Futer, 44, wasn’t likely to die on the operating table, but his fear was understandable. Ellermann and Bang in 1908 and Rous in 1911 transmitted avian leukemias and sarcomas, respectively, through cell-free tumor extracts, suggesting a viral etiology [1,2,3]. For example, the UL39 gene encodes the large subunit of ribonucleotide reductase (ICP6), which is required for efficient viral DNA synthesis (Goldstein and Weller, 1988). Several strategies were reported to render HSV replication selective for tumor cells: (i) deletion or mutation of viral genes needed for replication in postmitotic cells,15, 16, 17 (ii) deletion of the viral genes responsible for regulating viral progeny production,18, 19, 20 (iii) use of tumor-specific promoters to regulate the expression of essential viral genes,21, 22 (iv) altering the receptor specificity of HSV glycoproteins toward tumor rather than normal tissue23 and so on. One of these, mutant receptor 1 (MR1), was isolated by the Bigner Laboratory from an scFv phage display library by panning with successively decreasing amounts of EGFRvIII mutant-specific peptide.4 By mutagenesis and selection using a phage display library a variant of MR1 was identified, MR1-1, which has an approximately 15-fold higher binding affinity to the EGFRvIII extracellular domain as compared to MR1.28 This group also generated a mutated form of MR1-1, MRB, with no affinity for EGFRvIII. Latent HSV genomes express a family of latency-associated transcripts (LATs)13 in the absence of lytic cycle gene expression that can be detected at autopsy in neurons of the trigeminal ganglia in subjects with no evidence of active herpetic infection14. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process.
Second, we demonstrated, via neuronal-restricted expression of IFN-β, that complete regression could be achieved without the need for transduction of tumor cells. We started a dose-escalation study with an initial dose of 1 × 104 p.f.u. The linearized pRBAC-6GpA-FL DNA was co-transfected with MGH1 virion DNA into Vero cells and the progeny viruses were harvested 3 days after transfection. The patient then commenced radiotherapy (2 Gy per day, 5 days per week for 6 weeks) and received concomitant dexamethasone 2 mg daily. HHV-6 has been shown to infect human oligodendrocytes and astrocytes in vitro and in vivo, altering cytokine production, cellular proliferation, and differentiation4-7. Recently, we showed that equine major histocompatibility complex class I (MHC-I) is a cellular entry receptor for EHV-1 (12). Finally, various animal models available to test novel GBM therapies are discussed.
Consequently, the development of novel alternative treatment options is crucial. Recent studies hypothesized a role of mobile use/cordless phone and brain tumorigenesis in adults . Here we present a hypothesis that highlights a potential link between the major tumor suppressor p53, its transcriptional target microRNA-34a, and susceptibility of cells to infection with viruses that are either proven or actively studied for their possible role in the initiation or progression of cancers. Open Virol J 4: 123-156.