bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2704: A role of the ADCC in the antibody therapy for gastrointestinal carcinoma
Authors: Matsuyama Tatsuzo , Kokura Satoshi , Matsumoto Tsuguhiro , Okajima Manabu , Okajima Manabu , Ishikawa Takeshi , Funaki Jun , Adachi Satoko , Matsuura Yuko , Sakamoto Naoyuki , Naito Yuji , Yosikawa Toshikazu 
Published: June 2012

Abstract
(Background and Aim) Both cetuximab and trastuzumab inhibit growth signal by binding to growth factor receptors, and also have an alternative function regarded as ADCC. In this study, we examined cetuximab-mediated ADCC against EGFR-positive colon cancer cells and trastuzumab-mediated ADCC against HER2-positive gastric cancer cells. Moreover, we investigated the new methods to enhance those ADCC activities.
(Materials and Methods) We used human gastric cancer cell lines (MKN1, MKN45) and colon cancer cells (HT-29), cetuximab and trastuzumab as an antibody which potentially had ADCC, and non-specific IgG1 antibody as a control. ADCC was measured by Europium release assay: First, we used peripheral blood mononuclear cells (PBMCs) from healthy volunteers as effector, and we prepared those cancer cell lines combined with those kinds of antibodies as target. Next, we used PBMCs activated by IL-2 instead of normal PBMCs. At same time, CD16, perforin, granzyneB on PBMCs were evaluated by Flow Cytometer and PCR. NK activity of PBMN and activated PBMC against for K562 cell and ADCC activity of PBMN and activated PBMC were evaluated.
(Results) Cetuximab and trastuzumab didn't kill cancer cells by themselves, but the cytotoxicity of PBMCs was increased when the target cells were treated with these antibodies in advance. This increase was further strengthened by activated PBMCs with IL-2. But IL-2 didn't enhance CD16 expression on PBMCs. Finally PBMC, which have high potential of NK activity shows high ADCC activity,
(Conclusion) These two antibody therapy shows ADCC in vitro, As a next step, we have to start in vivo study
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2704. doi:10.1158/1538-7445.AM2011-2704
Abstract 2733: KITENIN and ErbB4 contribute to further malignant changes in colorectal cancer through c-Jun/AP-1 activation
Authors: Bae Jeong A , Sun Eun Gene , Kim Hangun , Park So Yeon , Lee Hyun Jong , Ryu Hee Won , Kim Kyung Keun 
Published: June 2012

Abstract
KITENIN (KAI1 C-terminal interacting tetraspanin, Vangl1) is not only a major component of PCP pathway but also a functional protein promoting colorectal cancer (CRC) cell motility and invasiveness. Here, we report the mechanism of which KITENIN leads further malignant changes in CRC progression after loss of tumor suppressor Adenomatous polyposis coli (APC). KITENIN increases the level of AP-1 activity through interaction with Dvl2, which is subsequently being degraded. Decreasing Dvl2 via interaction with KITENIN or via treatment of si-RNA to Dvl2 significantly increases the AP-1 activity through elevating the level of c-jun and c-jun phosphorylation. EGF acts upstream of KITENIN/AP-1 signaling and induces synergic AP-1 activation in the presence of elevated KITENIN, which requires the interaction of KITENIN with ErbB4. The morphological characteristics of adenocarcinoma were observed in intestinal tumor tissues from compound villin-KITENIN transgenic/APCmin/+ mice but not from APCmin/+ mice, both of which express the elevated level of ErbB4. This result demonstrates that further malignant phenotype of intestinal tumor can be induced by elevated KITENIN and ErbB4 via promoting c-Jun/AP-1 activation within an APC loss-associated tumor microenvironment. Our present results suggest the possibility of the addition of anti-KITENIN therapy to the use of EGFR inhibitors in the treatment of CRC patients with APC mutation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2733. doi:10.1158/1538-7445.AM2011-2733
Abstract 2734: Genome-wide analysis of direct Nkx3.1 target genes
Authors: Logan Monica , Anderson Philip , Abdulkadir Sarki 
Published: June 2012

