Kallikrein-binding protein inhibits growth of gastric carcinoma by reducing vascular endothelial growth factor production and angiogenesis

Zhu, Bin; Lü, Lei; Cai, Weibin; Yang, Xia; Li, Chaoyang; Yang, Zhonghan; Zhan, Wei; Xing, Jian; Gao, Guoquan

doi:10.1158/1535-7163.mct-06-0798

Cited by 35 publications

(42 citation statements)

References 45 publications

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“…The monoclonal IgG 1 antibody, Bevacizumab (Avastin), which binds VEGF preventing receptor binding, has been evaluated in the first-and second-line treatment in patients with colorectal cancer (Willett et al, 2004(Willett et al, , 2006Chua and Cunningham, 2006;Rasheed et al, 2008). Interestingly, novel antiangiogenic compounds have been developed that decrease HIF-1a and other HIFs (Mackay et al, 2005;Zhu et al, 2007;Singh et al, 2008).…”

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confidence: 99%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1a (HIF-1a) and HIF-2a protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n ¼ 90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1a and HIF-2a expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1a and HIF-2a, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (Po0.001) and associated with poor survival (hazard ratio (HR) ¼ 8.7, Po0.005) and decreased disease-free survival (HR ¼ 4.7, Po0.005). hypoxia-inducible factor-1a and -2a were expressed in 450% of rectal cancers (HIF-1a, 54%, 48/90; HIF-2a, 64%, 58/90). HIF-1a positivity was associated with both TNM stage (Po0.05) and vascular invasion (Po0.005). In contrast, no associations were shown between HIF-2a expression and any pathological features, and HIF-1a positivity had no effect on outcome. The study showed an independent association between HIF-1a expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1a, but not HIF-2a, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.

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confidence: 99%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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“…Tumor microvessel density (MVD) was quantified by the Weidner's method. 35 PEDF expression in human cervical tissues was determined by previously described, 33 and cultured in M199 medium (Gibco) supplemented with 15% FBS and endothelial cell growth supplement (ECGS; BD Biosciences, Bedford, MA, USA), and also incubated at 37°C in a humidified incubator at 5% CO 2 . For HUVECs, all experiments were carried out between cell passages 2 and 6.…”

Section: Methodsmentioning

confidence: 99%

“…[30][31][32] Our recent results showed that KBP, another angiogenic inhibitor, significantly reduced VEGF expression via inhibition of HIF-1α in gastric and liver cancer. 33,34 Therefore, the regulation of PEDF on HIF-1α was examined in this study. We found that hypoxia apparently induced a lot more HIF-1α in Hela cells compared with normoxia and HIF-1α protein mainly translocated into nucleus under hypoxia.…”

Section: Control) Pedf Induces Apoptosis Of Huvecs But Has No Effectmentioning

confidence: 99%

Growth suppression of cervical carcinoma by pigment epithelium-derived factor via anti-angiogenesis

Yang

Chen²,

Huang³

et al. 2010

Cancer Biology & Therapy

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“…(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) …”

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“…(9) It has been reported that kallikrein-binding protein suppressed growth of gastric and hepatocellular carcinomas by its anti-angiogenic activity. (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.…”

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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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Kallikrein-binding protein inhibits growth of gastric carcinoma by reducing vascular endothelial growth factor production and angiogenesis

Cited by 35 publications

References 45 publications

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Growth suppression of cervical carcinoma by pigment epithelium-derived factor via anti-angiogenesis

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

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