Abstract: A method involving the administration of nucleoside analogs to circumvent resistance attributable to the enhanced DNA repair capacity of cancer cells is described. The nucleoside analogs function as suicide substrates for DNA repair enzymes. A method of screening nucleoside analogs for utility as antitumor agents and a screening assay to individual recurrent tumors is described.

Abstract: The effects of suppressing c-fos oncogene expression on drug or radiation resistant mammalian cells are described. A2780S human ovarian carcinoma cells with resistance to actinomycin D were isolated and the resultant A2780AD cells exhibited the MDR phenotype. A hammerhead ribozyme designed to cleave fos RNA cloned into the pMAMneo plasmid was transfected into A2780AD cells. Induction of the ribozyme resulted in decreased expression of c-fos, followed by that of mdr-1, c-jun, and p53. Reversal of the MDR phenotype by the anti-mdr ribozyme occurred one-fourth as rapidly as that induced by the anti-fos ribozyme. These studies demonstrate the primacy of the c-fos oncogene in maintaining the resistant phenotype in human cancer cells. Thus, down regulation of fos/jun will make resistant cancer cells more sensitive to conventional treatment, i.e., cancer chemotherapeutic agents and/or radiation.

Abstract: The steroid enzyme 5.alpha.-reductase is responsible for the conversion of testosterone to the more-potent androgen dihydrotestosterone (DHT). The catalytic cleavage of nucleic acid encoding 5.alpha.-reductase by a ribozyme which selectively recognizes such nucleic acid reduces the level of expression of 5.alpha.-reductase by mammalian cells including human cells treated with such ribozyme. The reduction of nucleic acid (e.g. mRNA) levels leads to a corresponding reduction of enzyme levels and dihydrotestosterone levels in surrounding tissues, thus providing a therapeutic effect. The transformation of 5.alpha.-reductase producing cells with an expression vector containing a structural gene for a ribozyme is shown to decrease 5.alpha.-reductase expression. Pharmaceutical compositions and methods useful for topically administering effective amounts of such a ribozyme to hair follicle cells also are exemplified.

Abstract: A method for producing a contaminating DNA free single stranded PCR amplification product of mRNA is disclosed. The mRNA amplification product is of lower molecular weight and is readily separated, e.g., by gel electrophoresis, from any amplified cellular DNA contaminant.

Abstract: This invention provides a process for detecting acquired resistance to any chemotherapeutic agent by any type of human cancer cell. The process comprises assaying RNA from human cancer cells to determine whether the expression of at least one of a preselected spectrum of least two different genes is increased in comparison to a control.

Abstract: A method for producing a contaminating DNA free PCR amplification product of mRNA is disclosed. The mRNA amplification product is of lower molecular weight and is readily separated, e.g., by gel electrophoresis, from any amplified cellular DNA contaminant.

Abstract: A method involving the administration of nucleoside analogs to circumvent resistance attributable to the enhanced DNA repair capacity of cancer cells is described. The nucleoside analogs function as suicide substrates for DNA repair enzymes. A method of screening nucleoside analogs for utility as antitumor agents and a screening assay to individual recurrent tumors is described.

Abstract: A method involving the administration of nucleoside analogs to circumvent resistance attributable to the enhanced DNA repair capacity of cancer cells is described. The nucleoside analogs function as suicide substrates for DNA repair enzymes. A method of screening nucleoside analogs for utility as antitumor agents and a screening assay to individual recurrent tumors is described.

Abstract: Changes in tumor cell RNA and DNA are utilized to detect the progression and the temporal changes in resistance to chemotherapy in human tumors.