Linked Life Data

3047266

Source:http://linkedlifedata.com/resource/pubmed/id/3047266

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1988-10-25
pubmed:abstractText
Hexamethylene bisacetamide (HMBA), a highly polar compound, induces murine erythroleukemia (MEL) cells to express the erythroid phenotype, including cessation of proliferation. Inducer-mediated differentiation of MEL (DS19) cells is a multistep process characterized by a latent period during which a number of changes occur including alterations in ion flux, an increase in membrane-bound protein kinase C (PKC) activity, the appearance of Ca2+ and phospholipid-independent PKC activity in the cytosol, and modulation in expression of a number of genes such as c-myc, c-myb, c-fos and the p53 genes. HMBA-mediated commitment to terminal differentiation is first detected at about 12 hours and increases in a stochastic fashion until over 95% of the population is recruited to terminal differentiation by 48 to 60 hours. Commitment is associated with persistent suppression of c-myb gene expression. By 36 to 48 hours, transcription of the globin genes has increased 10 to 30 fold, whereas transcription from rRNA genes is suppressed. The steroid, dexamethasone, or the tumor promoter, phorbol-12-myristate-13-acetate (TPA), suppress HMBA-induced MEL cell terminal differentiation. These agents appear to act at a late step during the latent period. MEL cell lines derived from DS19 by selection for resistance to vincristine are: 1) induced to commit without a detectable latent period, 2) markedly more sensitive to HMBA, and 3) resistant to dexamethasone or TPA inhibition of HMBA-induced commitment. The data suggests that vincristine-resistant MEL cells express a factor which circumvents essential HMBA-mediated early events. In vitro studies with HMBA provide a basis for the application of HMBA to clinical therapy of human cancers. Clinical trials with HMBA have been initiated.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0737-1454
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Hexamethylene bisacetamide-induced differentiation of transformed cells: molecular and cellular effects and therapeutic application.
pubmed:affiliation
DeWitt Wallace Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review