Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Advances in Male Contraception: When Will the Novel Male Contraception be Available?

Many contraceptive methods have been developed over the years due to high demand. However, female contraceptive pills and devices do not work for all females due to health conditions and side effects. Also, the number of males who want to actively participate in family planning is gradually increasing. However, the only contraceptive options currently available to males are condoms and vasectomy. Therefore, many male contraceptive methods, including medication (hormonal and non-hormonal therapy) and mechanical methods, are under development. Reversibility, safety, persistence, degree of invasion, promptness, and the suppression of anti-sperm antibody formation are essential factors in the development of male contraceptive methods. In this paper, male contraceptive methods under development are reviewed according to those essential factors. Furthermore, the timeline for the availability of a new male contraception is discussed.

Penile Erection Morphometry: The Need for a Novel Approach.

For many males, sexual function holds significant value in determining their quality of life. Despite the importance of male erectile function, no quantitative method to measure it accurately is currently available. Standardized assessment methods such as RigiScan™, International Index of Erectile Function (IIEF-5), and the stamp test are used to evaluate sexual function, but those methods cannot repetitively and quantitatively measure erectile function. Only direct measurement can quantitatively assess the shape of an erect penis. This paper presents the essential requirements for developing an ideal measurement method for penile erection. It also introduces current approaches for diagnosing male sexual function and reviews ongoing research to quantitatively measure erectile function. The paper further summarizes and analyzes the advantages and disadvantages of each method with respect to the essential requirements. Finally, the paper discusses the future direction toward the development of Penile Erection Morphometry.

Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Effect of Diabetes Mellitus on Symptomatic Improvement After Surgery for Benign Prostatic Hyperplasia in Patients With Lower Urinary Tract Symptom and its Relations With Prostatic Urethral Angulation.

PURPOSE: To compare improvement of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia in diabetic versus nondiabetic patients after transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). METHODS: The medical records of 437 patients who underwent TURP or HoLEP at a tertiary referral center from January 2006 to January 2022 were retrospectively analyzed. Among them, 71 patients had type 2 diabetes. Patients in the diabetic mellitus (DM) and non-DM groups were matched 1:1 according to age, baseline International Prostate Symptom Score (IPSS), and ultrasound measured prostate volume. Changes in LUTS were assessed at 3 months after surgery using IPSS and evaluated by categorizing patients according to prostatic urethral angulation (PUA; <50° vs. ≥50°). Medication-free survival after surgery was also investigated. RESULTS: No significant differences were noted between the DM and non-DM groups in baseline characteristics except for comorbidities (i.e., hypertension, cerebrovascular disease, and ischemic heart disease, P=0.021, P=0.002, and P=0.017, respectively) and postvoid residual urine volume (115±98 mL vs. 76±105 mL, P=0.028). Non-DM patients showed significant symptomatic improvement regardless of PUA, while DM patients demonstrated improvement in obstructive symptoms only in those with large PUA (≥51°). Among patients with small PUA, DM patients had worse medication-free survival after surgery compared to controls (P=0.044) and DM was an independent predictor of medication reuse (hazard ratio, 1.422; 95% confidence interval, 1.285-2.373; P=0.038). CONCLUSION: DM patients experienced symptomatic improvement after surgery only in those with large PUA. Among patients with small PUA, DM patients were more likely to reuse medication after surgery.

Risk analysis of metformin use in prostate cancer: a national population-based study.

