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Original article

New forms of induction of apoptosis in aggressive lymphoma using peptides that interrupt the RAS / RAF interaction

Authors:

C. Bergna ,

National University of La Plata, AR
About C.
Faculty of Medical Science
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G. H. Marin,

National University of La Plata, AR
About G. H.

Faculty of Medical Science

 

CONICET-UNLP

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M. Maiz,

National University of La Plata, AR
About M.
Faculty of Medical Science
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H. Bruzzoni Giovanelli,

Université Paris 7- Hôpital Saint Louis, FR
About H.
Pharmacology - Centre d’Investigations Cliniques
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C. Ponzinibbio,

National University of La Plata, AR
About C.
Faculty of Medical Science
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G. Schinella,

National University of La Plata, AR
About G.

Faculty of Medical Science

 

CIC- Scientific Research Commission- Buenos Aires

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J. Errecalde,

National University of La Plata, AR
About J.
Faculty of Medical Science
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A. Rebollo

CIMI, Inserm/UPMC/CNRS- Université Pierre et Marie Curie, Paris 6, FR
About A.
Centre d’Immunologie et des Maladies Infectieuses
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Abstract

RAS-RAF-MEK-ERK is a key pathway for apoptosis regulation in cancer cells. B-Raf-inhibitors such as PLX4032 peptide was developed by Institute Curie-Université Pierre et Marie Curie in order to induce apoptosis in cancer cells.

OBJECTIVE

To demonstrate pro-apoptotic properties and survival outcome of EP2014/064243 peptide in murine aggressive lymphoma.

MATERIAL AND METHODS

BALBc mice with T-lymphoma were randomized assigned either in Group A (peptide+cyclophosphamide-CFM); Group B (peptides), Group C (CFM-control) or Control D (Cl-Na 0.9%-SF control group). Survival probability was calculated by Kaplan-Meier analysis. Apoptosis was detected using TUNEL technique. The protocol was approved by the Institutional Committee for Animal Care (CICUAL: T04-01-2015)

RESULTS

The median survival was 24 days (21.6-26.4) for placebo, 33 days (28.0-35.4) for the CFM monotherapy group, 33 (27.1-35.8) for the peptide group and 34 days (24,4-40) for CFM-peptide combined treatment (p<0.05). In lymph node tissue the mean TUNEL positive cells per field for each treatment group was 2, 12 and 13 and 35 for SF, CFM, peptide and combined therapy (p<0.05).

CONCLUSION

These findings suggest that in murine aggressive lymphoma treated by an experimental peptide in addition with CFM, had an exponentially pro-apoptotic effect than CFM alone, suggesting that the peptide potentiated the anti-tumoural effect of CFM.

DOI: https://doi.org/10.4038/cmj.v64i2.8890
How to Cite: Bergna, C., Marin, G.H., Maiz, M., Bruzzoni Giovanelli, H., Ponzinibbio, C., Schinella, G., Errecalde, J. and Rebollo, A., 2019. New forms of induction of apoptosis in aggressive lymphoma using peptides that interrupt the RAS / RAF interaction. Ceylon Medical Journal, 64(2), pp.46–51. DOI: http://doi.org/10.4038/cmj.v64i2.8890
Published on 26 Jul 2019.
Peer Reviewed

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