Prognostic Significance of Vascular Endothelial Growth Factor Protein in Node-Negative Breast Carcinoma

Gasparini, Giampietro; Toi, Masakazu; Gion, Massimo; Verderio, Paolo; Dittadi, Ruggero; Hanatani, Mitsuya; Matsubara, Isamu; Vinante, O.; Bonoldi, Emanuela; Boracchi, Patrizia; Gatti, Carlo; Suzuki, Hideo; Tominaga, Takeshi

doi:10.1093/jnci/89.2.139

Cited by 453 publications

(255 citation statements)

References 40 publications

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“…Possibly, the release of tumour associated antigens at the time of diagnosis proves blood supply respectively vascularisation of the tumour and by consequence the possibility of already existing micrometastases and bad prognosis from the beginning (Gasparini et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

et al. 2002

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In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre-and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

et al. 2002

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“…Angiogenesis is necessary for the growth and invasion of primary tumor and is also an essential step in tumor metastasis [1][2][3]. Neovascularization promotes the progression of tumor by delivering nutrients and oxygen necessary for tumor cells to grow, facilitating the penetration of tumor cells through vessel wall and their transport to distant organs, and secreting cytokines and growth factors from endothelial cells that stimulate tumor cells [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…Neovascularization promotes the progression of tumor by delivering nutrients and oxygen necessary for tumor cells to grow, facilitating the penetration of tumor cells through vessel wall and their transport to distant organs, and secreting cytokines and growth factors from endothelial cells that stimulate tumor cells [1][2][3]. Many angiogenic factors including fibroblast growth factor, vascular endothelial growth factor (VEGF), transforming growth factor-a, platelet-derived endothelial cell growth factor, and hepatocyte growth factor have been identified [1].…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts

et al. 2001

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“…VEGF expression in clinical tissue specimens of BC is known to be related to patient outcome 6. In our analysis using the METABRIC study data (Supporting Information Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Newly formed vessels provide oxygen and nutrients to assist tumor growth. Clinically, VEGF expression in BC tumors has been reported to be associated with worse prognosis 6. Bevacizumab, an antibody that neutralizes VEGF, suppresses tumor angiogenesis by blocking the VEGF signals in endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

Kiso

Tanaka

Toi

et al. 2018

Intl Journal of Cancer

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VEGF stimulates endothelial cells as a key molecule in angiogenesis. VEGF also works as a multifunction molecule, which targets a variety of cell members in the tumor microenvironment. We aimed to reveal VEGF‐related molecular mechanisms on breast cancer cells. VEGF‐knocked‐out MDA‐MB‐231 cells (231VEGFKOex3) showed rounded morphology and shorter perimeter (1.6‐fold, p < 0.0001). The 231VEGFKOex3 cells also showed impaired cell migration (2.6‐fold, p = 0.002). Bevacizumab treatment did not induce any change in morphology and mobility. Soluble neuropilin‐1 overexpressing MDA‐MB‐231 cells (231sNRP1) exhibited rounded morphology and shorter perimeter (1.3‐fold, p < 0.0001). The 231sNRP1 cells also showed impaired cell migration (1.7‐fold, p = 0.003). These changes were similar to that of 231VEGFKOex3 cells. As MDA‐MB‐231 cells express almost no VEGFR, these results indicate that the interaction between NRP1 and long isoform of VEGF containing a NRP‐binding domain regulates the morphology and migration ability of MDA‐MB‐231 cells. Genome‐wide gene expression profiling identified ARHGAP17 as one of the target genes in the downstream of the VEGF/NRP1 signal. We also show that VEGF/NRP1 signal controls filopodia formation of the cells by modulating Cdc42 activity via ARHGAP17. Among 1,980 breast cancer cases from a public database, the ratio of VEGF and SEMA3A in primary tumors (n = 450) of hormone‐receptor‐negative breast cancer is associated with ARHGAP17 expression inversely, and with disease free survival. Altogether, the bevacizumab‐independent VEGF/NRP1/ARHGAP17/Cdc42 regulatory network plays important roles in malignant behavior of breast cancer.

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Prognostic Significance of Vascular Endothelial Growth Factor Protein in Node-Negative Breast Carcinoma

Abstract: The results show that cytosolic levels of VEGF in tumor tissue samples are indicative of prognosis for patients with node-negative breast carcinoma.

Cited by 453 publications

References 40 publications

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

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