs than the open/laparoscopic RP group in the early (aHR, 0.77; 95% CI, 0.77-0.78; p < 0.001) and late (aHR, 0.90; 95% CI, 0.89-0.91; p < 0.001) follow-up periods. In patients with UTI, Charlson Comorbidity Index score, primary treatment, age at UTI diagnosis, type of UTI, hospitalization, and sepsis from UTI were risk factors for overall survival. CONCLUSIONS: In patients treated with RP or RT, the incidence of UTIs was higher than that in the general population. RP posed a higher risk of UTIs than RT did in early follow-up period. Robot-assisted RP had a lower risk of UTIs than open/laparoscopic RP group in total period. UTI characteristics might be related to poor prognosis.

Co-transient expression of PSA-Fc and PAP-Fc fusion protein in plant as prostate cancer vaccine candidates and immune responses in mice.

KEY MESSAGE: PAP-FcK and PSA-FcK prostate cancer antigenic proteins transiently co-expressed in plant induce their specific humoral immune responses in mice. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been considered as immunotherapeutic antigens for prostate cancer. The use of a single antigenic agent is unlikely to be effective in eliciting immunotherapeutic responses due to the heterogeneous and multifocal nature of prostate cancer. Thus, multiple antigens have been combined to enhance their anti-cancer effects. In the current study, PSA and PAP were fused to the crystallizable region (Fc region) of immunoglobulin G1 and tagged with KDEL, the endoplasmic reticulum (ER) retention signal motif, to generate PSA-FcK and PAP-FcK, respectively, and were transiently co-expressed in Nicotiana benthamiana. Western blot analysis confirmed the co-expression of PSA-FcK and PAP-FcK (PSA-FcK + PAP-FcK) with a 1:3 ratios in the co-infiltrated plants. PSA-FcK, PAP-FcK, and PSA-FcK + PAP-FcK proteins were successfully purified from N. benthamiana by protein A affinity chromatography. ELISA showed that anti-PAP and anti-PSA antibodies successfully detected PAP-FcK and PSA-FcK, respectively, and both detected PSA-FcK + PAP-FcK. Surface plasmon resonance (SPR) analysis confirmed the binding affinity of the plant-derived Fc fusion proteins to FcγRI/CD64. Furthermore, we also confirmed that mice injected with PSA-FcK + PAP-FcK produced both PSA- and PAP-specific IgGs, demonstrating their immunogenicity. This study suggested that the transient plant expression system can be applied to produce the dual-antigen Fc fusion protein (PSA-FcK + PAP-FcK) for prostate cancer immunotherapy.

Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study.

PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.

Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume.

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9'α-O-ß-d-xylopyranoside (3), (+)-catechin (4), (-)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 5-7 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 5-7 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1ß. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis.

Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression.

We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02-0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author's knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors.

Nicotine in high concentration causes contraction of isolated strips of rabbit corpus cavernosum.

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

Single nucleotide polymorphisms in fibroblast growth factor 23 gene, FGF23, are associated with prostate cancer risk.

OBJECTIVE: To determine whether sequence variants within the FGF23 gene are associated with the risk of developing prostate cancer in a Korean population. PATIENTS AND METHODS: Five common single nucleotide polymorphisms (SNPs) in the FGF23 gene were assessed in 272 patients with prostate cancer and 173 control subjects with benign prostatic hyperplasia. Single-locus analyses were conducted using conditional logistic regression. In addition, we performed a haplotype analysis for the five FGF23 SNPs tested. RESULTS: Three SNPs in the FGF23 gene (rs11063118, rs13312789 and rs7955866) were associated with an increased risk of prostate cancer in our study population. Odds ratios for homozygous variants vs wild-type variants ranged from 1.68 (95% confidence interval [CI]: 1.15-2.46) to 1.79 (95% CI: 1.16-2.75). CONCLUSION: This is the first study showing that genetic variations in FGF23 increase prostate cancer susceptibility.

The association between KL polymorphism and prostate cancer risk in Korean patients.

