bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3741: Identification of differentially expressed genes in breast tumors from African American compared with Caucasian women
Authors: Ellsworth Rachel E. , Field Lori A. , Deyarmin Brenda , Love Brad , Hooke Jeffrey , Shriver Craig 
Published: June 2012

Abstract
Background: Breast tumors from African American women (AAW) have less favorable pathological characteristics and higher mortality rates than Caucasian women. While socioeconomic status may influence prognosis, biological factors are also likely to contribute to tumor behavior.
Methods: Patients treated within an equal-access military medical center were matched by age, grade and ER status. Tumors were subjected to laser microdissection and RNA hybridized to HG U133A 2.0 microarrays. Data was analyzed using Partek Genomics Suite using a cutoff of P&lt;0.001, 1.5-fold change. Microarray results were validated by qRT-PCR.
Results: Twenty-six pairs of matched tumor samples were identified. Clinico-pathological factors did not differ significantly for age at diagnosis, tumor size or stage, lymph node, hormone receptor, or HER2 status. Mortality was similar between the two groups. One putative and nineteen known genes were differentially expressed between populations with five genes expressed at higher and 15 genes at lower levels in tumors from AAW; hierarchical clustering classified 23/26 AAW and 26/26 CW correctly. Differential expression was validated (P&lt;0.001) for PSPHL (higher in AAW) and LTF and PSD3 (lower in AAW).
Conclusions: Despite matching of tumors by pathological characteristics and provision of medical care in an equal-access health care system, a molecular signature differentiating AAW from CW tumors was detected, supporting a model in which aggressive tumor phenotypes are driven by molecular differences within the tumors. These differentially expressed genes are involved in immune response, cell cycle and metastasis and thus may contribute to the poor outcome in AAW.
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 3741. doi:10.1158/1538-7445.AM2011-3741
Abstract 3742: Gene-environment Interactions in esophageal adenocarcinoma risk: A case-only analysis
Authors: Zhai Rihong , Zhao Yang , Liu Geoffrey , Ter-Minassian Monica , Wang Zhaoxi , Wu I-Chen , Su Li , Asomaning Kofi , Chen Feng , Kulke Matthew H. , Lin Xihong , Heist Rebecca S. , Wain John C. , Christiani David C. 
Published: June 2012

Abstract
The incidence of esophageal adenocarcinoma (EA) has increased approximately 500% in Western countries over the last four decades. The rapidly increasing incidence and sporadically development feature of EA suggest that gene-environment (G-E) interactions dominate the etiology. However, how G-E contributes to EA carcinogenesis is still poorly understood. We used a case-only approach to test the effect of G-E interactions in the occurrence of EA. 1330 functional and/or tagging SNPs selected from 354 cancer-associated genes were genotyped in 335 Caucasian EA cases. G-E (gastroesophageal reflux symptoms, GERD; BMI; and smoking) interactions were assessed by a two-step approach. First, we applied random forest (RF) to screen for important SNPs that had main effects as well as interaction effects. Second, we used case-only logistic regression (LR) models to estimate the G-E interaction effect, adjusting for covariates and false-discovery rate (FDR). RF analyses identified three sets of SNPs (94 SNPs-GERD, 38 SNPs-smoking, and 44 SNPs-BMI, respectively) that had the highest importance scores and lowest classification error rates. Further case-only LR analysis revealed that multiple interaction markers were significantly associated with EA risk: GERD*rs2237051 of EGF(OR = 1.39, P = 3.50E-07), GERD*rs2440 of XRCC5 (OR = 1,80, P = 0.0008), GERD*rs2237051*rs2440 (OR = 1.85, P = 0.004), smoking*rs10842514 of KRAS (OR = 0.85, P = 0.012), BMI*rs2305742 of IL12RB1 (OR = 0.84, P = 0.003), BMI*rs11568820 of VDR (OR = 0.97, P = 0.0005), BMI*rs11244142 of ABL1 (OR = 1.47, P = 2.09E-05), BMI*rs2800975 of XPA*rs743572 of CYP17A (OR = 3.62, P = 0.0009), and BMI*rs11244142*rs20547 of IL13 (OR = 1.89, P = 0.023). These results indicate that genetic variability may contribute to EA development through interactions with environmental factors. Our data also suggest that G-E interactions may be G- and E-specific in modulating the risk of EA.
Supported by grants: NIH grants CA92824, CA74386, CA90578, and CA119650); Flight Attendant Medical Research Institute (FAMRI) grant 062459_YCSA; the Kevin Jackson Memorial Fund and Alan Brown Chair of Molecular Genomics.
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 3742. doi:10.1158/1538-7445.AM2011-3742
Abstract 3755: Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk
Authors: Huang Wen-Yi , Su Joseph L. , Hayes Richard B. , Moore Lee E. , Katki Hormuzd A. , Berndt Sonja I. , Weissfeld Joel L. , Yegnasubramanian Srinivasan , Purdue Mark P. 
Published: June 2012

