bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2837: Diverse associations between ESR1 polymorphisms and breast cancer development and progression
Authors: DING Shian-Ling , Yu Jyh-Cherng , Chen Shou-Tung , Chen Shou-Tung , Hsu Giu-Cheng , Wu Pei-Ei , Shen Chen-Yang 
Published: February 2011

Abstract
Purpose: To test the hypothesis that polymorphisms of ESR1, encoding estrogen receptor α (ERα), are associated with susceptibility, clinical phenotype, and progression of breast cancer.
Patients and Methods: A case-control study was performed on 940 patients with incident breast cancer and 1547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNPs) tagging all major polymorphisms of this gene were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility, and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression.
Results. Three SNPs, located in one cluster in intron 1, were found to be important and the variant alleles showed a significant association with a decreased breast cancer risk and, coincidently, with low ERα expression in tumors. The tumorigenic contribution of these intron-1 SNPs was more obvious in combination with reproductive risk factors (p for interaction&lt;0.05). Interestingly, the same SNPs showed a significant correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the five-year survival rate of all patients, but had opposite effects in ERα-negative and ERα-positive early-stage patients.
Conclusions: Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERα in these two populations.
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 2837.
Abstract 284: FGFR2 is required for growth and survival in a rare subset of FGFR2 amplified colorectal cancer
Authors: Mathur Anjili , Davis Lenora , Bacco Alessandra Di , Gazdar Adi , Lutterbach Bart 
Published: February 2011

Abstract
FGFR2 amplification has been reported in subsets of gastric cancer and breast cancer. We describe FGFR2 amplification in a cell line derived from a colorectal carcinoma arising in a young patient with ulcerative colitis. The cell line has features of endocrine differentiation, representing a rare (&lt; 1%) subset of colorectal cancer. FGFR2 amplification in this cell line results in an overexpressed and highly activated FGFR2 kinase. The FGFR selective inhibitor PD173074 blocked FGFR2 phosphorylation and inhibited Erk, Akt, and S6 ribosomal protein phosphorylation. FGFR2 inhibition resulted in profound cell death as measured by robust accumulation of cells in subG1 by flow cytometry and PARP cleavage by western analysis. A structurally unrelated FGFR2 inhibitor, MK2461, also caused cell death and inhibited downstream signaling pathways. RTK arrays revealed coactivation of EGFR family kinases, and a functional role for these kinases is being investigated. Interestingly, an FGFR2 isoform in this cell line migrated at 160kD, in contrast to the 140kD isoform observed in SNU16 and other cell lines. However, C-terminal FGFR2 antibodies did not react with the 160kD FGFR2 isoform, suggesting that it has a C-terminal deletion similar to the FGFR2 isoform in OCUM2M and KatoIII cell lines. We are currently defining the frequency of FGFR2 overexpression and activation in colon cancer tissue microarrays. The strong growth inhibition and induction of cell death observed in vitro suggests that colorectal cancer tumor cells harboring FGFR2 amplification / activation may show similar response to FGFR inhibitor therapy.
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 284.
Abstract 2841: A SNP in the 3′-UTR of the MDMX gene is strongly correlated with decreased overall and disease-free survival in ovarian carcinoma patients in an estrogen-receptor-dependent manner
Authors: Boehnke Anja , Wynendale Jessica , Lambertz Irina , Wolf Anja , Hammer Stefanie , Gradhand Elise , Balschun Katharina , Hauptmann Steffen , Marine Jean-Christophe , Bartel Frank 
Published: February 2011

