Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 25.873
1.
BMJ Case Rep ; 17(6)2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834309

Rhabdomyosarcomas are the most common soft-tissue sarcomas, found usually in the younger age group. Histologically, they are subdivided into embryonal, alveolar, pleomorphic and not otherwise specified. They have a heterogenous appearance on imaging with few additional characteristic features based on the subtype. Botryoid variant of embryonal rhabdomyosarcoma commonly involves the genitourinary and the biliary system. They can be multifocal. Most of these lesions have a heterogenous appearance on imaging with areas of necrosis and haemorrhage. On ultrasound, they are polypoidal with cystic areas and are vascular. The lesions are hyperintense on T2 sequences, isointense to the skeletal muscle on T1 sequences and show heterogenous enhancement. Surgery is the mainstay of treatment along with radiotherapy or chemotherapy depending on the site and the stage of the tumour. We report a case of botryoid variant of rhabdomyosarcoma involving the vagina and the urinary bladder.


Rhabdomyosarcoma, Embryonal , Urinary Bladder Neoplasms , Vaginal Neoplasms , Humans , Rhabdomyosarcoma, Embryonal/pathology , Rhabdomyosarcoma, Embryonal/diagnosis , Rhabdomyosarcoma, Embryonal/diagnostic imaging , Rhabdomyosarcoma, Embryonal/surgery , Female , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Vaginal Neoplasms/pathology , Vaginal Neoplasms/diagnostic imaging , Vaginal Neoplasms/surgery , Vaginal Neoplasms/diagnosis , Magnetic Resonance Imaging , Child , Ultrasonography
2.
Nat Commun ; 15(1): 4690, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824132

Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients. The algorithm is validated on a dataset of 350 patients, achieving an area under the curve of 0.75, specificity of 31.8% at 88.7% sensitivity, and projected 28.7% reduction in molecular testing. We successfully deploy the system in a non-interventional study comprising 89 global study clinical sites and demonstrate its potential to prioritize/deprioritize molecular testing resources and provide substantial cost savings in the drug development and clinical settings.


Algorithms , Deep Learning , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Clinical Trials as Topic , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/diagnosis , Male , Female , Patient Selection , Urologic Neoplasms/pathology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/genetics
3.
Oncol Res ; 32(6): 1021-1030, 2024.
Article En | MEDLINE | ID: mdl-38827321

Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.


Ataxia Telangiectasia Mutated Proteins , Cisplatin , Cytidine Deaminase , Minor Histocompatibility Antigens , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , Cell Line, Tumor , Male , Minor Histocompatibility Antigens/metabolism , Minor Histocompatibility Antigens/genetics , Middle Aged , Female , Checkpoint Kinase 1/metabolism , Checkpoint Kinase 1/antagonists & inhibitors , Checkpoint Kinase 1/genetics , Apoptosis , Aged , Neoplasm Invasiveness , Cell Proliferation , Cell Survival/drug effects
4.
Sci Rep ; 14(1): 12659, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830942

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.


Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/urine , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Male , Female , Risk Factors , Aged , Middle Aged , Retrospective Studies , Case-Control Studies , Cell Nucleus
5.
Int J Oncol ; 65(1)2024 Jul.
Article En | MEDLINE | ID: mdl-38847230

CD46, a transmembrane protein known for protecting cells from complement­mediated damage, is frequently dysregulated in various types of cancer. Its overexpression in bladder cancers safeguards the cancer cells against both complement and antibody­mediated cytotoxicity. The present study explored a new role of CD46 in facilitating cancer cell invasion and metastasis, examining its regulatory effect on matrix metalloproteases (MMPs) and their effect on the metastatic capability of bladder cancer cells. Specifically, CD46 alteration positively influenced MMP9 expression, but not MMP2, in several bladder cancer cell lines. Furthermore, CD46 overexpression triggered phosphorylation of p38 MAPK and protein kinase B (AKT), leading to enhanced activator protein 1 (AP­1) activity via c­Jun upregulation. The inhibition of p38 or AKT pathways attenuated the CD46­induced MMP9 and AP­1 upregulation, indicating that the promotion of MMP9 by CD46 involved activating both p38 MAPK and AKT. Functionally, the upregulation of MMP9 by CD46 translated to increased migratory and invasive capabilities of bladder cancer cells, as well as enhanced in vivo metastasis. Overall, the present study revealed a novel role for CD46 as a metastasis promoter through MMP9 activation in bladder cancers and highlighted the regulatory mechanism of CD46­mediated MMP9 promotion via p38 MAPK and AKT activation.


