Studies on bone formation during transplantation of an experimental osteogenic sarcoma.
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The effects of blood transfusion, blood components, and surgical trauma on the growth of an experimental sarcoma have been examined. Recipient animals were inbred adult female WAB rats, which received allogeneic transfusions from inbred adult female PVG rats, syngeneic blood from inbred colony-mates, or saline infusions. Small volume transfusions (1-4 ml) of whole blood had no effect on tumour growth, but growth of the MC7 sarcoma was significantly enhanced following allogeneic transfusions of 5 ml whole blood, or when 4 ml was combined with sham laparotomy. Maximal enhancement of tumour growth occurred when 4 ml transfusions of allogeneic washed cells were given, but allogeneic plasma was also able, to a lesser degree, to enhance tumour growth. These data confirm that blood transfusion may enhance growth of the MC7 sarcoma, that the effect may be dose dependent, and synergistic with the immunosuppression of surgery. Many components of an allogeneic transfusion may be responsible for this effect.
The response of an experimental sarcoma to single doses and two fractions of x-rays and fast neutrons has been investigated to test the hypothesis that slowly shrinking sarcomata will reoxygenate poorly and therefore will benefit more from fractionated neutron treatment than from fractionated x-ray treatment, in contrast with rapidly shrinking carcinomata. Neutrons were approximately three times more effective than x-rays, both for single doses and for two fractions given in 48 hours, when regrowth was used as a measure of response. This observation is closely similar to results previously obtained on a rat fibrosarcoma and contrasts with previous results from a mouse mammary carcinoma, and is in agreement with the hypothesis.
We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.
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Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected controls over a 21-day experimental period. Before challenge, immunoreactive plasma fibronectin was 1050-1150 μg/ml. Minimal tumour growth occurred until 6 days after tumour challenge. There was then a rapid increase in primary tumour size, especially over the 7-14-day interval, with a plateau of growth over the 18-21-day interval. Immunoreactive plasma fibronectin was significantly (P < 0·05) raised at 3 and 7 days after tumour challenge. A rapid rise (P < 0·001) to 2816·6 ± 158·9 μg/ml was observed at 14 days followed by a modest decline at 21 days. Bioassayable opsonic activity increased (P < 0·5) with the rise in immunoreactive fibronectin 3 and 7 days after tumour challenge, but the rapid rise in immunoreactive fibronectin over the 7-14-day interval was associated with a significant (P < 0·5) fall in bioassayable opsonic activity. Thus, the rapid rise in immunoreactive plasma fibronectin parallels the rapid rate of tumour growth, but is associated with a fall in opsonically active plasma fibronectin. Dissociation between immunoreactive and opsonically active plasma fibronectin may be mediated by inhibition and/or alteration of circulating fibronectin during rapid tumour growth. Alternatively, it may reflect increased release of antigenically related protein (i.e. cell-surface fibronectin) during rapid tumour growth, which may have limited biological opsonic activity.
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BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.
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The antifungal antibiotic, prumycin, was studied for antitumor activity against several tumor systems. It was found to possess potential antitumor activity against a well-established mouse mammary adenocarcinoma in C3H/He mice. It was also active in prolongation of the lifespan of mice bearing P-388 lymphocytic leukemia. Moreover, prumycin did not depress the white blood cell counts in the mouse peripheral blood. However, severe alopecia was observed in mice treated with this agent at dosage level near the LD50.
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