C.52. EUROCANCER 1998


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June 3-5, PARIS, France.


French Version

BRAIN GLIOMA, POLYOMAVIRUS,

SV 40-CONTAMINATED ANTI-POLIOMYELITIS VACCINE AND

GROWTH FACTORS (EGF, FGF, PDGF, IGF 1).

TRAN Mong Ky Guy*, KIRKIACHARIAN S.**

* University Paris V, Corresp. : 31 Av. du Bois, 92290 Chatenay Malabry
** University Paris XI, Faculty of Pharmacy,92 296 Cedex, Chatenay Malabry, FRANCE.


Background: In HIV patients, progressive multifocal leucoencephalopathy (PML) is characterized by an intense gliosis and caused by a polyomavirus (PV).Brain glioma are induced in newborn hamsters by PV. OHGAKI H (1998) found PV with a high frequency in human glioma. More worrying is the anti-poliomyelitis vaccine contamination by SV 40 in the 1950s., because authentic SV 40 was found in childhood brain tumors. An increase in neural tumors was reported in children born from mothers receiving this vaccine during pregnancy. PV large T (= Tumor) antigen also binds to anti-oncogens p53 and Rb.

Method: We compared, by amino acid sequences alignment, PV t antigens (which in transgenic mice induced glioma ) to Growth Factors (GF): Epidermal GF, Fibroblast GF, Platelet-derived GF, sis oncogene of Simian Sarcoma Virus (SSV), because glioma have amplification of EGF Receptor in 40% cases and also of the other GFs and their receptors. Insulin like GF-1 antisense therapy blocked glioma formation in animals. SSV inoculation in marmosets induced astrocytomas.

Results:

1°) PV ( JCV, BKV , SV 4O) are homologous to EGF active site, Notch 4 and

2°) to bFGF, FGF-7, FHF-4 :

3°) The PDGF active site (79-81) ( R K K is read in normal sense, IFKK & IVP in antisense because of the 3 dimensional structure) matched with BKV and JC.

4°) IGF 1 is homologous to mouse PV.

5°) Mouse PV sequence LRMLNGGTGFQV (NL is read in antisense) to the proto-oncogene Notch (EGF family) LRCLNGGTCRQTand heregulin.

Conclusion: Polyomavirus t antigen contains the same growth factors (EGF, FGF, PDGF, IGF 1)which are amplified, with their receptors, in glioma.This is coherent with a viral etiology (SV4O, polyomavirus; SSV) of glioma & possible antiviral drug trial (Ara-C, cidofovir; antiretroviral). The long term safety (cancers) of SV4O-contaminated antipoliomyelitis vaccine may also be questioned.



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