bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2750: Associations between genetic variability in folate metabolism and breast cancer survival
Authors: Das Nandita , Baumgartner Kathy B. , Kerber Richard A. , Rai Shesh N. , Ulrich Cornelia M. , Neuhouser Marian L. , Bernstein Leslie , Tiernan Anne Mc , Ballard-Barbash Rachel , Baumgartner Richard N. 
Published: June 2012

Abstract
Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in folate metabolism that is critical for DNA methylation, synthesis and repair. Since genetic polymorphisms may modify the efficiency of this enzyme, we tested the hypothesis that MTHFR modifies breast cancer (BC) survival using data from the Health, Eating, Activity and Lifestyle (HEAL) Study for 772 incident primary invasive cases (Stage I-IIIA). Over the 5-year follow-up there were 50 women diagnosed with a recurrence and 39 with a new primary. Over 7-years of follow-up, there were 160 deaths; 97 due to BC. In Cox proportional-hazards analysis, carriers of variant alleles of MTHFR polymorphisms, C677T (HR = 0.76, 95% confidence interval [CI]: 0.51, 1.14) and A1298C (HR = 0.66, 95% CI: 0.44, 1.00), had reduced mortality rates, adjusting for ER status and stage. In women with more severe disease who received chemotherapy, the HR was 5.6(95% CI: 2.8-10.9) for those without the T allele, and 4.3(95% CI: 2.1-9.1) for those with it present (p = 0.09) compared to those without the T allele and no chemotherapy treatment (Table 1). No interaction with chemotherapy was observed for A1298C. C677T may modify the association of chemotherapy in predicting BC survival. There is strong linkage disequilibrium between C677T and A1298C (Lewontin's D’ = 0.94) suggesting two different inheritance patterns; however, recombination between them is documented to be rare. These results should be explored further in clinical populations. Study of interactions with other genes in the folate metabolism pathway (BHMT, TS, MTR, MTRR, SHMT) with BC survival is under investigation

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 2750. doi:10.1158/1538-7445.AM2011-2750
Abstract 2767: Genetic variation in obesity-related genes ADBR2, ADBR3, GHRL, HSD11B1, and SHC1 and risk of prostate cancer: A VA case-control study
Authors: Masko Elizabeth M. , Moreira Daniel M. , Banez Lionel L. , Hoyo Cathrine , Grant Delores J. , Calloway Elizabeth E. , Shuler Kathleen H. , Newman Kathryn A. , Gaines Alexis R. , Taylor Loretta A. , Robertson Cary N. , Freedland Stephen J. 
Published: June 2012

Abstract
INTRODUCTION: Single nucleotide polymorphisms (SNPs) are single nucleotide variations that occur within alleles among individuals. It is believed that SNPs may predispose a person to diseases such as obesity or cancer. One study showed that SNPs within genes linked with obesity were also associated with breast cancer risk. As prostate cancer (PC) mortality is linked with obesity, we determined if SNPs within 5 obesity-related genes were also linked to PC risk in a similar manner to the breast cancer study.
METHODS: A total of 53 SNPs were tagged in the genes ADBR2, ADBR3, GHRL, HSD11B1, and SHC1 using the program HAPMAP. DNA collected from 216 subjects (108 incident cases, 108 “healthy” controls) from the Durham VA Hospital were then genotyped for these SNPs. Cases and controls were frequency matched on age and BMI. Logistic regression models were used to determine the risk of obesity (BMI &gt;30 kg/m2) and PC (and high-grade defined as Gleason &gt;7 vs. low-grade/control) for each SNP, adjusting for age and race.
RESULTS: In our study population, 83 men were Caucasian and 133 African American. There was no significant differences in age (p=0.18), race (p=0.96), and BMI (p=0.12) for cases and controls. Among the 53 SNPs genotyped, 5 SNPs in ADRB2, ADRB3, and SHC1 were associated with an increased risk of PC (OR 1.88-2.21; p=0.01-0.04), particularly high-grade disease (OR 2.50-3.26; p=0.0004-0.05). Another 4 SNPs in ADRB2 and HSD11B1 were associated with a decreased risk of PC (p=0.01-0.05). A total of 7 SNPs were associated with an increased risk of obesity (p=0.004-0.02).
CONCLUSION: In this small pilot study, we found 14 of the 53 analyzed single SNPs in genes previously linked with obesity that were associated with PC risk, both positively and negatively at an alpha of &lt;0.05. This is more than the 3 SNPs that would be predicted based upon random chance. Future studies will validate these results in an independent cohort, with the hope of further confirming SNPs that may be used for personalized medicine as well as providing a genetic link between obesity and PC.
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 2767. doi:10.1158/1538-7445.AM2011-2767
Abstract 2776: Prostate cancer and dietary calcium: Effect modification by the vitamin D receptor Cdx-2 polymorphism in the California Collaborative Prostate Cancer Study
Authors: Rowland Glovioell W. , Ingles Sue A. 
Published: June 2012

