Boosting bladder cancer treatment by intravesical nitazoxanide and bacillus calmette-guérin association

Kiehl, Isis Ga; Riccetto, Eduardo; Salustiano, Ana Clara C; Ossick, Marina Vian; Ferrari, Karen L.; Assalin, Heloísa Balan; Ikari, Osamu; Reis, Leonardo Oliveira

doi:10.1007/s00345-020-03294-w

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…In this case, repurposing was based on evaluation of retrospective/observational studies providing evidence that the incidence of BC in patients with schizophrenia was significantly lower in comparison to individuals without schizophrenia [23]. Along the same lines, the repurposing potential of Nitazoxanide, a cysticidal drug with immuno-anticarcinogenic action, was investigated in a NMIBC animal model and showed therapeutic potential when used simultaneously with BCG treatment [24]. A high-throughput screening using a library of known chemicals and drugs identified disulfiram as a repurposed drug that enhances sensitivity to cisplatin in BC [25].…”

Section: Discussionmentioning

confidence: 99%

“…To elucidate the possible impact of the WYE-354 mTOR inhibitor onto the malignant phenotype of BC cells in vitro, a panel of multi-origin BC cell lines, including benign (HBLAK), non-muscle invasive (BFTC-905, SW1710) and muscle invasive (T24, T24M, VM-CUB1, 253J, HT-1376) cells, were employed. The above cell lines were subjected to treatment with WYE-354 at different concentrations (100 nM, 1 µM, and 3 µM) and the impact was examined on cell proliferation using the MTS assay at different time points (24,48, and 72 h). As shown in Figure 3, WYE-354 administration resulted in a significant reduction on the proliferation rate of all the tested BC cell lines in a concentration-dependent manner.…”

Section: Wye-354 Reduces the Growth Of Bc Cellsmentioning

confidence: 99%

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A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients’ Omics Signatures

Mokou

Lygirou

Angelioudaki

et al. 2020

Cancers

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Multi-omics signatures of patients with bladder cancer (BC) can guide the identification of known de-risked therapeutic compounds through drug repurposing, an approach not extensively explored yet. In this study, we target drug repurposing in the context of BC, driven by tissue omics signatures. To identify compounds that can reverse aggressive high-risk Non-Muscle Invasive BC (NMIBC) to less aggressive low-risk molecular subtypes, the next generation Connectivity Map (CMap) was employed using as input previously published proteomics and transcriptomics respective signatures. Among the identified compounds, the ATP-competitive inhibitor of mTOR, WYE-354, showed a consistently very high score for reversing the aggressive BC molecular signatures. WYE-354 impact was assessed in a panel of eight multi-origin BC cell lines and included impaired colony growth and proliferation rate without any impact on apoptosis. Overall, with this study we introduce a promising pipeline for the repurposing of drugs for BC treatment, based on patients’ omics signatures.

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Section: Discussionmentioning

confidence: 99%

Section: Wye-354 Reduces the Growth Of Bc Cellsmentioning

confidence: 99%

A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients’ Omics Signatures

Mokou

Lygirou

Angelioudaki

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…This calcium mobilisation disrupts ER/Golgi glycoprotein trafficking and induces ER stress, thus triggering PKR phosphorylation (152). Several in vivo studies conducted in animal models have investigated the effects of NTZ in disease contexts such as viral infections, protozoan infections, cancer, Parkinson's disease, neuroinflammation, and bacterial infections (Table 2) (153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163)(164)(165)(166). Indeed, in vivo studies have shown that NTZ is effective in treating bacterial pathogens such as C. difficile, E. coli, M. leprae, and M. tuberculosis (153)(154)(155)(156)159).…”

Section: Pharmacological Modulation Of Pkr Pkr Activatorsmentioning

confidence: 99%

Protein Kinase R in Bacterial Infections: Friend or Foe?

Smyth

Sun

2021

Front. Immunol.

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The global antimicrobial resistance crisis poses a significant threat to humankind in the coming decades. Challenges associated with the development of novel antibiotics underscore the urgent need to develop alternative treatment strategies to combat bacterial infections. Host-directed therapy is a promising new therapeutic strategy that aims to boost the host immune response to bacteria rather than target the pathogen itself, thereby circumventing the development of antibiotic resistance. However, host-directed therapy depends on the identification of druggable host targets or proteins with key functions in antibacterial defense. Protein Kinase R (PKR) is a well-characterized human kinase with established roles in cancer, metabolic disorders, neurodegeneration, and antiviral defense. However, its role in antibacterial defense has been surprisingly underappreciated. Although the canonical role of PKR is to inhibit protein translation during viral infection, this kinase senses and responds to multiple types of cellular stress by regulating cell-signaling pathways involved in inflammation, cell death, and autophagy – mechanisms that are all critical for a protective host response against bacterial pathogens. Indeed, there is accumulating evidence to demonstrate that PKR contributes significantly to the immune response to a variety of bacterial pathogens. Importantly, there are existing pharmacological modulators of PKR that are well-tolerated in animals, indicating that PKR is a feasible target for host-directed therapy. In this review, we provide an overview of immune cell functions regulated by PKR and summarize the current knowledge on the role and functions of PKR in bacterial infections. We also review the non-canonical activators of PKR and speculate on the potential mechanisms that trigger activation of PKR during bacterial infection. Finally, we provide an overview of existing pharmacological modulators of PKR that could be explored as novel treatment strategies for bacterial infections.

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Bladder cancer immunomodulatory effects of intravesical Nitazoxanide, Rapamycin, Thalidomide and Bacillus Calmette–Guérin (BCG)

et al. 2023

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Boosting bladder cancer treatment by intravesical nitazoxanide and bacillus calmette-guérin association

Cited by 5 publications

References 28 publications

A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients’ Omics Signatures

A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients’ Omics Signatures

Protein Kinase R in Bacterial Infections: Friend or Foe?

Bladder cancer immunomodulatory effects of intravesical Nitazoxanide, Rapamycin, Thalidomide and Bacillus Calmette–Guérin (BCG)

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