The Klotho (KL) gene is a classical "aging suppressor" gene. Although recent studies have shown that KL participates in the progression of several types of human cancers, the relationship between KL polymorphism and prostate cancer was unknown. The present study aimed to investigate the association between KL genetic polymorphisms and prostate cancer. Twenty-five common single nucleotide polymorphisms (SNPs) in KL gene (including KL gene polymorphism C1818T in exon 4) were assessed in 272 prostate cancer cases and 173 controls. Single-locus analyses were conducted using unconditional logistic regression. In addition, we did a haplotype analysis for the 25 KL SNPs tested. CC genotype of C1548T KL polymorphism had approximately twofold increased prostate cancer risk compared with the homozygous genotype TT and heterozygote CT (odds ratio 1.85 [95% CI, 1.09-3.12], P = 0.02). We also found that non-T allele carriers had significantly higher prostate cancer risk associated with the prostate cancer clinical characteristics (tumor stage or Gleason score). Our findings suggested that the C1548T polymorphism of KL gene is associated with the prostate cancer and may act as a risk factor for the development of prostate cancer.

Corrigendum: Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

This corrects the article on p. 446 in vol. 41, PMID: 36649918.

Selection of Convolutional Neural Network Model for Bladder Tumor Classification of Cystoscopy Images and Comparison with Humans.

Purpose: An investigation of various convolutional neural network (CNN)-based deep learning algorithms was conducted to select the appropriate artificial intelligence (AI) model for calculating the diagnostic performance of bladder tumor classification on cystoscopy images, with the performance of the selected model to be compared against that of medical students and urologists. Methods: A total of 3,731 cystoscopic images that contained 2,191 tumor images were obtained from 543 bladder tumor cases and 219 normal cases were evaluated. A total of 17 CNN models were trained for tumor classification with various hyperparameters. The diagnostic performance of the selected AI model was compared with the results obtained from urologists and medical students by using the receiver operating characteristic (ROC) curve graph and metrics. Results: EfficientNetB0 was selected as the appropriate AI model. In the test results, EfficientNetB0 achieved a balanced accuracy of 81%, sensitivity of 88%, specificity of 74%, and an area under the curve (AUC) of 92%. In contrast, human-derived diagnostic statistics for the test data showed an average balanced accuracy of 75%, sensitivity of 94%, and specificity of 55%. Specifically, urologists had an average balanced accuracy of 91%, sensitivity of 95%, and specificity of 88%, while medical students had an average balanced accuracy of 69%, sensitivity of 94%, and specificity of 44%. Conclusions: Among the various AI models, we suggest that EfficientNetB0 is an appropriate AI classification model for determining the presence of bladder tumors in cystoscopic images. EfficientNetB0 showed the highest performance among several models and showed high accuracy and specificity compared to medical students. This AI technology will be helpful for less experienced urologists or nonurologists in making diagnoses. Image-based deep learning classifies bladder cancer using cystoscopy images and shows promise for generalized applications in biomedical image analysis and clinical decision making.

Ethanol Extracts of Cornus alba Improve Benign Prostatic Hyperplasia by Inhibiting Prostate Cell Proliferation through Modulating 5 Alpha-Reductase/Androgen Receptor Axis-Mediated Signaling.

PURPOSE: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. MATERIALS AND METHODS: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. RESULTS: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. CONCLUSIONS: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.

Algoriphagus chungangensis sp. nov., isolated from a tidal flat sediment.

A Gram-stain-negative, non-spore-forming, non-motile, strictly aerobic, rod-shaped bacterial strain, designated CAU 1002(T), was isolated from a tidal flat sediment and its taxonomic position was investigated using a polyphasic approach. Strain CAU 1002(T) grew optimally at 30 °C and pH 7.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1002(T) formed a distinct lineage within the genus Algoriphagus and was most closely related to Algoriphagus lutimaris KCTC 22630(T) and Algoriphagus halophilus KCTC 12051(T) (97.75 and 97.74 % 16S rRNA gene sequence similarity, respectively). The strain contained MK-7 as the major isoprenoid quinone and iso-C(15 : 0) and C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH (summed feature 3) as the major fatty acids. The cell-wall peptidoglycan of strain CAU 1002(T) contained meso-diaminopimelic acids. The major whole-cell sugars were glucose, arabinose, sucrose, and ribose. The polar lipid profile was composed of phosphatidylethanolamine, five unidentified aminolipids, one unidentified aminophospholipid, one unidentified phospholipid, one unidentified aminoglycolipid, one unidentified glycolipid and twelve unidentified lipids. The DNA G+C content of strain CAU 1002(T) was 38.0 mol%. On the basis of phylogenetic inference, phenotypic, chemotaxonomic and genotypic data, strain CAU 1002(T) should be classified into the genus Algoriphagus as a member of a novel species, for which the name Algoriphagus chungangensis sp. nov. is proposed. The type strain is CAU 1002(T) ( = KCTC 23759(T) = CCUG 61890(T)). The description of the genus Algoriphagus is emended.

