bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for GATA-3 in control of estrogen receptor alpha expression.
Authors: Hostetter C , Licata LA , Keen JC 
Published: December 2010

Abstract
Abstract #3050
Expression of the GATA-3 binding protein correlates with estrogen receptor (ER) alpha expression in primary and cultured breast cancer cells. While the significance of this correlation and role of GATA-3 in breast cancer remains unclear, GATA-3 may serve as a good prognostic indicator in breast tumors. Recently, a reciprocal interaction between GATA-3 and ER has been demonstrated. GATA-3 may regulate ER levels through binding to an enhancer region upstream of the ER gene while ER can associate with and regulate GATA-3 expression. Meta-analyses of several cancer microarrays indicate that GATA-3 is co-expressed with ER and other ER responsive genes, further suggesting a role of GATA-3 in the ER signaling pathway. Our laboratory has been investigating the role of the RNA binding protein HuR/ELAV1 in control of mRNA stability in breast cancer cells. We have previously reported that ER mRNA stability is increased through binding of HuR to the 3'UTR. Microarray analysis of those transcripts associated with HuR in MCF7 cells showed that GATA-3 mRNA associates with HuR compared to an IgG control. Biotin pulldown assays using a biotinylated GATA-3 RNA probe confirmed that HuR binds to the GATA-3 3'untranslated region (UTR). Inhibition of HuR using siRNA probes decreased GATA-3 mRNA and protein expression, further indicating a role for HuR in regulation of GATA-3 mRNA stability. siRNA mediated inhibition of GATA-3 expression significantly reduced ER mRNA and protein levels. Surprisingly, we found that GATA-3 bound to the ER mRNA by binding to two out of four regions within the ER 3'UTR, suggesting that while GATA-3 may play a role in upregulation of ER mRNA transcription through the enhancer interaction, GATA-3 may stabilize ER mRNA once transcribed by binding to the ER 3'UTR. Studies are ongoing to fully characterize this role of GATA-3 in control of ER mRNA stability.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3050.
Targeting the peroxisome proliferator-activated receptor gamma one in the treatment of breast cancer.
Authors: Kilgore MW , Zaytseva YY , Wang X , Southard RC 
Published: December 2010

Abstract
Abstract #3055
Peroxisome proliferator-activated receptor gamma 1 (PPARγ1) is a member of the nuclear hormone receptor superfamily and is over expressed in breast cancer compared to human mammary epithelial cells (HMEC). Although synthetic ligands of PPARγ have been reported to mediate differentiation, inhibit proliferation, and induce apoptosis of cancer cells in culture it remains unclear whether these are mediated through PPARγ or by off target effects. Furthermore, the controversial nature of these studies and the disappointing results from clinical trials raise questions about the efficacy of these drugs in treating breast cancer. Recent work from our lab and others suggests that targeting the expression or endogenous transactivation of PPARγ represents a novel strategy in the treatment of breast cancer. We have previously demonstrated that the increase in PPARγ1 expression in seen in breast cancer cells is driven by a tumor-specific promoter. Furthermore, we have identified the myc-associated zinc finger protein (MAZ) as a critical mediator of PPARγ1 expression in these cells. In this study, we further demonstrated the significance of MAZ in the transcriptional regulation of PPARγ1 and confirmed that high expression of PPARγ1 in MCF-7 breast cancer cells is MAZ dependent. Additionally, using RNA interference (RNAi) techniques to knockdown PPARγ1 or MAZ or driving the expression of a dominant negative form of PPARγ1 in MCF-7 breast cancer cells, we demonstrated that blocking the expression of either protein resulted in reduced cellular proliferation and enhanced apoptosis. These findings suggest that in the absence of any exogenous ligand an increase in PPARγ1 signaling, driven at least in part by MAZ, contributes to an imbalance between proliferation and apoptosis, and may be an important mediator or of breast cancer progression. These results also highlight the need to understand the molecular mechanisms that drives tumor specific expression of PPARγ1 and development pure antagonist as a therapeutic treatment of this devastating disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3055.
Does the recurrence of pregnancy-associated breast cancer during subsequent pregnancy 10 years after mastectomy support the unique hormonal milieu of pregnancy as a cause of tumorigenesis? A case and literature review.
Authors: Schlager A , Unger JG , Schnabel F 
Published: December 2010

