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T. Masui, H. Nakanishi, K. Inada, T. Imai, Y. Mizoguchi, H. Yada, M. Futakuchi, T. Shirai and M. Tatematsu, “Highly Metastatic Hepatocellular Carcinomas Induced in Male F344 Rats Treated with N-Nitrosomorpholine in Combination with Other Hepatocarcinogens Show a High Incidence of p53 Gene Mutations Along with Altered mRNA Expression of Tumor-Related Genes,” Cancer Letters, Vol. 112, No. 1, 1997, pp. 33-45. doi:10.1016/S0304-3835(96)04543-0

has been cited by the following article:

• TITLE: Animal Model of Lung Metastasis of Hepatocellular Carcinoma: A Tool for the Development of Anti-Metastatic Therapeutics

  AUTHORS: Mitsuru Futakuchi

  KEYWORDS: Lung Metastasis; Hepatocellular Carcinoma; NF-κB Inhibitor

  JOURNAL NAME: Journal of Cancer Therapy, Vol.4 No.2A, February 28, 2013

  ABSTRACT: We observed that N-nitrosomorpholine (NMOR) given after a multi-carcinogenic treatment induces liver carcinomas with 56% lung metastasis. An additional treatment with diethylnitrosamine (DEN) with NMOR further enhanced the incidence of hepatocellular carcinoma (HCC) with lung metastasis. We have further revised the duration of NMOR treatment to establish an animal model with a simple experimental protocol and an appropriate experimental duration to facilitate investigation exploring the mechanisms of HCC metastasis and development of anti-metastatic therapeutics. We observed that DEN exposure followed by a 16-week treatment with NMOR to be a most efficient protocol for the induction of HCC metastasizing to the lung. In this review, we will discuss about the usefulness of animal models for induction of highly metastatic HCC and the assessment of the efficacy of anti-metastatic therapeutics. Additionally, we will also discuss use of these models in analysis of individual steps in the metastatic process by using non-steroidal anti-inflammatory drugs, aspirin and indomethacin, two nuclear factor kappa B (NF-κB) inhibitors, pentoxifylline and N-acetyl-L-cysteine.