Abstract:
:Microcalcifications containing calcium hydroxyapatite (HA) are often associated with malignant human breast lesions. Frequently, they are the only mammographic features that indicate the presence of a tumoural lesion. We previously reported the induction of both mitogenesis and prostaglandin E2 (PGE2) production and the increased activities of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in normal human mammary epithelial cells and breast cancer cell lines, treated with HA. In the present study we attempted to elucidate the mechanism of these biological effects. Firstly, we found that direct cell-crystal contact was required for induction of mitogenesis as the effect was not merely a result of isotopic exchange of calcium into the culture medium. Treatment with bafilomycin A1, a proton pump inhibitor, abrogated HA-induced mitogenesis to control cell levels. These results suggest that phagocytosis and intracellular crystal dissolution is required for HA-induced mitogenesis. We also demonstrated that the increase in prostaglandin E2, previously reported, is due, at least in part, to HA-induced upregulation of cyclooxygenase-2 (COX-2) in Hs578T cells. An accumulation of MMP-1 mRNA was also shown in response to HA stimulation in Hs578T cells. Furthermore, a HA-induced increase in interleukin-1beta (IL-1beta), a potent inducer of MMP-1 gene expression, was demonstrated in Hs578T cells at 2 and 4 h. Treatment with phosphocitrate (PC) (a naturally occurring inhibitor of calcium phosphate crystallisation, which is known to block a number of HA-induced biological effects in other cell types) blocked HA-mediated mitogenesis, as well as, COX-2, MMP-1 and IL-1beta induction, at the transcriptional level. These results show that calcium HA crystals are capable of exerting significant biological effects on surrounding cells which can be abrogated by PC and emphasise the role of calcium HA in amplifying the pathological process involved in breast cancer.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Cooke MM,McCarthy GM,Sallis JD,Morgan MPdoi
10.1023/a:1023908307108subject
Has Abstractpub_date
2003-05-01 00:00:00pages
253-63issue
2eissn
0167-6806issn
1573-7217journal_volume
79pub_type
杂志文章abstract:PURPOSE:Triple-negative breast cancer (TNBC)/basal-like breast cancer (BLBC) is a highly aggressive form of breast cancer. We previously reported that a small molecule agonist ligand for the orphan nuclear receptor estrogen-related receptor beta (ERRβ or ESRRB) has growth inhibitory and anti-mitotic activity in TNBC ce...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05485-5
更新日期:2020-02-01 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:PURPOSE:Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to i...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05192-1
更新日期:2019-07-01 00:00:00
abstract::The objective of this nationwide prospective cohort study is to find out the risk of breast cancer (BC) in relatives of patients with multiple BCs by laterality and age at diagnosis of first BC. Having family history of single (HR 1.8; 95 % CI 1.8-1.9) or multiple (HR 2.7; 95 % CI 2.6-2.9) BC was associated with highe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2848-3
更新日期:2014-02-01 00:00:00
abstract::Progression of breast cancer from an estrogen-dependent, slowly growing tumor amenable to tamoxifen treatment to an aggressive, metastatic, estrogen-independent phenotype has been mimicked by the transfection of MCF-7 breast carcinoma cells with fibroblast growth factors 1 or 4. FGF-transfected cells are aggressively ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806082
更新日期:1996-01-01 00:00:00
abstract::Theophylline reduces cell number in MDA-MB-231 cells through mechanisms over and above phosphodiesterase inhibition. In the current study, we used an intracellular fluorescent dye to show that theophylline and, to a much greater extent, 3-isobutyl-1-methylxanthine, evoke the generation of reactive oxygen species and a...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1010603816003
更新日期:2001-03-01 00:00:00
abstract:PURPOSE:The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. METHODS:A total of 335 consecutive patients with 346 invasive and in situ breast cancers were treat...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-008-0187-y
更新日期:2009-07-01 00:00:00
abstract::NF-E2-related factor 2 (Nrf2) is an important transcription factor involved in antioxidant response. Nrf2 binds antioxidant response elements (ARE) within promoters of genes encoding detoxification enzymes (e.g., NAD (P) H-quinone oxidoreductase 1 (NQO1)) leading to their transcriptional activation. Nrf2 function is r...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1604-1
更新日期:2011-10-01 00:00:00
abstract::To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p5...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006159016703
更新日期:1999-05-01 00:00:00
abstract::Steroid receptor coactivators are important in regulating the function of the receptors in endocrine organ development and in cancers, including breast. Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to the ret oncogene and later characterized as an AR coactivator. We previously reporte...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1131-5
更新日期:2011-07-01 00:00:00
abstract:PURPOSE:Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with early metastasis, drug resistance, and poor patient survival. Fork head box M1 (FOXM1) is considered as an emerging molecular target due to its oncogenic role and high overexpression profile in 85% in TNBC. However, ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4207-7
更新日期:2017-06-01 00:00:00
abstract::Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirty-nine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%; cut-off level 10 fmol/mg protein) b...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666582
更新日期:1993-12-01 00:00:00
abstract::Current evidence suggests that the majority of DCIS lesions do not progress to invasive carcinoma, and overtreatment of DCIS is a significant problem. We previously reported an 8-gene signature that differentiated microdissected low-grade (LG) DCIS lesions with and without associated stromal invasion, based on differe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3838-4
