bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1789: Estrogen receptor alpha and beta gene expression in benign breast tissue of high risk premenopausal women treated with the SERM acolbifene
Authors: Kimler Bruce F. , Phillips Teresa A. , Fabian Carol J. 
Published: July 2016

Abstract
Background
We conducted a pilot study to assess the feasibility of a 4th generation selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women at high risk for development of breast cancer [Cancer Prev Res 8, December 2015]. Favorable modulation of biomarkers was observed in benign breast tissue acquired before and after intervention. This included reduction in proliferation (Ki-67 immunocytochemistry) and decreases in expression of genes that code for ERα, pS2, and PgR. While ERα is over-expressed and stimulatory in breast carcinogenesis, ERβ which would be inhibitory is down-regulated. Thus, a change in the ratio of gene expression might be most informative. We have now analyzed gene expression of ERβ so as to examine whether it, or the ratio of ERα to ERβ, may contribute to assessment of response.
Methods
Premenopausal women at elevated risk for breast cancer were screened by random periareolar fine needle aspiration (RPFNA) performed during the follicular phase of the menstrual cycle. Eligible women (n = 25) received 6-8 months of open-label acolbifene (20 mg/d), followed by repeat RPFNA. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed on 16 paired specimens for several genes associated with estrogen activity: estrogen receptor 1 (ESR1) for ERα, trefoil factor 1 (TFF1) for pS2, GREB1 for growth regulation by estrogen in breast cancer 1, PGR for progesterone receptor, and estrogen receptor 2 (ESR2) for ERβ. The quantity of each biomarker transcript was expressed relative to the reference transcript HPRT1. Further normalization by epithelial cell markers (KRT19 for cytokeratin 19 or CDH1 for E-Cadherin) did not materially alter the results.
Results
Significant changes had been previously shown for transcripts that code for pS2 (15 decreases, 1 increases; p = 0.002), ERα (11↓, 5↑; p = 0.013), and PgR (15↓, 1↑; p = 0.001); plus a suggestion of effect of GREB-1α (10↓, 6↑; p = 0.074). ERβ exhibited a general increase, but this was not statistically significant (5↓, 11↑; p = 0.24). However, the reduction of the ratio of ERα to ERβ was statistically significant (15↓, 1↑; p = 0.002).
Conclusions
Assessment of the ratio of gene expression for ERα to ERβ, and possibly their protein products by immunocytochemistry, may provide a useful surrogate endpoint biomarker by which to monitor response to SERMs used for breast cancer chemoprevention in premenopausal women.
Supported by NO1-CN-35135.
Citation Format: Bruce F. Kimler, Teresa A. Phillips, Carol J. Fabian. Estrogen receptor alpha and beta gene expression in benign breast tissue of high risk premenopausal women treated with the SERM acolbifene. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1789.
Abstract 1818: Coregulation of progesterone receptor and O-GlcNAc in breast cancer
Authors: Trinca Gloria , Goodman Merit , Workman Lauren , Carroll Jason , D’Santos Clive , Slawson Chad , Hagan Christy R. 
Published: July 2016

