Linked Life Data

8170835

Source:http://linkedlifedata.com/resource/pubmed/id/8170835

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-6-2
pubmed:abstractText
The endocrine treatment of metastatic prostate cancer includes castration which reliably lowers the serum testosterone (T); however, the effect on intratumor levels of T and dihydrotestosterone (DHT) is less predictable. In vitro work demonstrated that the human prostate cancer cell line PC-3 had significant 5-a-reductase activity that could be inhibited with 17b-N,N-diethylcarbamoyl-4-aza-5a-androstan-3-one (4MA). In this study, we examined the effect of 5-a-reductase inhibition with 4MA and androgen suppression with dexamethasone on the growth characteristics and intratumor androgen levels in the PC-3 cell line in male athymic nude mice (Balb/c). The mice were randomized into six treatment groups: 1) noncastrate vehicle control, 2) 4MA, 0.25 mg/day, 3) 4MA, 1 mg/day, 4) dexamethasone, 25 micrograms/day, 5) 4MA, 1 mg/day, and dexamethasone, 25 micrograms/day, and 6) castrate control group. After 21 days of treatment the animals were sacrificed, serum collected, and tumors harvested. Each treatment produced intratumor DHT levels equivalent to the castrate group. Only the low dose 4MA caused a reduction in intratumor DHT without producing castrate levels of circulating T. The combination of dexamethasone and 4MA was less effective in lowering the intratumor DHT/T ratio than 4MA alone. No significant differences in tumor growth parameters were noted between intact control animals and any of the treatment arms. Serum T levels correlated poorly with intratumor androgen levels. Five-a-reductase inhibition produced castrate levels of intratumor DHT in the nonandrogen-dependent prostate cancer cell line PC-3. The combination of dexamethasone and 5-a-reductase inhibition with 4MA appears to be less effective in lowering intratumor androgen levels than either therapy alone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0270-4137
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
229-36
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8170835-5-alpha Reductase Inhibitors, pubmed-meshheading:8170835-Androgen Antagonists, pubmed-meshheading:8170835-Androgens, pubmed-meshheading:8170835-Animals, pubmed-meshheading:8170835-Azasteroids, pubmed-meshheading:8170835-Dexamethasone, pubmed-meshheading:8170835-Dihydrotestosterone, pubmed-meshheading:8170835-Dose-Response Relationship, Drug, pubmed-meshheading:8170835-Humans, pubmed-meshheading:8170835-Male, pubmed-meshheading:8170835-Mice, pubmed-meshheading:8170835-Mice, Inbred BALB C, pubmed-meshheading:8170835-Mice, Nude, pubmed-meshheading:8170835-Neoplasm Transplantation, pubmed-meshheading:8170835-Neoplasms, Hormone-Dependent, pubmed-meshheading:8170835-Orchiectomy, pubmed-meshheading:8170835-Prostatic Neoplasms, pubmed-meshheading:8170835-Random Allocation, pubmed-meshheading:8170835-Testosterone, pubmed-meshheading:8170835-Tumor Cells, Cultured
pubmed:year
1994
pubmed:articleTitle
Effect of 5-alpha-reductase inhibition and dexamethasone administration on the growth characteristics and intratumor androgen levels of the human prostate cancer cell line PC-3.
pubmed:affiliation
Madigan Army Medical Center, Tacoma, Washington.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.