Like other cancers, brain tumors could be benign or malignant, primary starting in the brain or secondary, metastasized from elsewhere. The brain tumors also could arise from its outside covering or meninges or from its own brain matter, which consists of grey (neurons) and white (glia cells). Half of the brain tumors are gliomas and about 8% of myelin or nerve sheath, both of white matter, over 20% meningiomas, 15% of Pituitary adenomas and only over 5% from the brain or grey matter tissue. The cause of most brain tumors are yet unknown and the genetic cases such as neurofibromatosis, tuberous sclerosis are very rare (2). This leaves epigenetic factors such as radiation and microbial invasions as the principal causative agents that will be the main focus of this article.
For over a century the medical field has been well aware of infesting cysts throughout the body that anchor in different tissues and organs including the brain, where hydatid cysts have been reported in the brain as primary and secondary target (3-5). Other than hydatid cysts that caused by parasitic tapeworms getting into humans from intermediate hosts (e.g. sheep, goats) and definite hosts (e.g. dogs), other microbial, fungal and viral infections such as tuberculosis and mycosis have been reported as different cysts and cystic tumors in the different parts of the brain since over a half century ago (6-7). Although majority of the microbial brain invasions are limited to the defensive wall (cover) of the brain or meninges or in the viral cases only causing a generalized encephalitis, some aggressive ones rise to create cysts and tumors often malignancies.
In their frontier and heroic study, Schuman, Choi and Gullen showed that the parasitic toxoplasma gondii infection that simply passes to humans from domestic chickens and other fowls could be the causative agents of several brain tumors. Investigating 171 primary central nervous system neoplasms over 18 months period in 1963-1964 from four Minnesota’s hospitals, they traced down the pathogenic routes of several cases of gilomas, acoustic neuromas, neurofibromatosis, mengiomas, pituitary tumors, craniopharyngiomas and miscellaneous brain tumors back to toxoplasmosis infestations (8).
Finn, Ward and Mattison in 1972 reported previous tuberculosis infection in a quarter of 26 patients with cerebral gliomas (9). This group a year later to replicate their surprised finding, noted previous tuberculosis infection in 21.7% of 92 patients with cerebral gliomas compared with only 7% of 100 controls (10). Such association between previous tuberculosis and cerebral gliomas were replicated later on and in larger samples by others (e.g. 11). Of viral invasion causing brain tumors, Copeland and Bigner in 1977 inoculated an avian sarcoma virus in the brain of rats at different ages and showed 100% causation of brain tumors, with higher such chance at earlier age of inoculation (12). Similar result in rats was published a year later by Roszman, Brooks, Markesbery and Bigner who showed a parallel immunological suppression by the virus between rats and humans (13). Soon other viruses such as Herpes virus were also shown to be causative agents of different brain tumors in animal studies (e.g. 14).
A decade later in 1987, Corallini and colleagues demonstrated the presence of BK virus DNA in 25.6% of human brain tumors of 74 patients and 44.4% in 9 patients with pancreatic islets tumors (15). BK virus that is widespread worldwide except for isolated regions of Brazil, Paraguay, and Malaysia in its primary invasion or infection is mild and unapparent, manifesting generally as mild respiratory or urinary tract infections. During its primary invasion, the virus through blood spreads to several body organs and remains in a dormant state. The reactivation of virus to cause more damages and tumors across different organs occur upon immunological impairment (16-17). While the brain tumors have been reported to be the more common neoplasms caused by this virus (18-21), bone tumors, insulinomas, Hodgkin’s Lymphoma, Kaposic’s Sarcoma and urinary tract tumors have also been reported (e.g. 22-23). Other viruses such as human JC virus and HIV have also been reported causing brain tumors in animal and human studies (e.g. 24-26).
Soon the idea of vaccination therapy for brain tumors such as malignant gliomas started to grow and have an application. Different viral-mediated (Herpes Virus, Rertovirus, Adenoma Virus, and Epstein Barr Virus) gene therapy started to be applied effectively in animal then clinical studies as vaccinations (27-34). In the recent years the gene or vaccination therapy has progressed so that even RNA-binding and other gene proteins instead of viral vectors have been used in the treatment of different brain tumors such as medulloblastomas in children (e.g.35-36). Altogether these gene therapies in the cancer treatment research filed is known as Suicide gene therapy (SGT), as the brain tumor cells are killed and suppressed in growth (37).
Even our precious brain with its defensive blood-brain barrier that protects our brains from many toxins and invasions, is not immune and exempted from the microbial invasions. From simple and acute brain infections such as meningitis and encephalitis to longer processes of developing tumors in different part and layers of the brain, microbes are the offending agents. From the tinniest viruses such as BK virus with unapparent and mild primary generalized body infection like a flu to the largest such as tapeworms all invade every parts of our being including our precious brain.
Knowing the microbial invasions underlying brain tumors for almost a century, but calling the cause of these malignancies as idiopathic (unknown) in the official medical textbooks and literature is ignorance. Acknowledging the underlying pathogenesis of brain tumors by microbial invasions holds the vital promise of prevention and early intervention and right treatments. For example monitoring patients with past history of tuberculosis infections, we could identify and save a quarter of them from developing tuberculomas and gliomas. Also identifying and monitoring other viral, bacterial, fungal or even parasitic infections could prevent or early detect development of different brain tumors caused by these insulting agents.
Finally it has been the diligent observations of some medical scientists into the underlying pathogenesis of brain malignancies by microbes that has led to the recent developments of different viral-mediated or RNA- and related protein-mediated vaccines for the treatment of different brain tumors. In fact these novel treatments cleverly have used the microbial invasion strategies at the service of defense and treatment.
Dr.Mostafa Showraki, MD, FRCPC
Lecturer, School of Medicine, University of Toronto
Author: ADHD: Revisited Book, Amazon Kindle Books
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