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S Cao

Publications and source records attributed to S Cao.

117 records · Page 7Linked to original sources

Proliferation kinetics and specific behaviour of G2 cells of the Bp8 mouse ascites sarcoma in vivo.

Growth characteristics of the Bp8 ascites sarcoma were investigated by means of evaluation of total cell number, the cellular DNA content, the mitotic index and the percentage of dead cells. Following intraperitoneal inoculation of 18 x 10(6) cells into NMRI mice a plateau level of about 1400 x 10(6) cells was reached after 7 days followed by a daily decline of 5 per cent up to day 14, the terminal stage of life. Based on the increase of the cell number and the distribution of cells in the cell cycle the flow rate through and the duration of the various parts of the cell cycle were calculated. Generally, the durations of all phases of the cell cycle including mitosis increased with age, most markedly after day 8 when the durations tended to become infinite. At the plateau phase the total number of G1, S-phase and mitotic cells decreased significantly while G2 cells remained at a constant level. This finding may be of interest in view of the concept of ascites tumour cells behaving as a regulated cell system.

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Growth kinetics of Bp8 mouse ascites sarcoma after single dose whole body irradiation. I. Analysis of the relative and total numbers of cells in various parts of the cell cycle.

The effects of irradiation on the growth of the Bp8 mouse ascites sarcoma were analysed following doses of 1.75, 2.5, 5.0 and 8.0 Gy. From the total number of cells and the percentage of cells in G1, S-phase, G2 + M as measured by flow cytofluorometric DNA analysis and the mitotic index the total number of cells in the various parts of the cell cycle was estimated. After an initial delay in the increase in the cell numbers during the period of rapid growth the total number of cells shows a dose dependent decrease at the plateau stage of the ascites growth. This dose relationship is characterized by a shoulder type of curve with a D0 of about 6.5 Gy and Dq of about 2 Gy. This decrease in the total number of cells is caused by a decreasing number of G1, S-phase and mitotic cells while G2 cells generally remain at unchanged levels. This behaviour of the G2 cells reflects the preference of long-lasting blocking events in G2 of the cell cycle but may also indicate specific regulating processes linked to this type of cell. The ratio between the number of mitotic and G2 cells also decreases in a dose dependent way and is a sensitive indicator for irradiation effects even below the lowest dose (1.75 Gy) used in the present experiments.

Animals↗

Growth kinetics of Bp8 mouse ascites sarcoma after single doses of whole body irradiation. II. Analysis of the progression of cells through the cell cycle.

Bp8 ascites sarcoma cells growing in vivo were whole body irradiated with doses of 1.75 to 8 Gy. The inflow and outflow rates of cells in the various compartments of the cell cycle were estimated on the basis of sequential analysis of the total number of cells and from the proportion of cells in G1, S-phase, G2 and M. The flow through the compartments was calculated from these data and from the sizes of the cell pools. The durations of the mitotic delay, the G1-depletion and the early G2 blockage were linearly related to the dose. After release of the mitotic division delay the accumulation rate of cells in M and G1 decreased linearly with the dose; for G2, plateau values for the accumulation rate were found after 2.5 Gy. The outflow rates from G2 and M after release of the G2 blockage showed a shoulder type of dose-response with a D0 of 2.5 Gy and a n value of 1.5. In addition to an increase in the duration of G2, generally responsible for the increase in the total cell cycle time at about 24 hours after irradiation and an increase in the duration of the S-phase up to 12 hours after irradiation, an early increase in the duration of G1 and M was observed.

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Behaviour of the Bp8 mouse ascites sarcoma after partial body irradiation.

Mice bearing the Bp8 mouse ascites sarcoma were 4 days after inoculation irradiated with 2.5, 5 and 8 Gy. By shielding the head and the upper part of the thorax the mice survival, compared with whole body irradiation, was markedly prolonged and the behaviour of the ascites tumour could be evaluated up to 30 days after inoculation. While about 10 days after irradiation the total number of tumour cells started to decrease and amounted to only 4 per cent 20 days later, the ascites volume increased up to 30 ml. Using flow-cytometric cellular DNA analysis, the proportions of cells in the various parts of the cell cycle were determined. After an initial G2 blockage, a partial blockage with an increase proportion of G2 cells was found up to 20 days after inoculation. While the total number of G1, S-phase and mitotic cells started to decrease on day 10, the total number of G2 cells was independent of the dose and was constant up to day 18. This behaviour may indicate specific regulating processes linked to G2 cells.

