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.

Placental-type alkaline phosphatase in cervical neoplasia.

Monoclonal antibodies reactive with placental-type alkaline phosphatase have formed the basis of methods for detection of this oncodevelopmental antigen in patients with pre-invasive and invasive cervical neoplasia, with or without evidence of papilloma virus infection. Disease-related elevations of placental-type alkaline phosphatase were not observed in patients' sera. Solubilised cervical smears or biopsy material, and cervical mucus swabs, often contained substantial amounts of this isoenzyme; however, there was no significant difference between any of the patient and control groups. Thus, serological and smear test assays for placental-type alkaline phosphatase were not useful in differential diagnosis of cervical lesions. However, its presence in most biopsy specimens, often at high levels, indicated possible application for in vivo radioimmunoimaging studies of invasive or metastatic cervical cancer.

Reduction of vincristine toxicity by Cronassial.

A mixture of gangliosides (Cronassial) protects against the chronic but not the acute lethal toxicity of vincristine in mice and affords some protection against the acute lethal toxicity of vincristine in chicks. The protective effect of Cronassial appears to be greatest near the LD50 of vincristine and then diminishes as the dose of vincristine increases further. Cronassial does not, however, reduce the vincristine antitumour activity, so that the net effect is an improvement in the vincristine therapeutic index. Clinical trials are underway to examine the effect of the combination on the development of neurotoxicity in cancer patients.

Placental-type alkaline phosphatase in human seminal plasma from fertile and infertile men.

Solid-phase enzyme immunoassays, based on monoclonal antibodies reactive with different forms of human placental-type alkaline phosphatases, were applied to their detection in human seminal plasma from fertile and infertile men. The placental-like form of alkaline phosphatase (PLAP-like AP), known to occur in testicular tissue, was found in normal seminal plasma. The incidence of detection and levels of this isoenzyme correlated significantly with the designated fertility status of the donor. Seminal plasma (PLAP-like AP) may reflect germ cell function and/or access of testicular products to the ejaculate.

Effect of AT1727 on growth and metastasis of murine tumours.

AT1727 was tested on 5 different murine tumour systems. Compared with its analogue, razoxane, AT1727 was less effective at multiple low doses against sarcoma 180 and L1210 leukaemia. A single high-dose treatment with AT1727 was, however, more active than razoxane. AT1727 inhibited the growth of the Lewis lung primary tumour and significantly reduced the number of pulmonary metastases. Although AT1727 showed a slight inhibitory effect on the growth of the B16 primary, it had no effect on the metastases.

Sodium dynamics in a northern ecosystem.

Analyses of terrestrial sources of sodium and estimates of the sodium requirement of moose (Alces alces) on Isle Royale, Lake Superior, suggest that availability of the element controls the moose population. The terrestrial vegetation is very poor in the element, but, as elsewhere, submerged and floating leaved water-plants are relatively rich. Consumption of such plants in summer would provide an adequate source, if the animal can store the element. The fairly high sodium contents of freshwater vegetation have been little appreciated. In general, sodium concentration in water-plants, unlike that of potassium, is not correlated with chloride but the latter is ordinarily in excess of the sodium, so that uptake of the latter implies an equivalent supply of NaCl.