The pattern of c-myc gene organization and expression has been examined in resected colonic tumors and in the adjacent normal colon from 15 patients undergoing radical surgery. DNA hybridization showed no evidence of gene amplification or rearrangement. Transcripts of the c-myc messenger ribonucleic acid (mRNA) were elevated up to 32-fold in 12 of 15 tumors. The gene product, p62c-myc, was detected by both immunoblotting and immunohistology using a monoclonal antibody raised against a synthetic peptide immunogen. There was close correlation between c-myc mRNA copy number and p62c-myc abundance. Three well differentiated tumors contained high levels of transcript and protein, whereas four poorly differentiated tumors had the lowest levels. The assay of oncogene products may provide new biologically relevant tumor markers for determining prognosis and guiding treatment.
The results of this study, the first targeted gene therapy for breast cancer and the first to use the cytosine deaminase system in human subjects, are encouraging for the development of genetic prodrug activation therapies that exploit the transcriptional profile of cancer cells.
Ten women with advanced locally recurrent breast cancer who had failed to respond to radiation and hormonal and cytotoxic agents were given up to 12 weeks of recombinant leucocyte interferon 20 x 106 U/M2 daily or 50 X 106 U/M2 three times a week. Within one hour of administration influenza-like symptoms began, which one week later were superseded by lethargy, anorexia, and nausea, with a consequent loss of weight in most patients. Other side effects included profound somnolence, confusion, paraesthesia, and (in one patient) signs of an upper motor neurone lesion in the legs. All these effects together with increased slow wave activity in electroencephalograms from all patients during treatment disappeared when interferon was withdrawn and did not recur on reintroducing the drug at a lower dosage. Studies are continuing to determine the mechanisms of these effects.
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