The potential mechanism of ursolic acid in the treatment of bladder cancer based on network pharmacology and molecular docking.

OBJECTIVE: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking. METHODS: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, in vitro experiments were performed to further validate the predicted results. RESULTS: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes (STAT3, VEGFA, CASP3, TP53, IL1B, and CCND1). The in vitro experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway. CONCLUSIONS: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

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

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

Mild magnetic hyperthermia-activated immuno-responses for primary bladder cancer therapy.

Surgical intervention followed by chemotherapy is the principal treatment strategy for bladder cancer, which is hindered by significant surgical risks, toxicity from chemotherapy, and high rates of recurrence after surgery. In this context, a novel approach using mild magnetic hyperthermia therapy (MHT) for bladder cancer treatment through the intra-bladder delivery of magnetic nanoparticles is presented for the first time. This method overcomes the limitations of low magnetic thermal efficiency, inadequate tumor targeting, and reduced therapeutic effectiveness associated with the traditional intravenous administration of magnetic nanoparticles. Core-shell Zn-CoFe2O4@Zn-MnFe2O4 (MNP) nanoparticles were developed and further modified with hyaluronic acid (HA) to enhance their targeting ability toward tumor cells. The application of controlled mild MHT using MNP-HA at temperatures of 43-44 °C successfully suppressed the proliferation of bladder tumor cells and tumor growth, while also decreasing the expression levels of heat shock protein 70 (HSP70). Crucially, this therapeutic approach also activated the body's innate immune response involving macrophages, as well as the adaptive immune responses of dendritic cells (DCs) and T cells, thereby reversing the immunosuppressive environment of the bladder tumor and effectively reducing tumor recurrence. This study uncovers the potential immune-activating mechanism of mild MHT in the treatment of bladder cancer and confirms the effectiveness and safety of this strategy, indicating its promising potential for the clinical management of bladder cancer with a high tendency for relapse.

Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1.

BACKGROUND: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive. PURPOSE: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1. METHODS: To examine the mechanisms by which oridonin directly binds to cysteines of HK1 and inhibits bladder cancer growth, this study utilized a variety of methods. These included the Human Proteome Microarray, Streptavidin-agarose affinity assay, Biolayer Interferometry (BLI) ainding analysis, Mass Spectrometry, Cellular Thermal Shift Assay, Extracellular Acidification Rate measurement, and Xenotransplant mouse models. RESULTS: As indicated by our current findings, oridonin forms a covalent bond with Cys-813, located adjacently to glucose-binding domain of HK1. This suppresses the enzymatic activity of HK1, leading to an effective reduction of glycolysis, which triggers cell death via apoptosis in cells derived from human bladder cancer. Significantly, oridonin also inhibits lactate-induced PD-L1 expression in bladder cancer. Furthermore, pairing oridonin with a PD-L1 inhibitor amplifies the cytotoxicity of CD8+ T cells against bladder cancer. CONCLUSION: This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.

BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.

A systematic review and meta-analysis of the anti-tumor effects of Paeoniae Radix Rubra in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Rubra (PRR) is the dried root of Paeonia lactiflora Pall, which has been widely used to anti-thrombotic, lipid-lowering, anti-spasmodic, antioxidant, antibacterial, hepatoprotective, and anti-tumor in Chinese clinical practice. Recent research has demonstrated that PRR plays a significant anti-tumor role in animal models of tumor-bearing. AIM OF THE STUDY: There has not been the evaluation of the anti-tumor effects of PRR. This study conducts a meta-analysis to assess the anti-tumor efficacy of PRR on animal models, providing scientific evidence for clinical application of PRR in the adjuvant therapy of tumors. MATERIALS AND METHODS: English databases (PubMed, The Cochrane Library, Embase, and Web of Science) and Chinese databases (CNKI, WanFang, SinoMed, CTSJ-VIP) were used to search all pertinent animal studies investigating the anti-tumor effects of PRR and its extracts. The quality of the included studies was evaluated using the SYRCLE animal experiment risk assessment tool, and statistical analysis was carried out using Revman 5.3 software. Egger's test and funnel plots were used to assess potential publication bias in the studies. RESULTS: The initial search produced a total of 3905 potentially pertinent studies, and 24 studies met the inclusion criteria. These studies included animal tumor models of hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. The meta-analysis findings demonstrated that both PRR and its extracts significantly inhibited tumor growth in animals. Compared with the control group, PRR substantively inhibited tumor volume (SMD, -3.09; 95% CI, [-4.05, -2.13]; P < 0.0001), reduced tumor weight (SMD, -1.08; 95% CI, [-1.37, -0.78]; P < 0.0001), decreased tumor number (SMD, -2.16; 95% CI, [-3.45, -0.86]; P = 0.001), and prolonged the survival duration time (SMD, 0.97; 95% CI, [0.23, 1.71]; P = 0.01) on the experimental animals. CONCLUSIONS: PRR displayed a potential therapeutic efficacy on eight tumors in animal models including hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. However, the quality and quantity of included studies may affect the accuracy of positive results. In the future, more high-quality randomized controlled animal experiments are need for meta-analysis.

