Abstract:
PURPOSE:Elevated expression of PAI-1 has been widely linked with adverse outcomes in a variety of human cancers, such as breast, gastric and ovarian cancers, rendering PAI-1 a prognostic biomarker. As a result, several chemical inhibitors are currently being developed against PAI-1; however, the clinical setting where they might confer survival benefits has not yet been elucidated. METHODS:RNA sequencing data analysis from the TCGA/GTEx cancer portals (n = 3607 samples). In silico molecular docking analyses to predict functional macromolecule interactions. ER-/PR- (MDA-MB-231) and ER+/PR+ (MCF-7) breast cancer cell lines implemented to assess the effect of oleuropein as a natural inhibitor of PAI-1-mediated oncogenic proliferation. RESULTS:We show that high PAI-1 levels inversely correlate with ER and PR expressions in a wide panel of estrogen/progesterone-responsive human malignancies. By implementing an in silico molecular docking analysis, we identify oleuropein, a phenolic component of olive oil, as a potent PAI-1-binding molecule displaying increased affinity compared to the other olive oil constituents. We demonstrate that EVOO or oleuropein treatment alone may act as a natural PAI-1 inhibitor by incrementally destabilising PAI-1 levels selectively in ER-/PR- breast cancer cells, accompanied by downstream caspase activation and cell growth inhibition. In contrast, ER+/PR+ breast cancer cells, where PAI-1 expression is absent or low, do not adequately respond to treatment. CONCLUSIONS:Our study demonstrates an inverse correlation between PAI-1 and ESR1/PGR levels, as well as overall patient survival in estrogen/progesterone-responsive human tumours. With a focus on breast cancer, our data identify oleuropein as a natural PAI-1 inhibitor and suggest that oleuropein-mediated PAI-1 destabilisation may confer clinical benefit only in ER-/PR- tumours.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Tzekaki EE,Geromichalos G,Lavrentiadou SN,Tsantarliotou MP,Pantazaki AA,Papaspyropoulos Adoi
10.1007/s10549-020-06054-xsubject
Has Abstractpub_date
2021-01-03 00:00:00eissn
0167-6806issn
1573-7217pii
10.1007/s10549-020-06054-xpub_type
杂志文章abstract::Estrogen has an important role in stimulating the growth of breast carcinomas. Inhibition of estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against aromatase, a cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of est...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00682736
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. METHODS:Of the 53,670 patients registered between 2004 and 2006 and su...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3984-8
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor 'dimensions' were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying g...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-05097-5
更新日期:2019-05-01 00:00:00
abstract::Circulating CA 15-3 antigen levels were evaluated in patients with benign diseases and breast cancer patients with no clinical evidence of disease after surgery (NED). Patients with breast cancer NED were followed for tumor recurrence or death during a median of 12.9 months (range 1 to 25 months). CA 15-3 and carcinoe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806524
更新日期:1989-03-01 00:00:00
abstract::Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006268426526
更新日期:1999-09-01 00:00:00
abstract:PURPOSE:APOBEC3B belongs to the family of DNA-editing enzymes. A copy number variant targeting the genomic APOBEC3A-APOBEC3B locus has a significant impact on breast cancer risk, but the relative contribution of APOBEC3B is uncertain. In this study, we investigate a loss-of-function mutation that selectively targets AP...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-016-4100-9
更新日期:2017-02-01 00:00:00
abstract::The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antige...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF01803781
更新日期:1996-01-01 00:00:00
abstract::The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00665785
更新日期:1995-05-01 00:00:00
abstract::The Rho family of GTPases has been intensively studied for their roles in signal transduction processes leading to cytoskeletal-dependent responses, including cell migration and phagocytosis. In addition, they are important regulators of cell cycle progression and affect the expression of a number of genes, including ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/B:BREA.0000018423.47497.c6
更新日期:2004-03-01 00:00:00
abstract::Expression of the oestrogen producing enzyme, aromatase, is regulated in a tissue-specific manner by its encoding gene CYP19A1. In post-menopausal women, the major site for oestrogen production in the breast is the adipose, where CYP19A1 transcription is driven by the distal promoter I.4 (PI.4). Transcripts via this p...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2413-5
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice. METHODS:The observatio...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-5058-6
更新日期:2019-02-01 00:00:00
abstract::ALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-f...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-009-0646-0
更新日期:2010-02-01 00:00:00
abstract::Conflicting theories of epithelial carcinogenesis disagree on the clonal composition of primary tumors and on the time at which metastases occur. In order to study the spatial distribution of disparate clonal populations within breast carcinomas and the extent of the genetic relationship between primary tumors and reg...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9317-6
