Abstract:
:Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate with demonstrated anti-proliferative and anti-cancer activity in mammary cells. We hypothesized that IP6 modulates cell cycle proteins by action on cytoplasmic signaling molecules. The effects of both pharmacological (2 mM) and physiological (100 microM) doses of IP6 on major PKC isoforms (PKCalpha, delta, epsilon, beta and zeta), PI3-K/Akt and ras/Erk1/2 were evaluated. Treatment of MCF-7 human breast cancer cells with 2 mM IP6 for 24 h caused a 3.1-fold increase in the expression of anti-proliferative PKCdelta. Similar results were observed with 100 microM IP6 at only 30-60 min post-treatment. IP6 also caused an increase in PKCdelta activity, shown by its translocation from cytosol to membrane. No changes in expression of PKC alpha, delta, epsilon, beta and zeta were detected. Additionally, IP6 caused a decrease of Erk1/2 and Akt activity. Among cell cycle control proteins, IP6 resulted in increased p27Kip1 protein levels and marked reduction of pRb phosphorylation. Specificity of the IP6 effects on p27Kip1 and pRb in MCF-7 cells (hormone-dependent) were additionally confirmed in highly invasive hormone-independent MDA-MB 231 breast cancer cells. Use of specific pharmaclogical inhibitors of PKC delta, MEK/Erk, and PI3K/Akt pathways indicated that the IP6-mediated effects on PKC delta were responsible for up-regulation of p27Kip, and pRb hypo-phosphorylation. In addition, IP6-induced apoptosis detected in MCF-7 cells appeared also to be PKC delta-dependent. Our data suggest potential usefulness of IP6 as a novel therapeutic modulator of PKC delta and p27Kip1, an important prognostic factor in human breast cancers.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Vucenik I,Ramakrishna G,Tantivejkul K,Anderson LM,Ramljak Ddoi
10.1007/s10549-004-6456-5subject
Has Abstractpub_date
2005-05-01 00:00:00pages
35-45issue
1eissn
0167-6806issn
1573-7217journal_volume
91pub_type
杂志文章abstract::Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects in patients with HER2+ breast cancer. Adults with measurable, locally advanced or metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-013-2510-5
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:To examine the trends in the prevalence of breast cancer risk factors in relation to breast cancer incidence trends and to explore whether the changes in risk factors differed by ethnicity in Hawaii over a 25-year period. METHODS:We pooled 17 population-based epidemiological studies conducted in Hawaii be...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9129-0
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND:Staging procedures used to detect metastatic breast cancer at the time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS) and laboratory parameters (LP). These procedures are expensive and not all patients need them. We aimed to identify groups of patients with different risks fo...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1014900600815
更新日期:2002-03-01 00:00:00
abstract::We calculated hazard rates for recurrence in patients with primary breast cancer (stage I, II; no adjuvant therapy). Previous publications have indicated a peak in hazard rates for recurrence (or death) at approximately 2-3 years after diagnosis of primary breast cancer. However, there have been conflicting reports co...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-1722-0
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:We sought to determine if bioimpedance spectroscopy (BIS) measurements can accurately assess changes in breast cancer-related lymphedema (BCRL) in patients undergoing lymphovenous bypass (LVB). METHODS:Patients undergoing LVB for BCRL refractory to conservative treatment from 1/2015 to 12/2018 were identified ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-020-06059-6
更新日期:2021-01-04 00:00:00
abstract::Although new chemotherapeutic drugs for metastatic breast cancer (MBC) have been approved over the past decade, it is unclear whether this has changed the overall outcome of patients. This study assessed the clinical and economic impacts of these drugs. We retrospectively studied MBC patients receiving chemotherapy in...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1311-3
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:Previous meta-analyses have examined the prognosis of women with pregnancy-associated breast cancer (PABC) as well as pregnancy that follows breast cancer diagnosis. Since then, many additional studies have been performed. We conducted an updated meta-analysis to examine the prognosis for women who become pre...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-016-3989-3
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-016-4028-0
更新日期:2017-01-01 00:00:00
abstract::Although a significant proportion of familial aggregation of breast cancer remains unexplained, many of the currently known breast cancer susceptibility genes, including BRCA1, BRCA2 and TP53, play a role in maintaining genome integrity by engaging in DNA repair. RAD51L1 is one of the five RAD51 paralogs involved in h...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1539-6
更新日期:2011-08-01 00:00:00
abstract::Mortality due to causes other than breast cancer is a potential competing risk which may alter the incidence probability of breast cancer and as such should be taken into account in predictive modelling. We used data from the Canadian National Breast Screening Study (CNBSS), which consist of two randomized controlled ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2113-6
更新日期:2012-07-01 00:00:00