Cell Movement , Matrix Metalloproteinase 9 , Membrane Cofactor Protein , Proto-Oncogene Proteins c-akt , Urinary Bladder Neoplasms , p38 Mitogen-Activated Protein Kinases , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/genetics , Humans , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Cell Line, Tumor , p38 Mitogen-Activated Protein Kinases/metabolism , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Membrane Cofactor Protein/metabolism , Membrane Cofactor Protein/genetics , Gene Expression Regulation, Neoplastic , Neoplasm Metastasis , Neoplasm Invasiveness , Transcription Factor AP-1/metabolism , Up-Regulation , Signal Transduction
6.
J Cell Mol Med ; 28(11): e18473, 2024 Jun.
Article En | MEDLINE | ID: mdl-38847477

Bladder cancer is one of the most prevalent cancers worldwide, and its morbidity and mortality rates have been increasing over the years. However, how RAC family small GTPase 3 (RAC3) affects the proliferation, migration and invasion of cisplatin-resistant bladder cancer cells remains unclear. Bioinformatics techniques were used to investigate the expression of RAC3 in bladder cancer tissues. Influences of RAC3 in the grade, stage, distant metastasis, and survival rate of bladder cancer were also examined. Analysis of the relationship between RAC3 expression and the immune microenvironment (TIME), genomic mutations, and stemness index. In normal bladder cancer cells (T24, 5637, and BIU-87) and cisplatin-resistant bladder cancer cells (BIU-87-DDP), the expression of RAC3 was detected separately with Western blotting. Plasmid transfection was used to overexpress or silence the expression of RAC3 in bladder cancer cells resistant to cisplatin (BIU-87-DDP). By adding activators and inhibitors, the activities of the JNK/MAPK signalling pathway were altered. Cell viability, invasion, and its level of apoptosis were measured in vitro using CCK-8, transwell, and flow cytometry. The bioinformatics analyses found RAC3 levels were elevated in bladder cancer tissues and were associated with a poor prognosis in bladder cancer. RAC3 in BIU-87-DDP cells expressed a higher level than normal bladder cancer cells. RAC3 overexpression promoted BIU-87-DDP proliferation. The growth of BIU-87-DDP cells slowed after the knockdown of RAC3, and RAC3 may have had an impact on the activation of the JNK/MAPK pathway.


Apoptosis , Cell Movement , Cell Proliferation , Cisplatin , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness , Urinary Bladder Neoplasms , rac GTP-Binding Proteins , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , rac GTP-Binding Proteins/metabolism , rac GTP-Binding Proteins/genetics , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Female , Male , Middle Aged , Tumor Microenvironment , MAP Kinase Signaling System/drug effects
7.
J Exp Med ; 221(8)2024 Aug 05.
Article En | MEDLINE | ID: mdl-38847806

Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.


Tumor Microenvironment , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Humans , Tumor Microenvironment/immunology , Male , Killer Cells, Natural/immunology , Female , CD8-Positive T-Lymphocytes/immunology , Aged , CD4-Positive T-Lymphocytes/immunology , Single-Cell Analysis/methods , Dendritic Cells/immunology , Middle Aged , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , RNA-Seq , Single-Cell Gene Expression Analysis
8.
Sci Rep ; 14(1): 10550, 2024 05 08.
Article En | MEDLINE | ID: mdl-38719836

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.


Cystectomy , Postoperative Complications , Robotic Surgical Procedures , Smoking , Urinary Bladder Neoplasms , Humans , Cystectomy/adverse effects , Cystectomy/methods , Male , Female , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Aged , Smoking/adverse effects , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Databases, Factual , Treatment Outcome , Republic of Korea/epidemiology , Preoperative Period
9.
World J Urol ; 42(1): 307, 2024 May 09.
Article En | MEDLINE | ID: mdl-38722418

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.


Carcinoma, Transitional Cell , Humans , Male , Retrospective Studies , Female , Aged , Middle Aged , Risk Assessment , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Survival Rate , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , Neoplasm Staging , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Risk Factors
10.
PLoS One ; 19(5): e0302548, 2024.
Article En | MEDLINE | ID: mdl-38728337

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.


Antibodies, Monoclonal, Humanized , Cost-Benefit Analysis , Humans , Antibodies, Monoclonal, Humanized/economics , Antibodies, Monoclonal, Humanized/therapeutic use , France , Male , Female , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/economics , Urinary Bladder Neoplasms/pathology , Quality-Adjusted Life Years , Aged , Middle Aged , Adult , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/economics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Neoplasm Metastasis , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/economics , Urologic Neoplasms/pathology , Maintenance Chemotherapy/economics
11.
Investig Clin Urol ; 65(3): 256-262, 2024 May.
Article En | MEDLINE | ID: mdl-38714516

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.


Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Deoxycytidine , Gemcitabine , Neoadjuvant Therapy , Neoplasm Invasiveness , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Male , Cisplatin/administration & dosage , Female , Aged , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Risk Factors , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Retrospective Studies , Treatment Failure , Cystectomy/methods , Chemotherapy, Adjuvant
12.
Investig Clin Urol ; 65(3): 263-278, 2024 May.
Article En | MEDLINE | ID: mdl-38714517

PURPOSE: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). MATERIALS AND METHODS: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. RESULTS: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. CONCLUSIONS: Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.


Biomarkers, Tumor , Cancer-Associated Fibroblasts , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/drug therapy , Prognosis , Biomarkers, Tumor/genetics , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Male , Female , Transcriptome , Treatment Outcome , Myofibroblasts
13.
Investig Clin Urol ; 65(3): 279-285, 2024 May.
Article En | MEDLINE | ID: mdl-38714518

PURPOSE: To investigate the relationship between urine cytology results after overnight continuous saline irrigation (OCSI) following transurethral resection of bladder tumor (TURBT) and bladder tumor recurrence in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective study was conducted on patients diagnosed with NMIBC between 2016 and 2020 after undergoing TURBT at our hospital. All patients received OCSI following TURBT and had urine cytology test at postoperative 1 day. Urine cytology was classified into three groups: Negative, low-grade urothelial neoplasm (LGUN)+atypical urothelial cells (AUC), and suspicious for high-grade urothelial carcinoma (SHGUC)+high-grade urothelial carcinoma (HGUC). Recurrence-free survival (RFS) in each group was compared using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate independent prognostic factors. RESULTS: A total of 172 patients were included in this study. Based on urine cytology group (after OCSI), RFS did not reach the median value in the Negative group. In the LGUN+AUC group, the median RFS was 615.00 days. In the SHGUC+HGUC group, the median RFS was 377.00 days. In survival analysis, the Negative group had a longer RFS than the SHGUC+HGUC group (p=0.013). However, Cox regression analysis showed that SHGUC+HGUC was not an independent prognostic factor for recurrence. CONCLUSIONS: Urine cytology results after OCSI following TURBT in NMIBC were associated with bladder tumor recurrence. Specifically, SHGUC or HGUC in urine cytology after OCSI showed earlier recurrence than negative cases. However, further research is needed to accurately determine whether it is an independent prognostic factor.


Neoplasm Recurrence, Local , Saline Solution , Therapeutic Irrigation , Urinary Bladder Neoplasms , Urine , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/urine , Urinary Bladder Neoplasms/surgery , Neoplasm Recurrence, Local/urine , Retrospective Studies , Male , Female , Aged , Middle Aged , Urine/cytology , Saline Solution/administration & dosage , Cystectomy/methods , Time Factors , Urethra/pathology , Urinalysis , Transurethral Resection of Bladder , Cytology
15.
Genet Res (Camb) ; 2024: 4285171, 2024.
Article En | MEDLINE | ID: mdl-38715622

Bladder cancer has recently seen an alarming increase in global diagnoses, ascending as a predominant cause of cancer-related mortalities. Given this pressing scenario, there is a burgeoning need to identify effective biomarkers for both the diagnosis and therapeutic guidance of bladder cancer. This study focuses on evaluating the potential of high-definition computed tomography (CT) imagery coupled with RNA-sequencing analysis to accurately predict bladder tumor stages, utilizing deep residual networks. Data for this study, including CT images and RNA-Seq datasets for 82 high-grade bladder cancer patients, were sourced from the TCIA and TCGA databases. We employed Cox and lasso regression analyses to determine radiomics and gene signatures, leading to the identification of a three-factor radiomics signature and a four-gene signature in our bladder cancer cohort. ROC curve analyses underscored the strong predictive capacities of both these signatures. Furthermore, we formulated a nomogram integrating clinical features, radiomics, and gene signatures. This nomogram's AUC scores stood at 0.870, 0.873, and 0.971 for 1-year, 3-year, and 5-year predictions, respectively. Our model, leveraging radiomics and gene signatures, presents significant promise for enhancing diagnostic precision in bladder cancer prognosis, advocating for its clinical adoption.


Neoplasm Staging , Neural Networks, Computer , Tomography, X-Ray Computed , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Humans , Tomography, X-Ray Computed/methods , Male , Female , RNA-Seq/methods , Aged , Nomograms , Middle Aged , Biomarkers, Tumor/genetics , ROC Curve , Prognosis , Transcriptome , Radiomics
16.
Arch Esp Urol ; 77(3): 303-314, 2024 Apr.
Article En | MEDLINE | ID: mdl-38715172

