Dequalinium has previously been shown to be an anticarcinoma agent (M. J. Weiss et al., Proc. Nati. Acad. Sci. USA, 84: 5444-5448, 1987). The present study demonstrates that it can inhibit protein kinase C-ß, isolated from an overproducing cell line with a 50% inhibitory concentra tion of 8-15 MM-Further examination of the inhibition by using structural analogues of dequalinium reveals that th...

Loss of E-cadherin (CDH1) function is thought to contribute to pro gression in breast cancer and other solid tumors by increasing prolifera tion, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutat...

In the MCF-7 breast iunior cell line, induction of bulk damage to DNA (measured either as total strand breaks or as double-strand breaks I fails to correspond »¡Hi the antiprciliferative activity of the demethylepipodophyllotoxin derivative, VM-26. In contrast, VM-26 produces an early (within 2-3 h) concentration-dependent reduction in e-myc expression (and of UNA synthesis) which parallels i...

We studied the effect of fenretinide [/V-(4-hydroxyphenyl)retinamide (4-HPR)], a synthetic analogue of retinoic acid, on plasma insulin-like growth factor I (IGF-I) levels in a consecutive cohort of stage I breast cancer patients belonging to a randomized phase III trial of breast cancer chemoprevention. Thirty-two women receiving 4-HPR 200 mg/daily and 28 untreated controls entered the study. ...

Taxol, 1-ß-D-arabinofuranosy Icytosine (ara-C), and etoposide induce apoptosis in HL-60 cells that is blocked by overexpression of Bcl-2 or Ikl-\,, A ~60-amino acid "loop"domain of Bcl-2 and Bcl-xLthat contains phosphorylation sites is known to negatively regulate their antiapoptotic function. In the present studies, Taxol-, ara-C-, or etoposide-induced apoptosis was examined in HL-60/Bcl-2A a...

The transplacental host-mediated hamster cell culture assay was used to test a series of solvents, control chemicals, and pesticides and their corresponding /V-nitroso derivatives for transforming activity. In addition to testing for morphological transformation, growth of cells suspended in 0.3% agar and tumorigenicity in nude mice were also determined. No trans forming activity was detected d...

Imiquimod [l-(2-methylpropyl)-l//-imidazo[4,5c]quinolin-4-amine] is a compound of low molecular weight that, when administered p.o., induces interferon-a in several animal species and inhibits tumor growth in mice. To determine maximum tolerated dose, toxicity, and biological response in humans, a phase I clinical trial was conducted with 14 eligible cancer patients who received 100-500 mg imiq...

Imiquimod [l-(2-methylpropyl)-l//-imidazo[4,5c]quinolin-4-amine] is a compound of low molecular weight that, when administered p.o., induces interferon-a in several animal species and inhibits tumor growth in mice. To determine maximum tolerated dose, toxicity, and biological response in humans, a phase I clinical trial was conducted with 14 eligible cancer patients who received 100-500 mg imiq...

n*flfac4ICDIN2nfFSl gene encodes two structurally different pro teins: a cyclin-dcpendent kinase inhibitor called pl6INK4u,which regulates retinohlastoma protein-dependent G, arrest, and a cell cycle inhibitor designated |il')U!l. which arrests cell growth in C,-S and also in G2-M. Whereas inactivation of pI6INK4"has been described as a frequent event in lung cancer, the current function of pl9...

HCT-8 cells become rapidly resistant to either 4-h (HCT-8/4hR) or 7-day (HCT-8/7dR) repeated exposures to fluorouracil (FUra). The HCT8/7dR cells were studied in more detail to determine their mechanism of resistance to FUra. Thymidylate synthase activity, binding of 5-fluorodeoxyuridylate to thymidylate synthase, and incorporation of FUra into RNA were not different between the parental and re...