Abstract：
:2-Methoxyestradiol (2ME(2)), a physiologic metabolite of 17beta-estradiol (estrogen), has emerged as a promising cancer therapy because of its potent growth-inhibitory and proapoptotic effects on both endothelial and tumor cells. 2ME(2) also suppresses osteoclast differentiation and induces apoptosis of mature osteoclasts, and has been shown to effectively repress bone loss in an animal model of postmenopausal osteoporosis. Given these observations, we have examined whether 2ME(2) could effectively target metastasis to bone, osteolytic tumors, and soft tissue tumors. A 4T1 murine metastatic breast cancer cell line was generated that stably expressed Far Red fluorescence protein (4T1/Red) to visualize tumor development and metastasis to bone. In an intervention study, 4T1/Red cells were injected into bone marrow of the left femur and the mammary pad. In the latter study, 2ME(2) (10, 25, and 50 mg/kg/d) treatment began on the same day as surgery and was continued for the 16-day duration of study. Tumor cell growth and metastasis to bone were monitored and bone volume was determined by micro-computed tomography. 2ME(2) inhibited tumor growth in soft tissue, metastasis to bone, osteolysis, and tumor growth in bone, with maximum effects at 50 mg/kg/d. Furthermore, tumor-induced osteolysis was significantly reduced in mice receiving 2ME(2). In vitro, 2ME(2) repressed osteoclast number by inducing apoptosis of osteoclast precursors as well as mature osteoclasts. Our data support the conclusion that 2ME(2) could be an important new therapy in the arsenal to fight metastatic breast cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Cicek M,Iwaniec UT,Goblirsch MJ,Vrabel A,Ruan M,Clohisy DR,Turner RR,Oursler MJdoi
10.1158/0008-5472.CAN-07-1362subject
Has Abstractpub_date
2007-11-01 00:00:00pages
10106-11issue
21eissn
0008-5472issn
1538-7445pii
67/21/10106journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Cytosol estradiol receptor from MTW9-D (ovarian dependent) and MTW9-MtT (ovarian independent) rat mammary tumors were fractionated by chromatofocusing, a procedure which separates proteins on an ion-exchange column as a function of isoelectric point. Receptor from MTW9-D usually fractionated as three peaks with mean p...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1)...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Cigarette smoking causes cancer and DNA mutations. However, long-term chronic exposure to smoke is believed to be necessary for carcinogenesis. Here, we investigate the relationship between short-term exposure to smoke and the frequency of deletions in the mouse embryo. Deletions and other genome rearrangements are as...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-06-15 00:00:00
abstract：:Although the aromatase inhibitor anastrozole has been shown to be very effective in the treatment of hormone-dependent postmenopausal breast cancer, some patients with advanced disease will develop resistance to treatment. To investigate therapeutic strategies to overcome resistance to anastrozole treatment, we have u...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6807
更新日期：2008-05-01 00:00:00
abstract：:The possibility that neoplastic transformation may characteristically alter cell surface morphology prompted a comparison by scanning electron microscopy of nonneoplastic and tumorigenic cell lines from a single clone of mouse embryo cells. Among those studied by scanning electron microscopy, six lines of this clone p...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-03-01 00:00:00
abstract：:Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignan...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6682
更新日期：2008-08-15 00:00:00
abstract：:The response to Photofrin II-induced photosensitization on the activities of mitochondrial monoamine oxidase (MAO) and adenylate kinase (AK) were studied in order to gain further insight into site specific effects. Utilizing intact mitochondria in vitro, both MAO, located on the cytoplasmic side of the outer mitochond...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-08-15 00:00:00
abstract：:We have recently reported a simple and reproducible technique for the purification and rapid expansion of homogeneous populations of large granular lymphocytes expressing a natural killer cell phenotype and high levels of broad antitumor cytotoxic activity [lymphokine-activated killer (LAK) activity]. This technique e...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-03-15 00:00:00
abstract：:Dioxin and pesticides with xenoestrogenic activity are environmental contaminants that are suspected of promoting human diseases such as cancers. However, few studies have addressed the molecular consequences of a combination of these contaminants, a situation that is likely to occur in the environment. We investigate...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-05-15 00:00:00
abstract：:The adhesive characteristics of cultured acute lymphocytic leukemia cells (CCRF-CEM), lymphoma cells (Raji), and freshly isolated acute lymphocytic leukemia cells to human cultured endothelial cells were studied. An assay system was used whereby these neoplastic cells were allowed to interact with endothelial cells wh...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：:IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surv...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-17-0428
更新日期：2017-06-01 00:00:00