Abstract
Abstract #3058
We report a case of pregnancy-associated chest wall recurrence of breast adenocarcinoma 10 years following mastectomy and reconstruction for initial pregnancy-associated breast cancer (PABC). This represents the first reported case in the literature of a pregnancy-associated recurrence of pregnancy-associated breast cancer. The patient had no episodes of recurrent breast cancer during the interim 10 years, and only experienced a recurrence with a rapidly growing left chest mass during the subsequent pregnancy. Thus, the possibility that the malignancy may have been triggered by the pregnancy cannot be ignored.&#x2028; Although prior studies following breast cancer patients and their subsequent pregnancy have not shown an increase risk of recurrence, these studies were performed in “all comers” with breast cancer, and would not have had the statistical power to distinguish a small subset of patients with an increased risk, such as PABC patients. As a result, these patients have been assumed to be at no greater risk for recurrence with pregnancy and have been advised as such.&#x2028; It is reasonable to assume that PABC patients may, in fact, represent a unique subset of breast cancer patients with the unique hormonal milieu of pregnancy playing a mechanistic role in the propagation and proliferation of the disease. In this case a patient with prior PABC had a rapidly growing progesterone receptor positive breast cancer during a subsequent pregnancy. Further, studies have indicated that there is a possibility that the hormone status of women during pregnancy may in fact lead to a change in tumor characteristics, and therefore their risks. This instance would support the concern and represent the sentinel report describing a new subset of breast cancer with a unique spectrum of risk factors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3058.
Blocking internalization of pBP1, a secreted homeoprotein, kills breast cancer cells but not normal breast epithelial cells.
Authors: Rheey J , Bivona L , Berg P 
Published: December 2010

Abstract
Abstract #3068
Background: BP1 is a member of the homeobox gene family, a highly conserved family of transcription factor genes. pBP1 is a homeotic protein that is upregulated in 80% of invasive ductal breast tumors. We have previously shown that the percentage of pBP1 positive breast cancer cases increases with the extent of cellular proliferation and carcinogenesis. BP1 expression is associated with aggressive tumors: 100% of ER negative tumors were BP1 positive, compared with 73% of ER positive tumors. pBP1 is secreted by MCF-7 cells, T47D cells, and MDA-MB-231 breast cancer cells, but not by MCF10A or H16N2 normal breast epithelial cells. In all cell lines tested, secreted pBP1 is internalized, resulting in stimulation of growth. Moreover, incubation of MCF-7 or MCF10A cells in recombinant pBP1 results in stimulation of several oncogenes, including bcl-2, Twist, and Met. These results led us to ask whether we could abrogate mitogenic stimulation by addition of anti-pBP1 antibody.&#x2028; Materials and Methods. Cells were incubated in 10 µg/ml anti-BP1 Ab (Novus) or 10 µg/ml IgG for three days. Growth was measured using MTT assays and apoptosis was assessed by flow cytometry after staining with Annexin V (Trevigen).&#x2028; Results. Addition of anti-BP1 Ab to the growth medium of MCF-7 cells, T47D cells, and MDA-MB-231 cells caused significant growth inhibition and apoptosis. In contrast, addition of anti-BP1 Ab to the growth medium of MCF10A and H16N2 cells did not lead to significant growth inhibition or apoptosis.&#x2028; Discussion. Our novel finding that pBP1 is secreted by breast cancer cells but not normal breast epithelial cells was the impetus to test the effect of adding anti-BP1 Ab to the growth media of both types of cells. Remarkably, anti-BP1 Ab kills only the breast cancer cells, suggesting they may be BP1-dependent. Our data indicate it may be possible to specifically target BP1 positive breast cancer cells in the 80% of women with BP1 positive tumors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3068.
Protein tyrosine kinase 6 (PTK6): a new/potential therapy target in breast cancer?.
Authors: Aubele M , Walch AK , Braselmann H , Ludyga N , Atkinson MJ , Luber B , Auer G , Bartlett JM 
Published: December 2010

