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, including the efficacy in a xenograft breast cancer model and pharmacokinetics, of three potent STS inhibitors. MCF-7 cells stably over-expressing STS cDNA (MCF-7STS) were generated. Ovariectomised, MF-1, female nude mice receiving subcutaneous injections of estradiol sulfate (E2S) and bearing MCF-7STS xenografts, were orally treated with the STS inhibitors STX64, STX213, and STX1938. Treatment was administered once weekly at a dose of 1 mg/kg for 35 days during which animals received E2S thrice weekly. Mice were weighed and tumor measurements taken weekly. Furthermore, the pharmacokinetics for STX213 was determined in rats. STX213 and STX1938 exhibited potent STS inhibition in vivo. However, STX1938 demonstrated a greater duration of activity. In vehicle treated nude mice receiving E2S, tumor volumes increased by 260% after 35 days compared to day zero. STX64 (1 mg/kg) failed to reduce tumor growth when given once weekly. STX213 and STX1938 (once weekly, 1 mg/kg) significantly inhibited (P < 0.05) tumor growth over this same time period. These compounds completely inhibited liver and tumor STS activity and significantly reduced the levels of plasma E2. This study indicates that the STS inhibitor, STX213, exhibits excellent efficacy and pharmacokinetics and therefore offers a potentially novel treatment for hormone-dependent breast cancer.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Foster PA,Chander SK,Parsons MF,Newman SP,Woo LW,Potter BV,Reed MJ,Purohit Adoi
10.1007/s10549-007-9769-3subject
Has Abstractpub_date
2008-09-01 00:00:00pages
129-38issue
1eissn
0167-6806issn
1573-7217journal_volume
111pub_type
杂志文章abstract:PURPOSE:Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-4037-z
更新日期:2017-01-01 00:00:00
abstract::Breast cancer is the second leading cause of cancer death in women in the United States. Metastasis accounts for the death of ~90 % of these patients, yet the mechanisms underlying this event remain poorly defined. WAVE3 belongs to the WASP/WAVE family of actin-binding proteins that play essential roles in regulating ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2753-1
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:The current standard of treatment for non-palpable breast cancers is wire-guided localization (WGL). WGL has its drawbacks and alternatives such as radio-guided surgery (RGL) and intra-operative ultrasound (IOUS) have been developed. The clinical effectiveness of all forms of RGL has been assessed against ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-013-2639-2
更新日期:2013-08-01 00:00:00
abstract::Invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy (CTX) in women with primary breast cancer. They define a high-risk group with strong benefit from adjuvant CTX and a low-risk group with uncertain benefit and excellent survival without CTX....
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-013-2496-z
更新日期:2013-04-01 00:00:00
abstract::Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cance...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF01834637
更新日期:1992-01-01 00:00:00
abstract::Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast we...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-4321-9
更新日期:2005-09-01 00:00:00
abstract::The mechanism of action of the pure antiestrogens ICI 164384 and ICI 182780 has been investigated. Both antagonists are steroidal antiestrogens with 7 alpha-alkylamide side-chains. The antiestrogens reduce the cellular content of the estrogen receptor by reducing the half-life of the protein. A potential mechanism for...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00689686
更新日期:1993-01-01 00:00:00
abstract::Our previous studies have shown that social housing conditions can significantly alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study extended our investigations to the molecular level by examining stressor effects on the expression of a group of stress-responsive proteins, the heat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006314010958
更新日期:2000-02-01 00:00:00
abstract::Tamoxifen is currently the adjuvant treatment of choice for postmenopausal women with hormone-sensitive breast cancer. However, in the treatment of postmenopausal women with advanced disease, the third-generation aromatase inhibitor anastrozole ('Arimidex') has been shown to be at least as effective as tamoxifen, and ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1025455130476
更新日期:2003-01-01 00:00:00
abstract::Sustained breast cancer growth and metastasis requires paracrine signals between the tumor cells and the normal surrounding host tissue. One crucial function of these signals is to recruit endothelial cells and thus new blood vessels for the nourishment of the expanding tumor mass. This proliferation and migration of ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666148
更新日期:1994-01-01 00:00:00
abstract::Although the psychosocial concomitants of early-stage breast cancer have been well-documented, the relationship between cancer recurrence and quality of life remains less clear. We conducted a prospective, longitudinal study in order to clarify the relationship between recurrent cancer and quality of life, and to dete...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1006172024218
