bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA19: Cooperation between androgen receptor and Polycomb in prostate cancer
Authors: Zhao Jonathan C. , Runkle Christine , Yu Jianjun , Wu Longtao , Jin Hongjian , Kuzel Timothy , Lee Chung , Yu Jindan 
Published: May 2013

Abstract
Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development, function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has been primarily known as a transcriptional activator inducing prostate-specific gene expression. Although androgen stimulation has been shown to also suppress genes, little attention has been paid to the mechanisms and functions of AR-mediated gene repression. Through integrative analysis of genome-wide AR occupancy and androgen-regulated gene expression, here we report AR as a globally acting transcriptional repressor. This repression is dictated, at least in part, by the Polycomb group protein EZH2 and repressive chromatin remodeling. In embryonic stem cells (ESC), AR-repressed genes harbor bivalent H3K4me3 and H3K27me3 modifications that are characteristic of developmental regulators, the silencing of which maintains the undifferentiated ESC state. Similarly, these genes are down-regulated in poorlydifferentiated, castration-resistant prostate tumors rendering a stem cell-like cellular state. To characterize the function of AR-repressed genes, we nominated NOV as a top AR-repressed gene. We show that NOV is robustly suppressed by androgen through the AR. Using NOV as a model gene we present evidence that AR directly inhibits gene expression through physically binding to the enhancer, establishing promoter-enhancer DNA looping, and inducing repressive chromatin remodeling. We further demonstrate that NOV is down-regulated in aggressive prostate cancer. Concordantly, NOV expression inhibits prostate cancer cell growth, migration, and invasion in vitro and xenograft tumor growth in mice. Collectively, our data reveal an unexpected role of AR in inhibiting non-prostatic differentiation and, upon aberrant signaling, promoting cancerous de-differentiation. Our findings support AR-mediated inhibition of tumor suppressors as a novel mechanism to prostate cancer progression.
Citation Format: Jonathan C. Zhao, Christine Runkle, Jianjun Yu, Longtao Wu, Hongjian Jin, Timothy Kuzel, Chung Lee, Jindan Yu. Cooperation between androgen receptor and Polycomb in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA19.
Abstract IA2: Genomic comparisons of coincident prostate cancer foci
Authors: Mardis Elaine R. , Humphrey Peter , McGrath Sean , Demeter Ryan , Magrini Vincent , Dees Nathan , Kanthi Krishna , Maher Christopher , Ding Li , Kibel Adam 
Published: May 2013

Abstract
We have an interest in distinguishing patients with aggressive from those with indolent prostate cancer. The present best indicator of disease aggressiveness is Gleason grade, assigned by histopathological examination of carcinoma in prostate tissue. Clinically speaking, Gleason pattern 4 tumors are more aggressive while Gleason pattern 3 tumors are more indolent. As such, we sought to characterize both patterns at the genomic level by sequencing and analyzing foci of Gleason 3 and 4 patterns from the same patient. By combining laser capture microdissection of coincident Gleason 3 and 4 foci in the same patients, with next-generation sequencing of the derived DNA by our ultr-alow input sequencing library construction techniques, we were able to generate whole genome sequencing data for these samples. Advanced analysis of the aligned whole genome data has permitted an examination of the genomic relatedness of Gleason 3 and 4 foci for two patients. I will present our results to-date from these analyses, shedding light on the fundamental genomic progression evident as Gleason scores increase. More recently, we have complimented these studies with additional whole genome sequencing and analysis of aggressive prostate cancers. Our preliminary findings for these samples also will be reported.
Citation Format: Elaine R. Mardis, Peter Humphrey, Sean McGrath, Ryan Demeter, Vincent Magrini, Nathan Dees, Krishna Kanthi, Christopher Maher, Li Ding, Adam Kibel. Genomic comparisons of coincident prostate cancer foci [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA2.
Abstract IA23: Diagnosing prostate cancer with image fusion (MRI, PET, CT, US)
Authors: Choyke Peter L. 
Published: May 2013

