Significance of growth rates, cell kinetics, and histology in the irradiation and chemotherapy of squamous cell carcinoma of the mouth

Friedman, Milton; Nervi, Carlo; Casale, C.; Starace, Giuseppe; Arcangeli, Giorgio; Page, Giorgio; Ziparo, Elio

doi:10.1002/1097-0142(197301)31:1<10::aid-cncr2820310103>3.0.co;2-z

Cited by 22 publications

(5 citation statements)

References 4 publications

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“…Determination of cell cycle parameters by autoradiographic methods is biased by grain count thresholds underlying the construction of FLM curves. This has been documented for malignant cell populations in vivo (Harris & Hoelzer, 1971;Friedman et al, 1973;Pickard et al, 1975) and in vitro (Shackney et al, 1973) and is confirmed in the present study for normal cells. Mitotic grain count thresholds are decisive for the configuration of FLM curves for hepatocytes and thus imply differences in cell cycle parameters derived from the curves.…”

Section: Discussionsupporting

confidence: 90%

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GRAIN COUNT THRESHOLD DEPENDENCE OF FLM CURVE PATTERN AND CELL CYCLE PARAMETERS OF HEPATOCYTES IN VIVO

Wirsching

Rabes

1977

Cell Proliferation

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FLM curves from hepatocytes of regenerating rat liver in vivo were compared at different grain count thresholds. Estimates of cell cycle phases derived from curves with thresholds decreasing from 15 to 1 grain (background 0.2 grains per nuclear area) revealed a prolongation of ts from 6.6 to 9.5 hr, at the expense of tG2M, and tG1, whereas tc remained constant. A similar pattern was observed in FLM curves at various threshold levels for hepatocytes localized in subunits of the liver lobule along the vascular axis from afferent to efferent pole. The shapes of these FLM curves indicated an intralobular gradient of reutilizable labelled material. The use of two different threshold levels is crucial for proper selection of FLM curves to evaluate cell cycle phases in regenerating rat liver: first, a threshold to exclude the autoradiographic background, and a second one to avoid errors due to reutilization of labelled DNA precursors. Each threshold has its own implications for the estimation of cell cycle phases.

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Section: Discussionsupporting

confidence: 90%

“…Only few data are available on the influence of silver grain thresholds on FLM curves and cell cycle parameters (Harriss & Hoelzer, 1971;Friedman et al, 1973;Shackney, Ford & Wittig, 1973;Pickard, Cobb & Steel, 1975). They showed changes of cell cycle parameters with alterations in the thresholds.…”

Section: Introductionmentioning

confidence: 99%

GRAIN COUNT THRESHOLD DEPENDENCE OF FLM CURVE PATTERN AND CELL CYCLE PARAMETERS OF HEPATOCYTES IN VIVO

Wirsching

Rabes

1977

Cell Proliferation

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“…Recently this test system has been evaluated for head and neck carcinomas (Wennerberg et al, 1983(Wennerberg et al, ,1984 with respect to differences and similarities between heterotransplants and tumours in situ. Though differences in 3HTdR-incorporation into DNA, volume doubling times and clonal composition were found, the cell cycle times for heterotransplants were close to those of their human counterparts (Frindel et al, 1968;Bresciani etal., 1974;Tannock, 1978). This makes the nude mouse model suitable for studies on some important aspects of chemotherapeutically induced changes as, e.g., the course of perturbations in cell cycle phase distribution.…”

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confidence: 62%

Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck afterMitomycin C andCisplatin treatment

et al. 1984

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Cell kinetic studies are of interest for clarifying the concepts of chemotherapeutic strategy in the multimodality therapy of advanced squamous-cell carcinoma of the head and neck. A poorly-differentiated squamous-cell carcinoma of the head and neck heterotransplanted to nude mice was used for analyses of chemotherapeutically induced cell cycle perturbations. The heterotransplanted tumour, in its 15th or later passages in nude mice, was treated with either Mitomycin C or cisplatin. After determination of dose-response relationships and toxicity, treated tumours were biopsied at different times and cell cycle distribution pattern, 3HTdR incorporation into DNA, histology and tumour volume were recorded. Mitomycin C and cisplatin gave the same pattern of cell cycle perturbations, although the changes induced by cisplatin were more profound. There was an initial increase of the fraction of cells in the S phase, concomitant with a reduction of the fraction of cells in G0 + G1 phase. When these perturbations were normalized a transient increase of the fraction of cells in G2 + M phase was observed. However, while cisplatin caused an initial transient depression of DNA synthesis, the Mitomycin-C-treated tumours exhibited a short-lasting increase of DNA-synthesis. The maxima of the induced changes in cell cycle phase distribution and DNA-synthesis lasted for only 24-48 h, which may be of importance for scheduling combinations of drugs. Though both drugs induced profound changes in tumour volume growth and cell kinetics, there was no change in the histopathological picture of the treated tumours. Routine histopathological examination is thus not likely to be of value evaluating the effect of chemotherapy.

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“…Comparisons of the TLI measured by in vivo vs. in vitro exposure to radiothymidine have consistently demonstrated close correspondence of the two methods (Denenkamp and Kallman, 1973;Fabrikant et al, 1969;Steel and Bensted 1965;Meyer and Bauer, in press). Authors have commented on nonhomogeneity of nuclear labeling in tumors (Friedman et al, 1973;Hainau and Dombernowsky, 1974) and this clearly is a problem in comparing the TLI of tumors. When replicate counts of 2,000 cells by our protocol are performed on the same aliquot of a tumor with a high TLI, a coefficient of variation approximately 4% will be obtained (Meyer and Bauer, in press).…”

Section: Accuracy and Reproducibility Of The In Vitro Tlimentioning

confidence: 99%

Tritiated thymidine labeling index of benign and malignant human breast epithelium

Meyer

Bauer

1976

Journal of Surgical Oncology

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38 specimens of benign breast tissue from young women and 92 primary breast carcinomas were evaluated for tritiated thymidine ([3H]TdR) labeling index (TLI) by in vitro pulse labeling. The TLI on nonneoplastic, terminal breast ducts was significantly higher during the latter half than during the first half of the menstrual cycle (P less than 0.001), and a geometric mean TLI of 1.5 during the latter half of the cycle is consistent with approximately 47% turnover of these cells during the menstrual cycle. Ducts of fibroadenomas showed similar menstrual variation TLI. The range of TLI observed in the carcinomas was 0.04-18.6, arithmetic mean 3.7, geometric mean 2.1. The TLI of carcinomas was not significantly correlated with size of the tumor, but tended to be higher in women less than 50 yr old than in women older than 50 yr (P less than 0.05), and in the presence of two or more metastatic axillary lymph nodes than when fewer than two nodes were involved (P less than 0.02).

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Significance of growth rates, cell kinetics, and histology in the irradiation and chemotherapy of squamous cell carcinoma of the mouth

Cited by 22 publications

References 4 publications

GRAIN COUNT THRESHOLD DEPENDENCE OF FLM CURVE PATTERN AND CELL CYCLE PARAMETERS OF HEPATOCYTES IN VIVO

GRAIN COUNT THRESHOLD DEPENDENCE OF FLM CURVE PATTERN AND CELL CYCLE PARAMETERS OF HEPATOCYTES IN VIVO

Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck afterMitomycin C andCisplatin treatment

Tritiated thymidine labeling index of benign and malignant human breast epithelium

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