Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions.

Numerous research works have emphasized the critical role that circadian rhythm plays in the tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment in clinical settings is a continuous endeavor. Consequently, to enhance the use of time-based pharmaceutical therapies in oncology, combining existing knowledge on circadian rhythms' roles within the TME is essential. This perspective elucidates the functions of circadian rhythms in the TME across various stages of cancer development, progression, and metastasis. Specifically, aging, angiogenesis, and inflammation are implicated in modulating circadian rhythm within the TME. Furthermore, circadian rhythm exerts a profound influence on current cancer treatments and thereby generates chronotheray to manage tumors. From a TME perspective, circadian rhythm offers promising opportunities for cancer prevention and treatment; nevertheless, further study is needed to address unanswered scientific problems.

Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.

A pan-cancer analysis of the oncogenic and immunological roles of transglutaminase 1 (TGM1) in human cancer.

BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF).

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

Targeting Prolyl 4-Hydroxylase Subunit Beta (P4HB) in Cancer: New Roads to Travel.

Prolyl 4-hydroxylase subunit beta (P4HB) can catalyze the formation, breakage and rearrangement of disulfide bonds through two thioredoxin domains, which is important for the maintenance of oxidizing environment in endoplasmic reticulum. Recently, P4HB has been demonstrated its oncogenic role of tumorigenesis and development in cancers. Therefore, we comprehensively deciphered P4HB in human cancer from various aspects, including pan-cancer analysis and narrative summary. We also provided some possible interacted molecules and the top 10 predicted drugs targeting P4HB to contribute to future research. We proposed that P4HB was a potential target and brought new therapeutic opportunities for cancer patients.

Characteristics of recurrent acute urinary retention in BPH patients in the United States: Retrospective analysis of US-based insurance claims database.

PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.

Expression of AKT1 Related with Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma.

Pathways such as VEGF, EGF and mTOR are known to be one of the major mechanisms of tumorigenesis including kidney cancer. To identify potential signaling pathway proteins, we performed differential/correlation analyses of mTOR-associated genes from three public datasets. AKT1 protein, one of the PI3K/AKT/mTOR pathways, turned out to be the potential by showing a consistent discrepancy between ccRCC-associated conditions as well as strong correlation with other mTOR-associated genes across the datasets. Then, we analyzed how AKT1 alteration affects clear cell renal cell carcinoma. The pathology of 58 kidney cancer patients was constructed to analyze the relationship between the expression level of AKT1 through immunohistochemical staining and their clinicopathological data. Gender, age and TNM stage did not show significant results. AKT1 is a known oncogene. However, in this study, high expression of AKT1 showed a slight correlation with lower WHO/ISUP grade, longer recurrence-free and progression-free survival rates.

Prevalence of Bladder Pain Syndrome-like Symptoms: a Population-based Study in Korea.

OBJECTIVES: To investigate the prevalence of bladder pain syndrome (BPS)-like symptoms in the general population of South Korea. METHODS: Between April 16, 2016 and April 29, 2016, we conducted an online survey and computer-assisted personal interviews with adults aged 40-79 years in Korea using structured questionnaires. The sample size was 3,000 (95% confidence level standard error ± 1.79%), and the sampling method was simple randomization according to sex, age, and residential area in proportion to the resident registration demographics of the Korean Ministry of Interior and Safety as of March 2016. All participants were surveyed using the Korean version of the Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale and Geriatric Depression Scale (GDS). The primary outcome was the prevalence of BPS-like symptoms, defined as a total PUF score of ≥ 12. RESULTS: Overall, the prevalence of BPS-like symptoms was 16.4% (483 of 3,000 participants). Women (21.4%) had a significantly higher prevalence of BPS-like symptoms than men (10.7%) (P < 0.01). The prevalence by age was significantly higher in the 70s group than in the other age groups (P < 0.01), and increased significantly with the increasing severity of depression on the GDS (P < 0.01). The prevalence of BPS-like symptoms according to the marital status was significantly different, that is, the prevalence among divorced/bereaved individuals was higher than those of married or unmarried individuals (P < 0.01). CONCLUSION: Our large, representative population-based study showed that BPS-like symptoms are widespread among the general population of South Korea. BPS is considered a disease that deserves greater attention as it is far more common than previously thought and can negatively affect many people's quality of life.

Rapid Recurrence of Giant Multilocular Prostatic Cystadenoma after Laparoscopic Excision for Primary Case: A Case Report.

Giant multilocular prostatic cystadenoma is a rare benign tumor of the prostate gland that presents as a large retroperitoneal pelvic mass. The mass is usually located between the urinary bladder and rectum, and results in obstructive voiding symptoms and a change in bowel habits. Complete surgical excision is the treatment of choice. We present a case of rapid recurrent giant multilocular prostatic cystadenoma after laparoscopic excision for primary case. A previously healthy 54-year-old man presented with acute urinary retention. Prostate MRI showed a large cystic mass approximately 13 cm in size, multiple septa and lobulation in the prostate, and no visible solid lesions. Laparoscopic marsupialization of giant multilocular prostatic cystadenoma cysts was performed. One year later, the patient presented with local recurrence. Repeated laparoscopic complete resection was performed without any complications and further recurrence. Giant multilocular prostatic cystadenoma has the risk of recurrence in case of incomplete resection. Surgical treatment should be performed with the goal of complete removal following the same principles as cancer surgery.

