bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 940: AR overexpression confers resistance to an aromatase inhibitor in ERα-positive breast cancer cells
Authors: Rechoum Yassine , Iacopetta Domenico , Barone Ines , Ando’ Sebastiano , Morales Stephanie , Weigel Nancy L. , Fuqua Suzanne A W 
Published: June 2012

Abstract
Background: Aromatase inhibitors (AIs) have emerged as the therapy of choice for the treatment of estrogen receptor alpha (ERα)-positive breast cancer. However, many patients develop resistance to AI treatment. Although the involvement of the ERα in AI resistance is well established, the role of the androgen receptor (AR) is not known. It has been estimated that about 60%-70% of ERα-positive breast cancer co-express the AR, and we have previously shown a role for AR-overexpression in tamoxifen resistance in ERα-positive MCF-7 breast cancer cells. Thus we hypothesized that AR overexpression might similarly be involved in resistance to the AI anastrazole (Anas).
Materials and Methods: Stable transfection of MCF-7 cells was performed to generate cell lines that express the aromatase gene (MCF-7 BK Arom) and then co-transfected with an AR expression vector (MCF-7 AR Arom). Aromatase and AR expression levels were evaluated by western blot analysis. Proliferation was tested using anchorage independent soft agar assays and MTT in the presence of the androgen substrate androstenedione (AD), or AD plus Anas. ERα and AR transcriptional activities were tested with ERE-luciferase reporter assays.
Results: Several clones expressing aromatase alone or aromatase plus AR were generated. MCF-7 aromatase clones overexpressing AR were resistant to the growth inhibitory effects of Anas when stimulated with the androgen AD. As expected AD treatment stimulated ERα transcriptional activity, but Anas was unable to block AD-stimulated activity in AR Arom-overexpressing cells. In addition, the growth of several of the AR Arom-overexpressing cells was stimulated with treatment of Anas alone. Resistance was not associated with activation of known mechanisms of resistance, such as HER2, or Akt activation. Inhibitors of various signaling and receptor growth pathways are currently being tested for their effects on blocking Anas resistance.
Conclusion: Using a model of ERα-positive breast cancer cells expressing endogenous aromatase and AR, we have demonstrated that AR overexpression confers resistance to the AI Anas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 940. doi:10.1158/1538-7445.AM2011-940
Abstract 946: Interaction between smoking and obesity and the risk of developing breast cancer among postmenopausal women: The Women's Health Initiative Observational Study
Authors: Luo Juhua , Horn Kimberly , Ockene Judith K. , Simon Michael S. , Stefanick Marcia L. , Tong Elisa , Margolis Karen L. 
Published: June 2012

Abstract
Background: Recent studies suggest that smoking increases breast cancer risk, and obesity is an established risk factor for postmenopausal breast cancer. Since there is a complex relation between smoking, weight and fat distribution, we hypothesized that the effect of smoking on breast cancer risk may be modified by obesity among postmenopausal women.
Methods: 76,628 women with no previous history of cancer aged 50-79 enrolled in the Women's Health Initiative Observational Study were recruited at 40 centers across the United States from 1993 to 1998, and were followed up through 2009. Cox proportional hazards regression models estimated hazard ratios (HRs) for invasive breast cancer risk associated with smoking, stratified by obesity status, and adjusting for other breast cancer risk factors. Interactions between obesity status and different metrics of smoking were tested by entering multiplicative interaction terms into the model.
Results: 3,378 incident cases of invasive breast were identified. A significant association between smoking and breast cancer risk was noted in non-obese women, but not in obese women defined by BMI &gt; 30 (p for interaction=0.047). A significantly higher breast cancer risk was observed in non-obese women with long duration of smoking, but not in obese women (p for interaction = 0.03). Similar results were obtained when obesity status was defined by waist circumference &gt; 88 cm.

