[A Case of Primary Adenocarcinoma Mucinous Subtype of the Bladder].

A 48-year-old man who presented with asymptomatic gross hematuria in July 202X had been followed up without treatment. In January 202X, he was referred to our department due to the exacerbation of his hematuria. Contrast-enhanced magnetic resonance imaging revealed bladder cancer suggested bilateral seminal vesicle and prostate invasion, and enlarged right internal and external iliac lymph nodes. The pathological diagnosis was mucinous bladder adenocarcinoma. Prostate biopsy results were negative. Upper and lower gastrointestinal examinations were unremarkable. We suspected bladder cancer cT4aN2M0. In March 202X＋1, the patient underwent robotic-assisted laparoscopic total bladder resection, pelvic lymph node dissection, and intracorporeal urinary tract modification (ileal conduit creation). The final diagnosis was primary mucinous adenocarcinoma pT4aN2M0 of the bladder. Given the heightened risk of recurrence, the patient was administered a three-month course of oxaliplatin and capecitabine (XELOX) as adjuvant postoperative chemotherapy. The patient remains free of progression at 8 months postoperatively. Adenocarcinoma of the bladder is an exceedingly rare entity, with no established chemotherapeutic protocols. Primary mucinous adenocarcinoma of the bladder is even more exceptional. Presently, only regimens similar to those for colorectal cancer or adenocarcinoma of unknown primary, including 5-fluorouracil, are considered. In our particular case, we elected to pursue XELOX therapy, aligning with the principles governing the management of colorectal cancer.

[A Case of Successful Treatment of Small Cell Carcinoma of the Bladder with Pembrolizumab].

Small cell carcinoma of the bladder (SCCB) is a rare cancer that accounts for approximately 1% of primary malignant bladder tumors. It is highly malignant and has a poor prognosis. Similar to small cell lung cancer, platinum-based chemotherapy is recommended as the first-line therapy, and amrubicin (AMR) is recommended as the second-line therapy, but there is no established therapy after the second line. We report a case of SCCB that was refractory to multiple chemotherapies but responded to pembrolizumab. A 77-year-old male, diagnosed with clinical stage T3N0M0 small cell carcinoma and invasive urothelial carcinoma by transurethral resection of bladder tumor (TURBT), underwent robot-assisted radical cystectomy after three cycles of neoadjuvant cisplatin-irinotecan chemotherapy, and pathological examination revealed only small cell carcinoma in his cystectomy specimen. After three courses of adjuvant carboplatin-etoposide chemotherapy, the patient developed liver and bone metastases. Furthermore, after two courses of amrubicin, we started pembrolizumab due to the progression of metastases. Metastases decreased after starting pembrolizumab and continued to decrease after discontinuation because of immunerelated adverse events (irAEs). Therefore, pembrolizumab may be an option for the treatment of refractory SCCB.

Concomitant decrease of E- and A-FABP expression predicts worse survival in urothelial bladder cancer patients.

Non-muscle invasive bladder cancers (NMIBC) pTa-pT1 are depicted by a high risk of recurrence and/or progression with an unpredictable clinical evolution. Our aim was to identify, from the original resection specimen, tumors that will progress to better manage patients. We previously showed that A-FABP (Adipocyte- Fatty Acid Binding Protein) loss predicted NMIBC progression. Here we determined by immunohistochemistry the prognostic value of E-FABP (Epidermal-Fatty Acid Binding Protein) expression in 210 tumors (80 pTa, 75 pT1, 55 pT2-T4). Thus, E-FABP low expression was correlated with a high grade/stage, the presence of metastatic lymph nodes, and visceral metastases (p < 0.001). Unlike A-FABP in NMIBC, E-FABP low expression was not associated with RFS or PFS in Kaplan-Meier analysis. But patients of the overall cohort with a high E-FABP expression had a longer mOS (53.8 months vs. 29.3 months, p = 0.029). The immunohistochemical analysis on the same NMIBC tissue sections revealed that when A-FABP is absent, a high E-FABP expression is detected. E-FABP could compensate A-FABP loss. Interestingly, patients, whose original tumor presents both low E-FABP and negative A-FABP, had the worse survival, those maintaining the expression of both markers had better survival. To conclude, the combined evaluation of A- and E-FABP expression allowed to stratify patients with urothelial carcinoma for optimizing treatment and follow-up.

Impairment of α-tubulin and F-actin interactions of GJB3 induces aneuploidy in urothelial cells and promotes bladder cancer cell invasion.

