bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1858: Estrogen receptor beta as a tractable therapeutic target
Authors: Filgueira Carly S. , Benod Cindy , Lou Xiaohua , Strom Anders , Gustafsson Jan-Åke , Berkenstam Anders , Webb Paul 
Published: August 2015

Abstract
Nuclear receptors (NRs) regulate a variety of biological processes and are critically important in the emergence, prevention, and treatment of cancers. Many NRs represent well-validated drug targets as their ligands are used extensively in medicine. However, there still remains an active search for novel agonists and antagonists with enhanced selectivity. Estrogen receptor β (ERβ) is an attractive target for drug development. It plays different roles in gene expression from ERα, implicated in breast and uterine cancers, and displays overlapping but distinctive tissue distributions from ERα and non-redundant roles. Further, emerging evidence indicates that ERβ plays anti-proliferative and anti-apoptotic roles in a variety of cancers. These considerations have led to the suggestion that ERβ is an appealing tractable target for development of selective agonists to treat and prevent colon, breast, prostate, lung, and skin cancer and natural and synthetic estrogens for ERβ are being studied in colon, breast, and lung cancers. However, because of the high sequence similarities between ERα and ERβ, preferentially targeting one subtype can prove challenging. Repositioning of existing approved drugs with known side effect profiles can provide advantages because de novo drug design suffers from high developmental failure rates and undesirable side effects which have dramatically increased costs. Our research strategy is to identify and develop an ERβ agonist lead compound by using a systematic step-wise hit-to-lead campaign. We have identified a series of ERβ-selective lead compounds derived from screening libraries of clinically relevant compounds and have shown that some of these compounds display interesting and desirable selective modulator activities.
Citation Format: Carly S. Filgueira, Cindy Benod, Xiaohua Lou, Anders Strom, Jan-Åke Gustafsson, Anders Berkenstam, Paul Webb. Estrogen receptor beta as a tractable therapeutic target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1858. doi:10.1158/1538-7445.AM2015-1858
Abstract 1859: Discerning the molecular basis of DNA-PK pro-tumorigenic functions and translational capacity as a therapeutic target in prostate cancer
Authors: Dylgjeri Emanuela , Goodwin Jonathan , Knudsen Karen 
Published: August 2015

Abstract
Prostatic adenocarcinoma (PCa) is dependent on androgen receptor (AR) signaling at all stages of disease, as AR activation induces both cell proliferation and survival. Though organ-confined disease can be treated, the response is transient and reactivation of AR results in incurable state of disease (castration resistant prostate cancer, CRPC). Thus, there is a significant need to discern the mechanisms by which aberrant AR activity arises, and to develop new means to clinically target advanced disease. Recently, AR activation was found to promote tumor cell survival and proliferation through a feed-forward loop involving the repair factor DNA-dependent protein kinase (DNA-PK). Emerging new data correlates elevated DNA-PK expression with poor prognosis and identifies DNA-PK as a driver of metastatic signaling. Although the role of DNA-PK activity in DNA repair is well characterized, the underpinning mechanisms and consequences of DNA-PK in transcriptional regulation are understudied. Data to be discussed will build on our new preliminary DNA-PK interactome data to identify sequence-specific transcription factors found in complex with DNA-PK. In order to molecularly dissect DNA-PK transcriptional events, the DNA-PK cistrome and transcriptome will be defined using clinically relevant models, resulting in a detailed understanding of DNA-PK mediated transcriptional regulation. The correlation of high expression of DNA-PK with poor prognosis in advanced PCa, as well as the known roles of DNA-PK in cancer-relevant pathways make DNA-PK a viable therapeutic target for PCa. Despite the current clinical assessment of DNA-PK inhibitors in multiple tumor types, there are no existing trials targeting PCa. Additional studies that assess the efficacy of current DNA-PK inhibitors in PCa will be presented and used to determine the best clinical space for their use.
Citation Format: Emanuela Dylgjeri, Jonathan Goodwin, Karen Knudsen. Discerning the molecular basis of DNA-PK pro-tumorigenic functions and translational capacity as a therapeutic target in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1859. doi:10.1158/1538-7445.AM2015-1859
Abstract 186: microRNA-146a inhibits epithelial mesenchymal transition in non small cell lung cancer by targeting insulin receptor substrate 2
Authors: Son Ji Woong , Lee Soo Young , Na Moon Jun , Kwan Sun Jung , Jeon Hyo Sung 
Published: August 2015

