Abstract
Primary hepatocarcinoma is the most common type of malignant tumor and a leading cause of cancer mortality. Standard treatment for patients with advanced primary hepatocarcinoma for whom surgery is not recommended includes transcatheter arterial chemoembolization (TACE). Within these patients 44% develop metastasis within 1 year. Thus, understanding the events underlying the recurrent tumors and developing therapies in conjunction with TACE would be of great benefit. Reducing tumor angiogenesis by combining the somatostatin analog octreotide with small doses of heparin is one approach in decreasing metastasis rates by targeting VEGF and heparinase, respectively. Given this, we investigated whether a heparin and octreotide combination treatment administered post-TACE would decrease the tumor metastasizing rate in primary hepatocarcinoma. A total of 147 patients diagnosed with primary hepatocarcinoma were admitted to the study and received 2–4 TACE treatments and were monitored for 1 year. Of these 84 received the heparin plus octreotide combination treatment and 63 did not (control group). All patients were monitored for adverse reactions, coagulation ability, and tumor metastasis. We found a significant decrease in the incidence of tumor metastasis in patients receiving the combination treatment post-TACE for up to 1 year with no significant toxic or adverse effects. Thus, we propose using the combination treatment of heparin and octreotide post-TACE in the treatment of recurrent tumorigenesis in primary hepatocarcinoma.
Similar content being viewed by others
References
Dank, M. (2010). Treatment of primary hepatocellular carcinoma. Orvosi Hetilap, 151(36), 1445–1449.
Xiong, Z. P., Yang, S. R., Liang, Z. Y., et al. (2004). Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Hepatobiliary and Pancreatic Disease International, 3, 386–390.
Guan, Y. S., & Liu, Y. (2006). Interventional treatments for hepatocellular carcinoma. Hepatobiliary and Pancreatic Disease International, 5(4), 495–500.
Takayasu, K., Arii, S., Ikai, I., et al. (2006). Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology, 131(2), 461.
Zhang, J. W., Feng, X. Y., Liu, H. Q., Yao, Z. W., Yang, Y. M., Liu, B., et al. (2010). CT volume measurement for prognostic evaluation of unresectable hepatocellular carcinoma after TACE. World Journal of Gastroenterology, 16, 2038–2045.
Zhou, X. D. (2002). Recurrence and metastasis of hepatocellular carcinoma: Progress and prospects. Hepatobiliary and Pancreatic Disease International, 1, 35–41.
Tang, Z. (1999). Recurrence and metastasis. A focus of the study of primary liver cancer. Chinese Journal of Hepatobiliary Surgery, 5, 3–5.
TenCate, H., Timmerman, J. J., & Levi, M. (1999). The pathophysiology of disseminated intravascular coagulation. Thrombosis and Haemostasis, 82, 82–713.
Zheng, Q., Tang, Z., & Xue, Q. (1998). Effect of heparins on tumor growth and metastasis in human liver cancer metastasis in nude mice model. Journal of Chinese Hepatology, 6, 151–152.
Drixler, F. A., Borel, R. I. H. M., Ritchie, E. D., et al. (2000). Continuous administration of angiostatin inhibits accelerate growth of colorectal liver metastases after partial hepatectomy. Cancer Research, 60(6), 1761–1765.
Sanderson, R. D., Yang, Y., et al. (2004). Heparan sulfate proteogly-cans and heparanase partners in osteolytic tumor growth and metastasis. Matrix Biology, 23(6), 341–352.
Qu, Y., Zhang, S., Xu, X., Wang, H., et al. (2009). Octreotide inhibits choroidal neovascularization in rats. Ophthalmic Research, 42(1), 36–42.
Huang, J., Duan, Q., Fan, P., et al. (2010). Clinical evaluation of targeted arterial infusion of verapamil in the interventional chemotherapy of primary hepatocellular carcinoma. Cell Biochemistry and Biophysics, 59(2), 127–132.
Jia, W. D., Xu, G. L., Wang, W., et al. (2009). A somatostatin analogue, octreotide, inhibits the occurrence of second primary tumors and lung metastasis after resection of hepatocellular carcinoma in mice. Tohoku Journal of Experimental Medicine, 218(2), 155–160.
