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G Feichter

Publications and source records attributed to G Feichter.

25 records · Page 2Linked to original sources

Influence of systematic errors on the evaluation of the S phase portions from DNA distributions of solid tumors as shown for 328 breast carcinomas.

The portion of cells in S phase has proved to be a valuable prognostic indicator of early relapse and life expectancy, particularly in breast carcinoma. Comparisons of published data on samples of primary breast carcinoma biopsies showed that the values obtained by analyses of flow cytometric DNA distributions were generally higher than those of determinations based on the tritiated thymidine (3H-ThdR) labeling index (LI). Flow cytometric DNA analyses of 328 biopsy samples of primary breast carcinomas revealed that these differences could be explained by varying contributions of debris background. Since this influence is inversely proportional to the cell counts in each channel, it may cause considerable errors, particularly in the S phase channels, which normally contain the lowest counts of the DNA distributions. Two different mathematical rationales were tested in order to separate DNA distributions from the debris superimposition. No appreciable differences were found with respect to the essential results. After appropriate subtraction of the background levels, the previously reported discrepancies between cytometrically determined S phase portions and 3H-ThdR LI values disappeared, and good agreement was achieved for the comparable tumor samples of the present study. In conclusion, debris background subtractions should generally precede the DNA histogram analyses, particularly of solid tumors, in order to obtain reliable S phase values.

Breast Neoplasms↗

Does in vitro colony formation and chemosensitivity relate to DNA ploidy and S-phase fractions?

In vitro colony formation and chemosensitivity were analyzed in 65 human solid tumors and compared to proliferation parameters simultaneously obtained by DNA flow cytometry of the same tumor specimens. Colony growth in the human tumor colony assay was enhanced in aneuploid tumors (39/65) in comparison to diploid tumors (26/65, P less than 0.05). In addition, there was a relationship between % S-phase and colony growth. The existence of polyploid sublines (23/65) improved in vitro growth even in tumors with a diploid main G0/1-peak or with a low % S-phase. Metastases exhibited a higher proportion of aneuploidy and showed slightly better growth in vitro than primary tumors. Sensitivity testing in 34 of the 65 tumors showed no convincing relation between DNA parameters and the inhibition of colony formation by five standard anticancer agents with different mechanisms of action. This indicates additional factors other than the proliferative activity of the tumor to be responsible for drug sensitivity or resistance.

Antineoplastic Agents↗

Stereology and flow-cytometry of well-differentiated follicular neoplasms of the thyroid gland.

A retrospective analysis of surgically resected thyroid nodules by stereology and DNA flow cytometry was performed in 15 follicular adenomas and 15 well-differentiated follicular carcinomas. The criteria for diagnosis were based on the WHO classification of thyroid tumours. By area-weighted random sampling of the visual fields for light-microscopic stereology, any subjective selection bias was precluded, and each point within the embedded neoplastic tissue was given equal probability of being analyzed. 150-250 tumour cell nucleus (TCN) profiles were studied per case by a semiautomatic image analyzing system. Flow cytometric analyses included measurement of the DNA-index, and the percentages of cells in S-phase and in G2/M-phase. Adenomas and carcinomas did not differ in stereological estimates related to TCN size. As examination of the stereological techniques by nested analysis of variance showed that this result cannot be ascribed to inaccurate methods, it follows that determination of TCN size is not a useful tool for the diagnosis of malignancy in well-differentiated thyroid tumours. Both groups included similar proportions of diploid and aneuploid neoplasms. In the carcinoma group the percentage of tumour cells in the G2/M-phase was more than twice as high than in the adenoma group (P less than 0.01). The ratio of short to long TCN profile axis was significantly smaller, and the coefficient of variation of TCN profile area was significantly higher in carcinomas than in adenomas. These findings are consistent with more unequiaxed TCN and higher anisokaryosis in the malignant tumours. Despite the significant differences, however, overlap of data from individual cases precludes the use of these estimates as diagnostic criteria. Pooling of the follicular tumours and dichotomizing the sample by the DNA-index showed that mean TCN profile area is increased and surface-to-volume ratio of TCN is decreased in aneuploid as compared to diploid tumours. This finding indicates that aneuploidy is associated with an increase of TCN size.

Adenocarcinoma↗

Fluorescence in situ hybridization for detecting erbB-2 amplification in breast tumor fine needle aspiration biopsies.

OBJECTIVE: To evaluate the feasibility of erbB-2 amplification analysis of fine needle aspiration (FNA) biopsies. STUDY DESIGN: FNA smears and dissociated nuclei from 58 breast cancer samples were examined by dual-labeling fluorescence in situ hybridization (FISH) with probes for centromere 17 and the erbB-2 gene. The results were compared with the outcome of erbB-2 immunohistochemistry. RESULTS: Tumors were categorized according to the erbB-2/centromere 17 signal ratio. There were 23 tumors with high-level amplification, four cases with a low-level erbB-2 gain and 27 tumors with normal erbB-2 content. Four tumors showed an erbB-2 deletion, all in patients < or = 42 years of age. ErbB-2 amplification was strongly associated with positive erbB-2 immunostaining (P < .0001). Comparison of FISH analysis on dissociated cells and on FNA biopsies showed high correspondence (P < .0001). CONCLUSION: FISH allows reliable detection of erbB-2 gene amplification on FNA biopsies.

Adult↗

A fluorescent study of ligands for guanidinobenzoatase, a protease associated with tumour cells.

We have employed ethanol-fixed wax embedded sections of human breast tumours and smears of rat leukaemia cells to provide test systems with recognisable tumour cells amongst normal cells. We have used 9-aminoacridine to locate cells possesing guanidinobenzoatase, an enzyme which degrades fibronectin and which binds 9-aminoacridine to its active centre. The binding of 9-aminoacridine to tumour cells allows these cells to be located by fluorescent microscopy. Pre-treatment of these sections with BZAR, a known inhibitor of guanidinobenzoatase inhibited the binding of 9-aminoacridine to the tumour cells. These techniques defined the tumour cells in the sections; we then demonstrated by fluorescent microscopy that both Texas red-agmatine and BZAR also bound to the guanidinobenzoatase of these tumour cells. These fluorescent probes have been used as model compounds to illustrate the ability of both N-substituted agmatines and N-substituted arginines to deliver desired molecules to an enzyme on the surface of tumour cells. Replacement of these fluorescent moieties by cytotoxic moieties attached to the same ligands could lead to selective drug delivery to tumour cells.

Animals↗