Monocytes and macrophages in malignant melanoma. I. Peripheral blood macrophage precursorsCurrie, G A; Hedley, D W
doi: 10.1038/bjc.1977.147pmid: 889676
A micro-assay designed to assess the capacity of peripheral blood mononuclear cells to differentiate in vitro into mature macrophages is described. In patients with "final common pathway" malignant melanoma, there was a highly significant deficiency in macrophage precursors (MPs). By conventional morphological criteria such patients did not show a significant monocytopenia. Serum factors do not seem to contribute to the MP defect in the patients. We conclude that these patients have an intrinsic functional defect in their peripheral blood monocytes, but the mechanisms responsible for this defect are as yet unknown.
Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patientsMurray, E; McCarthy, W H; Hersey, P
doi: 10.1038/bjc.1977.148pmid: 19029
Previous studies, using plasmapheresis to remove blocking factors of cell-mediated cytotoxicity to melanoma cells from the circulation of melanoma patients, suggested that leucocyte-dependent antibody to melanoma cells may also be blocked by factors in their sera. The present study confirms these findings, by showing that most patients with disseminated melanoma had melanoma LDA activity in the IgG fraction when this was separated from their sera. This also applied to a high percentage of patients with primary melanoma. Evidence that the blocking factors may be immune complexes was shown by experiments in which LDA activity to melanoma cells was revealed after acidification of melanoma sera to dissociate immune complexes, followed by ultrafiltration through membranes retaining molecules of size greater than 100,000 daltons. Blocking of LDA activity in the retentate recurred when the retentate was recombined with the filtrate. Further studies indicated that the blocking activity showed affinity for the target cell and not the effector cell. Preliminary analysis of the specificity of the blocking suggests that this was similar to that of melanoma antisera. These results appear to show that blocking of LDA activity to melanoma cells is common in melanoma patients and that the assay system may provide a quantitative method for their analysis that may yield information of biological importance in the management of melanoma patients.
Facilitation of nodal metastasis from a non-immunogenic murine carcinoma by previous whole-body irradiation of tumour recipientsHewitt, H B; Blake, E R
doi: 10.1038/bjc.1977.150pmid: 329849
Of 193 CBA mice kept under prolonged observation after excision of small intradermal transplants of a non-immunogenic tumour (CBA Carcinoma NT), 27 (14%) presented with local recurrence, 19 (10%) with regional lymphnodal metastasis (RNM) and 72 (37%), with pulmonary metastasis +/- other systemic metastases. When mice were exposed to sublethal whole-body irradiation (WBI) before tumour transplantation, the incidence of RNM rose to approximately 80% and the latent period was reduced from approximately 60 days to approximately 40 days after tumour transplantation. This enhancement of RNM by WBI was undiminished when the interval between WBI and tumour transplantation was increased from 1 to 90 days. An explanation for this effect in terms of immunosuppression by the WBI is unlikely for the following reasons: the tumour was non-immunogenic by standard quantitative tests, the effect persisted long after the expected time for recovery of immune reactivity, and i.v. injection of normal marrow and lymphoid cells after WBI failed to reduce the effect. That the effect was systemic was proved by failure of local pre-irradiation of the tumour bed or regional node to enhance RNM. The effect was not observed when WBI was given 4 days after excision of tumours. These and other experiments failed to indicate the mechanism of the effect of WBI, but its long persistence suggests that it may relate to stored lethal radiation damage in migrating cells of slow turnover tissues.
Non-specific cytotoxicity of spleen cells in mice bearing transplanted chemically induced fibrosarcomasMantovani, A; Evans, R; Alexander, P
doi: 10.1038/bjc.1977.151pmid: 889683
Spleen cells collected from mice bearing transplanted chemically induced syngeneic fibrosarcomas non-specifically inhibited DNA synthesis of sarcoma and lymphoma target cells in vitro. Splenocytes from mice hyper-immunized against a syngeneic sarcoma specifically inhibited DNA synthesis of the tumour used for immunization. The impairment of tumour-cell DNA synthesis was associated in vitro with cytostasis, and lysis of the target cells was not seen. Since treatment with anti-theta serum and complement did not impair cytostatic action of the spleen cells, and since thymus-deprived animals showed similar activity to normal mice, T lymphocytes were not involved in non-specific cytostasis. Removal of phagocytic adherent cells by carbonyl iron markedly inhibited the cytostatic activity of the spleen cells, suggesting a role in this reaction for cells of the monocyte-macrophage series. The presence of an actively growing sarcoma was a prerequisite for the expression of non-specific cytostasis, since surgical excision resulted in complete disappearance of this activity of spleen cells.
