ITM2A inhibits the progression of bladder cancer by downregulating the phosphorylation of STAT3.

Bladder cancer stands as one of the prevalent malignancies in urological clinics, highlighting the pressing need to uncover prognostic or therapeutic avenues. ITM2A, a transmembrane protein, has been identified as a suppressor in tumor progression recently. Our study underscored a significant correlation between low ITM2A expression in bladder cancer tissues and high tumor grade, AJCC stage, and poor overall survival time. Additionally, our findings demonstrated that reinstating ITM2A expression impeded cell proliferation, migration, and invasion, while conversely, its suppression enhanced these malignant behaviors. Furthermore, we elucidated that ITM2A could suppress malignant phenotypes of bladder cancer cells via inhibiting activation of the STAT3 induced by IL-6. In conclusion, our research unveiled the mechanistic role of ITM2A in inhibiting tumor progression, shedding light on its potential as a prognostic predictor and therapeutic target in bladder cancer management.

The relationship between oxidative balance score and erectile dysfunction in the U.S. male adult population.

Oxidative stress strongly influences the pathophysiology of erectile dysfunction (ED). In this study, we used the oxidative balance score (OBS), a composite index, to measure the effects of oxidative stress triggered by diet and lifestyle factors. Here, we conducted a cross-sectional study to determine the statistical relationship between OBS and ED among adult males in the U.S. The data from 3318 participants in the National Health and Nutrition Examination Survey (NHANES) 2001-2004 were analyzed. Weighted logistic regression was used to correct for confounding factors and acquire nationwide representative estimates. Generalized additive modeling was used to explore the nonlinear relationship. We also supplemented subgroup and sensitivity analysis to examine the robustness of the main results. Multivariate logistic regression indicated a consistent negative linear association between OBS and ED across all participants [OR (95% CI) = 0.96 (0.94, 0.98)]. After categorizing OBS into tertiles, participants in the highest tertile had 43% lower odds of having ED than those in the lowest tertile [OR (95% CI) = 0.57 (0.37, 0.87)]. The generalized additive model also visualized the linear trend of this association. Furthermore, this linear relationship remained relatively consistent, regardless of whether subgroup or sensitivity analyses were performed. Our findings suggest that adopting a lifestyle and diet pattern that promotes favorable OBS may effectively protect against the development of ED, regardless of the underlying causes.

Bladder Cancer in Exosomal Perspective: Unraveling New Regulatory Mechanisms.

Bladder cancer, a prevalent malignant neoplasm of the urinary tract, exhibits escalating morbidity and mortality rates. Current diagnosis standards rely on invasive and costly cystoscopy and histopathology, underscoring the urgency for non-invasive, high-throughput, and cost-effective novel diagnostic techniques to ensure timely detection and standardized treatment. Recent years have witnessed the rise of exosome research in bladder cancer studies. Exosomes contain abundant bioactive molecules that can help elucidate the intricate mechanisms underlying bladder cancer pathogenesis and metastasis. Exosomes hold potential as biomarkers for early bladder cancer diagnosis while also serving as targeted drug delivery vehicles to enhance treatment efficacy and mitigate adverse effects. Furthermore, exosome analyses offer insights into the complex molecular signaling networks implicated in bladder cancer progression, revealing novel therapeutic targets. This review provides a comprehensive overview of prevalent exosome isolation techniques and highlights the promising clinical utility of exosomes in both diagnostic and therapeutic applications in bladder cancer management.

