Impact of intravesical instillation of a novel biological response modifier (P-MAPA) on progress of non-muscle invasive bladder cancer treatment in a rat model.

Wagner J Fávaro,Ianny B Reis,Patrick V Garcia,Nelson Durán,Eduardo A R Socca,Petra K Böckelmann

doi:10.1007/s12032-021-01612-9

Abstract

This work describes the effects of immunotherapy with Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride in the treatment of non-muscle invasive bladder cancer in an animal model. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea. After treatment with MNU, the rats were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU-BCG (Bacillus Calmette-Guerin) group, and MNU-P-MAPA group. P-MAPA intravesical treatment was more effective in histopathological recovery from cancer state in relation to BCG treatment. Western blot assays showed an increase in the protein levels of c-Myc, COUP-TFII, and wild-type p53 in P-MAPA-treated rats in relation to BCG-treated rats. In addition, rats treated with P-MAPA intravesical immunotherapy showed the highest BAX protein levels and the lowest proliferation/apoptotic ratio in relation to BCG-treated rats, pointing out a preponderance of apoptosis. P-MAPA intravesical treatment increased the wild-type p53 levels and enhanced c-Myc/COUP-TFII-induced apoptosis mediated by p53. These alterations were fundamental for histopathological recovery from cancer and for suppress abnormal cell proliferation. This action of P-MAPA on apoptotic pathways may represent a new strategy for treating NMIBC.

Highlights

Bladder cancer (BC) among other cancers one of the most common malignancy of the urinary tract and is the second causing of death amid urogenital tumours
P-MAPA, a biological response modifier that shows novel therapeutic properties compared to standard treatments, appears to be a valuable candidate drug for the treatment of non-muscle invasive bladder cancer (NMIBC)
We described several therapeutic properties of P-MAPA.[9, 10, 12], (Fávaro et al, 2012; Garcia et al, 2015; Garcia et al, 2016) all the studies performed in animal models to assess the therapeutic potential of P-MAPA on NMIBC compared with BCG does not involve tumoral resection (TURBT) due experimental restrictions, all of them, used a model of tumoral induction based on intravesical instillations of MNU

Summary

1- Introduction

Bladder cancer (BC) among other cancers one of the most common malignancy of the urinary tract and is the second causing of death amid urogenital tumours. Possible pro-apoptotic pathways mediated by c-Myc, p19ARF activation is important since, in cooperation with Ras protein, this protein represses Mdm-2 (negative regulator of p53), thereby inducing p53 release and triggering apoptotic mechanisms [17, 20] (Faria and Rabenhorst, 2006; Evan et al, 1992) In contrast to these studies, the role of c-Myc in mediating apoptosis in NMIBC is still not clear. In view of the remarkable antitumor activity of P-MAPA against NMIBC and its immunomodulatory action on TLRs and p53, we hypothesized that P-MAPA could trigger apoptosis in NMIBC by increasing p53, COUP-TFII and c-Myc protein levels To address this question, we examined the effect of treatment with PMAPA in an animal model of chemically-induced NMIBC and compared the results with those obtained by treating the animals with BCG

2.1- Experimental Procedures

3- Results

4- Discussion And Conclusions

Findings

Ethical approval