Abstract
BACKGROUND: During cancer progression, some tumor cells show changes in their plasticity by morphological and phenotypical conversions, as an expression of mesenchymal markers and loss of epithelial markers, collectively referred to as epithelial-mesenchymal transition (EMT). EMT has been increasingly recognized as a critical phenomenon in lung cancer progression. The goal of this study was to identify microRNAs involved in lung cancer progression.
METHODS: A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in mesenchymal like lung cancer cells. The role of miR-146a in lung cancer progression was measured by invasion and migration assays in vitro. Bioinformatics and luciferase report assays were used to identify the target of miR-146a.
RESULTS: The expression of miR-146a was reduced in mesenchymal like lung cancer cell lines. The over-expression of miR-146a induced a marked reduction of mesenchymal marker and increase epithelial marker in lung cancer cell lines. Moreover, the over-expression of miR-146a suppressed lung cancer cells migration and invasion. The expression of miR-146a was down-regulated in advanced lung cancer tissues. Insulin receptor substrate 2 (IRS2), an adaptor proteins that modulates normal growth, metabolism, survival, and differentiation, was identified as a target of miR-146a. miR-146a regulated the expression of IRS2 at the mRNA and protein levels.
CONCLUSION: These data demonstrate for the first time that miR-146a suppresses lung cancer progression by repressing IRS2 expression. This provides a new insight into the post-transcriptional regulation of lung cancer progression by miRNAs, a potential approach for the treatment of lung cancer.
Citation Format: Ji Woong Son, Soo Young Lee, Moon Jun Na, Sun Jung Kwan, Hyo Sung Jeon. microRNA-146a inhibits epithelial mesenchymal transition in non small cell lung cancer by targeting insulin receptor substrate 2. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 186. doi:10.1158/1538-7445.AM2015-186
Abstract 1860: DNA-PK-mediated transcriptional regulation drives tumor progression and metastasis
Authors: Goodwin Jonathan F. , Kothari Vishal , Drake Justin M. , Zhao Shuang , Dylgjeri Emanuela , Dean Jeffry L. , Schiewer Matthew J. , McNair Christopher , Magee Michael S. , Den Robert B. , Zhu Ziqi , Graham Nicholas A. , Vashisht Ajay A. , Wohlschlegel James A. , Graeber Thomas G. , Karnes R Jeffrey , Takhar Mandeep , Davicioni Elai , Tomlins Scott A. , Sharifi Nima , Witte Owen N. , Feng Felix Y. , Knudsen Karen E. 
Published: August 2015

Abstract
Emerging evidence demonstrates that the DNA repair kinase DNA-PK exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PK functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PK inhibits tumor metastases. Clinical assessment revealed that DNA-PK is significantly elevated in advanced disease, and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PK in advanced tumors is highly activated, independently of DNA damage indicators. Combined, these findings put forth new paradigms for DNA-PK function, identify DNA-PK as a potent driver of tumor progression and metastases, and nominate DNA-PK as a therapeutic target for advanced malignancies.
Citation Format: Jonathan F. Goodwin, Vishal Kothari, Justin M. Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher McNair, Michael S. Magee, Robert B. Den, Ziqi Zhu, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen. DNA-PK-mediated transcriptional regulation drives tumor progression and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1860. doi:10.1158/1538-7445.AM2015-1860
Abstract 1862: Discerning the role of USP22 in prostate cancer development and progression
Authors: Jones Jennifer , Dean Jeffry L. , Schrecengost Randy S. , Knudsen Karen 
Published: August 2015

Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death for men in the United States. While organ-confined disease is manageable, advanced and disseminated PCa currently has no durable treatment options. Thus, understanding the causes and consequences of the transition from early stage to late stage castrate-resistant PCa (CRPC) are critical. While this transition has a requisite for the androgen receptor (AR) activity, the mechanisms by which AR and other oncogenes are functionally increased, even after initial treatment with androgen deprivation therapy (ADT) have not been completely characterized. USP22, a known deubiquitinase associated with the SAGA transcriptional activation complex, was originally designated in a “death from cancer” gene signature. Importantly, USP22 is significantly upregulated in PCa patients with late-stage disease, and specifically indicates for poor outcome in PCa patients. Moreover, tumor-associated USP22 increases AR levels and activity as well as the oncogene MYC function, partially defining the mechanism by which tumor-associated USP22 drives PCa progression. Thus, while certain consequences of tumor-associated USP22 expression have been elucidated, the remaining downstream effects have not been thoroughly characterized. Newly generated data begin to establish the biochemical events controlled by USP22 that confer proliferation and survival on PCa cells. Through use of novel proteomic technology, specifically Ubiscan analysis, tumor-associated USP22 will be shown to participate in driving PCa development and progression as well as therapeutic bypass through differential regulation of the ubiquitylome.
Citation Format: Jennifer Jones, Jeffry L. Dean, Randy S. Schrecengost, Karen Knudsen. Discerning the role of USP22 in prostate cancer development and progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1862. doi:10.1158/1538-7445.AM2015-1862
Abstract 1863: Using a cell based model system to characterize CYP17A1 genetic variants
Authors: Capper Cameron P. , Liu Jiayan , McIntosh Lauren , Larios José M. , Johnson Michael D. , Hollenberg Paul F. , Auchus Richard J. , Rae James M. 
Published: August 2015