Abstract
Progesterone receptor (PR) activity is highly regulated by post-translational modifications. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analysis identified O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) as a PR-interacting protein. OGT catalyzes the addition of N-acetylglucosamine sugar moieties to serine/threonine residues in order to coordinate several cellular processes—including transcription, metabolism, and cell fate. Further investigation revealed that PR is O-GlcNAcylated, and enhanced OGT activity subsequently decreases PR protein stability. Interestingly, PR-expressing breast cancer cells display lower OGT levels in comparison to PR-null counterparts, suggesting that PR may govern its own O-GlcNAcylation or that of other key regulatory proteins. Our lab previously identified a phosphorylation site at Ser-81 in PR that potentiates the expression of PR proliferative target genes. Phosphorylation and O-GlcNAcylation are known to compete for the same residue substrates; and our preliminary data suggests that PR O-GlcNAcylation may also alter its transcriptional activity for a subset of target genes. While the role of PR in breast cancer progression is well characterized, the overall effect of protein O-GlcNAcylation within these tumors remains highly controversial. Collectively, our data supports a potential regulatory mechanism wherein OGT serves to restrain PR function in early PR+ tumors; whereas those that have lost PR expression may exhibit the elevated pro-tumorigenic OGT activity previously associated with more advanced breast cancers. As such, the continued study of O-GlcNAcylation with respect to PR stability, phosphorylation, and transcriptional activity may lead to a clearer understanding of these effectors and their contribution to breast cancer progression.
Citation Format: Gloria Trinca, Merit Goodman, Lauren Workman, Jason Carroll, Clive D’Santos, Chad Slawson, Christy R. Hagan. Coregulation of progesterone receptor and O-GlcNAc in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1818.
Abstract 1891: PDGF signaling maintains survival of proneural glioma cells by regulating USP1 to stabilize ID2
Authors: Rahme Gilbert J. , Zhang Zhonghua , Young Alison L. , Cheng Chao , Bivona Eric J. , Fiering Steven N. , Hitoshi Yasuyuki , Israel Mark A. 
Published: July 2016

Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of GBM has identified distinct molecular subtypes of GBM with the latest report identifying four molecular subtypes: proneural, neural, classical, and mesenchymal. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are commonly observed in proneural GBM and can drive proneural gliomagenesis. However, little is known about the critical determinants of malignancy mediated by PDGF signaling in proneural glioma. Using a mouse model of proneural glioma and comparative transcriptomics, we determined that PDGF signaling upregulates ubiquitin specific peptidase 1 (Usp1) to promote survival of murine proneural glioma cells. Further experimentation revealed that PDGF-mediated expression of USP1 post-translationally stabilized Inhibitor of DNA-binding 2 (ID2), which we found to be required for glioma cell survival. Deletion of the Id2 gene delayed tumor-induced mortality. Pharmacological inhibition of USP1 decreased ID2 levels, and delayed tumorigenesis in mice. Importantly, decreased USP1 expression is associated with prolonged survival in patients with proneural GBM but not with other subtypes of GBM. Our data describe a signaling cascade downstream of PDGF that is required for the survival of proneural GBM cells and suggest that inhibition of the PDGF-USP1-ID2 axis could serve as a therapeutic strategy for the treatment of proneural GBM with increased PDGF signaling.
Citation Format: Gilbert J. Rahme, Zhonghua Zhang, Alison L. Young, Chao Cheng, Eric J. Bivona, Steven N. Fiering, Yasuyuki Hitoshi, Mark A. Israel. PDGF signaling maintains survival of proneural glioma cells by regulating USP1 to stabilize ID2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1891.
Abstract 1936: Comprehensive long non-coding RNA expression profiling from the TCGA HNSCC RNA-sequencing data
Authors: Nohata Nijiro , Abba Martin , Amornphimoltham Panomwat , Gutkind J. Silvio 
Published: July 2016