Abstract
Background: Systematic genome-wide (global) reductions of methylated cytosine levels have been observed in most cancer tissues, including colorectal cancer, and are hypothesized to contribute to carcinogenesis through genomic instability and protooncogene activation. Recently, genomic DNA hypomethylation has been measured in peripheral blood leukocytes and associated with colorectal tumors. However, as these studies used post-diagnostic specimens, it is possible that the observed findings reflect disease- and/or treatment-induced effects on leukocyte DNA methylation.
Methods: Using prospectively collected blood specimens and questionnaire data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we studied genomic leukocyte DNA methylation status in relation to subsequent colorectal cancer risk in a nested case-control study of 370 cases and 493 controls with no cancer diagnosis prior to the blood draw. Genomic leukocyte DNA methylation status was determined by an HPLC/Tandem Mass Spectrometry method and expressed as the relative amount of methyl-cytosine to total cytosine residues, or %5-mC. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression models, adjusting for age, gender, race, time since initial sigmoidoscopy screening, and year of randomization. Inclusion of other suspected colorectal cancer risk factors in the models did not materially change the results.
Results: We observed a relatively narrow range of genomic leukocyte DNA methylation levels among cases and controls, with %5-mC ranging from 3.57 to 4.60 (median = 4.03, standard deviation = 0.19). Categorizing subjects by quartiles of %5-mC content in controls, using the lowest quartile as the reference category (Q1), we observed no trend in risk with adjusted ORs (95% CIs) for Q2, 1.44 (1.01-2.08); Q3, 1.06 (0.75-1.51); and Q4, 1.01 (0.70-1.47) (P-trend = 0.49). Dichotomizing subjects by median of %5-mC in controls with the lower %5-mC group as the reference, we found a borderline-significantly decreased risk for subjects with %5-mC above the median (OR = 0.81, CI = 0.61-1.06), particularly among subjects whose natural folate intake levels were above the median (OR = 0.60, CI = 0.39-0.95; P-interaction = 0.06).
Conclusion: Preliminary findings from our study, to our knowledge the first prospective investigation of DNA methylation and colorectal cancer, show no clear dose-dependent association between genomic leukocyte DNA methylation status and subsequent cancer risk.
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 3755. doi:10.1158/1538-7445.AM2011-3755
Abstract 3759: Meat consumption, ornithine decarboxylase gene polymorphism, and outcomes after colorectal cancer diagnosis
Authors: Lin Bruce S. , Zell Jason A. , Ziogas Argyrios , Anton-Culver Hoda 
Published: June 2012