Identification of ATP6V0A4 as a potential biomarker in renal cell carcinoma using integrated bioinformatics analysis.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cancer, and is associated with a high mortality rate, which is related to high rates of tumor recurrence and metastasis. The aim of the present study was to identify reliable molecular biomarkers with high specificity and sensitivity for ccRCC. A total of eight ccRCC-related expression profiles were downloaded from Gene Expression Omnibus for integrated bioinformatics analysis to screen for significantly differentially expressed genes (DEGs). Reverse transcription-quantitative (RT-q)PCR, western blotting and immunohistochemistry staining assays were performed to evaluate the expression levels of candidate biomarkers in ccRCC tissues and cell lines. In total, 255 ccRCC specimens and 165 adjacent normal kidney specimens were analyzed, and 344 significant DEGs, consisting of 115 upregulated DEGs and 229 downregulated DEGs, were identified. The results of Gene Ontology analysis suggested a significant enrichment of DEGs in 'organic anion transport' and 'small molecule catabolic process' in biological processes, in 'apical plasma membrane' and 'apical part of the cell' in cell components, and in 'anion transmembrane transporter activity' and 'active transmembrane transporter activity' in molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were significantly enriched in the 'phagosome', the 'PPAR signaling pathway', 'complement and coagulation cascades', the 'HIF-1 signaling pathway' and 'carbon metabolism'. Next, 7 hub genes (SUCNR1, CXCR4, VCAN, CASR, ATP6V0A4, VEGFA and SERPINE1) were identified and validated using The Cancer Genome Atlas database. Survival analysis showed that low expression of ATP6V0A4 was associated with a poor prognosis in patients with ccRCC. Additionally, received operating characteristic curves indicated that ATP6V0A4 could distinguish ccRCC samples from normal kidney samples. Furthermore, RT-qPCR, western blotting and immunohistochemistry staining results showed that ATP6V0A4 was significantly downregulated in ccRCC tissues and cell lines. In conclusion, ATP6V0A4 may be involved in tumor progression and regarded as a potential therapeutic target for the recurrence and metastasis of ccRCC.

Renal pseudoaneurysm after holmium laser lithotripsy with flexible ureteroscopy: an unusual case report and literature review.

Pseudoaneurysms of the renal arteries are caused by focal rupture or perforation of the arterial wall, resulting in local bleeding. Such pseudoaneurysms can be observed in conditions such as nodular polyarteritis, penetrating or closed renal injury, and medically induced injuries (such as renal puncture biopsy, percutaneous nephrostomy, or partial nephrectomy). Flexible ureteroscopy (FURS) is performed entirely through the urethra to prevent potentially severe kidney damage. Because of this, almost no renal parenchymal hemorrhage occurs after FURS laser lithotripsy. Only four cases had been documented in the literature as of December 2022. In this report, we describe a 53-year-old man with a history of recurrent kidney stones who underwent FURS laser lithotripsy for bilateral kidney stones. The procedure was smoothly performed, and no active bleeding occurred. However, the patient developed recurrent macroscopic hematuria after discharge from the hospital, and renal angiography revealed a pseudoaneurysm in the distal right kidney. The pseudoaneurysm was treated with selective arterial embolization. Serious complications of FURS surgery are rare, particularly the formation of pseudoaneurysms. We report the present case to bring this potential complication to the attention of urologists.

ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear. METHODS: We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments. RESULTS: ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT. CONCLUSIONS: High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.

SMARCC1 Enters the Nucleus via KPNA2 and Plays an Oncogenic Role in Bladder Cancer.

Background: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1), a component of the SWI/SNF complex, is thought to be an oncogene in several kinds of cancer. Materials and methods: The potential interaction between SMARCC1 and KPNA2 was inquired by Spearman's correlation analysis, immunofluorescence staining and co-immunoprecipitation (Co-IP) assays. The immunohistochemistry staining, RT-PCR and western blot assay were taken for determining the expression levels of SMARCC1. And CCK-8, transwell assay, cell apoptosis assay, cell cycle analysis and subcutaneous tumor model were conducted to explore the role of SMARCC1 in carcinogenesis of bladder cancer. Results: In our experiments, Spearman's correlation analysis, immunofluorescence staining and co-immunoprecipitation (Co-IP) assays showed that SMARCC1 interacted with KPNA2, and after knockdown of KPNA2, Nup50 and Nup153, the nuclear content of SMARCC1 decreased while the amount of SMARCC1 protein remaining in the cytoplasm increased, indicating that SMARCC1 could be transported into the nucleus via KPNA2 and thus acted as an oncogene. We found that both the mRNA and protein expression levels of SMARCC1 were increased in bladder cancer, and increased SMARCC1 expression was significantly associated with a higher T stage and poorer prognosis in bladder cancer patients. Knockdown of SMARCC1 slowed the growth of the two tested cell lines and clearly arrested the cell cycle at the G0/G1 phase checkpoint. Moreover, the migratory ability was significantly decreased and the number of apoptotic cells was increased. Conclusion: On the whole, our results demonstrate KPNA2, Nup50 and Nup153 regulate the process of SMARCC1 nuclear translocation in BC. SMARCC1 may be a competent candidate as a diagnostic and therapeutic target for BC. Further studies are required to research the mechanism and assess the role of SMARCC1 in vivo.

