scholarly journals 4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 158
Author(s):  
Giulio Sturaro ◽  
Alessia Tasso ◽  
Luca Menilli ◽  
Rosa Di Liddo ◽  
Giorgia Miolo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Blue Light ◽  
Biological Effects ◽  
In Vitro Study ◽  
Partial Recovery ◽  
T24 Cells ◽  
Muscle Invasive ◽  
Nuclear Levels ◽  
Bladder Carcinomas

Photodynamic therapy (PDT) is frequently used to treat non-muscle invasive bladder cancer due its low toxicity and high selectivity. Since recurrence often occurs, alternative approaches and/or designs of combined therapies to improve PDT effectiveness are needed. This work aimed to evaluate the cytotoxicity of 4,6,4′-trimethylangelicin (TMA) photoactivated by blue light (BL) on human bladder cancer T24 cells and investigate the mechanisms underlying its biological effects. TMA/BL exerted antiproliferative activity through the induction of apoptosis without genotoxicity, as demonstrated by the expression levels of phospho-H2AX, an indicator of DNA double-stranded breaks. It also modulated the Wnt canonical signal pathway by increasing the phospho-β-catenin and decreasing the nuclear levels of β-catenin. The inhibition of this pathway was due to the modulation of the GSK3β phosphorylation state (Tyr 216) that induces a proteasomal degradation of β-catenin. Indeed, a partial recovery of nuclear β-catenin expression and reduction of its phosphorylated form after treatment with LiCl were detected. As demonstrated by RT-PCR and cytofluorimetric analysis, TMA/BL also decreased the expression of CD44v6, a marker of cancer stem cells. Taken together, our data suggest that TMA photoactivated by BL may represent an interesting option for the photochemotherapy of noninvasive bladder carcinomas, since this treatment is able to inhibit key pathways for tumour growth and progression in the absence of genotoxic effects.

Evans blue as a selective dye marker for white-light diagnosis of non-muscle-invasive bladder cancer: an in vitro study

2011 ◽  
Vol 109 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Mieke Roelants ◽  
Ann Huygens ◽  
Ivo Crnolatac ◽  
Ben Van Cleynenbreugel ◽  
Evelyne Lerut ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
White Light ◽  
Evans Blue ◽  
In Vitro Study ◽  
Vitro Study ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Defining molecular determinants of sensitivity to EGFR inhibition in urothelial carinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 268-268
Author(s):  
W. Y. Kim ◽  
T. Hadzic ◽  
S. A. Heathcote ◽  
D. T. Gammons ◽  
K. Rathmell ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Expression Profiles ◽  
Clinical Activity ◽  
Egfr Inhibition ◽  
T24 Cells ◽  
Molecular Determinants ◽  
Muscle Invasive

268 Background: Activation of EGFR in cancer patients has been shown to correlate with tumor proliferation, angiogenesis, and metastasis. EGFR inhibition has been shown to be clinically beneficial in several solid tumors and appears to be a tractable therapeutic target. EGFR is over-expressed in bladder cancer and a phase II trial of neoadjuvant erlotinib in patients with muscle invasive bladder cancer suggests possible clinical activity. We therefore hypothesized that we could define molecular correlates to predict response to EGFR inhibition. Methods: Correlative tumor samples derived from a phase II trial of neoadjuvant erlotinib in muscle invasive urothelial carcinoma of the bladder were analyzed to define molecular determinants of response to EGFR inhibition. The effect of silencing a candidate molecular predictor of resistance to EGFR inhibition, HRAS, was assessed by changes in the IC50 of T24 cells (harbor mutant HRAS) expressing short hairpin RNAs to HRAS or a control shRNA. Results: Analysis of the gene expression profiles of TURB-T (pretreatment) samples show that tumors from non-pT0 patients had significantly elevated levels of HRAS relative to tumors from pT0 patients. Furthermore, knock-down of HRAS in T24 cells enhanced the sensitivity of these cells to erlotinib. Conclusions: Elevated HRAS expression is correlated with a lack of response to erlotinib in vivo and silencing of HRAS in T24 cells results in enhanced sensitivity to erlotinib in vitro. Further molecular analyses are ongoing. No significant financial relationships to disclose.

