bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 922: Association of the hSRBC gene polymorphism with endometrial cancer
Authors: Tong Seo-yun , Lee Jong-Min , Lee Seon-Kyung , Han Hyeyeon , Kang Min-Ju , Chi Sung-Gil 
Published: February 2011

Abstract
Background: hSRBC is a putative tumor suppressor located at 11p15.4, at which frequent genomic loss has been observed in several human malignancies. We previously reported that hSRBC expression is frequently downregulated in many types of human cancers due to aberrant promoter CpG sites hypermethylation, and hSRBC activation induces cell cycle arrest and apoptosis by enhancing the protein stability of p53. Interestingly, our recent studies suggest that hSRBC might be a novel transcription target of TNFα, which plays a crucial role in inflammation and tumorigenesis. We explored the possible association of an intreaexonic SNP (T509C), which results in a Leu to Pro substitution, with risk for endometrial cancer development. Methods: TNFα regulation of hSRBC expression was examined using semi-quantitative RT-PCR and immunoblot assays. Endometrial tissues from 147 cancer patients and 191 healthy individuals were included for test for SNP T509C by restriction endonuclease PvuII-based genotyping. Allele frequencies in cancer specimens were compared with those in healthy controls. Results: Allelic frequencies of T and C at the T509C position was 30.27% and 69.73% in healthy control and 37.17% and 62.83% in cancer specimens, respectively. Allelic frequency at T509C in cancer specimens showed no significant difference compared to controls. However, genotype frequencies of TT, CT, and CC in healthy controls were 16.75%, 40.84%, and 42.412%, respectively, while cancer specimens displayed 14.97%, 30.61%, and 54.42%. The CC genotype frequency in cancer specimens was significantly higher (p &lt; 0.05) compared with that in healthy controls. Conclusion: Although the number of specimens used in this study is not enough, this study raises the possibility that the T509C SNP of hSRBC, a putative novel transcription target of TNFα and proapoptotic tumor suppressor, might be associated with endometrial cancer development. Further genotype screening of several other SNPs within hSRBC in cancer patients would provide valuable diagnostic and prognostic information for human cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 922.
Abstract 927: Interleukin-23 receptor tagSNPs and colorectal neoplasia risk
Authors: Poole Elizabeth M. , Xiao Liren , Galbraith Rachel L. , Slattery Martha L. , Duggan David , Coghill Anna E. , Koepl Lisel , Hsu Li , Makar Karen W. , Curtin Karen , Muehling Jill , Taverna Darren , Caan Bette J. , Carlson Christopher S. , Peters Ulrike , Potter John D. , Ulrich Cornelia M. 
Published: February 2011

Abstract
Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory conditions that predispose to colorectal cancer. Genetic variation in the interleukin-23 receptor (IL23R), specifically rs11209026 (Arg381Gln) and rs11465804 (68723 T&gt;G), have been consistently associated with CD and UC. We investigated IL23R candidate and tagSNPs in relation to colorectal neoplasia risk. All SNPs were genotyped on an identical Illumina platform in three independent study populations capturing the range of colorectal carcinogenesis.
Methods: A linkage-disequilibrium (LD)-based tagSNP selection algorithm (r2=0.90, MAF=4%) identified 23 tagSNPs, including the candidates rs11209026 and rs11465804, representing common genetic variation in Europeans. In three US population-based case-control studies of colon cancer (n=1424 cases/1780 controls), rectal cancer (n=583 cases/775 controls), and colorectal adenomas (n=485 cases/578 controls), we investigated IL23R SNPs. Gene-level analyses were conducted using principal components and haplotype analyses. Single SNPs were analyzed using logistic regression. All analyses were adjusted for age, sex, and study center, and were restricted to Caucasians (&gt;90% of all study populations).