FAM107A as a Tumor Suppressor in Bladder Cancer Inhibits Cell Proliferation, Migration, and Invasion.

OBJECTIVE: Bladder cancer (BC) is the most common cancer in urinary system. Recently, the function of family with sequence similarity 107 member A (FAM107A) has been reported in several carcinomas. This study aimed to reveal the potential role of FAM107A in bladder cancer. METHODS: Bioinformatics analysis was performed to assess the expression level of FAM107A in BC tissues and adjacent tumor-free bladder tissues. The results were confirmed by quantitative real-time polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry staining in BC tissues and adjacent tumor-free bladder tissues as well as BC cell lines. In addition, plasmid was constructed to increase FAM107A protein level in BC cell lines. The effect of FM107A on cell growth, cell migration and invasion were analyzed by CCK8 assay, wound healing assay and transwell-invasion assay. RESULTS: The data showed that FAM107A was remarkably down-regulated in bladder cancer tissues and bladder cancer cell lines. Besides, low FAM107A expression was associated with high tumor grade of patients with bladder cancer. Moreover, the restoration of FAM107A remarkably suppressed the cell growth, migration, and invasion of BC cells. CONCLUSION: In summary, FAM107A might serve as a tumor suppressor which inhibits BC cell proliferation, migration, and invasion. This study suggests that FAM107A can be a candidate new diagnostic marker and possible therapeutic target gene of bladder cancer.

FAM64A is an androgen receptor-regulated feedback tumor promoter in prostate cancer.

Endocrine therapy for prostate cancer (PCa) mainly inhibits androgen receptor (AR) signaling, due to increased androgen synthesis and AR changes, PCa evolved into castration-resistant prostate cancer (CRPC). The function of Family With Sequence Similarity 64 Member A (FAM64A) and its association with prostate cancer has not been reported. In our research, we first reported that FAM64A is up-regulated and positively associated with poor prognosis of patients with prostate cancer (PCa) by TCGA database and immunohistochemistry staining. Moreover, knockdown of FAM64A significantly suppressed the proliferation, migration, invasion, and cell cycle of PCa cells in vitro. Mechanistically, FAM64A expression was increased by dihydrotestosterone (DHT) through direct binding of AR to FAM64A promoter, and notably promoted the proliferation, migration, invasion, and cell cycle of androgen-dependent cell line of PCa. In addition, abnormal expression of FAM64A affects the immune and interferon signaling pathway of PCa cells. In conclusion, FAM64A was up-regulated by AR through directly binding to its specific promoter region to promote the development of PCa, and was associated with the immune mechanism and interferon signaling pathway, which provided a better understanding and a new potential for treating PCa.

Multilocular cystic renal cell carcinoma: A case report and review of the literature.

Multilocular cystic renal cell carcinoma (MCRCC), which exhibits low-stage and low-grade characteristics, is a special type of RCC. MCRCC is extremely rare and generally develops at ages >50 years. We herein report a case of MCRCC in a 28-year-old man, which, to the best of our knowledge, is the youngest case reported worldwide to date. The patient presented with irritative bladder symptoms for 1 year. Dynamic enhanced computed tomography (CT) imaging revealed a mass with inhomogeneous enhancement in the left kidney, with a rich blood supply. B-ultrasonography also revealed a renal protruding mass. As the mass was highly suspicious to be a malignant tumor, laparoscopic radical nephrectomy was performed and MCRCC was definitively diagnosed by pathological examination. The patient has been regularly followed up for 6 months, without complications or disease recurrence.

Urachal carcinoma: Report of two cases and review of the literature.

