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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 199 records · Page 11Linked to original sources

Recycling of resting cells in the JB-1 ascites tumour after treatment with 1-beta-D-arabinofuranosylcytosine (ara-C).

Resting cells in tumours present a major problem in cancer chemotherapy. In the plateau phase of grwoth of the murine JB-1 ascites tumour (i.e. 10 days after 2-5 X 10(6) cells i.p.) large fractions of non-cycling cells with G1 and G2 DNA content (Q1 and Q2 cells) are present, and the fate of these resting cells was investigated after treatment with 1-beta-D-arabinofuranosylcytosine (Ara-C). The experimental work of growth curves, percentage of labelled mitoses curves after continuous labelling with 3H-TdR, and cytophotometric determination of single-cell DNA content in unlabelled tumour cells. Treatment with an i.p. single injection of Ara-C 200 mg/kg in the plateau JB-1 tumour resulted in a significant reduction in the number of tumour cells 1 and 2 days later as compared with untreated controls, while no difference in the number of tumour cells was observed after 3 days. In tumours prelabelled with 3H-TdR 24 hr before Ara-C treatment, a significant decrease in the percentage of labelled mitoses was observed 6-8 hr later followed by a return to the initial value after 12 hr, and a new pronounced fall from 20 hr after Ara-C. The second fall in the percentage of labelled mitoses disappeared when the labelling with 3H-TdR was continued also after Ara-C treatment. Cytophotometry of unlabelled tumour cells prelabelled for 24 hr with 3H-TdR before Ara-C treatment showed 20 hr after Ara-C a pronounced decrease in the fraction of Q1 cells paralleled by an increase in the fraction of unlabelled cells with S DNA content. The results indicate recycling of resting cells first with G2 and later with G1 DNA content, which contribute to the regrowth of the tumours.

Animals↗

Vincristine (NSC-67574) in the treatment of small-cell anaplastic carcinoma of the lung.

In a phase II trial the effect of vincristine as a single agent was evaluated in patients with small-cell anaplastic carcinoma of the lung. The dosage of vincristine was 1.5 mg/m2/week given iv for 4 weeks, followed by 1.5 mg/m2 given every other week with dose modifications according to neurologic tolerance. Nineteen of 27 patients included in the study were evaluable. Objective response was observed in eight patients (42%) including three who were not previously treated and five who were previously treated. The median duration of response was 60 days (range, 21-182 days) with the response always occurring within 4 weeks. This study demonstrates that vincristine is an active agent for small-cell anaplastic carcinoma without cross resistance to CCNU, cyclophosphamide, or methotrexate.

Aged↗

Phase II study of vinblastine, adriamycin, and procarbazine in small cell carcinoma of the lung.

Twenty-four patients with small cell carcinoma of the lung were treated with a combination of vinblastine, 5 mg/m2 iv on Day 1; adriamycin, 40 mg/m2 iv on Day 1; and procarbazine, 100 mg/m2 orally on Days 1-7. The courses were repeated every 21 days. Tumor regression was noted in five of eight previously untreated patients, in two of six patients with previous chemotherapy, and in one of ten patients with previous chemotherapy and irradiation. The median duration of response was 130 days (range, 42-488+ days). The major toxic effects were bone marrow depression, gastrointestinal disturbances, and alopecia. This drug combination deserves consideration for inclusion into sequential combination chemotherapy regimens used in the treatment of this tumor type.

Adult↗

Cytokinetic variations during ageing and regenerative growth in the jb-1 ascites tumour studied by impulse cytophotometry.

The variation in the DNA distributions in the murine JB-1 ascites tumour was investigated by means of impulse cytophotometry (ICP) on days 2, 4, 7, 10 and 14 after i.p. inoculation of 2.5 times 10-6 tumour cells and on days 1, 2, 3 and 4 after aspiration of the main part of 10-day plateau tumours. The study showed that a considerable fraction of cells with a DNA content of about 2 and 4 n (p smaller than 0.001) accumulated from day 2 to 10. During the same period the fraction of cells in S decreased significantly (p smaller than 0.001). One and two days after aspiration, a rapid rearrangement in the distribution pattern occurred, leading to a predominance of cells with S DNA content, while the fraction of cells around 2 n and 4 n decreased. Three and four days after aspiration the cells again accumulated around the 2 and 4 n values while the fraction of cells with S DNA content decreased. The ICP results were in agreement with our data obtained by autoradiography and Feulgen microspectrophotometry, and ICP is recommended as a rapid and statistically precise method in cytokinetic analysis.

Animals↗