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：:Erratum to: Breast Cancer Res Treat (2013),138:369–381,DOI 10.1007/s10549-012-2389-6. In the original publication of the article, the Fig. 4c and d were published erroneously. The revised Fig. 4 is given in this erratum. ...
journal_title：Breast cancer research and treatment
pub_type： 已发布勘误
doi：10.1007/s10549-016-3752-9
更新日期：2016-04-01 00:00:00
abstract：PURPOSE:Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcome...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,meta分析
doi：10.1007/s10549-019-05352-3
更新日期：2019-10-01 00:00:00
abstract：:We have previously shown that the anti-proliferative effect of retinoic acid in human breast cancer cell line MCF-7 is dependent on HES-1 expression. Here we show that retinoic acid induces HES-1 expression via upregulation of transcription factor SOX9. By expressing a dominant negative form of SOX9, disrupting endoge...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-009-0381-6
更新日期：2010-04-01 00:00:00
abstract：PURPOSE:Glutathione S-transferase mu 3 (GSTM3) is an enzyme involving in the detoxification of electrophilic compounds by conjugation with glutathione. Higher GSTM3 mRNA levels were reported in patients with ERα-positive breast cancer who received only tamoxifen therapy after surgery. Thus, this study aimed to clarify ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-4897-5
更新日期：2018-11-01 00:00:00
abstract：BACKGROUND:Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent diseas...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4301-x
更新日期：2017-08-01 00:00:00
abstract：:The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the othe...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-011-1802-x
更新日期：2012-01-01 00:00:00
abstract：PURPOSE:Contralateral prophylactic mastectomy is increasing, despite unclear evidence of improving survival. To investigate the age-related risk factors for contralateral breast cancer (CBC). METHODS:This study included 8716 patients diagnosed with non-metastatic unilateral invasive breast cancer between 1989 and 2008...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-5031-4
更新日期：2019-02-01 00:00:00
abstract：PURPOSE:Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and Rho...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-005-9002-1
更新日期：2006-02-01 00:00:00
abstract：PURPOSE:Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear. METHODS:To address these questions, totall...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4645-2
更新日期：2018-05-01 00:00:00
abstract：PURPOSE:The role of sentinel lymph node biopsy (SLNB) in breast cancer patients who undergo neoadjuvant chemotherapy (NAC) remains controversial. This study aims to investigate if axillary lymph node dissection (ALND) could be safely omitted after a negative SLNB in cN1/2 patients who become cN0 after NAC. METHODS:We ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-020-06011-8
更新日期：2020-11-09 00:00:00
abstract：:Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-015-3554-5
更新日期：2015-09-01 00:00:00
abstract：PURPOSE:Radiotherapy (RT) constitutes an important part of breast cancer treatment. However, triple negative breast cancers (TNBC) exhibit remarkable resistance to most therapies, including RT. Developing new ways to radiosensitize TNBC cells could result in improved patient outcomes. The M2 isoform of pyruvate kinase ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-019-05376-9
更新日期：2019-11-01 00:00:00
abstract：:Stearoyl-CoA desaturase 1 (SCD1) is an essential regulator of fatty acid synthesis. We have previously shown that overexpression of SCD1 increases the growth of breast cancer cell lines. The purpose of this study was to determine the relationship between SCD1 expression level and clinical-pathologic characteristics an...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-012-2354-4
更新日期：2013-01-01 00:00:00
abstract：:Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor bi...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-012-2377-x
更新日期：2013-01-01 00:00:00
abstract：PURPOSE:Chemotherapy-induced amenorrhea (CIA) by newer taxane-containing regimens was evaluated in early breast cancer (EBC) patients. METHODS:A prospective cohort of 122 premenopausal EBC patients participated in a phase III trial of preoperative docetaxel/capecitabine (TX) versus doxorubicin/cyclophosphamide (AC); 3...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10549-008-0071-9
更新日期：2009-05-01 00:00:00
abstract：PURPOSE:Cytokine milieu of tumor microenvironment affects tumorigenesis in breast cancer. The aim of the present study was to investigate the potential association of functional single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer. METHODS:The study included 127 individuals comprising 40 breast c...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-008-0006-5
更新日期：2009-03-01 00:00:00
abstract：:In contrast to antigen-specific alphabeta-T cells (adaptive immune system), gammadelta-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the well-documented capacity o...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-009-0527-6
更新日期：2010-07-01 00:00:00
abstract：PURPOSE:Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and d...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-019-05497-1
更新日期：2020-02-01 00:00:00
abstract：PURPOSE:The independent predictive information from progesterone receptor (PgR) positivity for breast cancer treated with tamoxifen has been questioned after an overview by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). However, the studies in the overview were to a large content performed before mode...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-016-4007-5
更新日期：2016-11-01 00:00:00
abstract：:The epidermal growth factor (EGF) is one of several growth factors involved in normal breast epithelial development and tumor proliferation. EGF and EGF-like peptide TGF alpha bind and activate the same membrane receptor protein. This receptor (EGF-R) has been recently studied in breast tumor biopsies and its detectab...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01834623
更新日期：1992-03-01 00:00:00
abstract：:Thirty-eight patients treated for primary breast cancer as part of a prospective randomized clinical trial were questioned retrospectively as to their psychosocial adaptation to treatment. Twenty patients had received mastectomy and eighteen had received excisional biopsy plus radiation of the intact breast. Aside fro...
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/BF01807591
更新日期：1983-01-01 00:00:00
abstract：:The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogen...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF00666043
更新日期：1995-01-01 00:00:00
abstract：:There has been increasing interest in the role of cultural and ethnic factors in breast cancer risk perceptions and screening practices. This study examined ethnic differences in breast cancer risk perception in 112 African American and 224 white women ages 35 and older who had at least one first-degree relative diagn...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,多中心研究
doi：10.1007/BF01806000
更新日期：1996-01-01 00:00:00
abstract：:A human estrogen receptor (ER) cDNA probe was used to examine genomic DNA extracted from 59 primary invasive breast cancers. The tumors were also studied histopathologically, and their ER status was assessed by hormone-binding assay and immunohistochemical analysis. Southern blots of genomic DNA samples digested with ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01805976
更新日期：1989-10-01 00:00:00
abstract：PURPOSE:This study aimed to identify and classify genetic variants in consensus moderate-to-high-risk predisposition genes associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), in BRCA1/2-negative patients from Brazil. METHODS:The study comprised 126 index patients who met NCCN clinical criteria and te...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-020-05985-9
更新日期：2020-10-30 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：:We have qualitatively evaluated the retention of the fluorescent dye rhodamine 123 by malignant or non-malignant breast epithelial cells in passively-infused fresh surgical specimens. Our findings demonstrate a microscopically-visible increase in the ability of primary and metastatic tumor cells to retain the dye, as ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01975444
更新日期：1991-03-01 00:00:00
abstract：BACKGROUND:Analysis of cytokines and growth factors in human milk offers a noninvasive approach for studying the microenvironment of the postpartum breast, which may better reflect tissue levels than testing blood samples. Given that Black women have a higher incidence of early-onset breast cancers than White women, we...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-4907-7
更新日期：2018-11-01 00:00:00
abstract：:Few studies have assessed the agreement between subjects' self-report and medical records among patients with breast cancer (BC), and none has addressed this issue in low-income women with BC. We assessed the level of agreement between self-report and medical records data for key BC treatment and prognostic characteri...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-009-0447-5
更新日期：2010-02-01 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
