Search

Peripheral lymphocytes from normal subjects and from patients with impaired T cell function were compared with respect to sialic acid. Mean values for total and neuraminidase-susceptible sialic acid were abnormally high in metastatic cancer patients. Spontaneous release of sialic during incubation of lymphocytes in saline was measured for nine metastatic cancer patients and three non-cancers (two anergy, one sarcoidosis). Mean values for both groups were significantly elevated. Correlation between sialic acid release and clinical status was observed in 11 out of the 12 cases tested. Spontaneously released sialic acid was mainly in protein-bound form in normal and cancer cases but the non-cancer group showed high proportions in free and non-protein-bound form. This latter phenomenon was also observed in all groups, normal and diseased, on exposure of the cells to protease 1 from A. oryzae.

The T lymphocytes populations of 22 young healthy adults, 21 healthy middle aged and older blood donors, 35 non-pregnant women of child bearing age and 14 patients with advanced malignant disease were assessed and compared. It was found that the mean T cell counts in the middle aged and older controls were significantly lower than in the healthy young adults and were further reduced in the patients with malignant disease. The addition of the proteolytic agent brinase (protease 1 obtained from Aspergillus oryzae) to the rosetting test increased the T cell counts signficantly in all groups. This was mot marked in the older age groups and the patients with malignant disease. The proteolytic agent is shown to exert its effect on the lymphocytes in the test. Slow intravenous infusion of either brinase or streptokinase into patients with malignant disease is shown to result in increased T lymphocyte counts pari passu with a restoration of skin allergy. The significance of these findings and possible mode of action of the proteolytic agents in increasing T cell activity are discussed.

The value of the oral anticoagulant warfarin sodium and fibrinolytic agents is discussed in relation to cancer surgery. A controlled trial of 128 patients showed that in a variety of recurrent cases the addition of warfarin to chemotherapy doubled the 2-year survival rate. The best results were obtained in postmenopausal patients with breast cancer. Warfarin depresses cellular immune responses which might militate against its use for cases undergoing "curative" surgery. Instead, induction of fibrinolysis by streptokinase or Brinase is suggested, because it increases the activity of the cellular immune mechanism. The results to date of an ongoing controlled randomized trial of streptokinase with surgery of tumors of the large bowel are presented, showing that the trends are in favor of streptokinase therapy; however, insufficient time has elapsed to make it, as yet, statistically significant. The action of streptokinase-induced plasmin and Brinase on lymphocytes is described.

A method of testing for neutralisation of the cancer coagulative factor is described. Of a wide range of substances tested, protamine sulphate, placentalα 1 globulin and placental albumin were found to possess activity worthy of clinical investigation in the treatment of cancer. Plasmin is also highly active in counteracting the clotting effect of the cancer coagulative factor. Its probable mode of action is unspecific proteolysis, comparable with its effect on many of the recognised factors concerned in coagulation of the blood.

The coagulative activity of cancers is in general higher, often much higher, than that of the tissues from which they spring.