Research Topics
Genomes and Genes | Leena Hilakivi-ClarkeSummaryAffiliation: Georgetown University Country: USA Publications
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Publications
Exposures to synthetic estrogens at different times during the life, and their effect on breast cancer riskLeena Hilakivi-Clarke
Department of Oncology, Georgetown University, Washington, DC 20057, USA
J Mammary Gland Biol Neoplasia 18:25-42. 2013..New data suggest that these exposures induce epigenetic modifications in the mammary gland and germ cells, thereby causing an inheritable increase in breast cancer risk for multiple generations...
Effect of dietary intervention on serum lignan levels in pregnant women - a controlled trialRiitta Luoto
UKK Institute for Health Promotion, Tampere, Finland
Reprod Health 7:26. 2010..abstract:..- Dietary fat intake and gestational weight gain in relation to estradiol and progesterone plasma levels during pregnancy: a longitudinal study in Swedish womenMarie Lof
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Box 281, SE 171 77 Stockholm, Sweden
BMC Womens Health 9:10. 2009.... 
Pregnancy weight gain and premenopausal breast cancer riskLeena Hilakivi-Clarke
Department of Oncology, Georgetown University, Washington, DC 20057, USA
J Reprod Med 50:811-6. 2005..To investigate whether excessive weight gain during pregnancy alters a woman's risk of developing premenopausal breast cancer...- Nutritional modulation of terminal end buds: its relevance to breast cancer preventionLeena Hilakivi-Clarke
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington DC, USA
Curr Cancer Drug Targets 7:465-74. 2007..This hypothesis may imply that adult intake of some bioactive dietary components reduces cancer risk increased by early life dietary exposures or inhibits tumor growth by reversing epigenetic changes in various molecular targets... - Fetal origins of breast cancerLeena Hilakivi-Clarke
Georgetown University, Washington DC 20057, USA
Trends Endocrinol Metab 17:340-8. 2006..Identifying the epigenetically altered target genes and their ligands might lead to strategies to prevent this disease in some women... - Differentiation of mammary gland as a mechanism to reduce breast cancer riskLeena Hilakivi-Clarke
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC 20057, USA
J Nutr 136:2697S-9S. 2006 - Is soy consumption good or bad for the breast?Leena Hilakivi-Clarke
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
J Nutr 140:2326S-2334S. 2010..More research is needed to understand why soy intake during early life may both reduce breast cancer risk and risk of recurrence... - Mechanisms mediating the effects of prepubertal (n-3) polyunsaturated fatty acid diet on breast cancer risk in ratsLeena Hilakivi-Clarke
Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
J Nutr 135:2946S-2952S. 2005.... - In utero alcohol exposure increases mammary tumorigenesis in ratsL Hilakivi-Clarke
Lombardi Cancer Center and Department of Oncology, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20007, USA
Br J Cancer 90:2225-31. 2004..It remains to be determined whether an increase in pregnancy oestradiol levels mediated alcohol's effects on offspring's mammary tumorigenesis... - Dietary modulation of pregnancy estrogen levels and breast cancer risk among female rat offspringLeena Hilakivi-Clarke
Department of Oncology, Lombardi Cancer Center, Washington, DC 20007, USA
Clin Cancer Res 8:3601-10. 2002.... - Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780)Zhiping Gu
Vincent T Lombardi Cancer Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA
Cancer Res 62:3428-37. 2002..Thus, some breast cancer cells may survive antiestrogen treatment by bypassing specific growth inhibitory signals induced by antagonist-occupied estrogen receptors... - Prepubertal estradiol and genistein exposures up-regulate BRCA1 mRNA and reduce mammary tumorigenesisAnna Cabanes
Lombardi Cancer Center and Department of Oncology, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20007, USA
Carcinogenesis 25:741-8. 2004..Our results suggest that prepubertal estrogenic exposures may reduce later breast cancer risk by inducing a persistent up-regulation of BRCA1 in the mammary gland... - Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesisGalam Khan
Lombardi Cancer Center, Department of Oncology, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057, USA
Reprod Toxicol 23:397-406. 2007.... - Excessive weight gain during pregnancy increases carcinogen-induced mammary tumorigenesis in Sprague-Dawley and lean and obese Zucker ratsSonia de Assis
Lombardi Cancer Center, Department of Oncology, Georgetown University, Washington, DC, USA
J Nutr 136:998-1004. 2006..It remains to be determined whether an increase in leptin levels was causally associated with an increase in the dams' mammary tumorigenesis, including in obese Zucker rats with dramatically reduced leptin signaling... - Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell linesBianca P Gomez
