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T Skovsgaard

Publications and source records attributed to T Skovsgaard.

71 records · Page 4Linked to original sources
PubMed1983

Increased uptake of actinomycin D in Ehrlich ascites tumour cells induced by daunorubicin.

The influence of anthracyclines on the uptake of actinomycin D in Ehrlich ascites tumour cells was studied in vitro. The anthracycline daunorubicin significantly increased the [3H]actinomycin D uptake both in whole tumour cells and in isolated nuclei of tumour cells. On the other hand, actinomycin D increased daunorubicin uptake only to a very small degree. Experiments with other intercalating drugs did not influence [3H]actinomycin D binding, suggesting a specific interaction between actinomycin D and the anthracyclines. The mechanism behind this interference is discussed. The increased cellular uptake of actinomycin D in the presence of daunorubicin may have implications for antineoplastic combination chemotherapy.

Animals↗
PubMed1983

Intermittent high-dose aclarubicin in patients with advanced cancer: a phase I study with special reference to cardiac toxicity.

Aclarubicin was given iv every 3 weeks to 21 patients with a variety of solid tumors. Four dose levels were tested: 80, 100, 120, and 140 mg/m2. The median cumulative dose was 270 mg/m2 (range, 80-900). No objective responses were observed. Hematologic toxicity was dose-limiting. All patients experienced moderate to severe gastrointestinal toxicity. Five of 13 patients evaluable for cardiac function showed clinical signs and ECG changes suggestive of cardiac dysfunction. The suggested maximum dose for phase II trials is 120-140 mg/m2 iv given in an intermittent 3-week schedule.

Aclarubicin↗
PubMed1983

Mechanism of resistance to anthracyclines and vinca alkaloids.

Occurrence of cross-resistance between anthracyclines and vinca alkaloids is the rule in experimental tumors with acquired resistance to these drugs. So far, there is no indication that this phenomenon is due to an intracellular mechanism of action common to the two groups of drugs. In nearly all reported studies, acquired experimental resistance and cross-resistance are related to a decreased cellular accumulation of both types of drugs, although other factors also are involved. In Ehrlich ascites tumors, a number of findings at steady-state conditions indicate that the decreased accumulation is dependent on a cellular mechanism for active outward drug transport, which is common to anthracyclines and vinca alkaloids, but changes in inward transport and intracellular binding capacity also contribute. Similar findings have been reported for resistance and cross-resistance in P388 leukemia. Recent results with counteraction of acquired experimental resistance in animal tumors by inhibition of outward drug transport and studies on the effect of different anthracycline derivatives on accumulation of daunomycin in resistant cells are discussed.

Animals↗
PubMed1982

The liver in Hodgkin's disease--I. Clinico-pathological relations.

A retrospective analysis of staging results from 308 patients with Hodgkin's disease (HD) was performed in order to relate clinico-pathological findings with respect to the liver to other staging results and to prognosis. Thirty-four patients had clinically enlarged liver, 80 had increased serum-enzyme levels indicating possible liver damage, but only 10 patients had biopsy-proven histologic evidence of HD in the liver (7 primary biopsies, 3 re-biopsies). Among the prognostic correlations not only advanced stage and liver infiltrates were connected to poor prognosis, but also--even in early stages--elevated serum enzyme values (S-GOT and alkaline phosphate).

Adolescent↗
PubMed1982

The liver in Hodgkin's disease--II. Histopathologic findings.

Histopathologic findings in 459 liver biopsies performed in 308 patients with Hodgkin's disease were reviewed. Typical Hodgkin infiltrates were found in only 11/459 biopsies (2.4%) and infiltrates suspect for Hodgkin's disease in only 8/459 (1.7%), whereas unspecific changes were more common. Lymphocytic infiltration was seen in 47% of the biopsies and focal necrosis in 19%. No correlation could be demonstrated between unspecific changes and clinical characteristics, including prognosis.

Adolescent↗
PubMed1981

Cross resistance and cellular uptake of 4'-O-methyldoxorubicin in experimental tumors with acquired resistance to doxorubicin.

A new analog of doxorubicin, 4'-O-methyldoxorubicin, was previously reported to have a pronounced activity against L1210 leukemia, which shows a natural partial resistance to doxorubicin itself. In the present study, lines of P388 leukemia and Ehrlich ascites tumor with acquired resistance to doxorubicin were found to be cross-resistant to 4'-O-methyldoxorubicin, indicating that the natural and the acquired resistance to doxorubicin involve different mechanisms. In vitro studies on the uptake of 4'-O-methyldoxorubicin in the Ehrlich ascites tumor cells indicated that the observed cross-resistance was partly due to a decreased drug uptake in the resistant cells because of an increased extrusion of the drug, in accordance with previous findings on the mechanism of acquired resistance to doxorubicin.

Absorption↗
PubMed1980

Circumvention of resistance to daunorubicin by N-acetyldaunorubicin in Ehrlich ascites tumor.