BACKGROUND: We have previously identified an unsuspected role for GJB3 showing that the deficiency of this connexin protein induces aneuploidy in human and murine cells and accelerates cell transformation as well as tumor formation in xenograft models. The molecular mechanisms by which loss of GJB3 leads to aneuploidy and cancer initiation and progression remain unsolved. METHODS: GJB3 expression levels were determined by RT-qPCR and Western blot. The consequences of GJB3 knockdown on genome instability were assessed by metaphase chromosome counting, multinucleation of cells, by micronuclei formation and by the determination of spindle orientation. Interactions of GJB3 with α-tubulin and F-actin was analyzed by immunoprecipitation and immunocytochemistry. Consequences of GJB3 deficiency on microtubule and actin dynamics were measured by live cell imaging and fluorescence recovery after photobleaching experiments, respectively. Immunohistochemistry was used to determine GJB3 levels on human and murine bladder cancer tissue sections. Bladder cancer in mice was chemically induced by BBN-treatment. RESULTS: We find that GJB3 is highly expressed in the ureter and bladder epithelium, but it is downregulated in invasive bladder cancer cell lines and during tumor progression in both human and mouse bladder cancer. Downregulation of GJB3 expression leads to aneuploidy and genomic instability in karyotypically stable urothelial cells and experimental modulation of GJB3 levels alters the migration and invasive capacity of bladder cancer cell lines. Importantly, GJB3 interacts both with α-tubulin and F-actin. The impairment of these interactions alters the dynamics of these cytoskeletal components and leads to defective spindle orientation. CONCLUSION: We conclude that deregulated microtubule and actin dynamics have an impact on proper chromosome separation and tumor cell invasion and migration. Consequently, these observations indicate a possible role for GJB3 in the onset and spreading of bladder cancer and demonstrate a molecular link between enhanced aneuploidy and invasive capacity cancer cells during tumor cell dissemination.

Knockdown of AMIGO2 suppresses proliferation and migration through regulating PPAR-γ in bladder cancer.

PURPOSE: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. METHODS: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. RESULTS: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell-cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. CONCLUSION: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway.

Bladder Cancer Patients with Elevated SPRR1B Expression Experiencing a Poor Prognosis.

BACKGROUND: SPRR1B, a member of the small proline-rich protein family, is implicated in various epithelial cancers as a potential oncogene linked to tumour growth and poor survival outcomes. However, its role in urothelial bladder carcinoma (UBC) remains to be fully elucidated. METHODS: Transcriptional profiling data from The Cancer Genome Atlas grouped UBC samples in accordance with SPRR1B expression. Bioinformatic analysis was conducted to evaluate whether SPRR1B is a prognostic factor and a survival factor in UBC. Gene set enrichment analysis (GSEA) was performed to study immune cells and pathways. Reverse transcription quantitative real-time polymerase chain reaction detected gene expression. Immunohistochemistry assessed protein expression. Spearman correlation test analysed the correlation between SPRR1B and the protein p53. RESULTS: The bioinformatics results indicated that the expression level of SPRR1B in UBC tissues was significantly increased compared with that in normal bladder tissues, correlating with clinical characteristics. A high expression predicted poor prognosis and survival. Univariate Cox statistics showed that a high expression level of SPRR1B was correlated with UBC patients having poor overall survival (OS) (p < 0.05). In addition, on the basis of the multivariate Cox analysis, SPRR1B expression was independently correlated with OS (p = 0.005). GSEA analysis revealed enrichment in the p53, apoptosis, and cell cycle signalling pathways, and an association with B cells, lymphocytes, and natural killer cells. In addition, SPRR1B was found to be associated with immune infiltration based on the analysis of immune cell infiltration. Performing corresponding verification on a small number of tissues collected from bladder cancer patients revealed that the expression of this protein was negatively correlated with the expression of p53. CONCLUSIONS: SPRR1B overexpression predicts poor UBC outcomes, suggesting its role as a prognostic marker and therapeutic target. Further research is necessary to elucidate its role in UBC progression.

Clinical, Pathological Characteristics and Progression of Urothelial Bladder Cancer in Young Adult Patients. Our Experience and Literature Review.

