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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum and plasma concentrations of vascular endothelial growth factor (sVEGF and pVEGF), serum concentrations of interleukin 6 (IL-6), and VEGF platelet load (VEGF/pl) in the blood of healthy controls (n = 26), breast cancer patients with locoregional disease (n = 31), and patients with progressive advanced disease (n = 73) have been compared. The 95th percentile values for the control population were 250 pg/mL for sVEGF, 30 pg/mL for pVEGF, and 1.6 pg/mL for IL-6. The 95th percentile value of the calculated VEGF/pl was 1.0 pg/10(6) platelets in the control population. Serum VEGF concentrations correlated with platelet number in all the groups. Patients with thrombocytosis had a median sVEGF concentration of 833 pg/mL, compared to 249 pg/mL in other patients (P = 0.018). Serum IL-6 levels correlated with sVEGF levels and with the calculated VEGF/pl. Serum IL-6 concentration was significantly higher in patients with breast cancer compared to healthy controls (P < 0.0001). Median IL-6 serum levels were nearly 10 times higher in patients with metastatic breast cancer as compared to the those with locoregional disease (6.0 pg/mL versus 0.7 pg/mL, respectively). Plasma VEGF and the VEGF/pl were also significantly different in the 3 groups. The ratio between sVEGF and pVEGF tended to be smaller in the metastatic breast cancer group compared to the patients with locoregional disease (median, 7.5 versus 10.1, respectively; P = 0.066), suggestive of more intravasal platelet degranulation in the former group. Serum IL-6 level is the most discriminative factor separating healthy controls and the locoregional and metastatic breast cancer patient groups. These results suggest a role for tumor-derived IL-6 in regulating VEGF expression in platelets and their precursors and also confirm the role of circulating platelets in the storage of VEGF.
Clin Breast Cancer 2002 Jan
PMID:Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. 1189 64

The spread of cancer cells to regional lymph nodes through the lymphatic system is the first step in the dissemination of breast cancer. In several human cancers including those of the breast and prostate, the expression of vascular endothelial growth factor C (VEGF-C) is associated with lymph node metastasis. Our study was undertaken to evaluate the effect of VEGF-C on metastasis of poorly invasive, estrogen dependent human MCF-7 breast cancer cells. MCF-7 breast cancer cells transfected with VEGF-C (MCF-7-VEGF-C) were grown as tumors in the mammary fat pads of nude mice implanted with subcutaneous estrogen pellets. Tumor lymphangiogenesis and lymph node metastasis were studied immunohistochemically using antibodies against lymphatic vessel hyaluronan receptor -1 (LYVE-1), VEGF receptor-3 (VEGFR-3), PECAM-1, pan-cytokeratin and estrogen dependent pS2 protein. Overexpression of VEGF-C in transfected MCF-7 cells stimulated in vivo tumor growth in xenotransplanted mice without affecting estrogen responsiveness. The resulting tumors metastasized to the regional lymph nodes in 75% (in 6 mice out of 8, Experiment I) and in 62% (in 5 mice out of 8, Experiment II) of mice bearing orthotopic tumors formed by MCF-7-VEGF-C cells whereas no metastases were observed in mice bearing tumors of control vector-transfected MCF-7 cells (MCF-7-Mock). The density of intratumoral and peritumoral lymphatic vessels was increased in tumors derived from MCF-7-VEGF-C cells but not MCF-7-Mock cells. Taken together, our results show that VEGF-C overexpression stimulates tumor lymphangiogenesis and induces normally poorly metastatic estrogen-dependent MCF-7 tumors to disseminate to local lymph nodes. These data suggest that VEGF-C has an important role in lymph node metastasis of breast cancer even at its hormone-dependent early stage.
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PMID:VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. 1194 78

