Nutrition and the cancer patient.
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Biomedical subjects
Publications and source records attributed to G C Easty.
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23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2. Of the 23 patients with active tumours, 7 either had, or have since developed bone metastases; in 4 of these hypercalcaemia also developed. 14 tumours, chosen at random, were tested for in-vitro osteolytic activity in the presence and absence of aspirin, which inhibits prostaglandin synthetase. The activity of 8 of the 9 osteolytically active tumours was significantly, though not completely inhibited by aspirin. Although the number of patients is limited, these results indicate that the in-vitro osteolysis assay may detect substances, perhaps including prostaglandins, produced by breast tumours which affect prognosis and contribute to the subsequent formation of bone metastases.
Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate in vitro bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.
Many patients with advanced non-thyroid malignancies have elevated plasma immunoreactive calcitonin concentrations. Breast and bronchial carcinomas contain immunoreactive calcitonin and an epidermoid bronchial carcinoma has been shown to produce immunoreactive calcitonin in vitro. We have established monolayer cultures of breast carcinomas and eight out of fifteen consecutive carcinomas released immunoreactive calcitonin; some released HCG (human chorionic gonadotrophin) or CEA (carcinoembryonic antigen). In addition, a primary human breast carcinoma has been shown to release and contain calcitonin after being passaged in 'nude' mice over 1 year. Chromatography of extracts and culture media of a bronchical carcinoma demonstrated that, in contrast with the other tumours, it secreted a form or forms of calcitonin having size, charge and immunological differences when compared to calcitonin M. Preliminary evaluation of plasma immunoreactive calcitonin estimations in patients with breast carcinoma showed that twenty-three out of twenty-eight patients with metastatic disease had elevated plasma calcitonin concentrations, whereas only one out of thirteen with localized disease had high levels.
Twenty-three out of 28 patients with metastatic breast carcinoma and one out of 13 patients with localised disease had raised levels of plasma immunoreactive calcitonin. Monolayer cultures of breast carcinomas maintained for up to 10 weeks released immunoreactive calcitonin, and a primary breast carcinoma passaged in "nude" mice for over a year contained material immunologically and chromatographically resembling the monomeric form of human calcitonin. These studies indicate that breast carcinomas can produce calcitonin and that plasma calcitonin measurements may be useful in staging patients with breast carcinomas.
Twenty-eight mammary carcinomata were maintained in organ culture in the presence of various hormones. The effects of the hormones have been assessed histologically by estimation of total dehydrogenases activity of the pentose glycolytic pathway and by the incorporation of tritiated thymidine or uridine into DNA or RNA. No significant effects on tumour cell activity due to hormones have been observed.
The carcinoembryonic antigen (CEA) was produced and released by human colorectal carcinomata and also the normal attached mucosa when maintained in both monolayer and organ culture. Immunoperoxidase cytochemical methods were employed for the cellular localization of CEA which was demonstrable only on the neoplastic cells. Gel filtration and immunological methods confirmed that CEA, produced by normal and neoplastic cells, had properties similar to "authentic" CEA derived from metastatic colorectal carcinomata. In addition, two other CEA cross-reacting macromolecules, neither of which was CCEA-2, were produced by these tumours in culture.
A hypernephroma removed from a male patient who had lost 30 kg in weight in the two months preceding surgery was grown as a non-metastasizing transplantable xenograft in immune-suppressed mice. The tumour produced a considerable weight loss (greater than 25 per cent) in the mice at a stage when it comprised less than 5 per cent of the total body weight. A slight fall in food intake of the tumour-bearing mice was noted, but animals bearing other non-cachectic mouse and human tumours had much lower food intakes without accompanying weight loss. No obvious defects in gastrointestinal absorption were detected nor was any gross increase in basal metabolic rate observed. The precise mechanism producing the severe cachexia remains to be established, but elaboration of humoral factors by the tumour seems probable. This model of cachexia bears a closer relation to the clinical situation than do other experimental animal tumour models currently available.