Prevention of Bladder Cancer Recurrence With the Botanical Formula LCS103: A Case Series Study.

Despite effective chemotherapy and other available oncology treatments, recurrence rates for non-muscle invasive bladder cancer (NMIBC) remain high, with as many as 60% of patients requiring repeat intravesical treatments with BCG or other agents within a 24-month period. The botanical formula LCS103 has displayed anti-cancer activity on bladder cancer cells, though its clinical efficacy remains to be proven. A consecutive series of 30 patients with bladder cancer was examined retrospectively, of which a cohort of 20 patients (18 with NMIBC, 2 with metastatic disease) was treated with LCS103 for between 14 months and 16 years, in addition to their conventional oncology care. Only 3 patients (15%) had a single tumor recurrence after initiation of the botanical treatment, as opposed to pre-treatment recurrence reported among 11 patients (55%; range, 1-5). The majority of LCS103-treated patients reported reduced severity for urological symptoms (pain, frequency, and urgency on urination; and nocturia), as well as for weakness and fatigue, and for general wellbeing. No adverse events were associated with use of the botanical formula. Further prospective randomized trials are needed to confirm and better understand these initial findings.

Symptomatic and functional recovery after transurethral resection of bladder tumor: Data from ecological momentary symptom assessment.

OBJECTIVES: To quantitatively describe the nature, severity, and duration of symptoms and functional impairment during recovery from transurethral resection of bladder tumors. MATERIALS AND METHODS: All patients scheduled for transurethral resection were approached for enrollment in a text-message based ecological momentary symptom assessment platform. Nine patients reported outcomes were measured 7 days before surgery and on postoperative days 1, 2, 3, 5, 7, 10, and 14 using a 5-point Likert scale. Self-reported degree of hematuria was collected using a visual scale. Clinical data was collected via retrospective chart review. RESULTS: A total of 159 patients were analyzed. Postoperative symptoms were overall mild, with the largest differences from baseline to postoperative day 1 seen in dysuria (median 0/5 vs. 3/5) and ability to work (median 5/5 vs. 4/5). Recovery was generally rapid, with 76% of patients reporting ≥4/5 agreement with the statement "I feel recovered from surgery" by postoperative day 2, although 15% of patients reported persistently lower levels of agreement on postoperative day 10 or 14. Patients undergoing larger resections (≥2cm) did take longer to return to baseline in multiple symptom domains, but the difference of medians vs. those undergoing smaller resections was less than 1 day across all domains. Multivariable analysis suggested that receiving perioperative intravesical chemotherapy was associated with longer time to recovery. 84% of patients reported clear yellow urine by postoperative day 3. CONCLUSION: In this population, hematuria and negative effects on quality of life resulting from transurethral resection of bladder tumors were generally mild and short-lived, although a small number of patients experienced longer recoveries.

A systematic review and meta-analysis of intraarterial chemotherapy for non muscle invasive bladder cancer: Promising alternative therapy in high tuberculosis burden countries.

INTRODUCTION: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. METHODS: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. RESULTS: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. CONCLUSIONS: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.

[6]-Shogaol Induces Apoptosis of Murine Bladder Cancer Cells.