Tumor growth and local invasion are greatly dependent on the malignant potential of a tumor cell, but are also significantly modulated by a variety of local factors. These factors comprise cytokines, growth factors and extracellular matrix proteins (ECM), which act through a complex system of auto-, para- and juxtacrine interactions. Some factors are produced by the malignant cell itself, others are expressed by adjacent tumor stroma, migrated inflammatory cells, or resident macrophages. We have investigated the influences of cytokines and growth factors known to be expressed by tumor stroma on the cytokine expression pattern of three human breast cancer cell lines of different malignant potential. MCF-7, T47D and MDA-MB-231 were incubated with human recombinant TNF-alpha, IGF-I, IGF-II, bFGF, HGF or G-CSF and the pattern of tumor-cell-derived TGF-beta1, bFGF, IL-1alpha and VEGF was analyzed. Among the three cell lines used we observed a heterogenous response to stromal cytokines by measuring above mentioned factors in the cell culture's supernatants, but no clear correlation between malignant potential and cytokine expression pattern seemed obvious. We hypothesize that local growth factors may have a significant modulatory effect on malignant behavior in vivo. We conclude that this effect might depend on individual responses and on the differentiation state of tumor cells.
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PMID:Influences of stroma-derived growth factors on the cytokine expression pattern of human breast cancer cell lines. 1204 92

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.
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PMID:Biomarkers for breast cancer. 1214 73

VEGF (vascular endothelial growth factor) secreted from tumor cells including breast cancer serves as a potent angiogenic factor which favors tumor growth and metastasis. Indeed, a higher concentration of serum VEGF has been shown to associate with a poorer prognosis in patients with breast cancer. On the other hand, constitutive expression of a transcription factor, NF-kappaB was correlated with progression and metastasis in a number of human breast cancers, suggesting a possible regulation of VEGF expression by NF-kappaB. We thus investigated the relationship between the expression of VEGF and constitutive NF-kappaB activity in three breast cancer cell lines, MCF-7, T47D, and MDA-MB-231. The basal levels of VEGF mRNA expression correlated with those of nuclear NF-kappaB activity in these cell lines. The highest NF-KB activity in MDA-MB-231 cells was associated with the highest expression of VEGF mRNA, while the activity and the mRNA levels were moderate in MCF cells and the lowest in T47D cells. In MDA-MB-231 cells, inhibition of NF-KB by adenovirus-mediated expression of a dominant negative NF-kappaB or by a proteasome inhibitor, MG132, decreased the VEGF mRNA. These results suggest that NF-kappaB is involved in the upregulation of VEGF mRNA and inhibition of the activity could be a new approach for the treatment of breast cancer by preventing angiogenesis.
Breast Cancer Res Treat 2002 Jun
PMID:Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells. 1216 Mar 29

Although cloning of ER beta has prompted a reevaluation of the role of ERs in human breast cancer and there have been many studies focusing on the clinical value of ER beta detection, however, few reports evaluated the prognostic significance of ER beta based on follow-up data. The VEGF gene transcription may be mediated by different ER subtypes directly. The aim of this study was to evaluate the relationship of angiogenesis factor VEGF with different ER subtypes and the prognostic value of ER beta and VEGF in 116 human breast cancer patients. Of these patients, 40 (34.5%) were ER beta protein high expressed and 76 (65.5%) were ER beta protein low expressed. When correlated the ER beta protein levels with other clinical characteristics, statistical significance (p<0.05) was found between ER beta protein expression and menopausal status, and tumor grade. No significance was found between ER beta protein level and node status, stage, or tumor size. Inverse relationship was found between ER beta protein expression and PR status (p<0.05). When comparing the VEGF levels with different ER subtypes a significant difference between ERs and VEGF was found. In ER beta protein high expression group, the VEGF protein was highly expressed (p<0.01), inverse relationship was also found between ER alpha and VEGF. In univariate analysis ER alpha, ER beta and VEGF levels had prognostic value for both relapse-free survival and overall survival (p<0.05). However, in a multivariate study, ER beta and ER alpha protein levels lost the prognostic value either to relapse-free survival or to overall survival. Only VEGF levels acted as an independent prognostic factor to disease-free survival. The result suggested that ER beta protein may have important prognostic value in human breast cancer patients. VEGF expression may be mediated through different ER subtypes.
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PMID:The expression of ER beta protein correlates with vascular endothelial growth factor and its prognostic significance in human breast cancer. 1216 51

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.
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PMID:Age-associated biomarker profiles of human breast cancer. 1220 28

