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R E Moran

Publications and source records attributed to R E Moran.

16 recordsLinked to original sources
PubMed1984

Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer.

DNA ploidy and percent of (%S-phase) S-phase cells were determined from the DNA content distribution of 21 benign and 76 malignant (69 primary, 7 metastatic) breast tumors using flow cytometry. All of the benign tumors were diploid, whereas 89% of the malignant tumors had measurable aneuploidy. Multiple stem-lines were observed in approximately 10% of the malignant tumors. The ploidy distribution of the malignant tumors was bimodal with an increased frequency of tumors with a near diploid DNA index (DI), and a second group with DI ranging from triploid to tetraploid. The percentage of cells in S-phase ranged from less than 1% to 37.4%. DI and %S were significantly higher in poorly differentiated duct carcinomas, medullary carcinomas, and recurrent tumor metastases. DI and %S were also significantly higher in estrogen-receptor-negative tumors. There was no correlation between DI or %S and the extent of axillary nodal metastases. However, within the groups of node-negative and node-positive patients, DI and %S were not randomly distributed but were significantly correlated with degree of nuclear differentiation. Both parameters were higher in poorly differentiated tumors compared with well-differentiated tumors, indicating significant intrastage heterogeneity in tumor ploidy and proliferation characteristics. Determination of the prognostic significance of DI and %S will require a longer follow-up time.

Breast Neoplasms↗
PubMed1984

Flow cytometric analysis of human lung cancer. Correlation with histologic type and stage.

DNA ploidy and cell-cycle characteristics of 65 operable lung cancers (41 adenocarcinomas, 19 epidermoid carcinomas, 3 large-cell carcinomas and 2 small-cell carcinomas) were analyzed using flow cytometry. Eighty percent of the tumors were aneuploid. The mean DNA index was lower in epidermoid than in adenocarcinoma. In adenocarcinoma, a low DNA index was correlated with early-stage disease; no correlation between DNA index and stage was observed in the other cell types. The %S-phase cells was highest in two cases of undifferentiated large-cell carcinoma and lowest in adenocarcinoma. The RNA index was increased approximately two-fold in all cell types. Longer follow-ups will be required to establish any correlation between the cell kinetic measurements reported here and survival times.

Adenocarcinoma↗
PubMed1983

Localization of globoside and Forssman glycolipids on erythrocyte membranes.

Using the freeze-etch technique, the membrane localization of globoside, a principal glycolipid in human erythrocytes, and Forssman antigen, the chief glycolipid in sheep erythrocytes was evaluated using ferritin and colloidal gold as morphological markers for rabbit antibodies prepared against these glycolipids. Brief trypsinization of human red cell ghosts markedly aggregated intramembranous particles and permitted labeling of globoside, which appeared in a clustered arrangement. The aggregates of ferritin-anti-globoside differed from those of ferritin-wheat germ agglutinin, a label for glycophorin, which corresponded with the aggregates of intramembranous particles. Double-labeling of human trypsinized ghosts with anti-globoside/ Staphylococcal protein A-colloidal gold and ferritin-wheat germ agglutinin indicated that the patterns of labeling were different and that the aggregates of globoside did not bear a direct relationship to the intramembranous particles, which represent transmembrane proteins. Resealed sheep erythrocyte ghosts labeled with ferritin-conjugated rabbit anti-Forssman showed small clusters of Forssman glycolipid on the erythrocyte surface, which could be markedly aggregated with a second goat anti-rabbit antibody, indicating relative mobility of the small glycolipid domains. The distribution of ferritin-anti-Forssman label in sheep ghosts treated at pH 5.5 to aggregate intramembranous particles also did not show definite correspondence between intramembranous particles and the clusters of ferritin-anti-Forssman.

Antigens, Heterophile↗
PubMed1983

Labeling indices of human lung cancer. Correlation with histologic type and survival.

The labeling index (LI) of tumor specimens from 28 patients (9 primary, 21 metastases) with lung cancer was analyzed after in vivo 3H-thymidine labeling. The mean LI was 11.1 (range, 1.4 to 37.6), and the median was 10.6. The average LI for adenocarcinoma (1.8) was significantly lower than those of small-cell, large-cell and poorly differentiated epidermoid carcinoma (12.8, 11.5 and 13.6, respectively). The variation in LI from site to site was less than 50% in 72% of lesions. Among the nonadenocarcinomas, no significant differences in average LI were observed between primary and metastatic tumors. For 17 previously untreated patients, mean survival times for patients with tumors whose LIs were below and above the mean were 63 and 30 weeks, respectively (0.10 greater than P greater than 0.05).

Adenocarcinoma↗
PubMed1981

Effects of pulse and continuous intravenous infusion of cis-diamminedichloroplatinum on L1210 leukemia in vivo.

The in vivo effects of cis-diamminedichloroplatinum on L1210 leukemia were determined using DNA content distribution analysis by flow microfluorometry and pulse [3H]thymidine labeling indices. Pulse and continuous infusion schedules were investigated. Pulse cis-diamminedichloroplatinum (2 and 6 mg/kg) resulted in progression delay of cells in S and G2 phases and at higher doses (greater than or equal to 12 mg/kg) in G1 as well. Equivalent total doses administered by continuous infusion over 24 to 72 hr delayed cells in G2 with little apparent affect on G1 or S progression. A maximum survival of 70% increased life span over controls was achieved with a 12-mg/kg pulse. Infusion doses at least 2-fold higher were required to achieve similar increases in survival. Cell cycle changes did not predict for therapeutic benefit, suggesting that, at suboptimal doses, cells were capable of repair. The therapeutic index for both modes of administration was narrow.