Abstract
Abstract #3073
Background: Elevated expression of the cytoplasmic tyrosine kinase PTK6 (breast tumor kinase, BRK) occurs in approximately two-thirds of primary breast tumors, where it is implicated in EGF receptor-dependent signaling and epithelial tumorigenesis. The role of PTK6 in breast cancer development and prognosis is unclear, its function in-vivo remains undefined.&#x2028; Material and Methods: We performed a retrospective study of PTK6 expression in 426 archival breast cancer samples from patients with long term (≥240 months) follow up. Immunohistochemical analysis of the following proteins was determined: PTK6, all 4 HER receptors, Sam68 (a substrate of PTK6), and the signalling proteins MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. Correlations between markers were determined, and the prognostic value of parameters by univariate and multivariate survival analysis. We compared PTK6 gene copy number with the protein expression levels using FISH analysis.&#x2028; Results: The disease-free survival of patients ( ≥240 months) was positively correlated with PTK6 protein expression, and was inversely correlated with nodal status and tumor size (p≤0.01). A time dependence for the prognostic value of key markers was evident, with HER2/neu only showing prognostic significance at early time points (60 months).&#x2028; PTK6 expression in tumor tissue significantly correlated with the expression of PTEN, MAPK, P-MAPK, and Sam68 (p≤0.05). To investigate whether these correlations may be due to molecular interactions, we used the T47D cell line for immunoprecipitation and Western Blot analysis. Co-precipitation-type protein-protein interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68.&#x2028; Quantitative analysis revealed an increased PTK6 gene copy number in 75% of the tumors. Polysomy of chromosome 20 was responsible for most cases (47%) whilst gene amplifications were less frequent (28%).&#x2028; Discussion: We show that PTK6 protein expression is of significant prognostic value in predicting the long term outcome of breast carcinomas. Further, several potential binding partners were identified, indicating the involvement of PTK6 in three main signal transduction pathways.&#x2028; Supported by: Deutsche Krebshilfe # 10379 / EU LSHC-CT-2004-503426.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3073.
Synergisitic inhibition of DNA repair by combining ß-lapachone with Nu7026 as a strategy for killing primary and metastatic breast cancers.
Authors: Bey EA , Kessinger C , Blanco E , Bachoo R , Williams N , Boothman DA 
Published: December 2010

Abstract
Abstract #3078
The primary tumors of most breast cancer patients are removed via resection or complete mastectomy. However, years after having their primary tumors removed many patients will need chemotherapy for metastatic disease that arises in distal sites such as lung and brain. It has been reported that many breast cancers overexpress the 2 electron oxidoreducase NQO1, a marker of tumorigenesis for a variety of cancers. Since NQO1 expression levels are low in normal tissue but elevated 10-100 fold in breast cancers, we hypothesized that NQO1 levels could be exploited for chemotherapy with ß-lapachone. ß-lapachone is a naturally derived plant product that is bioactivated by NQO1. In this study we show that ß-lapachone (a DNA repair inhibitor) synergizes with the DNA-PK inhibitor Nu7026 to kill human breast cancer cell lines that express NQO1. Normal human breast tissues and breast cancer cell lines that did not express NQO1 were not affected by ß-lapachone. In addition by using in vivo breast cancer models we demonstrated that ß-lapachone effectively inhibited breast tumor growth in athymic mice. We also showed that ß-lap was efficacious against lung tumors derived from MDA-MB-231 breast cancer cell lines. Finally, our simulated brain metastatic model showed that ß-lap accumulated in brain tumors derived from MDA-MB-2331 cells. Together these data suggest that ß-lap and ß-lap in combination Nu7026 may be a potent combination for treating primary and metastatic breast cancer disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3078.
Prophylactic surgical uptake in a cohort of BRCA carriers: an Irish perspective.
Authors: Carroll PA , Kennedy J , Boyle T , Connolly EM 
Published: December 2010

