Associations between organic erectile dysfunction and the risk of herpes zoster and postherpetic neuralgia in men.

BACKGROUND: Whether erectile dysfunction (ED) leads to considerable stress for affected men remains unclear? In this study, we investigated whether organic ED (OED) is associated with increased risks of herpes zoster (HZ) and postherpetic neuralgia (PHN). METHODS: A representative subset of Taiwan's National Health Insurance Research Database was employed for this study. Enrollees with OED from the years 2000 to 2018 were selected. To ensure comparability between the case and control groups, we implemented 1:1 propensity score matching based on age, index year, comorbidities, and medications. RESULTS: The case group included 20,808 patients with OED, while the control group consisted of 20,808 individuals without OED. The OED group exhibited a significantly elevated risk of HZ (adjusted hazard ratio [aHR] = 1.74) and PHN (aHR = 1.56) compared to the non-OED group. CONCLUSIONS: Men experiencing OED seem to face elevated risks of HZ and PHN compared to those without OED. ED may serve as a warning sign for individuals at HZ risk.

The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie's Disease: A Systematic Narrative Review.

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.

Sertindole, an Antipsychotic Drug, Curbs the STAT3/BCL-xL Axis to Elicit Human Bladder Cancer Cell Apoptosis In Vitro.

Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.

Chondromalacia patella increases the risk of herpes zoster: a population-based study.

BACKGROUND: The reactivation of herpes zoster (HZ) is associated with disease stress. However, the relationship between chondromalacia patella (CMP) and HZ remains poorly understood. This study investigated the relationship between CMP and the risk of developing HZ. METHODS: Data were collected from the Taiwan's National Health Insurance Research Database. Patients with CMP diagnosed between 2000 and 2017 were assigned to the case group; patients without CMP were randomly selected from the same database and paired with controls matched by age and sex. The primary outcome was a diagnosis of HZ. All patients were followed until their diagnosis of HZ, their withdrawal from the NHI program, their death, or the end of 2017, whichever was earliest. The risk of developing HZ was compared between the case and control groups. RESULTS: In total, 22,710 patients with CMP and 90,840 matched controls were enrolled. The overall incidence rates of HZ in the CMP and control cohorts were 7.94 and 7.35 per 1,000 person-years, respectively. After potential confounders were controlled for, the case group exhibited a higher risk of HZ than did the control group [adjusted hazard ratio (aHR) = 1.06, p < 0.05]. In a stratification analysis by age, patients over 65 years old in the CMP group exhibited a higher risk of HZ than did those in the control group (aHR = 1.22, p < 0.01). In a stratification analysis by sex, women with CMP were at greater risk of developing HZ than women without CMP (aHR = 1.18, p < 0.01). CONCLUSION: Patients with CMP, especially elder adults and women, exhibited a higher risk of HZ. The HZ risk of patients with CMP should thus be assessed, and the necessity of HZ vaccination should be informed.

Hispolon Methyl Ether, a Hispolon Analog, Suppresses the SRC/STAT3/Survivin Signaling Axis to Induce Cytotoxicity in Human Urinary Bladder Transitional Carcinoma Cell Lines.

Bladder cancer is a leading human malignancy worldwide. Signal transducer and activator of transcription (STAT) 3 is an oncogenic transcription factor commonly hyperactivated in most human cancers, including bladder cancer. Notably, preclinical evidence has validated STAT3 blockade as a promising therapeutic strategy for bladder cancer. Hispolon Methyl Ether (HME) is a structural analog of hispolon, an anticancer component of the medicinal mushroom Phellinus linteus. Thus far, HME's anticancer activity and mechanisms remain largely unknown. We herein report HME was cytotoxic, more potent than cisplatin, and proapoptotic to various human bladder transitional carcinoma cell lines. Of note, HME blocked STAT3 activation, evidenced by HME-elicited reduction in tyrosine 705-phosphorylated STAT3 levels constitutively expressed or induced by interleukin-6. Significantly, HME-induced cytotoxicity was abrogated in cells expressing a dominant-active STAT3 mutant (STAT3-C), confirming STAT3 blockage as a pivotal mechanism of HME's cytotoxic action. We further revealed that survivin was downregulated by HME, while its levels were rescued in STAT3-C-expressing cells. Moreover, survivin overexpression abolished HME-induced cytotoxicity, illustrating survivin as a central downstream mediator of STAT3 targeted by HME. Lastly, HME was shown to lower tyrosine 416-phosphorylated SRC levels, suggesting that HME inhibits STAT3 by repressing the activation of SRC, a STAT3 upstream kinase. In conclusion, we present the first evidence of HME's anti-bladder cancer effect, likely proceeding by evoking apoptosis through suppression of the antiapoptotic SRC/STAT3/survivin signaling axis.