Abstract
Background: Calcium is classified as a probable cause of prostate cancer by the World Cancer Research Fund. We previously showed that the relationship between dietary calcium intake and prostate cancer risk was modified by a the vitamin D receptor, Cdx-2 polymorphism among African Americans. The high absorption A allele increases calcium absorption and is common among African Americans. The A alleles is less common among Caucasians, who have a lower incidence of prostate cancer compared to African Americans.
Methods: We examined Caucasian and African American prostate cancer cases and controls from the California Collaborative Prostate Cancer Study. Of 1854 cases, 1140 were advanced stage at diagnosis and 714 were localized; 500 were African American and 1354 were Caucasian. Dietary calcium was assessed from a 74-item modified Block food frequency questionnaire. The VDR Cdx-2 genotype was measured by TaqMan assay. Main effects of genotype and of dietary calcium, and diet-gene interactions were estimated using conditional logistic regression, adjusting for study site (Northern/Southern California), Hispanic ancestry, socio-economic status, age, and family history of prostate cancer.
Results: Analysis of race-specific quartiles of calcium intake showed that intake of more than 680 mg/day (above the median for African Americans or above the first quartile for whites) was associated with increased prostate cancer risk (odds ratio 1.48, 95% confidence interval 1.25 – 1.77). The effect of calcium intake on risk of advanced (but not localized) prostate cancer was modified by the VDR Cdx-2 genotype for both African Americans and whites. High calcium intake (&gt;680 mg/day) was significantly associated with increased risk only among those with the VDR Cdx-2 GG low calcium absorption genotype (OR=1.90, 95% CI 1.40 – 2.57). High absorption genotypes (GA and AA) were associated with increased risk only among those consuming less than 680 mg/day of calcium. Odds ratios were 1.24 (95% CI: 0.82 – 1.87) for genotype GA and 1.69 (95% CI: 1.05 – 2.74) for genotype AA compared to genotype GG.
Conclusions: Our findings suggest that genetically-determined high calcium absorption among African Americans could contribute to racial ethnic disparities in prostate cancer incidence.
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 2776. doi:10.1158/1538-7445.AM2011-2776
Abstract 2796: Suppressive effect of DNA hypomethylation on gastric carcinogenesis
Authors: Tomita Hiroyuki , Hirata Akihiro , Yamada Yasuhiro , Hara Akira 
Published: June 2012