A Case of Incidental Schwannoma Mimicking Necrotic Metastatic Lymph Node from Bladder Cancer.

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.

Diabetes Mellitus Promotes Smooth Muscle Cell Proliferation in Mouse Ureteral Tissue through the P-ERK/P-JNK/VEGF/PKC Signaling Pathway.

Background and objectives: The aim of our study was to evaluate the role of diabetes mellitus (DM) as a significant factor affecting spontaneous stone expulsion, as suggested by previous research. Materials and methods: We investigated the influence of DM on the ureter using a murine model. The mouse-model arm of this study used 20 15 -week-old mice, including 10 normal (control) mice and 10 DM mice. We measured the proximal, middle and distal ureteral smooth muscle thickness in each mouse and the differences among ureteral sections were analyzed. Mouse ureteral specimens were also analyzed via western blotting to detect relative protein expression of phosphor-extracellular signal regulated kinases (P-ERK), phosphor-C-Jun N-terminal kinase (P-JNK), vascular endothelial growth factor (VEGF), and protein kinase C (PKC), which are representative factors involved in cell regulation. Results: We observed significant hyperproliferation of ureteral smooth muscle in DM mice compared to normal mice, which may provoke reduced peristalsis. The ureteral smooth muscle of DM mice was significantly thicker than that of normal mice in all ureteral tissues: proximal (p = 0.040), mid (p = 0.010), and distal (p = 0.028). The relative protein expression of P-ERK (p = 0.005) and P-JNK (p = 0.001) was higher in the diabetic group compared to the normal group. Additionally, protein expression of VEGF (p = 0.002) and PKC (p = 0.001) were remarkably up-regulated in DM mice. Conclusions: Hyperproliferation of ureteral smooth muscle was observed in DM mice, but not in normal mice. The pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role in pathological ureteral conditions.

Clinical Outcomes and Risk Factor Analysis of Patients Presenting with Emphysematous Cystitis: A 15-Year Retrospective Multicenter Study.

Background and objectives: To investigate the risk factors for emphysematous cystitis (EC) compared to those of acute cystitis (AC) to increase clinicians awareness of the possibility for the aggravation of patient status. Materials and methods: We retrospectively reviewed a total of 54 patients who were hospitalized with a diagnosis of EC by abdominal computed tomography (CT) scan from 2006 to 2020. The control group included 92 patients who were hospitalized for the treatment of AC in the same period. We sought to identify the clinical features and predisposing diseases, such as age, sex, diabetes mellitus (DM), hypertension (HTN), cerebrovascular accident (CVA), chronic kidney disease (CKD), neurogenic bladder (NB), history of urinary tract infection (UTI), and emphysematous pyelonephritis (EPN), that were associated with the development of EC. Results: The median (interquartile range (IQR)) age of the patients with EC was older than that of the patients with AC (78.5 (15.3) years (range: 52-100) vs. 70.0 (26.5) years (range: 28-97 years)). Sepsis and mortality occurred only in the EC group (48.1% and 11.1%, respectively). The univariate analysis of predisposing factors revealed that age, DM, HTN, CVA, CKD, and NB were significantly associated with EC. In the multivariate analysis, DM (OR, 6.251; 95% CI, 2.254-17.250; p < 0.001), CKD (OR, 18.439; 95% CI, 3.421-99.404; p = 0.001), NB (OR, 7.374; 95% CI, 1.993-27.285; p = 0.003) were associated with EC. Conclusions: The results of this study revealed that DM, CKD, and NB were significant risk factors for EC. The tendency toward sepsis and high mortality underscore the need for careful observation while treating patients with EC with the risk noted above.

Risk factors of febrile urinary tract infections following retrograde intrarenal surgery for renal stones.

ABSTRACT: We aimed to evaluate the risk factors of febrile urinary tract infection (UTI) following retrograde intrarenal surgery (RIRS) for treating renal stones.We retrospectively reviewed the data of patients with 10 - 30 mm kidney stones who underwent RIRS from January 2014 to July 2017. Evaluation included age, gender, body mass index, stone size, stone location, and operative time. All surgeries were performed by a single surgeon and ureteral stenting was not done prior surgery. The risk factors of febrile UTI after RIRS were assessed by univariate and multivariate logistic regression analysis.A total of 150 patients were included in the present study, and 17 patients (11.3%) had febrile UTI after RIRS. Mean patient age was 56.64 ±â€Š13.91 years, and both genders were evenly distributed. Mean stone size was 14.16 ±â€Š5.89 mm. and mean operation time was 74.50 ±â€Š42.56 minutes. According to univariate analysis, preoperative pyuria was associated with postoperative febrile UTI. Multivariate logistic regression analysis showed that preoperative pyuria was the only independent risk factor of infectious complications after RIRS (odds ratios 8.311, 95% confidence intervals 1.759 - 39.275, P = .008). Age, gender, body mass index, comorbidity, preoperative bacteriuria, presence of hydronephrosis, renal stone characteristics, and operative time were not associated with febrile UTI after RIRS.Preoperative pyuria was the only risk factor of infectious complications following RIRS. Therefore, careful management after RIRS is necessary especially when preoperative urinalysis shows pyuria.

