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 used an intratumoral aromatase model that simulates postmenopausal breast cancer patients with estrogen-dependent tumors. Growth of the tumors in the mice was inhibited by both anastrozole and fulvestrant compared with the control tumors. Nevertheless, tumors had doubled in size at 5 weeks of treatment. We therefore investigated whether switching the original treatments to anastrozole or fulvestrant alone or the combination of anastrozole plus fulvestrant would reduce tumor growth. The results showed that the best strategy to reverse the insensitivity to anastrozole or fulvestrant is to combine the two agents. Additionally, the tumors treated with anastrozole plus fulvestrant from the beginning had only just doubled their size after 14 weeks of treatment, whereas the anastrozole and fulvestrant treatments alone resulted in 9- and 12-fold increases in tumor size, respectively, in the same time period. Anastrozole plus fulvestrant from the beginning or in sequence was associated with down-regulation of signaling proteins involved in the development of hormonal resistance such as insulin-like growth factor type I receptor beta, mitogen-activated protein kinase (MAPK), p-MAPK, AKT, mammalian target of rapamycin (mTOR), p-mTOR, and estrogen receptor alpha compared with tumors treated with anastrozole or fulvestrant alone. These results suggest that blocking the estrogen receptor and aromatase may delay or reverse the development of resistance to aromatase inhibitors in advanced breast cancer patients.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Macedo LF,Sabnis GJ,Goloubeva OG,Brodie Adoi
10.1158/0008-5472.CAN-07-6807subject
Has Abstractpub_date
2008-05-01 00:00:00pages
3516-22issue
9eissn
0008-5472issn
1538-7445pii
68/9/3516journal_volume
68pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Endometria of normal histology from postmenopausal women receiving either estrogen or estrogen plus a progestin have been analyzed for nuclear estradiol receptor, epithelial DNA synthesis, isocitric dehydrogenase, and estradiol dehydrogenase activities. Epithelial DNA synthesis correlated positively with nuclear estra...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract::Patients with lung cancer often present with metastatic disease and therefore have a very poor prognosis. The recent discovery of several novel ROS receptor tyrosine kinase molecular alterations in non-small cell lung cancer (NSCLC) presents a therapeutic opportunity for the development of new targeted treatment strat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3990
更新日期:2012-08-01 00:00:00
abstract::The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MC...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2914
更新日期:2004-04-15 00:00:00
abstract::Imatinib currently represents the standard treatment in the early chronic phase of chronic myelogenous leukemia (CML), thanks to the high percentage of cytogenetic complete remission achieved, but it is yet unclear to what extent it can eradicate leukemia. Therefore, different vaccination strategies have been suggeste...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3737
更新日期:2007-06-01 00:00:00
abstract::Treatment of human HL-60 or KG1A leukemia cells with the topoisomerase II inhibitor etoposide resulted in extensive DNA degradation. When DNA integrity was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 1.5-2 h after addition of etoposide to cells, increased in intensity over 6 h, and per...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::Mice lacking N-acetylglucosaminyltransferase III (GlcNAc-TIII) exhibit slightly but significantly retarded liver tumor progression after a single injection of 10 micro g/g diethylnitrosamine (DEN) and continued administration of phenobarbital (PB) in drinking water. A key question is whether the absence of GlcNAc-TIII...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-11-15 00:00:00
abstract::Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0358
更新日期:2013-10-01 00:00:00
abstract::The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could emp...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1655
更新日期:2017-04-15 00:00:00
abstract::The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1898
更新日期:2007-05-01 00:00:00
abstract::The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We used fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in PIN (6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::The transcription factor NF-E2-related factor 2 (Nrf2) binds the antioxidant DNA response element (ARE) to activate important cellular cytoprotective defense systems. Recently several types of cancers have been shown to overexpress Nrf2, but its role in the cellular response to radiation therapy has yet to be fully de...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0171
更新日期:2010-11-01 00:00:00
abstract::We used three techniques to examine excision repair in human cells treated with ultraviolet radiation, N-acetoxy-2-acetylaminofluorene, and a combination of the two. The three techniques gave similar results. Two types of human cells were used: (a) excision repair proficient (normal human fibroblasts and xeroderma pig...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Natural killer (NK) immune cells mediate antibody-dependent cellular cytotoxicity (ADCC) by aggregating FcγRIIIA/CD16, contributing significantly to the therapeutic effect of CD20 monoclonal antibodies (mAb). In this study, we show that CD16 ligation on primary human NK cells by the anti-CD20 mAb rituximab or ofatumum...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-0781
更新日期:2015-10-01 00:00:00
abstract::It has been reported that replacement of a functional retinoblastoma (RB) gene in RB defective WERI-27 retinoblastoma cells results in complete loss of their tumorigenic potential in nude mice following s.c. injection. We have repeated the identical studies and found that although tumors did not develop s.c., the RB r...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-08-15 00:00:00