scholarly journals The effect of hypoxia on PD-L1 expression in bladder cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vicky Smith ◽  
Debayan Mukherjee ◽  
Sapna Lunj ◽  
Ananya Choudhury ◽  
Peter Hoskin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
In Silico ◽  
Statistical Tests ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
T24 Cells ◽  
Muscle Invasive ◽  
L1 Protein ◽  
Hypoxia Signature

Abstract Introduction Recent data has demonstrated that hypoxia drives an immunosuppressive tumour microenvironment (TME) via various mechanisms including hypoxia inducible factor (HIF)-dependent upregulation of programmed death ligand 1 (PD-L1). Both hypoxia and an immunosuppressive TME are targetable independent negative prognostic factors for bladder cancer. Therefore we sought to investigate whether hypoxia is associated with upregulation of PD-L1 in the disease. Materials and methods Three human muscle-invasive bladder cancer cell lines (T24, J82, UMUC3) were cultured in normoxia (20% oxygen) or hypoxia (1 and 0.1% oxygen) for 24 h. Differences in PD-L1 expression were measured using Western blotting, quantitative polymerase chain reaction (qPCR) and flow cytometry (≥3 independent experiments). Statistical tests performed were unpaired t tests and ANOVA. For in silico work an hypoxia signature was used to apply hypoxia scores to muscle-invasive bladder cancers from a clinical trial (BCON; n = 142) and TCGA (n = 404). Analyses were carried out using R and RStudio and statistical tests performed were linear models and one-way ANOVA. Results When T24 cells were seeded at < 70% confluence, there was decreased PD-L1 protein (p = 0.009) and mRNA (p < 0.001) expression after culture in 0.1% oxygen. PD-L1 protein expression decreased in both 0.1% oxygen and 1% oxygen in a panel of muscle-invasive bladder cancer cells: T24 (p = 0.009 and 0.001), J82 (p = 0.008 and 0.013) and UMUC3 (p = 0.003 and 0.289). Increasing seeding density decreased PD-L1 protein (p < 0.001) and mRNA (p = 0.001) expression in T24 cells grown in both 20 and 1% oxygen. Only when cells were 100% confluent, were PD-L1 protein and mRNA levels higher in 1% versus 20% oxygen (p = 0.056 and p = 0.037). In silico analyses showed a positive correlation between hypoxia signature scores and PD-L1 expression in both BCON (p = 0.003) and TCGA (p < 0.001) cohorts, and between hypoxia and IFNγ signature scores (p < 0.001 for both). Conclusion Tumour hypoxia correlates with increased PD-L1 expression in patient derived bladder cancer tumours. In vitro PD-L1 expression was affected by cell density and decreased PD-L1 expression was observed after culture in hypoxia in muscle-invasive bladder cancer cell lines. As cell density has such an important effect on PD-L1 expression, it should be considered when investigating PD-L1 expression in vitro.

scholarly journals Evaluation of the In Vitro and In Vivo Antitumor Efficacy of Peanut Sprout Extracts Cultivated with Fermented Sawdust Medium Against Bladder Cancer

2020 ◽  
Vol 10 (23) ◽  
pp. 8758
Author(s):  
Hongbeom Park ◽  
Jun-Hui Song ◽  
Byungdoo Hwang ◽  
BoKyung Moon ◽  
Seok-Joong Yun ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Biological Effects ◽  
Binding Activity ◽  
Mitogen Activated Protein Kinase ◽  
Antitumor Efficacy ◽  
Tumor Growth Rate ◽  
Potential Candidate ◽  
T24 Cells