BACKGROUND: Bladder cancer is highly prevalent even though its incidence is considerably lower in patients younger than 40 years, thus raising the issue of the influence of age at diagnosis on the natural history of this disease. This study aimed to evaluate the characteristics and progression of young patients with urothelial bladder carcinoma with at least 10 years of follow-up and to compare the results with those of previously reported studies. MATERIAL AND METHODS: A retrospective study between 1990 and 2007 was conducted. The medical records and tissue samples of patients with urothelial bladder tumours were reviewed, and patients with a first diagnosis of urothelial carcinoma of the bladder at age 40 years or younger were selected. Their clinical and pathological data and disease-free survival were analysed. RESULTS: This study included 43 patients, with a median follow-up of 152 months (interquartile range (IQR): 96-222) and a mean age at diagnosis of 34 years (SD: 4.6). Thirty-five patients (81.4%) had non-muscle invasive tumours at diagnosis, and 53.5%, 27.9% and 18.6% had tumour grades of G1, G2 and G3, respectively. Fifteen patients (34.9%) experienced recurrence, and eight (18.6%) progressed. At 24 and 60 months, the recurrence-free survival rates were 84.8% (95% confidence interval (CI): 69.2%-92.9%) and 68.9% (95% CI: 51.7%-81%), respectively, and the progression-free survival rates were 94.9% (95% CI: 81%-98.7%) and 92.2% (95% CI: 77.8%-97.4%), respectively. CONCLUSIONS: Bladder cancer is an uncommon disease in young patients. In most cases, it consists of non-muscle-invasive tumours, with a low rate of recurrence and progression. The prognosis is based on the tumour's characteristics and not on the patient's age.

A histopathological and epidemiological study of urothelial carcinoma at a tertiary care centre in Peshawar, Pakistan.

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer.

Cisplatin resistance is a major challenge for systemic therapy against advanced bladder cancer (BC). Little information is available on the regulation of cisplatin resistance and the underlying mechanisms require elucidation. Here, we detected that downregulation of the tumor suppressor, PPP2R2B (a serine/threonine protein phosphatase 2 A regulatory subunit), in BC promoted cell proliferation and migration. What's more, low PPP2R2B expression was correlated with cisplatin resistance. In vitro and in vivo experiments verified that PPP2R2B could promote BC sensitivity to cisplatin. In terms of mechanism, we identified a novel function of PPP2R2B as a nucleocytoplasmic transport molecule. PPP2R2B promoted ISG15 entry into the nucleus by mediating binding of IPO5 with ISG15. Nuclear translocation of ISG15 inhibited DNA repair, further increasing ISG15 expression through activation of the STING pathway. Besides, PPP2R2B was down-regulated by SUV39H1-mediated histone 3 lysine 9 trimethylation, which could be restored by the SUV39H1-specific inhibitor, chaetocin. Our data suggest that PPP2R2B expression level is a potential biomarker for chemotherapy response and that chemotherapy in combination with chaetocin may be a feasible treatment strategy for patients with BC.

Construction and validation of a prognostic model for bladder cancer based on disulfidptosis-related lncRNAs.

BACKGROUND: Bladder cancer (BLCA) is a prevalent and aggressive cancer associated with high mortality and poor prognosis. Currently, studies on the role of disulfidptosis-related long non-coding RNAs (DRLs) in BLCA are limited. This study aims to construct a prognostic model based on DRLs to improve the accuracy of survival predictions for patients and identify novel targets for therapeutic intervention in BLCA management. METHODS: Transcriptomic and clinical datasets for patients with BLCA were obtained from The Cancer Genome Atlas. Using multivariate Cox regression and least absolute shrinkage and selection operator techniques, a risk prognostic signature defined by DRLs was developed. The model's accuracy and prognostic relevance were assessed through Kaplan-Meier survival plots, receiver operating characteristic curves, concordance index, and principal component analysis. Functional and pathway enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, were conducted to elucidate the underlying biological processes. Immune cell infiltration was quantified using the CIBERSORT algorithm. Differences and functions of immune cells in different risk groups were evaluated through single-sample Gene Set Enrichment Analysis. The Tumor Immune Dysfunction and Exclusion predictor and tumor mutational burden (TMB) assessments were utilized to gauge the likelihood of response to immunotherapy. Drug sensitivity predictions were made using the Genomics of Drug Sensitivity in Cancer database. RESULTS: A robust 8-DRL risk prognostic model, comprising LINC00513, SMARCA5-AS1, MIR4435-2HG, MIR4713HG, AL122035.1, AL359762.3, AC006160.1, and AL590428.1, was identified as an independent prognostic indicator. This model demonstrated strong predictive power for overall survival in patients with BLCA, revealing significant disparities between high- and low-risk groups regarding tumor microenvironment, immune infiltration, immune functions, TMB, Tumor Immune Dysfunction and Exclusion scores, and drug susceptibility. CONCLUSION: This study introduces an innovative prognostic signature of 8 DRLs, offering a valuable prognostic tool and potential therapeutic targets for bladder carcinoma. The findings have significant implications for TMB, the immune landscape, and patient responsiveness to immunotherapy and targeted treatments.

