bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 808: Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology
Authors: Gravendeel Lonneke , Kouwenhoven Mathilde , Gevaert Olivier , de Rooi Johan , Stubbs Andrew , Duijm Elza , Daemen Anneleen , Bleeker Fonnet , Bralten Linda , Kloosterhof Nanne , de Moor Bart , Eilers Paul , van der Spek Peter , Kros Johan M. , Smitt Peter Sillevis , van den Bent Martin , French Pim 
Published: February 2011

Abstract
Gliomas are the most common primary brain tumors with heterogeneous morphology and variable prognosis. Treatment decisions in patients rely mainly on histological classification and clinical parameters. However, differences between histological subclasses and grades are subtle, and classifying gliomas is subject to a large inter-observer variability. To improve current classification standards, we have performed gene expression profiling on a large cohort of glioma samples of all histological subtypes and grades. We identified seven distinct molecular subgroups that correlate with survival. These include two favorable prognostic subgroups (median survival &gt;4.7 years), two with intermediate prognosis (median survival 1-4 years), two with poor prognosis (median survival &lt;1 year), and one control group. The intrinsic molecular subtypes of glioma are different from histological subgroups and correlate better to patient survival. The prognostic value of molecular subgroups was validated on five independent sample cohorts (TCGA, REMBRANDT, GSE12907, GSE4271, and Li et al.). The power of intrinsic subtyping is demonstrated by its ability to identify a subset of prognostically favorable tumors within an external dataset that contains only histologically confirmed glioblastomas. Specific genetic changes (EGFR amplification, IDH1 mutation, 1p/19q LOH) segregate in distinct molecular subgroups. We identified a subgroup with molecular features associated with secondary glioblastoma, suggesting that different genetic changes drive gene expression profiles. Finally, we assessed response to treatment in molecular subgroups. Our data provides compelling evidence that expression profiling is a more accurate and objective method to classify gliomas than histological classification. Molecular classification therefore may aid diagnosis and can guide clinical decision making.
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 808.
Abstract 836: In vivo PET imaging of MET receptor in human cancer using [11C]SU11274
Authors: Ma Patrick C. , Wu Chunying , Tang Zhe , Fan Weiwen , Zhu Wenxia , Wang Changning , Somoza Edurado , Owino Norbert , Li Ruoshi , Wang Yanming 
Published: February 2011

Abstract
The mesenchymal-epithelial transition (MET) receptor plays prominent role in human tumorigenesis, tumor progression and metastasis. Overexpression or mutation of MET results in activation of oncogenic signaling pathways and leads to upregulation of diverse tumor cell functions. Mounting evidence has validated MET receptor as novel target for anticancer therapy. For efficacy evaluation of various MET-targeted anticancer therapies currently under development, it is critical to develop an imaging tool that permits detection and quantification of MET expression in vivo. To date, a number of small molecule MET inhibitors have been developed, including SU11274, which is a specific, reversible MET inhibitor that induces apoptosis in cells transformed by activated MET kinase. Here, we report the radiosynthesis and evaluation of a molecular imaging probe, [11C]SU11274, for quantification of MET receptors in human cancers in vivo. The radiolabeling with C-11 was accomplished through radiomethylation using 3-[3,5-Dimethyl-4-(piperazine-1-carbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2,3-dihyro-1H-indole-5-sulfonic acid (3-chlorophenyl)-methyl amide hydrochloride as a key precursor. Following the synthesis of the precursor that was achieved in 10 steps with a total yield of 9.7%, [11C]SU11274 was obtained through radiomethylation in a range of 5-10 % radiochemical yield and over 95% radiochemical purity. For in vivo PET studies, two human lung adenocarcinoma cancer xenograft models were established using MET-positive H1975 and MET-negative H520 cell lines. The time-radioactivity curves showed that the uptake of [11C]SU11274 in the H1975 xenograft was significantly higher than in the H520 xenograft (p = 0.00019). Compared to H520, the H1975 xenograft mice exhibited an increased tumor uptake of [11C]SU11274 throughout the entire measurement period of 90 min. At 65 min post-injection, the radioactivity concentration ratio of H1975/H520 reached a statistically significant and enhanced ratio of 2.1, and peaked at 2.6 at 80 min. The PET imaging results were consistent with their corresponding immunohistochemical tissue staining patterns of MET receptors from the same animals. Hence, our results suggest that [11C]SU11274-PET is a specific imaging marker that can differentiate and quantify MET receptor expression in vivo. These studies demonstrated that [11C]SU11274-PET can facilitate the clinical development of MET-targeted cancer therapeutics.
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 836.
Abstract 852: Prognostic value of circulating endothelial and progenitor cells in advanced cancer patients enrolled in phase 1 in association with clinical prognostic scores
Authors: Massard Christophe , Deley Marie-Cecile Le , Roca Carlos Gomez , Borget Isabelle , Soria Jean-Charles , Farace Françoise 
Published: February 2011