Abstract
The tumor suppressor p53 is inactivated in the vast majority of cancers, either by mutations of the p53 gene itself or by alterations of p53-regulating factors. The MDM2 homologue, MDMX, is another critical negative regulator of p53. Only a few data exist so far, demonstrating the clinical importance of SNPs in the MDMX gene. The aim of our study was therefore to perform sequencing analyses to identify mutations and/or SNPs in the MDMX gene. A single nucleotide polymorphism (A/C) was identified in the 3′-UTR, 31 bp downstream of the stop codon (SNP34091; rs4245739). In high-grade carcinomas, we found the SNP at a relatively high frequency in the wild-type (A/A) state (62.5%) and in 36% in the heterozygous (A/C) state compared with low-grade carcinomas (45.5%, 45.5%, respectively). The A-allele was associated with increased expression of the full-length MDMX-mRNA. Furthermore, tumors of females who were homozygous for the A-allele showed an increased expression of the MDMX protein. By Cox-regression analysis we found that in estrogen receptor negative tumors the A-allele of SNP34091 was strongly associated with an increased risk of recurrence (RR=8.2; p=0.009) and decreased overall survival time (RR=6.7; p=0.014). According to miRNA-databases the SNP34091 of the MDMX gene is a potential target of miR-191 if the C-allele is present. Therefore, we subsequently analyzed the impact of miR-191 on MDMX expression. We found that mimics of miR-191 resulted in a significantly decrease of MDMX protein levels in C/C ovarian carcinoma cells (Efo-21) but not in cells homozygous for the A-allele (OAW-42). Since MDMX-mRNA levels remained unchanged after transfection, we suggest that miR-191 blocks translation of the MDMX-mRNA and does not lead to its destabilization. These data show that the A-allele increases translation of the MDMX-mRNA which in turn results in a weakened p53-tumor suppressor pathway.
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 2841.
Abstract 2844: Association of genetic variants in TNFRSF10B and breast cancer
Authors: Abo Ryan P. , Parry Marina , Rigas Sushila H. , Cox Angela , Camp Nicola J. 
Published: February 2011

Abstract
Susceptibility to non-Mendelian forms of breast cancer likely involves many low penetrance variants from multiple genes. Recent associations between genetic variants in CASP8 and breast cancer suggest that CASP8 is one such gene contributing to breast cancer risk (Cox et al. 2007; Shephard et al. 2009). Here we investigate TNFRSF10B for associations with breast cancer. TNFRSF10B is a death receptor gene whose protein signals via caspase-8 in the extrinsic apoptosis pathway.
We selected 11 tagging-SNPs (tSNPs) to represent the majority of the common genetic variation in the TNFTRSF10B gene. These tSNPs were genotyped on 1,992 independent cases and controls from Sheffield, UK. We performed 11 single marker association analyses and a haplotype-mining analysis using hapConstructor (Abo et al. 2008). HapConstructor implements a stepwise forward-backward procedure to search for haplotypes associated with disease. The algorithm allows for automatic consideration of non-contiguous SNP sets and the construction of numerous different genetic models that consider haplotypes, composite genotypes, and both monotype (chromosome-based) and diplotype (individual-based) tests. Briefly, all single locus tests are performed, then loci that surpass predefined significance thresholds are considered in all two-locus combinations, and so on.
For the single marker association testing, dominant, recessive, and trend tests were performed. For the hapConstructor analysis, monotype haplotype tests and diplotype dominant and recessive tests were considered. HapConstructor is implemented within a Monte Carlo testing framework, with all p-values estimated empirically from 100,000 simulations under the null.
Seven SNPs reached nominal significance in at least one of the association tests performed in the single SNP tests. Five of these were based on a recessive model (most significant single SNP yielded p = 0.002). Using hapConstructor, the most significant finding was a 4-SNP haplotype that was associated with an increase of risk (p=0.0006; OR=1.75). Four haplotypes were also identified that were associated with a decrease in risk and each obtained the same level of significance and risk (p=0.00096; OR=0.35). These results for reduced risk were obtained using the diplotype recessive model, similar to the single SNP findings. These results provide initial evidence that further common genetic variants in genes in the extrinsic apoptosis pathway, beyond CASP8, are involved in breast cancer susceptibility.
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 2844.
Abstract 2861: Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice
Authors: Yasuda Yoichi , Shimizu Masahito , Sakai Hiroyasu , Kubota Masaya , Tanaka Takuji , Moriwaki Hisataka 
Published: February 2011

Abstract
Obesity and related metabolic abnormalities are risk factors for colorectal cancer. A state of chronic inflammation and adipocytokine imbalance may play a role in this carcinogenesis. Statins, which are commonly used for the treatment of hyperlipidemia, are known to possess anti-inflammatory effects. Statins also exert chemopreventive properties against various cancers. The present study examined the effects of pitavastatin, a recently developed lipophilic statin, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administrated weekly subcutaneous injections of AOM (15 mg/kg body weight) for 4 weeks and then were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 8 weeks. Feeding with either dose of pitavastatin significantly reduced the number of colonic premalignant lesions, β-catenin accumulated crypts, by inhibiting their proliferation and surrounding inflammation. Pitavastatin increased the serum levels of adiponectin while conversely decreasing the serum levels of total cholesterol, TNF-α and leptin. In addition, pitavastatin caused a significant decrease in the expression of TNF-α, IL-6, IL-18 and COX-2 mRNAs on the colonic mucosa of AOM-treated mice. These findings suggest that pitavastatin attenuates chronic inflammation and improves the imbalance of adipocytokines, thereby preventing the development of colonic premalignancies in an obesity-related colon cancer model. Therefore, some types of statin, including pitavastatin, may be a useful chemoprevention modality for colon cancer in obese individuals.
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 2861.
Abstract 2868: EGCG inhibits pancreatic cancer growth in xenografts and KrasG12D transgenic mice models
Authors: Marsh Luke , Shankar Sharmila , Srivastava Rakesh K. 
Published: February 2011

