Spontaneous tumor regression in a syngeneic rat model of liver cancer: Implications for survival studies

Manon Buijs, Jean Francois H. Geschwind, Labiq H. Syed, Shanmugasundaram Ganapathy-Kanniappan, Rani Kunjithapatham, Joost W. Wijlemans, Byung Kook Kwak, Shinichi Ota, Mustafa Vali

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To characterize tumor growth of N1S1 cells implanted into the liver of Sprague-Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH7777 cells. Materials and Methods: N1S1 or McA-RH7777 cells were implanted into the liver of Sprague-Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats. Results: Both types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm3 vs 82.3 mm3, respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm3 and 160 mm3 in N1S1 and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%. Conclusions: The model of N1S1 cell implantation in the liver of Sprague-Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.

Original languageEnglish (US)
Pages (from-to)1685-1691
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume23
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • H&E
  • HCC
  • IL
  • hematoxylin and eosin
  • hepatocellular carcinoma
  • interleukin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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