Conclusion: Our study suggests the effect of smoking on breast cancer risk was modified by obesity among post-menopausal women. The modification effect did not differ by general vs. abdominal obesity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 946. doi:10.1158/1538-7445.AM2011-946
Abstract 949: PathSeq: A comprehensive computational tool for pathogen discovery by deep sequencing of human cancer tissues
Authors: Ojesina Akinyemi I. , Kostic Aleksandar , Pedamallu Chandra Sekhar , Jung Joonil , Duke Fujiko , Getz Gad , Meyerson Matthew 
Published: June 2012

Abstract
BACKGROUND: It is thought that pathogens cause a significant fraction of human cancers. However, many of these pathogens are unknown. Our project is based on the premise that if a cancer is caused by a microbial infection, the cancer tissue should contain both human and microbial DNA/RNA. High throughput sequencing, followed by computational subtraction of human reads should then yield non-human candidate sequences for further validation.
METHODS: We have developed an integrated pathogen discovery process to address this need. cDNA libraries are generated from tumor tissues and subjected to high-throughput Illumina sequencing to generate 30-60 million sequence reads per sample. Quality filtered reads are analyzed using our automated pipeline, PathSeq, comprising several subtraction steps: i) aligning to human sequence databases; ii) aligning to other vertebrate sequence databases; iii) filtering for low-complexity reads; iv) aligning using BLAST to genome databases; and v) de novo assembly and searching against microbial databases.
RESULTS: We have generated and analyzed both transcriptome and whole genome sequencing data across several cancers, and have identified microbial sequences in both frozen and formalin-fixed paraffin-embedded (FFPE) tissues. The details will be presented during the meeting.
CONCLUSION: The PathSeq software package is implemented in a cloud-computing environment and is available for public use. It therefore has the potential to make pathogen discovery accessible to any researcher with access to human deep sequencing data.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 949. doi:10.1158/1538-7445.AM2011-949
Abstract 95: Increased hypomethylation of LINE-1 and Alu in human colorectal cancer metastasis
Authors: Hur Keun , Balaguer Francesc , Takahashi Masanobu , Nagasaka Takeshi , Koike Junichi , Hemmi Hiromichi , Koi Minoru , Boland Clement Richard , Goel Ajay 
Published: June 2012

Abstract
Background: Global hypomethylation of cytosines within CpG dinucleotides is one of the distinguishing features of the neoplastic cells in human cancers. More specifically, hypomethylation of evolutionarily conserved repetitive elements (Alu and LINE-1) is associated with increased chromosomal instability in colorectal cancer (CRC). Recent data indicates that transcription start sites of certain proto-oncogenes are located within these repeat elements, and increased hypomethylation of these regions may induce the expression of illegitimate oncogenic transcripts. Primary CRCs demonstrate frequent global Alu and LINE-1 hypomethylation; however, it is unclear whether hypomethylation of these repeat sequences may be associated with a metastatic phenotype Aim: This study was aimed to determine the role of increased hypomethylation of Alu and LINE-1 sequences in CRC metastasis development. Materials and Methods: We analyzed a panel of CRC cells with different metastatic potential, as well as tissues from 50 CRC patients with matched primary colon cancer and corresponding liver metastasis tissues. Alu and LINE-1 methylation levels were determined by quantitative bisulfite pyrosequencing. Results: Lower levels of Alu and LINE-1 methylation were observed in CRC cell lines that came from metastatic foci. When we analyzed Alu and LINE-1 methylation levels in clinical specimens, the levels of Alu methylation in liver metastatis were significantly lower compared to the matched primary CRC tissues (77.2%±8.3 and 80.9%±10.7, respectively; P&lt;0.01). Similarly, the levels of LINE-1 methylation in metastasized liver foci was significantly lower compared to the corresponding matched primary CRC (61.2%±9.7 vs 65.8%±7.0 (P&lt;0.01). The relative demethylation level was higher in LINE-1 (4.6%) than Alu (3.7%) sequences. In further support of our results, methylation analysis of surrounding normal liver tissue showed higher methylation levels for Alu (82.2%±4.7) and LINE1 (71.3%±8.3) compared with both primary CRC and liver metastasis. Conclusion: Our results provide evidence that increased Alu and LINE-1 hypomethylation is a novel feature of liver metastasis from CRC. We speculate that hypomethylation of these repeat elements may inadvertently permit activation of previously silenced proto-oncogenes, which may facilitate a more aggressive malignant phenotype in these advanced stage cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 95. doi:10.1158/1538-7445.AM2011-95
Abstract 973: Targeting cancer stem cells by a novel anti-frizzled antibody inhibits pancreatic tumor growth and induces differentiation
Authors: Yen Wan-Ching , Fischer Marcus , Lewicki John , Gurney Austin , Hoey Timothy 
Published: June 2012