Abstract
The localization of cancer within the prostate is important for diagnosis, staging, biopsy guidance, focal therapy and active surveillance. Among the available imaging methods ultrasound offers real time monitoring but poor sensitivity, MRI offers higher sensitivity but is not real time, PET has the highest sensitivity but poor resolution and CT offers high resolution with poor sensitivity. Thus, no single imaging modality is ideal for this challenging application. This talk will focus on how we can use image fusion to combine the best aspects of each modality into a “hybrid scan” that is more than additive in its value.
MRI is the best current modality for localizing prostate cancer. MRI depends on the use of multiple parameters such as T2 weighting, diffusion weighting, spectroscopy and dynamic contrast enhancement. Since each of these methods are slightly different in their acquisition parameters, these images must first be fused to create a composite multiparametric MRI. However, having localized a suspicious area on MRI, it is necessary to direct a biopsy into it. Unfortunately, doing this under MR is a tedious and imperfect process. Thus, MRI can be fused to transrectal Ultrasound for purposes of biopsy. Under ultrasound (with MR guidance), real time biopsies and even focal therapies can be performed. One disadvantage of this approach is that with focal therapies the ability to perform real time MR thermometry is lost.
PET scanning has the highest sensitivity among the available modalities. To date, however, there is no ideal PET agent for localizing prostate cancer while it is still confined to the gland. However, there are a growing number of exciting PET agents that will be useful in the setting of local recurrence and advanced disease. For instance, agents such as Sodium Fluoride (F18 NaF), Dihydrotestosterone (F18-DHT), Prostate Specific Membrane Antigen (F18 DCFBC) and synthetic leucine analogs (F18-FACBC) are among the promising agents available for advanced prostate cancer. Unfortunately, PET suffers from poor spatial resolution, however fusion with CT is now commonplace. Newer scanners combine PET and MRI, thus completing the circle of possible fusions between MRI, PET, CT and Ultrasound. Such hybrid imaging promises great dividends for the management of patients with prostate cancer.
Citation Format: Peter L. Choyke. Diagnosing prostate cancer with image fusion (MRI, PET, CT, US) [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA23.
Abstract IA24: Molecular imaging agents for prostate cancer: Focus on PSMA
Authors: Pomper Martin G. 
Published: May 2013

Abstract
Although most clinical diagnostic imaging studies employ anatomic techniques such as computed tomography and magnetic resonance imaging, much of radiology research currently focuses on adapting these conventional methods to physiologic imaging as well as on introducing new techniques and probes for studying processes at the cellular and molecular levels in vivo, i.e. molecular imaging. Molecular imaging promises to provide new methods for the detection of minimal disease and support for personalized therapy. This summary will focus on experimental and near-term translational molecular imaging agents and methods for prostate cancer, with a focus on radiopharmaceuticals and optical agents, the former primarily for staging and the latter for surgical guidance.
Citation Format: Martin G. Pomper. Molecular imaging agents for prostate cancer: Focus on PSMA [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA24.
Abstract IA3: Functional implications of relocation of regulated transcription units in prostate cancer
Authors: Yang Liuqing , Lin Chunru , Nunez Esperanza , Li Wenbo , Destici Eugin , Rosenfeld Michael G. 
Published: May 2013

Abstract
Despite the long-standing recognition of distinct subnuclear architectural features and the recent discovery of noncoding RNAs (ncRNAs), their potential interacting roles in gene regulation remain elusive. We have found that two ncRNAs, TUG1 and NEAT2, located in Polycomb body (PcGs) and interchromatin granules, respectively, control relocation of growth control genes required for regulation of cell cycle between these two subnuclear structures, depending on the status of Polycomb 2 protein (Pc2) methylation in response to growth signals. These ncRNAs direct the assembly of multiple transcriptional co-repressor/coactivator complexes and, surprisingly, can alter “reading” of the histone tail marks by the Pc2 chromodomain, thereby specifying growth control gene expression and cell proliferation in a spatially organized manner. Binding of NEAT2 to demethylated Pc2, which promotes the SUMOylation of E2F1, which culminates in activation of the growth control gene program. These observations provide a molecular logic integrating actions of transcription factor/co-regulators, non-histone protein methylation, and ncRNAs resident in distinct subnuclear architectural structures to achieve coordinated programs of regulated gene expression in the three-dimensional space of the nucleus. We also will present data linking these strategies to mechanisms of ligand-induced activation of AR target genes in prostate cancer cells.
Citation Format: Liuqing Yang, Chunru Lin, Esperanza Nunez, Wenbo Li, Eugin Destici, Michael G Rosenfeld. Functional implications of relocation of regulated transcription units in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA3.
Abstract PR1: Oncogenic ETS over-expression mimics RAS/MAPK signaling in prostate cells
Authors: Hollenhorst Peter C. , Ferris Mary W. , Hull Megan A. , Chae Heejoon , Kim Sun , Graves Barbara J. 
Published: May 2013

