bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CT-03: Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer
Authors: Meric-Bernstam Funda , Chen Huiqin , Akcakanat Argun , Do Kim-Anh , Lluch Ana , Hennessy Bryan , Hortobagyi Gabriel , Mills Gordon , Gonzalez-Angulo Ana 
Published: August 2012

Abstract
Purpose: Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer. Methods: Primary tumors were collected from 190 patients with stage I-III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays.: Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed. Results: High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node-positivity. Median follow-up for alive patients was 96 months. High p4E-BP1 T36/47, p4E-BP1 S65, p4E-BP1 T70 and 4E-BP1 were associated with worse RFS. High p4E-BP1 T70 and pS6 S235/236, and low pdcd4, were associated with worse OS. In multivariable analysis, in addition to positive nodes, p4E-BP1 S65 remained a significant predictor of RFS (HR=1.62, 95%CI=1.13-2.31; P=0.008). In addition to age, pS6 S235/236 (HR=1.73, 95%CI=1.03-2.90, P=0.039), eEF2K (HR=2.19, 95%CI=1.35-3.56, P=0.002) and pdcd4 (HR=0.42, 95%CI=0.25-0.70, P=0.001) were associated with OS. Conclusions: Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer; suggesting their role as prognostic markers and therapeutic targets.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr CT-03. doi:1538-7445.AM2012-CT-03
Abstract LB-101: Quantitative imaging of protein expression using multiplex quantum dot immunohistochemistry
Authors: Cooper Lee A.D. , Yacoub Rami , Gutman David A. , Wang Fusheng , Moreno Carlos S. , Brat Daniel J. , Bostick Roberd M. , Saltz Joel H. 
Published: August 2012

Abstract
Introduction: Immunohistochemistry (IHC) is an important tool for studying protein expression in the tumor microenvironment. Advances in imaging hardware now permit an entire slide to be digitized at high magnification so that software can analyze protein expression within individual cells across the entire tissue section. The chromaphores and organic fluorescent probes used in traditional IHC limit the utility of quantitative IHC, since only relatively few proteins can be measured simultaneously. A new class of fluorescent labels made of semiconductor nanocrystals, known as quantum dots (QD) has unique optical properties that have the potential to overcome limitations of traditional IHC techniques and expand the usefulness of quantitative image analysis approaches. The narrowband emission spectra of these novel probes enable them to be highly multiplexed without significant spectral overlap, providing independent measurements of protein expression with minimal crosstalk. Methods: We have developed a collection of software algorithms around the QD-IHC protocol to analyze protein expression, co-expression, and subcellular localization in whole-slide QD-IHC images. This system segments the digitized tissue into individual cells, their subcellular compartments and multicellular structures to generate comprehensive digital descriptions. Features are calculated for each cell to represent the morphology, protein expression, co-expression, and subcellular localization. Each cell is mapped to their closest multicellular structure, enabling protein expression features to be analyzed as a function of distance to vessels, necrosis, etc. We evaluated the use of QD-IHC for analysis of formalin-fixed, paraffin-embedded glioblastoma tissues against known pathways using streptavidin-biotin detection and applied our software system to analyze expression and co-expression patterns. Features of protein expression were calculated for individual cells along with distance-to-vessel measurements. Results: A five-plex staining was achieved and sections were stained and digitized on a whole-slide scanner (Pannoramic from 3D Histech). The digitized tissues were analyzed using our software system to generate measurements of protein expression in millions of cells. These measurements were used to generate visualizations, including analyses of the variations of expression with respect to distance-to-nearest-vessel. We are continuing to enhance our software capabilities to include statistical tests and updated imaging and analysis capabilities will be presented.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-101. doi:1538-7445.AM2012-LB-101
Abstract LB-115: NAC1 is an actin binding protein essential for the cytokinesis of cancer cells and plays a role in the patterning of murine vertebral axis
Authors: Yap Kai Lee , Fraley Stephanie I. , Shah Polina Sysa , Wang Fengying , Thiaville Michelle M. , Jinawath Natini , Nakayama Kentaro , Wang Jianlong , Brayton Cory , Bolon Brad , Gabrielson Kathleen , Wirtz Denis , Wang Tian-Li , Shih Ie-Ming 
Published: August 2012