Animals↗
PubMed1980

The cell cycle kinetics of human breast cancer.

Cell kinetic parameters were determined in 32 patients with breast cancer following intravenous [3H]thymidine injection. The mean labelling index (LI) was 8.6, range 1.2 to 24.1. The LI increased significantly with increased stage of disease. The highest values were noted in patients with chest wall metastases with a mean LI of 15.9. In one patient with multiple discrete tumor foci, the larger foci had significantly decreased LI consistent with classic cytokinetic theory. The intralesional variation in LI was measured in 31 lesions. The average variation of LI/lesion was 1.2. Therefore, three samples should provide a representative LI. The interlesional LI was compared by taking multiple samples of two or three lesions per patient in seven patients. For each patient, there was little variation in mean LI from lesion to lesion. The data suggest that higher LI are associated with a poorer prognosis. Among patients with advanced T4 or metastatic disease, the median survivals for patients with LI less than 8 and greater than or equal to 8 were 79 weeks and 21 weeks, respectively. For patients with metastatic disease, the survivals were 56 and 9 weeks, respectively. The tumor growth fraction analyzed in one patient was 40%. In summary, the growth rate of this cancer in an individual patient is relatively homogeneous and LI may provide important prognostic information. Further studies are required to establish the value of LI in the staging and treatment of breast cancer.

Age Factors↗
PubMed1980

Synchronization of L1210 leukemia with hydroxyurea infusion and the effect of subsequent pulse dose chemotherapy.

Studies were performed to synchronize L1210 tumor cells in S phase in an effort to maximize the effect of subsequent pulse dose chemotherapy. Hydroxyurea (HU) was administered by continuous iv infusion 5 days after tumor implantation. Perturbation effects on the S-phase cells were measured by serial tritiated thymidine labeling indices. Effects on cell-cycle progression were measured by DNA content distribution analysis using flow cytometry. Synchronization of tumor cells was achieved with HU infusion (48 mg/kg/hour x 24 hours), resulting in 90% of the cells in S phase. Following infusion, synchronous progression of S-phase cells into G2/M and then G1 was apparent from +0 to +10 hours later. The susceptibility of HU-synchronized cells to subsequent chemotherapy was determined by treating mice with cytosine arabinoside (Ara-C), methotrexate (MTX), or Adriamycin (ADR) pulse doses at various intervals following infusion. Synergy, measured by prolongation of survival times, resulted when Ara-C was administered immediately after the end of the infusion. Survival times then decreased as the fraction of cells in S phase decreased. In contrast, the survival times of mice treated with MTX or ADR pulse doses after HU infusion were additive at best and did not correlate with fluctuations in the S phase compartment. Therefore, prior synchronization of tumor cells in S phase was therapeutically advantageous when coupled with appropriately timed Ara-C pulse doses. There was little advantage in combining HU infusion with subsequent MTX or ADR therapy.

Animals↗
PubMed1980

A method for establishing prolonged intravenous infusions in mice.

A simple and rapid method for establishing prolonged intravenous infusions in mice was developed. The major advantages of this system were ease of establishing infusions, ability to infuse large numbers of mice simultaneously, low incidence or perivenous infiltration, and little apparent stress to the mouse.

Animals↗
PubMed1978

Dose-dependent cytokinetic changes following 1-beta-D-arabinofuranosylcytosine and hydroxyurea in L1210 and S-180 in vivo.

DNA synthesis inhibition and recovery in L1210 and S-180 ascites tumors following 1-beta-D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (HU) were measured autoradiographically as a basis for optimizing drug schedules. Tumor bearing mice, 10(6) cells day 0, were treated on day 4 with 20, 200 or 2000 mg/kg Ara-C or 50, 300 or 1800 mg/kg HU. At various intervals following drug, [3H]thymidine was administered i.p. and mice were killed 1 hr later. Tumor cells were analyzed for labeling index (LI) and grain count (GC) to determine the percentage of cells in S phase and the distribution of DNA synthesis rates among the labeled cells, respectively. Following each dose of HU, DNA synthesis was inhibited completely. Recovery of LI was rapid and approached control values by 6 hr. Following each dose of Ara-C, DNA synthesis was inhibited completely for at least 6 hr. Recovery of LI was first noted 6 hr following 20 mg/kg Ara-C and 9 hr following 200 mg/kg. Following both doses the LI reached 100% of the control value by 26 hr. GC analysis indicated that following Ara-C treatment, DNA synthesis was reinitiated first with cells with low GC from 6 to 12 hr followed by cells with increasing GC from 12 to 20 hr. The labeling intensity reached control values by 20 hr and an 'overshoot' occurred by 26 hr. These data suggest that the recovery of DNA synthesis rate is a gradual process. Survival data for mice receiving two doses of Ara-C indicated that the optimal interval for retreatment following the lower dose of Ara-C occurred by 6 hr as compared to 12--16 hr for the higher dose. These times coincided in both instances with recovery of LI to 33--50% of control values. Early recovery of LI may be the best method currently available for estimating the optimal time for retreatment with an S phase specific drug.

Animals↗