Abstract
The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers. The prostate cancer chromosomal rearrangements that drive over-expression are associated with one of four ETS genes, ERG, ETV1, ETV4 and ETV5. It is not clear how these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate. We report that these oncogenic ETS proteins, but not other ETS factors, enhance prostate cell migration. Genome-wide binding analysis matched this specific biological function to occupancy of a unique set of genomic sites highlighted by the presence of ETS and AP-1 binding sequences. ETS/AP-1 binding sequences are prototypical RAS-responsive elements, but oncogenic ETS proteins activated a RAS/MAPK transcriptional program in the absence of MAPK activation. Thus, overexpression of oncogenic ETS proteins can replace RAS/MAPK pathway activation in prostate cells. The genomic description of this ETS/AP-1 regulated, RAS-responsive, gene expression program provides a resource for understanding the role of ETS factors in both prostate cancer and other cancers with either ETS or RAS pathway mutations.
This abstract is also presented as Poster B26.
Citation Format: Peter C. Hollenhorst, Mary W. Ferris, Megan A. Hull, Heejoon Chae, Sun Kim, Barbara J. Graves. Oncogenic ETS overexpression mimics RAS/MAPK signaling in prostate cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR1.
Abstract PR5: Therapeutic targeting of oncogene-specific tyrosine kinase networks during prostate cancer progression
Authors: Drake Justin M. , Huang Jiaoti , Graeber Thomas G. , Witte Owen N. , Graham Nicholas A. , Stoyanova Tanya , Sedghi Amir , Goldstein Andrew S. , Cai Houjian , Smith Daniel A. , Zhang Hong , Evangelia Komisopoulou 
Published: May 2013

Abstract
Dominant activating mutations or DNA amplification of tyrosine kinases are not readily observed despite the numerous oncogenic alterations implicated in prostate cancer. We demonstrate that castration resistant prostate cancer (CRPC) exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in this disease in the absence of specific tyrosine kinase mutations. We generated a mouse model of prostate cancer progression using combinations of commonly perturbed non-tyrosine kinase oncogenes and pathways, including myristoylated Akt (Akt), androgen receptor (AR), Erg, and activated Kras (KrasG12V). We recapitulated the different stages of prostate cancer ranging from prostatic intraepithelial neoplasia (PIN) (Akt) to low grade cancer (Akt+Erg) to highly aggressive prostatic adenocarcinoma (Akt+AR or Akt+KrasG12V). We detected a significant upregulation of tyrosine phosphorylation at the advanced adenocarcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of Egfr Y1172 (Akt+Erg), EphA2 Y595 (Akt+KrasG12V), and Jak2 Y1007/08 (Akt+AR). Kinase:substrate relationship analysis of the phosphopeptides also revealed Abl Y245 and Src Y416 tyrosine kinase activation in Akt+AR tumors; known targets of the tyrosine kinase inhibitor Dasatinib. We are currently evaluating the efficacy of tyrosine kinase inhibitors Dasatinib or Erlotinib on non-tyrosine kinase driven tumors Akt+AR or Akt+Erg, respectively. In summary, the observation of elevated phosphotyrosine signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically-defined tumor models points to new therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer.
This abstract is also presented as Poster C35.
Citation Format: Justin M. Drake, Jiaoti Huang, Thomas G. Graeber, Owen N. Witte, Nicholas A. Graham, Tanya Stoyanova, Amir Sedghi, Andrew S. Goldstein, Houjian Cai, Daniel A. Smith, Hong Zhang, Evangelia Komisopoulou. Therapeutic targeting of oncogene-specific tyrosine kinase networks during prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR5.
Lactobacillus Salivarius REN Inhibits Rat Oral Cancer Induced by 4-Nitroquioline 1-Oxide
Authors: Zhang Ming , Wang Fang , Jiang Lu , Liu Ruihai , Zhang Lian , Lei Xingen , Li Jiyou , Jiang Jingli , Guo Huiyuan , Fang Bing , Zhao Liang , Ren Fazheng 
Published: May 2013

Abstract
Despite significant advances in cancer therapy, cancer-related mobility and mortality are still rising. Alternative strategies such as cancer prevention thus become essential. Probiotics represent an emerging option for cancer prevention, but studies are limited to colon cancers. The efficiency of probiotics in the prevention of other cancers and the correlative mechanism remains to be explored. A novel probiotics Lactobacillus salivarius REN (L. salivarius REN) was isolated from centenarians at Bama of China, which showed highly potent antigenotoxicity in an initial assay. 4-nitroquioline 1-oxide (4NQO)-induced oral cancer model was introduced to study the anticancer activity of L. salivarius REN in vivo. The results indicated that oral administration of probiotic L. salivarius REN or its secretions could effectively suppress 4NQO-induced oral carcinogenesis in the initial and postinitial stage, and the inhibition was in a dose-dependent manner. A significant decrease of neoplasm incidence (65%–0%) was detected in rats fed with the high dose of L. salivarius REN [5 × 1010 CFU/kg body weight (bw)/d]. In vivo evidences indicated that the probiotics inhibited 4NQO-induced oral cancer by protecting DNA against oxidative damage and downregulating COX-2 expression. L. salivarius REN treatment significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and induced apoptosis in a dose-dependent manner. Our findings suggest that probiotics may act as potential agents for oral cancer prevention. This is the first report showing the inhibitory effect of the probiotics on oral carcinogenesis. Cancer Prev Res; 6(7); 686–94. ©2013 AACR.
Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques
Authors: Kawahara Tetsuya , Nishikawa Masako , Kawahara Chie , Inazu Tetsuya , Sakai Kunio , Suzuki Gen 
Published: May 2013

Background—
Statins are not effective in reducing atherosclerotic plaques of the abdominal aorta, and accumulating evidence suggests that bisphosphonates have the potential to induce the regression of atherosclerotic plaques of the abdominal aorta.