Results: No associations were observed for the IL23R candidate SNPs, although there was a suggestion of increased adenoma and rectal cancer risk with rs11465804. Without correction for multiple testing, three SNPs were associated with rectal cancer risk at α=0.05 (see Table). Of these, rs10889675 was also associated with a non-significant decreased risk of adenomas. There were no significant associations with colon cancer; however, the homozygous variant genotype of rs10889676 was associated with increased adenoma risk.
Conclusion: These data provide evidence that genetic variability in IL23R may contribute to rectal cancer risk and adds some further support to the role of IL23R in gastrointestinal diseases. Functional follow-up studies are needed.Table.Selected tagSNPS in IL23R and risk of rectal cancer or adenomaSNPGenotypeCasesControlsOR95% CIp (2df)p-trendRectal cancer*rs10889675CC4675831.00- CA1091790.760.581.00 AA7130.680.271.730.110.04 rs11465770CC4786051.00- CT981530.800.611.07 TT2110.220.051.010.030.03 rs7542081CC2523141.00- CA2713480.970.771.22 AA581120.650.450.920.040.05 Colorectal Adenoma**rs10889676CC2352811.00- CA1962680.870.671.14 AA50331.610.982.660.050.50*Adjusted for age, sex, and study center.**Adjusted for age and sex.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 927.
Abstract 935: Genetic variants in chromosome 6p21.3 and risk of non-Hodgkin lymphoma
Authors: Wang Sophia S. , Menashe Idan , Cerhan James R. , Rothman Nathaniel , Severson Richard K. , Davis Scott , Chanock Stephen J. , Bernstein Leslie , Hartge Patricia , Morton Lindsay 
Published: February 2011

Abstract
Background. Non-Hodgkin lymphoma (NHL) case-control studies consistently demonstrate the G-308A promoter polymorphism in the tumor necrosis factor gene on chromosome 6p21.3 to be associated with increased risk of the NHL subtype, diffuse large B-cell lymphoma (DLBCL). Initial results from a genome-wide association study have implicated a polymorphism located on 6p21.33 with increased risk of the follicular lymphoma subtype. In the present analysis, we evaluated 488 candidate gene regions (defined as 20kb 5’, 10kb 3’) and their relation to risk for NHL and the DLBCL and follicular lymphoma subtypes with a particular focus on genes within the 6p21 chromosomal region.
Methods. We genotyped 6679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S.-based case-control study. Genotyping was conducted on a custom-designed Illumina Infinium assay at the NCI Core Genotyping Facility. We obtained a gene region-level summary of association by computing the minimum p-value (“minP test”). We used logistic regression to evaluate the association between single nucleotide polymorphism (SNP) genotypes and haplotypes with NHL (adjusted for sex, race and age). For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression. We evaluated tests for trend under the co-dominant model used a three-level ordinal variable for each SNP.
Results. We identified 34 gene regions significantly associated with all NHL (p &lt;0.05). The three most significant gene regions were all found on chromosome 6p21.3 (RING1/RXRB; AIF1/BAT2; BAT4, p=0.001). Within those gene regions, the most significant SNPs (p&lt;0.0002) were rs2855429 and rs213213 (RING1/RXRB), rs2857597 and rs3130071 (AIF1/BAT2), and rs3115667 (BAT4). All five SNPs were statistically significantly associated with both DLBCL and follicular lymphoma. Additional gene regions on 6p21.3 associated with NHL include MSH5 (p=0.009), FAM46A (p=0.01) and TNXB/CREBL1 (p=0.04). Stratification by age and gender did not alter our results; consistent results were observed in analyses restricted to non-Hispanic Caucasians. Haplotype analyses yielded the same regions and SNPs of significance. Detailed analysis of the 6p21.3 region will be presented.
Conclusions. Our results further implicate gene variants within the 6p21.3 chromosomal region in NHL etiology. Full characterization of the 6p21.3 region and identification of functional variants within this region are warranted for understanding lymphomagenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 935.