Differences between Risk Factors for Sepsis and Septic Shock in Obstructive Urolithiasis.

BACKGROUND: Complicated acute pyelonephritis (APN) is a life-threatening condition that requires immediate intervention. This study examined the characteristics of APN occurring as a complication of ureteral stone. METHODS: We retrospectively reviewed 85 patients diagnosed with APN complicated by ureteral stone between December 2006 and July 2017 at our institution. Patients with concomitant renal stone, multiple ureteral stones, ureteral strictures, ureteral cancer, and urogenital anomalies, including vesicoureteral reflux were excluded. Clinical characteristics including age, sex, underlying disease, medical history, stone characteristics, initial laboratory data, and the procedure used to correct urinary obstruction were summarized, and the risk factors associated with sepsis and septic shock were analyzed. RESULTS: Sepsis was diagnosed at initial presentation in 62 patients, 17 of whom suffered from septic shock. Disease-related death did not occur in any patient. Previous history of stone (P = 0.015), leukocytosis (P < 0.001), elevated C-reactive protein levels (P = 0.006), and low albumin (P = 0.038) were significant risk factors for progression to sepsis. The absence of hypertension (P = 0.047), thrombocytopenia (P = 0.006), decreased erythrocyte sedimentation rate (ESR) (P = 0.003), elevated blood urea nitrogen (P = 0.016), and positive blood culture (P = 0.018) were significant predictors for progression to septic shock. Multivariate analysis revealed that previous history of stone (P = 0.015) was an independent risk factor for sepsis, while the absence of hypertension (P = 0.047), thrombocytopenia (P = 0.013), and decreased ESR (P = 0.009) were risk factors for shock. CONCLUSION: The risk factors associated with the progression from APN to sepsis differed from those associated with the progression from sepsis to septic shock. Various factors should be considered while selecting treatment options based on the severity of APN associated with ureteral stone. It should be managed with aggressive treatment and close observation, especially in the presence of risk factors.

Aggressive Paraganglioma of the Urinary Bladder with Local Recurrence and Pelvic Metastasis.

Many pheochromocytoma and extra-adrenal paraganglioma are benign, but some are malignant. Pheochromocytoma of the Adrenal gland Scaled Score analyzed the histological characteristics of the tumor. Tumors with a Pheochromocytoma of the Adrenal gland Scaled Score of 4 or higher have a higher risk of recurrence. This pattern is thought to be applicable to paraganglioma as well, and to future patient follow-up efforts. We report a recurrent and metastatic paraganglioma of the urinary bladder.

Lump type crossed fused renal ectopia with bilateral vesicoureteral reflux: A case report.

BACKGROUND: Crossed fused renal ectopia is a rare congenital anomaly of the ascent of the kidney. This anomaly may be observed as a solitary kidney during initial evaluation. A solitary kidney must be evaluated for associated anomalies such as duplication, horseshoe kidney, or crossed renal ectopia. CASE SUMMARY: An anomaly was observed in a 9-mo-old male child who was subsequently diagnosed with crossed fused renal ectopia and vesicoureteral reflux (VUR). In this condition, recurrent febrile urinary tract infection can be a serious problem, and can easily cause renal damage due to relatively short ureters and high pressure in the kidney. CONCLUSION: To prevent urosepsis and preserve renal function, early diagnosis and proper management including surgical correction should be considered for the management of renal ectopia with VUR.

Trends in Testicular Injury in Korea, 1986-2015.

The objectives of this study were to investigate patients treated for scrotal trauma at our institute for the last three decades to describe our experience with an emphasis on the etiologies and ultrasonographic findings in these patients. We reviewed medical records of patients who underwent scrotal ultrasonography for evaluation of testicular trauma at our institutes from 1986 to 2015. Trends regarding the etiology of scrotal trauma were evaluated during each decade. The echo pattern and contour definition of the testicular parenchyma and the pattern of hematoma development were recorded to evaluate radiographic findings of testicular injury. The correlation between ultrasonographic and intraoperative findings was assessed. A total of 115 patients were analyzed. Most patients (92.2%) presented with blunt trauma. The most common etiology of testicular trauma was assault during the first and second decades, while injury related to a fall was most common during the third decade. Of the 77 patients (67.0%) who underwent urgent exploration, 46 patients (59.7%) had testicular rupture. Loss of contour definition, heterogeneous echo pattern of the testicular parenchyma, and testicular hematoma showed a moderate to strong degree of correlation with testicular rupture (Spearman correlation co-efficient: 0.5-0.8). Over the past 30 years, the etiology of testicular injury changed from assault to falls or athletic injury and the severity of injury has decreased. Our findings demonstrate the importance of ultrasonography for determining an appropriate management strategy in scrotal trauma. Surgical exploration should be considered in patients with abnormal ultrasonographic findings.