Abstract
Abstract #3095
Introduction: Women with BRCA 1/2 mutations have a lifetime risk of approximately 45-87%1 for developing breast cancer and a 20-60% risk for ovarian cancer. The managment of these patients including prophylactic surgery is contorversial and presents difficult choices for patients. Uptake of prophylactic surgery in BRCA carriers in an Irish setting has not previously been investigated.&#x2028; Methods: St. James hospital is a tertiary referral hospital for BRCA counselling and testing. All information was gathered and analysed from the Cancer genetics department database in our institution which provides a counselling service for a number of hereditary diseases.&#x2028; Results: Deleterious BRCA 1/2 mutations have been identified in 57 families since testing began in 1992. There are a total of 109 women in this cohort.&#x2028; 54% of these women were diagnosed with primary breast cancer. 23 (47.9%) women were symptomatic on presentation. Only 3 (6.3%) were detected during screening. Inital surgery and prophylactic surgery uptake in this group is displayed in table 1.&#x2028; 31% (n=34) of our BRCA carrier cohort remain unaffected. Uptake of surgical prohylaxis is outlined in table 2. 17 women in this group opted for no form of prophylaxis. 88% of the women will require regular screening for breast cancer.&#x2028; Age at bilateral prophylactic masectomy was 30.5 years. Of the 39 women in both groups who elected for bilateral salpingo oophorectomy, only 28% (11) women were under the age of 40 years.&#x2028; &#x2028; CPM Contralateral Prophylactic Mastectomy&#x2028; TAH/BSO Total Abd Hysterectomy/Bilat Salpingo oopherectomy&#x2028; &#x2028; TAH/BSO Total Abd Hysterectomy/Bilat Salpingo oopherectomy&#x2028; BPM Bilateral Prophylactic Mastectomy&#x2028; Discussion: Prophylactic mastectomy offers a 95% risk reduction for breast cancer of 95%, despite this, a survival benefit has not been proven. Prophylactic oophorectomy before the age of 40 years has been associated with a reduction in breast cancer of 50% and up to 80% reduction in ovarian/peritoneal malignancy.There is also data to support that oophorectomy provides a survival benefit in BRCA carriers. The rates of uptake of prophylactic surgery in both the affected and unaffected groups in our cohort are lower than that of international standards2. The reasons for this are currently under investigation.&#x2028; References:&#x2028; 1. Ford D et al. Genetic heterogeneity and penetrance analysis of the BRCA1/2 genes in breast cancer families. Am J Hum Genet 1998;62(3):676-89.&#x2028; 2. Metcalfe KA, et al.International variation in rates of uptake of preventive options in BRCA1/2 mutation carriers. Int J Cancer. 2008 May 1;122(9):2017-22.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3095.
BRCA mutation in Chinese population: results from the Hong Kong hereditary and high risk breast cancer programme (HRBCP) and the Hong Kong hereditary and high risk breast cancer family registry.
Authors: Kwong A , Wong CL , Ma ES , West DW , Ford JM 
Published: December 2010