Haloferula chungangensis sp. nov., isolated from marine sediment.

A Gram-stain-negative, non-spore-forming, non-motile, strictly aerobic, rod-shaped bacterial strain, designated CAU 1074(T), was isolated from marine sediment and its taxonomic position was investigated using a polyphasic approach. Strain CAU 1074(T) grew optimally at 30 °C and pH 6.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1074(T) formed a distinct lineage within the genus Haloferula and was most closely related to Haloferula harenae KCTC 22198(T) (96.0% similarity). Strain CAU 1074(T) contained MK-9 as the major isoprenoid quinone, and iso-C(14:0,) C(16:1)ω9c and C(16:0) as the major fatty acids. The cell wall peptidoglycan contained meso-diaminopimelic acid. The major whole-cell sugars were glucose, xylose, mannose and ribose. The polar lipids were composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, aminoglycolipid and two unidentified phospholipids. The DNA G+C content of the strain was 64.0 mol%. On the basis of phenotypic and chemotaxonomic data, and phylogenetic inference, strain CAU 1074(T) should be classified as a member of a novel species in the genus Haloferula, for which the name Haloferula chungangensis sp. nov. is proposed; the type strain is CAU 1074(T) (= KCTC 23578(T) = CCUG 61920(T)). An emended description of the genus Haloferula is also provided.

Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation.

BACKGROUND AND PURPOSE: Geldanamycin and licochalcone A induce apoptosis in cancer cells. However, whether the combination of geldanamycin and licochalcone A-induced apoptosis in epithelial ovarian cancer cells is mediated by the formation of reactive oxygen species, leading to the activation of apoptotic caspase, has not been studied. EXPERIMENTAL APPROACH: Using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3, we investigated the promoting effect of licochalcone A on geldanamycin-induced apoptosis. RESULTS: Geldanamycin induced changes in apoptosis-related protein levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, cleavage of PARP-1, formation of reactive oxygen species and depletion of glutathione (GSH). Licochalcone A enhanced geldanamycin-induced apoptosis-related protein activation, formation of reactive oxygen species, caspase activation and cell death. The combined effect was inhibited by the addition of oxidant scavengers. CONCLUSIONS: Licochalcone A may potentiate the apoptotic effect of geldanamycin on ovarian carcinoma cell lines by the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway. The apoptosis-promoting effect of licochalcone A may be mediated by its stimulatory action on the formation of reactive oxygen species and the depletion of GSH, which results in the activation of caspases.

Correlation of metabolic syndrome with urinary stone composition.

OBJECTIVE: To determine the correlation between metabolic syndrome and the distribution of stone components in patients with urolithiasis. METHODS: Between January 2007 and December 2010, renal or ureteral stones were collected from 712 patients (432 males, 280 females) who underwent surgical intervention at three hospitals in South Korea. Metabolic syndrome was defined according to the latest definition of the International Diabetes Federation, using ethnicity- and sex-specific cut-off values for central obesity. Patients were assessed by factors used in metabolic syndrome. All urinary stones were analyzed using infrared spectrophotometry and categorized according to their main component. RESULTS: The patients' mean age was 55.9 years (range 19-93 years). Of the 712 patients, 347 (48.7%; 205 males, 142 females) had a diagnosis of metabolic syndrome. Calcium oxalate (71.5%), uric acid (15.3%), carbonate apatite (8.0%) and struvite (4.1%) calculi were found as the main stone components. Overall, the proportion of uric acid calculi was markedly higher in patients with rather than without metabolic syndrome (19.6 vs 11.2%; P=0.002). However, the proportion of calcium oxalate, carbonate apatite and struvite calculi did not differ between the two groups. The multivariable-adjusted odds ratio for uric acid calculi according to the metabolic syndrome components indicated that the presence of metabolic syndrome was associated with a 93% increased odds ratio of uric acid calculi compared with the absence of metabolic syndrome. Impaired fasting glucose and hypertriglyceridemia were independent risk factors for uric acid calculi. CONCLUSIONS: Metabolic syndrome is associated with a significantly increased risk of uric acid calculi development, especially those with impaired fasting glucose and hypertriglyceridemia.

Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

PURPOSE: Testosterone hormonal replacement is the most commonly prescribed solution for men with reproductive issues; however, this treatment has various drawbacks. Hence, the identification of a natural product that promotes steroidogenesis is urgently needed. Ginseng is a popular traditional medicine. This study aimed to investigate steroidogenic effects of Korean ginseng berry extract (GBE; Panax ginseng C.A. Meyer) in vitro and in vivo. MATERIALS AND METHODS: In vitro model, mouse Leydig cells were treated with varying concentrations of GBE, and the levels of steroidogenesis-related genes and proteins and testosterone were measured using western blotting, qRT-PCR, and enzyme-linked immunosorbent assay (ELISA). Similarly, in an in vivo model using lipopolysaccharide-injected C57BL/6J mice, expression of steroidogenesis-related genes and proteins and testosterone levels were analyzed. Additionally, sleep deprivation was used to simulate common life stressors related to late-onset hypogonadism (LOH) and the natural effects of aging. Mice were fed sham or GBE before being subjected to paradoxical sleep deprivation. RESULTS: In vitro, GBE induced steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, steroidogenic acute regulatory protein (STAR), CYP11A1, and CYP17A1. In vivo, GBE significantly increased mRNA and protein levels of steroidogenic enzymes. Furthermore, the synthetic testosterone levels in mouse Leydig cell supernatants and blood sera were increased. In the sleep deprivation study, mice fed GBE showed increased testosterone production and survival under such stressful conditions. CONCLUSIONS: GBE increased mRNA and protein levels of steroidogenesis-related enzymes STAR, CYP11A1, and CYP17A1. These key enzymes induced the increased production of testosterone both in vivo and in vitro. Thus, GBE might be a promising therapeutic or additive nutritional agent for improving men's health by increasing steroidogenesis or improving LOH.

The ethanol extract of Cyperus exaltatus var. iwasakii exhibits cell cycle dysregulation, ERK1/2/p38 MAPK/AKT phosphorylation, and reduced MMP-9-mediated metastatic capacity in prostate cancer models in vitro and in vivo.

BACKGROUND: Prostate cancer is the second most common cause of cancer death worldwide in men. The development of novel and highly efficient therapeutic strategies is strongly recommended to treat prostate cancer. Cyperaceae are an ecologically and economically important family of plants with several pharmacological effects. However, the biological efficacy of Cyperus exaltatus var. iwasakii (CE) is unknown. PURPOSE: This study aimed to investigate the antitumor effect of the ethanol extract of CE against prostate cancer. METHODS: In vitro antitumor efficacy of CE was explored by the MTT assay, cell counting assay, FACS analysis, immunoblot, wound-healing migration, invasion assay, zymographic assay, and EMSA in prostate cancer cells, DU145 and LNCaP. For in vivo experiments, xenograft mice were injected with LNCaP cells. Histology (H&E and Ki-67) and biochemical enzyme assay were then performed. The toxicity test was evaluated by an acute toxicity assay. The phytochemical constituents of CE were identified by spectrometric and chromatographic analyses. RESULTS: CE exerted a significant antiproliferative effect against prostate cancer cells. CE-induced antiproliferative cells were associated with cell cycle arrest at G0/G1 (cyclin D1/CDK4, cyclin E/CDK2, p21Waf1) in DU145 cells, but G2/M (ATR, CHK1, Cdc2, Cdc25c, p21Waf1, and p53) in LNCaP cells. CE stimulated the phosphorylation of ERK1/2, p38 MAPK, and AKT in DU145 cells, but only p38 MAPK phosphorylation was increased in LNCaP cells. CE treatment suppressed migration and invasion in the two types of prostate cancer cells by inhibiting MMP-9 activity through the regulation of transcription factors, such as AP-1 and NF-κB. In vivo experiments showed a reduction in tumor weight and size following oral CE administration. Histochemistry confirmed that CE inhibited tumor growth in the mouse LNCaP xenograft model. The administration of CE had no adverse effects on body weight, behavioral patterns, blood biochemistry, and histopathology findings of vital organs in mice. Finally, a total of 13 phytochemical constituents were identified and quantified in CE. The most abundant secondary metabolites in CE were astragalin, tricin, and p-coumaric acid. CONCLUSION: Our results demonstrated the antitumor efficacy of CE against prostate cancer. These findings suggest that CE might be a potential candidate for prostate cancer prevention or treatment.