Abstract
Clinical management of pancreatic cancer over the past years has not been improved and this disease remains the fourth most common cause of cancer-related death. It has been suggested that cancer stem cells drive tumor growth and progression and are resistant to many current therapies. The WNT/beta-catenin pathway, which signals through the Frizzled (FZD) receptor family and co-receptors, plays an important role in regulating cell fate, stem cell self-renewal and maintenance. We have recently demonstrated that inhibition of WNT/beta-catenin pathway by an anti-FZD antibody 18R5 decreased tumorigenicity and induced differentiation in solid tumors. The present study evaluated the anti-tumor effect of OMP-18R5 in a panel of pancreatic tumors. In vivo studies using primary pancreatic xenograft tumor models showed that OMP-18R5 was efficacious against both high and low grade pancreatic tumors. Histologic and gene expression analyses indicated that the 18R5-mediated anti-tumor effect was associated with inhibition of WNT target genes while inducing of mucin expression and tumor cell differentiation. Furthermore, inclusion of OMP-18R5 delayed pancreatic tumor recurrence following termination of gemcitabine. The delay in tumor recurrence by OMP-18R5 treatment was associated with a decrease in cancer stem cell frequency. The combination of OMP-18R5 and gemcitabine further decreased cancer stem cell frequency compared to the single agents. Our findings provide a rationale to target cancer stem cells through interference with WNT/beta-catenin pathway as a therapeutic approach in pancreatic cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 973. doi:10.1158/1538-7445.AM2011-973
Abstract 981: Study of altered metabolism due to anoikis resistance in ovarian cancer
Authors: Caneba Christine A. , Bellance Nadège , Karedath Thasni , Nagrath Deepak 
Published: June 2012

Abstract
Cancer cells have recently been shown to be resistant to anoikis, a form of cell death due to detachment, thus decreasing responsiveness to therapy. Catecholamines, antioxidants, and oncogenes have been shown to rescue metabolic defects caused during cell detachment. Thus, there is a strong motivation to study metabolic alterations associated with anoikis resistance in cancer. Despite efforts to understand the link between anoikis and cancer metabolism, extensive metabolic analysis of cancer cells is lacking. Tissue engineering of cancer cells to create three-dimensional cell environments can also be used as a model system to study cancer metabolism. We postulate that anoikis can be regulated by metabolism in tissue engineered cultures of ovarian cancer (OC) cells. Our findings using quantification of metabolites by conducting Ultra Performance Liquid Chromatography and metabolic assays pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by anoxia in cancer cells, resulting in identification of dominant factors which regulate OC metabolism. Amino acid supplementation significantly increased the TCA cycle flux at the level of citrate synthase and the fatty acid-derived acetyl-CoA to CO2. The information we have gained elucidates the critical role of metabolism in anoikis resistance in OCC in tissue engineered cultures.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 981. doi:10.1158/1538-7445.AM2011-981
Abstract 982: Transgenic expression of NSAID-activated gene-1 (NAG-1) protects mice from high fat diet-induced obesity
Authors: Kim Jong-Sik , Chrysovergis Kaliopi , Kosak Justin , Kissling Grace , Eling Thomas 
Published: June 2012