abstract::While colony formation assays provide sensitive indices of tumor cell proliferation and growth inhibition imposed by many chemotherapeutic agents, drugs which require metabolic activation lack activity in such assays. In the present study, we have utilized freshly isolated rat hepatocytes for the activation of drugs w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-02-01 00:00:00
abstract::EphA2 receptor tyrosine kinase is frequently overexpressed in different human cancers, suggesting that it may promote tumor development and progression. However, evidence also exists that EphA2 may possess antitumorigenic properties, raising a critical question on the role of EphA2 kinase in tumorigenesis in vivo. We ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0004
更新日期:2006-07-15 00:00:00
abstract::Failure of cytokinesis results in tetraploidy and can increase the genomic instability frequently observed in cancer. The peptidyl-prolyl isomerase Pin1, which is deregulated in many tumors, regulates several processes, including cell cycle progression. Here, we show a novel role for Pin1 in cytokinesis. Pin1 knockout...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0825
更新日期:2009-08-15 00:00:00
abstract::Ten patients with metastatic adenocarcinomas of the colon or pancreas were treated with multiple injections of monoclonal antibody 17.1A. For each injection, antibody concentration in the patients' sera plateaued during the entire treatment course, and then decreased, with faster antibody clearance in patients given p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::The mechanism of albumin biosynthesis was studied in Morris hepatoma 5123tc in vivo and in hepatoma cell suspensions obtained by solubilizing the intercellular matrix with collagenase and hyaluronidase. In the in vivo experiments, L-[-14C]leucine was injected i.v. into rats bearing hepatomas in the muscles of both hin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is centrally involved in cell growth, metabolism, and angiogenesis. While showing clinical efficacy in a subset of tumors, rapamycin and rapalogs are specific and allosteric inhibitors of mTOR complex 1 (mTORC1), but they do not directly inhibit mTOR complex 2 (mTORC2), an emer...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0299
更新日期:2009-08-01 00:00:00
abstract::Despite the impressive results obtained in animal models, the clinical use of tumor necrosis factor-alpha (TNF) as an anticancer drug is limited by severe toxicity. We have shown previously that targeted delivery of TNF to aminopeptidase N (CD13), a marker of angiogenic vessels, improved the therapeutic index of this ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1753
更新日期:2004-01-15 00:00:00
abstract::Gli signaling is critical for central nervous system development and is implicated in tumorigenesis. To monitor Gli signaling in gliomas in vivo, we created platelet-derived growth factor-induced gliomas in a Gli-luciferase reporter mouse. We find that Gli activation is found in gliomas and correlates with grade. In a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6350
更新日期:2008-04-01 00:00:00
abstract::Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors d...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::The human AP endonuclease (Ape1 or ref-1) DNA base excision repair (BER) enzyme is a multifunctional protein that has an impact on a wide variety of important cellular functions including oxidative signaling, transcription factor regulation, and cell cycle control. It acts on mutagenic AP (baseless) sites in DNA as a ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::The association between the consumption of onions and leeks (vegetables belonging to the Allium genus), garlic supplements, and the risk of lung carcinoma was investigated in a large-scale prospective cohort study on diet and cancer in the Netherlands. The Netherlands Cohort Study was started in 1986 among 120,852 men...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::The concentration of estrogenic, androgenic, progestational, and adrenocortical steroid hormones in body fluids of mature intact Sprague-Dawley female rats was increased by s.c. implantation of 5 to 7 mg NaCl pellets containing 1 to 20% steroid 48 hr before administration p.o. of either 7,12-dimethylbenz(a) anthracene...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
abstract::Protein synthesis is a vital cellular process that regulates growth and metabolism. It is controlled via signaling networks in response to environmental changes, including the presence of nutrients, mitogens, or starvation. The phosphorylation state of proteins involved in translation initiation is a limiting factor t...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-12-0026
更新日期:2012-08-15 00:00:00
abstract::Prostate cancer develops through a stochastic mechanism whereby precancerous lesions on occasion progress to multifocal adenocarcinoma. Analysis of human benign and cancer prostate tissues revealed heterogeneous loss of TGF-β signaling in the cancer-associated stromal fibroblastic cell compartment. To test the hypothe...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2999
更新日期:2011-05-15 00:00:00
abstract::Previous work in our laboratory has indicated that free fatty acids stimulate synthesis of fibrinogen by the liver. The effect of the hypolipidemic agent clofibrate on hyperfibrinogenemia associated with tumors was evaluated by monitoring clofibrate-induced changes in plasma fibrinogen concentration and biosynthesis o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract::Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7- deoxyaglycone , is followed by reduction of the C-13 k...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-06-01 00:00:00