Abstract
Objectives; Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer types in the world. Despite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall 5-year survival rate for patients with HNSCC is only 40% - 50%. Although a growing body of evidence indicates that long non-coding RNAs (lncRNAs) contribute to the initiation and development of various types of cancers, the role of lncRNA expression in human HNSCC remains unknown. In this study, we aimed to establish the onco-lncRNAome profiling of HNSCC from The Cancer Genome Atlas (TCGA) project.
Materials and Methods; The Atlas of Noncoding RNAs in Cancer (TANRIC) database (http://ibl.mdanderson.org/tanric/_design/basic/index.html) was employed to retrieve the lncRNA expression information from the TCGA HNSCC RNA-sequencing data. Our recently generated RNA-sequencing data from 22 representative HNSCC cell lines (OPC-22 panel) were also included in this study. Bioinformatics approaches, such as differential gene expression analysis, survival analysis, principal component analysis, and Co-LncRNA enrichment analysis were performed.
Results; Using TCGA HNSCC RNA-sequencing data from 426 HNSCC and 42 adjacent normal tissues, we identified 728 lncRNA transcripts significantly and differentially expressed in HSNCC. Among the 728 lncRNAs, 55 lncRNAs were significantly associated with cancer prognosis (overall survival and/or recurrence free survival). We also identified 140 lncRNA transcripts significantly and differentially expressed between Human Papilloma Virus (HPV) positive tumors and HPV negative tumors. 30 lncRNA transcripts were distinctly expressed between TP53 mutated tumors and TP53 wild type tumors. Among them, there were 19 overlapping genes up-modulated in HPV positive and TP53 wild type tumors. Co-LncRNA enrichment analysis suggested that protein-coding genes that are co-expressed with cancer-associated lncRNAs might be involved in malignant progression. Of interest, many differentially expressed lncRNAs in HNSCC were reflected in the HNSCC cell line panel.
Conclusion; LncRNAs profiling could provide novel insights into the potential mechanisms of HNSCC oncogenesis. A unique set of lncRNAs may represent potential targets for diagnosis, therapy and prevention of HNSCC.
Citation Format: Nijiro Nohata, Martin Abba, Panomwat Amornphimoltham, J. Silvio Gutkind. Comprehensive long non-coding RNA expression profiling from the TCGA HNSCC RNA-sequencing data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1936.
Abstract 1948: MiRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples
Authors: Kent Michael , Zwingenberger Allison , Westropp Jodi , Barrett Laura , Ghosh Paramita , Vinall Ruth L. 
Published: July 2016

Abstract
Early symptoms of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC and decreased rates of survival. To determine whether miRNA can be used as non-invasive diagnostic biomarkers in this setting, we assessed miRNA expression in RNA extracted from urine and blood from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 18). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103, and miR-106b) were assessed by quantitative real-time PCR. Statistical analyses using ranked ANOVA identified significant differences in miR-103 and miR-16 levels between urine samples from LUTD and TCC patients (miR-103, fold change = 2.55, p = 0.015; and miR-16, fold change = 3.02, p = 0.002). However, logistic regression analyses determined miR-103, but not miR-16, can distinguish between canine LUTD and TCC patients (OR = 0.78 p = 0.031, AUC = 0.85). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103 levels in normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, cooordination of miR-34a, miR-16, let-7c, and miR-103 expression levels was maintained in blood samples from TCC patients. Our combined data indicate further investigation of miR-103 as a diagnostic urine biomarker for TCC, and investigation of the role of miR-103 as well as dysregulation of coordinated miRNA expression in bladder carcinogenesis, is warranted.
Citation Format: Michael Kent, Allison Zwingenberger, Jodi Westropp, Laura Barrett, Paramita Ghosh, Ruth L. Vinall. MiRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1948.
Abstract 1956: Mirnas hsa-miR-214-3p, -378a-3p e -34a-5p as biomarkers for uterine mesenchymal neoplasms
Authors: dos Anjos Laura G. , Maciel Gustavo A. , Cunha Isabela W. , Baracat Edmund C. , Carvalho Kátia C. 
Published: July 2016