Urachal carcinoma is a rare tumor that most commonly occurs in ovaries and less often in the adnexal region and urinary system. We herein present two cases of urachal carcinoma: One case was a 32-year-old male patient who presented with painless hematuria with blood clots for 1 month, whereas the other case was a 50-year-old woman who presented with gross hematuria with mild dysuria, urgency and frequent urination for 1 year. Following surgical resection, the two patients were diagnosed with urachal adenocarcinoma (mixed type) and urachal mucinous adenocarcinoma, respectively, based on the histopathological examination. A review of previously published cases and relevant literature is also presented. The aim of the present study was to help understand this disease better, in order to reduce the rate of clinical and pathological misdiagnosis.

Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer.

Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer.

Bellini's duct carcinoma: A report of two cases and a review of the literature.

Bellini's duct carcinoma (BDC) is a rare and aggressive variant of renal cell carcinoma that possesses an extremely poor prognosis. The greater the grade or stage of disease, the poorer the prognosis tends to be. This study presents two cases of BDC; one case of low grade BDC and one case of high grade BDC in a 47-year-old male and 74-year-old female, respectively. The 47-year-old male patient presented with painless gross hematuria, which had lasted for 3 weeks and subsequently underwent purely laparoscopic nephroureterectomy. After 4-years of follow-up, the patient remained disease-free. By contrast, a right renal tumor was identified in the 74-year-old female patient during a routine examination. Radical right nephrectomy and lymph node dissection were performed, however, 10 months after surgery the patient succumbed due to wide-spread metastasis. The two cases reported in the present study not only represent excellent examples of the disease spectrum, but also act as a reminder of the possibility of detecting BDC in an early stage of disease. Therefore, the epidemiology of BDC has been discussed, and the aggressive growth pattern of BDC has been presented in terms of signs, symptoms and imaging examinations, including ultrasonography, computed tomography (CT), angiography and single photon emission CT, in the early stage of disease.

Primary adrenal sarcomatoid carcinoma metastatic to the lung: Case report and review of the literature.

Adrenal sarcomatoid carcinoma is a rare adrenal carcinoma. To the best of our knowledge, only 11 cases have been reported since 1987. Adrenal sarcomatoid carcinoma presents a diagnostic challenge due to its atypical symptoms and histological patterns. At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. The present study reports a case of a 59-year-old man presenting with asthenia and weight loss with adrenal sarcomatoid carcinoma metastatic to the lung. A computed tomography (CT) scan and ultrasonography of the patient's abdomen suggested a large homogeneous mass in the right adrenal gland, and a CT scan of his chest suggested lung metastasis. Right adrenalectomy was performed. Histological examination revealed that the tumor was composed of sarcomatous and carcinomatous differentiation elements. Immunohistochemical examination revealed tumor cell positivity for vimentin and cytokeratin. At the 6-month follow-up the patient exhibited no disease progression and refused further proposed treatment. The patient was alive at the time of writing the current report. The present case report additionally reviews the literature, for the purpose of raising awareness of these rare lesions and assisting in achieving accurate diagnoses and effective treatment.

Primary mesenchymal chondrosarcoma with bilateral kidney invasion and calcification in renal pelvis: A case report and review of the literature.

Mesenchymal chondrosarcoma (MC) is a rare malignant cartilaginous forming tumor. MC of the kidney is extremely rare, with only seven cases reported in the literature. The present study described the case of a 17-year-old male, who presented with sudden severe pain in the right flank and a high fever. Imaging studies demonstrated a large soft heterogeneous mass (7.8×9.5×15 cm) located between the liver and right kidney with no clear demarcation, and a well-demarcated mass (1.3×2.4 cm) with patchy dense calcification occupying the left renal pelvis. Following the diagnosis of a Wilms' tumor, the patient underwent a right radical nephrectomy and the pathological diagnosis was MC of the kidney. To the best of our knowledge, the current study presents the first case of MC with bilateral kidney invasion and calcification in the renal pelvis. In addition, the clinical, radiological and pathological features, and the management of this unusual neoplasm were discussed.

