Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko; Matsuda, Masakazu; Baba, Kenichiro; Yamashita, H.; Fukuda, Makoto

doi:10.1007/bf02967636

Cited by 37 publications

(26 citation statements)

References 29 publications

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“…We also found that tumor size was positively related to post-chemotherapy IL-6 levels but negatively related to post-chemotherapy VEGF and sP-selectin levels. There are reports of a positive not negative association between tumor size and plasma VEGF levels in breast cancer (Nishimura et al, 2003;Wu et al, 2002). IL-6 expression is not typically associated with tumor size but with estrogen and progesterone receptor expression (Fontanini et al, 1999), as was observed in this study prior to chemotherapy.…”

Section: Discussionsupporting

confidence: 62%

“…Circulating levels of VEGF are elevated in breast cancer and are an independent predictor of poorer survival (Nishimura et al, 2003;Wu et al, 2002). Expression of the adhesion molecule ICAM-1, which aids in host immune surveillance of tumor cells (Ogawa et al, 1998;Shirai et al, 2003), has been implicated in tumor progression and metastases, with greater expression being associated with low growth potential, negative lymph node involvement, and good prognosis (O'Hanlon et al, 2002;Vasse et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Mills

Ancoli‐Israel

Parker

et al. 2008

Brain, Behavior, and Immunity

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Although chemotherapy for breast cancer can increase inflammation, few studies have examined predictors of this phenomenon. This study examined potential contributions of demographics, disease characteristics, and treatment regimens to markers of inflammation in response to chemotherapy for breast cancer. Thirty-five women with stage I -III-A breast cancer (mean age 50 years) were studied prior to cycle 1 and prior to cycle 4 of anthracycline-based chemotherapy. Circulating levels of inflammatory markers with high relevance to breast cancer were examined, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), Interleukin-1 receptor antagonist (IL1-RA), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), Interleukin-(IL-6), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). Chemotherapy was associated with elevations in VEGF (p≤0.01), sICAM-1 (p≤0.01), sP-selectin (p≤0.02) and vWf (p≤0.05). Multiple regression analysis controlling for age and body mass index (BMI) showed that higher post-chemotherapy levels of inflammation were consistently related to higher prechemotherapy levels of inflammation (p's ≤0.05) as well as to certain disease characteristics. Postchemotherapy IL-6 levels were higher in patients who had larger tumors (p≤0.05) while postchemotherapy VEGF levels were higher in patients who had smaller tumors (p≤0.05). Postchemotherapy sP-selectin levels were highest in women who had received epirubicin, cytoxan, 5fluorouracil chemotherapy (p≤0.01). These findings indicate that chemotherapy treatment can be associated with elevations in certain markers of inflammation, particularly markers of endothelial and platelet activation. Inflammation in response to chemotherapy is most significantly related to inflammation that existed prior to chemotherapy but also potentially to treatment regimen and to certain disease characteristics.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Mills

Ancoli‐Israel

Parker

et al. 2008

Brain, Behavior, and Immunity

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“…Although the utility of biomarkers for evaluating MVD was highly anticipated, these markers were not predictive for clinical response in patients treated with bevacizumab (7). Regarding growth factors and cytokines, the plasma VEGF level has been shown to be neither a pharmacodynamic nor a predictive biomarker of antiangiogenic drugs (7,8), although the plasma VEGF level is a well-known prognostic biomarker (9)(10)(11). Plasma-soluble VEGFR2, on the other hand, may be a promising and specific biomarker of antiangiogenic drugs for evaluating their effects (12,13).…”

Section: Introductionmentioning

confidence: 99%

Antitumor Activity of BIBF 1120, a Triple Angiokinase Inhibitor, and Use of VEGFR2+pTyr+ Peripheral Blood Leukocytes as a Pharmacodynamic Biomarker In Vivo

Kudo

Arao

Tanaka

et al. 2011

Clinical Cancer Research

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Purpose: BIBF 1120 is a potent, orally available triple angiokinase inhibitor that inhibits VEGF receptors (VEGFR) 1, 2, and 3, fibroblast growth factor receptors, and platelet-derived growth factor receptors. This study examined the antitumor effects of BIBF 1120 on hepatocellular carcinoma (HCC) and attempted to identify a pharmacodynamic biomarker for use in early clinical trials.Experimental Design: We evaluated the antitumor and antiangiogenic effects of BIBF 1120 against HCC cell line both in vitro and in vivo. For the pharmacodynamic study, the phosphorylation levels of VEGFR2 in VEGF-stimulated peripheral blood leukocytes (PBL) were evaluated in mice inoculated with HCC cells and treated with BIBF 1120.Results: BIBF 1120 (0.01 mmol/L) clearly inhibited the VEGFR2 signaling in vitro. The direct growth inhibitory effects of BIBF 1120 on four HCC cell lines were relatively mild in vitro (IC 50 values: 2-5 mmol/L); however, the oral administration of BIBF 1120 (50 or 100 mg/kg/d) significantly inhibited the tumor growth and angiogenesis in a HepG2 xenograft model. A flow cytometric analysis revealed that BIBF 1120 significantly decreased the phosphotyrosine (pTyr) levels of VEGFR2

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“…Multiple studies have demonstrated the prognostic significance of plasma VEGF-A concentrations as well as their suppression by antiangiogenic treatment (15)(16)(17)(18). The advantage of our study was that VEGF-A protein levels measured in plasma do not require correction, as is the case when they are measured in serum, because of VEGF release from activated platelets (19).…”

Section: Discussionmentioning

confidence: 97%

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

Pectasides

Papaxoinis²,

Kotoula³

et al. 2011

Oncol Rep

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Abstract.It is well known that low-dose metronomic chemotherapy has antiangiogenic activity. The aim of the present trial was to investigate the antiangiogenic properties of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic breast cancer patients received 35 mg/m 2 docetaxel weekly as a recommended treatment. Blood samples were collected before the start of chemotherapy (baseline) and during treatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) plasma levels were measured at baseline and during treatment, while VEGF-A, endothelial nitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNA levels were measured at baseline, in 127 patients and 39 female healthy controls. In general, the treatment was well-tolerated. Sixty-one patients (38%) achieved an objective response (4% complete and 34% partial response), while 52 (33%) had stable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range 2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) had died.Median progression-free survival (PFS) was 8.8 months and median overall survival (OS) was 27.7 months. Median baseline level of plasma NO was significantly lower in patients than in healthy controls (p=0.010), while none of the plasma markers significantly changed upon docetaxel treatment. In addition, the median relative quantification value for THBS-1 mRNA was significantly higher (p<0.001) in patients as compared to healthy controls. NO plasma levels were positively associated with the number of organs involved (p=0.008). In multivariate analysis, low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1 mRNA levels were found to be associated with shorter OS and PFS, independently from established clinical prognostic factors. Although an antiangiogenic activity of weekly docetaxel was not demonstrated in the present study, some interesting observations regarding the prognostic role of a number of blood angiogenic markers could be made.

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Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer

Abstract: These results suggest that plasma VEGF levels in breast cancer have a clinical significance in that they are associated with the extent or metastasis of malignant lesions and are involved in angiogenesis in postmenopausal patients.

Cited by 37 publications

References 29 publications

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Antitumor Activity of BIBF 1120, a Triple Angiokinase Inhibitor, and Use of VEGFR2+pTyr+ Peripheral Blood Leukocytes as a Pharmacodynamic Biomarker In Vivo

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

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