Abstract
Background: Uterine mesenchymal tumors have specific mechanisms of development that are largely unknown. One of the molecular mechanisms which may be involved in the appearance and progression of these tumors is the regulation of gene expression by miRNAs. These molecules are small non-coding RNAs that play important roles in several biological pathways. The identification of miRNAs that show particular differences in expression profile can help broaden the diagnostic methods available for these tumors. Objectives: To evaluate the expression profile of microRNAs described as sequences related to tumors development in uterine leiomyosarcomas samples, comparing to leiomyomas and normal myometrium. Methods: We selected 37 samples of uterine leiomyosarcoma (LMS), 16 unconventional leiomyomas (LMA), 10 conventional leiomyomas (LM) and 2 myometrium (used as reference samples). Samples were obtained from the Discipline of Gynecology of the Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo and Department of Pathology of the A C Camargo Cancer Center, both in Sao Paulo, Brazil. The total RNA was obtained and used to perform the synthesis of cDNA.The real time PCR reactions was performed using the Kit miScript SYBR Green PCR (Qiagen) for analysis from the 84 miRNAs sequences already described in the literature as tumor development related sequences. Results: The data analysis from the 84 sequences of microRNA showed wide variation in the regulation of these molecules expression. After computational analysis, we selected only those miRNAs with different expression profile between LM, LMA and LMS. The goal was to obtain a molecular signature that differentiate and identify each tumor using normal tissue as a reference. We found that hsa-mir-214-3p and hsa-miR-378-3p (fold regulation of -2.32 and -2.97; respectively) presented down-regulation in samples from the uterine LMS. In LMA we found a down regulation of hsa-miR-34a-5p (-3.12 fold regulation). Conclusions: We identified three miRNAs (hsa-mir-214-3p, and -378-3p and -34a-5p) differentially expressed in LMA and LMS. Analyzes of target genes of these miRNAs may identify specific proteins for use in the differential diagnosis, prognosis and patients management in these tumors.
Citation Format: Laura G. dos Anjos, Gustavo A. Maciel, Isabela W. Cunha, Edmund C. Baracat, Kátia C. Carvalho. Mirnas hsa-miR-214-3p, -378a-3p e -34a-5p as biomarkers for uterine mesenchymal neoplasms. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1956.
Abstract 1957: MicroRNA analysis paired with a novel live cell viability assay: a complete epigenetic workflow in human cancer cell lines
Authors: Lewis Samantha , Hook Brad , Smith Don , Horejsh Douglas , Schagat Trista 
Published: July 2016

Abstract
The requirements for nucleic acid purification for use in RNA profiling have expanded with the growing interest in the role of microRNAs (miRNAs) and other small non-coding RNAs in cancer cell growth and metastasis. This evolution of expression analysis has highlighted the need for more sophisticated tools for total RNA isolation from cancer cells and tissues, beyond traditional translated messenger RNAs (mRNA). To address this need, we describe tools to isolate total RNA, for mRNA and miRNA analyses, in the context of an epigenetic workflow with cancer cell lines.
In these experiments, histone deacetylase (HDAC) inhibitor treatment of different cancer cell lines was performed and expression of miRNA and mRNAs measured in parallel with assays for cell viability, cytotoxicity, and HDAC activity. This workflow multiplexes RNA and miRNA expression profiling with assays for viability and cytotoxicity to efficiently capture a more complete understanding of expression results.
With this improved cell viability workflow, one experiment from the same well can yield information about cell health, cytotoxicity, HDAC activity, and mRNA plus miRNA expression profiling. Our workflow incorporates monitoring of cell health in real-time during experimental treatments, simple and effective total RNA purification, and robust quantitative PCR reagents for a comprehensive experimental design.
Citation Format: Samantha Lewis, Brad Hook, Don Smith, Douglas Horejsh, Trista Schagat. MicroRNA analysis paired with a novel live cell viability assay: a complete epigenetic workflow in human cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1957.
Abstract 1971: BRD4 amplification facilitates an oncogenic gene expression program in high-grade serous ovarian cancer
Authors: Rhyasen Garrett W. , Yao Yi , Dulak Austin , Castriotta Lillian , Jacques Kelly , Hattersley Maureen , Mills Gordon B. , Zinda Michael , Fawell Stephen , Lyne Paul , Clark Edwin , Chen Huawei 
Published: July 2016

