Angiogenesis in epithelian ovarian cancer

Bamberger, E S; Perrett, CW

doi:10.1136/mp.55.6.348

Cited by 157 publications

(137 citation statements)

References 138 publications

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“…Furthermore CD31 staining of the tumor tissues of AuNP-treated mice also demonstrated a reduction in the number of tumor blood vessels compared with NT mice, consistent with the inhibitory effect of AuNPs toward HB-GF (Fig. 3 F and G) (45)(46)(47). Moreover, AuNP-mediated reversal of EMT and abrogation of MAPK activation leading to inhibition of tumor growth and metastasis was further confirmed by analysis of tumor tissues by Western blot analysis (Fig.…”

Section: Aunp Treatment Inhibits Tumor Growth and Metastasis In Vivo Bysupporting

confidence: 54%

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo¹,

Saha²,

Wang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

215

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Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size-and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single selftherapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.drug delivery | heparin-binding growth factors

show abstract

Section: Aunp Treatment Inhibits Tumor Growth and Metastasis In Vivo Bysupporting

confidence: 54%

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo¹,

Saha²,

Wang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

215

View full text Add to dashboard Cite

show abstract

“…Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress where it protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis (Toi et al, 2005). The degree of angiogenesis of a tumour as measured by vascular density has emerged as a powerful candidate for prognosis and as a predictive tool in breast cancer and melanomas (Bamberger and Perrett, 2002;Uzzan et al, 2004).…”

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confidence: 99%

Role of lymphangiogenesis in epithelial ovarian cancer

et al. 2006

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We investigated the significance of lymphatic count, vascular count and angiogenic growth factors using immunohistochemistry in 108 tumour specimens of epithelial ovarian cancer with antibodies to lymphatic vessel endothelial hyaluronan receptor (LYVE-1), platelet endothelial cell adhesion molecule CD31, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) in epithelial ovarian cancer to understand the pathogenesis of metastasis in ovarian cancer. The effect of prognostic variables on progression-free and overall survival was assessed. On multivariate analysis, bulky residual disease after surgery was the best prognostic indicator (Po0.001) for progression-free and overall survival (Po0.001). Lymphatic count was statistically significant as a prognostic factor for progression-free (P ¼ 0.05) and overall survival (P ¼ 0.04). However, lymphatic count did not impact on survival curves. No correlation was found between lymphatic count and age, histological subtype, FIGO stage or residual disease. Vascular count, VEGF or TP expressions were not significant in either analysis. Lymphatic spread may be significant in aiding metastases in ovarian cancer but requires other biological factors to act in conjunction, as it does not have clearcut prognostic significance. Dissemination of ovarian cancer does not occur primarily through vascular or lymphatic routes but may occur through direct intraperitoneal spread of disease.

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“…2,3 The angiogenic molecule vascular endothelial growth factor (VEGF) is more highly expressed in malignant versus benign ovarian tumors and associated with tumorigenicity and cancer progression. [3][4][5] Anti-VEGF therapies reduce tumor growth and ascites burden and enhance survival in murine models of EOC, [6][7][8] and treatment with the VEGF antagonist bevacizumab (Avastin) prolonged survival in mice when used as maintenance therapy after a complete response to cisplatin-based chemotherapy. 9 Several human phase II trials showed significant activity in EOC when bevacizumab was used as a single agent, suggesting that the blockade of VEGF signaling may prove effective in clinical disease.…”

mentioning

confidence: 99%

Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells

Adham

Sher

Coomber

2010

Laboratory Investigation

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Human epithelial ovarian cancer (EOC) is the most lethal neoplasm affecting the female genital tract, and is characterized by overexpression of vascular endothelial growth factor (VEGF) and growth as ascites. Anti-VEGF strategies are currently used in EOC therapy with promising results; however, molecular targeting of specific VEGF receptors on the cancer cells themselves has not been explored to date. We previously showed that activation of a VEGF/VEGFR2 signaling loop in EOC cells supports their survival in suspension, and short-term pharmacological inhibition of this loop increased EOC cell apoptosis in vitro. In this study, we stably knocked down VEGFR2 in OVCAR-3 and SKOV-3 EOC cells using short hairpin RNA (shRNA), an RNA interference strategy that could potentially overcome chemoresistance arising with angiogenic inhibitors. Unexpectedly, we observed an induction of more aggressive cellular behavior in transfected cells, leading to increased growth in mouse xenografts, enhanced accumulation of ascites, increased VEGF and neuropilin-1 (NRP-1) expression, and decreased expression of adhesion proteins, notably cadherins and integrins. Sonic hedgehog (SHH) pathways do not seem to be involved in the upregulation of NRP-1 message in VEGFR2 knockdown cells. Supporting our mouse model, we also found a significant increase in the ratio between NRP-1 and VEGFR2 with increasing tumor grade in 80 cases of human EOC. The change in EOC behavior that we report in this study occurred independent of the angiogenic response and shows the direct effect of VEGF blockade on the cancer cells themselves. Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites.

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Angiogenesis in epithelian ovarian cancer

Cited by 157 publications

References 138 publications

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Role of lymphangiogenesis in epithelial ovarian cancer

Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells

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