更新日期:2007-04-01 00:00:00
abstract::While overall survival (OS) has historically been the primary endpoint for clinical trials in oncology, progression-free survival (PFS) has gained acceptance as a valuable surrogate endpoint. However, there are no known published reports about the value of PFS from the patient's perspective. We developed a questionnai...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2734-4
更新日期:2013-12-01 00:00:00
abstract::Genome-Wide Association Studies have identified several loci associated with breast cancer (BC) in populations of different ethnic origins. One of the strongest associations was found in the FGFR2 gene, and MAP3K1 has been proposed as a low-penetrance BC risk factor. In this study, we evaluated the associations among ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2359-z
更新日期:2013-01-01 00:00:00
abstract:PURPOSE:The Chinese bridging study PUFFIN (NCT02896855) aimed to assess consistency of efficacy with CLEOPATRA (NCT00567190), investigating pertuzumab with trastuzumab and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive locally recurrent or metastatic breast canc...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05728-w
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described. METHODS:A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distan...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4529-5
更新日期:2018-01-01 00:00:00
abstract::GB3 and GB5 are mouse monoclonal antibodies raised against human amnion. GB3 detects the epidermal basement membrane, and GB5 reacts with the junctional substances between the epithelial cells. These two antibodies were studied on breast tissues by indirect immunofluorescence. All (n = 8) of the normal mammary glandul...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01807700
更新日期:1986-01-01 00:00:00
abstract::To compare overall survival between women with unilateral breast cancer (UBC) and contralateral breast cancer (CBC). Women with UBC (N = 182,562; 95 %) and CBC (N = 8,912; 5 %) recorded in the Netherlands Cancer Registry between 1989 and 2008 were included and followed until 2010. We incorporated CBC as a time-depende...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2588-9
更新日期:2013-06-01 00:00:00
abstract::It is still controversial whether the identification of micrometastases and isolated tumor cells in the axillary lymph nodes of patients with breast cancer has any prognostic value. We evaluated the prognostic role of isolated tumor cells and micrometastases in the axillary lymph nodes in 3,158 consecutive patients pT...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0446-6
更新日期:2009-11-01 00:00:00
abstract::Neural networks can be used as pattern recognition systems in complex data sets. We are exploring their utility in performing survival analysis to predict time to relapse or death. This technique has the potential to find easily some types of very complex interactions in data that would not be easily recognized by con...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666212
更新日期:1994-01-01 00:00:00
abstract::Knowledge about long-term consequences of breast cancer treatment on shoulder and arm function and volume in stages I-II breast cancer survivors is limited. The effects of shoulder-arm function shortly after surgery on long-term function are unknown. One hundred and ninety-four women were examined pre-surgery (T0) and...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2509-y
更新日期:2013-05-01 00:00:00
abstract::Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-010-1200-9
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:Estimated glomerular filtration rate (eGFR) is commonly used to calculate carboplatin doses and capping the eGFR may be used to reduce the risk of excessive dosing and toxicity. We sought to retrospectively examine the impact of our carboplatin guidelines on pathological complete response rates (pCR) and toxici...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05868-z
更新日期:2020-11-01 00:00:00
abstract::For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1900-9
更新日期:2012-02-01 00:00:00
abstract::Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women in...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10549-009-0309-1
更新日期:2009-10-01 00:00:00
abstract::The DNA repair pathway is known to play a role in the etiology of breast cancer. A number of studies have demonstrated that common germline variants in genes involved in the DNA repair pathway influence breast cancer risk. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 12 s...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0084-4
更新日期:2009-06-01 00:00:00
abstract::A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA) has been shown, when given at 55-60 days of age, to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-0270-6
更新日期:2005-07-01 00:00:00
abstract::Tumor necrosis factor-α (TNF-α) is an important pro-inflammatory cytokine in the development and progress in human cancer. TNF-α polymorphisms have been confirmed to influence the risk for several types of cancer, however, the associations between TNF-α polymorphisms and breast cancer (BC) remain controversial and amb...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-011-1494-2
更新日期:2011-09-01 00:00:00
abstract::Addition of epirubicin to adjuvant chemotherapy can provide important benefits for patients with early breast cancer, but the optimal dose remains unclear. Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC(6...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-008-9894-7
更新日期:2008-12-01 00:00:00