INTRODUCTION: Various approaches are required to prevent and treat heterogeneity-based prostate cancer. Here, we analyzed the anticancer effects of metformin, which has a good toxicity profile and is inexpensive. METHOD: From January 2010 to December 2019, analysis was conducted retrospectively in a cohort from the National Health Insurance Service database. The wash-out period was set for cancer diagnosis in 2010 and 2011, and subjects (105,279) diagnosed with prostate cancer (ICD C61) from 2012 to 2014 were excluded The final subjects (105,216) were defined as the metformin administration group when they took metformin for 180 days or more from January 2012 to December 2019. The non-metformin group was defined as those who took less than 180 days from January 2012 to December 2019. The prevalence of prostate cancer according to metformin administration and the risk according to the cumulative duration of metformin were analyzed. RESULTS: A total of 105,216 people were included in this study, with 59,844 in the metformin group and 45,372 in the metformin non-administration group. When calculating HRs (Hazard Rate) according to the cumulative period of metformin administration, metformin administration period length was inversely associated with prostate cancer risk (Q2 HR = 0.791 95% CI: 0.773-0.81, Q3 HR = 0.634 95% CI: 0.62-0.649, Q4 HR = 0.571 95% CI: 0.558-0.585). HRs tended to decrease with the cumulative duration of metformin administration. CONCLUSION: This study confirmed that prostate cancer risk decreased with increasing duration of metformin administration. Metformin should be considered as a new strategy in the treatment and prevention of prostate cancer characterized by heterogeneity.

Association between Psychological Suffering and Suicidal Thinking in Patients with Urologic Cancer Using Real-World Data.

Cancer is a leading cause of death in Korea, and depression and suicide are major psychiatric problems in cancer patients. This study aimed to explore the correlation between anxiety, depression, social support, cancer state, and suicidality among urologic cancer patients. Sixty patients with urologic cancer were admitted to a university hospital between October 2019 and February 2020. The patients were evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, Suicidality module of the Mini International Neuropsychiatric Interview (MINI), and the Lubben Social Network scales (LSNS). To determine which psychological or demographic factors affected suicide risk, Fisher's exact test, Wilcoxon rank-sum test, regression, and logistic regression were conducted. It was found that the greater the depressive symptoms, the higher the suicidal risk (OR = 1.32, 95% CI = 1.08-1.61). Furthermore, anxiety symptoms and the duration of cancer after diagnosis significantly increased depressive symptoms (p = 0.032). Clinicians should be able to identify the risk factors for suicide in patients with cancer, one of which is depression. To assess the risk of suicide, we must evaluate not only depressive symptoms but also the related anxiety and duration of the disease. Prevention and intervention efforts are needed to improve depressive moods and anxiety after cancer diagnosis.

A Comparative Study of Urinary Tests and Cultures for the Effectiveness of Fosfomycin in Catheter-Related Urinary Tract Infections.

As the elderly population increases due to an aging society, the number of patients with catheters is increasing, and treatment for urinary infections is needed. The current study analyzed the effectiveness of fosfomycin, the primary antibiotic used to treat urinary tract infections (UTIs), in these patients. Patients who received fosfomycin as the primary antibiotic for a UTI were selected, and the results of urine tests and cultures before and after fosfomycin administration were compared and analyzed. The degree of UTI in patients with a catheter was found to be more severe (p = 0.020), and the infecting strains were found to be different depending on whether a catheter was present (p = 0.014). There was a difference in the treatment success rate depending on whether or not a catheter was present (53.6% vs. 70.4%), but it was found that the treatment rate was more than 50% regardless of whether a catheter was present. The bacterial type, as well as the treatment rate based on the bacterium, differed depending on the presence of a catheter. Fosfomycin has a success rate of more than 50%, even in patients with catheters; therefore, it can be considered the primary antibiotic for treating UTIs.

Clinical significance of prostate volume and testosterone reduction on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy.

To investigate the effect of both prostate volume and serum testosterone changes on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy. A total of 167 patients who received androgen deprivation therapy for prostate cancer treatment from January 2010 to August 2020 were enrolled in this retrospective study. Changes in the International Prostate Symptom Score (IPSS) in the patient groups stratified by prostate volume and the amount of testosterone reduction were assessed every 4 weeks until 12 weeks after androgen deprivation therapy initiation. Longitudinal mixed models were used to assess the adjusted effects of prostate volume and testosterone reduction on IPSS change. All mean values of IPSS-total score (IPSS-total), voiding subscore (IPSS-vs), and storage subscore (IPSS-ss) significantly decreased from baseline to week 12 in both patients with small (< 33 mL) and large (≥ 33 mL) prostates. The mean values of IPSS-total, IPSS-vs, and IPSS-ss similarly decreased in patients with large prostate with a baseline IPSS-total of ≥ 13. However, in those with small prostate, IPSS-ss specifically remained unchanged, while IPSS-total and IPSS-vs significantly decreased. In addition, only in patients with small prostate (< 33 mL), patients with lesser testosterone reduction (< Δ400 ng/dL) showed greater improvement in IPSS-ss by 7.5% compared with those with greater testosterone reduction (≥ Δ400 ng/dL). In conclusion, although androgen deprivation therapy generally improves lower urinary tract symptoms, it may worsen specifically storage symptoms in patients with relatively small prostate and greater testosterone reduction. Our finding suggests that testosterone may influence lower urinary tract symptoms in these patients.