Peanut sprout extracts reportedly exhibit numerous beneficial effects; however, there are few investigations on the biological effects of peanut sprout extracts cultivated with fermented sawdust medium (PSEFS). Here, we examined whether PSEFS demonstrates antitumor activity against bladder cancer, in vitro and in vivo. The results showed that PSEFS prohibited the proliferation of bladder cancer T24 cells, with this effect attributed to induction of cell cycle arrest at the G1 phase through reduced expression of cyclins and cyclin-dependent kinases caused by a promotion of p21WAF1 expression. Additionally, PSEFS induced phosphorylation of p38 mitogen-activated protein kinase. Moreover, PSEFS treatment attenuated the invasive and migratory potential of T24 cells due to decreased matrix metalloproteinase-9 activity combined with downregulation of the transcriptional binding activity of SP1, activator protein -1, and nuclear factor-kappaB. Furthermore, PSEFS (20 mg/kg) attenuated the tumor-growth rate in xenograft mice bearing T24 cells, with an effect equivalent to that of cisplatin and in the absence of toxicity following weight-loss evaluation and hematobiochemical testing of PSEFS-treated mice. These results demonstrated the antitumor efficacy of PSEFS both in vitro and in vivo, thereby reporting it as a potential candidate for development of novel agents against bladder cancer.

Surface Labeling with Adhesion Protein FimH Improves Binding of Immunotherapeutic Agent Salmonella Ty21a to the Bladder Epithelium

2020 ◽  
pp. 1-12
Author(s):  
Maroeska J. Burggraaf ◽  
Lisette Waanders ◽  
Mariska Verlaan ◽  
Janneke Maaskant ◽  
Diane Houben ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Bladder Wall ◽  
Bladder Epithelium ◽  
Modest Improvement ◽  
Adhesion Protein ◽  
Survival Experiment ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is the ninth most common cancer in men. 70% of these tumors are classified as non-muscle invasive bladder cancer and those patients receive 6 intravesical instillations with Mycobacterium bovis BCG after transurethral resection. However, 30% of patients show recurrences after treatment and experience severe side effects that often lead to therapy discontinuation. Recently, another vaccine strain, Salmonella enterica typhi Ty21a, demonstrated promising antitumor activity in vivo. Here we focus on increasing bacterial retention in the bladder in order to reduce the number of instillations required and improve antitumor activity. OBJECTIVE: To increase the binding of Ty21a to the bladder wall by surface labeling of the bacteria with adhesion protein FimH and to study its effect in a bladder cancer mouse model. METHODS: Binding of Ty21a with surface-labeled FimH to the bladder wall was analyzed in vitro and in vivo. The antitumor effect of a single instillation of Ty21a+FimH in treatment was determined in a survival experiment. RESULTS: FimH-labeled Ty21a showed significant (p <  0.0001) improved binding to mouse and human cell lines in vitro. Furthermore, FimH labeled bacteria showed ∼5x more binding to the bladder than controls in vivo. Enhanced binding to the bladder via FimH labeling induced a modest improvement in median but not in overall mice survival. CONCLUSIONS: FimH labeling of Ty21a significantly improved binding to bladder tumor cells in vitro and the bladder wall in vivo. The improved binding leads to a modest increase in median survival in a single bladder cancer mouse study.

Modified Yukmijihwangtang Suppresses the Production of Proinflammatory Cytokines in the Intravesical Hydrochloric Acid-Induced Cystitis Rat Model via the NF-κB Pathway

2012 ◽  
Vol 40 (02) ◽  
pp. 321-334 ◽  
Author(s):  
Jeong-Won Lee ◽  
Sok Cheon Pak ◽  
Songhee Jeon ◽  
Dong-Il Kim
Keyword(s):  
Medicinal Plants ◽  
Rat Model ◽  
In Vitro Study ◽  
Intravesical Instillation ◽  
Bladder Function ◽  
No Production ◽  
Therapeutic Effects ◽  
T24 Cells ◽  
Injury Group