Abstract
Global DNA hypomethylation and concomitant site-specific gene hypermethylation are among the most common molecular alterations in human neoplasia. Although site-specific DNA hypermethylation has been shown to be associated with the development of various tumors accompanied by transcriptional silencing of target genes, the functional significance of global DNA hypomethylation in tumorigenesis remains unclear. Previous studies have revealed that a genetic reduction of the DNA methylation levels leads to opposing effects on tumor development, depending on the tumor cell type and the stage of tumorigenesis. In the present study, we investigated the effect of DNA hypomethylation on gastric carcinogenesis in mice. DNA methyltransferase 1 (Dnmt1) hypomorphic mice, which showed that Dnmt1 hypomorphic alleles induced global DNA hypomethylation in the gastric mucosa, were used in this study. The genetic reduction of DNA methylation levels suppressed the incidence, number and size of gastric tumors in two different mouse models for gastric tumorigenesis: the N-methyl-N-nitrosourea (MNU)-induced model and the Apc (Min/+) mouse model that spontaneously develops gastric tumors with aging. Histological analyses revealed DNA hypomethylation to completely inhibit the development of invasive gastric tumors. In the MNU model, DNA hypomethylation reduced the persistent increase in the cell proliferative activity in the non-cancerous gastric mucosa exposed to MNU. However, the aberrant site-specific methylations were not found in MNU-induced mouse gastric tumors unlike in the case of human gastric tumors, thus indicating that the pattern of the site-specific aberrant methylations in mouse gastric tumors is distinctly different from that in human gastric cancers. Taken together, these findings indicate that the reduction of DNA methylation levels suppresses gastric carcinogenesis and suggest that DNA methylation is closely associated with gastric tumorigenesis.
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 2796. doi:10.1158/1538-7445.AM2011-2796
Abstract 2802: Evaluation of metabolic changes induced by loss of extracellular matrix attachment using 13C Flux analysis
Authors: Grassian Alexandra R. , Metallo Christian M. , Stephanopoulos Gregory , Brugge Joan S. 
Published: June 2012

Abstract
Recent studies from our laboratory revealed the importance of extracellular matrix in regulating cellular metabolism. Briefly, detachment of mammary epithelial cells from extracellular matrix (ECM) causes a significant reduction in ATP levels due to reduced glucose uptake. ErbB2 overexpression restores ATP levels by maintaining glucose uptake in ECM detached cells. The loss of glucose uptake also increases ROS levels, and unexpectedly, antioxidants rescue the metabolic defect, by relieving an ROS-mediated inhibition of ATP generation by fatty acid oxidation.
These findings suggest that ECM contact is an important regulator of cellular metabolism, and that tumor cells may be able to circumvent the requirement for ECM-attachment via overexpression of certain oncogenes. We used 13C metabolic flux analysis to more thoroughly investigate the metabolic changes induced by ECM detachment and ErbB2 overexpression in the immortalized, non-transformed human mammary epithelial cell-line, MCF10A. Our results show that matrix-detachment leads to a dramatic decrease in nutrient uptake, including glucose, glutamine and pyruvate. Interestingly, we found that there is a substantial decrease in glucose flux to the tricarboxylic acid (TCA) cycle; this is due both to the decreased glucose uptake, as well as an increased diversion of glucose towards lactate production (aerobic glycolysis). ErbB2 overexpression partially reverses these defects in the ECM-detached cells. Glucose entrance to the TCA cycle is regulated by pyruvate dehydrogenase (PDH), which are in turn negatively regulated by PDH kinases (PDK1-4). Interesting, we find a dramatic increase in PDK4 levels in ECM-detached cells, which is partially prevented by ErbB2 overexpression. While PI3K signaling has previously been shown to negatively regulate PDK4 expression, we find that Mek, but not PI3K, regulates PDK4 levels in our system. Ongoing studies will further examine the regulation of glucose and pyruvate metabolism by ErbB2 and ECM. These analyses will allow us to identify unpredictable nodes of metabolic regulation by ErbB2 and ECM and may provide rational treatment approaches for targeting tumor metabolism.
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 2802. doi:10.1158/1538-7445.AM2011-2802
Abstract 2815: Urine TMPRSS2:ERG for prostate cancer risk stratification in men with elevated serum PSA
Authors: Tomlins Scott A. , Aubin Sheila , Siddiqui Javed , Lonigro Robert , Sefton-Miller Laurie , Miick Siobhan , Williamsen Sarah , Hodge Petrea , Meinke Jessica , Blase Amy , Penabella Yvonne , Day John , Rhodes Daniel R. , Sakamoto Kyoko , Silberstein Jonathan , Fradet Yves , Amberson James B. , Meyers Stephanie , Rittenhouse Harry , Wei John T. , Groskopf Jack , Chinnaiyan Arul M. 
Published: June 2012