Abstract
Background
New surrogate biomarkers such as circulating endothelial cell (CEC) and progenitor cell (CEP) have been proposed to monitor anti-vascular drug activity. During anti-angiogenic therapy, dramatic changes in both CEC and CEP levels were observed. Moreover, these biomarkers may also be used as a candidate prognostic and predictive biomarker in patients with advanced cancer.
Methods
Medical charts of patients treated in one centre and enrolled into five Phase I trials with anti-vascular therapies between October 2005 and April 2009 were reviewed for clinical characteristics and validated clinical prognostic factors (albumin, lactate dehydrogenase, number of metastatic sites)(Arkenau et al, JCO 2009).
Overall 70 patients had CEC or CEP evaluation at baseline. CECs were measured in one ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45-CD31+CD146+ 7-amino-actinomycin (7AAD)- phenotype… CEPs were measured in 10ml blood after progenitor cell enrichment and were identified by FCM as extremely rare events with a CD45dimCD34+VEGFR2+7AAD- phenotype.
We studied the impact of CEC and CEP values on the overall survival (OS) adjusted on the clinical prognostic score.
Results
The median age was 50 years (range, 21 to 78 years).
Median baseline CEC value was 12/ml (range, 0 to 154).
The CEPs were measured in 57 patients; the median CEP value was 1.3% of hematopoietic stem cells, with range from 0% to 32.5% (absolute counts: 12/ml, range, 0 to 392/ml). 31/57 had CEP values greater than 1% of HSC.
Median follow-up was 23 months. The risk of death was significantly increased in patients with prognostic score greater than 0 as compared to patients with score equal to 0 (Median OS 9.2 versus 24.2 respectively) as well as in patients with increased CEP (&gt;1%) as compared to those with lower values (Median OS 9.0 versus 13.3). Both factors remained significant in multivariate analysis (HR=3.9, 95%CI, 0.95-16.6, p=0.02 and HR=2.1, 95%CI, 1.0-4.3, p=0.04, respectively). We did not observe any relationship between the CEC level and the outcome.
Conclusion
This analysis suggests that a prognostic score based on CEP level combined with clinical characteristics could be a helpful tool to determine the prognosis of patients with advanced cancers enrolled into phase 1 trials. Further studies are requested to confirm these findings.
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 852.
Abstract 868: Regular aspirin use and risk of multiple myeloma: A prospective analysis
Authors: Birmann Brenda M. , Giovannucci Edward , Colditz Graham A. 
Published: February 2011

Abstract
Multiple myeloma (MM) is a lethal malignancy with a poorly understood etiology and no prevention strategies. Aspirin inhibits nuclear factor (NF)-κB, a transcription factor that mediates growth factors important to MM pathogenesis. We undertook the present analysis to evaluate whether regular aspirin use is associated with MM risk and thus may offer opportunities for MM chemoprevention. We conducted prospective analyses of regular aspirin use and MM risk in the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) populations. Questions on regular aspirin use were first asked of women in 1980 and of men in 1986, and were updated thereafter on biennial follow-up questionnaires. Participants reported height and weight at enrollment (1976 in NHS, 1986 in HPFS), and updated weight biennially. We followed participants from the year of first aspirin use questions through the earliest among a cancer diagnosis, death, or June 2006 (NHS) or January 2006 (HPFS). We excluded persons with missing baseline exposure data or a baseline history of cancer. We imposed a 4-year lag on aspirin use classification to minimize the influence of preclinical MM-related bone pain on use; exposures were updated biennially. We identified 164 women and 110 men with MM during follow-up (i.e., 1,586,035 NHS and 593,489 HPFS person-years). We obtained hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazard models stratified by age and adjusted for body mass index, to assess the association of updated quantity and duration of aspirin use with MM. In men, cumulative average aspirin tablets/week (tab/wk) was inversely associated with MM risk. Compared to non-users, the HR (95% CI) was 0.60 (CI=0.36-0.98) for &lt;3 tab/wk, 0.33 (0.12-0.92) for 3-&lt;6 tab/wk, and 0.22 (0.03-1.56) for 6-&lt;10 tab/wk. Duration of continuous aspirin use was also inversely associated with MM in men: compared to non-users, the HR (95% CI) was 0.62 (0.38-0.99) for ≤5 years, 0.54 (0.30-0.95) for 6-10 years, and 0.39 (0.12-1.25) for 11-20 years continuous use. Preliminary findings among women were suggestive of an inverse association of regular aspirin use with MM risk, but were not statistically significant. Analyses stratified by duration of use and BMI are ongoing. This prospective analysis offers evidence that regular aspirin use is associated with a diminished risk of MM. Thus, NF-κB dysregulation may contribute to MM etiology as well as to pathogenesis. However, the utility of aspirin for MM chemoprevention requires further clarification.
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 868.
Abstract 87: Differential effects of JNK1 and JNK2 on cell death in hypoxic colon cancer cell lines
Authors: Vasilevskaya Irina A. , Selvakumaran Muthu , Roberts David , O'Dwyer Peter J. 
Published: February 2011

