Liver metastasis model

R. Van Hillegersberg, J.W. Van den Berg, W.J. Kort, O.T. Terpstra, J.H. Wilson (1992). Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. Gastroenterology, 103, 647-651. 

In addition, DE-310 (qdxl) exhibited potent antitumor effects against human tumor xenografts in mice, and also significantly prolonged survival in the lung metastasis model (3LL) and in the liver metastasis model (M5076). 

Slooter GD, Breeman WAP, Marquet RL, Krenning EP, Van Eijck CHJ. Anti-prolifera-tive effect of radiolabelled octreotide in a metastasis model in rat liver. Int J Cancer 1999 81 767-771. 

Rashidi, B., Gamagami, R., Sasson, A., Sun, F.X., Geller, J., Moossa, A.R., and Hoffman, R.M. (2000) An orthotopic mouse model of remetastasis of human colon cancer liver metastasis. Clin. Cancer Res. 6, 2556-2561. 

Immunohistochemical studies relate polysialic acid-NCAM expression to tumor malignancy in neuroblastoma, alveolar rhabdomyosarcoma [189], neuroendocrine lung tumors [190], Wilm s tumor [191], aggressive colon cancers [192], and pancreatic cancer [193]. In studies on the role of polysialic acid in tumor cell behavior, endosialidase has been used as a tool to remove polysialic acid from the surface of cells and tumors. In a metastasis model using human rhabdomyosarcoma TE671 cells, endoNA injected intraperitoneally reduces the expression of polysialic acid and the number of lung and liver metastases formed from intraperi-toneal primary tumors [194]. For comparison, the effect was not seen with intramuscular primary tumors that cannot be reached by the intraperitoneally injected endosialidase. 

Orally administered 4-[3,5-bis(trimethylsilyl)phenylcarboxamido]benzoic acid (Am555S, or TAC-101) [143] reduced liver metastasis in experimental models in mice by decreasing liver weight and nodule number, thereby prolonging life [144]. These models included AZ-521 human gastric adenocarcinoma in male BALB/c nu/nu mice and Co-3 human colon adenocarcinoma in male KSN nude mice. 

In a mouse model of liver metastasis, B717 siRNA complexed with LIC-101 administered by tail vein injection almost completely suppressed the growth of HT-1080 cells, a human fibrosarcoma cell line, at a dose of 1 mg/kg (Fig. 4, left). No effect was produced by naked B717 or LIC-101 alone (Fig. 4, right). In contrast, a dose of 4.2 mg/kg was required for the same effect with antisense DNA (Fig. 4, left) [71]. We suspect that the effect observed at this high dose was nonspecific. 

Fig. 4 Antitumor activity in a mouse model of liver metastasis. Mice were inoculated with HT-1080 cells by direct intrasplenic injection on day 0. Spleens were removed 10 min after inoculation. Each compound was administered by tail vein injection from day 4 to day 8 and from day 11 to day 15 (two 5-day cycles of daily injections). The inhibitory effect of the treatments on the increase in liver weight was evaluated on day 20. Left B717 siRNA or antisense DNA complexed with LlC-101. Right Naked B717 or LIC-101 alone. In sham mice, the spleen was exposed but no cells were injected. Control mice were treated with 10% (w/v) maltose solution. significantly different from control alP < 0.02...

One of the obvious advantages of orthotopic models is that targeting processes involved in local invasion (e.g., angiogenesis) can be undertaken at a clinically relevant site (36). Since the early studies showing orthotopic transplantation of colon tumors and metastasis to the liver (39), tumor xenografts have been grown orthotopically in mice. However, despite the clinical relevance of orthotopic models, their utilization is hindered by a need for a high level of technical skill, time and cost. Therapeutic efficacy is also more difficult to assess with orthotopic models in contrast to the relative ease of subcutis tumor measurements (36). 

Bresalier, R. S., Hujanen, E. S., Raper, S. E., Roll, F. J., Itzkowitz, S. H., Martin, G. R. and Kim, Y. S. (1987). An animal model for colon cancer metastasis establishment and characterization of murine cell lines with enhanced liver-metastasizing ability. Cancer Res. 47, 1398-1406. 

Agard C, Ligeza C, Dupas B, Izembart A, El Kouri C, Moullier P, etal. (2001) Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. Cancer Gene Ther 8 128-136... 

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