Abstract
BACKGROUND. Arginine, and meat consumption (i.e., the primary dietary source of arginine) have been implicated in colorectal cancer (CRC) progression via polyamine-dependent processes. Genetic polymorphism in the polyamine-regulatory gene ornithine decarboxylase-1 (ODC1) has been shown to be prognostic for survival after CRC diagnosis. Here we examined the joint effects of meat consumption and ODC1 polymorphism on CRC-specific mortality among CRC cases.
METHODS. The study included 329 incident stage I-III CRC cases from the population-based UC Irvine Gene-Environment Study of Familial CRC (diagnosed 1994-1996 with follow-up through March 2008). Genotyping of the ODC1 (National Center for Biotechnology Information SNP database ID rs2302615) +316 SNP was conducted using oligonucleotide primers designed to amplify a 172-bp fragment containing the polymorphic base at +316 (Applied Biosystems, Foster City, CA). Meat intake (frequency and serving size) was ascertained via questionnaires administered at baseline (cohort entry), where patients were asked to report their usual eating habits during the one year prior to CRC diagnosis. Multivariate CRC-specific survival analyses were stratified by TNM stage, and adjusted for age, gender, race/ethnicity, family history, tumor subsite within the colorectum, histology, treatment with surgery, radiation, chemotherapy, weekly meat consumption, ODC1 genotype, and a term representing the interaction of meat consumption and ODC1 genotype. The primary outcome was to assess the interaction of meat consumption and ODC1 genotype (GG vs. GA/AA) on CRC-specific mortality.
RESULTS. ODC1 genotype distribution was 51% GG, 49% GA/AA). Median meat consumption was 6.95 and 7.40 servings per week in ODC1 GG group and GA/AA group respectively (P =0.31). In the multivariate model, a statistically significant interaction between ODC1 genotype, meat consumption, and CRC-specific mortality was observed, such that increasing levels of meat consumption were associated with higher CRC-specific mortality among ODC1 GA/AA compared to GG cases, adjusted colorectal cancer-specific survival hazards ratio, 12.75; 95% confidence interval, 2.71-60.12; P =0.001 (unadjusted HR 2.29; 95% CI 1.24-4.23; P =0.008). There was a strong interaction between meat consumption and ODC1 genotype, P-int =0.01.
CONCLUSIONS. Among CRC cases with ODC1 GA/AA genotypes, higher levels of meat consumption are associated with poor survival outcomes. These data provide further evidence that polyamine metabolism, and its modulation by specific dietary factors, have relevance to CRC outcomes.
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 3759. doi:10.1158/1538-7445.AM2011-3759
Abstract 377: Multifunctional magnetic nanoparticles for theranostic applications
Authors: Yallapu Murali M. , Othman Shadi F. , Curtis Evan T. , Gupta Brij K. , Jaggi Meena , Chauhan Subhash C. 
Published: June 2012

Abstract
Nanoparticle technology address efficacy of cancer chemotherapy and diagnosis which can be potentially used for image guided drug delivery. Herein, we have developed a multi-layer approach for the synthesis of water-dispersible iron oxide theranostic nanoparticles for drug delivery (therapy) and magnetic resonance imaging (MRI) (diagnostic) applications. For this novel approach, iron oxide core nanoparticles were prepared by precipitation of iron salts in the presence of ammonia and coated with beta-cyclodextrin and pluronic polymer (F127). This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in beta-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and beta-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Curcumin, a cancer preventive and anti-cancer drug, loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects of this formulation were verified by examining ultra structural changes and molecular effects in cancer cells. Interestingly, F127250-CUR formulation also exhibited good haemo-compatibility. In conclusion, our data suggest that the F127250-CUR formulation can be effectively used for the delivery of anti-cancer drug drugs and cancer imaging and its potential clinical application.
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 377. doi:10.1158/1538-7445.AM2011-377
Abstract 3778: Induction of autophagy and elimination of cancer stem-like cell in glioblastoma multiforme cells by a Magnolia officinalis active component honokiol
Authors: Yao Chih-Jung , Hong Chuang-Ye , Shih Ping-Hsiao , Yeh Chi-Tai , Chen Ruei-Ming , Chuang Shuang-En , Lin Pei-Chun , Yi Tsu-Yi , Lai Gi-Ming 
Published: June 2012