In cell culture, the compound 317615 2HCl, a potent inhibitor of VEGF-stimulated HUVEC proliferation, was not very effective against MX-1 breast cancer cells (IC50= 8.1 microM) or SKOV-3 ovarian carcinoma cells (IC50 = 9.5 microM). Exposure to combinations of paclitaxel or carboplatin and 317615 x 2HCl with MX-1 cells in culture resulted in cell survival that reflected primarily additivity of the two agents. Exposure of SKOV-3 cells to paclitaxel or carboplatin along with 317615 2HCl resulted in cell survivals that reflected additivity of 317615 x 2HCl with paclitaxel and greater-than-additive cytotoxicity with carboplatin. Administration of 317615 x 2HCI orally twice daily to nude mice bearing subcutaneous MX-1 tumors or SKOV-3 tumors resulted in a decreased number of intratumoral vessels as determined by CD31 and CD105 staining with decreases of 35% and 43% in MX-1 tumors and 60% and 75% in SKOV-3 tumors, respectively. 317615 x 2HCl was an active antitumor agent against the MX-1 xenograft and increased the tumor growth delay produced by paclitaxel by 1.7-fold and the tumor growth delay produced by carboplatin by 3.8-fold. Administration of 317615 x 2HCl also increased the tumor growth delay produced by fractionated radiation therapy in the MX-1 tumor. Treatment with 317615 x 2HCl alone increased the lifespan of animals bearing intraperitoneal SKOV-3 xenografts by 1.9 fold compared with untreated control animals. The combination of paclitaxel and 317615 x 2HCl resulted in 100% 120-day survival of SKOV-3 bearing animals. Administration of 317615 x 2HCl along with carboplatin to animals bearing the SKOV-3 tumor produced a 1.8-fold increase in lifespan compared with carboplatin alone. 317615 x 2HCl is a promising new antiangiogenic agent that is in early phase clinical testing.
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PMID:Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human breast cancer and ovarian cancer xenografts. 1220 87

Advances in molecular and cell biology have led to further understanding of the mechanisms of malignant growth and metastasis in human breast cancer cells. Initiation and progression of breast cancer results from mutations and the abnormal expression of many genes that control cellular proliferation, differentiation, invasion, metastasis and sensitivity to therapy (chemotherapy and radiation therapy). Inhibition of host immunity also plays a role in breast cancer progression. Many genes have been selected as targets for antisense therapy, including HER-2/neu, PKA, TGF-alpha, EGFR, TGF-beta, IGFIR, P12, MDM2, BRCA, Bcl-2, ER, VEGF, MDR, ferritin, transferrin receptor, IRE, C-fos, HSP27, C-myc, C-raf and metallothionein genes. The strategy behind antisense therapy is the development of specific therapeutic agents that aim to correct the mutations and abnormal expression of cellular genes in breast tumour cells by decreasing gene expression, inducing degradation of target mRNA and causing premature termination of transcription. Many in vitro and in vivo studies have investigated the therapeutic efficacy of oligonucleotides and antisense RNAs. These studies have demonstrated specific inhibition of tumour cell growth by antisense therapy and have shown synergistic inhibitory effects between antisense oligonucleotides or antisense RNA and conventional chemotherapeutic drugs used in the treatment of breast cancer. Antisense oligonucleotides have been modified to improve their ability to penetrate cells, bind to gene sequences and downregulate target gene function. Many delivery systems for antisense RNA and antisense oligonucleotides have been developed, including virus vectors (retrovirus, adenovirus and adeno-associate virus) and liposomes, to carry the antisense RNA or oligonucleotides through the cell membrane into the cytoplasm and nucleus of the tumour cells. However, in order to determine their feasibility antisense therapies need to be further investigated to determine their antitumour activity, pharmacokinetics and toxicity in breast cancer patients.
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PMID:Gene targets of antisense therapies in breast cancer. 1222 74

The transcription factor Ets-1 regulates the expression of several angiogenic and extracellular matrix remodeling factors, and might be implicated in disease progression of breast cancer. In the present study, the prognostic value of Ets-1 expression was assessed by quantitative real-time fluorescence RT-PCR in 123 sporadic primary breast cancer samples of patients with a median follow-up time of 62 months. Ets-1 expression levels correlated significantly with VEGF and PAI-1 in the same tissue. In univariate (P=0.0011) and multivariate (P=0.005) analyses, Ets-1 expression showed significant prognostic value for relapse-free survival. Ets-1 is a strong, independent predictor of poor prognosis in breast cancer. This seems - at least in part - to be attributable to its role in transcriptional regulation of factors involved in angiogenesis (VEGF), and extracellular matrix remodeling (PAI-1).
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PMID:Expression of the transcription factor Ets-1 is an independent prognostic marker for relapse-free survival in breast cancer. 1246 70


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