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. 2008 Mar;2(1):116-23.
doi: 10.1007/s12072-007-9040-3. Epub 2008 Jan 29.

Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma

Koichi Obara  1 , Nobuyuki Matsumoto, Masaru Okamoto, Minoru Kobayashi, Hiroki Ikeda, Hideaki Takahashi, Yoshiki Katakura, Kotaro Matsunaga, Toshiya Ishii, Chiaki Okuse, Michihiro Suzuki, Fumio Itoh
Affiliations

Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma

Koichi Obara et al. Hepatol Int. 2008 Mar.

Abstract

Background: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a thermoablative technique to kill tumor tissue by generating areas of coagulative necrosis. Recent reports have raised concern that RFA may lead to a local recurrence of HCC with an aggressive phenotype and unfavorable prognosis, suggesting that RFA may induce further malignant transformation of HCC. However, the biological effects of RFA on HCC cells have not been directly analyzed. The aim of this study was to determine whether heat stress of the type associated with RFA induces malignant transformation of HCC.

Methods: We assessed the sensitivity of three HCC cell lines (HepG2, Alexander, and Huh7) to heat treatment for 10 min. We then determined the temperature at which a heat-resistant subline can be generated. We established and expanded sublines that survived heat treatment. And their proliferation rates, heat sensitivities, and invasive capacities were further examined.

Results: All HepG2 died after 48 degrees C treatment, whereas 49 degrees C treatment was required to kill all Alexander and HuH7. We generated 20 sublines for each parental cell line. A HepG2 subline, HepG2#18, proliferated 100% faster than parental HepG2. Moreover, HepG2#18 survived after 50 degrees C treatment, whereas all parental HepG2 died after heat treatments at 48 degrees C or higher.

Conclusion: Our results showed that even a single heat treatment could induce further transformation of an HCC cell line. Our results suggest that an insufficient treatment of HCC by RFA that enables survival of some cells might induce further malignant transformation in vivo.

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Figures

Fig. 1
Fig. 1
Time courses of cell numbers after heat treatment. Heat treatments were performed at temperatures from 37°C to 55°C. Cell numbers was assessed 0, 4, 40, and 72 h after the heat treatments
Fig. 2
Fig. 2
Fourteen days of continuous culture after heat treatments revealed that there is a clear threshold at which to obtain total cell kill by a short-time heat treatment. Cells were cultured for 14 days after heat treatments, and Tetracolor One assay was then performed
Fig. 3
Fig. 3
Evaluation of effects of heat treatments on HCC cells by Trypan blue dye exclusion test. The ratios of alive cell numbers in total HCC cells were calculated. (a) HepG2 before heat treatment. (b, c) HepG2 4 and 72 h after 45°C treatment. (d, e) HepG2 4 and 72 h after 50°C treatment. (f, g) HepG2 4 and 72 h after 55°C treatment. (h) HuH7 before heat treatment. (i, j) HuH7 4 and 72 h after 45°C treatment. (k, l) HuH7 4 and 72 h after 50°C treatment. (m, n) HuH7 4 and 72 h after 55°C treatment. (o) Alexander before heat treatment. (p, q) Alexander 4 and 72 h after 45°C treatment. (r, s) Alexander 4 and 72 h after 50°C treatment. (t, u) Alexander 4 and 72 h after 55°C treatment
Fig. 4
Fig. 4
Proliferation rates of sublines derived from (a) HepG2, (b) HuH7, and (c) Alexander. Twenty sublines were established from each of the three HCC cell lines. Proliferation rate during 3 days of culture was calculated. Relative proliferation rates of the sublines were compared with those of the parental cell lines. A HepG2 subline, HepG2#18, proliferated more than 100% faster than parental HepG2
Fig. 5
Fig. 5
Heat sensitivities of HepG2 and sublines derived from HepG2. The heat sensitivities of five HepG2 sublines were compared with that of parental HepG2. Surviving cell number was assessed 72 h after heat treatments at increasing temperature. HepG2#18 obviously showed heat resistance
Fig. 6
Fig. 6
Invasive capacities of HepG2 and sublines derived from HepG2. The invasive capacities of sublines were compared with that of parental HepG2. There were no significant differences between HepG2 and the sublines
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References

    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1053/gast.2002.33411', 'is_inner': False, 'url': 'https://doi.org/10.1053/gast.2002.33411'}, {'type': 'PubMed', 'value': '12016426', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/12016426/'}]}
    2. Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 2002;122:1609–19. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '11268953', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11268953/'}]}
    2. Buscarini L, Buscarini E. Therapy of HCC-radiofrequency ablation. Hepatogastroenterology 2001;48:15–9. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/S0929-8266(01)00128-8', 'is_inner': False, 'url': 'https://doi.org/10.1016/s0929-8266(01)00128-8'}, {'type': 'PubMed', 'value': '11369527', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11369527/'}]}
    2. Livraghi T, Lazzaroni S, Meloni F. Radiofrequency thermal ablation of hepatocellular carcinoma. Eur J Ultrasound 2001;13:159–66. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1111/j.1365-2036.2006.02932.x', 'is_inner': False, 'url': 'https://doi.org/10.1111/j.1365-2036.2006.02932.x'}, {'type': 'PubMed', 'value': '16696801', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/16696801/'}]}
    2. Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma—an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 2006;23:1535–47. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1097/01.mog.0000218961.86182.8c', 'is_inner': False, 'url': 'https://doi.org/10.1097/01.mog.0000218961.86182.8c'}, {'type': 'PubMed', 'value': '16550039', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/16550039/'}]}
    2. Marrero JA. Hepatocellular carcinoma. Curr Opin Gastroenterol 2006;22:248–53. - PubMed

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