Shifting role of cytoreductive nephrectomy according to type of systemic therapy: A nationwide cohort study.

PURPOSE: The best protocol of cytoreductive nephrectomy (CN) and systemic therapy (ST) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear. We sought to evaluate overall survival (OS) in patients with mRCC treated with ST with or without CN. METHODS: We collected data from the National Health Insurance Service database. We excluded 2 years of washout period, 2 years of follow-up period, other cancer diagnoses within 2 years, and ≥4 months interval between ST and CN. The patients were divided into two groups according to whether CN was performed. Kaplan-Meier, propensity score matching, Cox regression model, and incremental survival analyses were conducted. Additionally, we performed subgroup analysis according to whether cytokine therapy or targeted therapy was used as first-line ST. RESULTS: Of 6478 patients, 1707 (26.4%) underwent CN. The CN group showed significantly better OS than the no CN group (p < 0.001). In the cytokine therapy subgroup, patients who underwent CN had significantly higher OS than those who did not (p < 0.001). In the targeted therapy subgroup, no significant difference was found (p = 0.867). In multivariate analysis, CN was associated with better OS in the total cohort (hazard ratio 0.819, p < 0.001). The incremental OS benefit of CN ranged from +0.98 in patients who survived for <24 months to +2.13 in those who survived during all periods. CONCLUSION: About a quarter patients with mRCC from a nationwide database were treated with CN and ST. CN was beneficial in specific patients with mRCC. Patient selection is crucial for obtaining the benefits of CN.

Changes in patient perceptions regarding ChatGPT-written explanations on lifestyle modifications for preventing urolithiasis recurrence.

Purpose: Artificial Intelligence (AI) imitating human-like language, such as ChatGPT, has impacted lives throughout various multidisciplinary fields. However, despite these innovations, it is unclear how well its implementation will assist patients in clinical situations. We evaluated changes in patient perceptions regarding AI before and after reading a ChatGPT-written explanation. Materials and methods: In total, 24 South Korean patients receiving urolithiasis treatment were surveyed through questionnaires. The ChatGPT explanatory note was provided between the first and second questionnaires, detailing lifestyle modifications for preventing urolithiasis recurrence. The study questionnaire was the Korean version of the General Attitudes toward Artificial Intelligence Scale, including positive and negative attitude items. Wilcoxon signed-rank tests were accomplished to compare questionnaire scores before and after receiving the explanatory note. A linear regression analysis with stepwise elimination was used to assess variable (demographic data) accuracy in predicting outcomes. Results: There were significant differences between total negative questionnaire scores pre- and post-surveys of ChatGPT, but not in the positive scores. Among variables, only education level significantly influenced mean score differences in the negative questionnaires. Conclusions: The negative perception change among urolithiasis patients after receiving the explanatory note provided by the AI chatbot program was observed, evidencing that patients with lower education levels expressed a more negative response. The explanatory note provided by the AI chatbot program could provoke an adverse change in AI perception. Negative human responses must be considered to improve and adapt new technology in health care. Only through changing patient perspectives will upgraded AI technology integrate into medical healthcare.

Oral chemotherapeutic agents in metastatic hormone-sensitive prostate cancer: A network meta-analysis of randomized controlled trials.

Background: Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents. Materials and methods: We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate. Results: We identified 18 RCTs (n = 13,509). Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide. ADT + docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis. Conclusions: Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.