Abstract
NKX3.1 is an androgen-regulated, prostate-specific tumor suppressor gene that is essential for development and maintenance of the prostate gland. Loss of Nkx3.1 expression results in the formation of premalignant lesions called prostatic intraepithelial neoplasia lesions (PIN). With additional mutations, these PIN lesions will progress to invasive carcinoma and eventually to metastatic disease in which there is currently no effective treatment. The specific mechanism(s) by which Nkx3.1 suppresses prostate tumorigenesis remains unknown. Previous gene expression profiling studies in Nkx3.1-deficient mouse prostates have shown aberrant expression of many genes that may be involved in prostate tumorigenesis. However, it is unknown whether these genes are direct targets of Nkx3.1 in vivo. To identify direct Nkx3.1 target gens, we used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to identify Nkx3.1 binding sites in the genomes of a human prostate cancer cell line (LNCaP) as well as the normal mouse prostate. We obtained 7 to 15 million uniquely mapped tags each from Nkx3.1 ChIP-seq using LNCaP cells or Nkx3.1+/+, Nkx3.1+/−, and Nkx3.1−/− mouse prostates. This led to the identification of about 8000 Nkx3.1 binding sites in the genome (the Nkx3.1 cistrome). The binding site data were integrated with gene expression profiling results from Nkx3.1 mutant mice to yield a core set of “direct” Nkx3.1 target genes. One gene in particular that is upregulated in Nkx3.1 mutant mice and in human prostate tumors and bound by Nkx3.1 in our ChIP-Seq studies is the receptor activity modifying protein 1 (RAMP1) gene. Ramp1 is a single transmembrane protein that is required for trafficking of the calcitonin gene-related peptide (CGRP) receptor to the plasma membrane. The CGRP receptor binds CGRP, a neuropeptide that has been shown to promote cancer progression. Current studies are focused on whether RAMP1 expression in human prostate cancer cells function to promote tumorigenesis. Given that Ramp1 is localized to the plasma membrane, data from my project may provide support for investigating Ramp1 as a therapeutic target for prostate cancer or for imaging prostate lesions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2734. doi:10.1158/1538-7445.AM2011-2734
Abstract 2740: Decision tree-based modeling of androgen pathway genes and prostate cancer risk
Authors: Barnholtz-Sloan Jill S. , Guan Xiaowei , Zeigler-Johnson Charnita , Meropol Neal J. , Rebbeck Timothy 
Published: June 2012

Abstract
Background: Inherited variability in genes that influence androgen metabolism has been implicated in the etiology of prostate cancer. However, joint effects of these genes have not been fully defined in terms of risk.
Objective: The objective of this analysis was to evaluate gene-gene and gene-environment interactions for prostate cancer risk using classification and regression tree (CART) models (i.e. decision trees), and to evaluate whether these interactive effects add information about prostate cancer risk prediction beyond that of “traditional” risk factors.
Methods: We compared CART models to traditional logistic regression models for associations of factors with prostate cancer risk using 1084 prostate cancer cases and 941 controls. All analyses were stratified by race. We used unconditional logistic regression (LR) to complement and compare to the race-stratified CART results using the area under curve (AUC) for the receiver operating characteristic (ROC) curves.
Results: In European Americans, single SNP or haplotype associations were found with CYP3A5 (OR=2.11 (1.13, 3.97)); increasing number of CAG repeats in the AR gene (OR=0.90 (0.83, 0.98)); and the CYP3A4/CYP3A5 AG haplotype (OR=2.86 (1.15, 7.12)). No significant single SNP or haplotype associations were found in African Americans. The CART modeling of prostate cancer risk showed different interaction profiles by race. For European Americans, interactions among CYP3A43 genotype, history of BPH, family history of prostate cancer and age at consent revealed a distinct hierarchy of gene-environment and gene-gene interactions. While for African Americans, interactions among family history of prostate cancer, individual proportion of European ancestry, number of GGC AR repeats and CYP3A4/CYP3A5 haplotype revealed distinct interaction effects from those found in European Americans. For European Americans the CART model had the highest AUC while for African Americans, the LR model with the CART discovered factors had the largest AUC.
Conclusion: These results show novel gene-gene and gene-environment interactions specific for European Americans and African Americans discovered using CART as compared to standard LR techniques.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2740. doi:10.1158/1538-7445.AM2011-2740
Abstract 2746: Genomic data mining for selecting informative markers for ancestry
Authors: Baye Tesfaye Mersha 
Published: June 2012

