Tumour VEGF/Non Tumour VEGF protein expression ratio as a biomarker for survival in colorectal cancer patients

Morales-Gutiérrez, Carlos; Abad-Barahona, Alfredo; Moreno‐González, E.; Salamanca, Rafael Enrı́quez de; Vegh, Irene

doi:10.1016/j.ejso.2011.02.005

Cited by 10 publications

(10 citation statements)

References 26 publications

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“…37 In fact, the VEGF expression was described to be increased in the center of the neoplastic mass and progressively reduced approaching the borders with an intensity that finds its apex in the first 5-10 cm around the tumor. 38 However, Hanrahan et al 36 observed that VEGF-A mRNA did not correlate with vascular and lymphatic invasion, while in our series VEGF-A levels at immunoassay were significantly higher in adenocarcinoma with lymphovascular invasion compared with those without it, and low levels of VEGF-C predicted the presence of lymphovascular invasion. The discrepancy between the two observations may be due to the different transcriptional stages of the two observations (our mRNA VEGF-A data also did not correlate with lymphovascular invasion).…”

Section: Discussioncontrasting

confidence: 69%

Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients

et al. 2017

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Colorectal cancer incidence in patients undergoing screening protocols is decreasing because of the higher rate of discovered preneoplastic colonic lesions; however, adenomatous polyps may not always be removable endoscopically and surgery may still be necessary. The aim of this study was to assess the vascular endothelial growth factor expression in the different steps of colorectal carcinogenesis to explore its potential role as a marker of malignancy in polypoid lesions. A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Real-time reverse transcription polymerase chain reaction for VEGF-A messenger RNA expression and immunohistochemistry for VEGF-A were performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Non-parametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. VEGF-A messenger RNA expression was higher in patients with high-grade dysplasia or colorectal cancer than in those with low-grade dysplasia adenomas (p = 0.01). At immunohistochemistry, VEGF-A expression was significantly higher in colorectal cancer patients compared to dysplastic adenomas (p < 0.001), and the accuracy of VEGF-A expression for prediction of malignancy was 91.7 (95% confidence interval = 78.7-97.9). VEGF-C protein expression was lower in colorectal cancer patients than in simple adenomas (p = 0.02). VEGF-A levels were directly correlated to polyp size (rho = 0.73, p = 0.0062). Multivariate analysis demonstrated that malignancy and polyp size were independent predictors of VEGF-A mucosal levels. This study demonstrated that the VEGF-A expression changes along the colorectal carcinogenesis pathway showing a neat step up at the passage from high-grade dysplasia to invasive cancer. This feature might potentially be useful to stratify colorectal polyps in different risks of progression classes. Moreover, the high level of VEGF-A expression predicted the presence of lymphovascular invasion with good accuracy.

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Section: Discussioncontrasting

confidence: 69%

Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients

et al. 2017

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“…HIF regulates several pro-survival pathways and further affects VEGF secretion from the tumor cells. VEGF activates pro-survival signaling pathways leading to tumor growth and ultimately malignancy [5][6][7][8][9][10]. Therefore, a number of studies have been performed to investigate VEGF expression from solid tumors; it is critical and necessary to understand the intricate balance between pro-survival and anti-survival tendencies of tumors and detect potential malignancy [4,9,[11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, studies of VEGF secretion from the spheroids using microfluidic systems are limited to qualitative or semi-quantitative analysis based on analysis of RNA [7,16,17,43] rather than direct measurement of the protein itself. Several studies using anti-cancer agents on spheroid systems have concluded that physical properties of spheroids are related to drug efficacy [50,51].…”

Section: Introductionmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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Vascular endothelial growth factor (VEGF) is a major cytokine in tumor biology affecting tumor survival, aggressiveness and pro-angiogenetic activities. In addition, cellular stresses often result in aggressive pro-angiogenetic behavior in tumors. For in vitro study, conventional monolayer cell culture has been broadly exploited; however, it often provides limited information due to its different microenvironment from that in vivo. Recently, three-dimensional (3D) cell spheroid culture provides in vivo-like microenvironments to study tumor biology and their survival mechanisms with better predictive power. In this work, vascular endothelial growth factor of type A (VEGF-A) secretion from osteosarcoma (MG-63) cells cultured using monolayer and 3D spheroid models under two stress conditions: nutrient deficiency (reduced serum culture) and hypoxia-inducible factor (HIF) inhibition (HIF inhibitor, YC-1) are characterized and systematically compared. In order to obtain ample sample size for consistent characterization of cellular responses from cancer spheroids under the stresses and compare the responses to those from the conventional monolayer model, a microfluidic spheroid formation and culture device is utilized in the experiments. In the analysis, cell viability is estimated from captured images, and quantification of VEGF-A secreted from the cells is achieved using enzyme-linked immunosorbent assay (ELISA). The experimental results show that the viabilities decrease when the cells face higher stress levels in both monolayer and 3D spheroid culture models; however, the VEGF-A secretion profiles between the cell culture models are different. The VEGF-A secretion decreases when the cells face higher stress conditions in the monolayer cell culture. In contrast, for the 3D spheroid culture, the VEGF-A concentration decreases for low stress levels but increases while the stress level is high. The VEGF-A regulation in the 3D models mimics in vivo cases of tumor survival and can provide insightful information to investigate tumor angiogenesis in vitro. The approach developed in this paper provides an efficient method to quantitatively and statistically study tumor growth kinetics and stress responses from highly uniform samples and it can also be applied to compare the underlying biomolecular mechanisms in monolayer and 3D spheroid culture models to elucidate the effects of microenvironments on cellular response in cancer research.

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“…Vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) as well as bloodvessel formation (angiogenesis) in the adult. In mammals, five VEGF ligands, which occur in several different splice variants and processed forms, have been identified so far (Morales-Gutiérrez et al, 2011;Small et al, 2008;Mahjoub et al, 2012;Wang et al, 2012;Sher et al, 2012). The ability of tumours to induce new bloodvessel formation has been a major focus of cancer research over the past few decades, and vascular endothelial growth factor (VEGF) is now known to be central to this process.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of antitumour action of Ganoderma lucidum extract in hepatocarcinoma mice

Wu¹,

Guan²,

Jianzhong³

et al. 2012

Afr. J. Pharm. Pharmacol.

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The present study shows the protective effects of the Ganoderma lucidum aqueous crude extract (GLE) against mice liver cancer. The mice were randomized into four groups, namely, controls and tumor bearers that were G. lucidum extract-treated or untreated. Tumor bearers were inoculated intraperitoneally (ip) with 108 Yoshida AH-130 ascites hepatoma cells, whereas the controls received saline alone. The treatment began 1 day after tumor cell inoculation, and continued for 14 days. Administration of G. lucidum extract reduced the tumour weight of G. lucidum-treated groups in a dose dependent way (1.627 ± 0.135, 1.142 ± 0.144 versus 2.163 ± 0.316) as compared to model control group. The inhibition rate was 24.84, and 47.31 by G. lucidum extract administration at concentrations of 200 and 400 mg/kg body weight, respectively. Results of this investigation justify continuing with further studies of G. lucidum extract components to develop chemoprevention strategies as an option in the treatment of cancer.

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Tumour VEGF/Non Tumour VEGF protein expression ratio as a biomarker for survival in colorectal cancer patients

Cited by 10 publications

References 26 publications

Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients

Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

Evaluation of antitumour action of Ganoderma lucidum extract in hepatocarcinoma mice

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