Abstract
Nucleus accumbens-associated protein 1 (NAC1) is a member of the BTB (Bric-a-Brac Tramtrack Broad complex) family of proteins. Recent studies have demonstrated NAC1 expression is essential for sustaining cancer cell proliferation and migration, but its molecular mechanisms remain elusive. In this report, we show that NAC1 is an actin monomer binding protein with a Kd of 0.78 μM, and the BTB domain is the actin-binding domain. Disrupting NAC1 protein complex function using a dominant-negative construct or RNA-interference resulted in reduced traction and incomplete abscission during late stage cytokinesis leading to multi-nucleation of cancer cells. We examined the phenotype of Nac1 knockout mice, and discovered the loss in expression of the Nac1 protein led to a patterning defect of the vertebral skeletal axis. Nac1-null mice were correlated with morphological transformation of the sixth lumbar vertebra into a sacral identity; a decreased total number of pre-sacral vertebrae elements from 26 in wild type mice to 25. Taken together, we explored the role of NAC1 as an actin binding protein essential for the cytokinesis of cancer cells, and its effects on patterning of the murine vertebral axis. These findings advance our knowledge of this physiologically-relevant protein in the field of mammalian development and cancer biology.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-115. doi:1538-7445.AM2012-LB-115
Abstract LB-160: CYP4F isoform expression and 20-HETE synthesis in prostate cancer cells are regulated by androgen and contribute to growth
Authors: Wu Cheng-Chia , Liu Yunmeng , Chen Jonathan , Gotlinger Katherine H. , Ramu Errabelli , Falck John R. , Schwartzman Michal L. 
Published: August 2012

Abstract
20-hydroxyeicosatetraenoic acid (20-HETE), a CYP450-derived arachidonic acid metabolite in the microcirculation, contributes to vascular tone and stimulates vascular and epithelial cell proliferation, angiogenesis and inflammation, all of which play a role in cancer progression. Our laboratory identified 20-HETE as the mediator of androgen-induced hypertension. Given that androgen contributes to the pathogenesis of prostate cancer, we examined the presence and function of 20-HETE in human prostate cancer cells. Androgen-responsive prostate cancer cells, LNCaP, produced 2-fold more 20-HETE compared to androgen-nonresponsive C4-2 cells (565±139 pg/mg protein vs 223±50 pg/mg protein). Both C4-2 and LNCaP produced greater amount of 20-HETE compared with U87 glioma, MCF-7 breast cancer and ML-1 thyroid cancer cells. 20-HETE levels in prostate primary stromal cells and epithelial RWPE-1 cells were barely detected (16±26 and 23±40 pg/mg protein respectively). Treatment of LNCaP with 5 alpha-dihydrotestosterone (DHT) stimulated 20-HETE production by 65% when compared to vehicle control. DHT treatment did not alter 20-HETE levels in C4-2. Treatment of C4-2 and LNCaP with HET0016, an inhibitor of 20-HETE synthesis, selectively decreased endogenous 20-HETE production while inhibiting cell growth in a dose-dependent manner. Further addition of exogenous 20-HETE stimulated growth. CYP4F2, CYP4F3 and CYP4F8 mRNA levels were several fold higher in LNCaP compared with C4-2, while levels of CYP4A11 and CYP4A22 mRNA were unchanged. In LNCaP, DHT increased CYP4F isoform expression without altering the CYP4A expression; flutamide abrogated DHT-induced expression of CYP4F2 and CYP4F3 but did not affect expression of CYP4F8. Importantly, flutamide inhibited DHT-stimulated 20-HETE production. These results suggest that 20-HETE has an important role in cancer cell proliferation and CYP4F2/3 might be the source of androgen-driven 20-HETE synthesis via androgen receptor dependent pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-160. doi:1538-7445.AM2012-LB-160
Abstract LB-178: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair
Authors: Seo Young Rok 
Published: August 2012

Abstract
Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53 wild type cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53 wild-type RKO cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating cell nucleus antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild-type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-178. doi:1538-7445.AM2012-LB-178
Abstract LB-19: Interaction of GPR56 with TG2 regulates melanoma progression
Authors: Yang Liquan , Friedland Scott , Mohanty Sonali , Xu Lei 
Published: August 2012

