Intravesical therapy for bladder cancer

Patel, Sanjay G.; Cohen, Andrew J.; Weiner, Adam B.; Steinberg, Gary D.

doi:10.1517/14656566.2015.1024656

Cited by 30 publications

(29 citation statements)

References 110 publications

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“…The greatest successes of BCG for the treatment of malignancies have been obtained in superficial, non-muscle-invasive bladder cancer. Transurethral resection of the bladder tumor followed by intravesical instillations of the vaccine are the standard of care for patients with intermediate-and high-risk tumors [31]. Although BCG has been in use for this indication for more than 30 years, the immunologic mechanisms by which BCG works have not been fully elucidated.…”

Section: Immunotherapy Against Cancer: the Role Of Vaccinesmentioning

confidence: 99%

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

Netea¹,

Joosten²,

Meer³

2017

Journal of Leukocyte Biology

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Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells. TI is considered to have beneficial effects in improving host response to infections and vaccination, and increasing evidence suggests that TI-mediated mechanisms also have useful and potent antitumor effects. We hypothesized that novel and more effective approaches for immunotherapy in cancer may involve induction of TI, alone or in combination with current immunotherapies.

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Section: Immunotherapy Against Cancer: the Role Of Vaccinesmentioning

confidence: 99%

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

Netea¹,

Joosten²,

Meer³

2017

Journal of Leukocyte Biology

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“…Current evidence suggests that BCG therapy prevents recurrence and progression, which prolongs the patient’s survival23. Although the benefits of BCG immunotherapy are clear, the drawbacks should not be underestimated.…”

mentioning

confidence: 99%

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Noguera-Ortega

Blanco-Cabra

Rabanal

et al. 2016

Sci Rep

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The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer.

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“…Unfortunately, transurethral resection or other adjuvant treatments do not achieve much in preventing tumor metastasis and recurrence. Finally, 20–30 % of those tumors progress into more aggressive tumors and cause death of patients [27, 28]. …”

Section: Discussionmentioning

confidence: 99%

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Zhuang

Zhong

et al. 2016

J Exp Clin Cancer Res

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BackgroundIntegrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial–mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β. ILK and RI gene both locate on chromosome 11p15 and the two genes are always at the adjacent position of same chromosome during evolution, which suggest that ILK and RI could have some relationship. However, underlying interacting mechanisms remain unclear between them. Here, we postulate that RI might regulate ILK signaling pathway via interacting with ILK.MethodsCo-immunoprecipitation, GST pull-down and co-localization under laser confocal microscope assay were used to determine the interaction between ILK and RI exogenously and endogenously. Furthermore, we further verified that there is a direct binding between the two proteins by fluorescence resonance energy transfer (FRET) in cells. Next, The effects of interplay between ILK and RI on the key target protein expressions of PI3K/AKT/mTOR signaling pathway were determined by western blot, immunohistochemistry and immunofluorescence assay in vivo and in vitro. Finally, the interaction was assessed using nude mice xenograft model.ResultsWe first found that ILK could combine with RI both in vivo and in vitro by GST pull-down, co-immunoprecipitation (Co-IP) and FRET. The protein levels of ILK and RI revealed a significant inverse correlation in vivo and in vitro. Subsequently, The results showed that up-regulating ILK could increase cell proliferation, change cell morphology and regulate cell cycle. We also demonstrated that the overexpression of ILK remarkably promoted EMT and expressions of target molecules of ILK signaling pathways in vitro and in vivo. Finally, we found that ILK overexpression significantly enhanced growth, metastasis and angiogenesis of xenograft tumor; Whereas, RI has a contrary role compared to ILK in vivo and in vitro.ConclusionsOur findings, for the first time, directly proved that the interplay between ILK and RI regulated EMT via ILK/PI3K/AKT signaling pathways for bladder cancer, which highlights the possibilities that ILK/RI could be valuable markers together for the therapy and diagnosis of human carcinoma of urinary bladder.

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Intravesical therapy for bladder cancer

Cited by 30 publications

References 110 publications

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

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