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Biomedical subjects

K Hellmann

Publications and source records attributed to K Hellmann.

105 records · Page 6Linked to original sources
PubMedDate not supplied

Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia.

Mice given mitozantrone (MTZ) in doses close to the LD100 (high dose, HD) all survive if they also receive at the same time a mixture of four defined gangliosides--Cronassial (CRN). The protective action of CRN against the toxic effects of MTZ is not accompanied by a reduction of the antitumour activity of MTZ; on the contrary the reduced toxicity permits higher doses of MTZ to be given with the result that better antitumour activity can be achieved. This is illustrated by the highly effective action of MTZ and CRN in preventing the appearance of Lewis lung carcinoma (3LL) metastases, a tumour against which MTZ when used alone is inactive even at maximum tolerated doses (MTD). However, the effect of the combination on the primary 3LL is less pronounced. HD-MTZ and CRN are also more effective than MTD-MTZ alone in preventing dissemination and proliferation of L1210 leukaemia. Although the mechanism of the CRN protective effect is as yet unclear it appears that CRN prevents the lethal effects of necrotizing enteritis produced by HD-MTZ. It is concluded that CRN by reducing MTZ toxicity without interfering with its activity increases the therapeutic index of MTZ and permits an expanded exploration of its dose response curve against a variety of malignancies.

Animals↗
PubMedDate not supplied

Effect of RA233 alone and combined with radiation on experimental tumour metastasis. Part 1.

The effect of the platelet aggregation inhibitor RA233 alone or in combination with radiation was investigated on the spontaneously metastasizing B16 melanoma and on the Lewis lung carcinoma. The effect of this, agent on intravenously injected cells from these tumours was also studied. When single viable 3LL or B16 melanoma cells were injected intravenously, RA233 significantly increased the number of 3LL lung colonies but decreased significantly the B16 lung colonies. RA233 alone did not influence the number of pulmonary metastases arising spontaneously from the B16 or 3LL tumours either with the primary in situ or following excision. When lungs were irradiated before implantation of the 3LL an increase in the number of metastases resulted. This increase was unaffected by RA233 administration. When the primary B16 was irradiated 14 days after implantation and excised 7 days later, a significant decrease in numbers and distribution of metastases resulted in animals treated with RA233. This was accompanied by a considerable increase in long-term survivors.

Animals↗
PubMedDate not supplied

Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases.

Metrazol enhanced the penetration of two proteins (125I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.

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PubMedDate not supplied

Antitumor effect of RA233 alone and combined with radiotherapy.

The effect of RA233 alone or in combination with radiation was investigated in vivo on the S180 sarcoma, the B16 melanoma and the Lewis lung carcinoma. The combined treatment was a significant improvement over radiation alone for the B16 and S180 tumours. RA233 alone did not influence the growth of these tumours. When the primary 3LL was irradiated, tumour size was unaffected but the number of pulmonary metastases was reduced. They were further reduced by the combination of RA233 and radiation. The number, volume and cytokinetics of the B16 cells and the 3LL cells were affected to varying degrees by RA233. The significance of these changes relative to the effects of RA233 are discussed.

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PubMedDate not supplied

Metrazol enhances brain penetration and therapeutic efficacy of some anticancer agents: implications for brain metastases.

The concurrent administration of Metrazol (60 mg/kg, i.v.) to anaesthetized rats enhances the cerebral penetration of the anticancer agent razoxane. Such an enhancement leads to an increase in the therapeutic efficacy of razoxane against intracerebrally sequestered L1210 leukaemia cells in mice. The combination of Metrazol and melphalan was also examined to see if the concentration of other anticancer agents in CSF could be enhanced.

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PubMedDate not supplied

Effect of razoxane on metastases from colorectal cancer.

At a median follow-up of 5 years, adjuvant razoxane (125 mg b.d.) given 5 days/week indefinitely following resection of colorectal cancer provided no benefit in terms of survival or recurrence for Dukes' A or B patients when compared to untreated controls. However in Dukes' C patients this treatment reduced the recurrence rate (P = 0.05) and possibly increased survival time (P = 0.08). Analysis now of the development of metastases in this trial which entered 272 patients over 7 years shows that in the Dukes' C group the incidence of liver metastases in the razoxane-treated patients is only about half that of the untreated patients (18 per cent versus 34 per cent) and that the time to first appearance of the liver metastases is twice as long in the razoxane-treated group as it is in the untreated group (80 weeks versus 40 weeks). It is concluded that the benefit of adjuvant razoxane observed in the Dukes' C patients is due to the antimetastatic activity of the drug in reducing and slowing down the development of hepatic secondaries.

Antineoplastic Combined Chemotherapy Protocols↗