A Biochemical Concept of Tumour Growth, Infiltration, and Cachexia

Abstract

MBmicTJo= oestrogen excreted by the four patients who failed to benefit from operation (Table II) was 7 ,ug./24 hours-a value slightly higher than the mean level for all patients in this category, and higher than the mean pre-operative level of patients obtaining remission at hypophysectomy (Table 1). There are not enough patients in the series for these findings to have any statistical significance, but there may be a tendency for patients with a low pre-operative oestrogen level to benefit from hypophysectomy while those with a high level do not. Further work is needed to check the validity of this suggestion.In two instances patients who had been previously treated by oophorectomy and adrenalectomy were subjected to hypophysectomy. In neither case was oestrogen detected in the urine either before or after hypophysectomy, yet in both patients their objective regressions were short. Unless they were excreting amounts of oestrogen not detectable by the chemical method, these results suggest a direct participation of pituitary hormones in the maintenance of human breast cancer, as opposed to an indirect trophic effect on target organs. Similarly, in the patient already referred to (Case 7) objective regression occurred in spite of continued oestrogen excretion. Again, this result is explicable on the assumption that the levels of growth hormone, prolactin, or both had been reduced below a critical level.In the four patients referred to in Table II the most simple explanation for the failure of hypophysectomy to influence the growth of the breast cancer is the continued excretion of oestrogens due to incomplete hypophysectomy.We have, as yet, been unable to study the transition from remission to relapse in this series. However, Hortling et al.(1957), using the vaginal-smear technique, found that oestrogen secretion increased simultaneously with the deterioration of the patient's clinical condition.The explanation of failure or success following endocrine ablation for breast cancer must be largely speculative until we are able to assess directly the functional capacity of the human hypophysis with a reasonable degree of precision.The results of the investigations on the small number of patients in the present series suggest that repeated biochemical estimation of oestrogens before hypophysectomy may prove to be of some value in forecasting the clinical outcome of this operation.Continued post-operative excretion of oestrogen, by indicating incomplete removal, suggests that no significant clinical palliation is likely to occur, while cessation of oestrogen excretion would suggest the reverse. The exceptions to these generalizations provide cogent reasons for supposing that the growth of some human breast cancers is maintained by the direct action on the tumour cells of anterior pituitary hormones. Summary The effect of hypophysectomy on the clinical state and on oestrogen excretion has been studied in 15 women and one man with metastatic breast cancer.Patients obtaining regression following hypophysectomy tended to ...

The inhibition of accumulation of [1-14C]glycine and its incorporation into protein of Ehrlich ascites-carcinoma cells by dl-methionine

“…It can therefore be supposed that when cancer cells, which possess a strong ability to accumulate amino acid, find themselves close to normal cells they cause, among other things, such imbalance, which leads to damage and destruction of cells. Some authors (Wiseman & Ghadially, 1958;Quastrel & Bickis, 1959) consider this to be one of the main processes responsible for the infiltration of malignant neoplasm and subsequently of cachexy of the organism.…”

As You Like It, Part 3: A Critique and Historical Review of Calcification as Seen with the Electron Microscope

“…The appearances seen are more in keeping with the idea that a gradual atrophy of normal tissue occurs at the tumor± normal interface and that it is probably engendered by a competitive withdrawal or``starving´´of normal cells of nutrients by tumor cells. This hypothesis, proposed by us ( on basis of biochemical studies ) in 1957 and 1958 [ 16,17 ], is now reiterated almost 30 years later by others [ 15 ]. The ludicrousness of the proposition by Carr et al [ 13 ] that spherical microparticles are extruded lysosomes responsible for tumor in ltration is also evidenced by the fact that spherical microparticles are ubiquitous entities seen much more frequently in nonneoplastic than neoplastic tissues.…”

Cancer cachexia - A review.

“…4,6 It was postulated that those tumors which are only slightly more active than the normal in their ability to concentrate amino-acids will grow slowly and produce only minor metabolic disturbances, while the more active ones will infiltrate faster, cause anorexia, and produce rapid cachexia and eventual death. 12 Anorexia is a common manifestation of cancer and the hypothalamus and probably other parts of the brain produce anorexigenic peptides. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumorbearing host are responsible for the genesis of the anorexia.…”