Abstract：
:The sensitivity of breast neoplasms to hormonal control provides the basis of novel investigational treatments with steroidal alkylators. An androsterone D-lactam steroidal ester, the 3beta-hydroxy-13alpha-amino-13,17-seco- 5alpha-androstan-17-oic-13,17-lactam, p-bis(2-chloroethyl)amino phenyl acetate (lactandrate) was synthesized and tested for antitumor activity against six human breast cancer cell lines in vitro and against two murine and one xenograft mammary tumors in vivo. A docking study on the binding interactions of lactandrate with the ligand-binding domain (LBD) of estrogen receptor-alpha (ERalpha) was inquired. In vitro testing of lactandrate cytostatic and cytotoxic activity was performed on T47D, MCF7, MDA-MB-231, BT-549, Hs578T, MDA-MB-435 breast adenocarcinoma human cell lines. In vivo testing was performed on two murine mammary tumors, the MXT tumor and CD8F1 adenocarcinoma, as well as on human mammary carcinoma MX-1 xenograft. Molecular modeling techniques were adopted to predict a possible location and interaction mode of the molecule into LBD. Lactandrate induced significantly high antitumor effect against all tested in vitro and in vivo models. The cell lines with positive ER expression found to be significantly more sensitive to lactandrate. Moreover, lactandrate found to be positioned inside the binding cavity with its steroidal moiety, whilst the alkylating moiety protrudes out of receptor's pocket. Lactandrate produced important anticancer activity on breast cancer in vitro and in vivo. Some correlation between ER and lactandrate effect was demonstrated. Docking studies provide the basis for the structure-based design of improved steroidal alkylating esters for the treatment of estrogen-related cancers.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Trafalis DT,Geromichalos GD,Koukoulitsa C,Papageorgiou A,Karamanakos P,Camoutsis Cdoi
10.1007/s10549-005-9083-xsubject
Has Abstractpub_date
2006-05-01 00:00:00pages
17-31issue
1eissn
0167-6806issn
1573-7217journal_volume
97pub_type
杂志文章abstract：:Considerable effort has been placed into the identification of new antineoplastic agents to treat breast cancer and other malignant diseases. The basic approaches, in terms of model selection, endpoints, and data analysis, have changed in the previous few decades. This article deals with many of the issues associated ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1023/a:1005938428456
更新日期：1997-11-01 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：:The aim of this study is to identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information a...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-013-2796-3
更新日期：2014-01-01 00:00:00
abstract：PURPOSE:When combined with anthracyclines, the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) provides significant clinical benefit for women with HER2-overexpressing metastatic breast cancer. However, its use is limited by severe cardiotoxicity. To clarify whether myocardial HER2 and HER4 expression i...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/b:brea.0000003916.39959.73
更新日期：2003-11-01 00:00:00
abstract：BACKGROUND:To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. METHODS:The pathological specimens from 73 patients with breast canc...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1012269804578
更新日期：2001-08-01 00:00:00
abstract：:Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9504-0
更新日期：2007-12-01 00:00:00
abstract：PURPOSE:Breast cancer is the most common cancer among females worldwide. Axillary lymph node involvement is an important prognostic factor in pre-operative evaluation. The aim of this study was to evaluate the sensitivity and accuracy of AUS during the initial breast cancer diagnosis and the contribution of ultrasound ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-020-05830-z
更新日期：2020-10-01 00:00:00
abstract：PURPOSE:A positive margin after breast conserving surgery has consistently been shown to be a significant predictor for ipsilateral breast tumor recurrence. Currently, there is no standard for intraoperative margin assessment during lumpectomy, and up to 20% of cases result in positive margins. MarginProbe is a device ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-020-05773-5
更新日期：2020-08-01 00:00:00
abstract：:The effect of 17-beta-estradiol (E2) on the induction of osteolytic lesions by estrogen receptor (ER)-negative breast cancer cells was investigated in 4-week-old female nude mice. Exposure to exogenous E2 was found to increase osteolytic areas on radiographs up to 5.3 times in mice inoculated intracardially with MDA-2...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1022943127689
更新日期：2003-03-01 00:00:00
abstract：:Numerous independent groups from a range of countries have reported a high prevalence of Mouse Mammary Tumour Virus (MMTV)-like env sequences in human breast cancer specimens, including a prevalence of almost 40% in Australia. MMTV-like sag sequences and a completely integrated provirus have also been described. Recen...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-010-0946-4
更新日期：2011-01-01 00:00:00
abstract：:The epidermal growth factor system is a well characterized growth factor receptor pathway, the deregulation of which has been be associated with neoplastic growth. Overexpression or amplification of the epidermal growth factor receptor (EGFR) or one of its ligands has been linked with the malignant transformation of c...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/B:BREA.0000010702.10130.29
