Biomedical subjects
Publications and source records attributed to C Benz.
During high speed cavity preparation the vibration burden of human teeth was evaluated in comparison between turbine- and micromotor-driven handpieces. The acceleration spectra of different burs showed an advantage of the air-driven handpiece.
The effects of estradiol (E2) on c-myc proto-oncogene expression were studied in the estrogen receptor (ER)-positive human breast cancer cell line, MCF-7. A biphasic modulation in c-myc mRNA levels occurs during the first 24 h of E2 (1 nM) exposure and in the absence of changes in MCF-7 culture growth, with transcript levels rising 4-6-fold within 1 h, returning to near base-line level after 3-6 h, and increasing again after 24 h of exposure. In contrast, the growth-inhibiting antiestrogen, tamoxifen (1 microM), reduces c-myc to 20% of the pretreatment level within 3-6 h of exposure, and this early decline is followed by a gradual return toward base-line level after continuous 72-h treatment. In ER-negative cells there is no change in c-myc expression following E2 exposure. MCF-7 nuclear runon assays show that c-myc transcription rates remain unchanged from base line for 24 h after E2 administration; as well, cycloheximide inhibition of protein synthesis superinduces c-myc expression and prevents E2 modulation of transcript levels. These results indicate that post-transcriptional modulation of c-myc by E2 is mediated by a labile degradative protein or otherwise dependent on active protein synthesis. We also developed MCF/nm and MCF/dm sublines by transfecting normal cells with human c-myc exons 2-3, transcriptionally driven by a retroviral long terminal repeat. Expression of the transfected c-myc genes in these sublines remains constant and elevated 10-fold, while transcript levels from the endogenous proto-oncogene continue to be modulated by E2. These findings suggest that in ER-positive breast cancer cells, E2 can modulate c-myc mRNA levels by a post-transcriptional mechanism that depends on gene sequences upstream from c-myc exon 2.
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The antitumor toxicity of gossypol was measured in 6 human carcinoma cell lines and compared with its toxicity against human bone marrow stem cells. Marrow cells were more resistant than any of the tumor cell lines, and tumor cell sensitivity depended on the content of intracellular LDH-M. [31P]-Magnetic resonance spectroscopy showed decline in tumor ATP levels occurring within 24 hours of treatment, suggesting that this non-invasive technique may serve as an early biochemical monitor of gossypol toxicity.
Specific genetic alterations are observed in human breast cancer, but little is known about when these occur in the evolution of the disease. Three breast cancer effusions that occurred sequentially in a single patient were examined. Common cytogenic abnormalities were found in all effusion samples suggesting a single progenitor metastatic cell. Only the last effusion, however, exhibited a mutation of the c-K-ras gene and a loss of heterozygosity at the c-H-ras locus. These specific genetic abnormalities detected in the last effusion was correlated with improved in vitro growth of the primary cells, and with the ability to establish breast cancer cell lines. Thus a mutant ras gene and the loss of heterozygosity at the c-H-ras locus were associated with a more aggressive tumor phenotype occurring late in the course of this patient's disease and not with the initiation of the primary breast cancer, or in the establishment of metastases.
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Three compounds that share specific antimitochondrial properties are gossypol, rhodamine-123, and lonidamine. We compare the antiproliferative activities of these drugs against six human cell lines derived from breast (T47-D), pancreas (MiaPaCa, RWP-2), prostate (DU-145), colon (HCT-8), and cervix (HeLa) carcinomas. Tumor cells enriched in cathodal LDH isozymes (LDH4 and LDH5) are significantly more sensitive to gossypol and rhodamine-123. When compared for ability to inhibit growth of human marrow in soft agar, 10 microM gossypol shows little effect on colony formation whereas 10 microM rhodamine-123 completely prevents stem cell growth, suggesting that gossypol may have the most favorable therapeutic index. Within 24 h of drug administration, there is a relative increase in intracellular inorganic phosphate pools and a marked decline in soluble high-energy phosphates in sensitive tumor cells, as measured by 31P magnetic resonance spectroscopy. These studies suggest that specific antimitochondrial agents might be selectively administered on the basis of tumor LDH isozyme content and noninvasively monitored for antiproliferative activity by 31P spectroscopy.
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