Expression of the vascular endothelial growth factor receptor-2/Flk-1 in breast carcinomas: Correlation with proliferation

Nakopoulou, Lydia; Stefanaki, Kalliopi; Panayotopoulou, Effie; Giannopoulou, Ioanna; Athanassiadou, Pauline; Gakiopoulou-Givalou, H; Louvrou, Androniki

doi:10.1053/hupa.2002.126879

Cited by 97 publications

(65 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vascular endothelial growth factor receptors are in most cases specifically expressed on vascular endothelial cells, but certain tumour cells also express VEGFR2 (Masood et al, 1997;Dias et al, 2000;Masood et al, 2001;Podar et al, 2001;Strizzi et al, 2001;Jackson et al, 2002;Nakopoulou et al, 2002). The expression of VEGFR2 by tumour cells may be a mechanism to become less dependent on VEGF signalling for tumour angiogenesis as well as to negatively regulate the VEGF expression (Hiratsuka et al, 1998;Kearney et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models

et al. 2004

View full text Add to dashboard Cite

During the development of indazolylpyrimidines as novel and potent inhibitors of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) tyrosine kinase, we observed that some human tumour xenografts are more sensitive to VEGFR2 kinase inhibitors than others. A better understanding of the basis for this differential response may help to identify a predictive marker that would greatly aid in the identification of a suitable patient population for treatment. One representative compound from the indazolylpyrimidine series is GW654652 that inhibited all three VEGFRs with similar potency. The inhibition of VEGFR2 kinase by GW654652 was about 150 to 48800 more potent than the inhibition of eight other kinases tested. GW654652 inhibited VEGFand bFGF-induced proliferation in endothelial cells with an IC 50 of 110 and 1980 nM, respectively, and has good pharmacokinetic profile in mouse and dog. We investigated the association between VEGF and VEGFR2 expression and the antitumour efficacy of GW654652, in various xenograft models. Statistically significant associations were observed between the antitumour efficacy of GW654652 in xenografts and VEGF protein (P ¼ 0.005) and VEGFR2 expression (P ¼ 0.041). The oral dose of GW654652 producing 50% inhibition of tumour growth (ED 50 ) decreased with increasing levels of VEGF (r ¼ À0.94); and, in contrast, the ED 50 increased with the increased expression of VEGFR2 (r ¼ 0.82). These results are consistent with the observed inverse correlation between VEGF and VEGFR2 expression in tumours. These findings support the hypothesis that VEGF and VEGFR2 expression by tumours may predict the therapeutic outcome of VEGFR kinase inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The receptors EGFR/ErbB-1 (Nakopoulou et al, 1994;Kira et al, 1997;Ito et al, 2001b), neu/Her2/ ErbB-2 (Nakopoulou et al, 1994;Ito et al, 2001b), Her3/ErbB-3 (Ito et al, 2001b) and Her4/ErbB-4 (Ito et al, 2001b) are expressed in HCCs; however, staining frequency and intensity of the tumor tissues in comparison to the surrounding non-tumorous liver tissues differ between these studies (Table 1). It is noteworthy that in contrast to other carcinomas (e.g.…”

Section: Transforming Growth Factor A/epidermal Growth Factor Signalimentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

View full text Add to dashboard Cite

“…The median number of treatment cycles was three (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] in the 20 evaluable patients ( Table 2). Fifteen (75%) discontinued treatment because of progressive disease and five (25%) discontinued treatment because of adverse events, including: grade 3 headache (n ϭ 1), grade 3 transaminitis (n ϭ 1), grade 2 dyspepsia and weight loss (n ϭ 1), grade 3 headache, hypertension, and chest pain (n ϭ 1), and grade 3 gastrointestinal hemorrhage (n ϭ 1).…”

Section: Treatmentmentioning

confidence: 99%

“…A number of key proangiogenic factors, including vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) [4,5] and the class III receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR) [6,7] and stem cell factor receptor (KIT), are overexpressed in breast cancer [8 -10]. Many of these are associated with a poor prognosis [11][12][13][14] and a poor response to systemic chemotherapy in advanced breast cancer patients [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

et al. 2010

View full text Add to dashboard Cite

Purpose. Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of singleagent pazopanib in recurrent or metastatic breast cancer (MBC).Patients and Methods. Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2.Results. Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease

show abstract

Expression of the vascular endothelial growth factor receptor-2/Flk-1 in breast carcinomas: Correlation with proliferation

Cited by 97 publications

References 45 publications

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models

Dysregulation of growth factor signaling in human hepatocellular carcinoma

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

Contact Info

Product

Resources

About