Abstract
Previously, we generated transgenic mice which over-express human NAG-1/GDF15 gene. These mice are resistant to the development of colorectal cancer and have reduced responses to inflammatory stimuli. In the present study, we observed that NAG-1 transgenic mice (NAG-1 Tg) are smaller and leaner than their wild-type counterparts and have less abdominal fat despite comparable food intake. Interestingly, the transgenic mice have lower circulating levels of the inflammatory adipokine, leptin, and lower expression in abdominal fat, the major source of leptin. Placed on a high fat diet (60% fat), body weight gain in NAG-1 Tg mice is very small or negligible compared to wild-type mice. Analysis of the metabolic activity showed that NAG-1 Tg mice on the high fat diet have higher energy expenditure than WT mice. In addition, global gene expression profiling analysis showed that expression of several genes involved in lipid metabolism were significantly down-regulated in the liver of NAG-1 Tg mice. Real-time PCR analysis confirmed decreased expression of genes such as Cidea, Cidec, Mogat1, CD36, and Apoa4, while the expression of SIRT-1 and phosphorylated SIRT-1 was not altered in the NAG-1 Tg mice. Taken together, our data indicate increased energy expenditure and decreased expression of lipid metabolism genes have pivotal roles for the lower observed abdominal fat levels. Furthermore, lower leptin levels, a critical mediator of intestinal inflammation, found in NAG-1 transgenic mice, may contribute to lower intestinal tumor growth and reduced inflammatory responses reported for the NAG-1 Tg mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 982. doi:10.1158/1538-7445.AM2011-982
Abstract LB-101: Y-box binding protein-1 (YB-1) inhibition triggers differentiation of normal and cancer stem cells from the brain
Authors: Fotovati Abbas , Abu-Ali Sam , Wang Pei-Shan , Deleyrolle Loic , Lee Cathy , Tricott Joanna , Chen James , Franciosi Sonia , Nakamura Yas , Sugita Yasuo , Uchiumi Takeshi , Kuwano Michihiko , Leavitt Blair R. , Singh Sheila , Jury Alexa , Jones Chris , Wakimoto Hiroaki , Reynolds Brent A. , Pallen Catherine J. , Dunn Sandra E. 
Published: June 2012

Abstract
The Y-box-binding protein-1 (YB-1) is up-regulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knock-out mice had reduced Sox-2, nestin and musashi expression in the SVZ. While primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Likewise, YB-1, Sox-2, mushashi, Bmi-1 and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary CSCs. Silencing YB-1 with small interfering RNA attenuated the expression of these NSC markers, reduced neurosphere growth and triggered differentiation via coordinate loss of GSK3-β. Further, differentiation of CSCs with 1% serum or bone morphogenetic protein-4 (BMP-4) suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 was preferentially expressed in highly undifferentiated primary gliomas based on the analysis of WHO grade 1-IV tumors (n=49 cases). YB-1 was also co-expressed with Bmi-1 (Spearmans 0.80, p&gt;0.001) and Sox-2 (Spearmans 0.66, p&gt;0.001) based on the analysis of 282 cases of high-grade gliomas. These CSC markers were also highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 is a key feature of stem cells where it functions to suppress differentiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-101. doi:10.1158/1538-7445.AM2011-LB-101
Abstract LB-110: Bioinformatic discovery of repositioned drugs to target breast tumor initiating cells
Authors: Dave Bhuvanesh , Zhao Hong , Vahdat Linda T. , Chang Jenny C. , Wong Stephen TC 
Published: June 2012