Abstract
Abstract #3097
Background: Little is known about the frequency and spectrum of BRCA 1/2 mutations among Chinese population. Previous research suggests possible differences in the prevalence and penetrance of inherited mutations in these genes among Asians and the earlier presentation of breast cancer in Asian population may have more relevance to genetic causes. The access to genetic counseling and testing in Asia have been limited. The HRBCP (www.HRBCP.org) was established in 2007. This is first in Hong Kong and provides genetic testing, counseling and research on the spectrum of the disease in Asia and in particular Chinese population. The data from this programme will be entered in the newly established The Hong Kong Hereditary Breast Cancer Family Registry.&#x2028; Methods: Probands who were diagnosed to have breast cancer age 50 or below, have a family history or personal history of breast and/or ovarian cancer, bilateral breast cancer, male breast cancer, triple negative breast carcinoma were recruited. Genetic counseling were given and consent for testing were obtained. Blood and tumor samples were collected. The entire coding regions of the extracted DNA/RNA and flanking introns of BRCA1 and 2 were screened for germline mutations using full gene sequencing and MLPA.&#x2028; Results: A total of 119 Chinese have been sequenced and analysed. 21 (18%) deleterious mutations were identified of which 4 were novel mutations. 8 (38%) were BRCA 1 mutations and 13 (62%) were BRCA 2 mutations. 66.6% had first degree relatives with breast cancer. 49 (41.2%) were under the age of 40 years old of which 11 (22%) were found to carry a BRCA mutation. 7 (64%) of this younger age group with mutation have family history of breast cancer. For the other 4, 1 had triple negative cancer, 1 had a family history of ovarian cancer, 1 unknown and 1 with no risk except for young age. Of the 37 family members tested, 21 (57%) have BRCA mutations and only 9 of them have breast or ovarian cancers. 1 only had stomach cancer. 6 male family members were found to carry the BRCA mutation with no history of cancer.&#x2028; Conclusions: Approximately 18% of the tested blood samples from clinically high risk Chinese women carry a deleterious mutation in BRCA1 or 2. In contrast to Caucasian data, there was a comparative higher rate of BRCA2 mutations. Further research on the spectrum of the mutations in Chinese and other Asian population will allow the tailor-making of an ethnic-based risk assessment model and also screening, prophylactic and preventative measures to be taken.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3097.
The benefit using an integrated electronic trial platform for a neoadjuvant therapy trial (HEDON) in primary breast cancer – results of an evaluation study.
Authors: Schwarz-Boeger U , Zahlmann G , Paepke S , Schmidt M , Jacobs VR , Kiechle M , Harbeck N 
Published: December 2010

Abstract
Abstract #3114
Background: At present, academic medical centers conducting investigator initiated trials (IIT) have the choice of relying on paper or going electronic regarding electronic data capture and data management solutions. Many of the electronic systems have originally been developed for requirements of the pharmaceutical industry and all of the currently available systems would thus be isolated in the existing IT setting of the medical centers.&#x2028; We here suggest an approach to integrate a data management system into existing hospital information systems (HIS) and to provide the end users (e.g. physicians, investigators, study nurses) with consolidated user interfaces and integrated systems.&#x2028; Methods: In 2005, a collaboration between the Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich and Siemens Medical Solutions was initiated as a pilot project.&#x2028; An integrated platform for clinical trials was developed and implemented to support the HEDON trial (Herceptin-Docetaxel-Neoadjuvant), an investigator initiated clinical phase II trial concerning primary systemic therapy of breast cancer. The HEDON trial started in February 2006 and will have recruited all of a total of 90 planned patients in the end of this year. In addition, a translational research trial (TransHEDON) evaluating therapy response markers is an essential component of the clinical trial.&#x2028; Using the integrated platform, clinical data as well as laboratory data are automatically populated from the HIS into the electronical study CRFs, after data confirmation by investigators or study nurses (depending on their defined role) using the validation buffer of the system. The existing PACS and HIS are made accessible from the platform which has special capabilities to greatly improve user interactions with all relevant systems. To quantify the benefit of such an integrated system, an integrated evaluation project was set up including the quantification time savings for all involved personnel. For a pre-defined time period, data capture and data management processes are performed paper based and electronically. This allows thorough and critical analysis of all involved processes&#x2028; Resukts; Errors that occur specially due to manually entering laboratory data can be dramatically minimized using such an electronical data capture system. Another important benefit is time savings. The data will be presented.&#x2028; Conclusion:This single-sign-on electronic platform for clinical trials has been validated in its whole and fulfils the regulatory requirements as specified by GCP or 21 CFR part 11 compliance for trials of the FDA. We consider this integrated system to be very helpful for implementation of clinical trials into a routine hospital setting.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3114.