Biologic modulation of chemotherapy in patients with hepatic colorectal metastases: The role of anti‐VEGF and anti‐EGFR antibodies

Prenen, Hans; Topal, Baki; Aerts, Raymond; Vannoote, Jaarke; Cutsem, Éric Van

doi:10.1002/jso.21760

Cited by 8 publications

(5 citation statements)

References 86 publications

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“…However, recent studies have showed that the tumor can generate their own vascular system independent of the host blood vessels [26]. VEGF appears to play a crucial role in either exogenous or endogenous neo-angiogenesis [27]. In addition to its angiogenic effect, previous studies have also shown that hematopoietic stem cells (HSC), leukemia, human pancreatic cancer cells and multiple myeloma express VEGF receptors, and are able to generate functional autocrine loops supporting their proliferation, migration, adhesion and survival[6,7,28,29–32].…”

Section: Discussionmentioning

confidence: 99%

VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

et al. 2011

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Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF induces new vessel formation and tumor growth by inducing mitogenesis and chemotaxis of normal endothelial cells and increasing vascular permeability. However, little is known about VEGF function in the proliferation, survival or migration of hepatocellular carcinoma cells (HCC). In the present study, we have found that VEGF receptors are expressed in HCC line BEL7402 and human hepatocellular carcinoma specimens. Importantly, VEGF receptor expression correlates with the development of the carcinoma. By using a comprehensive approaches including TUNEL assay, transwell and wound healing assays, migration and invasion assays, adhesion assay, western blot and quantitative RT-PCR, we have shown that knockdown of VEGF165 expression by shRNA inhibits the proliferation, migration, survival and adhesion ability of BEL7402. Knockdown of VEGF165 decreased the expression of NF-κB p65 and PKCα while increased the expression of p53 signaling molecules, suggesting that VEGF functions in HCC proliferation and migration are mediated by P65, PKCα and/or p53.

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Section: Discussionmentioning

confidence: 99%

VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

et al. 2011

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“…Hepatocellular carcinoma is one of the most common malignancies worldwide and is increasingly prevalent. Both primary and secondary tumors are being increasingly treated by targeted anti-vascular therapies [6, 7]. These agents are typically cytostatic rather than cytotoxic and therapeutic efficacy may be reflected more by changes in perfusion than by changes in size [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dual Vascular Input Functions on CT Perfusion Parameter Values and Reproducibility in Liver Tumors and Normal Liver

Chandler

Wei

et al. 2012

Journal of Computer Assisted Tomography

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Objective To assess the impact on absolute values and reproducibility of adding portal venous (PV) to arterial input functions in computed tomography perfusion (CTp) evaluations of liver tumors and normal liver. Methods Institutional review board approval and written informed consent were obtained; the study complied with HIPAA regulations. CTp source datasets, obtained from seven patients (containing 9 liver tumors) on two occasions, 2-7 days apart, were analyzed by deconvolution modeling using dual (“Liver” protocol, PV and aorta) and single (“Body” protocol, aorta only) vascular inputs. Identical tumor, normal liver, aortic and, where applicable, PV ROIs were used in corresponding analyses to generate tissue blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PS) values. Test-retest variability was assessed by within-patient coefficients of variation (wCV). Results For liver tumor and normal liver, median BF, BV and PS were significantly higher for the Liver protocol than Body protocol: 171.3-177.8 vs. 39.4-42.0 mL/min/100g, 17.2-18.7 vs. 3.1-4.2 mL/100g, 65.1-78.9 vs. 50.4- 66.1 mL/min/100g, respectively (all p<0.01). There were no differences in MTT between protocols. wCVs were lower for all parameters with the Liver protocol than Body protocol: BF, 7.5-11.2% vs 11.7-20.8%; BV, 10.1-14.4% vs. 16.6-30.1%; MTT, 4.2-5.5% vs. 10.4-12.9%; and PS, 7.3-12.1% vs. 12.6-20.3%, respectively. Conclusion Utilization of dual vascular input CTp liver analyses has substantial impact on absolute CTp parameter values and test-retest variability. Incorporation of the portal venous inputs may yield more precise results, however, it imposes substantial practical constraints on acquiring the necessary data.

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“…VEGF-A is believed to stimulate angiogenesis by activating endothelial cell proliferation via the intracellular tyrosine phosphorylation pathway through a paracrine or autocrine mechanism. In addition, VEGF-A acts as a major anti-apoptotic factor for endothelial cells observed in immature, newly formed blood vessels (38)(39)(40). Therefore, blocking VEGF-A expression should effectively suppress intra-tumoral angiogenesis, vascular permeability and tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting the proliferation and metastasis of hilar cholangiocarcinoma cells by blocking the expression of vascular endothelial growth factor with small interfering RNA

Ouyang

Tang

2018

Oncol Lett

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The aim of the present study was to investigate whether the proliferation and metastasis of hilar cholangiocarcinoma cells can be suppressed and whether apoptosis can be induced by small interfering RNA (siRNA) repression of vascular endothelial growth factor (VEGF). siRNA sequences targeting the gene were designed and the human hilar cholangiocarcinoma QBC939, HCCC-9810 and RBE cell lines were transfected with VEGF-siRNA plasmids for 48 h. Reverse transcription-quantitative polymerase chain reaction and western blotting measured the levels of VEGF-A, VEGF-C and matrix metalloproteinase 2 (MMP2) mRNA expression and protein content. The cell invasion potential was evaluated using the Transwell invasion and migration assay and the MTT assay was employed to detect the proliferation of hilar cholangiocarcinoma cells. Flow cytometry was used to quantify cell apoptosis and necrosis. Following the transfection of VEGF-siRNA, a significant reduction of mRNA and protein levels of VEGF-A, VEGF-C and MMP2 was observed in the hilar cholangiocarcinoma cells. The invasion, migration and proliferation of tumor cells were also notably decreased. The rate of tumor cell apoptosis was increased in the VEGF-siRNA group (15.42%) compared with the non-siRNA control (2.22%) and the negative control (2.71%) groups. It was concluded that blocking the expression of VEGF via VEGF-siRNA effectively inhibited the invasion, migration and proliferation, and induced apoptosis in hilar cholangiocarcinoma cells. These observations suggested that targeting VEGF with RNAi may be an effective therapeutic strategy for treating hilar cholangiocarcinoma.

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Biologic modulation of chemotherapy in patients with hepatic colorectal metastases: The role of anti‐VEGF and anti‐EGFR antibodies

Cited by 8 publications

References 86 publications

VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

Effect of Dual Vascular Input Functions on CT Perfusion Parameter Values and Reproducibility in Liver Tumors and Normal Liver

Inhibiting the proliferation and metastasis of hilar cholangiocarcinoma cells by blocking the expression of vascular endothelial growth factor with small interfering RNA

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