Similar genetic profile in early and late stage urothelial tract cancer.

INTRODUCTION: Urothelial tract cancer (UTC) ranks as the tenth most prevalent cancer and holds the seventh position in terms of mortality worldwide. Despite its prevalence and mortality ranking, there are still gaps in the knowledge of the mutational landscape in patients with advanced disease who have limited therapeutic options after multiple lines of prior treatment. This study compares the genomic and transcriptomic landscape, and targeted treatment options between metastatic UTC (mUTC) patients treated with multiple lines of therapy compared to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC). METHODS: We compared genomic and clinical data from two cohorts: mUTC patients who received multiple lines of therapy and were referred to the Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University of Copenhagen. Data for MIBC UTC patients were acquired from the Cancer Genome Atlas Bladder Cancer (TCGA BLCA) cohort. Biopsies in CoPPO were performed at the time of enrollment. 523 highly important cancer-related genes (TrueSight Oncology-500 targeted sequencing panel) were used from both cohorts for comparative analysis. Analyses included RNA count data to compare predicted molecular subtypes in each cohort separately. RESULTS: Patients from the CoPPO cohort had a lower median age at first-line treatment than the TCGA BLCA cohort, with no significant gender disparity. The predominant histology was urothelial cell carcinoma in both cohorts. Genomic analysis revealed no significant difference between the top mutated genes in the two cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated a higher frequency of neuroendocrine differentiation in the CoPPO cohort. 13% of patients in the CoPPO cohort received targeted therapy based on genomic findings, and 16% received non-targeted treatment, totaling 29% receiving CoPPO treatment (9 patients). The remaining 71% received best supportive care. Kaplan-Meier analysis showed a non-significant survival benefit for the intervention group in the CoPPO cohort. CONCLUSION: When focusing on 523 highly relevant cancer genes, the mutational profile of mUTC patients who have undergone numerous treatment lines resembles that of newly diagnosed MIBC. These alterations can be targeted, indicating the potential advantage of early genomic testing for personalized treatment within clinical trials.

Diagnostic performance of photodynamic diagnosis with oral 5-aminolevulinic acid for upper tract- and bladder urothelial carcinoma: a single-centre, retrospective analysis.

PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.

MyD88 Signaling Accompanied by Microbiota Changes Supports Urinary Bladder Carcinogenesis.

Urinary bladder cancer (BC) inflicts a significant impairment of life quality and poses a high mortality risk. Schistosoma haematobium infection can cause BC, and the urinary microbiota of BC patients differs from healthy controls. Importantly, intravesical instillation of the bacterium Bacillus Calmette-Guerin stands as the foremost therapy for non-muscle invasive BC. Hence, studying the receptors and signaling molecules orchestrating bacterial recognition and the cellular response in the context of BC is of paramount importance. Thus, we challenged Toll-like receptor 4 (Tlr4) and myeloid differentiation factor 88 (Myd88) knock-out (KO) mice with N-butyl-N-(4-hydroxylbutyl)-nitrosamine (BBN), a well-known urinary bladder carcinogen. Gut microbiota, gene expression, and urinary bladder pathology were followed. Acute exposure to BBN did not reveal a difference in bladder pathology despite differences in the animal's ability to recognize and react to bacteria. However, chronic treatment resulted in reduced cancer invasiveness among Myd88KO mice while the absence of functional Tlr4 did not influence BC development or progression. These differences correlate with a heightened abundance of the Faecalibaculum genus and the lowest microbial diversity observed among Myd88KO mice. The presented data underscore the important role of microbiota composition and MyD88-mediated signaling during bladder carcinogenesis.

Utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in elderly patients: a retrospective cohort study.

Neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). Older patients often do not receive NAC due to its potential toxicities. We examined treatment patterns of elderly MIBC patients as well as impact of NAC on survival in this population. The National Cancer Database was queried from 2006 to 2019 for stage T2-T4a MIBC patients ≥ 80 years old. Treatment exposures (extirpative surgery; chemotherapy; radiation) were ascertained. Kaplan-Meier survival curves were generated based on treatment modalities (no treatment; radiation only; chemotherapy only; chemoradiation; surgery only; NAC with surgery). Multivariable Cox proportional hazards regression assessed associations with overall survival (OS). The cohort included 16,391 patients (mean age 86 years); 51% received treatment. MIBC treatment was less common with advancing age; patients receiving NAC then surgery were younger and had lower comorbidity scores. From 2006 to 2019, more patients received chemoradiation, while rates of NAC rose modestly. Median OS for the NAC with surgery group was 48 months versus 9 months for the no treatment group. Log-rank tests showed significantly improved survival in the NAC with surgery group compared to the surgery only group, while Cox proportional hazards regression analysis showed highest survival benefit in the NAC with surgery group. Only half of elderly MIBC patients received treatment, with fewer undergoing curative intent. NAC with surgery was associated with the greatest survival benefit. While our findings should be taken in the context of potential selection bias and patient preferences, they support NAC as part of shared-decision making regardless of age.

PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer.

Background: Cisplatin (DDP) based combination chemotherapy is a vital method for the treatment of bladder cancer (BLca). Chemoresistance easily occurs in the course of cisplatin chemotherapy, which is one of the important reasons for the unfavorable prognosis of BLca patients. Circular RNAs (circRNAs) are widely recognized for their role in the development and advancement of BLca. Nevertheless, the precise role of circRNAs in DDP resistance for BLca remains unclear. Methods: To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. RT-qPCR assay was utilized to assess the expression levels of circRNA, miRNA and mRNA in BLca tissues and cells. Functional experiments were conducted to assess the function of circATIC in BLca progression and chemosensitivity in vitro. Various techniques such as FISH, Dual-luciferase reporter assay, TRAP, RNA digestion assay, RIP and ChIRP assay were used to investigate the relationships between PTBP1, circATIC, miR-1247-5p and RCC2. Orthotopic bladder cancer model, xenograft subcutaneous tumor model and xenograft lung metastasis tumor model were performed to indicate the function and mechanism of circATIC in BLca progression and chemosensitivity in vivo. Results: In our study, we observed that circATIC expression was significantly enhanced in BLca tissues and cells and DDP resistant cells. Patients with higher circATIC expression have larger tumor diameter, higher incidence of postoperative metastasis and lower overall survival rate. Further experiments showed that circATIC accelerated BLca cell growth and metastasis and induced DDP resistance. Mechanistically, alternative splicing enzyme PTBP1 mediated the synthesis of circATIC. circATIC could enhance RCC2 mRNA stability via sponging miR-1247-5p or constructing a circATIC/LIN28A/RCC2 RNA-protein ternary complex. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Conclusion: Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.

The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear. AIMS: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA). OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease. METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays. RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels. CONCLUSION: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.

Inflammatory myofibroblastic tumor in the urinary bladder in a dog.

An 8-year-old castrated male Maltese dog was presented with a urinary bladder mass, urolithiasis, and hematuria. A solitary, pedunculated, intraluminal mass on the caudodorsal wall was identified with extensive irregular bladder wall thickening, and the mass was surgically removed. Postoperative histopathology demonstrated a submucosal lesion comprising spindle cells with marked inflammatory cell infiltration, without malignant changes. Immunohistochemical staining revealed vimentin and desmin positivity in the mass. An inflammatory myofibroblastic tumor (IMT) was definitively diagnosed. No recurrence was observed during a 43-month follow-up period. Although IMTs are rare in dogs, they should be considered a differential diagnosis for mass-like urinary bladder lesions accompanying a chronic inflammatory disease process. Key clinical message: Canine IMT should be included in the differential diagnoses of bladder masses, especially when dogs exhibit chronic irritation and inflammation.

Tumeur myofibroblastique inflammatoire de la vessie chez un chienUn chien maltais mâle castré de 8 ans a été présenté avec une masse à la vessie, une lithiase urinaire et une hématurie. Une masse intraluminale pédonculée solitaire sur la paroi caudodorsale a été identifiée avec un épaississement important et irrégulier de la paroi vésicale, et la masse a été retirée chirurgicalement. L'histopathologie postopératoire a mis en évidence une lésion à la sous-muqueuse comprenant des cellules fusiformes avec une infiltration cellulaire inflammatoire marquée, sans modification maligne. La coloration immunohistochimique a révélé une positivité à la vimentine et à la desmine dans la masse. Une tumeur myofibroblastique inflammatoire (IMT) a été définitivement diagnostiquée. Aucune récidive n'a été observée au cours d'une période de suivi de 43 mois. Bien que les IMT soient rares chez le chien, ils doivent être considérés comme un diagnostic différentiel des lésions de la vessie de type masse accompagnant un processus de maladie inflammatoire chronique.Message clinique clé:L'IMT canine doit être incluse dans les diagnostics différentiels des masses vésicales, en particulier lorsque les chiens présentent une irritation et une inflammation chroniques.(Traduit par Dr Serge Messier).