Abstract 94: DrugPath: A web database for academic investigators to identify drugs that match oncology molecular targets
Authors: Shah Eric D. , Zhao Peng , Ghent Matthew V. , Arceci Robert J. , Buckley Jonathan D. , Reaman Gregory H. , Sorensen Poul H. , Triche Timothy J. , Reynolds C Patrick 
Published: February 2011

Abstract
High-throughput genomics can identify oncology molecular targets, but translation into novel therapeutics requires access to relevant drugs. Pharmaceutical pipeline databases, such as MedTRACK (www.medtrack.com), can identify such drugs, but these databases are geared for commercial operations and present significant cost barriers to non-profit academic research. We have developed the DrugPath database (www.drugpath.org) as a comprehensive, free-of-charge resource for academic investigators. DrugPath can identify drugs within the cancer pipeline that may act against molecular targets of interest. DrugPath searchable data include names and mechanisms of drugs in the oncology pipeline (organized by clinical trial phase and route of administration), drug sponsor, and also tested combinations with other drugs. Drugs and drug sponsors are initially identified from ClinicalTrials.gov, biotech company websites, and other online resources; specific pipeline information is extracted by DrugPath personnel according to written protocols. PERL scripts to automate a portion of the data mining are being developed, although manual verification will remain to ensure data accuracy and relevance. The website is authored in XHTML and PHP, and content is stored in a MySQL database. We compared the extent of the DrugPath database to that of MedTRACK. DrugPath covers more than 475 companies, or 50% of 938 companies with oncology therapeutics in development as identified by MedTRACK. A search of DrugPath for inhibitors of VEGF, a well-established target, yielded 58 lead drug candidates (17% of 332 drugs identified by MedTRACK) from 45 total companies (47% of 95 companies identified by MedTRACK). A search for Hsp90 inhibitors yielded 15 companies (78% of 19 in MedTRACK) and 17 lead drug candidates (30% of 56 in MedTRACK), and a search for aurora kinase inhibitors yielded 17 companies (94% of 18 in MedTRACK) and 17 lead drug candidates (70% of 24 in MedTRACK). Ongoing efforts to populate the DrugPath database are focused on identifying drug development programs for emerging drug targets rather than expanding existing coverage of drug candidates against well-known targets. To support the end-goal of DrugPath–to facilitate obtaining drugs for academic research–DrugPath contains contact information (when available) for each company to assist with the process of developing material transfer agreements (MTAs). This database should be useful to academic investigators studying particular molecular targets and also to clinical investigators seeking to develop novel clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 94.
Abstract 97: In silico computational modeling and virtual screening of novel noscapinoid library as potent microtubule interacting anticancer drugs
Authors: Naik Pradeep K. , Aneja Ritu , Vangapandu Surya , Santoshi Seneha , Joshi Harish C. 
Published: February 2011

Abstract
Tubulin remains a persistent and promising target for anti-cancer therapy. This is well validated by the already approved clinically used drug classes such as taxoids and vincas. We have previously discovered a new class of anti-microtubule (MT) drugs, noscapinoids. The lead compound, noscapine, is an orally available anti-cough plant alkaloid that binds tubulin and makes MTs less dynamic. Using computational algorithms such as Glide Extra Precision, Quantum Polarized Ligand Docking (QPLD), Molecular Mechanics Generalized Born Surface Area (MM-GB/SA), EmBrace and Solvation Generalized Born-Linear Interaction Energy (SGB-LIE), we have generated molecular models of noscapine-tubulin complex. Furthermore, based upon structure-function analyses of noscapine, we have identified a key residue on the isoquinoline ring of noscapine that can be modified without losing its biological activity. We report a library of novel derivatives, based upon combinatorial in silico approaches that can be chemically synthesized and tested in vitro and in vivo in animal models of human tumor xenografts in immune compromised mice. The prototype analogs synthesized so far have non-toxic to normally dividing healthy tissues but pro-apoptotic in a wide variety of cancer cells in vitro and in vivo. Some of these prototypes have shown already that these approaches can generate compounds more effective than the lead compound. Unlike currently available clinical anticancer MT-drugs, noscapine and its derivatives are orally available, and display no toxicities such as myelosuppression and immunosuppression, peripheral neuropathies, or pathology of gastrointestinal tract. Moreover, noscapine readily crosses the blood brain barrier. The in silico libraries generated here promise to be even more effective. Additionally, because the mechanisms by which different anti-MT drugs induce apoptosis can vary widely in both, the same cell lineage as well as in distinct lineages, there is a tremendous opportunity for a better therapeutic outcome by combining noscapinoids with already approved MT-drugs in a cancer type specific manner.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 97.