Herpes zoster in patients with sciatica.

BACKGROUND: Several diseases are associated with herpes zoster (HZ). However, whether sciatica is a stressor leading to HZ development remains unclear. Here, we evaluated the occurrence of HZ in patients with sciatica. METHODS: The sciatica cohort consisted of patients first diagnosed as having sciatica between 2000 and 2012. All patients with sciatica were randomly age, sex and index year matched with control individuals without sciatica. The primary outcome was diagnosis of HZ. All individuals were followed until HZ diagnosis, withdrawal from the insurance, death, or December 31, 2013, whichever occurred first. HZ risk in the two cohorts was further analyzed with age, sex and comorbidity stratification. RESULTS: In total, 49,023 patients with sciatica and 49,023 matched controls were included. Female patients were more likely to have HZ development than were male patients [adjusted hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.12]. After adjustments for all the covariates, HZ risk was significantly higher in the sciatica cohort than in the control cohort (adjusted HR = 1.19; 95% CI = 1.12-1.25). CONCLUSION: Sciatica increased HZ risk. Thus, HZ risk should be addressed whenever physicians encounter patients with sciatica, HZ vaccination should be considered especially those aged over 50.

Appearance of ureterorenal stones after gouty arthropathy: a retrospective cohort study for ethnic disparity.

INTRODUCTION: This study aimed to investigate the differences in ureterorenal stone appearance after gouty arthropathy between Taiwanese aboriginal and non-aboriginal patients. METHODS: Between 2007 and 2015, patients with first diagnoses of ureterorenal stones after diagnosis of gouty arthropathy at Puli Christian Hospital were enrolled in this study. Characteristics, underlying diseases and laboratory data for aboriginal and non-aboriginal patients were recorded. All categorical variables were analysed by χ2 test and continuous variables were compared by t-test. RESULTS: A total of 201 patients (66 aboriginal and 135 non-aboriginal) were enrolled in the study. Serum uric acid levels did not differ significantly between aboriginal and non-aboriginal groups. There was a significant difference in the time until ureterorenal stone appearance after gouty arthropathy between aboriginal and non-aboriginal patients (38.0 v 29.3 months, p=0.015). Among males, aboriginal patients exhibited gouty arthropathy at a younger age than non-aboriginal patients (46.0 v 50.2 years, p=0.035). Furthermore, male aboriginal patients exhibited a higher rate of alcoholic hepatitis (26.7% v 12.2%, p=0.046). CONCLUSION: Among males, aboriginal Taiwanese patients exhibited gouty arthropathy at younger ages than did non-aboriginal Taiwanese because of a higher rate of alcoholic hepatitis. The longer time until stone appearance after gouty arthropathy was attributed to alcoholic diuresis. Decreasing alcohol consumption may postpone or halt the development of gouty arthropathy.

Ethnic differences in risk factors of acute pancreatitis.

