Loss of Bacillus Calmette-Guérin Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to Bacillus Calmette-Guérin Exposure

Shah, Gopitkumar; Zhang, Guangjian; Chen, Fanghong; Cao, Yanli; Kalyanaraman, Balaraman; See, William A.

doi:10.1016/j.juro.2013.09.012

Cited by 7 publications

(2 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As intravenous injection of BCG instead of coinjection failed to reduce the relative tumor size of the xenografts, direct BCG-cell contact was shown to also be important in the ZTX models. The second requirement pertains to using therapy containing viable BCG bacteria [11,54]. In this study, heat inactivation of BCG before co-injection significantly reduced the efficacy of the BCG therapy compared to viable BCG.…”

Section: Discussionmentioning

confidence: 91%

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer

Kowald

Huge

Tandiono³

et al. 2023

Cells

View full text Add to dashboard Cite

Background: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. Methods: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. Results: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. Conclusions: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.

show abstract

Section: Discussionmentioning

confidence: 91%

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer

Kowald

Huge

Tandiono³

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…phlei, or HK MIP, inhibit BC proliferation similarly to live mycobacteria [63,[65][66][67], while other works found less growth inhibition of 253J and T24 cells significantly when HK BCG was used [68]. Unlike the observations made by the above mentioned authors, other authors found that HK BCG had no inhibitory effect in MGH BC cells [69].…”

Section: Purified Mycobacteria Antigens and Non-viable Mycobacteriamentioning

confidence: 99%

Mycobacteria-Derived Agents for the Treatment of Urological and Renal Cancers

Noguera-Ortega¹,

Julián²

2018

Mycobacterium - Research and Development

View full text Add to dashboard Cite

Mycobacteria are the unique group of bacteria that are currently used in antitumoral immunotherapy. Specifically, intravesical instillation of viable cells of Mycobacterium bovis Bacillus Calmette-Guérin (BCG), after transurethral resection of non-muscle invasive bladder cancer, is the most efficacious treatment for avoiding recurrence and progression of the disease. BCG has been used for the last 35 years for bladder cancer treatment, but other mycobacteria or mycobacteria components are currently under preclinical and clinical studies for the immunotherapeutic treatment of non-invasive bladder cancer and also of other types of tumors located at the urinary system. Those are, for instance, cell wall extracts or heat-killed forms from BCG or other mycobacteria such as Mycobacterium phlei or Mycobacterium indicus pranii (MIP) or even viable cells from non-pathogenic mycobacteria such us Mycobacterium brumae. A review of the literature in which mycobacteria components, non-viable mycobacteria, and viable mycobacteria have been used for these different cancers will be performed. In this chapter, the function of mycobacteria as antitumor agents will be then analyzed, awarding the audience a broad knowledge of one of the beneficial applications of mycobacteria, which are usually introduced as dangerous microorganisms.

show abstract

Clinical Scenario: Management of Side Effects from Bacillus Calmette-Guérin Bladder Instillation

Lamm

Gandhi

2014

Management of Bladder Cancer

View full text Add to dashboard Cite

Loss of Bacillus Calmette-Guérin Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to Bacillus Calmette-Guérin Exposure

Cited by 7 publications

References 19 publications

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer

Mycobacteria-Derived Agents for the Treatment of Urological and Renal Cancers

Clinical Scenario: Management of Side Effects from Bacillus Calmette-Guérin Bladder Instillation

Contact Info

Product

Resources

About