Abstract
Androgen and estrogen steroid hormones are potent growth stimuli for both prostate and breast cancer. Cytochrome P450 17A1 (CYP17A1), a P450 monooxygenase, is required for the synthesis of these hormones and is the target of abiraterone, a drug approved for the treatment of castration-resistant prostate cancer. CYP17A1 catalyzes the 17α hydroxylation of the C21 steroids pregnenolone and progesterone and has a lyase activity that cleaves the C17-20 bond to produce the sex steroid precursors, dehydroepiandrosterone (DHEA) and androstenedione. We identified twelve nonsynonymous single nucleotide polymorphisms (SNPs) in CYP17A1 and hypothesized that the resultant amino acid changes might alter hydroxylase and lyase activity and thereby impact steroid hormone synthesis. This hypothesis was examined by transiently transfecting HEK293T cells, with either wild-type or polymorphic CYP17A1 constructs. Cells were treated for 3 hours with tritiated ([3H]) progesterone and the production of hydroxylated (OH) metabolites analyzed by HPLC. In cells transfected with wild-type CYP17A1, 8.11% and 55.5% of the [3H]-progesterone was recovered as 16-OH progesterone, and 17-OH progesterone, respectively. Using the ratio of 17-OH progesterone to 16-OH progesterone as a quantitative measure of CYP17A1 enzyme activity, wild-type CYP17A1 yields a ratio of 6.9+/- 0.05. In contrast, the SNP (rs200063521) which causes an aspartic acid to histidine amino acid change at residue 216, results in a 2.2 fold decrease in 16OH-progesterone synthesis compared to wild-type suggesting altered hydroxylase function. CYP17A1 protein expression, as determined by western blot analysis, suggests that a glycine to arginine conversion at residue 162 (rs141821705) results in decreased protein levels. Studies to further characterize the CYP17A1 variants are underway. This work could lead to a better understanding of the role of CYP17A1 SNPs in cancer progression and response to CYP17A1 targeted therapies.
Citation Format: Cameron P. Capper, Jiayan Liu, Lauren McIntosh, José M. Larios, Michael D. Johnson, Paul F. Hollenberg, Richard J. Auchus, James M. Rae. Using a cell based model system to characterize CYP17A1 genetic variants. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1863. doi:10.1158/1538-7445.AM2015-1863
Abstract 1865: TRIM24 acts as a transcriptional co-activator of the androgen receptor during prostate cancer progression
Authors: Groner Anna C. , de Tribolet-Hardy Jonas , Theurillat Jean-Philippe , Wild Peter J. , Brown Myles 
Published: August 2015

Abstract
The steroid hormone androgen mediates a wide range of developmental, physiological and malignant responses by acting as an agonist for the androgen receptor (AR). AR in turn functions as a nuclear receptor transcription factor and executes specific gene expression programs in an androgen-dependent manner. Since the growth of prostate cancer cells initially depends on androgen, cancer therapy uses hormone-deprivation approaches to reduce the levels of androgen. While prostate cancer (PC) initially responds to androgen-ablation, most tumors progress to a castration resistant (CR) state insensitive to treatment. Both the androgen-dependent and the CRPC state depend on AR, which is probably activated by alternative molecular pathways in CRPC in response to low androgen levels. Here, we assessed the role of the transcriptional co-activator TRIM24 in mediating AR-dependent gene expression and growth in our CRPC cell model LNCaP-abl. We observed that knock-down of TRIM24 impairs CRPC cell growth, while TRIM24 and AR physically interact in these cells in the absence of androgen. When we identified TRIM24-dependent gene expression programs by combining genome-wide binding analyses with microarray studies, we found that TRIM24 and AR co-regulated many genes in CRPC cells. TRIM24- and AR-co-activated genes often function in mitosis and their expression is higher in patients with an increased chance of prostate cancer recurrence. These findings are corroborated by IHC-analyses of prostate cancer patients, where higher TRIM24 protein levels correlated with a greater chance of biochemical recurrence, higher Gleason scores and larger tumor sizes. Importantly, TRIM24 staining was positively correlated with AR staining. This supports a model where TRIM24 acts as an important activator of AR in the castration-resistant setting and therefore may harbor therapeutic potential.
Citation Format: Anna C. Groner, Jonas de Tribolet-Hardy, Jean-Philippe Theurillat, Peter J. Wild, Myles Brown. TRIM24 acts as a transcriptional co-activator of the androgen receptor during prostate cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1865. doi:10.1158/1538-7445.AM2015-1865
Abstract 1877: Age at introduction to solids is associated with the odds ratio of pediatric acute lymphoblastic leukemia
Authors: Schraw Jeremy M. , Scheurer Michael , Forman Michele R. 
Published: August 2015