OBJECTIVE: Bladder cancer (BC) is the most common malignant tumour of the urinary system, and radical cystectomy combined with pelvic lymph node dissection (LND) is the standard treatment for BC. We conducted this meta-analysis to explore the efficacy and safety of extended lymph node dissection in radical cystectomy for BC. METHODS: PubMed, Embase, ProQuest PsycINFO, CINAHL, Web of Science and The Cochrane Library databases were searched for studies on extended lymph node dissection during radical BC surgery. The search time limit was from the establishment of the database to December 2023. Screening and quality assessment of literature were conducted. This meta-analysis was conducted to evaluate the influence of different lymph node dissection methods on recurrence-free survival (RFS), overall survival (OS), operation time, 90-day readmission rate and postoperative complication rate. RESULTS: A total of 15 studies were included, including 4854 patients. All studies were of high quality. This meta-analysis showed no statistically significant difference in the operation time, postoperative complications and 90-day hospitalisation rate between the two groups of patients. The harvested volume of lymph nodes, RFS and OS rate were not statistically different. CONCLUSIONS: Among patients with BC undergoing radical cystectomy, extended lymph node dissection did not have a significant effect on operative time, 90-day readmission rates or postoperative complication rates. Thus, extended lymph node dissection is a safe treatment that does not increase the patient's surgical risk.


Cystectomy , Lymph Node Excision , Urinary Bladder Neoplasms , Humans , Lymph Node Excision/methods , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/pathology , Cystectomy/methods , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology
17.
J Natl Compr Canc Netw ; 22(4): 216-225, 2024 05.
Article En | MEDLINE | ID: mdl-38754471

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.


Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Male , Neoplasm Staging , BCG Vaccine/therapeutic use
18.
Proc Natl Acad Sci U S A ; 121(20): e2312855121, 2024 May 14.
Article En | MEDLINE | ID: mdl-38713626

The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3highPD-L1high super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8+ T cells in mice. These findings reveal the mechanism by which tumor-neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.


Disease Progression , Interleukin-8 , Neutrophils , Tumor Microenvironment , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/immunology , Tumor Microenvironment/immunology , Humans , Neutrophils/immunology , Neutrophils/metabolism , Animals , Mice , Interleukin-8/metabolism , Cell Line, Tumor , Hepatocyte Growth Factor/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , B7-H1 Antigen/metabolism , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Female , Male , Neutrophil Infiltration
19.
Microbiome ; 12(1): 89, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745230

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.


Dietary Fiber , Dietary Supplements , Gastrointestinal Microbiome , Inulin , Mice, Inbred C57BL , Psyllium , Urinary Bladder Neoplasms , Animals , Mice , Gastrointestinal Microbiome/drug effects , Inulin/administration & dosage , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/pathology , Humans , Female , Radiation Injuries/prevention & control , Intestines/microbiology , Intestines/radiation effects , CD8-Positive T-Lymphocytes
20.
Medicine (Baltimore) ; 103(20): e38228, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758868

Hematuria is the most common symptom of bladder cancer (BCa). It is well-known that the frequency of hematuria increases with the use of antithrombotic drugs (ATDs). We designed our study with the hypothesis that patients using antithrombotic drugs who present with the complaint of hematuria and are subsequently diagnosed with BCa may receive an earlier diagnosis, leading to lower tumor grades and stages. Data of 441 consecutive patients who presented to our urology outpatient clinic with macroscopic hematuria between 2020 and 2023 were retrospectively evaluated. A total of 88 patients (21.4%) with a primary diagnosis of BCa were included in our study. Patients were divided into 2 groups: those using ATDs during the episode of macroscopic hematuria (group 1) and those not using ATDs (group 2). Univariate and multivariate binary logistic regression analysis was performed to identify risk factors that could predict tumor grade. The incidence of multiple tumors (>1) was significantly lower in patients using ATDs (P = .033). The number of patients with tumor size larger than 3 cm was significantly higher in the group not using ATDs (P = .005). The rates of pathological T1 stage in the group using ATDs were significantly lower than those in the nonuser group (P = .038). According to the results of the multivariate model, the effect of pathology stage and ATD use on predicting tumor grade was significant (P = .002 and P < .001, respectively). The probability of having a high-grade tumor in patients with pathology stage T1 was 5.32 times higher than in patients with pathology stage TA. The probability of having a high-grade tumor in patients not using ATDs was 7.73 times higher than in those using ATDs. The effect of pathology stage and ATD use on predicting tumor grade was found to be significant. The probability of having a high-grade tumor was higher in patients not using ATDs compared to those using ATDs. In light of these results, we can state that the use of ATDs is a positive predictive factor in the early diagnosis of BCa, bringing along the chance of early diagnosis and treatment.


Early Detection of Cancer , Fibrinolytic Agents , Hematuria , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/diagnosis , Male , Female , Retrospective Studies , Aged , Middle Aged , Early Detection of Cancer/methods , Hematuria/etiology , Fibrinolytic Agents/therapeutic use , Risk Factors , Neoplasm Staging , Neoplasm Grading
...