更新日期：2004-01-01 00:00:00
abstract：PURPOSE:The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer pa...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10549-019-05332-7
更新日期：2019-09-01 00:00:00
abstract：:We report a series of breast cancer patients with invasive skin and nail infections with Staphylococcus species that we attribute to the addition of pertuzumab to trastuzumab-based therapy. With the suspicion of an increased incidence of cutaneous infection in patients treated with pertuzumab and trastuzumab-based che...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10549-014-3190-5
更新日期：2014-12-01 00:00:00
abstract：:In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-014-3055-y
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-014-3149-6
更新日期：2014-11-01 00:00:00
abstract：:Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Surviv...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-013-2662-3
更新日期：2013-08-01 00:00:00
abstract：:After more than 100 reported randomized trials of systemic adjuvant therapy in breast cancer, it is clear that this therapy will prolong the time to recurrence and the survival time significantly, at least in some patient subsets. But there is less than complete agreement as to which subsets, which therapies, how much...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,随机对照试验,评审
doi：10.1007/BF01805971
更新日期：1989-10-01 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:Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-020-05810-3
更新日期：2020-10-01 00:00:00
abstract：:Histological grading of 160 primary infiltrating breast carcinomas showed that both oestrogen and progesterone receptor status are strongly related to grade, tumours that are receptor positive tending to be of lower grade than the receptor negative. The nuclear factors used in grading were those that determined this a...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01806938
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading t...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4178-8
更新日期：2017-06-01 00:00:00
abstract：:Women with diabetes have higher breast cancer incidence and mortality. The purpose of this study was to examine the impact of diabetes on stage at breast cancer diagnosis, as a possible reason for their higher mortality. Using population-based health databases from Ontario, Canada, this retrospective cohort study exam...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-015-3323-5
更新日期：2015-04-01 00:00:00
abstract：:The present study was undertaken to compare ROH growth responsiveness between normal human mammary epithelial cells (HMECs), estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cells, and assess whether this responsiveness is correlated with differences in ROH metabolism, particularly RA synthes...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1014815112078
更新日期：2002-03-01 00:00:00
abstract：:A major goal of cancer chemotherapy is the identification of cytotoxic compounds that are highly selective for cancer cells. We describe here one such compound - a novel iron chelator, desferri-exochelin 772SM. This desferri-exochelin has unique chemical and pharmacological properties, including extremely high iron bi...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1012211828319
更新日期：2001-09-01 00:00:00
abstract：:In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease-free and overall survival of 248 premenopausal patients with stage I/II breast cancer who underwent surgery followed by anthracycline-containing adjuvant chemotherapy. With a median follow-up of 5 y...
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：10.1023/a:1006276120841
更新日期：1999-06-01 00:00:00
abstract：:Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains of immune-deficient m...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01833265
更新日期：1993-01-01 00:00:00
abstract：:Wide fluctuations in results obtained by different laboratories for the content of estrogen receptors from a single source of tissue powder were reported by several investigators at the 1979 NCI Consensus Committee Meeting for Steroid Receptors in Breast Cancer and were further supported by data collected by our labor...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01805724
更新日期：1982-01-01 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：:We previously identified a polymorphism in the human estrogen receptor (ER) gene, within the coding region for the protein's amino terminal B-domain. In estrogen receptor-positive (ER+) breast tumors, the variant allele was preferentially associated with lower levels of ER, and was clinically correlated with frequent ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01980941
更新日期：1991-10-01 00:00:00
abstract：:Feulgen-stained samples from 460 small (pT1) primary breast cancers were investigated by means of an image analysis system. Several DNA, morphometrical and textural parameters were evaluated for each patient, and the prognostic meaning of these parameters was then investigated by the Cox regression analysis. As progno...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF00690188
更新日期：1995-01-01 00:00:00