Jia, W. D., Xu, G. L., Xu, R. N., et al. (2003). Octreotide acts as an antitumor angiogenesis compound and suppresses tumor growth in nude mice bearing human hepatocellular carcinoma xenografts. Journal of Cancer Research and Clinical Oncology, 129(6), 327–334.
Professional committee of Chinese anti-cancer association of liver cancer. (2001). Clinical diagnostic/staging criteria of primary liver cancer. Zhonghua Gan Zang Bing Za Zhi, 9(6), 324.
Zhou J (2003). Practical Tumor Sciences. Medicine (2nd edition) Beijing: People’s Medical Publishing House. p 47.
Trotti, A., Byhardt, R., Stetz, J., Gwede, C., Corn, B., Fu, K., et al. (2000). Common toxicity criteria: Version 2.0. An improved reference for grading the acute effects of cancer treatment: Impact on radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 47(1), 13–47.
Cohen, E., Atzmon, R., Vlodavsky, I., & Ilan, N. (2005). Heparanase processing by lysosomal/endosomal protein preparation. FEBS Letters, 579(11), 2334–2338.
Vlodavsky, I., & Friedmann, Y. (2001). Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. Journal of Clinical Investigation, 108(3), 341–347.
Goldshmidt, O., Zcharia, E., Abramovitch, R., et al. (2002). Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis. Proceedings of National Academy of Sciences USA, 99(15), 10031–10036.
Cui, J., Dong, B. W., Liang, P., Yu, X. L., & Yu, D. J. (2004). Effect of c-myc, Ki-67, MMP-2 and VEGF expression on prognosis of hepatocellular carcinoma patients undergoing tumor resection. World Journal of Gastroenterology, 10(10), 1533–1536.
Xu, G., Fu, B., & Xu, R. (2004). Effect of somatostatin on expression and synthesis of vascular endothelial growth factor of human hepatoma cell line BEC-7420. Chinese Journal of Surgery, 11(22), 1527–1538.
Liu, J., & Yi, J. (2007). Relationship between the changes of VEGF level and dendritic cells in peripheral blood of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization. Journal of Huazhong University of Science and Technology [Medical Sciences], 27(1), 58–60.
Li, X. R., Yang, Z. F., & Yi, J. L. (2006). Expression of CD44v6 and vascular endothelial growth factor in hepatocellular carcinoma after transcatheter hepatic arterial chemoembolization. Shijie Huaren Xiaohua Zazhi, 14(13), 1305–1308.
Xiong, Z. P., Yang, S. R., Liang, Z. Y., et al. (2004). Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Hepatobiliary and Pancreatic Disease International, 3(3), 386–390.
Smorenburg, S. M., & Van Noorden, C. J. (2001). The complex effects of heparins on cancer progression and metastasis in experimental studies. Pharmacological Reviews, 53(1), 93–105.
Kragh, M., Binderup, L., Vig Hjarnaa, P. J., et al. (2005). Non anti-coagulant heparin inhibits metastasis but not primary tumor growth. Oncology Reports, 14(1), 99–104.
Yoshitomi, Y., Nakanishi, H., Kusano, Y., et al. (2004). Inhibition of experimental lung metastases of Lewis lung carcinoma cells by chemically modified heparin with reduced anticoagulant activity. Cancer Letters, 207(2), 165–174.
Wang, C. H., Tang, C. W., Liu, C. L., et al. (2003). Inhibitory effect of octreotide on gastric cancer growth via MAPK pathway. World Journal of Gastroenterology, 9(9), 1904–1908.
Author information
Authors and Affiliations
Corresponding author
Additional information
Weidong Jia and Kehai Feng are co-first authors.
Rights and permissions
About this article
Cite this article
Jia, W., Feng, K., Fan, P. et al. Post-TACE Combination Therapy of Heparin and Octreotide Results in Decreased Tumor Metastasis in Extrahepatic Tumorigenesis. Cell Biochem Biophys 62, 35–40 (2012). https://doi.org/10.1007/s12013-011-9255-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-011-9255-8