Abstract
Given the huge amount of single nucleotide polymorphism (SNP) data available from high-throughput sources such as HapMap, data mining using various methods is a reasonable approach to identify SNPs that are informative for genetic ancestry. We extensively investigated the distribution and density of the SNPs across the genome of African and European populations available within the framework HapMap database to prioritize potential candidate SNPs useful for ancestry mapping in an admixed population. About 4 million SNPs were compared between Africans and Europeans using various measures of ancestry informativeness in use today viz. absolute allele frequency differences (Δ), Fisher Information Content (FIC), Shannon Information Content (SIC), informativeness for assignment (I), and Fixation Index (FST). Each method provides different sets of candidate ancestry informative markers (AIMs). The selected SNPs represent valuable resources for both controlling population structure and gene mapping studies. The overlap and non-overlap between selected AIMs by different measures of informativeness, data filtering strategies and the accuracy of each measure in classifying ancestral populations and applications in cancer genomics are discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2746. doi:10.1158/1538-7445.AM2011-2746
Abstract 2758: Genetic variability in tobacco-specific nitrosamine NNK to NNAL metabolism
Authors: Ter-Minassian Monica , Asomaning Kofi , Zhao Yang , Chen Feng , Su Li , Carmella Steven G. , Lin Xihong , Hecht Stephen S. , Christiani David C. 
Published: June 2012

Abstract
Introduction: Tobacco-specific nitrosamine (TSNA) NNK metabolites NNAL and NNAL-gluc) together, (total NNAL), have recently been shown to be good predictors of lung cancer risk, years prior to diagnosis. However, the inter-individual variability in the metabolism of NNK evaluated by the total NNAL output could be explained in part by genetic variability in the genes of NNK metabolism. We sought to determine the contribution of several genetic polymorphisms to total NNAL output by a regression analysis of NNAL levels on genotyping results, controlling for measures of smoking, age and sex.
Methods: The study subjects were derived from the Harvard/ Massachusetts General Hospital Lung cancer case-control study. We selected 92 subjects (39 lung cancer cases and 53 controls) smokers at time of diagnosis and urine collection (1992-1996). We tested 77 tagging SNPs in 16 genes related to NNK to NNAL metabolism. Using case status as a mediator, we tested for the association of each SNP with square-root (sqrt) transformed NNAL (pmol per mg creatinine), controlling for age, sex, sqrt packyears and sqrt nicotine (ng per mg creatinine).
Results: After a sqrt transformation, nicotine significantly predicted a 0.02 (0.015, 0.023) pmol/mg creatinine unit increase in NNAL for every ng/mg creatinine increase in nicotine at p = 2.85E-12. Three HSD11B1 SNPs, located in a 14kb region flanked by rs2235543 and rs3753519 in intron 1, were significantly associated with decreasing NNAL levels. Two of these SNPs, rs2235543 (p = 4.84E-08) and rs3753519 (p = 0.0017), passed multiple testing correction at FDR q value=1.07E-05 and 0.06 respectively. AKR1C4 rs7083869 G&gt;A was also to be significantly associated with decreasing NNAL levels, p=0.019, FDR q=0.48.
Conclusions: HSD11B1 and AKR1C4 enzymes are carbonyl reductases directly involved in the single step reduction of NNK to NNAL. The HSD11B1 SNPs may be correlated with the functional variant rs13306401 and the AKR1C4 SNP correlated with the enzyme activity reducing variant rs17134592, L311V.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2758. doi:10.1158/1538-7445.AM2011-2758
Abstract 2765: Genetic variants in immunoregulaion and DNA repair related genes and risk of lymphoma among children in Korea
Authors: Song Nan , Kang Daehee 
Published: June 2012