Mechanism of the anti-tumour effect of glucans and fructosans: a comparison with C. parvumBomford, R; Moreno, C
doi: 10.1038/bjc.1977.152pmid: 889684
The anti-tumour activity induced by glucans (lentinan, yeast cell walls, pseudonigeran, dextran, DEAE-dextran and dextran sulphate) and fructosans (levan and carboxymethyl-levan) was compared with the activity of C. parvum. The following effects on tumour systems in CBA mice were assayed: (a) adjuvant activity on the immune response against tumour-specific transplantation antigens (TSTA) with a methylcholanthrene-induced fibrosarcoma, (b) cytostatic activity of peritoneal macrophages against radiation-induced leukaemia cells, and (c) inhibition of tumour nodule formation in the lungs following i.v. injection of fibrosarcoma cells. All the polysaccharides induced cytostatic macrophages, but the dextrans and levans did so only after i.p. and not i.v. injection. Only lentinan, yeast cell walls and pseudonigeran were active in the lung-nodule inhibition test, and only lentinan and dextran sulphate showed slight adjuvant activity for TSTA. It is concluded that the anti-tumour activity induced by these polysaccharides is predominantly non-specific macrophage-mediated and much weaker than that found with C. parvum.
Lymphocyte markers in non-Hodgkin's lymphomasPayne, S V; Smith, J L; Jones, D B; Wright, D H
doi: 10.1038/bjc.1977.154pmid: 329850
The lymphocyte marker pattern of non-Hodgkin's lymphoma cells was related to current concepts of lymphoma classification. In a series of 28 lymphomas lymphocyte markers indicated that 2 were of histiocytic origin, 2 were unclassifiable, none were derived from T cells and the remainder were B-cell neoplasms. The immunoglobulin heavy chain associated with the B-cell tumours was gamma in one case, alpha in one case but was mu in the majority of cases, reflecting the predominance of this heavy chain, together with delta chains, on normal lymph node lymphocytes in man. delta chains accompanied mu chains on the tumour cells in 6/17 lymphomas in which anti-delta staining was performed. delta chains were not found on any lymphomas other than well differentiated diffuse lymphocytic types. There was evidence of a reduction in surface immunoglobulin, Fcgamma and C3 receptors on undifferentiated lymphoma cells. T lymphocytes of normal morphology were present in all lymphomas except one, and were more numerous in follicular lymphomas than in diffuse tumours.
Hamster cells, untreated and treated with chemical carcinogens, maintained in vitro for 2½ yearsPapadopoulo, D; Levy, S; Chamaillard, L; Beesau, O; Hubert-Harbart, M; Markovits, P
doi: 10.1038/bjc.1977.155pmid: 407916
We have maintained in culture, for a prolonged period, untreated hamster cells from whole embryo, foetal brain and lung from newborn animals. Among the 7 lines studied we observed only one spontaneous transformation during the first year of culture. The cells of the 6 other control lines remained normal and diploid, and were not transplantable during the first 9 to 12 months of culture. After the 12th month, changes appeared in their in vitro behaviour and their transplantability: grafts of 0-5-2 X 10(6) cells induced tumours in the hamster, fewer cells did not. in vitro chemically transformed hamster cells were fundamentally different from untreated cells of the same origin, not only in morphological and growth characteristics but also in transplantability, of the 9 lines obtained, 7 induced tumours after injection of 10(1)-10(4) cells, and 2 after injection of 10(5) cells per animal.
Sulphated acid mucopolysaccharides in SV40-transformed human cells from normal and mucopolysaccharidosis patientsWebb, T
doi: 10.1038/bjc.1977.156pmid: 196610
Lines of fibroblasts have been established from normal individuals and from patients diagnosed as suffering from one of the mucopolysaccharidoses or mucopolysaccharide-storage diseases. Transformation of these lines with SV40 virus has been found to reduce their capacity to secrete sulphated mucopolysaccharides into the growth medium. No differences were detected between the individual cell types in their secretory capacity, either before or after viral transformation. A direct relationship was found to exist between the rate of acid mucopolysaccharide production and cell-doubling time. The level of sulphated mucopolysaccharide detected within the cell was also reduced for all cell types after transformation by SV40. Transformed fibroblasts from mucopolysaccharidosis patients, however, showed a relatively greater reduction in storage capacity than those derived from normal individuals.