Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct.
Summary of "Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct."
ABSTRACT:
Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir.
Affiliation
Journal Details
This article was published in the following journal.
Name: Journal of neuroinflammation
ISSN: 1742-2094
Pages: 44
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20691089
- DOI: http://dx.doi.org/10.1186/1742-2094-7-44
Medical and Biotech [MESH] Definitions
Acetazolamide
One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)
Glioma
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
Cortical Spreading Depression
The decrease in neuronal activity (related to a decrease in metabolic demand) extending from the site of cortical stimulation. It is believed to be responsible for the decrease in cerebral blood flow that accompanies the aura of MIGRAINE WITH AURA. (Campbell's Psychiatric Dictionary, 8th ed.)
Viscosupplementation
A therapeutic treatment typically involving INTRA-ARTICULAR INJECTIONS of HYALURONIC ACID and related compounds. The procedure is commonly used in the treatment of OSTEOARTHRITIS with the therapeutic goal to restore the viscoelasticity of SYNOVIAL FLUID, decrease pain, improve mobility and restore the natural protective functions of hyaluronan in the joint.
Oxyphenonium
A quaternary ammonium anticholinergic agent with peripheral side effects similar to those of ATROPINE. It is used as an adjunct in the treatment of gastric and duodenal ulcer, and to relieve visceral spasms. The drug has also been used in the form of eye drops for mydriatic effect.
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