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At least 55 records · Page 3Linked to original sources
PubMed1997

Increase in immunoreactivity for endothelin-1 in blood vessels of rat liver metastases: experimental sarcoma and carcinoma.

Using electron immunocytochemistry, blood vessels in the normal rat liver and in 2 different animal models of liver metastases: (1) Hooded Lister rat with MC28 tumour, a sarcoma, and (2) nude rat with HT29 tumour, a carcinoma, were investigated for the presence of endothelin-1. In the normal livers, small subpopulations of vascular endothelial cells displayed discrete immunoreactivity for endothelin-1. In the livers with malignant tumours, there was a substantial increase in endothelin-1-immunoreactive endothelial cells in vessels located at the tumour periphery. In the controls, antibody to endothelin-1 also labelled sporadically some fibroblast/fibroblast-like cells associated with the blood vessels. In contrast, intense immunoreactivity for endothelin-1 was frequently associated with the tumour cells and/or fibroblast cells in both types of tumour examined.

Animals↗
PubMed1997

Experimental pulmonary sarcoma metastases in athymic nude mice.

BACKGROUND: Pulmonary metastases remain a challenging therapeutic problem in the treatment of patients with soft tissue sarcomas. A pulmonary sarcoma metastases animal model might facilitate studying the biology of metastases, diagnosis, and treatment modalities of this disease. Intravenous injection of human tumor cells into nude mice has been reported using human melanoma and colorectal carcinoma to produce pulmonary metastases. Human fibrosarcoma cells were intravenously administered to athymic nude mice to simulate clinical pulmonary metastases. METHODS: HT-1080 human sarcoma cells derived from a poorly differentiated fibrosarcoma were used to prepare inoculant at a concentration of 5 x 10(6) cells per ml. Male athymic nude mice were injected subcutaneously with 1 x 10(6) cells in the right hind flank and sacrificed when the tumors were 1-2 cm in diameter. Age- and weight-matched athymic nude mice were intravenously injected through tail veins with 10(4), 10(5), and 10(6) cells. The mice were sacrificed at 7, 14, and 21 days after intravenous injection of the tumor cells. Tissues were histologically examined for pulmonary metastases. RESULTS: Neither gross nor microscopic spontaneous metastases were found in any of the animals that received subcutaneous xenografts, and no pulmonary metastases were identified in mice intravenously injected with < 10(5). All mice inoculated with 10(6) cells developed tumor colonies in the lungs, which were microscopically evident as early as day 7. No metastases were found in the liver, spleen, heart, or other tissues. In a second experiment, HT-1080 cells were injected at 10(6); all animals developed lung metastases and died of lung tumor involvement, with an average survival of 35 days. CONCLUSIONS: These experiments identify a sarcoma animal pulmonary metastases model that is readily available, relatively inexpensive, easily utilized, and reproducible.

Animals↗
PubMed1996

Sustained release of adriamycin from implanted hydroxyapatite blocks for the treatment of experimental osteogenic sarcoma in mice.

A sustained-release drug delivery system was developed using a hydroxyapatite (HA) block loaded with adriamycin (ADR) by cenrifugation. Release of ADR was sustained for 66 days in vitro and for 4 weeks in vivo following intramuscular implantation in mice. ADR concentrations in plasma, liver, and kidney were from 0.25% to 10% of that at the implantation site. ADR-HA blocks implanted into osteogenic sarcomas in mice markedly inhibited tumor growth. This drug delivery system provides sustained release of the cancer chemotherapeutic agent and may prove useful for treating malignant tumours while minimising systemic side effects.

Animals↗
PubMed1995

Isolated single-lung perfusion: a study of the optimal perfusate and other pharmacokinetic factors.

BACKGROUND: Isolated single-lung perfusion with doxorubicin hydrochloride was shown to be effective in clearing experimental sarcoma lung metastases in the rat. The best perfusate to be used for isolated lung perfusion and factors affecting the final lung concentration of doxorubicin are the subject of the present study. METHODS: In experiment 1, 60 animals were randomized to undergo isolated left lung perfusion with doxorubicin with six different perfusates (n = 10 per group): saline, low-potassium-dextran, 5% albumin, 6% hetastarch, 5% buffered albumin, and 6% buffered hetastarch. Five animals served as negative controls. After perfusion, the lung wet to dry ratio and final lung doxorubicin concentration were determined. In experiment 2, 60 animals underwent isolated left lung perfusion with either 80 micrograms/mL or 320 micrograms/mL of doxorubicin. Animals were perfused at either 0.5 mL/min or 1 mL/min and for 2, 6, or 10 minutes. At the end of the perfusion period, the left lung doxorubicin concentration was measured. Statistical analysis included analysis of variance, the Duncan test for multiple comparisons, and multiple linear regression analysis. Significance was defined as a p value of less than 0.05. RESULTS: In experiment 1, perfusion with 6% buffered hetastarch resulted in the lowest lung wet to dry ratio, significantly different from all groups except the controls. Perfusion with low-potassium-dextran solution led to the highest final lung concentration of doxorubicin. In experiment 2, a model to predict final lung doxorubicin concentration was constructed: Log (final lung concentration) = 1.9 + 0.0071.P + 0.186.T, where P is the measured perfusate concentration of doxorubicin, and T is the time of perfusion in minutes. The R2 was 0.91 and p, less than 0.001. The dose of doxorubicin per kilogram of animal body weight, the dose of doxorubicin per square meter of body surface area, the total amount of doxorubicin delivered, and the rate of perfusion did not meet the criteria to enter the equation. CONCLUSIONS: Isolated lung perfusion experiments should use 6% buffered hetastarch as the perfusate. The perfusate doxorubicin concentration and the duration of perfusion are the only factors determining the final lung concentration of doxorubicin. In lung perfusion experiments, the dose of chemotherapy is not as important as the perfusate concentration and the duration of the perfusion. Animals should be perfused at a lower rate so the lungs are exposed to less doxorubicin without changing the final lung concentration.

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