Animals↗

Radiation therapy of nasopharyngeal carcinoma.

Carcinoma of the nasopharynx is one of the most frequent malignant tumors in the southern parts of China. A total of 3 263 cases treated with irradiation in the course of the thirty years since the Liberation have been analysed retrospectively. The 5-year survival rate has risen from 27.7 per cent for cases treated during 1955 to 1960 to 54 per cent for those treated in 1973. The technique of irradiation is described, emphasizing the importance of suitable techniques for the treatment of the cervical lymph nodes. The value of elective irradiation of cervical regions not involved clinically is elucidated. Finally, the causes of failure of treatment are discussed.

Cobalt Radioisotopes↗

Some observations on the localization of mitomycin C-induced aberrations in human lymphocytes.

Actively cycling human lymphocytes were treated with mitomycin C for 1 h (1.4 micrograms/ml) and then grown in medium containing 10 micrograms/ml bromodeoxyuridine. Serial 5-h colcemid accumulation samples were taken up to 35 h and the air-dried methaphase spreads stained for replication banding. A complete cell-cycle subphasing analysis was made, and classified cells scored for all categories of chromatid-type aberrations and their location. In spite of the high dose which produced massive delay and cycle perturbation, there was no evidence for selective lethality of early-S cells, in fact such cells were in excess. Extreme localization of aberrations to late-replicating (mostly centromeric) regions was found at all subphases and in pre-S cells. This rules out 'localization by default' as an explanation for the observed preferential occurrence of 'break points' in these regions. The frequency of incomplete intrachanges, low in late S, rises dramatically in early S to become maximal in pre-S cells.

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DNA immunization of infants: potential and limitations.

DNA immunization is a relatively new and efficacious approach to vaccination. Only recently have we begun to test the efficacy of DNA vaccines in infants. DNA vaccines for a retrovirus, hepatitis B, influenza, rabies, measles, tetanus toxoid, and sendai virus, have now been proven to induce cellular and humoral immune responses in infant animals. Here we review the field of DNA immunization of newborn animals, some new promising immunization strategies, and the rapid progress obtained in this field.

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Rationale for treatment design: biochemical modulation of 5-fluorouracil by leucovorin.

Preclinical in vitro and in vivo results have demonstrated the conditions required for optimal modulation of 5-FU activity by LV. The ability to increase intracellular concentrations of higher chain length polyglutamates was a function of duration of longer exposure to LV rather than the dose. In rats bearing advanced colorectal tumors, the role of LV dosage was more clearly evident with the weekly 5-FU treatment schedule than with the daily schedule. Phase III clinical trials in patients with advanced colorectal cancer demonstrated that low-dose and high-dose LV (daily x 5) and weekly high-dose LV schedules yielded similar response rates with different toxicity profiles. A phase III trial demonstrated significant therapeutic advantages for a bimonthly schedule of high-dose LV over a monthly schedule of low-dose LV. Taken together, these results provide insight into LV biomodulation, but the optimal conditions for these regimens for individual patients remain undetermined. To date it has not been possible to identify the optimal conditions for modulation of 5-FU by LV in individual patients with advanced colorectal cancer, and response rates are comparable. A regimen that offers the opportunity to manage treatment-induced toxicity is recommended. With diarrhea being the primary dose-limiting toxicity with the weekly 5-FU and high-dose LV (manifested during the 2-3 weeks of treatment), management of toxicity can be achieved by delaying treatment, by dose reduction, and/or by treatment with octreotide47 without compromising efficacy. In contrast, with the daily x 5 schedule, multiple toxicities (mucositis [stomatitis], diarrhea, neutropenia, and hand and foot syndrome) are manifested regardless of the dose of LV administered. An additional advantage to the weekly schedule is that it provides the opportunity to use 5-FU/LV treatment in sequence or combination with other drugs, such as topoisomerase I inhibitors (CPT-11), antifolates (methotrexate, trimetrexate), and platins (oxaliplatin).

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