Linked Life Data

9195217

Source:http://linkedlifedata.com/resource/pubmed/id/9195217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-8-6
pubmed:abstractText
Replication-defective adenovirus expressing the herpes simplex thymidine kinase gene (H5.010RSVtk) may be useful in treating human gliomas. To determine the toxicity of this therapeutic strategy, we injected H5.010RSVtk stereotactically into the normal brain of Wistar rats, cotton rats, and rhesus monkeys in conjunction with systemic ganciclovir (GCV) at 10 mg/kg per day. In the Wistar rat, 5.7 x 10(9) pfu resulted in histopathologic injury consisting of localized necrosis, mild gliosis, marked malacia, and focal astrocytosis; however, 1.0 x 10(8) pfu resulted in only mild gliosis and trace meningitis and approximates a "no toxic effect" dose. A dose of 1.0 x 10(9) pfu in both adenoviral immune and adenoviral naive cotton rats resulted in similar findings. In the rhesus monkey, doses ranging from 1.4 x 10(8) pfu to 1.5 x 10(11) pfu resulted in localized gliosis, necrosis, perivascular cuffing, meningitis, and roughly correlated in severity with increasing dose. No histologic evidence of toxicity was found in non-central nervous system (CNS) tissues, and no virus could be cultured from cerebrospinal fluid (CSF), blood, urine, and stool samples. All animals survived to prescribed end points without signs of general toxicity or neurologic symptoms, except for 2 of the rhesus monkeys, one of which became febrile and the other of which developed a grand mal seizure (both subsequently resolved). These toxicology studies define the parameters for developing a phase I clinical trial.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
943-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Intracranial administration of adenovirus expressing HSV-TK in combination with ganciclovir produces a dose-dependent, self-limiting inflammatory response.
pubmed:affiliation
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't