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:The homeobox (HOX) family consists of 39 genes whose expressions are tightly controlled and coordinated within the family, during development. We performed a comprehensive analysis of this gene family in cancer settings. METHODS:Gene correlation analysis was performed using breast cancer data available in T...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06087-2
更新日期:2021-01-18 00:00:00
abstract:RATIONALE:Survival after loco-regional failure (LRF) of breast cancer was investigated at the population level. METHODS:Using the Stockholm cancer registry, 2698 patients diagnosed with LRF between 1980 and 2014 were identified and divided into three cohorts by year of LRF diagnosis. Post-relapse event-free survival (...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4936-2
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:The objective was to determine the additional value of pathologic examination using three-level sectioning and immunocytokeratin (ICK) staining of sentinel lymph node (SN) biopsies in cT1-2N0M0 breast carcinoma patients regarding lymph node staging and eligibility of systemic therapy taking primary tumor cha...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9434-2
更新日期:2007-09-01 00:00:00
abstract::Estrogenic steroids, such as estradiol, are known to play a crucial role in the development and growth of hormone-dependent breast cancer. Steroid sulfatase (STS) inhibitors that can prevent the biosynthesis of these steroids via the sulfatase pathway offer therapeutic potential. We show here the in vivo profile, incl...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9769-3
更新日期:2008-09-01 00:00:00
abstract::Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited w...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-010-0990-0
更新日期:2010-10-01 00:00:00
abstract::One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnormality is preferentially associated with estrogen-receptor positive tumors and may define a sub-class of patients with an adverse prognosis. Although CCND1 has the credentials of ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00682720
更新日期:1995-01-01 00:00:00
abstract::This study clarified the difference in the effects on serum lipids between toremifene (TOR) and tamoxifen (TAM). To remove influencing factors, we investigated adjuvant therapy for hormone receptor-positive patients with breast cancer without lymph node metastasis. The subjects were 65 patients who were enrolled in a ...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-004-4384-z
更新日期:2004-11-01 00:00:00
abstract::Estrogen receptor beta (ERbeta) is widely expressed in mammary epithelium. ERbeta expression is reported to decline during carcinogenesis of the breast and other tissues. In this study, we examined the consequences of a loss of ERbeta expression in mammary epithelial cells. We knocked down ERbeta transcript levels in ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0413-2
更新日期:2010-04-01 00:00:00
abstract::Feasibility of utilizing the 6-day subrenal capsule (SRC) assay to screen drugs against fresh surgical explants of human tumors was confirmed by testing six clinically active chemotherapeutic agents against 141 human breast cancers. Response rates of the six drugs obtained in the assay compared favorably with clinical...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806232
更新日期:1983-01-01 00:00:00
abstract::Cyclin D1 (CCND1), a key cell cycle regulatory protein that governs the cell cycle progression from G1 to S phase, can promote cell proliferation or induce growth arrest and apoptosis. Since the identification of a well-characterized functional polymorphism, G870A in exon 4 of CCND1, several molecular epidemiological ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-008-0195-y
更新日期:2009-08-01 00:00:00
abstract::In order to assess the impact of modern combination chemotherapy on overall survival of metastatic breast cancer patients, we retrospectively analysed survival data of those patients who presented with breast cancer and developed metastases at our clinic from 1971-78 inclusive. Our results indicate a trend towards imp...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806751
更新日期:1981-01-01 00:00:00
abstract::Circulating tumor cells (CTCs) can be identified in approximately 25 % of stage I-III breast cancer patients; CTCs presence is a predictor of poor outcome in metastatic breast cancer, but little is known regarding the prognostic significance of CTCs in non-metastatic triple-negative breast cancer (TNBC) patients. The ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3103-7
更新日期:2014-09-01 00:00:00
abstract::The mechanisms by which breast cancer (BrC) can successfully metastasize are complex and not yet fully understood. Our goal was to identify tumor-induced stromal changes that influence metastatic cell behavior, and may serve as better targets for therapy. To identify stromal changes in cancer-bearing tissue, dual-spec...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3122-4
更新日期:2014-11-01 00:00:00
abstract::The epidermal growth factor receptor (EGFR) is expressed in benign and malignant breast epithelium. The EGFR, when mutated or over-expressed in the presence of its ligand, is transforming in other tissues or cell types. It is therefore of major interest in the pathogenesis of human breast cancer to understand the role...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666176
更新日期:1994-01-01 00:00:00
abstract::We describe a method for the isolation of free DNA from ductal lavage (DL) and nipple aspirate fluid (NAF), and its evaluation for the presence of LOH at the BRCA1 and FHIT genes and for mitochondrial DNA (mtDNA) mutations at the D310 marker, to improve early detection of breast cancer. We evaluated 26 DL and six NAF ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000018406.03679.2e
更新日期:2004-03-01 00:00:00
abstract:AIMS:Rapamycin and its analogues are currently being tested in clinical trials as novel-targeted anticancer agents. Pre-clinical studies that used breast cancer cell lines have suggested that p-Akt or p-S6K1 expressing tumors, as well as PTEN negative tumors, were sensitive to rapamycin. The aims of this study were to ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9746-x
更新日期:2008-08-01 00:00:00
abstract::Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging (MRI) studies of breast cancer patients after cancer treatment. Here we report the first prospective MRI study of women undergoing treatment for breast cancer, with or without chemotherapy, as well as healthy controls. We hy...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1088-4
更新日期:2010-10-01 00:00:00