Abstract
Introduction: Breastfeeding for &gt; 6 months is associated with protection from acute lymphoblastic leukemia (ALL) (OR 0.81 95% CI 0.72-0.91), the most common pediatric cancer in the United States. These data are based on any breastfeeding. There is little research concerning infant formula or solid food consumption patterns and risk of pediatric ALL. We previously identified greater duration of milk formula feeding and later age at introduction to solid foods as risk factors for ALL. The purpose of this study was to determine whether the increased OR of ALL was confined to children who began receiving solids after 4 or 6 months of age.
Methods: 172 incident cases of ALL aged 0-14 years were recruited at Texas Children's Cancer Center (TCCC) and matched on sex, age at diagnosis/interview and ethnicity to 344 healthy population-based controls from Houston, San Antonio and Austin, Texas. Data were collected on sociodemographics, infant feeding patterns and known or hypothesized risk factors for ALL. Logistic regression was used to model the OR of ALL according to quartile of age at introduction of solids with the first/earliest quartile as the reference group.
Results: In adjusted models, the OR of ALL among children in quartile 3 (7-9 months) was 3.43, 95% CI 1.66 - 7.09; for children in quartile 4 (≥ 10 months) the OR was 4.19, 95% CI 2.00 - 8.75. Each additional month of milk formula feeding was associated with a 7% increase in the OR of ALL (95% CI 1.02 - 1.12). The OR of ALL among non-Hispanic compared to Hispanic children was 1.76 (95% CI 1.10 - 2.84).
Discussion: These results support our published findings that later introduction to solids is positively associated with ALL. Our finding of lower risk among Hispanic children contrasts with previous research indicating this group is at greater risk than non-Hispanics.
Citation Format: Jeremy M. Schraw, Michael Scheurer, Michele R. Forman. Age at introduction to solids is associated with the odds ratio of pediatric acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1877. doi:10.1158/1538-7445.AM2015-1877
Abstract 1886: Dietary scores and cancer incidence, mortality and survival: Epidemiologic evidence and meta-analysis
Authors: Mccullough Marjorie L. , Wang Ying , Shah Roma , Gapstur Susan 
Published: August 2015

Abstract
Diet scores or indices assess the degree to which an individual's reported diet conforms to dietary recommendations or culturally-defined healthful diets. Characterizing diet exposures in this way provides a more complete picture of individual dietary behavior, and potentially captures additive and/or interactive effects on disease risk. Such metrics, where higher points reflect better diets, and lower scores reflect worse diets, have been examined in relation to cancer incidence, mortality and survival. To date, the literature on the association between diet scores and cancer risk is inconsistent across and within scores. We conducted a literature search for prospective cohort studies of a priori dietary scores or indices in relation to cancer incidence, mortality or survival using PubMed. Meta-analyses were performed when at least five separate studies published results on a cancer outcome, using the same diet score. When studies on both incident and fatal outcomes were available from the same cohort for the same cancer/s, estimates from incident outcomes were used. If more than one version of the same score in the same cohort was evaluated, we used the most recent score. Estimates in men and women were included separately. Meta-analyses of four out of six diet scores and the outcome “total cancer incidence or mortality” showed significant inverse associations comparing top vs bottom quantiles, often with significant study heterogeneity: the Alternate Healthy Eating Index (AHEI) Relative Risk (RR) = 0.88, 95% confidence interval (CI) 0.84-0.93, p heterogeneity = 0.02; Healthy Eating Index (HEI) RR = 0.84, 95% CI 0.77-0.92, p heterogeneity&lt;0.001; Mediterranean Diet Score (MDS) RR = 0.81, 95% CI 0.78-0.85, p heterogeneity = 0.35; and WCRF/AICR RR = 0.77, 95% CI 0.68-0.86, p heterogeneity = 0.046. The associations with the Recommended Food Score (RFS) and Diet Quality Index (DQI) were not statistically significant. The MDS was associated with significantly lower colorectal cancer risk (RR = 0.82, 95% CI 0.73-0.91, p heterogeneity = 0.034). In studies of cancer survivors, less than three studies were available for each diet score/outcome combination; thus no meta-analyses of cancer survival were conducted. These results suggest that following recommended dietary guidelines or the Mediterranean healthy diet pattern may significantly reduce overall cancer risk. The limited number of studies in cancer survivors indicates a need for further research.
Citation Format: Marjorie L. Mccullough, Ying Wang, Roma Shah, Susan Gapstur. Dietary scores and cancer incidence, mortality and survival: Epidemiologic evidence and meta-analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1886. doi:10.1158/1538-7445.AM2015-1886