bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1643: MicroRNA processing genes and implications for complex traits
Authors: Gamazon Eric R. , Im Hae Kyung , LaCroix Bonnie , Ziliak Dana , Huang R. Stephanie 
Published: August 2012

Abstract
Given the fundamental role of microRNA (miRNA) expression in physiological, developmental and pathological processes, we hypothesize that genes involved in miRNA biogenesis and processing are also important in human complex traits. We identified fifty two such genes and evaluated their expression for their roles in cellular growth and sensitivity to various chemotherapeutic agents in a set of 120 International HapMap cell lines. Gene expression data were obtained through microarray-based gene expression profiling (Affymetrix GeneChip® Human Exon 1.0 ST array) and high-throughput sequencing of the transcriptome (RNA-Seq); data on sensitivity to chemotherapeutic drugs carboplatin, cisplatin, daunorubicin and etoposide were queried using a publicly available pharmacogenomics resource we developed (www.PACdb.org). We found 14 (27%) and 24 (47%) of these miRNA processing gene expression correlated with cellular growth rate and at least one of the 4 chemotherapeutic sensitivities, respectively. Regression analysis for expression between miRNA processing genes and genome-wide miRNAs (quantified using Exiqon miRCURYTM LNA arrays) suggests that the miRNA processing genes affect miRNAs and downstream target genes, leading to complex traits variability. Furthermore, from the results of genome-wide association studies we conducted between genetic variations (in the form of single nucleotide polymorphisms (SNPs) and copy number variations (CNVs)) and miRNA processing genes, we demonstrated that genetic variations that affect the expression of these miRNA processing genes as potential expression quantitative trait loci (eQTLs) also have downstream effects on human complex phenotypes, including cellular growth, sensitivity to chemotherapy and disease susceptibility.
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 1643. doi:1538-7445.AM2012-1643
Abstract 1655: Genome-wide association study for age at onset in breast cancer: results from the Seoul Breast Cancer Study
Authors: Sung Hyuna , Choi Ji-Yeob , Song Minkyo , Jeon Sujee , Park Sue K. , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee 
Published: August 2012

Abstract
Introduction: While the incidence of breast cancer is relatively low in Korean women, the proportion of breast cancer that develops in younger age is much higher than in western countries. Family-based linkage study has focused on the identification of a region which is associated with the age at onset in familial breast cancer. However, genetic factors for onset age of breast cancer are still largely unknown. While genome-wide association studies (GWAS) have identified over 20 susceptibility loci for breast cancer, no previous study has examined the relationship between the common genetic variations and the age at onset in breast cancer. Methods: To identify genetic factors underlying onset age of breast cancer, we investigated the association between genetic variants and age at diagnosis in 2,155 breast cancer cases. Over 1.9 million SNPs either directly genotyped using Affymetrix 6.0 or imputed with HapMap 2.0 as a reference panel were evaluated after quality control. Tests of association were conducted with Plink v1.01 using the additive genetic model and Mach2qtl with allelic dosages in a linear regression model in which onset age was included as a dependent variable (continuous). The differences of mean age across genotype-groups were also compared using one-way analysis of variance. Results: The mean age at onset in breast cancer was 48.1 ± 9.31. The SNPs with p-value less than 1×10-5 obtained from linear regression were clustered into two regions: two SNPs (rs6684400 and rs6659875) are at 1q25.3 in intergenic region between ZNF648 and GLUL gene; the other two (rs669576 and rs667007) are at 11q25 in intronic region of NTM gene. Per-allele effect size was 1.4 ± 0.30 (p = 4.84E-06) for rs6684400 C allele and 3.1 ± 0.68 for rs669576 T allele (p = 7.11E-06). The mean age at onset for the rs6684400 G/G, C/G and C/C groups were found to be 47.2 ± 9.00, 48.1 ± 9.32 and 49.7 ± 9.59, respectively (p = 0.0001). As for the rs669576, the mean age at onset for G/G, G/T and T/T groups were 47.8 ± 9.15, 50.9 ± 10.38 and 54.3 ± 7.80, respectively (p &lt; 0.0001) Conclusions: Our study suggests that the common genetic variants may be closely linked to age at onset in breast cancer. Further validation with a larger sample size is required to validate our result.
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 1655. doi:1538-7445.AM2012-1655
Abstract 1656: Genome wide identification of susceptibility loci in breast cancer survival
Authors: Jeon Sujee , Sung Hyuna , Choi Ji-Yeob , Song Minkyo , Park Sue K. , Yoo Keun-Young , Noh Dong-Young , Han Wonsik , Ahn Sei-Hyun , Kang Daehee 
Published: August 2012