Abstract 976: Consumption of vitamins and calcium reduces breast cancer risk by their regulation of the DNA repair capacity
Authors: Vergne Yeidyly , Matta Jaime L. , Morales Luisa , Vargas Wanda , Alvarez-Garriga Carolina , Bayona Manuel 
Published: February 2011

Abstract
Background- Breast cancer (BC) is the most common cancer in women with over one million new cases diagnosed annually worldwide. The capacity of the DNA to repair itself (DRC) is a complex biological process involving over 200 proteins. This process involves at least five pathways and is critical in maintaining genomic stability. The objective of this study was to examine the association of DRC and BC risk in terms of consumption of vitamin and calcium supplements by means of a large scale case-control study.
Methods.- This was an incident-case case-control study design involving Puerto Rican women. The selection of potential predictors under study was based on previous published research in BC including information on vitamins, calcium, and variables that could provide an estimate of BC risk including age, BMI, family history, gynecological history, hormonal and environmental factors. The host reactivation assay with a luciferase reporter gene was used to measure the DRC in the lymphocytes from all participants. Cases were compared to controls, regarding diet supplement intake, DRC, and other selected covariates. The crude and multiple logistic regression adjusted Odds Ratio (OR) were used as measures of association and the 95% confidence interval of the OR was utilized to asses the precision of this estimate.
Results.- A total of 268 breast cancer cases and 457 controls were included in this analysis. Statistically significant associations were found between BC and ageing, low DRC levels, family history of BC, and no breastfeeding. Vitamins and calcium intake were found to be protective reducing 30% and 40% the odds of having BC respectively. Calcium reduced considerably its protective effect becoming negligibly and not statistically significant when DRC was included in the logistic regression model. This suggests that DRC explains this association. In contrast, vitamin's intake did not show an important change in the association with BC when adjusting for DRC. Calcium and vitamins’ intake were strongly associated with higher levels of DRC.
Discussion.- Vitamins and calcium intake are protective for breast cancer and are associated with higher DRC levels. Vitamins’ intake is an independent protective factor for BC while the protective effect of calcium may be explained by an increased DRC. DRC can be used to monitor the protective effect of calcium in terms of breast cancer risk. This study is supported by grants from the NCI Center to Reduce Health Disparities and NIH-MBRS Program grant #: S06 GM008239-23.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 976.