The Diagnosis of Chronic Pelvic Pain: How Can We Detect Urological Pain?

Chronic pelvic pain (CPP) refers to pain perceived in the pelvic region for over 6 months. It is described more specifically according to the organs involved. The diagnosis and classification of CPP are not easy because of the vague diagnostic criteria, variety of presenting symptoms, absence of diagnostic tools, and coexisting symptoms due to accompanying other diseases. This concise review aims to help urologists diagnose CPP by focusing on identifying urological pain.

Ability and accuracy of the smartphone-based O`VIEW-M® sperm test: Useful tool in the era of Covid-19.

Male infertility affects up to 12% of men. Although manual testing using microscope examination and computer-assisted semen analysis are standard methods of measuring sperm count and motility, these methods are limited by being laboratory based. To investigate the usefulness of a novel semen analysis device using a smartphone camera. This prospective multicenter randomized parallel design trial enrolled 200 men aged ≥19 years of age between August and December 2018. Each subject was advised to use the Smart Sperm Test for OVIEW-M at home after 5 days of abstinence. The accuracy of the OVIEW-M test relative to the in-hospital test was determined. A questionnaire was administered to assess subject likelihood of using the OVIEW-M. Measurements using standard methods and the OVIEW-M showed similar sperm counts and similar motile sperm counts. Correlation analysis showed significant correlations between sperm count and sperm motility when measured by OVIEW-M tests (r = 0.893, p < 0.01) and standard microscope examination (r = 0.883, p < 0.01). Of the subjects who responded to questionnaires, 43% regarded the results of the OVIEW-M tests as reliable and 18% as unreliable. Semen analysis with the smartphone-based application and accessories yielded results not inferior to those of laboratory tests. Men who visit the hospital for evaluation of infertility can easily perform OVIEW-M semen tests at home.

3D-Printing-Assisted Extraluminal Anti-Reflux Diodes for Preventing Vesicoureteral Reflux through Double-J Stents.

This paper presents novel umbrella-shaped flexible devices to prevent vesicoureteral reflux along double-J stents, which is a backward flow of urine from the bladder to the kidney and is a critical issue in patients with urinary stones. The anti-reflux devices were designed to mechanically attach to the stent and were manufactured using three-dimensional (3D) printing and polymer casting methods. Based on the umbrella shapes, four different devices were manufactured, and the anti-reflux efficiency was demonstrated through in vitro experiments using a urination model. Consequently, penta-shaped devices exhibited the best anti-reflux performance (44% decrease in reflux compared to the stent without the device), and maximum efficiency occurred when the device was attached near the bladder-ureter junction. In addition, a disadvantage of 3D printing (i.e., unwanted rough surface) helped the device strongly adhere to the surface of the stent during the insertion operation. Finally, long-term soaking experiments revealed that the fabricated devices were mechanically robust and chemically stable (safe) even being soaked in urine for 4 weeks. The findings of this study support the use of additive manufacturing to make various flexible and biocompatible urological devices to mitigate critical issues in patients with urinary stones.

The Relationships between Abnormal Serum Lipid Levels, Depression, and Suicidal Ideation According to Sex.