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::Human mammary epithelial antigens (HME-Ags) are released into the circulation by breast tumors and not by normal breast tissue (Proc. Natl. Acad. Sci. USA 74: 582-586, 1977). This characteristic made them valuable, together with other breast cancer related antigens later identified, to develop immunoassays useful in t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806353
更新日期:1990-05-01 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::The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7 alpha-hydroxy DHA (7 alpha DHA), and tumour oestrogen receptor (ER...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00665771
更新日期:1994-01-01 00:00:00
abstract::Co-transfection studies indicate that HER2 (erbB-2) overexpression results in the phosphorylation and enhanced transcriptional activity of the androgen receptor (AR). This amplification of AR action is further enhanced by the expression of ARA70, a putative co-activator with a predilection for the AR. Because androgen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1017938608460
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing. METHODS:Germline DNAs were te...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05429-z
更新日期:2019-12-01 00:00:00
abstract:AIMS:To examine the frequency of axillary lymph node (ALN) invasion of operable breast cancers by their combined oestrogen receptor (ER), progesterone receptor (PR) and HER-2 status. METHODS:2227 recently operated cases in one centre were retrieved from the Multidisciplinary Breast Centre database and stratified accor...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-9914-7
更新日期:2009-01-01 00:00:00
abstract::A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1888-1
更新日期:2012-04-01 00:00:00
abstract:PURPOSE:Rates of contralateral prophylactic mastectomy (CPM) have increased over the last decade; it is important for surgeons and hospital systems to understand the economic drivers of increased costs in these patients. This study aims to identify factors affecting charges in those undergoing CPM and reconstruction. ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4315-4
更新日期:2017-09-01 00:00:00
abstract::Forty-one women with non-metastatic but locally advanced breast cancer were treated by modified radical or radical mastectomy, and were then randomized to receive one of two adjuvant chemotherapy regimens. Regimen A consisted of 6 months of cyclophosphamide, adriamycin, and fluorouracil (CAF) followed by 6 months of c...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01806692
更新日期:1987-01-01 00:00:00
abstract::Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer ce...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9597-5
更新日期:2008-03-01 00:00:00
abstract::Identifying risk factors for lymphedema in patients treated for breast cancer has become increasingly important, given the current lack of standardization surrounding diagnosis and treatment. Reports on the association of body mass index (BMI) and weight change with lymphedema risk are conflicting. We sought to examin...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2715-7
更新日期:2013-11-01 00:00:00
abstract::It has recently been proposed that a three-gene model (SCMGENE) that measures ESR1, ERBB2, and AURKA identifies the major breast cancer intrinsic subtypes and provides robust discrimination for clinical use in a manner very similar to a 50-gene subtype predictor (PAM50). However, the clinical relevance of both predict...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2143-0
更新日期:2012-08-01 00:00:00
abstract::Prognostication of breast cancer patients, not operated at diagnosis, poses a clinically difficult problem. To use gene amplification we examined cytological samples and determined c-erb-B2 gene copy number with semi-quantitative PCR. Control experiments showed the same gene-copy number in aliquots that were either ai...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806188
更新日期:1996-01-01 00:00:00
abstract::Recent studies in patients with breast cancer suggest the immune microenvironment influences response to therapy. We aimed to evaluate the relationship between growth rates of tumors in common spontaneous mammary tumor models and immune biomarkers evaluated in the tumor and blood. TgMMTV-neu and C3(1)-Tag transgenic m...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3199-9
更新日期:2014-12-01 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:BACKGROUND:Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, lacking effective targeted therapies, and whose underlying mechanisms are still unclear. The gene coding for Gametogenetin-binding protein (GGNBP2), also known as Zinc Finger Protein 403 (ZNF403), is located on chromosome 1...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-5052-z
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Telomerase is a ribonucleoprotein enzyme that synthesises telomeres in human germ cells, embryogenesis and in cancer, maintaining chromosomal length, stability and cellular immortality. The hTERT gene is the rate-limiting determinant of telomerase reactivation during immortalization and malignant transformat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9622-8
更新日期:2008-05-01 00:00:00
abstract::Nipple-sparing mastectomy (NSM) provides a cosmetic and psychological benefit for patients, but concerns on nipple involvement (NI) of tumor continue to persist. Several studies have reported factors for predicting NI, but the results were inconsistent and uncomprehensive, making patient selection difficult. The aim o...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-015-3385-4
更新日期:2015-06-01 00:00:00
abstract::The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organizat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2571-5
更新日期:2013-06-01 00:00:00