Abstract
GPR56 is a member of a newly described adhesion G protein-coupled receptor family. We previously reported that the expression of GPR56 significantly inhibited tumor progression of human melanoma cells, and its N-terminus binds to tissue transglutaminase (TG2), a major crosslinking enzyme in ECM. To investigate the contribution of TG2 to GPR56-regulated melanoma progression, we analyzed the tumor growth of the melanoma cell line, MC-1, in the presence or absence of TG2. Our data showed that ectopic GPR56 expression abolished the influence of TG2 on tumor growth, whereas knocking down GPR56 in tumor cells dramatically enhanced TG2's tumor promoting effect. Consistently, interrupting the interaction of constitutive GPR56 with TG2 by overexpression of a free GPR56-N fragment significantly increased tumor growth. However, removing TG2 almost completely blocked tumor formation from GPR56-knocking down cells but not from control or GPR56-overexpressing cells. Collectively, our data revealed a model in which GPR56 plays dual roles during melanoma progression: it antagonizes the tumor-promoting effects of TG2 but positively regulates the tumor initiation/maintenance of melanomas. To investigate further how GPR56 might antagonize the function of TG2 in melanoma progression, we examined the expression/deposition of ECM components in cells and in tumor. Our data demonstrated that GPR56 regulates the distribution of TG2 and its partners in tumor ECM in vivo. Taken together, we present evidence here that a novel adhesion receptor, GPR56, regulates melanoma progression by modulating TG2 in the tumor microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-19. doi:1538-7445.AM2012-LB-19
Abstract LB-194: The Wnt inhibitor VS-507 reduces cancer stem cell (CSC) function in vitro and tumorigenicity in mice
Authors: Pachter Jonathan A. , Ring Jennifer , Neill Alissa , Vidal Christian , Sullivan Brian T. , Sprott Kevin T. , Padval Mahesh , Xu Qunli 
Published: August 2012

Abstract
VS-507 was previously identified as a selective inhibitor of cancer stem cells (Gupta et al., Cell, 2009) using a high throughput screen that capitalized on the cancer stem cell (CSC) phenotype of cells pushed through EMT (epithelial-mesenchymal transition). We have now characterized the mechanism, CSC selectivity and anti-tumor activity of VS-507. In Wnt3A-stimulated MDA-MB-231 breast cancer cells, VS-507 was found to preferentially inhibit β-catenin signaling in a dose-dependent manner as indicated by a TOP-Flash reporter assay. Inhibition of β-catenin signaling in VS-507-treated cells correlated with decreased protein expression of LRP6, the common co-receptor of the Wnt signaling pathway. Since human mammary cells driven through EMT by stable overexpression of the transcription factor Twist have been shown to demonstrate the hallmarks of CSCs, we used HMLE-Twist cells to assess selectivity of VS-507 for CSC inhibition. In proliferation assays, VS-507 showed 10-fold greater potency against CSC-like mesenchymal HMLE-Twist cells as compared to non-CSC-like epithelial control HMLE cells. In addition, VS-507 induced dose-dependent inhibition of tumorsphere formation by MDA-MB-231 cells, further indicating inhibition of the CSC phenotype. The preferential effects of VS-507 on mesenchymal breast cancer cell lines relative to epithelial breast cancer cell lines was further probed among a panel of 13 adherent human breast cancer cell lines. In general, triple negative mesenchymal breast cancer cell lines such as MDA-MB-436 or HCC1395 were more potently inhibited by VS-507 than were epithelial breast cancer cell lines such as MCF7 or HCC1937. Finally, efficacy of VS-507 was characterized upon systemic administration of the compound to mice. Inhibition of both primary tumor growth and experimental metastasis were observed in triple negative breast cancer models. These observations suggest that VS-507 is a potent anti-tumor agent that attenuates Wnt/β-catenin signaling, cancer stem cell self-renewal, tumor growth and metastasis. These results support clinical development of VS-507 for the treatment of triple negative breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-194. doi:1538-7445.AM2012-LB-194
Abstract LB-323: Self-reported sleep duration and subsequent risk of colorectal cancer in two large cohorts of women and men
Authors: Zhang Xuehong , Giovannucci Edward , Wu Kana , Gao Xiang , Hu Frank , Ogino Shuji , Schernhammer Eva , Fuchs Charles , Pollak Michael , Willett Walter , Ma Jing 
Published: August 2012

