Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1-40 microM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (>/=5 microM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w(-1)) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 microM and 0.11 and 63 nmol g(-1), respectively. Cells were exposed to tricin (0.11, 1.1 or 11 microM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 microM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 microM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious.
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PMID:Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo. 1531 67

We investigated the expression levels of human lactoferrin (Lf), a steroid hormone-inducible gene product the expression of which is often altered during oncogenesis, and of Delta-lactoferrin (DeltaLf), its alternative isoform, which has been shown to be absent from tumor cell lines in commonly used human breast epithelial cell lines, using semiquantitative RT-PCR. Both mRNAs were detected but with levels of expression lower than those found in normal breast epithelial cells. This downregulation was much more visible for DeltaLf since its expression was either significantly diminished (BT-20, MCF-7 cell lines) or practically absent (MDA-MB-231, T-47D, HBL 100 cell lines). In order to determine whether Lf gene products are useful prognosic tools, we further analyzed their expression levels in 99 primary breast cancer biopsies. DeltaLf transcripts were found in all of the samples, whereas Lf transcripts were found in 88% of them. Lf and DeltaLf expression levels were positively correlated (p = 0.003). Lf expression was related to tumor type with a higher recovery in lobular-type tumors (p = 0.04). DeltaLf expression was related to the histoprognostic grading (p = 0.02). In univariate analyses, DeltaLf and Lf expressions were prognosis parameters, high concentrations being associated with a longer overall survival.
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PMID:Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer. 1554 12

Previous studies have demonstrated the potential significance of Endothelin (ET)-1 and its receptors, ETAR and ETBR, in the development and progression of breast cancer. The objective of this study was to assess the expression levels and potential regulation of the "ET axis" in human non-neoplastic and neoplastic breast tissue as well as in various human breast cancer cell lines. Expression of ET-1, ETAR and ETBR was evaluated in 31 neoplastic and 7 non-neoplastic breast tissue samples and in six human breast cancer cell lines using conventional and quantitative real-time RT-PCR, Western blotting and immunohistochemistry. The effects of 17beta-estradiol (E2) and cobalt-chloride (CoCl2) treatment on ET-1, ETAR and ETBR expression were studied in vitro. ETAR mRNA expression levels were found to be statistically significantly higher in breast cancer specimens than in non-neoplastic breast tissue (p<0.001). For ET-1 and ETBR mRNA expression, no significant difference was observed between the two groups. All cell lines exhibited expression of ET-1 and ETAR mRNA, whereas none showed significant ETBR mRNA expression. We observed a strong and reproducible induction of ETAR mRNA and protein expression by E2 and CoCl2 in MDA-MB-468 and BT-474 cells and in MDA-MB-453 and SK-BR-3 cells with a maximum increase after 8 and 16 h of treatment, respectively, while MCF-7 and HBL-100 cells showed a constitutive expression pattern. The present data suggest a novel mechanism in the regulation of ETAR expression in breast cancer. Based on these findings, a combination of ETAR-antagonists with adjuvant endocrine treatment seems to be a reasonable therapeutic strategy.
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PMID:Overexpression of Endothelin-A-receptor in breast cancer: regulation by estradiol and cobalt-chloride induced hypoxia. 1575 89

Cycloheximide, a protein synthesis inhibitor, was encapsulated in cross-linked gelatin nanoparticles (Type B, Bovine skin, 75 Bloom) of 168 nm diameter with 26% entrapment efficiency. In-vitro release kinetics of the drug from the nanoparticles was done in phosphate buffer saline (PBS) at pH 7.4 and pH 5.8. The release kinetics showed a bi-phasic curve. Interestingly, the release of drug is approx 90% in acidic pH as compared to 50% release in neutral pH. The particle size was determined by Dynamic Light Scattering (DLS) technique, and size distribution spectra at different pH were observed to vary inversely with increase in pH. These drug loaded nanoparticles were found to be stable in whole blood showing negligible haemolysis. Cytotoxicity in HBL-100 and MCF-7, breast cancer cell lines was done in a 24-72 hrs assay, showing increased anti-tumour activity over a period of time indicating slow release. Dose dependent cytotoxicity was observed after 24 hours upto 72 hours of incubation of nanoparticles while the drug per se (<4 microg) showed 93% toxicity within 24 hours. Phase contrast microscopy of nanoparticle-cell interaction, clearly indicated aggregation along the lipid cell-membrane. Electron Microscopy (TEM, SEM) studies revealed its size and spherical shape. The stability of the particle, the slow and controlled release of drug from the gelatin nanoparticles indicate that it is a good candidate to deliver bio-pharmaceuticals. These behave as "intelligent" carriers for drug delivery, and can be exploited to empty their drug load in acidic medium. The paper focuses on the release kinetics of the gelatin nanoparticles that can be successfully exploited to treat solid tumors.
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PMID:Release kinetics from bio-polymeric nanoparticles encapsulating protein synthesis inhibitor- cycloheximide, for possible therapeutic applications. 1585 91

