Adeno‐associated virus‐mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas

Tse, Lai Yin; Sun, Xueying; Jiang, Hongchi; Dong, Xuesong; Fung, Peter C. W.; Farzaneh, Farzin; Xu, Rui‐hua

doi:10.1002/jgm.1180

Cited by 31 publications

(30 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With this system, we demonstrated that intraportal delivery of AAV vectors led to long-term and high-level expression of the transgenes localized to the mouse liver [18,19]. Similar results have been obtained in rats by using this method [20,21].…”

Section: Introductionsupporting

confidence: 84%

Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells

Sun

Shi

Qiao

et al. 2011

Journal of Surgical Research

Self Cite

View full text Add to dashboard Cite

Section: Introductionsupporting

confidence: 84%

Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells

Sun

Shi

Qiao

et al. 2011

Journal of Surgical Research

Self Cite

View full text Add to dashboard Cite

“…(13) But the mechanisms are not clear as kallistatin showed no effect on expression of PCNA, nor the apoptosis-related proteins including Bal-2, Bax, and caspase-3. As caspase-3 is the key 'effector' protease in the apoptotic cascade, the results might suggest that kallistatininduced cell apoptosis may be caspase-independent.…”

Section: Discussionmentioning

confidence: 99%

“…(10,11) We have recently reported that adeno-associated virus-mediated expression of kallistatin inhibited angiogenesis and growth of colon and HCC tumors in mice. (12,13) …”

mentioning

confidence: 99%

“…(10,11) We have recently reported that adeno-associated virus-mediated expression of kallistatin inhibited angiogenesis and growth of colon and HCC tumors in mice. (12,13) Selective COX-2 inhibitors have been regarded as a new group of anticancer drugs based on the observation that expression of COX-2 is elevated in a variety of human cancers (14)(15)(16)(17)(18) including HCC, (19,20) and COX-2 has been shown to promote growth and inhibit apoptosis of cancer cells. (21) A number of studies have investigated the use of meloxicam, a selective COX-2 inhibitor, in inhibiting growth of cancers of ovarian, (22) bladder, (23) biliary duct, (24) breast, (25) lung, (26) and colon.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Jiang

Qiao

et al. 2009

Cancer Science

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…In vitro, the virus could deplete PTTG1 in hepatoma cells, resulting in apoptosis. Furthermore, intratumoural injections of the virus led to inhibition of tumour growth in a xenograft tumour in mice 59 . Another recent study concerns RNAi cancer gene therapy in a mouse model of hepatocellular carcinoma (test-O-MYC; LAP-tTa).…”

Section: Issn: 0975-8232mentioning

confidence: 99%

Untitled

2013

IJPSR

View full text Add to dashboard Cite

Adeno‐associated virus‐mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas

Abstract: Intraportal injection of rAAV-kallistatin suppressed hepatic and subcutaneous HCC tumors, relying on its anti-angiogenic and anti-proliferative activities.

Cited by 31 publications

References 42 publications

Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells

Hepatic Overexpression of Heme Oxygenase-1 Improves Liver Allograft Survival by Expanding T Regulatory Cells

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

Untitled

Contact Info

Product

Resources

About