Eur J Pediatr Surg 2013; 23(05): 400-404
DOI: 10.1055/s-0033-1333637
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Increased Expression of Survivin in Hepatoblastoma after Chemotherapy

Shuichiro Uehara
1   Department of Pediatric Surgery, Osaka University, Osaka, Japan
,
Takaharu Oue
1   Department of Pediatric Surgery, Osaka University, Osaka, Japan
,
Miyoko Kawatsu
1   Department of Pediatric Surgery, Osaka University, Osaka, Japan
,
Keigo Nara
1   Department of Pediatric Surgery, Osaka University, Osaka, Japan
,
Masahiro Fukuzawa
1   Department of Pediatric Surgery, Osaka University, Osaka, Japan
› Author Affiliations
Further Information

Publication History

17 October 2012

08 December 2012

Publication Date:
26 February 2013 (online)

Abstract

Background Survivin, an inhibitor of apoptosis, has been reported to be associated with a worse prognosis in some malignancies. However, its expression in hepatoblastoma (HB) remains to be elucidated. We assessed the survivin expression in HB specimens collected before and after chemotherapy to elucidate the impact of survivin on the outcome of HB therapy.

Methods HB specimens were collected before and after 2 to 4 cycles of cisplatin-based chemotherapy from 16 patients. The survivin expression level was assessed by immunohistochemical staining and real-time polymerase chain reaction.

Results Out of 16, 12 HB sections collected before chemotherapy were positive for survivin as determined by immunohistochemical staining. The intensity of survivin expression was found to significantly increase after chemotherapy. Surprisingly, all of the HB specimens obtained after chemotherapy were positive for survivin. The expression of survivin messenger ribonucleic acid from a human HB cell line, Huh-6 was significantly higher when the cells were cultured with cis-diamminedichloroplatinum(II) than when the cells were cultured without the drug.

Conclusion Our results indicate that most of the primary HB tissue specimens express survivin, and its expression increased after chemotherapy, thus suggesting that survivin may concern with the survival of tumor cells, therefore be a candidate for the target of the treatment of HB.

 
  • References

  • 1 Perilongo G, Shafford E, Plaschkes J. Liver Tumour Study Group of the International Society of Paediatric Oncology. SIOPEL trials using preoperative chemotherapy in hepatoblastoma. Lancet Oncol 2000; 1: 94-100
  • 2 Stiller CA, Pritchard J, Steliarova-Foucher E. Liver cancer in European children: incidence and survival, 1978-1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42 (13) 2115-2123
  • 3 Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3 (8) 917-921
  • 4 Tamm I, Wang Y, Sausville E , et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58 (23) 5315-5320
  • 5 Ito R, Asami S, Motohashi S , et al. Significance of survivin mRNA expression in prognosis of neuroblastoma. Biol Pharm Bull 2005; 28 (4) 565-568
  • 6 Kappler M, Köhler T, Kampf C , et al. Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients. Int J Cancer 2001; 95 (6) 360-363
  • 7 Hishiki T, Matsunaga T, Sasaki F , et al. Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT. Pediatr Surg Int 2011; 27 (1) 1-8
  • 8 Sasaki F, Matsunaga T, Iwafuchi M , et al; (Japanese Study Group for Pediatric Liver Tumor).. Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: A report from the Japanese Study Group for Pediatric Liver Tumor. J Pediatr Surg 2002; 37 (6) 851-856
  • 9 Wang Z, Xie Y, Wang H. Changes in survivin messenger RNA level during chemotherapy treatment in ovarian cancer cells. Cancer Biol Ther 2005; 4 (7) 716-719
  • 10 Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003; 22 (53) 8581-8589
  • 11 Mita AC, Mita MM, Nawrocki ST, Giles FJ. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res 2008; 14 (16) 5000-5005
  • 12 Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer 2008; 8 (1) 61-70
  • 13 Tang H, Shao H, Yu C, Hou J. Mcl-1 downregulation by YM155 contributes to its synergistic anti-tumor activities with ABT-263. Biochem Pharmacol 2011; 82 (9) 1066-1072
  • 14 Tsuruma T, Hata F, Torigoe T , et al. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J Transl Med 2004; 2 (1) 19
  • 15 Burris III HA, Moore MJ, Andersen J , et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15 (6) 2403-2413
  • 16 Guo Q, Chen Y, Zhang B, Kang M, Xie Q, Wu Y. Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition. Biochem Pharmacol 2009; 77 (11) 1674-1683
  • 17 Tsuruma T, Hata F, Torigoe T , et al. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J Transl Med 2004; 2 (1) 19