Abstract
Background: Over 1,000,000 men undergo prostate biopsy each year in the U.S., most for “elevated” serum PSA. Given the lack of sensitivity and specificity, and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. We evaluated urine expression of TMPRSS2:ERG, a gene fusion occurring in 50% of prostate cancers, for risk-stratifying men presenting for biopsy.
Methods: TMPRSS2:ERG was measured by a clinical grade, transcription-mediated-amplification assay in prospectively collected whole-urine from 1,094 men undergoing biopsy at 10 academic and community clinics.
Findings: Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high prostatectomy Gleason score and upgrading at prostatectomy. TMPRSS2:ERG in combination with urine PCA3, improved the multivariate PCPT risk calculator performance for predicting cancer on biopsy (AUC in test set, 0.79 vs. 0.64, p&lt;0.001). Using a three-class stratification, men in the highest and lowest TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer (69% vs. 21%, p&lt;0.001), clinically significant cancer by Epstein criteria (61% vs. 15%, p&lt;0.001) and high grade cancer (40% vs. 7%, p&lt;0.001) on biopsy.
Interpretation: Urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer and clinically relevant cancer on biopsy.
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 2815. doi:10.1158/1538-7445.AM2011-2815
Abstract 282: PAI-2 promotes astrocyte differentiation from glial precursor cells via enhancing STAT3 signaling
Authors: Li Zaibo , Proschel Chris , Noble Mark 
Published: June 2012

Abstract
Regulation of the generation of astrocytes and oligodendrocytes is a key process in the development of normal central nervous system (CNS) and glial tumors including oligodendrocytoma, astrocytoma and glioblastoma. Glial cell differentiation occurs in two sequentially generated glial progenitor cells, the glial-restricted precursor (GRP) cells and the oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. The molecular mechanisms of cell generation in these precursor cells are only incompletely understood.
In this study, PAI-2 (Plasminogen Activator inhibitor-2) was identified to be upregulated during glial cell differentiation. Ectopic expression of PAI-2 induced GRP cells to differentiate into astrocytes and inhibited their proliferation. In contrast, suppression of endogenous PAI-2 by small interfering RNA in GRP cells promoted cell proliferation and inhibited their ability to differentiate into astrocytes. More interestingly, we observed a higher Rb protein level and a correlated lower E2F1 transcriptional activity during glial differentiation due to increased PAI-2 protein level. In consistent with these findings, ectopic expression of PAI-2 indeed stabilized Rb protein.
We also found that PAI-2 upregulated GFAP expression in glial progenitor cells, an antigenic marker for astrocytes. Astrocytogenesis is controlled by two different signaling, the IL-6, LIF or CNTF-induced STAT3 pathway and the BMP-4-induced SMAD1 pathway. Interestingly, PAI-2 significantly enhanced CNTF, LIF or IL-6-induced GFAP expression as illustrated by both reporter assay and immunostaining, but not BMP4-induced GFAP expression. Furthermore, We demonstrated that PAI-2 could enhance CNTF-induced STAT3 phosphorylation and the complex formation between STAT3 and p300. It has also been reported that Rb could enhance the transcriptional activity of several transcription factors via enhancing p300/CBP activity by releasing them from some inhibitory transcriptional repressors such as EID1 (E1A-like inhibitor of differentiation). Indeed, suppression of Rb by small interfering RNA or overexpression of EID1 abrogated PAI-2's effect on STAT3 activity. Also, suppression of endogenous EID1 by small interfering RNA could further enhance PAI-2's effect. Finally, we illustrated Glial precursor cells from PAI-2 knockout mice are less responsive to CNTF and IL-6 than wild-type cells. Based on these data, we concluded that PAI-2 promotes glial progenitor cells to differentiate into astrocytes via stabilizing Rb, which can abrogate EID's inhibitory effect, and then enhancing STAT3 transcriptional activity induced by CNTF or IL-6.
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 282. doi:10.1158/1538-7445.AM2011-282
Abstract 2844: Systems biology analysis of tumor and stromal genes in different metastatic microenvironments
Authors: Sevenich Lisa , Mason Steve , Rapaport Franck , Massague Joan , Leslie Christina , Joyce Johanna 
Published: June 2012