OBJECTIVE: The ethnic difference in the risk factors of acute pancreatitis remains unknown. The objective of this study is to investigate the differences in the risk factors of acute pancreatitis between Taiwanese aborigines and nonaborigines. DESIGN: A retrospective study of 622 patients with acute pancreatitis admitted to our hospital (Puli Christian Hospital) from 2006 to 2014. The risk factors and biochemical properties of acute pancreatitis were comapred between aborgines and nonaborgines. RESULTS: The first episode of acute pancreatitis amongst the aboriginal group was commonly observed in young age groups (39.3 versus 47.8 years, p < 0.05), female patients (0.61 versus 0.27, p < 0.05), and patients with a habit of drinking alcohol (84% versus 65%, p < 0.05). Analysis of the biochemical properties and risk factors demonstrated siginifcantly high uric acid levels (7.63 versus 6.56 mg/dL, p < 0.05), and an increased prevalence of alcohol-related pancreatitis (60.0% versus 49.6%, p < 0.05) in the aboriginal group. CONCLUSIONS: Taiwanese aborigines were reported to be more susceptible to alcohol-related pancreatitis than nonaborigines. The decreasing levels of excessive alcohol consumption may reduce the disease burden of acute pancreatitis.

Early perfusion changes within 1 week of systemic treatment measured by dynamic contrast-enhanced MRI may predict survival in patients with advanced hepatocellular carcinoma.

OBJECTIVES: To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan-Meier model and the double-sided log-rank test. RESULTS: All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status. CONCLUSIONS: Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC. KEY POINTS: • DCE-MRI is helpful to evaluate perfusion changes of HCC after systemic treatment. • Early perfusion changes within 1 week after treatment may predict overall survival. • High Peak reduction was an independent favourable prognostic factor after systemic treatment.

Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma: Comparison with the Liver Parenchyma and Correlation with the Survival of Patients Receiving Systemic Therapy.

Purpose To retrospectively compare the perfusion parameters of advanced hepatocellular carcinoma (HCC) measured with dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with surrounding liver parenchyma to determine the relationship between these parameters and uncensored overall survival (OS). Materials and Methods This retrospective study had institutional review board approval, and informed consent was waived. DCE MR imaging was performed in 92 patients with advanced HCC before systemic treatment was administered (19 patients received a placebo). Three semiquantitative (peak, slope, and area under the gadolinium concentration-time curve [AUC]) and six quantitative (arterial fraction, arterial flow, portal flow, total blood flow, distribution volume, and mean transit time) parameters were calculated by placing regions of interest in the largest area of the tumor and background liver parenchyma. The DCE MR imaging parameters between the tumor and normal liver were compared with paired Wilcoxon test. By using the Cox proportional hazards model for univariate and multivariate analyses, the association of DCE MR imaging parameters and OS was investigated. Results HCC demonstrated significantly higher peak, slope, AUC, arterial fraction, and arterial flow but lower portal flow, distribution volume, and mean transit time than did the background liver (all P < .05). Patients with high peak in the tumor had longer OS (P = .005) than did those with low peak. Cox multivariate analysis identified peak as an independent predictor of OS (P = .032) after adjusting for age, sex, treatment, tumor size, and portal vein thrombosis. Conclusion DCE MR imaging parameters can be used to differentiate advanced HCC from the background liver, and peak, a semiquantitative parameter, is associated with outcome in patients with advanced HCC before systemic therapy. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on July 22, 2016.

A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer.

BACKGROUND: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. METHODS: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. RESULTS: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. CONCLUSION: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010.

Splenectomy increases the subsequent risk of systemic lupus erythematosus.

Splenectomy may be necessary to treat systemic lupus erythematosus (SLE) patients with thrombocytopenia; however, whether performing a splenectomy on patients without SLE increases the subsequent risk of SLE remains unknown. Therefore, this study was conducted to determine the association between splenectomy and SLE. We conducted a cohort study by using data from the Taiwan National Health Institute Research Database to identify 10,298 patients with received a splenectomy between 2000 and 2006 and 41,192 participants without received a splenectomy who were selected by frequency matched based on sex, age, and the index year. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of developing SLE associated with splenectomy compared with patients who did not receive a splenectomy. During the study period, the overall incidence density rate of SLE was higher in the splenectomy cohort than in the non-splenectomy cohort (adjusted HR 10.55; 95 % CI 50.55-20.05). The incidence density rates of SLE in women and men who received a splenectomy were higher than those of patients who did not receive a splenectomy. Non-traumatic splenectomy increases the subsequent risk of SLE. The risk of SLE should be considered before performing a splenectomy, particularly in women and younger patients.

Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis.

Risk factors for gestational diabetes mellitus: ethnic disparities.

OBJECTIVE: Gestational diabetes mellitus (GDM) increases the risk of poor maternal and infant health outcomes; therefore, the objective of this study was to compare the ethnic disparities and identify the risk factors for GDM. DESIGN: We performed a cross-sectional analysis using patient records from a hospital located in the Puli area of Central Taiwan. SETTING: A teaching hospital located in a rural mountainous area of Central Taiwan. PARTICIPANTS: Between 2002 and 2012, the hospital admitted 154 patients (107 non-aborigines, 30 aborigines, and 17 non-Taiwanese) who exhibited glucose intolerance during their pregnancy. MAIN OUTCOME MEASURES: GDM was confirmed using the oral-glucose-tolerance-test administered in dose of either 100 g or 75 g. The incidence and risk factors for GDM in the aboriginal and non-aboriginal women was compared. RESULTS: We excluded the patients who had overt diabetes or were non-Taiwanese. Thus, 132 patients (28 aboriginal and 104 non-aboriginal women; mean age 30 years) were enrolled in the final study. A total of 51 patients (15 aboriginal, 36 non-aboriginal women) had GDM, which was more prevalent among the aboriginal mothers (53.6% versus 34.6%). The risk factors for GDM among the aboriginal women were persistent glycosuria and prior macrosomia. CONCLUSION: The Taiwanese aboriginal women exhibited higher incidence of GDM; thus, we recommend that early screening and health education for pregnant aboriginal women be provided.

Quantification of hepatic steatosis: a comparison of the accuracy among multiple magnetic resonance techniques.

BACKGROUND AND AIM: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are important diagnostic tools for the non-invasive assessment of hepatic steatosis (HS). This study was conducted to compare different magnetic resonance (MR) techniques and correlate the MR findings with histological and intracellular lipid density findings. METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective study, 60 patients scheduled for liver resection were included in this study. Fat fraction in the non-tumorous liver parenchyma was estimated using double-echo MRI, triple-echo MRI (TE-MRI), and MRS. HS was defined by the histologic steatosis percentage (HSP), and intrahepatocellular triglyceride density (IHTGD) of the surgical specimen used as the reference standard. Imaging quantification results were evaluated using Pearson's correlation. Lin's concordance coefficient and Bland-Altman 95% limits of agreement were used to evaluate the concordance of IHTGDs estimated by the three MR techniques. The diagnostic performance was compared using receiver operating characteristic curve analysis. RESULTS: HS assessed by TE-MRI and MRS had a stronger relationship with HS assessed by HSP and IHTGD. The TE-MRI method had the highest concordance correlation coefficients (ρ = 0.881) and percentage (95%, 57/60) within the Bland-Altman 95% limits of agreement. Receiver operating characteristic curve analysis for diagnosing > 5% HSP showed significantly larger area under the curve (0.9783) for TE-MRI than for double-echo MRI (0.8773, P = 0.0121). CONCLUSIONS: Among the three MR techniques, TE-MRI and MRS may be the preferred techniques for non-invasive assessment of HS.

Obstructive sleep apnea increases the risk of herpes zoster and postherpetic neuralgia.

