Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level

Li, Xin; Feng, Gan Sheng; Zheng, Chuan; Chen, Zhuo; Liu, Xi

doi:10.3748/wjg.v10.i19.2878

Cited by 261 publications

(216 citation statements)

References 32 publications

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“…37 The stimulated angiogenesis is possibly due to hypoxia induced by TAE, as it has been demonstrated that expression of HIF-1a and its subsequent VEGF could be upregulated by ligation of hepatic artery, 38 a similar hypoxia-inducing procedure to TAE. However, in one report by Li et al, 39 transurethral chemoembolization (TACE) had little influence on tumor angiogenesis, possibly due to the application of chemotherapeutic drugs, which have been shown to inhibit the tumor angiogenesis. 40 Potential advantages of AAV mediated antiangiogenic gene therapy are the sustained expression of the antiangiogenic factors and highly-localized delivery.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Jiang

Meng

Tan

et al. 2007

Intl Journal of Cancer

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Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers. ' 2007 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; transcatheter arterial embolization; angiogenesis; adeno-associated virus; angiostatin; gene therapy Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with an estimated incidence of more than one million new cases per year.1,2 HCC has a very poor prognosis with less than a 6% 5-year survival rate. Only surgery offers a cure, but liver resection is feasible for less than 15% of patients, and recurrence rates remain high after tumor resection.3 Chemotherapy and radiotherapy offer unsatisfactory response rates. Therefore, new strategies to combat HCC are urgently needed.The application of transcatheter arterial embolization (TAE) to treat liver cancers has developed conceptually based on the observation that both primary and secondary liver tumors derive their blood supply mainly from the hepatic artery, 4 while blood supply to normal liver mainly depends on the portal system. 5,6 Thus, artery obstruction by embolization can cause extensive ischemic tumor necrosis, which provides the rational for its wide use as a standard treatment for unresectable HCC. 7,8 However, the effectiveness of TAE in treating HCC is debatable as any beneficial results are short-lived because collateral arterial circulations rapidly develop. It has been reported that TAE enhances the rate of intrahepatic and extrahepatic metastases, and even results in a shorter survival.9-11 Recanalization of the embo...

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Jiang

Meng

Tan

et al. 2007

Intl Journal of Cancer

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“…This is attributable to the fact that most VEGF in the peripheral circulation is carried in the platelets, and the VEGF is released when the platelets are activated during blood clotting. It has been postulated that platelets may serve as a scavenger or storage of VEGF from the tumor, and the release of VEGF from the platelets at distant metastasis may play a central role in the process of hematogenous dissemination of cancers [30] . A study has demonstrated that increased levels of bone marrow-derived endothelial progenitor cells in the peripheral circulation of patients with advanced HCC, and a high correlation between serum VEGF levels and levels of circulating endothelial progenitor cells were observed [31] .…”

Section: Discussionmentioning

confidence: 99%

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Guo

Zhu

et al. 2012

Chin. J. Cancer Res.

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Objective: To investigate the expression level of serum vascular endothelial growth factor (VEGF) in patients with unresectable hepatocellular carcinoma (HCC) and its relationship with the clinicopathological characteristics, and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization (TACE) treatments.Methods: Serum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) in 60 random patients who underwent TACE or transarterial infusion (TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients' clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients' survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results: The median serum VEGF level in the HCC patients was 285 pg/ml (range 14−1,207 pg/ml), significantly higher than that of healthy controls (P=0.021). The serum VEGF levels were significantly correlated with platelet counts (r=0.396, P=0.002) but not other clinicopathological features. Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml (P=0.002). By multivariate analysis, the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.

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“…The drug should be present long enough to cover the early proliferative response to the ischemic effect after the embolization procedure, which is known to peak at day 1 and then gradually decrease (35). In comparison, the Sutent® monography (34) reported a t max between 6 and 12 h after capsule (sunitinib malate) intake and Speed et al (36) determined an elimination half time of 51 h in humans after an oral dose of 50 mg.…”

Section: Chow Et Al (18) Stated 20 To 40 Mg/kg Po As a Minimal Daimentioning

confidence: 99%

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Fuchs

Bize

Dormond

et al. 2014

Journal of Vascular and Interventional Radiology

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Purpose: The combination of embolic beads with a multi-targeted tyrosine kinase inhibitor that inhibits tumor vessel growth is suggested as an alternative and improvement to the current standard doxorubicin-eluting beads for use in transarterial chemoembolization. This study demonstrates the in vitro loading and release kinetics of sunitinib using commercially available embolization microspheres, and evaluates the in vitro biological efficacy on cell cultures and the resulting in vivo pharmacokinetic profiles in an animal model. Materials and Methods:DC Bead microspheres, 70-150 µm and 100-300 µm (Biocompatibles Ltd., Farnham, United Kingdom), were loaded by immersion in sunitinib solution. Drug release was measured in saline in a USP-approved flow-through apparatus and quantified by spectrophotometry. Activity after release was confirmed in cell culture. For pharmacokinetics and in vivo toxicity evaluation, New-Zealand white rabbits received sunitinib either by intra-arterial injection of 100-300 µm sized beads or per os. Drug concentrations in the plasma and liver tissue were assessed by liquid chromatography-tandem mass spectrometry.Results: Sunitinib loading on beads was close to complete and homogeneous. A total release of 80% in saline was measured, with similar fast release profiles for both sphere sizes. After embolization, drug plasma levels remained below the therapeutic threshold (< 50 ng/ml), but high concentrations at 6 h (14.9 µg/g) and 24 h (3.4 µg/g) were found in the liver tissue.Conclusions: DC Bead microspheres of two sizes were efficiently loaded with sunitinib and displayed a fast and almost complete release in saline. High liver drug concentrations and low systemic levels indicated the potential of sunitinib-eluting beads for use in embolization.

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Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level

Cited by 261 publications

References 32 publications

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

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