Abstract
Background: Recently, many studies have been conducted to identify the susceptibility loci related with breast cancer risk, but few studies have examined the genetic variations for survival. Objectives & Methods: To identify the susceptibility loci for breast cancer recurrence or all-cause of death, genome wide survival analysis were performed with 2,171 histologically confirmed incident breast cancer cases. For a genetic association study, DNA was genotyped using Affymetrix SNP Array 6.0 including about 0.9 million single nucleotide polymorphisms (SNPs). We examined the association between genetic variance and disease-free survival (DFS) and overall survival (OS) using Cox proportional hazard regression model adjusting for known prognostic factors. Results: During a median of 5.8 years of follow-up, 297 women recurred and 152 women died. Three SNPs in 2 genes (ARHGAP28 and LGI4) and four intergenic SNPs were identified for DFS (Padjusted &lt;10−6) and five SNPs in 4 genes (CADPS, KCNH7, LGI4, and TGFBRAP1) and one intergenic SNP were associated with OS (Padjusted &lt;10−6). Most significant associated SNP with DFS was located in ARHGAP28 (Padjusted =7.40 X 10−7) and this showed decreased risk of recurrence (aHR=0.6, 95% CI=0.50-0.74). SNP of CADPS was most significantly associated with OS (Padjusted = 9.04 X 10−7), and showed increased risk of all-cause of death (aHR=2.1, 95% CI=1.56-2.83). Conclusions: Our results suggest that the promising SNPs might associate with the breast cancer recurrence and survival in Korean women. We will confirm these findings in the replication stages further.
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 1656. doi:1538-7445.AM2012-1656
Abstract 1669: Discovery of nasopharyngeal carcinoma susceptible variants from whole genome imputation of genome-wide association study
Authors: Su Wen-Hui , Chang Kai-Ping , Chang Yu-Sun 
Published: August 2012

Abstract
Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy closely associated with genetic factors and Epstein-Barr virus (EBV) infection. To identify the common genetic variants linked to NPC susceptibility, we have conducted a genome-wide association study (GWAS) within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). In this study, only 12 SNPs that can pass the statistical criteria for GWAS were reported and all of them located within chromosome 6 MHC region. However, those 12 SNPs can only explain a small fraction of genetic risk. The vase majority of the genetic risks remain undiscovered. Additional analytical procedures are vary likely to provide valuable information for NPC susceptibility. By utilizing 1000 genome data, we successfully expend SNP number to 37,512,779 SNPs. After removed SNPs with low quality (info &lt;0.5) and no heterozygosity, we discovered additional 57,212 SNPs from whole genome imputation including 3,751 SNPs with P values &lt;0.05. SNPs located in chromosome 1, 2, 3, 8, 15, 17 were selected for further validation. This work taking advantage of current genome sequencing database and significantly expand the range of associated SNPs that can also increase the chance to discover true association signals. Following functional investigation and experimental application of these findings are expected to produce new advances in the prevention and treatment of NPC.
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 1669. doi:1538-7445.AM2012-1669
Abstract 1675: Effects of calcium and vitamin D on TGFβ and TGFβ1 expression in rectal mucosa of sporadic colorectal adenoma patients: A randomized controlled trial
Authors: Tu Huakang , Daniel Carrie , Ahearn Thomas , Bostick Roberd , Gonzalez-Feliciano Amparo 
Published: August 2012

Abstract
Aim: To estimate the effects of supplemental calcium and vitamin D3 on the expression of TGFβ and TGFβ1 (growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively) in the normal-appearing colorectal mucosa in sporadic colorectal adenoma patients. Methods: We conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial (n = 92) of calcium 2 g and/or vitamin D3 800 IU/day versus placebo over 6 months. TGFβ and TGFβ1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-months follow-up. Results: The mean overall expression of TGFβ1 in the whole crypts increased by 14% (P = 0.25), 19% (P = 0.17), and 22% (P = 0.09) in the calcium, vitamin D, and calcium plus vitamin D groups, respectively, relative to the placebo group. The increases in TGFβ1 appeared to be uniform along the full length of the crypts. While there were no substantial changes in the overall expression of TGFβ in the whole crypts, in the calcium, vitamin D, and calcium plus vitamin D groups, TGFβ decreased by 14% (P = 0.35), 2% (P = 0.86), and 1% (P = 0.93), respectively, in the upper 40% (differentiation zone) of the crypts, but increased by 29% (P = 0.30), 38% (P = 0.17), and 25% (P = 0.32) in the bottom 60% of the crypts (proliferative zone). Also, a TGFβ/TGFβ1 ratio was created as an indicator of the balance between the growth-promoting and -inhibiting factors; in the upper 40% of the crypts it was found to have decreased by 35% (P = 0.24), 25% (P = 0.42), and 51% (P = 0.09) in the calcium, vitamin D, and calcium plus vitamin D groups, respectively, relative to the placebo group, but not to have changed substantially in the whole or bottom 60% of the crypts. Conclusions: These preliminary results suggest that supplemental calcium and vitamin D3 may increase the expression of TGFβ1, shift the expression of TGFβ downward in the colorectal crypts, and decrease the ratio of TGFβ to TGFβ1 in the upper 40% (differentiation zone) of the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms.
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 1675. doi:1538-7445.AM2012-1675
Abstract 1680: Age-associated gene expression in normal breast tissue provide insights regarding associations between aging and aggressive tumor characteristics
Authors: D'Arcy Monica , Pirone Jason R. , Stewart Delisha A. , Casbas-Hernandez Patricia , Gould Michael N. , Jerry Joseph Jerry , Yaswen Paul , Schneider Sallie Smith , Troester Melissa A. 
Published: August 2012