Parthenolide, a sesquiterpene lactone, shows antitumor activity in vitro, which correlates with its ability to inhibit the DNA binding of the antiapoptotic transcription factor nuclear factor kappaB (NF-kappaB) and activation of the c-Jun NH(2)-terminal kinase. In this study, we investigated the chemosensitizing activity of parthenolide in vitro as well as in MDA-MB-231 cell-derived xenograft metastasis model of breast cancer. HBL-100 and MDA-MB-231 cells were used to measure the antitumor and chemosensitizing activity of parthenolide in vitro. Parthenolide was effective either alone or in combination with docetaxel in reducing colony formation, inducing apoptosis and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1 in vitro. In an adjuvant setting, animals treated with parthenolide and docetaxel combination showed significantly enhanced survival compared with untreated animals or animals treated with either drug. The enhanced survival in the combination arm was associated with reduced lung metastases. In addition, nuclear NF-kappaB levels were lower in residual tumors and lung metastasis of animals treated with parthenolide, docetaxel, or both. In the established orthotopic model, there was a trend toward slower growth in the parthenolide-treated animals but no statistically significant findings were seen. These results for the first time reveal the significant in vivo chemosensitizing properties of parthenolide in the metastatic breast cancer setting and support the contention that metastases are very reliant on activation of NF-kappaB.
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PMID:The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer. 1595 58

MDR1 is upregulated in many tumors. We have previously detected activation of the MDR1 upstream promoter in metastatic breast cancer cells. MDR1 overlaps with an uncharacterized gene transcribed from the opposite strand, coding for Rap2 interacting protein 9 (RPIP9). Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown. We developed sensitive methods for detecting and quantifying RPIP9 mRNA and used it to identify these transcripts in normal human tissues, 60 biopsies of primary breast carcinoma, in isolated epithelial cells both from the primary tumor and from associated lymph nodes, and from bone marrow biopsies of 74 breast cancer patients. RPIP9 is expressed at high levels in normal testis, brain and adrenal gland, and at very low levels in normal breast. Tumorigenic breast carcinoma cell lines expressed RPIP9, whereas MCF-10A and HBL-100 that do not form tumors in nude mice had undetectable levels of RPIP9 mRNA. RPIP9 was activated in a high proportion of breast carcinomas (61.6%; n = 60) and a significant correlation with metastatic lymph node invasion (N = 0-3 vs. N > 3, where N = number of lymph nodes invaded; p = 0.031) was found. RPIP9 mRNA could be detected in malignant epithelial cells isolated from the primary tumor and from metastasized lymph nodes as well as in the bone marrow of significantly more poor-prognosis (N > 3) than better-prognosis (N = 0-3) patients (p = 0.001). Therefore, activation of RPIP9 occurs during the malignant breast epithelial transformation and increases with progression toward an invasive phenotype.
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PMID:Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma and correlates with a poor prognosis. 1598 26

Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins, preferentially recognizes Galbeta1-4GlcNAc (LacNAc) sequences of oligosaccharides associated with several cell surface glycoconjugates. As demonstrated histochemically, gal-1 recognizes appropriate glycoepitopes on human breast cancer cells (MCF7) and on human chorionic carcinoma cells (BeWo). Gal-1 is expressed in many malignant and normal tissues. A high level of expression is found in lymphatic organs, which feature high rates of apoptosis. Furthermore, it is known that galectin-1 can initiate T cell apoptosis. In this study, we examined the apoptotic potential of gal-1 in vitro on MCF7 and BeWo cells. After growing both cell lines on chamber-slides for three days, apoptosis was induced by incubation with 30 microg gal-1 per ml serum-free medium for 6, 9 and 20 hours. To avoid false increased rates of apoptosis by deletion of FCS, all approaches were done with and without FCS. Apoptotic cells were detected by in situ nick translation. The rate of apoptosis was determined by counting 1500 cells per chamberslide. The normal rate of apoptosis ranged between 0.1% and 0.3%. The incubation of both cell lines with 30 microg/ml gal-1 in serum-free medium for 6 and 9 hours marginally raised the number of apoptotic cells. An increase of apoptosis was only shown by additional stimuli like hyperthermia, removal of CO2 and FCS for 20 hours. Impressing findings were manifested in an older passage of BeWo cells, in which only omission of FCS caused apoptotic rates for up to 25% after 6 hours. The presence of mycoplasma in this BeWo passage was shown by PCR. Our results demonstrated, that galectin-1 shows apoptotic potential in both the epithelial tumour cell lines examined only with additional stress stimuli.
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PMID:Induction of apoptosis in human breast cancer and trophoblast tumor cells by galectin-1. 1603 63

The chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata (EBV) was evaluated in N-nitrosodiethylamine (DEN, 200 mg/kg) induced experimental liver tumor in rats and human cancer cell lines. Oral administration of ethanol extract of Bauhinia variegata (250 mg/kg) effectively suppressed liver tumor induced by DEN as revealed by decrease in DEN induced elevated levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (GPx) and glutathione S-transferase (GST). The extract produced an increase in enzymatic antioxidant (superoxide dismutase and catalase) levels and total proteins when compared to those in liver tumor bearing rats. The histopathological changes of liver samples were compared with respective controls. EBV was found to be cytotoxic against human epithelial larynx cancer (HEp2) and human breast cancer (HBL-100) cells. These results show a significant chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata against DEN induced liver tumor and human cancer cell lines.
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PMID:Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human cancer cell lines. 1625 58

Inhibition of angiogenesis has become a major target in experimental cancer therapies. Vascular endothelial growth factor (VEGF) and its receptors are essential for breast cancer progression and relevant targets in experimental anti-angiogenesis. VEGF, produced by carcinoma cells, acts in a paracrine fashion on endothelial cells and displays autocrine activity on carcinoma cells. Breast cancer cells express VEGF-A, VEGF-B, VEGF-C and their receptors VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR) and neuropilin (NP-1/NP-2). VEGF-A triggers cellular signalling, an invasive phenotype of certain breast cancer cell lines and influences cell survival. However, such an autocrine VEGF/VEGFR signalling loop remains to be established. We demonstrate production of VEGF-A in cell lines MDA-MB-468, T47d, MCF-7, HBL-100 and in a primary breast cancer culture. Moreover, these cells showed baseline VEGFR-2 tyrosine-phosphorylation that could be enhanced by VEGF-A stimulation. In addition, VEGF-A leads to increased phosphorylation of ERK1/2 and Akt indicating that VEGF-A stimulation plays a crucial role in the regulation of cell growth, apoptosis, survival and differentiation. Moreover, we have established a novel breast cancer cell culture MW1 that expresses high levels of VEGF-A. We demonstrate that VEGFR-2 on the surface of breast cancer cells is functional and is capable of being stimulated by external VEGF-A. VEGF-A production by and VEGFR-2 activation on the surface of breast cancer cells indicates the presence of a distinct autocrine signalling loop that enables breast cancer cells to promote their own growth and survival by phosphorylation and activation of VEGFR-2. Moreover, this autocrine loop represents an attractive therapeutic target.
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PMID:Autocrine vascular endothelial growth factor signalling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro. 1632 60

Understanding the molecular background of breast cancer biology is critical in developing new biomarkers for earlier diagnosis and more optimized treatment. We performed a proteomic analysis of human breast carcinoma tissues to investigate the tumor-specific protein expression in breast carcinoma. Using 2-dimensional electorphoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we were able to identify a list of proteins which are upregulated in cancerous tissue. There was significant increase of galectin-1 expression in all cancerous tissues compared to noncancerous tissues, and its increased expression was further confirmed by western blot immunostaining. Subsequent immunohistochemical staining against galectin-1 in 105 breast cancer specimens showed significant correlation between galectin-1 expression in cancer-associated stromal cells and tumor invasiveness, T stage, TNM stage, and axillary lymph node metastasis. Galectin-1 expressionin cancer cells showed no correlation to above-mentioned pathologic variables. Hormonal receptor status and galectin-1 expression showed no correlation. This study demonstrates the upregulation of galectin-1 in breast carcinoma tissues and the clinical significance of galectin-1 in breast cancer patients. Our data supports the recently highlighted roles of galectin-1 in cancer-associated stroma and in tumor immune privilege.
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PMID:Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. 1730 2


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