Abstract
The bromodomain and extra-terminal (BET) protein, BRD4 functions as a transcriptional co-activator through recruitment of regulatory complexes to acetylated chromatin. Among all malignancies, the most focal, and recurrent BRD4 gene amplification occurs in high-grade serous ovarian cancer (HGSOC). Despite the elucidation of BRD4 dependencies in cancer, it is unclear whether BRD4 gene amplification can result in oncogenic activity, and hence serve as a patient selection strategy for BET bromodomain inhibitors. To assess the oncogenic potential of BRD4 amplification in HGSOC, we assayed enforced BRD4 expression in non-transformed immortalized surface ovarian cells (IOSE). Physiologically relevant expression of either long or short BRD4 spliced isoforms in IOSE (BRD4-IOSE) resulted in marked phenotypic changes indicative of cellular transformation, including altered growth kinetics, chromatin reorganization, and acquisition of colony formation potential. Transcriptional profiling of BRD4-IOSE and BRD4-amplified HGSOC patients revealed shared expression patterns, including enriched MYC, E2F1, and VEGF gene signatures. Interrogation of BRD4 inhibitor pharmacodynamic markers, and transcripts upregulated through enforced BRD4 expression uncovered Neuregulin-1 as a critical BRD4 transcriptional effector. RNAi-mediated Neuregulin-1 depletion was capable of abolishing the oncogenic activity of BRD4-IOSE, and exogenous Neuregulin-1 was sufficient to transform IOSE without BRD4. A novel BRD4-SWI/SNF interaction was required for driving the oncogenic activity of BRD4-IOSE through maintaining NRG1 expression. The sensitivity of patient-derived HGSOC xenografts to a novel clinical candidate BRD4 inhibitor, AZD5153, correlated with BRD4 amplification and a pharmacodynamic NRG1 response. This study demonstrates the oncogenic potential of BRD4 amplification, defines a relationship between BRD4 and NRG1, and further establishes HGSOC as an appropriate patient population in which to test the therapeutic potential of BET bromodomain inhibitors.
Citation Format: Garrett W. Rhyasen, Yi Yao, Austin Dulak, Lillian Castriotta, Kelly Jacques, Maureen Hattersley, Gordon B. Mills, Michael Zinda, Stephen Fawell, Paul Lyne, Edwin Clark, Huawei Chen. BRD4 amplification facilitates an oncogenic gene expression program in high-grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1971.
Abstract 1974: Consequence of the tumor-associated deletion of CHD1 on transcriptional output and tumor progression
Authors: Augello Michael A. , Blattner-Johnson Mirjam , Rubin Mark , Barbieri Christopher 
Published: July 2016

Abstract
CHD1 is a member of the super-family of chromatin modifier proteins, and is characterized by the presence of several chromo-domains as well as an ATP dependent helicase domain. A multitude of studies across several model systems have demonstrated that CHD1 functions as a transcriptional co-activator, responsible for efficient RNA polymerase II (RNA pol II) ejection from the transcriptional start site as well as maintenance of RNA pol II processivity across the gene body. This is accomplished largely though nucleosome remodeling ahead of RNA pol II, which efficiently reorganizes nucleosome position to allow for optimal RNA pol II function. Consequently, as CHD1 plays a critical role in transcriptional competency, tumor associated deletions and/or mutations of the CHD1 gene that compromise its function are rare. Interestingly, prostate cancer proves to be the exception, where the CHD1 locus is deleted with high frequency in primary disease. Tumors harboring homozygous deletion of CHD1 belong to a subclass of prostate cancer that are enriched for either SPOP or FOXA1 mutations, suggesting a prostate-specific, tumor suppressive role for CHD1 in this genomic context. Importantly, while the oncogenic functions of both FOXA1 and SPOP mutations have been largely defined, little is known as to how CHD1 loss contributes to tumor initiation or progression. Here, using 3D organoid cultures derived from GEM models of inducible CHD1 loss, prostate specific cells were found to have dramatically altered transcriptionally competency upon CHD1 depletion. These events were correlated with an aberrant, tumor-associated transcriptome, resulting in changes in morphology and growth. Furthermore, while genome wide assessment of CHD1 occupancy in human prostate cancer models uncovered an enrichment of CHD1 at sites of active transcription, loss of CHD1 did not dramatically affect expression of genes associated with tumor progression. Inversely, genomic loss of CHD1 was associated with changes in lineage dependent markers, suggesting that a major function of CHD1 is to regulate the differentiation state of prostate cells. Collectively, these data help to define the tumor suppressive role for CHD1 in prostate cancer tumorigenesis, and suggest that loss of CHD1 could alter the function of key transcriptional regulators associated with prostate cancer initiation and progression.
Citation Format: Michael A. Augello, Mirjam Blattner-Johnson, Mark Rubin, Christopher Barbieri. Consequence of the tumor-associated deletion of CHD1 on transcriptional output and tumor progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1974.