(1) Background: Serum lipid levels affect not only nutritional status but also emotional state. The purpose of this study was to examine the effects of various socio-demographic characteristics, abnormal cholesterol levels, and BMI indicators on depressive symptoms and suicidal ideation in the Korean population. (2) Methods: A total of 23,692 people were surveyed using data from the Korea National Health and Nutrition Examination Survey (KNHNES) 2014, 2016, and 2018. Data from 11,653 patients were analyzed. Age, sex, chronic disease, smoking, alcohol consumption, total cholesterol (HDL, triglycerides), BMI, depression, and suicidal ideation were measured. (3) Results: According to sex, low HDL, high triglycerides, and suicidal ideation were significant, along with low education level, smoking, binge drinking, and high BMI. High triglyceride level was shown to significantly increase the risk of depression in males (OR = 1.535, 95% CI = 1.098-2.147). Factors affecting suicidal ideation in males were age, binge drinking, and depression, while blood lipid factors were not significant. (4) Conclusions: Of the types of serum lipid factors affecting depression and suicidal ideation, high triglycerides were found to be a risk factor for depression in men. Serum lipids can be used as biomarkers to reflect depressive symptoms in men depending on cholesterol level.

Efficacy of phosphodiesterase type 5 inhibitors in patients with erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis.

Background: Nerve-sparing radical prostatectomy (NSRP) had to be performed because approximately 94% of patients are diagnosed with localized prostate cancer (PCa). Although NSRP is generally done to improve functional outcomes, erectile dysfunction (ED) is one of the most prevailing complications after radical prostatectomy (RP). Phosphodiesterase type 5 inhibitors (PDE5-Is) are the most well-known treatment agent for postoperative ED. This study aimed to assess the efficacy of PDE5-Is in patients with ED after NSRP. Methods: In this systematic literature review, randomized controlled trials on the efficacy and safety of PDE5-Is in patients who underwent NSRP were searched in MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the OVID platform. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Review Methods. The quality of the evidence of the outcome data was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: A total of 14 trials involving 2,822 patients were included. Significant improvements in the International Index of Erectile Function-Erectile Function (IIEF) domain score [mean difference (MD) =4.93; 95% confidence interval (CI): 4.14-5.71; P<0.00001] and erectile function recovery events [odds ratio (OR) =2.06; 95% CI: 1.45-2.94; P<0.0001] were observed after PDE5-I treatment. A higher positive response to Sexual Encounter Profile (SEP) question 2 (OR =2.27; 95% CI: 1.80-2.86; P<0.00001) and question 3 (OR =2.78; 95% CI: 1.97-3.91; P<0.00001) was also found after PDE5-I treatment. However, the incidence of treatment-emergent adverse events (TEAEs) was higher after PDE5-I treatment than after placebo treatment (OR =2.91; 95% CI: 1.84-4.61). Furthermore, the incidence of headache (OR =3.38; 95% CI: 2.40-4.75) and flushing (OR =9.44; 95% CI: 4.30-20.70) was also significantly higher after PDE5-I treatment (P<0.00001). In terms of the quality of the evidence of the outcome data, inconsistency problems were detected in all outcomes and imprecision problems in most outcomes. Discussion: PDE5-I treatment was more effective to placebo treatment in patients with ED after NSRP. No clinically serious complications were found in spite of the incidence of TEAEs being higher after PDE5-I treatment.

CYLD destabilizes NoxO1 protein by promoting ubiquitination and regulates prostate cancer progression.

The NADPH oxidase (Nox) family of enzymes is solely dedicated in the generation of reactive oxygen species (ROS). ROS generated by Nox are involved in multiple signaling cascades and a myriad of pathophysiological conditions including cancer. As such, ROS seem to have both detrimental and beneficial roles in a number of cellular functions, including cell signaling, growth, apoptosis and proliferation. Regulatory mechanisms are required to control the activity of Nox enzymes in order to maintain ROS balance within the cell. Here, we performed genome-wide screening for deubiquitinating enzymes (DUBs) regulating Nox organizer 1 (NoxO1) protein expression using a CRISPR/Cas9-mediated DUB-knockout library. We identified cylindromatosis (CYLD) as a binding partner regulating NoxO1 protein expression. We demonstrated that the overexpression of CYLD promotes ubiquitination of NoxO1 protein and reduces the NoxO1 protein half-life. The destabilization of NoxO1 protein by CYLD suppressed excessive ROS generation. Additionally, CRISPR/Cas9-mediated knockout of CYLD in PC-3 cells promoted cell proliferation, migration, colony formation and invasion in vitro. In xenografted mice, injection of CYLD-depleted cells consistently led to tumor development with increased weight and volume. Taken together, these results indicate that CYLD acts as a destabilizer of NoxO1 protein and could be a potential tumor suppressor target for cancer therapeutics.