Abstract
BACKGROUND: We previously showed that hypoxic colon cancer cell lines exhibit higher sensitivity to oxaliplatin when SEK1 function is impaired, and greater resistance when MKK7 is down regulated. The MKK7 mutant lines exhibit more profound inhibition of JNK activation than those lacking SEK1, and their effects on the activation of JNK1 and JNK2 differ. The HT29 cells do not die readily by apoptosis under these conditions, and both oxaliplatin and hypoxia induce autophagy in these cells.
PURPOSE: The purpose of this study is to investigate further how modulation of signaling through JNK1 and JNK2 influences cell death pathways in hypoxic HT29 cells treated with oxaliplatin. For that, we employed HT29-derived cell lines stably expressing empty vector (HT.LX) and dominant negative constructs for JNK1 (HTJ1.3) and JNK2 (HTJ2.2).
RESULTS: We observed higher induction and activation of c-Jun in cells with dnJNK1, while introduction of dnJNK2 caused the opposite effect. Resistance to oxaliplatin under hypoxic conditions was also higher in the cell line with lowest c-Jun activation level (IC50 of 2.1 μM for HT.LX, 3 μM for HTJ2.2 and 0.8 μM for HTJ1.3), suggesting a pro-survival role for JNK1 under these conditions. Both oxaliplatin- and hypoxia-induced formation of autophagosomes was reduced significantly in HT29 cells treated with the JNK inhibitor SP600125. We also found differential sensitivity of these cell lines to an inhibitor of autophagy, chloroquine (CQ): HTJ1.3 and HTJ2.2 cell lines were slightly more resistant to CQ under normal conditions, as compared to parental line, but under hypoxia all of the lines demonstrated higher sensitivity to the drug. Notably, in light of the role of JNK1 in activating autophagy, cells with diminished JNK1 activity were the most sensitive to CQ under hypoxia. Moreover, when we treated the cell lines with 5 μM of CQ under hypoxia/reoxygenation, inhibition of autophagy and induction of apoptosis were most significant in dnJNK1-expressing cells. This effect of JNK1 down-regulation is specific to hypoxia, since the constructs do not differ in sensitivity to CQ and oxaliplatin in combination.
CONCLUSIONS: Our data demonstrate the differential effects of JNK1/JNK2 modulation on cell death of hypoxic HT29 cells treated with oxaliplatin or chloroquine, and imply pro-survival function for JNK1 versus JNK2 under these conditions.
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 87.
Abstract 891: Association of genetic polymorphisms of SIPA1 with breast cancer risk and survival among Chinese women
Authors: Qu Shimian , Cai Hui , Long Jirong , Cai Qiuyin , Courtney Regina , Shu Xiao-Ou , Gao Yu-Tang , Zheng Wei 
Published: February 2011

Abstract
Signal-induced proliferation-associated gene 1 (Sipa1), encodes a GTPase-activating protein (GAP), was identified as a candidate host metastasis-regulatory factor in mice. Several epidemiological studies have shown that SIPA1 may play an important role in breast cancer risk and metastasis with inconsistent results. We evaluated functional single nucleotide polymorphisms (SNPs) in SIPA1 in relation to breast cancer risk and survival in Chinese women. Included in the study were 1,134 cases and 1,234 age frequency-matched community controls that participated in the Shanghai Breast Cancer Study, a large scale population-basd case-control study. Breast cancer patients were followed to determine intervals of overall survival and disease-free survival. Functional SNPs were genotyped using TaqMan assays. Additional SNPs in this gene region, both genotyped and imputed from a genome-wide association study, were also included in the analyses. The SIPA1 polymorphisms were not associated with breast cancer risk. We found SIPA1 polymorphisms were associated with breast cancer overall survival. Patients carrying the GA/AA genotypes in the synonymous exonic SNP rs746429 were associated with a marginally significant poor overall survival (HR =1.2, 95% CI, 0.9-1.6) as compared with the common GG genotype. Furthermore, this association was more evident among patients with an early stage cancer (HR =1.4, 95% CI, 1.0-1.9) than those with a late stage cancer (HR=1.2, 95% CI, 0.7-2.1). Patients carrying the AA genotype of rs3741378, a nonsynonymous exonic SNP, were associated with a better overall survival (HR =0.6, 95% CI, 0.4-1.0) as compared to those with the common GG genotype. We found that the SIPA1 polymorphisms were not associated with disease-free survival. Our findings suggested that common SIPA1 genetic polymorphisms may be associated with breast cancer progression.
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 891.
Abstract 916: Functional significance of sulfotransferase 1A1 polymorphisms in the 3’ untranslated region in determination of enzymatic activity
Authors: Yu Xinfeng , Beggs Marjorie L. , Dhakal Ishwori B. , Zhang Xuemei , Edavana Vineetha Koroth , Williams Suzanne , Mercer Kelly E. , Kadlubar Fred F. , Kadlubar Susan 
Published: February 2011