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Rd, NW, Washington, DC 20057, USA
FASEB J 21:4013-27. 2007..XBP1 and/or the UPR may be a useful molecular target for the development of novel predictive and therapeutic strategies in breast cancer... - BCL2 and CASP8 regulation by NF-kappaB differentially affect mitochondrial function and cell fate in antiestrogen-sensitive and -resistant breast cancer cellsRuchi Nehra
Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057, USA
FASEB J 24:2040-55. 2010.... - High birth weight increases mammary tumorigenesis in ratsSonia de Assis
Lombardi Cancer Center and Department of Oncology, Georgetown University, Washington, DC, USA
Int J Cancer 119:1537-46. 2006.... - Timing of dietary estrogenic exposures and breast cancer riskSonia de Assis
Department of Oncology, Georgetown University, Research Building E407, 3970 Reservoir Road NW, Washington, DC 20057, USA
Ann N Y Acad Sci 1089:14-35. 2006..Thus, dietary exposures during pregnancy and puberty may play an important role in determining later risk by inducing epigenetic changes that modify vulnerability to breast cancer... - Protective effects of prepubertal genistein exposure on mammary tumorigenesis are dependent on BRCA1 expressionSonia de Assis
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University, Washington, District of Columbia, USA
Cancer Prev Res (Phila) 4:1436-48. 2011.... - IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosisYanxia Ning
Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
Mol Cancer Ther 9:1274-85. 2010..These observations support the exploration of clinical trials combining antiestrogens and compounds that can induce IRF1, such as IFNgamma, for the treatment of some ER-positive breast cancers... - The nuclear factor kappa B inhibitor parthenolide restores ICI 182,780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cellsRebecca B Riggins
Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Room W405A Research Building, 3970 Reservoir Road Northwest, Washington, DC 20057, USA
Mol Cancer Ther 4:33-41. 2005..Because parthenolide has shown safety in Phase I clinical trials, these findings have direct clinical relevance and provide support for the design of clinical studies combining antiestrogens and parthenolide in ER-positive breast cancer... - Do estrogens always increase breast cancer risk?Leena Hilakivi-Clarke
Lombardi Cancer Center and Department of Oncology, Georgetown University, Room W405, 3970 Reservoir Road NW, Washington, DC 20007, USA
J Steroid Biochem Mol Biol 80:163-74. 2002..We further propose that the timing of estrogenic exposures may play at least as important a role in affecting breast cancer risk as life-time exposure... - interferon regulatory factor-1 mediates the proapoptotic but not cell cycle arrest effects of the steroidal antiestrogen ICI 182,780 (faslodex, fulvestrant)Kerrie B Bouker
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20007, USA
Cancer Res 64:4030-9. 2004..These data identify a novel mechanism of antiestrogen resistance and implicate IRF-1 as a key component in signaling some ER-mediated effects on apoptosis/cell survival... - High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspringSonia de Assis
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, The Research Building, Room E407, Washington, District of Columbia 20057, USA
Nat Commun 3:1053. 2012..We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means... - Maternal dietary exposure to fiber during pregnancy and mammary tumorigenesis among rat offspringBin Yu
Lombardi Cancer Center and Department of Oncology, Georgetown University, NW, Washington, DC
Int J Cancer 119:2279-86. 2006.... - Expression patterns among interferon regulatory factor-1, human X-box binding protein-1, nuclear factor kappa B, nucleophosmin, estrogen receptor-alpha and progesterone receptor proteins in breast cancer tissue microarraysYuelin Zhu
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Int J Oncol 28:67-76. 2006..018) is observed. An inverse correlation exists between IRF-1n and NFkappaB (p=0.034). All four proteins are detected in breast tumors and their expression patterns support their role(s) in a key signaling network... - Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- miceWei Yu
Department of Oncology, Georgetown University, Washington, DC 20057, USA
Cancer Prev Res (Phila) 3:1246-58. 2010..Dietary exposure to VD(3) inhibited the carcinogenic effect of obesity on the endometrium. This protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin... - Opposing effects of prepubertal low- and high-fat n-3 polyunsaturated fatty acid diets on rat mammary tumorigenesisSusan E Olivo
Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, Washington, DC, USA
