Prognostic potential of flow cytometric S-phase and ploidy prospectively determined in primary breast carcinomas.

In a prospective study of a consecutive breast cancer series accumulated in the period 1978-82, the S-phase fraction (SPF) and ploidy status were determined by flow cytometry performed on cell nuclei derived from samples of 580 primary tumors. Sixty percent of the tumors were non-diploid. After correction for debris the median SPF values were 7.3% overall, 12% for non-diploid tumors, and 2.9% for diploid tumors (2.6% when nodal subsets N2 and N3 and cases with metastases at presentation were excluded). The SPF values correlated both to tumor size (p = 0.008) and to the number of positive axillary lymph nodes (p = 0.03). At clinical follow-up in 1986, 467 unilateral breast cancer patients who had undergone radical treatment for cure could be evaluated with respect to the prognostic value of both the SPF value and ploidy status. The median duration of follow-up was then 59 months (range 2-90), and the median time-to-recurrence 24 months (range 2-69, n = 137). At follow-up in 1991, 201/467 of the patients had died, the median duration of follow-up being 50 months (range 2-126) for the decreased, and 119 (range 6-148) for the survivors. In multivariate analysis (Cox's proportional hazards models), the strongest independent predictors of distant recurrence-free survival (DRFS) were the number of positive axillary lymph nodes (p less than 0.0001), the debris-corrected SPF value alone (p = 0.003, versus p = 0.05 for uncorrected value), and ploidy status combined with the corrected SPF value (p = 0.0002). When age was taken into account, both the corrected SPF value and the ploidy-SPF combination were predictors of crude survival (p = 0.006 and p = 0.002, respectively). In univariate life-table analysis, the 5-year DRFS rate was 93% in node-negative (N0) cases with an SPF less than 7.3%, as compared to 80% in those with an SPF greater than or equal to 7.3% (p = 0.005). Among node-positive cases, the prognostic value of the SPF was confined to those with 1-3 positive nodes, the 5-year DRFS rate being 68% in cases with an SPF less than 7.3%, as compared to 40% in cases with an SPF greater than or equal to 7.3% (p = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Portal radiographs: digital enhancement of contrast

The quality of low-contrast portal radiographs for radiation therapy can be improved with electronic contrast enhancement. After the image is copied digitally with a laser scanner microdensitometer into 4,096 gray-scale levels (12 bits) and 1,686 X 2,048 pixels, a special software package permits linear, logarithmic, exponential, or sigmoid transformations of the optical density. The precise representation of the portal image can then be interactively adjusted to emphasize the desired anatomy. Clinical examples demonstrate the value of the digital enhancement approach.     

Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic monkeys

Some models of visual cortical development are based on the assumption that the tangential organization of V1 is not determined prior to visual experience. In these models, correlated binocular activity is a key element in the formation of visual cortical columns, and when the degree of interocular correlation is reduced the models predict an increase in column spacing. To examine this prediction we measured the spacing of columns, as defined by cytochrome oxidase (CO) blobs, in the visual cortex of monkeys whose binocular vision was either normal or disrupted by a strabismus. The spatial distribution of blobs was examined in seven normal and five strabismic macaques. Tangential sections through the upper layers of the visual cortex were stained to reveal the two-dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to-center spacing, packing arrangement and density were calculated using 2D nearest-neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm for normally reared and 598 microm for strabismic macaques) and the mean density of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic macaques) were not significantly different. In addition, the 2D packing arrangement of the blobs was not affected by strabismus. While it is clear that neural activity plays a key role in the elaboration and refinement of ocular dominance cortical modules, we conclude that it does not determine the spatial period of the pattern of CO blobs. This suggests that aspects of the neural circuitry underlying the columnar architecture of the visual cortex are established prenatally and its fundamental periodicity is not modifiable by experience.      

Inhibited methionine incorporation in human squamous carcinomas of the oral cavity as a measure for response to 5-fluorouracil

Summary Human epithelial epithelial cells and fiborblasts from malignant tumors and healthy tissues of the oral cavity were exposed in vitro to increasing concentrations of 5-fluorouracil. In order to determine whether the two cell types showed a difference in uptake, accumulation was measured over time using tritiated fluorouracil. Maximal drug uptake occurred in highly proliferative epithelial cells from cancerous tissue at 3 h, whereas fibroblasts from the same tissue and other cell types from healthy tissue exhibited a steadily increasing uptake over a long period of time. By use of [³H]methionine, a direct correlation could be demonstrated between the amount of incorporated drug and the fall in the rate of de novo protein synthesis. Furthermore, suppression of protein synthesis was closely related to the inhibition of cell division. These results indicate that the level of de novo protein synthesis can be a direct measure of the anticancer effect of fluorouracilAbbreviations used PBS phosphate-buffered saline - FU 5-fluorouracil