title: Spontaneous tumor regression in a syngeneic rat model of liver cancer: implications for survival studies.
abstract: OBJECTIVE
  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.
  
  
  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 mm(3) vs 82.3 mm(3), respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm(3) and 160 mm(3) 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.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine,600 N. Wolfe St., Blalock 545, Baltimore, MD 21287, USA.
authors.forename: Manon
authors.initials: M
authors.lastname: Buijs
authors.forename: Jean-Francois H
authors.initials: JF
authors.lastname: Geschwind
authors.forename: Labiq H
authors.initials: LH
authors.lastname: Syed
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Ganapathy-Kanniappan
authors.forename: Rani
authors.initials: R
authors.lastname: Kunjithapatham
authors.forename: Joost W
authors.initials: JW
authors.lastname: Wijlemans
authors.forename: Byung
authors.initials: B
authors.lastname: Kook Kwak
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ota
authors.forename: Mustafa
authors.initials: M
authors.lastname: Vali
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality*; D009365:Neoplasm Regression, Spontaneous; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000401:mortality*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D015996:Survival Rate; D014185:Transplantation, Isogeneic; D014463:Ultrasonography