Abstract
Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. Though several genomic studies have characterized differences in the biology of tumors arising in younger vs. older women, understanding of age-related gene expression in the non-malignant tissue is lacking. Because non-malignant tissue represents the microenvironment and/or field from which the tumor arises, an improved characterization of the age-related change in normal breast may provide suggestions of important pathways in the etiology of distinct breast cancer subtypes. To identify age-related changes in the breast microenvironment, 96 normal tissue specimens from reduction mammoplasty patients ranging in age from 14 to 70 were assayed by gene expression microarray. Significant associations between gene expression levels and age were identified for 802 genes (481 increased and 321 decreased with increasing age). Enriched functions included ‘aging of cells’, ‘shape change’, and ‘chemotaxis’, and enriched pathways included Wnt/beta-catenin signaling, Ephrin Receptor Signaling, Oncostatin M signaling, and JAK/Stat Signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. The poor prognosis tumor group shared features of ‘younger’ breast tissue gene expression, providing a biological link to qualitative patterns in age at incidence. Aggressive tumors common in younger women (such as ER negative and basal-like breast cancers) harbor gene expression patterns that reflect the normal tissue from which they arise. For the young, these signatures portend more aggressive disease. These data show that studies of normal tissue gene expression can yield important insights about the pathways and biological selection factors that are relevant during tumor progression.
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 1680. doi:1538-7445.AM2012-1680
Abstract 169: Inhibition of focal adhesion kinase suppresses gastrin-releasing peptide receptor-mediated liver metastasis in neuroblastoma
Authors: Lee Sora , Qiao Jingbo , Paul Pritha , Chung Dai H. 
Published: August 2012

Abstract
We have previously reported that high expression of gastrin-releasing peptide receptors (GRP-R), a member of the G-protein coupled receptor family, is observed in more undifferentiated human neuroblastoma. We have also found that GRP-R-mediated cell signaling plays a critical role in neuroblastoma cell transformation; however, its molecular mechanisms are unknown. Here, we sought to determine the role of focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase, in GRP-R-mediated neuroblastoma cellular transformation. METHODS. Using human neuroblastoma tissue sections, the correlation of GRP-R and FAK expression was examined. Human neuroblastoma cell line, BE(2)-C and SK-N-SH were used for our experiments. Using transfection with Lipofectamine 2000, the level of knockdown and overexpression of GRP-R and FAK were modulated. MTT assay was carried out to measure the cell viability of neuroblastoma cells, and soft agar colony formation assay was performed to determine the capacity of cell transformation. Transwell migration and wound healing assay were employed to study cell motility. Rescue experiments by overexpression of FAK in GRP-R silencing cells were conducted to further validate the role of FAK in neuroblastoma cell transformation. Using FAK inhibitor and GRP-R agonist, animal experiment was performed. RESULTS. FAK expression correlated with GRP-R expression in BE(2)-C and SK-N-SH human neuroblastoma cells. GRP treatment induced phosphorylation of FAK at Y397 in both cell lines. Overexpression of GRP-R in SK-N-SH cells, which are known to express low endogenous levels of GRP-R, increased the levels of phosphorylated and total FAK. Moreover, overexpression of FAK increased cell viability and colony formation of SK-N-SH cells. These effects were reversed when cells were co-transfected with FAK siRNA in BE(2)-C cells, which endogenously express higher levels of GRP-R. Conversely, silencing of GRP-R decreased the levels of phosphorylated and total FAK in BE(2)-C cells. Interestingly, in cells with GRP-R silencing, FAK overexpression significantly enhanced cell viability and colony formation. GRP-R-mediated liver metastasis suppressed by FAK inhibitor in vivo. CONCLUSIONS. Our results suggest that FAK is a critical downstream regulator of GRP-R-mediated tumorigenesis. Furthermore, GRP-R and FAK expression correlate with morphological changes implicated in the malignant transformation of human neuroblastoma cells. Importantly, inhibition of FAK can suppress GRP-R-induced tumor progression in neuroblastoma in vivo.
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 169. doi:1538-7445.AM2012-169
Abstract 1708: LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer
Authors: Matsunoki Aika , Kawakami Kazuyuki , Kotake Masanori , Kaneko Mami , Watanabe Go , Minamoto Toshinari 
Published: August 2012