Forward-Looking Ultrasound Wearable Scanner System for Estimation of Urinary Bladder Volume.

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates. This study aims to estimate the volume of the bladder using a small number of piezoelectric transducers. A least-squares method was implemented to optimize an ellipsoid in a quadratic surface equation for bladder volume estimation. Ex-vivo experiments of a pig bladder were conducted to validate the proposed system. This work presents the potential of the approach for wearable bladder monitoring, which has similar measurement accuracy compared to the commercial bladder imaging system. The wearable bladder scanner can be improved further as electronic voiding diaries by adding a few more features to the current function.

The association between family history of prostate cancer and development of prostate cancer among Korean population: A prospective cohort study using KoGES data.

ABSTRACT: This study aimed to assess the impact of family history (FH) on prostate cancer (PCa) development among a general Korean population. We conducted a prospective cohort study based on the registry records of 211,789 participants in the database of the Korean Genome and Epidemiology Study from 2001 to 2013. A total of 69,693 men with appropriate records were evaluated by being categorizing into 2 groups; a PCa group (100) and control group (69,593). FH of PCa was also categorized as FH of total, father, or brother. Odds ratios (ORs) of PCa development were calculated by using stratified logistic regression models. The adjusted OR of PCa history of father was 27.7 (95% confidence interval [CI] = 9.7-79.2, P < .001) in PCa patients compared to control, and that of PCa history of brother was 15.8 (95% CI = 3.6-69.6, P < .001). Among the adjusted variables, age (OR, 1.17; 95% CI, 1.14-1.21; P < .001), and hyperlipidemia (OR, 2.25; CI, 1.32-3.84; P = .003) were also identified as significant predictors of PCa development. There was no difference in the impact of FH on PCa development between different age groups at PCa diagnosis (<60 vs ≥60 years). To our knowledge, this study represents the first prospective cohort study based on the registry data of a Korean population showing the significance of FH on PCa development. Additionally, the effect of FH on the early onset of PCa has not been confirmed in our analysis.

Changes in Prevalence and Treatment Pattern of Benign Prostatic Hyperplasia in Korea.

PURPOSE: Benign prostatic hyperplasia (BPH) is associated with lower urinary tract symptoms and negatively affects the quality of life. We aimed to investigate the treatment pattern of BPH in South Korea. METHODS: Information on treatment modalities and diagnoses of BPH was obtained from the Health Insurance Review and Assessment Service-Aged Patient Sample. Data on BPH patients aged ≥60 years from 2012 to 2016 were obtained. We surveyed the treatment pattern of BPH, including the types of drugs used and surgeries performed, according to the type of institution. RESULTS: In this study, 18,260-24,657 BPH patients treated between 2012 and 2016 were included. The number of patients showed an increasing pattern, and drug therapy was the major treatment method used for BPH (98.77%). Moreover, the pattern of increased pharmacotherapy use for BPH was reinforced by the increasing number of patients. Prescription of α-blockers only was dominant in this cohort (45.7%). Transurethral resection of the prostate (TURP) was the most commonly used surgical treatment for BPH (53.6%), but it showed a decreasing pattern over time. In contrast, holmium laser enucleation of the prostate (HoLEP) showed an increase from 19.4% to 39.7%. CONCLUSION: The most common treatment for BPH was drug therapy, predominantly only α-blocker therapy. The surgical treatment trend has changed from TURP to HoLEP.

A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells.

In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-γ-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.