High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

BACKGROUND: To analyze the expression of karyopherin alpha 2 (KPNA2) in upper tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression provides additional prognostic information following radical nephroureterectomy (RNU). METHODS: A tissue microarray (TMA) containing samples from 176 patients with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression using immunohistochemistry. KPNA2 expression in normal urothelial cell line and urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA interference in vitro, the effects of KPNA2 inhibition on cellular viability, migration and apoptosis were determined. RESULTS: KPNA2 expression was significantly upregulated in the UTUC samples compared with the adjacent normal urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the conventional predictive factors in a multivariate analysis. Additional in vitro experiments revealed that KPNA2 expression was higher in urothelial carcinoma cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific siRNA decreased cell viability and migration and increased apoptosis in urothelial carcinoma cell lines. CONCLUSIONS: KPNA2 is a novel independent prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have undergone RNU. Moreover, these data suggest that KPNA2 may be a promising therapeutic target for UTUC.

HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation.

BACKGROUND: High Mobility Group N (HMGN) proteins are a family of chromatin structural proteins that specifically bind to nucleosome core particles. HMGN5 is a novel and characteristic member of the HMGN protein family. We have previously found that HMGN5 is upregulated in prostate cancer and its downregulation had been demonstrated to induce apoptosis and G2-M cell cycle arrest. METHODS: The radiosensitization effect of HMGN5 knockdown on PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. The DNA double-strand break (DSB) repair kinetics of HMGN5 knockdown and control cells after radiation exposure was evaluated using immunocytofluorescence. The mitochondrial reactive oxygen species (ROS) levels were estimated using Dihydrorhodamine 123 (DHR 123) probes. Expression of mitochondrial antioxidant MnSOD was measured by real-time PCR and Western blot. The expression of antiapoptotic proteins Bcl-2 and Bcl-xL as well as cleavage of caspase-3, caspase-9, and PARP were also measured using Western blot. RESULTS: HMGN5 knockdown cells exhibit decreased clonogenic survival and increased apoptosis rate in response to 2-8 Gy ionizing radiation (IR). Loss of HMGN5 does not affect the DSB repair kinetics after radiation exposure. HMGN5 knockdown cells demonstrated increased mitochondrial ROS level and suppressed induction of MnSOD upon radiation compared with control cells upon radiation. Further, MnSOD knockdown resulted in inhibited cell viability as well as increased mitochondrial ROS level and apoptosis upon radiation in PC3 and DU145 cells. Finally, HMGN5 knockdown cells showed significantly decreased levels of antiapoptotic proteins Bcl-2 and Bcl-xL as well as increased cleavage of caspase-3, caspase-9, and PARP compared with control cells after radiation. CONCLUSIONS: HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation, and the radiosensitization effect may be partially mediated through suppressed induction of MnSOD and enhanced activation of apoptosis pathway in response to IR.

Investigating urachal carcinoma for more than 15 years.

Urachal carcinomas are rare bladder malignances, which usually present at an advanced stage with a high risk of distant metastases and a poor prognosis. To improve understanding of this uncommon carcinoma, a retrospective review was conducted for the cases observed at Peking University Shenzhen Hospital and Peking University First Hospital. The clinical outcomes were analyzed for 17 patients with a diagnosis of urachal cancer, who were admitted to Peking University Shenzhen Hospital (Shenzhen, China) and Peking University First Hospital (Beijing, China) between 1998 and 2013. The TNM staging system was used to predict outcomes. Among the 17 study patients, there were 10 males and seven females, with a median age at diagnosis of 50 years. A total of four (23%) patients presented with lymph node or distant metastasis. The median overall survival time for all stages was 57.6 months, with five patients (38.4%) alive for more than five years following treatment. The application of the TNM staging system demonstrated a median survival time of 6.2 years for stage I/II patients, compared with a median survival of 1.8 years (log-rank, P<0.001) for patients with advanced disease (stages III and IV). In addition, no significant correlation was observed between tumor size and age, and survival. In conclusion, urachal carcinomas are usually locally advanced at presentation. Surgical excision remains the predominant choice of treatment and lymph node dissection is not required unless lymph node involvement is confirmed by preoperative examination. The current results indicated that the most significant predictor of prognosis was the tumor grade.