OBJECTIVE: Diseases associated with chronic pain are typically a major source of stress for patients; and have been linked to herpes zoster (HZ) development. Here, we investigated whether obstructive sleep apnea (OSA) is a potential stressor that increases the risk of HZ and postherpetic neuralgia (PHN) in affected individuals. METHODS: The data used in this study were obtained from the National Health Insurance Research Database. The study cohort included patients aged between 20 and 100 years who had OSA during the period from 2000 to 2017 (with tracking completed until 2018). The case group and the control group were matched at a 1:1 ratio on the basis of age, sex, comorbidities, and index year, with patients who had outcomes before the index date being excluded. The outcomes considered in this study were HZ and PHN. The risk of HZ and PHN with and without OSA was calculated, and age, sex, comorbidities, and index year were adjusted for. RESULTS: There were 25,211 patients in each group. Patients with OSA had a significantly higher risk of HZ (adjusted hazard ratio [aHR] = 1.22) than those without did. The patients with OSA had also a significantly higher risk of PHN (aHR = 1.36) than those without did. In term of comorbidities, the patients with OSA without (aHR = 1.28) and with (aHR = 1.17) comorbidities had a significantly higher risk of HZ compared with those without OSA. In addition, the patients with OSA but no other comorbidities (aHR = 1.68) had a significantly higher risk of PHN than those without did. CONCLUSION: OSA increases the risk of not only HZ but also PHN. Therefore, patients with OSA should be aware of the potential effect of the disease on their stress levels, as well as the increased risk of developing HZ and PHN.

The risk of herpes zoster is positively associated with obesity, especially morbid obesity.

This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20-100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.

The Oncolytic Avian Reovirus p17 Protein Inhibits Invadopodia Formation in Murine Melanoma Cancer Cells by Suppressing the FAK/Src Pathway and the Formation of theTKs5/NCK1 Complex.

To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTENC124A. p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex.

Theranostic Robot-Assisted Radical Prostatectomy: Things Understood and Not Understood.

OBJECTIVE: This study aimed to explore the benefits of theranostic robot-assisted radical prostatectomy (T-RARP) for clinically highly suspicious prostate cancer (PCa) without proven biopsies. MATERIAL AND METHODS: Between February 2016 and December 2020, we included men with clinically highly suspicious PCa in this study. They were assessed to have possible localized PCa without any initial treatments, and were categorized into previous benign biopsies or without biopsies. Furthermore, another group of malignant biopsies with RARP in the same time frame was adopted as the control group. The endpoints were to compare the oncological outcome and functional outcome between malignant biopsies with RARP and T-RARP. p < 0.05 was considered to be significant. RESULTS: We included 164 men with proven malignant biopsies treated with RARP as the control group. For T-RARP, we included 192 men. Among them, 129 were preoperatively benign biopsies, and 63 had no biopsies before T-RARP. Approximately 75% of men in the T-RARP group had malignant pathology in their final reports, and the other 25% had benign pathology. T-RARP provides several oncological advantages, such as a higher initial pathological T stage, lower Gleason grade, and lower odds of positive surgical margins. However, the biochemical recurrence rates were not significantly decreased. From our cohort, T-RARP (odds ratio with 95% confidence interval; erectile recovery: 3.19 (1.84-5.52), p < 0.001; continence recovery: 2.25 (1.46-3.48), p < 0.001) could result in better recovery of functional outcomes than malignant biopsies with RARP. CONCLUSIONS: For clinically highly suspicious PCa, T-RARP was able to detect around 75% of PCa cases and preserved their functional outcomes maximally. However, in 25% of men with benign pathology, approximately 6% would have incontinence and 10% would have erectile impairment. This part should be sufficiently informed of the potential groups considering T-RARP.

One-Step Robot-Assisted Complete Urinary Tract Extirpation in Man with End-Stage Renal Disease on Dialysis: The First Case Report.

Urothelial carcinoma (UC) could be observed in urinary bladder (UBUC) and upper urinary tracts (UTUC). In the National Comprehensive Cancer Network guidelines for bladder cancer, extirpative surgery is indicated in certain cases. However, some extreme cases might also need the extirpation of the majority of the urinary tract, which is called complete urinary tract extirpation (CUTE). We present a patient diagnosed with high-grade UBUC and UTUC. He underwent dialysis for end-stage renal disease (ESRD) at the same time. Considering his non-functional kidneys and removing his high-risk urothelium at the same time, we performed robot-assisted CUTE to extirpate both his upper urinary tracts, urinary bladder, and prostate. In our experience, the console time was not significantly elongated, and the perioperative course was uneventful. To our knowledge, this is the first case report adopting a robotic system in such an extreme case. We conclude that robot-assisted CUTE is worth further study regarding its oncological survival outcomes and perioperative safety in patients with ESRD on dialysis.