BACKGROUND/AIMS: Bladder cancer is considered one of the most aggressive neoplasms due to its recurrence and progression profile, and even with the improvement in diagnosis and treatment methods, the mortality rate has not shown a declining trend in recent decades. From this perspective, the search and development of more effective and safer therapeutic alternatives are necessary. Phytochemicals are excellent sources of active principles with therapeutic potential. [6]-Shogaol is a phenolic compound extracted from the ginger rhizomes that has shown antitumor effects in a wide variety of cancer models. However, there is no record in the literature of studies reporting these effects in models of bladder cancer. Thus, this study aimed to investigate the in vitro cytotoxic and pro-apoptotic potential of [6]-Shogaol against murine bladder cancer urothelial cells (MB49). METHODS: The cytotoxic effects of [6]-Shogaol on cell viability (MTT method), cell morphology (light microscopy), alteration of proliferative processes (clonogenic assay), oxidative stress pathway (levels of reactive oxygen species) and the induction of apoptotic events (flow cytometry and high-resolution epifluorescence imaging) were evaluated in murine urothelial bladder cancer cell lines (MB49), relative to non-tumor murine fibroblasts (L929). RESULTS: The results showed that [6]-Shogaol was able to induce concentration-dependent cytotoxic effects, which compromised cell viability, exhibiting an inhibitory concentration of 50% of cells (IC50) of 146.8 µM for MB49 tumor cells and 236.0 µM for L929 non-tumor fibroblasts. In addition to inhibiting and altering the proliferative processes if colony formation, it presented pro-apoptotic activity identified through a quantitative analysis and the observation of apoptotic phenotypes, events apparently mediated by the induction of nuclear fragmentation. CONCLUSION: The data presented suggest that [6]-Shogaol has a higher concentration-dependent cytotoxic and apoptosis-inducing potential in MB49 cells than in L929 fibroblasts. These results may contribute to the development of therapeutic alternatives for bladder cancer.

Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Combinatorial Gene Expression Profiling of Serum HULC, HOTAIR, and UCA1 lncRNAs to Differentiate Hepatocellular Carcinoma from Liver Diseases: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.

Glomerular filtration rate measurement during platinum treatment for urothelial carcinoma: optimal methods for clinical practice.

BACKGROUND: We assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft-Gault, CKD-EPI, and Wright. METHOD: The four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements). RESULTS: The CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft-Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from - 32 ml/min (Cockcroft-Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (- 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min-considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min-allows for the safe omission of mGFR in 30% of patients in this cohort. CONCLUSION: CKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.

Near-infrared photoimmunotherapy targeting Nectin-4 in a preclinical model of bladder cancer.

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4, has shown promising results in the treatment of bladder cancer. However, multiple resistance mechanisms that are unique to ADCs limit the therapeutic potential of EV in clinical practice. Here, we developed and tested a Nectin-4-targeted near-infrared photoimmunotherapy (NIR-PIT) that utilizes the same target as EV but utilizes a distinct cytotoxic and immunotherapeutic pathway in preclinical models of bladder cancer. NIR-PIT was effective in vitro against luminal subtype human bladder cancer cell lines (RT4, RT112, MGH-U3, SW780, and HT1376-luc), but not against other subtype cell lines (UMUC3 and T24). In vivo, the tumor site was clearly visible by Nectin-4-IR700 fluorescence 24 h after its administration, suggesting the potential as an intraoperative imaging modality. NIR-PIT significantly suppressed tumor growth and prolonged survival in SW780 and RT112 xenograft models. Weekly treatment with NIR-PIT further improved tumor control in RT112 xenograft models. The effectiveness of NIR-PIT was also confirmed in HT1376-luc orthotopic xenograft models. Histological analysis verified that NIR-PIT induced a significant pathologic response. Taken together, Nectin-4-targeted NIR-PIT shows promise as a treatment for luminal subtype bladder cancers.

Unraveling neoantigen-associated genes in bladder cancer: An in-depth analysis employing 101 machine learning algorithms.

The therapeutic outcomes for bladder cancer (BLCA) remain suboptimal. Concurrently, there is a growing appreciation for the role of neoantigens in tumors. In this study, we explored the mechanisms underlying the involvement of neoantigen-associated genes in BLCA and their impact on prognosis. Our analysis incorporated both single-cell sequencing and bulk sequencing data sourced from publicly available databases. By employing a comprehensive set of 10 machine learning algorithms, we generated 101 algorithm combinations. The optimal combination, determined based on consistency indices, was utilized to construct a prognostic model comprising nine genes (CAPG, ACTA2, PDIA6, AKNA, PTMS, SNAP23, ID2, CD3G, SP140). Subsequently, we validated this model in an independent cohort, demonstrating its robust testing efficacy. Moreover, we explored the correlations between various clinical traits, model scores, and genes. Leveraging extensive public data resources, we conducted a drug sensitivity analysis to provide insights for targeted drug screening. Additionally, consensus clustering analysis and immune infiltration analysis were performed on bulk sequencing datasets and immunotherapy cohorts. These analyses yield valuable insights into the role of neoantigens in BLCA, guiding future research endeavors.

Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. METHODS: This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. RESULTS: In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). CONCLUSIONS: IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran.

BACKGROUND: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. METHODS: We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. RESULTS: We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69-1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16-2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21-4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11-6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24-4.42) than in current smokers (OR = 1.52; 95% CI, 0.72-3.15). All observed associations were consistently higher for urothelial histology. CONCLUSIONS: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. IMPACT: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers. See related In the Spotlight, p. 461.