Abstract
FoxO (forkhead box O) transcription factors are crucial regulators of cell fate. This function of FoxO proteins relies on their ability to control diverse functions such as proliferation, differentiation, DNA repair and apoptosis. Constitutively active AKT and ERK in cancer cells have been shown to phosphorylate FoxO transcription factors (FKHR, FKHRL1 and AFX), which bind to protein 14-3-3 and sequester in the cytoplasm. In the absence of survival signals, FoxO proteins dephosphorylate, translocate to the nucleus and upregulate a series of target genes, thereby promoting cell cycle arrest and apoptosis. EGCG, a component of green tea, exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines through diverse mechanisms. However, the mechanisms by which EGCG inhibits cell proliferation and induces apoptosis are poorly understood. EGCG inhibited viability and induced apoptosis in human pancreatic cancer cell lines. EGCG induces PTEN expression and inhibits Akt phosphorylation in pancreatic cancer Hs766T, AsPC-1, MIA PaCa-2 and PANC-1 cells. Treatment of PANC-1 cells with EGCG caused a decrease in ERK phosphorylation, and an increase in JNK phosphorylation. Overexpression of FOXO1, FOXO3a, and FOXO4 inhibited cell viability in PANC-1 cells. The inhibitory effects of EGCG on cell viability were further enhanced when cells were transfected with FOXO1, FOXO3a, and FOXO4. EGCG enhances FOXO-DNA binding activity. EGCG-induced FOXO transcriptional activity was further enhanced in the presence of FOXO1-TM, FOXO3a-TM, and FOXO4-TM. Interestingly, EGCG inhibited pancreatic cancer growth in xenograft, orthotopic and KrasG12D transgenic mice models. In conclusion, our data demonstrate that EGCG can inhibit pancreatic cancer growth through multiple mechanisms and thus can be used for the pancreatic cancer prevention.
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 2868.
Abstract 2872: Effects of ethanol and folate on peripubertal mouse mammary gland
Authors: Masso-Welch Patricia A. , Tobias Menachem E. , Kumar Shyam C. Vasantha , Tamburlin Judith , Koury Stephen T. 
Published: February 2011

Abstract
Alcohol consumption has been clearly linked with increased breast cancer risk in women, with risks incurred even at low levels of consumption. The proposed mechanisms whereby ethanol exerts its effects include decreased folate levels and diminished DNA repair capacity, coupled with acetaldehyde-generated DNA damage. Based on these proposed mechanisms, we hypothesized that ethanol would have increased deleterious effects during periods of rapid mammary gland epithelial proliferation, such as peripuberty. We also hypothesized that folate deficiency alone might mimic the effects of ethanol, and that folate deficiency would exacerbate the effects of ethanol. CD2/F1 female mice (N=8 per group) were pair-fed control and ethanol-containing liquid diets +/− 0.2g/L folate supplementation from 5 weeks until 9 weeks of age. Mice were sacrificed after this 4 week feeding regimen, and mammary glands were harvested for preparation of whole mounts and paraffin sections. Folate levels of liver and kidney were assessed to verify folate status. Analysis of mammary gland whole mounts revealed that mammary gland structure was significantly altered in folate-replete mice fed ethanol, compared to control-fed mice (no ethanol/ folate-replete). These ethanol/folate replete mice showed an increased total number of ductal branches, due to an increased number of terminal short branches; no effect was seen on the number of terminal end buds or primitive alveolar buds. Systematic histological analysis of paraffin sections using NIH Image J software revealed that diets containing ethanol in the presence of folate significantly increased the total number of ducts, ductal epithelial area, and number of ducts with epithelial multilayering. These results demonstrate that folate deficiency alone does not mimic the effects of ethanol, and that folate deficiency in the presence of ethanol blocks proliferative effects of ethanol on the mammary ductal tree. Future studies are examining the effects of peripubertal ethanol and folate exposure on gene expression in the mouse mammary gland.
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 2872.
Abstract 2873: Elucidation of dietary omega-6/omega-3 ratio effects on chemopreventive activity using mammographic density as a surrogate marker in rats
Authors: Zhu Zongjian , McGinley John N. , Jiang Weiqin , Manni Andrea , El-Bayoumy Karam , Thompson Henry J. 
Published: February 2011