Abstract
Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and colonize these foreign tissue environments. Each of these processes involves rate-limiting steps that are influenced by stromal cells of the tumor microenvironment.
Our goal is to dissect organ-site specific signatures of tumor-stroma interactions in metastasis. In this approach we devised an experimental and computational strategy to enable the simultaneous analysis of tumor and stromal genes in lesions from three distinct metastatic microenvironments. We took advantage of a recently developed system where organ-site specific metastatic variants were selected in vivo from a parental breast cancer cell line and home to the brain, the bone and the lung in xenografted animals. An important technological advance is the HuMu ProtIn (Protease/Inhibitor) array that was designed to distinguish between human (Hu) and mouse (Mu) gene expression. By using the HuMu ProtIn array we can determine whether differentially expressed proteases and endogenous protease inhibitors are of tumor (human) or stromal (mouse) origin. This allowed us to simultaneously capture the tumor and stromal contributions in intact tumors.
After profiling of brain, bone and lung metastases at different stages of development we employed knock-down and knock-out strategies to experimentally validate the biological relevance of predicted candidate genes including the serine protease Htra1 and the cysteine protease cathepsin S. Cathepsin S represents an interesting example as the expression of tumor-derived cathepsin S decreases during the progression from early to late brain metastasis, whereas the expression of stromal-derived cathepsin S increases over time. Targeting either tumor- or stromal derived cathepsin S did not significantly prolong tumor-free survival, however the combined ablation of tumor- and stromal derived cathepsin S resulted in a dramatic impairment of brain metastasis formation.
This study emphasizes the need for a better understanding of the complex reciprocal interactions between tumor cells and stromal cells with the ultimate goal to improve the predictive value of prognostic evaluation and to develop combination therapies that target the tumor along with its microenvironment.
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 2844. doi:10.1158/1538-7445.AM2011-2844
Abstract 2861: The C/EBPbeta isoform, liver-inhibitory protein (LIP), induces autophagy in breast cancer cell lines
Authors: Abreu Maria M. , Sealy Linda 
Published: June 2012

Abstract
Autophagy is an evolutionarily conserved cellular process involving the bulk degradation of cellular components in the cytoplasm via the lysosomal degradation pathway. Autophagy manifests a protective role in stressful conditions such as nutrient or growth factor depletion; however, extensive degradation of regulatory molecules or organelles essential for survival can lead to the demise of the cell, or autophagy-mediated cell death. The role of autophagy in cancer is controversial with roles in both tumor suppression and tumor promotion proposed.
Here we report that an isoform of the C/EBPbeta transcription factor, liver-enriched inhibitory protein (LIP), stimulates autophagy and induces cell death in human breast cancer cells. LIP overexpression is incompatible with cell growth and when cell cycle analysis was performed, a DNA profile of cells undergoing apoptosis was not observed. Instead, LIP expressing cells appeared to have large autophagic vesicles when examined via electron microscopy. Autophagy was further assessed in LIP expressing cells by monitoring the development of acidic vesicular organelles and conversion of LC3 from the cytoplasmic form to the membrane-bound form. Our work shows that C/EBPbeta isoform, LIP, is another member of the group of transcription factors, including E2F1 and p53, which are capable of playing a role in autophagy. Knowledge of the mechanisms controlling autophagy and identifying new agents capable of inducing cell death has vast potential to improve cancer therapeutics by enabling effective induction of an alternative death pathway, especially in, but not limited to, tumor cells that are resistant to 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 2861. doi:10.1158/1538-7445.AM2011-2861