Abstract
The anticancer effects of honokiol, an active component isolated from Chinese traditional herb Magnolia officinalis, had been noticed in recent decade. It had been reported to induce apoptosis, anti-agiogenesis and chemo/radio-sensitization on cancer cells. However, its effects on autophagy induction and cancer stem cell elimination have not yet been investigated. To more evaluate the potential of honokiol in cancer therapy, we explored its effects on these two critical events in glioblastoma multiforme (GBM) DBTRG-05MG cells. The honokiol-induced autophagy was evidenced by the time and dose-dependent increase of LC3-II in treated cells. During this autophagy induction, the phosphorylated AMP-dependent kinase alpha was dose-dependently increased in accompany with the decrease of phosphorylated mTOR protein level. In addition, the phosphorylated p38 was also markedly increased parallel with the elevation of LC3-II. Further investigation on the role of this MAPK p38 pathway in honokiol-induced autophagy is ongoing. In accordance with the growth inhibition and massive cell death induced by high dose of honokiol (50 μM), the phsphorylated Akt and Rb were dramatically suppressed in treated cells. As it is suggested that autophagy is a protective response of cancer cell to environmental stress, an autophagy inhibitor hydroxychloroquine was therefore co-administrated to enhance the effects of honokiol against GBM cells. Significantly, hydroxychloroquine augmented the honokiol-induced cell death, indicating the crucial role of autophagy in honokiol-induced anticancer effects. Moreover, honokiol appeared to have effects on the elimination of cancer stem-like cells. By UV laser-equipped flow cytometer, a small percentage of cancer stem-like side population (SP) cells was detected and sorted from another GBM cell line (GBM 8401). The expressions of stemness genes such as CD133, nestin, Oct4, NOTCH3, IHH and SMO in SP cells were much higher than those in non-SP cells. Treatment with honokiol (5 μM) for 48h decreased the percentage of GBM 8401 SP cells from 1.5% down to 0.2%. These results suggested the potential role of honokiol in GBM treatment.
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 3778. doi:10.1158/1538-7445.AM2011-3778
Abstract 3795: Mitochondrial complex I modulation regulates autophagy and breast cancer progression
Authors: Santidrian Antonio Fernandez , Seo Byoung B. , Matsuno-Yagi Akemi , Yagi Takao , Felding-Habermann Brunhilde 
Published: June 2012

Abstract
Tumor cells express altered metabolic activities often linked to mitochondrial dysfunction. Such mitochondrial defects can inhibit oxidative phosphorylation, change the cellular redox state (NAD+/NADH), increase production of reactive oxygen species (ROS), and cause DNA damage that further supports tumorigenesis and a metastatic phenotype.
Our study identified mitochondrial complex I (NADH dehydrogenase) as a modulator of tumorigenesis and metastatic progression in breast cancer. We used NDI1, the NADH dehydrogenase from yeast, to augment complex I activity in metastatic human breast cancer cells. The NDI1 protein is known to integrate into the inner mitochondrial membrane of mammalian cells, function as NADH dehydrogenase, pass electrons into the respiratory chain, and thereby fully augment intrinsic complex I activity. Thus, NDI1 identifies critical involvement of complex I NADH dehydrogenase activity in cellular functions that are altered upon its expression. We investigated a panel of aggressive human breast cancer cell lines, including MDA-MB 231, and found that augmentation of NADH dehydrogenase activity through NDI1 resulted in an enhanced NAD+/NADH ratio and inhibition of ROS production. Most importantly, NDI1 expression inhibited metastasis and tumor growth in the mammary fad pad of immune deficient mice, seen by non-invasive imaging and histology. The same effects were achieved by treatment with NAD precursors, demonstrating that normalization of the NAD+/NADH ratio is critical for inhibition of breast cancer progression. We found that the underlying mechanism is based on activation of PTEN, inhibition of the AKT/mTOR survival pathway, and stimulation of autophagy. Autophagy is responsible for NDI1-mediated inhibition of breast cancer progression, as knock-down of ATG5 reversed the anti-metastatic effect of NDI1. Our results demonstrate that tumorigenesis and metastasis in breast cancer are critically influenced by mitochondrial complex I activity. We show that augmentation of tumor cell complex I function can interfere with tumor formation and breast cancer spreading through modulating the NAD+/NADH ratio. Thus, normalization of complex I function appears as a promising new target for prevention and treatment of breast progression.
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 3795. doi:10.1158/1538-7445.AM2011-3795
Abstract 3796: Inhibition of mitochondrial respiration synergizes with tyrosine kinase inhibitors to eliminate Bcr-Abl+ leukemia
Authors: Alvarez-Calderon Francesca , Gregory Mark A. , DeGregori James 
Published: June 2012

