We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 évaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug »asadministered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14to 21-day intervals. Myelosuppression and mucositis were the limiting toxici...

The ability of organ cultures of normal human and rat bladder to metabolize the polycyclic hydrocarbon, benzo(a)pyrene (BP), and the arylamine, 2-acetylaminofluorene, has been stud ied. Cultures were maintained for 0 to 6 days in a chemically defined medium before incubation with [3H]BP (0.3 to 0.5 ¿IM) or 2-pC]acetylaminofluorene (18 to 25 ¡ÕM) for 24 hr. Ethyl acetate-soluble and water-sol...

Permanent cell culture lines derived from human breast cancer tissue are important experimental models in the study of human breast cancer cell proliferation. In the present work, pimozide, thioridazine, W-13, and W-12 were shown to inhibit MCF-7 human breast cancer cell growth. The 50% inhibition concentration values determined in two proliferation assays, | 'Hjthymidine incorporation and cell...

RAS mutations arise at high frequency in human malignancy and have been shown to play a role in the disruption of both normal differentiation and proliferation. In addition, RAS influences a number of intracellular signaling pathways, which impinge on proteins that regulate programmed cell death. In this study, we have examined whether this oncogene can influence the activation of the apoptotic...

Corticoid (CR)-, estrogen-, and progestin-binding sites were assayed in cytosol from 356 human breast tumors, using dexamethasone (DXM), 11ß-methoxy-1 7-ethynyl-1,3,5(10)estratriene-3,17/ß-diol (R2858; Moxestrol), or 17,21-dimethyl19-norpregna-4,9-diene-3,20-dione (R5020; promegestone), respectively. These sites were assayed on the fresh tumors or after storage for 15 days to 6 months in liqu...

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...

RAS mutations arise at high frequency in human malignancy and have been shown to play a role in the disruption of both normal differentiation and proliferation. In addition, RAS influences a number of intracellular signaling pathways, which impinge on proteins that regulate programmed cell death. In this study, we have examined whether this oncogene can influence the activation of the apoptotic...

The levels of milk-specific mRNAs (a-casein, whey acidic protein) and proteins (casein, a-lactalbumin) were examined in the DIM series of mammary preneoplastic outgrowth lines and tumors. The constitutive production of casein protein was variable among the preneoplastic DIM outgrowth lines maintained in virgin mice. Outgrowth line DIM-2 con sistently expressed a very low level of casein mRNA an...

Corticoid (CR)-, estrogen-, and progestin-binding sites were assayed in cytosol from 356 human breast tumors, using dexamethasone (DXM), 11ß-methoxy-1 7-ethynyl-1,3,5(10)estratriene-3,17/ß-diol (R2858; Moxestrol), or 17,21-dimethyl19-norpregna-4,9-diene-3,20-dione (R5020; promegestone), respectively. These sites were assayed on the fresh tumors or after storage for 15 days to 6 months in liqu...

The effects of the anticancer drugs 4'-demethylepipodophyllotoxin thenylidene /3-o-glucoside and 4'-demethylepipodophyllotoxin ethylidene 0-o-glucoside on the growth and viability of Chinese hamster ovary cells have been examined. Stable mu tants which are from 4to 12-fold more resistant to these drugs (VpmR mutants) are obtained in a single selection step in Chinese hamster ovary cells at a fr...