Abstract
Although lymphoma is recognized as a cancer of the immune system, little is known regarding a role for genes involved immune system. Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. In order to estimate the genetic susceptibility for childhood lymphoma, we investigated whether genetic variation 1536 tag single nucleotide polymorphisms (SNPs) selected in 138 candidate gene regions related to immune response, apoptosis, cell cycle, and DNA repair. We used the GoldenGate (Illumina) oligonucleotide pool assay (OPA) in 40 cases patients and 254 controls among Korean children. The association study was estimated as odds ratios and 95% confidence intervals adjusted for age. The minP test was used to identify statistically significant association at gene level. Five genes (IL1RA, IL2, IL12RB1, JAK3, and TNFRSF13B) in immune response and one gene (XRCC3) in DNA repair had statistical significance (minP &lt; 0.05). In these regions, total twelve SNPs (rs11677140, rs10857092, rs2069762, rs4833248, rs365179, rs3212701, rs3212711, rs7250423, rs3751987, rs3751991, rs4343329, rs861547) were significantly associated the risk of lymphoma (Ptrend &lt; 0.05). The most significant association with the risk of lymphoma was seen for IL2 rs2069762 (ORCC/AA = 10.1, 95% CI = 2.4-43.1, Ptrend = 0.002, minP = 0.005). These findings suggest that common genetic variants in immune response and DNA repair related genes might play a role in the genesis of childhood lymphoma with limited biological evidence. Additional larger studies are needed to identify these findings and understand the mechanisms of these genes in childhood lymphoma patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2765. doi:10.1158/1538-7445.AM2011-2765
Abstract 277: Genetic re-programming of the acute myeloid leukemia cell line HL-60
Authors: Roberts Michael , Bittner David , Brnich Sarah , Conner Bryan , Cox Carla , Filiberti Julia , Grant Michael , Mansuy Michael , Forrester Jeffrey 
Published: June 2012

Abstract
HL-60 cells represent an established line of human acute myeloid leukemia cells that can be induced to differentiate along several distinct myeloid lineages. Phorbol esters activate a signaling network, which includes the protein kinase C (PKC) signaling pathway, causing the leukemia cells to differentiate into macrophage-like cells. As the leukemia genetic program is converted to the macrophage program, the cells exit the cell cycle, undergo morphological changes, become adherent, display other macrophage properties, and ultimately initiate apoptosis. This study provides a detailed DNA microarray analysis of the genetic network of the leukemia cell during first 24 hours post-induction of differentiation. Approximately 1,000 genes were identified that exhibit significant changes in mRNA levels from the leukemia expression profile. A cluster analysis was performed to group these genes by their pattern of expression resulting in a collection of distinct expression profiles. Expression levels of selected genes within each cluster were validated by real time PCR. Among the most significant changes observed were dramatic increases in the expression of CCL chemokine family genes and a variety of transcription factor genes including members of the AP-1 and NF-κB families. Expression level changes in genes involved in cell cycle progression (ex. MYC and p21) were also observed along with genes involved in the regulation of apoptosis (ex. BCL2A1, TNF, IER2 and OLR1). Functional analysis at the protein level using the electrophoretic mobility shift assay (EMSA), western blotting and immunofluorescence imaging will also be presented. This study provides a comprehensive view of the re-programming events that occur in phorbol ester induced macrophage differentiation of HL-60 cells with regard to the inflammatory response, cell cycle exit, differentiation and initiation of apoptosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 277. doi:10.1158/1538-7445.AM2011-277
Abstract 2772: 2’-5’oligoadenylate synthetase polymorphism is associated with prostate cancer: Effect modified by age and race
Authors: Mandal Sanjay K. , Abebe Fisseha , Chaudhary Jaideep 
Published: June 2012