Abstract
Bcr-Abl kinase inhibitors are the standard therapy for chronic myelogenous leukemia (CML). While effective in controlling disease in chronic phase, these inhibitors often fail to completely eliminate Bcr-Abl+ CML cells and also fail to achieve durable remissions for advanced CML and Bcr-Abl+ acute lymphoblastic leukemias (ALL). Our lab employed a large-scale synthetic lethal shRNA screen to identify genes involved in CML survival upon treatment with the Bcr-Abl kinase inhibitor imatinib (IM) [Cancer Cell. 2010;18(1):74-87]. This screen identified several genes involved in energy utilization including a component of pyruvate dehydrogenase, dihydrolipoyllysine-residue acetyltransferase. This target was identified by two independent shRNAs, each underrepresented over 22 fold in treated cells compared to untreated. CML proliferation depends on Bcr-Abl-driven glycolysis for energy production. Upon IM treatment, I hypothesized that these cells are forced to rely on other sources of energy including the TCA cycle and mitochondrial respiration, and that targeting alternative energy production pathways will enhance IM-mediated elimination of CML cells. Thus, I predicted that inhibition of mitochondrial respiration by knockdown or pharmacologic inhibition would cooperate with tyrosine kinase inhibitors to eliminate Bcr-Abl+ leukemias. My experiments have shown that knocking down pyruvate dehydrogenase in human blast crisis Bcr-Abl+ CML cells (K562) greatly sensitizes cells to IM in vitro. Conversely, supplementing the cell culture media with increasing concentrations of methyl-pyruvate protects K562 cells from IM treatment. Moreover, I find that the mitochondrial ATP-synthase inhibitor Oligomycin A also synergizes with IM to kill CML cells in vitro. In addition, inhibition of mitochondrial respiration with Oligomycin A enhances elimination of Bcr-Abl+ cells by a Bcr-Abl tyrosine kinase inhibitor in vivo and prolongs disease-free survival in a mouse model of Bcr-Abl+ B-ALL. The drug doses of Oligomycin A used are over 100-fold below the LD50, and have no apparent adverse effects on these mice. Targeting mitochondrial metabolism as an adjuvant drug therapy may prevent the survival of residual Bcr-Abl+ CML cells upon tyrosine kinase inhibitor treatment.
*This project is supported in part by pre-doctoral fellowship number F31CA157166 from the National Cancer Institute.
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 3796. doi:10.1158/1538-7445.AM2011-3796
Abstract 3798: P53R2 regulates oxidative phosphorylation complexII and III in keeping integrity of mitochondrial function
Authors: Xue LiJun , Kuo Mei-Ling , Liu Xiyong , Chen Linling , Zhou Bingsen , Yen Yun 
Published: June 2012

Abstract
It has been reported that there is a direct correlation between severe muscle mitochondrial DNA depletion and functionally important mutations in p53R2 in a number of children with mitochondrial depletion syndrome. However, there is no clear evidence how p53R2 involves in the regulation on mitochondrial function. Our current study demonstrated that p53R2 knock-down MCF7 and IMR90 cells displayed low expression level of core proteins in oxidative phosphorylation (OXPHOS) complex II, III, but not complex I, IV or V. Correspondently, activity of complex II and ATP quantity from p53R2-knockdown cells decreased significantly comparing to control cells expressing non-silencing short-hairpin RNA. Moreover, mitochondrial superoxide level increased in p53R2-knockdown cells, which was consistent with the notion that dysfunction of OXPHOS complex II and/or III generated toxic reactive oxygen species in mitochondria. The increased superoxide was not due to SOD2 degradation, since SOD2 expression level was unchanged in IMR90 and MCF7 cells following knockdown of p53R2. These results indicate that down-regulation of p53R2 reduces OXPHOS complex II and III protein expression and correspondent activity. The compromised complex II and III in electron transport chains thus result in premature electron leakage to oxygen to form superoxide in the mitochondria. These observations suggest that p53R2 might protect mitochondria through maintaining integrity of electron transport chains coupling with oxidative phosphorylation.
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 3798. doi:10.1158/1538-7445.AM2011-3798