This experimental study was designed to cause a large dominant visible lesion in the presence of multiple micrometastases from the same colon adenocarcinoma cell line, in order to investigate therapeutic treatments for primary and metastic hepatic malignancies.
In the first experiment, 30 rats were injected either with placebo, 1x104, 1x105, or 1x1016 concentrations of rat colonic carcinoma cells (DHD/K12/TRb) via direct inoculation into the liver parenchyma. The animals were sacrificed 2, 4, or 6 weeks post inoculation.
In the second experiment, 30 rats were injected through the superior mesenteric vein with either placebo, 1x104, 1x105, or 1x1016 concentrations of DHD/K12/TRb cells. The animals were sarificed at 2, 4, or 8 weeks post inoculation.
In the intraparenchymal inoculated group, 52% of the rats developed tumors. The results also showed that incubation time had no differential effect on the number of rats that had tumors, whereas concentration had a strong monotonic effect. 0% (1x104), 55% (1x105), and 100% (1x106) of the rats developed tumors. There were no observable increases in the number of metastases or mean tumor size in the 1x104 or the 1x105 concentration group. However, there appeared to be an increasing number of metastases and a substantially increased mean tumor size in the 1x106 concentration group.
In the superior mesenteric inoculated group 0% of rats developed tumors.
Our findings suggest that injecting 1x106 DHD/K12/TRb cells into the liver parenchyma and incubating for 5 weeks would likely produce solitary 5-8mm tumors with few systemic metastases. Additionally, given our negative findings with the superior mesenteric vein inoculations, further studies using greater than 1x106 cells or temporarily immunocompromising the rats should be used n order to try to produce widespread hepatic metastases.
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