Abstract
Introduction: Epigenetic alterations including hypermethylation of gene promoter regions and global hypomethylation of DNA are common in colorectal cancer (CRC). We recently reported that long interspersed nuclear element 1 (LINE-1) methylation level in tumor, a surrogate of global methylaiton, predicts prognosis and response to oral fluoropyrimidines of CRC patients. This suggests that the LINE-1 methylation level is a useful marker for tailored therapy in CRC. However, the LINE-1 methylation level in tumor may be heterogeneous because the DNA methylaion is reversible, which is a problem when the LINE-1 methylation level in tumor is used for decision making in clinic. In this study we investigated LINE-1 methylation level in cancer cells isolated from multiple tumor sites to evaluate intra-patient heterogeneity of the LINE-1 methylation level in tumor tissues. Methods: Primary tumor, metastatic lymph nodes, and distant metastases in 41 CRC patients were used for measurement of LINE-1 methylation level. Cancer cells in primary tumors were collected from tumor center and invasion front by laser capture microdissection (LCMD). Cancer cells in metastatic lymph nodes and distant metastases were also collected by LCMD. The LINE-1 methylation level was measured by multicolor MethyLight assay following bisulfite modification of DNA and was correlated with clinicopathological parameters. Results: There was no significant difference in the LINE-1 methylation level between cancer cells from the center and those from invasion front of the primary tumor tissue. In the same patient, there was no significant difference in the LINE-1 methylation level between the samples from primary tumor, metastatic lymph nodes, and distant metastases. The LINE-1 methylation level was decreased as the tumor stage advances. Discussion: The results suggest that the LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer. Prediction of patients’ prognosis using LINE-1 methylation level may be possible by multiple tumor specimen such as biopsy specimen by colonoscopy and surgically resected tumor. Measuring LINE-1 methylation level in primary tumor may be useful for prediction of response to fluoropyrimidines in metastatic tumor.
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 1708. doi:1538-7445.AM2012-1708
Abstract 1717: Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy
Authors: Shien Kazuhiko , Toyooka Shinichi , Ichimura Kouichi , Soh Junichi , Furukawa Masashi , Maki Yuho , Muraoka Takayuki , Tanaka Norimitsu , Ueno Tsuyoshi , Asano Hiroaki , Tsukuda Kazunori , Yamamoto Hiromasa , Yamane Masaomi , Oto Takahiro , Kiura Katsuyuki , Miyoshi Shinichiro 
Published: August 2012

Abstract
Background: Several cancer stem cell (CSC) related markers have been confirmed to be expressed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the prognostic role of CSC related markers expression in locally advanced NSCLC with induction chemoradiotherap (CRT).Methods: Fifty patients with clinically N2 or N3 NSCLC underwent induction CRT with cisplatin and docetaxel concurrently with thoracic radiation followed by surgery. Expressions of CSC related markers (CD133, ABCG2, ALDH1, and Bmi-1) were examined by immunohistochemical stain from surgical resected specimen. The prognostic factors were investigated by multivariate analysis using Cox proportional hazard model.Results: Among 50 patients, 20 patients had no pathologically residual tumor cell in the surgical resected specimen, and CSC related markers expressions were evaluated in other 30 patients. With a median follow-up duration of 71 months, the 5-year overall survival rate in the patients of CD133 or ALDH1 -positive was significantly worse than that in the patients of CD133 and ALDH1 -negative (90.0% vs. 44.9%, respectively, P = 0.042). In multivariate analysis, CD133 and ALDH1 negativity (Hazard ratio [HR] 0.16, 95% confidential interval [CI]: 0.0086-0.98, P = 0.047) and c-N2-3 single node metastasis (not multi node metastasis) (HR 0.19, 95% CI: 0.028-0.91, P = 0.03) were significant independent prognostic factors for the prolongation of survival.Discussion: The expressions of CSC related markers after CRT are significantly related to poor prognosis in NSCLC. The development of therapeutic strategy including adjuvant therapy, is a key for further improvement of prognosis in patients who underwent trimodality therapy.
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 1717. doi:1538-7445.AM2012-1717