Abstract
SULT1A1 is the most highly expressed hepatic sulfotransferase and is involved in the biotransformation of a wide variety of endo-and xenobiotics. The inter-individual variation of SULT1A1 enzyme activity can markedly influence drug toxicity and/or treatment efficacy in the clinical setting. We and others have examined a common SNP in the coding region of SULT1A1 (Arg213His, SULT1A1*1/2), as well as several SNPs in the proximal promoter that were associated with altered enzymatic activity. However, the SNPs account for only a small proportion of variation of SULT1A1 activity in human populations. In order to identify SNPs that markedly affect SULT1A1 activity, we resequenced the 3’UTR of SULT1A1 in 97 liver samples. Direct sequencing revealed 2 SNPs (902A&gt;G, 973C&gt;T) in the 3’UTR and 1 SNP (1307G&gt;A) in the 3’ flanking region. Interestingly, we found these SNPs are in absolute linkage disequilibrium and are closely associated with SULT1A1 expression and enzymatic activity. To further elucidate the important role of SNPs in 3’UTR, we performed haplotype analysis to predict the collective effects of functional genetic variants in the 3’ UTR regions, the SULT1A1*1/2 polymorphism and copy number variation on SULT1A1 enzymatic activity. Notably, two major haplotypes (ACGG and GTAA) were significantly correlated with SULT1A1 activity, Copy number did not influence on SULT1A1 activity in liver samples. 3’UTR SNPs are in linkage disequilibrium with SULT1A1*1/2 polymorphism, so to examine the effect of the SULT1A1*1/2 polymorphism, we performed haplotype-activity assay in 499 Caucasian and 129 African American subjects. Haplotype and regression analysis both strongly suggest that the 3’UTR SNPs are the pivotal predictor of SULT1A1 activity. MicroInspector predicts 3116C&gt;T influences the binding of miR-631 to SULT1A1 3’UTR. Furthermore, in vitro luciferase reporter assays and overexpression of miRNA mimics and inhibitors indicated that SULT1A1 is a direct target of miR-631 and miR-631 differentially regulates the C and T alleles of rs1042157. The results suggest, for the first time, that allele-specific regulation of SULT1A1 by miR-631 contributes to the activity variation of SULT1A1 in population.
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 916.
Abstract 936: Phytoestrogen level modifies the association of ornithine decarboxylase-polyamine pathway related gene polymorphisms and gastric cancer risk
Authors: Cho Lisa Y. , Yang Jae Jeong , Ko Kwang-Pil , Park Boyoung , Shin Aesun , Gwack Jin , Chang Soung Hoon , Shin Hai-Rim , Yoo Keun-Young , Park Sue K. 
Published: February 2011

Abstract
Objective: We investigated the role of single nucleotide polymorphisms (SNP) ODC-polyamine pathway related genes (ODC1, AMD1, OAZ2, NQO1, NOS2A) for gastric cancer risk. Additionally, we examined whether phytoestrogen levels modify the association of ODC-polyamine pathway SNPs and risk of gastric cancer. Materials and Methods: Twenty-five SNPs in five genes were genotyped in 59 incident gastric cancer cases and 175 matched controls recruited from the Korea Multi-Center Cancer Cohort. Candidate genes were selected based on genotype databases, and genotype assay was performed using Goldengate platform (Illumina). We calculated the unadjusted Wald p-value between each SNP and phytoestrogen level, as well as the false discovery rate (FDR) corrected p-values of the 25 SNPs according to each phytoestrogen biomarker. Unconditional logistic regression model was used to calculate the adjusted odds ratios (OR) and 95% CI for smoking history. Results: There was a significant association for NQO1 (rs1800566, rs1437135) and daidzein, AMD1 (rs1279599, rs7768897, rs811921) and equol, AMD1 (rs1279599, rs7768897, rs811921) and enterolactone (FDR p-value&lt;0.2). Conclusion: Certain phytoestrogens and ODC-polyamine related genes polymorphisms may interact to affect development of gastric cancer. Additional studies are needed to further elucidate the gene-environment interaction for gastric cancer risk.
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 936.