|
|
Experimental
basis of cancer combination chemotherapy with retinoids, cytokines,
1,25-dihydroxyvitamin D3, and analogs
Bollag W
F. Hoffmann-La Roche, Ltd., Basel, Switzerland
Retinoids, cytokines
as well as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and analogs possess properties
known to contribute potentially to cancer chemopreventive and chemotherapeutic
effects.
They induce cell differentiation, inhibit cell proliferation, suppress
expression of viral oncogenes, and inhibit angiogenesis necessary for tumor
growth.
Since clinical combination chemotherapy of cytotoxic agents has proven superior
to monotherapy, this modality might also be useful for other classes of
antitumor drugs.
A series of retinoids, such as all-trans-, 13-cis-, 9-cis retinoic acid, and
acitretin, cytokines, 1,25(OH)2D3, and analogs have been investigated in model
systems of differentiation, proliferation, viral oncogenes, and
angiogenesis.
The three classes of compounds have common effects but nevertheless show a
variance depending on the particular representative of each class.
Combination of compounds of the different classes led in the various models to a
higher efficacy compared with the compounds given alone.
Cytokines such as IFN alpha, IFN gamma, G-CSF, TNF alpha, IL-1, and IL-4
markedly potentiate the differentiation-inducing effect of retinoids.
Cytokines as well as retinoids combined with 1,25(OH)2D3 and analogs
synergistically enhanced differentiation induction in human transformed
hemopoietic cell lines.
On a series of human transformed epithelial cell lines a panel of cytokines,
such as IFN alpha, IFN gamma, TNF alpha, TGF beta, and EGF acted synergistically
with retinoids on inhibition of proliferation.
This was also observed by combining retinoids with 1,25(OH)2D3 and
analogs.
Retinoids as well as interferons alpha and gamma have the capacity to suppress
the oncogene expression of human papilloma viruses which are involved in
induction and growth of certain malignancies such as cervical cancer.
(ABSTRACT TRUNCATED AT 250 WORDS)
PMID:
7890801 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7890801&dopt=Abstract
|