Abstract
Background: We have previously identified a tumorigenic gene signature based on profile features in common in CD44+/CD24−/low cells vs. all other tumor cell subpopulations(13–15), and in cancer-derived mammospheres vs. bulk tumor tumor initiating cells (TICs) (CD44hi/CD24−/low). A novel method to expedite drug development is to reposition FDA-approved known drugs for any medical indication as anti-cancer therapy. By using bioinformatic approaches which combines protein-protein interactions, signaling pathways and drug information on 6000 drugs, we mapped these known drugs to critical pathways identified in our tumorigenic signature in order to target breast tumor initiating cells. Results: This bioinformatic approach identified 10 drugs which were then tested in vitro and in vivo for ability to inhibit tumor initiating cells. These in silico results were first confirmed by in vitro experiments by evaluating the effects of these repositioned drugs on mammosphere forming efficiency. In two “stem cell like” cell lines, SUM159 and BT549 treated with 10nM & 1μM of chloroquine, a dramatic reduction in MSFE was noted after a single treatment dose. Next, we performed limiting dilution transplantation assays, whereupon we treated SUM159 cells with 1μM chlorquine overnight and then transplanted the next day 200,000 cells/mouse (single sided). We observed a reduction in tumor initiation rate with only 1/12 xenografts growing within 10 weeks with chloroquine treatment vs 9/12 in control vehicle treated group. Conclusion: Bioinformatic approaches can be used to identify repositioned drugs against breast tumor initiating cells. This novel approach will allow the rapid translation of repositioned drugs that target breast tumor initiating cells into clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-110. doi:10.1158/1538-7445.AM2011-LB-110
Abstract LB-114: Molecular and lineage analysis of glioblastoma stem cells identifies clinically relevant models of glioblatoma
Authors: Fu Jun , Koul Dimpy , Yao Jun , Wang Shuzhen , Gumin Joy , Shen Ruijun , Vaillant Brian , Colman Howard , Lang Frederick F. , Aldape Kenneth D. , Yung W.K 
Published: June 2012

Abstract
The Cancer Genome Atlas project described a robust gene expression-based molecular classification of GBM. However, the functional and biological significance of the molecular subclasses are being determined. In this study, we hypothesize that Glioma Stem Cells (GSCs) isolated from individual patient tumor samples will recapitulate the molecular characteristics of tumor samples and provide a relevant model for functional analysis of the molecular subclasses. Thus we conducted a comprehensive analysis of 26 GSC lines with expression array, RPPA, and a series of neural lineage markers. Analysis of the expression data classified the 26 GSC lines into four subtypes (Classical, Proneural 1, Proneural 2 and Mesenchymal,) closely similar to the TCGA subclasses with a distinct profile for each subtype (c-Myc, Cyclin D2 for Classical; Olig2, NKX2–2, Notch-1, Notch-3 for Proneural 2; BMP4, DCX, p16INK4a, ID2 for Proneural 1; CD44, CAV1, TGFBR2 for Mesenchymal). Further analysis showed that GSC subtypes exhibit divergent patterns of signaling pathway activation. The major pathways activated in 4 subtypes were Notch pathway in Proneural 2, Wnt/β-Catenin in Proneural 2 and Classical, while FGF/VEGF and TGF-β in Mesenchymal. In vitro treatment with SB 431542, a TGF-βR inhibitor, showed that Mesenchymal subtype is more sensitive than other subtypes. More importantly, lineage analysis of GSCs subtypes show that Proneural and Classical GSCs differentially express lineage markers for neural stem/progenitor cells and were responsive to differentiating agent retinoic acid. In addition, GSC subtypes exhibit distinct biological behaviors in self-renewal capacity, proliferation, invasiveness, angiogenic potential, response to growth factor stimulus, and differentiation in vitro and in vivo with Classical subtype being more proliferative and Mesenchymal subtype being more angiogenic and invasive.
In conclusion, our comprehensive analysis showed that GSCs reflect patient tumor subclass and these subtypes showed distinct regulatory pathway activation, lineage profile and biological behaviors. Thus GSC is biologically and molecularly a more relevant model system for preclinical studies of therapeutic intervention and to expand our molecular understanding of human GBM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-114. doi:10.1158/1538-7445.AM2011-LB-114