Abstract
Background: Short sleep duration was associated with an increased risk of colorectal adenomas in a recent report. To date, no data are available on the relationship between sleep duration and colorectal cancer risk. Method: We prospectively followed 76,368 women aged 40 to 73 years in the Nurses’ Health Study and 28,676 men aged 41 to 79 years in the Health Professionals Follow-up Study who reported their habitual sleep duration in the mid-1980s. We used Cox proportional hazards regression models to estimate multivariable relative risks (MV RRs) and 95% confidence intervals (CIs) adjusting for known risk factors (dietary and non-dietary) for colorectal cancer. Results: A total of 1,925 incident colorectal cancer cases (1,264 in women and 661 in men) were documented during up to 22 years of follow-up. The median of sleep duration was 7 hours in both cohorts and was used as the reference group. In both age-adjusted and the multivariate models, long sleep duration (i.e., at least 9 hours of sleep) was significantly positively associated with risk of colorectal cancer in men (MV RR=1.49; 95%CI: 1.10, 2.03) but not in women (MV RR=1.10; 95%CI: 0.85, 1.43). However, for the same comparison (i.e., at least 9 hours vs. 7 hours of sleep), among overweight (body mass index at least 25 kg/m2) individuals, we found significant positive associations for both men (MV RR=2.66; 95%CI: 1.81, 3.90) and women (MV RR=1.42; 95%CI: 1.01, 1.99). Short sleep duration (i.e., 5 hours or less of sleep) was not associated with colorectal cancer risk in either men (MV RR=0.65; 95%CI: 0.33, 1.28) or women (MV RR=1.14; 95%CI: 0.88, 1.48). Results were essentially unchanged when we excluded cases occurred in the first 4 years of follow-up. In addition, the association was not significantly modified by physical activity, alcohol consumption, endoscopy screening, family history of colorectal cancer, menopausal status, or shift work (women only). Conclusion: These prospective data from two large cohorts suggest that overweight men and women with a sleep duration of 9 or longer hours had a significantly increased risk of developing colorectal cancer when compared to those with 7 hours of sleep, which cannot be explained by known risk factors or reverse causality. The potential mechanisms behind this association deserve further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-323. doi:1538-7445.AM2012-LB-323
Abstract LB-333: A case-parent-triad approach in assessing risk of osteosarcoma associated with genetic variation in insulin-like growth factor 1/growth hormone axis genes: a Children's Oncology Group (COG) study
Authors: Musselman Jessica , Bergemann Tracy , Krailo Mark , Malkin David , Ross Julie , Savage Sharon , Nagarajan Rajaram , Sklar Charles , Spector Logan 
Published: August 2012

Abstract
Osteosarcoma (OS) is a rare malignant bone tumor with an overall incidence rate of 4.6 cases per million children aged 0-19 years in the United States. OS incidence peaks sharply in adolescence coinciding with the pubertal growth spurt. While the etiology of OS is largely unknown, its distinctive age-incidence pattern suggests that growth and development is crucial in the genesis of OS. Prior studies have suggested that variants in genes in the insulin-like growth factor 1 (IGF1)/growth hormone (GH) axis pathway are associated with OS. We assessed this hypothesis by examining 307 single nucleotide polymorphisms (SNPs) in 12 genes from this pathway (GHRH, GH1, GHR, GHRHR, IGF1, IGF1R, IGF2, IGF2R, IGFBP1, IGFBP3, IGFBP6, AND IGFALS) in a case-parent-triad study of cases and their biological parents. The sample included 229 complete triads and 56 dyads diagnosed during 2008-2011 at Children's Oncology Group institutions. Buccal cell samples were collected via the Oragene kit (DNA Genotek, Ottawa, Ontario) and returned by mail; genotyping was conducted by Sequenom iPLEX Gold method. We used log-linear models to estimate relative risks (RR) and 95% confidence intervals (CI) associated with transmitting one or two copies of the variant compared to no copies. After Bonferroni correction, 2 SNPs in IGFBP1 (rs10231774: RR = 1.44 and 0.07 for 1 and 2 vs. 0 copies, respectively; p &lt; 0.001) and IGFALS (rs2575352: RR = 2.82 and 0.22 for 1 and 2 vs. 0 copies, respectively; p &lt; 0.001), both in the upstream coding regions of IGF pathway genes, were significantly associated with OS incidence. These results confirm previous findings that variation in the IGF1/GH axis influence OS risk and further support the axis’ biologically and epidemiologically plausible role in OS development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-333. doi:1538-7445.AM2012-LB-333