Vascular Endothelial Growth Factor Expression in Serous Ovarian Carcinoma: Relationship with High Mitotic Activity and High FIGO Stage

Brustmann, Hermann; Naudé, S. M.

doi:10.1006/gyno.2001.6467

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…Further studies are also needed to investigate ways of improving outcomes for women with high-risk early-stage EOC and to identify factors that can predict a benefi t from platinum adjuvant CT in order to individualise treatments [51][52][53][54]. In this regard, the identifi cation of targeted therapies that interfere with growth factors or angiogenesis may provide new therapeutic options in early stages.…”

Section: Authormentioning

confidence: 99%

Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review

et al. 2011

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The long-term outcome of this series is comparable to the published evidence and reflects the limited activity of platinum-based CT in the adjuvant setting. The potential survival advantage of the addition of paclitaxel to carboplatin cannot be definitively answered due to the small number of patients, the limited follow-up and the retrospective nature of the study. More effective and specific treatments are clearly required, in particular for those patients with stage II and undifferentiated tumours. Quality of surgery entails prognostic value.

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Section: Authormentioning

confidence: 99%

Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review

et al. 2011

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“…VEGF is commonly overexpressed in the malignant ovarian epithelium (27) and is thought to be a potent mediator of ascites accumulation (28)(29)(30)(31)(32). Studies on human ovarian cancer cell lines have implicated the PI3K͞Akt͞mTOR pathway in VEGF transcriptional activation and demonstrated that rapamycin treatment decreases VEGF protein levels (33,34).…”

Section: Rapamycin Only Inhibits Proliferation Of Cells and Tumors Thmentioning

confidence: 99%

A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance

Xing

Oršulić

2005

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

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Cell lines and tumors with defined genetic alterations provide ideal systems in which to test the molecular mechanisms of tumor sensitivity to pathway-targeted therapy. We have generated mouse ovarian epithelial tumor cell lines that contain various combinations of genetic alterations in the p53, c-myc, K-ras and Akt genes. Using both in vitro and in vivo approaches, we investigated the effect of rapamycin on cell proliferation, tumor growth, and the accumulation of peritoneal ascites. We demonstrated that rapamycin effectively inhibits the growth of tumors that rely on Akt signaling for proliferation, whereas tumors in which Akt signaling is not the driving force in proliferation are resistant to rapamycin. The introduction of activated Akt to the rapamycinresistant cells does not render the cells susceptible to rapamycin if they can use alternative pathways for survival and proliferation. Accordingly, the rapamycin-sensitive tumors develop resistance to rapamycin when presented with alternative survival pathways, such as the mitogen-activated extracellular kinase signaling pathway. The combination of rapamycin and the mitogen-activated extracellular kinase inhibitor PD98059 is required to diminish proliferation in these cell lines. Our results indicate that mammalian target of rapamycin inhibitors may be effective in a subset of tumors that depend on Akt activity for survival but not effective in all tumors that exhibit Akt activation. Tumors with alternative survival pathways may require the inactivation of multiple individual pathways for successful treatment.mouse model ͉ ovarian cancer ͉ rapamycin

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“…It is detected more often in peritoneal metastases than in primary tumors in women with advanced-stage EOC. [5][6][7][8] In early-stage EOC, increased VEGF expression has a poor clinical prognosis. [9][10][11] In addition, VEGF serum level correlates with stage of disease, which suggests the feasibility of using VEGF as a biomarker for EOC diagnosis and prognosis.…”

mentioning

confidence: 99%

Vascular endothelial growth factor–regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases

Wang

Reierstad

et al. 2005

Intl Journal of Cancer

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Vascular endothelial growth factor (VEGF) expression is elevated in primary ovarian tumors and metastases. We examined the effect of VEGF on epithelial ovarian cancer (EOC) in vitro invasion and migration and underlying mechanisms. Using the Matrigel invasion assay and colloidal gold phagokinetic track assay, we found that VEGF induced EOC DOV13 invasion and migration in a matrix metalloproteinase (MMP)-dependent manner. Using Western blotting, we show that VEGF, at 20-80 ng/ml, induced secretion of pro-MMP-7 and pro-MMP-9 and activation of pro-MMP-2 in DOV13 conditioned medium in a concentrationdependent manner. However, gelatinolytic activity and total MMP-7 protein in DOV13 conditioned medium reached the maximum upon VEGF treatment at 20-40 ng/ml and decreased at higher-concentration VEGF treatment (80 ng/ml), as shown by DQ-gelatin degradation assay and ELISA. In addition to the effect on MMP secretion/activation, VEGF stimulated secretion of TIMP-2; and blocking TIMP-2 activity by an anti-TIMP-2 MAb significantly increased VEGF (80 ng/ml)-induced DOV13 invasion (p < 0.05), suggesting that VEGF may regulate MMP-2 activity in DOV13 conditioned medium through TIMP-2. Using real-time PCR, we found that VEGF, at 20 ng/ml, significantly increased the expression of VEGFR-1 and VEGFR-2 by approximately 4-fold and 31-fold, respectively, compared to untreated control (p < 0.05). However, the inducing effect of VEGF on VEGFR-2 expression and the internal expression of VEGF121 in DOV13 cells decreased with increasing of VEGF concentration, suggesting the existence of a negative feedback regulatory mechanism. In summary, our results indicate that VEGF may regulate EOC invasion and migration through VEGFR-mediated secretion and activation of MMPs. ' 2005 Wiley-Liss, Inc.Key words: vascular endothelial growth factor; matrix metalloproteinase; gelatinase A/MMP-2; gelatinase B/MMP-9; matrilysin/MMP-7; membrane type 1 matrix metalloproteinase; tissue inhibitor of matrix metalloproteinase; epithelial ovarian cancer; tumor invasion; vascular endothelial growth factor receptor EOC is the leading cause of death among all gynecologic malignancies and the fifth most common cancer in women in the United States.1 At initial diagnosis, the majority of women are diagnosed with advanced-stage EOC, with a resultant poor prognosis because of widespread dissemination throughout the abdomen and pelvis.2,3 Therefore, understanding the mechanisms involved in EOC metastasis may significantly improve women's health care. EOC metastasis and the formation of malignant ascites require a coordinated series of events to support the survival and implantation of disseminated malignant ovarian epithelium. VEGF, also known as vascular permeability factor, has been found to be a potent mediator of those events.

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Vascular Endothelial Growth Factor Expression in Serous Ovarian Carcinoma: Relationship with High Mitotic Activity and High FIGO Stage

Cited by 35 publications

References 24 publications

Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review

Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review

A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance

Vascular endothelial growth factor–regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases

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