Carcinogenesis 26:1563-72. 2005.... - Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cellsRobert Clarke
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
J Steroid Biochem Mol Biol 114:8-20. 2009..Signaling proceeds through BCL2 gene family members and BECN1 ultimately to regulate cell fate... - ERRgamma mediates tamoxifen resistance in novel models of invasive lobular breast cancerRebecca B Riggins
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20057, USA
Cancer Res 68:8908-17. 2008..These data support a role for ERRgamma/AP1 signaling in the development of TAM resistance and suggest that expression of ERRgamma may be a marker of poor TAM response... - Multidrug resistance/P-glycoprotein and breast cancer: review and meta-analysisRobert Clarke
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Semin Oncol 32:S9-15. 2005..Future studies should also take into account the potentially multifactorial nature of multidrug resistance... - Block principal component analysis with application to gene microarray data classificationAiyi Liu
Biostatistics Unit, Lombardi Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA
Stat Med 21:3465-74. 2002..The method is illustrated with the well-known National Cancer Institute database of 60 human cancer cell lines data (NCI60) of gene microarray expressions, in the context of classification of cancer cell lines... - Development and validation of a method for using breast core needle biopsies for gene expression microarray analysesMatthew Ellis
Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA
Clin Cancer Res 8:1155-66. 2002..Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies... - Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structuresYuelin Zhu
Lombardi Comprehensive Cancer Center and Departments of Oncology, Georgetown University School of Medicine, Washington, DC, USA
Int J Oncol 29:1581-9. 2006.... - Classification algorithms for phenotype prediction in genomics and proteomicsHabtom W Ressom
Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW, Washington, DC 20057, USA
Front Biosci 13:691-708. 2008..The selected features are presented to a classifier for phenotype prediction... - Antiestrogen resistance in breast cancer and the role of estrogen receptor signalingRobert Clarke
Department of Oncology and Vincent T Lombardi Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Oncogene 22:7316-39. 2003..The network also may involve signaling through ras and MAPK, implicating crosstalk with growth factors and cytokines. Ultimately, signaling affects the expression/function of the proliferation and/or apoptotic machineries... - Antiestrogens, aromatase inhibitors, and apoptosis in breast cancerRebecca B Riggins
Department of Oncology and Physiology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Vitam Horm 71:201-37. 2005..Finally, we discuss the evidence supporting a role for apoptotic defects in acquired and de novo antiestrogen resistance... - Cadmium mimics the in vivo effects of estrogen in the uterus and mammary glandMichael D Johnson
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
Nat Med 9:1081-4. 2003..In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland... - The role of X-box binding protein-1 in tumorigenicityAyesha N Shajahan
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D C, USA
Drug News Perspect 22:241-6. 2009..Furthermore, combining inhibitors of XBP-1 with other anti-UPR drugs may enhance the activity of some antineoplastic therapies... - C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pumpFabio Leonessa
Department of Oncology and Lombardi Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road Northwest, Washington, DC 20007, USA
J Med Chem 45:390-8. 2002..These data identify C-7-substituted progesterone analogues and 5, in particular, as rationally designed antiPgp compounds worthy of further evaluation/development... - Evaluation of gene expression profile of keratinocytes in response to JP-8 jet fuelLuis A Espinoza
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA
Toxicol Appl Pharmacol 200:93-102. 2004..Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies... - Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosisAnatasha C Crawford
Lombardi Comprehensive Cancer Center and Department of Oncology, School of Medicine, Georgetown University, Washington, District of Columbia, United States of America
PLoS ONE 5:e8604. 2010..BCL-W, BCL2, and BECN1 integrate important functions in determining antiestrogen responsiveness, and the presence of functional autophagy may influence the balance between apoptosis and necrosis... - Functionally active estrogen receptor isoform profiles in the breast tumors of African American women are different from the profiles in breast tumors of Caucasian womenIndra Poola
Department of Anatomy, Howard University School of Medicine, Washington, DC 20059, USA
