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Article

Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology

  • Authors:
    • Jehoon Yang
    • Kyoung Doo Song
    • Jae-Hun Kim
    • Geun-Ho Im
    • Seulgi Yoon
    • Misun Namgung
    • Jung-Hyun Hwang
    • Jung Hee Lee
    • Dongil Choi
  • View Affiliations / Copyright

    Affiliations: Department of Medical Science, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea, Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Suwon, Republic of Korea, Laboratory Animal Research Center, Samsung Biomedical Research Institute, Suwon, Republic of Korea, Department of Chemistry, Hankook University of Foreign Studies, Seoul, Republic of Korea
  • Pages: 1425-1431
    |
    Published online on: September 18, 2013
       https://doi.org/10.3892/mmr.2013.1690
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Abstract

Angiogenesis inhibition is an attractive therapeutic strategy in the management of solid tumors. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are key factors in growth and neovascularization of hepatocellular carcinoma (HCC). Brivanib is a novel, orally available dual tyrosine kinase inhibitor that selectively targets the key angiogenesis receptors VEGF‑R2, FGF‑R1 and FGF‑R2. Recently, high‑resolution magic angle spinning magnetic resonance spectroscopy (HR‑MAS MRS) has provided the opportunity to investigate more detailed metabolic profiles from intact tissue specimens that are correlated with histopathology and is thus, a promising tool for monitoring changes induced by treatment. In the present study, 1H HR‑MAS MRS and immunohistochemistry were used to investigate the antitumor efficacy of brivanib in HCC xenograft models. Tumor growth was significantly suppressed in brivanib‑treated mice compared with the controls and treatment was associated with the inhibition of angiogenesis, increased apoptosis and inhibition of cell proliferation. Furthermore, HR‑MAS techniques showed altered metabolic profiles between the two groups. HR‑MAS spectra demonstrated a significant decrease in choline metabolite levels in the treated groups, concurrent with decreased cell proliferation and increased apoptosis. The results showed that 1H HR‑MAS MRS provides quantitative metabolite information that may be used to analyze the efficacy of brivanib treatment in Hep3B tumor xenografts. Thus, the HR‑MAS MRS technique may be a complementary method to support histopathological results and increase its potential for use in the clinic.
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1 

Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 82:4–6. 1990. View Article : Google Scholar : PubMed/NCBI

2 

Ferrara N: Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 9(Suppl 1): 2–10. 2004. View Article : Google Scholar

3 

Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Kerbel RS: Tumor angiogenesis. N Engl J Med. 358:2039–2049. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R and Rusnati M: Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 16:159–178. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Turner N and Grose R: Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 10:116–129. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R and Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009. View Article : Google Scholar

9 

Diaz-Padilla I and Siu LL: Brivanib alaninate for cancer. Expert Opin Investig Drugs. 20:577–586. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Huynh H, Ngo VC, Fargnoli J, Ayers M, Soo KC, Koong HN, Thng CH, Ong HS, Chung A, Chow P, Pollock P, Byron S and Tran E: Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res. 14:6146–6153. 2008. View Article : Google Scholar

11 

Marathe PH, Kamath AV, Zhang Y, D’Arienzo C, Bhide R and Fargnoli J: Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate. Cancer Chemother Pharmacol. 65:55–66. 2009. View Article : Google Scholar

12 

Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE and Gribbestad IS: Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed. 19:30–40. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Beckonert O, Coen M, Keun HC, Wang Y, Ebbels TM, Holmes E, Lindon JC and Nicholson JK: High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues. Nat Protoc. 5:1019–1032. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Cheng LL, Burns MA, Taylor JL, He W, Halpern EF, McDougal WS and Wu CL: Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy. Cancer Res. 65:3030–3034. 2005.PubMed/NCBI