更新日期:1999-03-01 00:00:00
abstract::We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC datab...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3787-y
更新日期:2016-05-01 00:00:00
abstract:PURPOSE:Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to vali...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4294-5
更新日期:2017-08-01 00:00:00
abstract:PURPOSE:Little is known about racial variations in the financial impact of cancer care. Using data from a national survey of racially diverse patients with metastatic breast cancer, we examined racial/ethnic patterns in employment and cost-management (i.e., financial coping) behaviors. METHODS:We conducted an online s...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05449-9
更新日期:2020-01-01 00:00:00
abstract::In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. S...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01807283
更新日期:1988-07-01 00:00:00
abstract:PURPOSE:Patients with spontaneous nipple discharge (SND) who have neither clinically palpable masses nor evidence of disease on imaging with mammogram and/or ultrasound are traditionally investigated with galactogram and duct excision. As breast imaging improves, it has raised the question whether galactography and mic...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-05109-4
更新日期:2019-04-01 00:00:00
abstract::Integrins are cell surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Some of them, e.g. alpha(V)beta(3), alpha(IIb)beta(3) and alpha(2)beta(1), have been suggested as key players for cancer development and tumor metastasis. Two polymorphisms in the gene for the alpha(2) component...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9089-4
更新日期:2006-05-01 00:00:00
abstract:PURPOSE:To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS:Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82)...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-017-4111-1
更新日期:2017-02-01 00:00:00
abstract::Breast cancer cells (BCC) frequently metastasize to bone where they may cause tumor-induced osteolysis (TIO). While the important eroding role of the osteoclasts in TIO is well admitted, the possibility that BCC and/or osteoblasts activated by tumoral factors could also directly degrade bone matrix in this pathology h...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006408916224
更新日期:2000-05-01 00:00:00
abstract::The taxanes and anthracyclines have emerged as the most active agents for treating women with advanced breast cancer. As such, investigation of the two drug classes in combination regimens has been eagerly pursued. The rationale for combining docetaxel with an anthracycline includes high clinical activity of each indi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1024369220605
更新日期:2003-01-01 00:00:00
abstract::Resistance to tamoxifen is a major clinical challenge in the treatment of breast cancer; however, it is still unclear which signaling pathways are the major drivers of tamoxifen-resistant growth. To characterize resistance mechanisms, we have generated different tamoxifen-resistant breast cancer cell lines from MCF-7....
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2485-2
更新日期:2013-05-01 00:00:00
abstract::We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00662403
更新日期:1993-01-01 00:00:00
abstract::The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2999-2
更新日期:2014-07-01 00:00:00
abstract::To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node-posit...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00689833
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Radial scar's stellate appearance may mimic carcinoma mammographically and histologically. Management of radial scar (RS) found on breast core needle biopsies (CNB) ranges from excision to clinical observation due to the variation in reported upgrades to malignancy at surgical excision. We examined the upgrade ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4741-y
更新日期:2018-07-01 00:00:00
abstract::Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patien...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-014-2876-z
更新日期:2014-04-01 00:00:00
abstract::The aim of this study was to evaluate the effectiveness of an additional, individualized, multi-component complementary medicine treatment offered to breast cancer patients at the Merano Hospital (South Tyrol) on health-related quality of life compared to patients receiving usual care only. A randomized pragmatic tria...
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/s10549-014-3249-3
更新日期:2015-01-01 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::We concluded a randomized crossover trial comparing tamoxifen 40 mg daily with ovarian ablation for treatment of metastatic breast cancer in premenopausal women. Objective responses (complete response (CR) plus partial response (PR)) were observed in 5/20 patients treated initially with tamoxifen and in 3/19 patients ...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1005895813401
更新日期:1997-07-01 00:00:00
abstract:PURPOSE:To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL). METHODS:The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminat...
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/s10549-016-4065-8
更新日期:2017-02-01 00:00:00