Abstract 99: The caBIG® life sciences distribution: Integrative tools to support translational research
Authors: Heiskanen Mervi A. , Klemm Juli , Nagarajan Rakesh , Sharma Mukesh , Talele Chandrakant , Goldstein Stephen , Piepenbring Chris , Jacob Shine , Tavela Eric , Marple John P. , Fore Ian , Andrews Timothy J. , Nguyen Ngoc , Floratos Aris , Basu Anand , Derr Leslie 
Published: February 2011

Abstract
The cancer Biomedical Informatics Grid® (caBIG®) is a collaborative network designed to accelerate the translation of discoveries from research to clinical care. This extensible informatics platform integrates diverse data types and supports interoperable software tools in the areas of clinical sciences, biospecimen management, imaging, and basic research. The Life Sciences Distribution (LSD) product bundle brings together a range of tools that support translational research, all connected via grid network technology. Tools included in the bundle support management and annotation of microarray data (caArray), biospecimens (caTissue Suite), imaging data (NBIA), clinical data (CTODS) and genome-wide association studies (caGWAS). LSD also includes integrative tools that allow scientist to search data across different data repositories connected to the grid, and analyze and integrate these data across different data types. geWorkbench supports integrative analysis and visualization of expression data, sequences, pathways and protein structures. cancer Bench-to-Bedside (caB2B) allows end-users to search biospecimens, images and array data across the grid and makes it possible to execute queries such as: “Are there any gene expression microarray data available from patients with Stage III lung cancer and are there corresponding in vivo images available for the affected patients?” Such a query would potentially span information federated across several instances of caArray, caTissue, and NBIA around the world. caIntegrator2 allows researchers to set up study specific custom web portals that bring together heterogeneous clinical, microarray and in vivo imaging data. This tool provides a graphical user interface to allow a study author to “point” to data of interest in systems on the grid and to then bring that data (or pointers to it, in the case of images) into the data warehouse. Once this information is in the caIntegrator2 environment, end user scientists can then run advanced queries, perform correlative outcomes analysis using Kaplan-Meier survival plots, and access analysis and visualization tools on and off the grid. All tools in the LSD are open source and community members are encouraged to participate and contribute. More information on the LSD suite of products, including installation packages, user and installation guides, and links to exemplar installations can be found at https://cabig.nci.nih.gov/adopt/LSD/
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 99.
Abstract 992: PR55alpha, a regulatory subunit of PP2A, specifically regulates PP2A-mediated beta-catenin dephosphorylation
Authors: Zhang Wen , Chen Xi , Yu Tianxin , jia jianhang , Liu Chunming 
Published: February 2011

Abstract
BACKGROUND: Wnt/beta-catenin signaling plays essential roles in development and tumorigenesis. A central question in Wnt signaling is the regulation of beta-catenin phosphorylation and degradation. Our previous work found that beta-catenin is sequentially phosphorylated by CKIalpha and GSK3, which creates binding site for beta-Trcp, leading to degradation via the ubiquitination/proteasome machinery. Mutations in beta-catenin or APC genes that prevent beta-catenin phosphorylation or ubiquitination/degradation lead ultimately to cancer. In addition to the involvement of kinases, protein phosphatases, such as PP1, PP2A and PP2C, are also implicated in Wnt/beta-catenin regulation. However, which phosphatase dephosphorylates beta-catenin in vivo and how the specificity of beta-catenin dephosphorylation is regulated are not clear. In this study, we show that PP2A regulates beta-catenin phosphorylation and degradation in vivo. PP2A consists of a catalytic subunit (PP2Ac), a structure subunit (PR65/A) and variable regulatory B subunit (PR/B, PR/B’, PR/B”, or PR/B’’’). The substrate specificity of PP2A is thought to be determined by its B subunit. We further identified that PR55alpha is the regulatory B subunit that controls PP2A-mediated beta-catenin dephosphorylation.
RESULTS: Toward the goal of understanding the mechanism of beta-catenin phosphorylation, we carried out siRNA screening targeting several major phosphatases, in which we found that PP2A dephosphorylates beta-catenin. We demonstrate that PP2A is required for Wnt/beta-catenin signaling in Drosophila. Moreover, by siRNA screening, we have identified PR55alpha as the regulatory subunit of PP2A that controls beta-catenin phosphorylation and degradation. Mechanistically, we found that PR55alpha directly interacts with beta-catenin and regulates PP2A-mediated beta-catenin dephosphorylation in Wnt signaling. PR55alpha but not the catalytic subunit, PP2Ac, directly interacts with beta-catenin. RNAi knockdown of PR55alpha elevates beta-catenin phosphorylation and decreases Wnt signaling, whereas overexpressing PR55alpha enhances Wnt signaling. Taken together, our results suggest that PR55alpha specifically regulates PP2A-mediated beta-catenin dephosphorylation and plays an essential role in Wnt signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 992.