Experimental evidence indicates that Ehrlich ascites tumor cells resistant to daunorubicin (DNR) have a higher active drug extrusion than do wild-type cells. In the present study, the possibility of circumventing this mechanism of resistance by addition of an analog of DNR, N-acetyldaunorubicin (N-acetyl-DNR), was investigated in vitro and in vivo. The affinity of N-acetyl-DNR was 7 times lower than that of DNR in the lysates of both wild-type and resistant cells. In agreement with this finding, N-acetyl-DNR reduced the binding of [3H]DNR to lysate from the two cell lines only to a minor extent. On the other hand, N-acetyl-DNR exerted a marked inhibition on both the active efflux and the unidirectional influx of [3H]DNR in both cell lines. Within certain limits, addition of N-acetyl-DNR resulted in increased steady-state uptake of [3H]DNR; in wildtype cells, the maximal obtainable elevation was 18%, compared to 142% in resistant cells. In vivo addition of N-acetyl-DNR, even at 80 mg/kg for 4 consecutive days, did not influence the toxicity of DNR in mice. In a therapeutic experiment, addition of N-acetyl-DNR increased the antitumor activity of DNR upon the resistant tumor line significantly, but no change was observed in the wild-type tumor. These data indicate that N-acetyl-DNR or related analogs may be used as adjuvants to circumvent acquired resistance to DNR.

Animals↗
PubMed1979

In vitro and in vivo study of cross resistance between daunorubicin and daunorubicin-DNA complex in Ehrlich ascites tumor.

The antitumor effect of daunorubicin and of two preparations of daunorubicin-DNA complexes were compared in equitoxic doses against the Ehrlich ascites tumor and in a subline of this tumor resistant to daunorubicin. The therapeutic efficacy of both complexes was significantly better than that of free daunorubicin in the sensitive tumor. The daunorubicin-resistant tumor was found to be cross resistant to both daunorubicin-DNA complexes. In vitro, the steady-state uptake of daunorubicin was considerably lower when the drug was added as a complex compared with addition as free drug. Experiments in which the uptake of daunorubicin and of DNA was determined simultaneously showed no significant uptake of DNA in either cell line. Together, these data indicate that even if daunorubicin is administered as a complex, the membrane transport in Ehrlich ascites tumor cells takes place solely as free drug.

Animals↗
PubMed1978

Clinical trial of rubidazone in solid tumors and malignant lymphomas.

Rubidazone, a semisynthetic daunorubicin derivative, was administered to 33 patients with advanced solid tumors or malignant lymphomas. The doses used were 200, 150, or 100 mg/m2 repeated at 3-week intervals. The antitumor effect was very modest. Partial remission was obtained in only one patient and stable disease was observed for periods of 4--18 weeks in seven additional patients. The major toxic effects were gastrointestinal and myelosuppressive. In two patients, cardiac toxic effects were noted and one patient had an anaphylactic-like reaction. No clinical cross-resistance seemed to exist between rubidazone and adriamycin.

Adult↗
PubMedDate not supplied

Phase II studies of 4'-iodo-4'-deoxydoxorubicin in advanced non-small cell lung, colon and breast cancers.

The new anthracycline analogue, 4'-iodo-4'-deoxydoxorubicin (I-DOX), was administered at 70 mg/m2 as first chemotherapy in 61 patients with advanced NSCL (19), colon (20) and breast cancers (22). Treatment was repeated every 3 weeks; the dose was decreased to 60 mg/m2 (19% of the cycles) or increased to 80 mg/m2 (17% of the cycles) according to the granulocyte count nadir. Partial responses were observed in 6% of the patients with NSCL, in 5.5% of those with colon and in 10% of those with breast cancers. The main toxicity was a selective granulocytopenia characterized by a duration of about 1 week, and a high inter-patient variability. Non-haematological toxicities were mild. The negative results obtained in breast cancer might be related to the dose administered. Further studies in this tumour type should be performed with a more aggressive schedule.

Adult↗
PubMedDate not supplied

Development of resistance to rubidazone (NSC-164011) in Ehrlich ascites tumor in vivo.

Resistance to a new daunorubicin derivative, rubidazone, was developed in a strain of Ehrlich ascites tumor in vivo by treatment with the drug during 11 weekly passages of the tumor. In this tumor reciprocal cross resistance was found between rubidazone, daunorubicin, adriamycin, vincristine, and vinblastine. There was no change in sensitivity of the tumor to methotrexate, 6-mercaptopurine, BCNU, cytosine arabinoside, or actinomycin D. The resistance was stable for at least 71 weeks when treatment was continued and for at least 18 weeks when treatment was discontinued. Rubidazone given intraperitoneally was significantly less toxic than daunorubicin and adriamycin; unlike the findings with daunorubicin and adriamycin, late toxic death (after 30 days) often occurred. In the wild-type tumor the growth inhibition with rubidazone was less than with daunorubicin and adriamycin on an equal weight basis. The LD10 of rubidazone inhibited the growth to nearly the same extent as did the LD10 of daunorubicin and adriamycin.

Animals↗