Cancer 94:615-23. 2002..The molecular factors responsible for these tumor characteristics are mostly unknown... - Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological dataYuji Zhang
Lombardi Comprehensive Cancer Center, Georgetown University, 4000 Reservoir Rd, Washington, DC, USA
BMC Bioinformatics 9:203. 2008..The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO) information... - Reverse engineering module networks by PSO-RNN hybrid modelingYuji Zhang
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
BMC Genomics 10:S15. 2009.... - The properties of high-dimensional data spaces: implications for exploring gene and protein expression dataRobert Clarke
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Nat Rev Cancer 8:37-49. 2008..From the perspective of translational science, this Review discusses the properties of high-dimensional data spaces that arise in genomic and proteomic studies and the challenges they can pose for data analysis and interpretation... - Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosisKerrie B Bouker
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Carcinogenesis 26:1527-35. 2005..03). These data establish a functional role for IRF-1 in the growth suppression of breast cancer cells and strongly implicate IRF-1 as a tumor suppressor gene in breast cancer that acts, independent of p53, to control apoptosis... - Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometryOffie P Soldin
Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University Medical Center, Washington, DC 20057 1465, USA
Fertil Steril 84:701-10. 2005.... - Iterative normalization of cDNA microarray dataYue Wang
Department of Electrical Engineering and Computer Science, The Catholic University of America, Washington, DC 20064, USA
IEEE Trans Inf Technol Biomed 6:29-37. 2002..In this way, the two processes bootstrap one another. We evaluate the technique on real microarray data from breast cancer cell lines and complement the experiment with a data cluster visualization study... - Orphan nuclear receptors in breast cancer pathogenesis and therapeutic responseRebecca B Riggins
Lombardi Comprehensive Cancer Center and Department of Oncology Department of Physiology and Biophysics, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Endocr Relat Cancer 17:R213-31. 2010..We also propose that a clearer understanding of the function of orphan nuclear receptors in mammary gland development and normal mammary tissues could significantly improve our ability to diagnose, treat, and prevent breast cancer... - The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survivalConstantinos G Broustas
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20057, USA
Clin Cancer Res 16:2939-48. 2010..BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer... - Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicityAyesha N Shajahan
Department of Oncology, Lombardi Comprehensive Cancer Center, and Departments of Physiology and Biophysics, Georgetown University, College of Medicine, Washington, D C 20057, USA
J Biol Chem 282:5934-43. 2007..Collectively, our findings underscore the importance of CAV1 phosphorylation in apoptosis and suggest that events that negate CAV1 tyrosine phosphorylation may contribute to anti-microtubule drug resistance... - Frequent loss of heterozygosity at the interferon regulatory factor-1 gene locus in breast cancerLuciane R Cavalli
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
Breast Cancer Res Treat 121:227-31. 2010..00; P = 0.003; n = 273 cases) and risk of death (OR = 4.18; P = 0.004; n = 191 cases). Our findings strongly imply a tumor suppressor role for the IRF1 gene in breast cancer... - The A4396G polymorphism in interferon regulatory factor 1 is frequently expressed in breast cancer cell linesKerrie B Bouker
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057, USA
Cancer Genet Cytogenet 175:61-4. 2007..001), leading to a significant difference in genotype distribution between these populations (P = 0.002)... - Inferring network interactions using recurrent neural networks and swarm intelligenceHabtom W Ressom
Dept. of Biostat, Bioinf, and Biomath, Georgetown Univ, Washington, DC 20057, USA
Conf Proc IEEE Eng Med Biol Soc 1:4241-4. 2006..The results indicate that the algorithm has a promising potential to infer complex interactions such as gene regulatory networks from time-series gene expression data...
Research Grants
- Pregnancy Estrogens, Diet, and Breast Cancer RiskLeena Hilakivi Clarke; Fiscal Year: 2005..abstract_text> ..
- In utero dietary exposure to endocrine disruptorsLeena Hilakivi Clarke; Fiscal Year: 2007....
- Timing of dietary exposure and breast cancer riskLeena Hilakivi Clarke; Fiscal Year: 2007..This program aims to develop novel means to prevent some breast cancers by dietary modifications that take place during pregnancy and puberty. ..