Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC

Graepler, Florian; Verbeek, Barbara; Graeter, Tilmann; Smirnow, Irina; Kong, Hwai Loong; Schuppan, Detlef; Bauer, Michael; Vonthein, Reinhard; Gregor, Michael; Lauer, Ulrich M.

doi:10.1002/hep.20613

Cited by 45 publications

(32 citation statements)

References 37 publications

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“…Given that HCC is a hypervascular tumor, anti-angiogenic therapy offers a promising approach to treatment. Potent angiogenesis inhibitors such as angiostatin [6], endostatin [7], TNP-470 [8], and soluble vascular endothelial growth factor receptor 1 [7] are effective in treating HCC in experimental animal models. Vasostatin, representing the N-terminal domain (amino acid residues 1-180) of calreticulin, is a potent angiogenic inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy

Luo

Qiao

et al. 2007

Journal of Hepatology

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Section: Introductionmentioning

confidence: 99%

Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy

Luo

Qiao

et al. 2007

Journal of Hepatology

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“…Endostatin is a potent antiangiogenic factor synthesized by proteolytic degradation of the long variant of collagen XVIII [7]. The ability of endostatin to inhibit tumor growth and angiogenesis has been extensively demonstrated in animal models [7][8][9][10][11], and a human trial with endostatin has begun [12]. Endostatin exerts its effects by blocking endothelial cell proliferation and migration, and promoting endothelial cell apoptosis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Serum Endostatin Levels and Regenerative Capacities of Normal and Cirrhotic Livers Following Partial Hepatectomy in Mice: The Response to Different Resection Sizes

Çolakoğlu

Keşkek

Çolakoğlu

et al. 2007

Journal of Surgical Research

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“…Given that HCC is a hypervascular tumor, anti-angiogenic therapy offers a promising approach to treatment. Previous studies have revealed that angiogenesis inhibitors including TNP-470, (3) angiostatin, (4) endostatin, (5) soluble VEGF receptor 1,…”

mentioning

confidence: 99%

Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice

Jiang

Qiao

et al. 2009

Cancer Science

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Hepatocellular carcinoma (HCC) is one of the most common cancerrelated causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its antiangiogenic activity, and meloxicam, a selective COX-2 inhibitor, inhibited proliferation and induced apoptosis of human HCC cells in vitro. The aim of this study was to determine whether combining kallistatin gene therapy and meloxicam could offer a better therapeutic effect to combat HCC in mice. A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB ⁄ c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis in situ, but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl-2, Bax, or activation of caspase-3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase-3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2009; 100: 2226-2233 H epatocellular carcinoma is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide with an estimated incidence of over one million new cases each year.(1) Surgery offers a cure, but the rate of liver resection is <15% and recurrence rate remains as high as 50% after resection.(2) The conventional treatments including chemotherapy and radiotherapy offer unsatisfactory response. Therefore, new strategies to combat HCC are urgently needed.Solid tumors including HCC must establish an adequate vascular network to acquire necessary nutrition. Given that HCC is a hypervascular tumor, anti-angiogenic therapy offers a promising approach to treatment. Previous studies have revealed that angiogenesis inhibitors including TNP-470, (3) angiostatin, (4) endostatin, (5) soluble VEGF receptor 1,and vasostatin (6) are effective in treating HCC in experimental animal models. Kallistatin, a serine proteinase inhibitor, was first identified as a tissue kallikrein-binding protein,and has recently emerged as a novel inhibitor of angiogenesis. (8) Kallistatin inhibits the proliferation, migration, and adhesion of endothelial cells a...

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Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC

Cited by 45 publications

References 37 publications

Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy

Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy

Serum Endostatin Levels and Regenerative Capacities of Normal and Cirrhotic Livers Following Partial Hepatectomy in Mice: The Response to Different Resection Sizes

Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice

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