Abstract
Although beneficial effects of omega-3 fatty acids in breast cancer prevention have been reported, the optimal dietary omega-6/omega-3 (n-6/n-3) ratio for chemoprevention has not been established. Although n-6 and n-3 fatty acids are essential for the normal development and maintenance of biological function, both classes of fatty acid share metabolizing enzymes and thus have the potential to antagonize each other's metabolism. Therefore, experiments were undertaken to elucidate the ratio(s) of dietary n-6/n-3 that is optimal for chemoprevention in the absence of adverse effects on normal development using mammographic density as a surrogate marker for breast cancer risk. Female Sprague Dawley rats (n=9/group, 32 days of age) were randomized to one of 7 dietary formulations that varied in their ratio of n-6/n-3 as follows: 25:1, 10:1, 5:1, 1:1, 1:5, 1:10, 1:25. The percent of dietary calories from fat was 30% across all 7 formulations. Mammary gland density was determined via digital analyses of abdominal-inguinal mammary gland whole mounts stained with alum carmine. Density was calculated using either area or integrated optical density and expressed as the percent of the mammary gland fat pad occupied by mammary epithelium. Mammographic density was unaffected in the high n-6 arm of the study; whereas, it was significantly reduced in the high omega-3 arm (16%, p&lt;0.03). Efforts are ongoing to determine: 1) whether reduced density is accounted for by effects on cell cycle flux or induction of a pro-apoptotic environment, 2) the extent to which these effects are mediated by altered signaling via activated protein kinase B (Akt), and 3) the mechanism(s) by which the n-6/n-3 ratio alters eicosanoid-mediated bioactivity. Supported by grant KG081632 from the Susan G. Komen Foundation.
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 2873.
Abstract 2879: Proteome changes in mouse prostate induced by oral administration of penta-O-galloyl-beta-D-glucose (PGG) suggest targets for cancer chemoprevention
Authors: Zhang Jinhui , Shaik Ahamd , Nhkata Katai , Wang Lei , Kim Kwan Hyun , Liao Joshua D. , Xing Chengguo , Kim Sung-Hoon , Lü Junxuan 
Published: February 2011

Abstract
1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG), a naturally occurring hydrolyzable gallotannin, has been shown by us and others to exhibit in vivo anti-cancer effects against prostate and breast cancer xenograft or lung cancer allograft when administrated by i.p injection or oral gavage. However, little is known of its safety for chronic chemoprevention use and virtually nothing is known of its in vivo target proteins. In the present study, we treated C57B6 mice with daily gavage of PGG from 7 weeks of age to 14 weeks of age with dosages of 1 and 2 mg per mouse (40-50 and 80-100mg/kg body weight). The dosage choices were made in reference to the efficacious anti-cancer dose of 20 mg/kg body weight. General health, body weights and food intake of mice were monitored. At necropsy, the organ weights were measured. Proteomic patterns in the prostate were profiled by 2D LC-MALDI-TOF/TOF analysis with iTRAQ labeling. Our results show that neither dose affected feed intake and body weight gain, but the 2 mg dose led to a statistically significant but very minor decrease of the weight of prostate and thymus. Proteome profiling by LC-MALDI-TOF/TOF identified 810 proteins from mouse prostates and 623 of them were identified with &gt;95% confidence. Expression of 56 proteins was significantly modulated by either 1mg or 2mg PGG daily treatment, four different kinds of dose responses of proteins modulated by PGG were observed. Protein quantization results were validated by another mass spectrometry, ESI-Q-TOF. Selected proteins were further validated by Western blots and mRNA level by real-time PCR.
The proteome profiles modulated by PGG include suppression of oncoproteins such as fatty acid synthase and induction of tumor suppressor proteins such as glutathione S-transferase M. Overall, the data show protein changes induced by tolerated dosages of PGG in the normal prostate are conducive for cancer chemoprevention. The chemopreventive efficacy of PGG is being evaluated in a primary carcinogenesis model.
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 2879.