abstract：:The ingestion of high levels of fats, especially unsaturated fats, has been shown to enhance carcinogenesis in a variety of experimental model systems. Recently attention has focused upon the unsaturated linoleic fatty acid (18:2 omega 6) as a key component for this postinitiation enhancement. We have investigated the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:The chemokine receptor CXCR4 plays a central role in organ-specific homing and tumor spreading and is induced by hypoxia. B lymphocytes are exposed to low oxygen tensions during their development, but the influence of hypoxia on their physiology is poorly understood. Here, we show that hypoxia is associated with up-re...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4722
更新日期：2007-09-15 00:00:00
abstract：:Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-1617
更新日期：2016-02-15 00:00:00
abstract：:In vitro experiments selected optimal conditions to radiolabel with 131I the whole immunoglobulin and F(ab')2 fragments of the monoclonal antibody (MoAb) 225.28S to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Injection of the radiolabeled whole immunoglobulin and F(ab')2 fragments of the MoAb 225.28...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Vaccination with irradiated tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF tumor vaccine) induces a potent systemic antitumor immunity. To develop a protocol for cancer therapy to further augment the host immune response, we examined the effects of the GM-CSF tumor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-04-15 00:00:00
abstract：:Cultures of human mammary epithelial cells (HMECs) contain a subpopulation of variant cells with the capacity to propagate beyond an in vitro proliferation barrier. These variant HMECs, which contain hypermethylated and silenced p16(INK4a) (p16) promoters, eventually accumulate multiple chromosomal changes, many of wh...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-04-01 00:00:00
abstract：:This study was undertaken to examine relationships of the phenotype of malignant cells to target cell properties and to events early in the transformation process. Eighteen transformed lines were obtained by Kirsten murine sarcoma virus infection of cells from adrenal glands of rats ages 4 to 30 weeks, at first or sec...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-05-01 00:00:00
abstract：:In an attempt to better understand breast tumors sensitivity or resistance to anticancer drugs, the main drug-metabolizing enzyme systems were evaluated in both breast tumors and their corresponding peritumoral tissues in 12 patients. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:We have developed a model system for assessing the demethylating potential of external agents. Disruption in the DNA methylation pattern was evaluated at the translational level of the Escherichia coli beta-galactosidase coding gene (lacZ). We have constructed a clonal cell line (A4/4 cells) derived from the adenoviru...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:Adrenocortical carcinoma (ACC) is a rare disease with an overall poor but heterogeneous prognosis. This heterogeneity could reflect different mechanisms of tumor development. Gene expression profiling by transcriptome analysis led to ACC being divided into two groups of tumors with very different outcomes. Somatic ina...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2014
更新日期：2010-11-01 00:00:00
abstract：:A cloned, virus-producing, tumorigenic, promonocytic leukemia cell line, AC8, derived from an Abelson murine leukemia virus-infected mouse can differentiate in vitro. Differentiated cells, purified from a population containing undifferentiated cells on the basis of expression of the macrophage differentiation antigens...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-03-15 00:00:00
abstract：:Estrogen receptor (ER)-positive human breast cancer cells are hormonally regulated and are inhibited by retinoids, whereas most ER-negative breast cancer cells are not. Here, we compared retinoid-induced transcriptional activation and growth inhibition in the ER-negative breast cancer cell line MDA-MB-231, stably tran...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-11-15 00:00:00
abstract：:We have measured glutathione content in small tissue samples derived from biopsies of primary and metastatic human colon tumors and from colon cancer cell lines in tissue culture and xenografts in athymic mice. Measurements were performed using an enzymatic cycling assay designed to quantitate extremely low levels of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The numbers of ultraviolet light (UV)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus UV endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-05-01 00:00:00
abstract：:We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-15 00:00:00
abstract：:We have evaluated immunohistochemical characteristics of tumors and the infiltrating cells in patients treated with various immunotherapy regimens. Forty-eight patients with advanced malignancies were treated with high dose i.v. recombinant interleukin-2 alone or in combination with cyclophosphamide, recombinant tumor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-12-15 00:00:00
abstract：:Phosphatidylinositol-3-kinase is an important enzyme for intracellular signaling. The microbial product wortmannin and some of its analogues have been shown to be potent inhibitors of phosphatidylinositol-3-kinase. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nM. Kinetic analysis demonstrate...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The nonspecific accumulation of radioactivity in bone marrow, liver, and spleen in patients with melanoma injected with radiolabeled whole IgG of anti-high molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibody (mAb) hampers the application of immunoscintigraphy to visualize melanoma lesions. This ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
