Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-5-26
pubmed:abstractText
Adenovirus-mediated transduction of the herpes simplex thymidine kinase gene (HSV-tk) in conjunction with ganciclovir (GCV) has been shown to result in significant growth suppression and to enhance survival in a model of mouse prostate cancer. However, this therapeutic activity is not sustained, because in most cases tumors eventually regrow and ultimately cause the death of the host. Androgen ablation, an inducer of apoptosis in prostate cells which is used widely as palliative therapy in patients with prostate cancer, was combined with HSV-tk plus GCV using an androgen-sensitive mouse prostate cancer cell line. The combination of castration and HSV-tk plus GCV led to markedly enhanced tumor growth suppression in both subcutaneous and orthotopic models compared with either treatment alone and resulted in an enhanced survival in which combination-treated animals lived twice as long as controls in the subcutaneous model and over 50% longer than controls in the orthotopic model. Further analysis of apoptotic activity demonstrated high levels of apoptosis only in combined androgen ablation and HSV-tk plus GCV-treated tumors after 14 days of growth in an androgen-depleted environment and 8 days after HSV-tk plus GCV therapy. At this time, the apoptotic index, but not the percent of necrotic tissue, was significantly higher for combination therapy-treated tumors relative to control-treated tumors or either treatment alone. These data indicate that the therapeutic effects of androgen ablation and HSV-tk plus GCV are cooperative and that increased apoptosis may, in part, underlie these activities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10078964-Adenoviridae, pubmed-meshheading:10078964-Androgens, pubmed-meshheading:10078964-Animals, pubmed-meshheading:10078964-Antimetabolites, pubmed-meshheading:10078964-Apoptosis, pubmed-meshheading:10078964-Castration, pubmed-meshheading:10078964-Combined Modality Therapy, pubmed-meshheading:10078964-Ganciclovir, pubmed-meshheading:10078964-Gene Therapy, pubmed-meshheading:10078964-Genetic Vectors, pubmed-meshheading:10078964-In Situ Nick-End Labeling, pubmed-meshheading:10078964-Male, pubmed-meshheading:10078964-Mice, pubmed-meshheading:10078964-Neoplasms, Hormone-Dependent, pubmed-meshheading:10078964-Prostatic Neoplasms, pubmed-meshheading:10078964-Simplexvirus, pubmed-meshheading:10078964-Survival, pubmed-meshheading:10078964-Thymidine Kinase, pubmed-meshheading:10078964-Time Factors, pubmed-meshheading:10078964-Tumor Cells, Cultured
pubmed:articleTitle
Cooperative therapeutic effects of androgen ablation and adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy in experimental prostate cancer.
pubmed:affiliation
Matsunaga-Conte Prostate Cancer Research Center and Scott Department of Urology, Veterans Affairs Medical Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't