15 

Swanson MG, Zektzer AS, Tabatabai ZL, Simko J, Jarso S, Keshari KR, Schmitt L, Carroll PR, Shinohara K, Vigneron DB and Kurhanewicz J: Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. Magn Reson Med. 55:1257–1264. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Erb G, Elbayed K, Piotto M, Raya J, Neuville A, Mohr M, Maitrot D, Kehrli P and Namer IJ: Toward improved grading of malignancy in oligodendrogliomas using metabolomics. Magn Reson Med. 59:959–965. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Humpfer E, Spraul M, Carreira IM, Melo JB, Bernardo J, Gomes A, Sousa V, Carvalho L and Duarte IF: Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J Proteome Res. 9:319–332. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Sitter B, Bathen T, Hagen B, Arentz C, Skjeldestad FE and Gribbestad IS: Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy. MAGMA. 16:174–181. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Yang J, Kim JH, Im GH, Heo H, Yoon S, Lee J, Lee JH and Jeon P: Evaluation of antiangiogenic effects of a new synthetic candidate drug KR-31831 on xenografted ovarian carcinoma using dynamic contrast enhanced MRI. Korean J Radiol. 12:602–610. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Frenette C and Gish R: Targeted systemic therapies for hepatocellular carcinoma: clinical perspectives, challenges and implications. World J Gastroenterol. 18:498–506. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Miura H, Miyazaki T, Kuroda M, Oka T, Machinami R, Kodama T, Shibuya M, Makuuchi M, Yazaki Y and Ohnishi S: Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma. J Hepatol. 27:854–861. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Torimura T, Sata M, Ueno T, Kin M, Tsuji R, Suzaku K, Hashimoto O, Sugawara H and Tanikawa K: Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma. Hum Pathol. 29:986–991. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Moon WS, Rhyu KH, Kang MJ, Lee DG, Yu HC, Yeum JH, Koh GY and Tarnawski AS: Overexpression of VEGF and angiopoietin 2: a key to high vascularity of hepatocellular carcinoma? Mod Pathol. 16:552–557. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Hsu PI, Chow NH, Lai KH, Yang HB, Chan SH, Lin XZ, Cheng JS, Huang JS, Ger LP, Huang SM, Yen MY and Yang YF: Implications of serum basic fibroblast growth factor levels in chronic liver diseases and hepatocellular carcinoma. Anticancer Res. 17:2803–2809. 1997.PubMed/NCBI

25 

Mise M, Arii S, Higashituji H, Furutani M, Niwano M, Harada T, Ishigami S, Toda Y, Nakayama H, Fukumoto M, Fujita J and Imamura M: Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology. 23:455–464. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Adams J, Huang P and Patrick D: A strategy for the design of multiplex inhibitors for kinase-mediated signalling in angiogenesis. Curr Opin Chem Biol. 6:486–492. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Laird AD and Cherrington JM: Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs. 12:51–64. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Li W, Liu ML, Cai JH, Tang YX, Zhai LY and Zhang J: Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo. Oncol Lett. 4:168–174. 2012.PubMed/NCBI

29 

Jensen LR, Huuse EM, Bathen TF, Goa PE, Bofin AM, Pedersen TB, Lundgren S and Gribbestad IS: Assessment of early docetaxel response in an experimental model of human breast cancer using DCE-MRI, ex vivo HR MAS, and in vivo 1H MRS. NMR Biomed. 23:56–65. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Moestue S, Sitter B, Bathen TF, Tessem MB and Gribbestad IS: HR MAS MR spectroscopy in metabolic characterization of cancer. Curr Top Med Chem. 11:2–26. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Seierstad T, Røe K, Sitter B, Halgunset J, Flatmark K, Ree AH, Olsen DR, Gribbestad IS and Bathen TF: Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy. Mol Cancer. 7:332008. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Yang J, Song KD, Kim J, Im G, Yoon S, Namgung M, Hwang J, Lee JH and Choi D: Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology. Mol Med Rep 8: 1425-1431, 2013.
APA
Yang, J., Song, K.D., Kim, J., Im, G., Yoon, S., Namgung, M. ... Choi, D. (2013). Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology. Molecular Medicine Reports, 8, 1425-1431. https://doi.org/10.3892/mmr.2013.1690
MLA
Yang, J., Song, K. D., Kim, J., Im, G., Yoon, S., Namgung, M., Hwang, J., Lee, J. H., Choi, D."Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology". Molecular Medicine Reports 8.5 (2013): 1425-1431.
Chicago
Yang, J., Song, K. D., Kim, J., Im, G., Yoon, S., Namgung, M., Hwang, J., Lee, J. H., Choi, D."Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology". Molecular Medicine Reports 8, no. 5 (2013): 1425-1431. https://doi.org/10.3892/mmr.2013.1690
Copy and paste a formatted citation
x
Spandidos Publications style
Yang J, Song KD, Kim J, Im G, Yoon S, Namgung M, Hwang J, Lee JH and Choi D: Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology. Mol Med Rep 8: 1425-1431, 2013.
APA
Yang, J., Song, K.D., Kim, J., Im, G., Yoon, S., Namgung, M. ... Choi, D. (2013). Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology. Molecular Medicine Reports, 8, 1425-1431. https://doi.org/10.3892/mmr.2013.1690
MLA
Yang, J., Song, K. D., Kim, J., Im, G., Yoon, S., Namgung, M., Hwang, J., Lee, J. H., Choi, D."Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology". Molecular Medicine Reports 8.5 (2013): 1425-1431.
Chicago
Yang, J., Song, K. D., Kim, J., Im, G., Yoon, S., Namgung, M., Hwang, J., Lee, J. H., Choi, D."Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology". Molecular Medicine Reports 8, no. 5 (2013): 1425-1431. https://doi.org/10.3892/mmr.2013.1690
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