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Biomedical subjects

E R Blake

Publications and source records attributed to E R Blake.

11 recordsLinked to original sources
PubMed1978

Stability of transplanted murine tumour systems after storage of cells at -196 degrees C for up to 13 years.

Two murine lymphomas of spontaneous origin were stored in liquid N2 as cell suspensions in DMSO for 8 and 13 years respectively. Isogenic transplantation assays done some years before freezing and immediately after thawing indicated no measurable loss of clonogenic cells during freezing, storage or thawing; the number of cells required for 50% successful transplantation remained close to unity in both cases. The overall data revealed no evidence of an alteration of the receptivity of the mouse colonies over a period of 13 or 20 years. We attribute this remarkable stability to close supervision of the systems within a single laboratory.

Animals↗
PubMed1978

Failure of preoperative C. parvum vaccine to modify secondary disease following excision of two non-immunogenic murine carcinomas.

Sadler and Castro (1976) reported that a single dose of C. parvum vaccine given i.p. or i.v. to mice 4 days before excision of subcutaneous transplants of Lewis lung carcinoma significantly reduced the incidence of lung metastases in the operated mice. In similarly designed experiments, using 2 different carcinomas of spontaneous origin in our own inbred mouse colonies, we were unable to demonstrate any influence of C. parvum vaccine on the incidence or latent period of secondary disease in operated mice. We discuss possible reasons for our failure to reproduce the findings of Sadler and Castro.

Adenocarcinoma↗
PubMed1977

Facilitation of nodal metastasis from a non-immunogenic murine carcinoma by previous whole-body irradiation of tumour recipients.

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.

Animals↗
PubMed1977

Further studies of the relationship between lymphatic dissemination and lymphnodal metastasis in non-immunogenic murine tumours.

In all 6 different murine tumours of spontaneous origin, a high proportion (22-95%) of the regional lympgh nodes draining small intradermal tumours gave rise to tumours after their isogeneic transplantation as whole nodes. In separate experiments with 4 of these tumours, equivalent tumour-bearing mice had their tumours surgically excised and were observed for the development of regional nodal corresponding frequency of tumour formation by transplanted nodes. After high-dose radiotherapy of intradermal carcinomas, there was a progressive fall in the incidence of positive regional node transplants from 48 to 96 h after irradiation. It is concluded that continual lymphatic dissemination of viable cancer cells is characteristic of malignant tumours, but that there is a relatively small chance of such cells giving rise to nodal metastatic growth. Related studies showed that the ability of a small number of cancer cells to give rise to tumours was very much greater if they were incorporated in a lymph node at transplantation than if they were transplanted directly as a suspension.

Animals↗
PubMed1976

A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin.

Extensive experience with isotransplants of 27 different tumours (leukaemias, sarcomata, carcinomata), all of strictly spontaneous origin in laboratory bred mice of low cancer strains CBA/Ht and WHT/Ht, has revealed no evidence of tumour immunogenicity. Of approximately 20,000 maintenance transplants, none failed and none regressed; of almost 10,000 carefully observed tumours arising from small or minimal inocula of tumour cells, none spontaneously regressed. The number of injected viable tumour cells required to give a 50% probability of successful transplantation (the TD50) ranged from approximately 1 cell to greater than 10,000 cells among the 27 tumours; high TD50 values, which were dramatically reduced by various procedures having no immunological significance, did not signify active "resistance" of the hosts. In the case of all of 7 randomly selected tumours, prior "immunization" of recipients with homologous lethally irradiated cells increased their tumour receptivity. Several experiments using various tumours failed to give evidence that immunity could be non-specifically induced or that a massive preponderance of lymphocytes from specifically sensitized mice could inhibit tumour transplantation or growth in vivo; no trace of "resistance" to tumour was adopted by isogeneic recipients of lymphocytes from regional nodes of tumour bearers. A limited review of the recent literature on tumour immunity shows that practically all the animal data presented in support of a general theory of tumour immunogenicity or to provide a basis for active clinical immunotherapy have been obtained from transplanted tumour systems which entail artefactual immunity associated with viral or chemical induction of the tumours or their allogeneic transplantation. It is suggested that isotransplants of spontaneously arising tumours are the only appropriate models of human cancer and that any genuine rapport between the animal laboratory and the clinic requires their exclusive use.

Adjuvants, Immunologic↗
PubMed1973

The transplantation kinetics of tumour cells.

The data from a dilution assay can be used not only to form an estimate of the TD50 (or log TD50), but also to throw light on the transplantation kinetics of tumours. Transplantation "by single cells" is the simplest sort of kinetics, and some tumours, of which we have given two examples, will transplant by single cells. Other tumours consistently transplant with anomalous kinetics-i.e. non-single-cell. A sensitive statistical test for single-cell behaviour has been developed, and we give three examples of tumours that clearly fail the test. The mechanism by which these anomalous tumours depart from single-cell behaviour is unknown, but we suggest an approximate statistical analysis for their assay.

Animals↗
PubMed1971

Effect of induced host anaemia on the viability and radiosensitivity of murine malignant cells in vivo.

Within 48 hours of the institution of severe phenylhydrazineinduced anaemia in mice bearing ascites tumours or generalised leukaemia, a substantial proportion of the malignant cells disappeared respectively from the peritoneal cavity or infiltrated liver. The results of radiobiological experiments permitting determination of the proportion of viable leukaemia cells which were severely hypoxic and relatively radioresistant in the livers of leukaemic mice, showed that induction of anaemia was associated with a several hundredfold increase in the proportion of such cells. The proportion of hypoxic cells was greatly reduced when the anaemic leukaemic mice were transfused with packed erythrocytes or allowed to breathe oxygen under high pressure. Similar experi - ments with solid sarcomas indicated that a high proportion of the tumour cells were hypoxic in non-anaemic mice breathing air. The hypoxic fraction was not significantly reduced when tumour-bearing mice were made severely anaemic during growth of the tumour and were later transfused. Thus, the hypoxic cells in leukaemic livers and those in solid tumours are markedly different in their capacity for oxygenation following the induction of relative hyperoxaemia.

Anemia, Hemolytic↗