Abstract
Introduction: 2’ -5’ -oligoadenylate synthetase (2-5 OAS1) is an antiviral gene that converts ATP to a series of (2-5A). 2-5A promotes dimerization of latent ribonuclease (RNASE L) to form catalytically active RNASEL, a candidate hereditary prostate cancer gene. Thus a defect in OAS1 can not only attenuate RNASEL function, but can also alter cell growth and apoptosis independent of RNASEL. OAS1 polymorphism (rs2660) has been associated with increased disease susceptibility and viral infection like, HCV, West Nile virus infection, SARS, diabetes and MS. The AA genotype, known to have lower enzymatic activity promotes disease susceptibility whereas GG genotype with higher enzyme activity confers protection. In the present study we investigated this functional polymorphism (rs2660) in OAS1 in a large prostate cohort.
Methods: Genomic DNA from Buffy coat samples was used from age matched controls (n=140) and prostate cancer patients (n=164) who had undergone prostatectomy for genotyping. Information regarding age, race, and cancer stage were available for all samples. PCR-RFLP, followed by direct sequencing was used for genotyping. SNPs rs2660, rs1131454 and rs34137742 were genotyped on all samples. Statistical analysis was performed using chi2 test and logistic regression model with NCSS software.
Results: The rs2660 genotype distribution is summarized in table 1. Genotype AA increases the risk of prostate cancer by 61%. Prostate cancer incidence increases with age, however when combined with rs2660 genotype AA the odds of prostate cancer incidence are higher.SNPs rs1131454 and rs34137742 were not associated with prostate cancer.
Conclusion: OAS1 SNP rs2660 AA genotype is significantly associated with prostate cancer whereas GG genotype protects against prostate cancer. The effect of this genotype distribution was more profound in African American population as compared to Caucasians.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2772. doi:10.1158/1538-7445.AM2011-2772
Abstract 2779: Plasma carotenoids and DNA methylation status modulate prostate cancer aggressiveness
Authors: Su L Joseph , Zabaleta Jovanny , Chiang Tung-Chin 
Published: June 2012

Abstract
Introduction: Prostate cancer is the most frequently diagnosed malignancy in men. Many low grade prostate cancer would never progress further through the life of the patients. Identifying nutritional factors that may be associated with epigenetic factors associated with high aggressive prostate cancer could potentially prevent the progression of prostate cancer.
Methods: A pilot study was conducted to examine the association between plasma carotenoids concentrations and DNA methylation status previously found to be associated with prostate cancer aggressiveness, defined using clinical criteria abstracted from medical records at time of prostate cancer diagnosis. Among 88 newly diagnosed prostate cancer patients (47 African Americans and 41 Caucasians), cancer on 18 subjects were classified as high aggressive and 70 subjects as low or intermediate aggressive. The GoldenGate Methylation Cancer Panel I was used to obtain DNA Methylation data. Plasma carotenoid concentrations were measured using High-performance liquid chromatography. Analysis of variance adjusting for age, race, and body mass index was used to evaluate the relationship between plasma carotenoids concentration and DNA methylation status among the low and the intermediate aggressive prostate cancer cases.
Results and Conclusions: This study found that EYA4, IGF1, PALM2AKAP2, and SNRPN were less likely to be hypomethylated (p &lt; 0.05) among subjects with higher plasma lutein-zeaxanthin level. Similarly, Elevated plasma lycopene is inversely associated with hypomethylation at EYA4, FYN, and SNRPN. Both EYA4 and IGF1 genes have previously demonstrated with anti-apoptotic function; while SNRPN have tumor suppressor function. The result of this pilot study suggests that carotenoids may modulate DNA methylation, possibility through their antioxidant property, that affects the aggressiveness of prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2779. doi:10.1158/1538-7445.AM2011-2779