Yukmijihwangtang (YM), a boiled extract of medicinal plants, has been prescribed for patients with kidney dysfunction in Korea; however, the mechanism underlying its therapeutic effects has not been fully elucidated. This study was conducted to evaluate the beneficial effects on bladder function by using modified YM (M-YM), which included Ulmi radicis cortex in addition to the six traditional medicinal plants in YM. Bladder irritation of the rats was caused by intravesical instillation of HCl . The animals were divided into six groups: sham group, cystitis-injury group with no treatment, cystitis-injury group with prednisolone treatment (5 mg/kg), and cystitis-injury with M-YM treatment (100, 200 or 500 mg/kg groups). Whole bladders were collected at day eight after injury. Samples were analyzed by histological and immunological examinations. An in vitro study was performed to determine whether M-YM extracts inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production and I κ B phosphorylation in a human uroepithelial cell line of T24 cells. Administration of M-YM notably improved bladder histological changes, and suppressed IL-6/TNF α production and I κ B phosphorylation in a rat model of chronic cystitis. M-YM also inhibited LPS-induced NO production and I κ B phosphorylation in T24 cells. This study suggests that administration of M-YM might be an applicable therapeutic traditional medicine for the treatment of interstitial cystitis.

ERYTHROSINE AS A PHOTOSENSITIZER FOR ANTIMICROBIAL PHOTODYNAMIC THERAPY WITH BLUE LIGHT-EMITTING DIODES – AN IN VITRO STUDY

2021 ◽  
pp. 102445
Author(s):  
Marcela Leticia Leal Gonçalves ◽  
Elaine Marcílio Santos ◽  
Ana Cláudia Muniz Renno ◽  
Anna Carolina Ratto Tempestini Horliana ◽  
Matheus de Almeida Cruz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Blue Light ◽  
Light Emitting Diodes ◽  
In Vitro Study ◽  
Vitro Study ◽  
Antimicrobial Photodynamic Therapy ◽  
Light Emitting

Synthesis, Characterization, and Biological Activity of Anthraquinone-Substituted Imidazolium Salts for the Treatment of Bladder Cancer

2020 ◽  
Vol 6 (4) ◽  
pp. 471-479
Author(s):  
Michael L. Stromyer ◽  
David J. Weader ◽  
Uttam Satyal ◽  
Philip H. Abbosh ◽  
Wiley J. Youngs
Keyword(s):  
Bladder Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Grade ◽  
Imidazolium Salts ◽  
Muscle Invasive Bladder Cancer ◽  
Imidazolium Salt ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is one of the most common types of cancer diagnosed each year, and more than half of patients have non-muscle invasive bladder cancer (NMIBC). The standard of care for patients with high-grade NMIBC is Bacillus Calmette-Guerin (BCG). Unfortunately, multiple BCG shortages have limited access to this treatment. Available alternatives using intravesical administration of chemotherapy have some efficacy, but lack prospective validation and long-term outcomes. Development of novel intravesical therapies may provide more active alternatives to BCG for patients with high-grade NMIBC. OBJECTIVE: To develop an optimal imidazolium salt for the intravesical treatment of NMIBC and determine preliminary in vitro activity of anthraquinone-substituted imidazolium salts. METHODS: The development of the anthraquinone-substituted imidazolium salts was undertaken in an attempt to increase the potency of this class of compounds by incorporating the quinone functional group observed in the chemotherapeutics doxorubicin, valrubicin, and mitomycin. All compounds were characterized by 1H and 13C NMR spectroscopy and infrared spectroscopy. Furthermore, these imidazolium salts were tested for in vitro cytotoxicity by the Developmental Therapeutics Program (DTP) on the NCI-60 human tumor cell line screening. Additional in vitro testing was performed against diverse bladder cancer cell lines (RT112, TCCSUP, J82, and UMUC13) using CellTiter-Glo® assays and colony-forming assays. RESULTS: The NCI-60 cell line screening indicated that compound 7 had the highest activity and was concluded to be the optimal compound for further study. Using CellTiter-Glo® assays on bladder cancer cell lines, 50% growth inhibitory concentration (IC50) values were determined to range from 32–50μM after an exposure of 1 h, for compound 7. Further evaluation of the compound by colony-forming assays showed the complete inhibition of growth at 10 days post a 100μM dose of compound 7 for 1 h. CONCLUSIONS: The most active lipophilic anthraquinone imidazolium salt, compound 7, could be a viable treatment for non-muscle invasive bladder cancer as it exhibits a cell-killing effect at a 1 h time period and completely inhibits cancer regrowth in colony-forming assays.

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