Methods and Results—

A prospective, randomized, open-label, blinded-end-point trial involving 108 participants with hypercholesterolemia was conducted. Participants received 20 mg atorvastatin daily, 400 mg etidronate daily, or both drugs daily. The primary end point was the percent change in maximal vessel wall thickness of atherosclerotic plaques in the thoracic and abdominal aortas as measured by magnetic resonance imaging after 12 months of treatment. In both the combination therapy and atorvastatin groups, maximal vessel wall thickness of the thoracic aorta was reduced by 13.8% (95% confidence interval, −16.4 to −11.3) and 12.3% (95% confidence interval, −14.9 to −9.7), respectively. These reduction rates were comparable between groups (
P
=0.61). Meanwhile, in the etidronate group, maximal vessel wall thickness of the thoracic aorta remained unchanged (2.2%; 95% confidence interval, −0.3 to 4.8). Conversely, maximal vessel wall thickness of the abdominal aorta was reduced more effectively in the combination therapy group (−11.4%) than in the atorvastatin group (−0.9%;
P
<0.001) and the etidronate group (5.5%;
P
=0.006).

Conclusions—
Atorvastatin plus etidronate combination therapy for 12 months significantly reduced both thoracic and abdominal aortic plaques, whereas atorvastatin monotherapy reduced only thoracic aortic plaques and etidronate monotherapy reduced only abdominal aortic plaques. The effectiveness of combination therapy in reducing atherosclerotic plaques in the abdominal aorta was significantly greater than for both atorvastatin and etidronate monotherapy.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp/ctr/
. Unique identifier: UMIN 000002635.
Idolatry and Fixation: Modern Jewish Thought and the Criticism of Cosmetically and Technologically Perfected Female Faces in Contemporary Popular Culture
Authors: Raphael Melissa 
Published: May 2013

Abstract
This article argues that the ‘halakhically’ (legally) governed representational techniques employed by Jewish art are founded upon a counter-idolatrous theology of appearance: both human and divine. In drawing upon a range of Jewish sources from the ancient to the contemporary period that understand idolatry as an estrangement of the world from God, this article presents a Jewish feminist theological critique of alienation in the late modern popular visual regime, while suggesting that it is nonetheless possible for public culture to behold the divine image in images of the human without such images becoming idolatrous.
Murder in Judaism: A Theological Perspective
Authors: Barmaki Reza 
Published: May 2013

Abstract
This article provides a theological account of murder, that is, its significance within the broader context of God’s plan for creation. It argues that God’s prohibition of murder, understood as abuse of the powerless, is due to God’s broader concern with the maintenance of cosmic justice (cosmic harmony), which is required for the preservation of creation. Murder detracts from God’s cosmic justice in that it damages an aspect of justice that is related to human beings: social justice. Social justice is achieved through protection of the weak. In short, murder, as the ultimate act of oppression of the weak, constitutes social injustice and results in the disruption of God’s cosmic harmony.
Autumn Precipitation Trends over Southern Hemisphere Midlatitudes as Simulated by CMIP5 Models
Authors: Purich Ariaan , Cowan Tim , Min Seung-Ki , Cai Wenju 
Published: May 2013

AbstractIn recent decades, Southern Hemisphere midlatitude regions such as southern Africa, southeastern Australia, and southern Chile have experienced a reduction in austral autumn precipitation; the cause of which is poorly understood. This study focuses on the ability of global climate models that form part of the Coupled Model Intercomparison Project phase 5 to simulate these trends, their relationship with extratropical and subtropical processes, and implications for future precipitation changes. Models underestimate both the historical autumn poleward expansion of the subtropical dry zone and the positive southern annular mode (SAM) trend. The multimodel ensemble (MME) is also unable to capture the spatial pattern of observed precipitation trends across semiarid midlatitude regions. However, in temperate regions that are located farther poleward such as southern Chile, the MME simulates observed precipitation declines. The MME shows a strong consensus in twenty-first-century declines in autumn precipitation across southern Chile in both the medium–low and high representative concentration pathway (RCP) scenarios and across southern Africa in the high RCP scenario, but little change across southeastern Australia. Projecting a strong positive SAM trend and continued subtropical dry-zone expansion, the models converge on large SAM and dry-zone-expansion-induced precipitation declines across southern midlatitudes. In these regions, the strength of future precipitation trends is proportional to the strength of modeled trends in these phenomena, suggesting that unabated greenhouse gas–induced climate change will have a large impact on austral autumn precipitation in such midlatitude regions.