bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4265: Automation-enabled 3D tumor chemosensitivity screening by imaging and flow cytometry analysis
Authors: Kowalski Michael , Raksakulthai Vipat , Prasauckas Kristin , Jones-Roe Tara 
Published: July 2016

Abstract
Three-dimensional (3D) cancer cell cultures are being utilized for drug screening with increasing frequency since they provide a more physiologically relevant solid tumor model than two-dimensional cell cultures. Spheroids are a well characterized, in vitro tumor model system that has been utilized with multiple cancer cell lines. Growth and manipulation of these cultures in hanging drop plates (HDPs) can be challenging to manipulate and these challenges are amplified as sample throughput increases. We automated the culture and compound treatment of cancer spheroids in HDPs, as well as the preparation of these spheroids for analysis by high content imaging and flow cytometry. Automated cancer spheroid cultures showed excellent consistency in size and shape, providing higher confidence in the screening results. Creating single cell suspensions from the cancer spheroids for flow cytometry analysis was another significant challenge overcome through automation. Imaging provided information such as the location of drug-responding cells within the cancer spheroid while flow cytometry removed the potential for spheroid exclusion of staining reagents leading to false negatives. Automation enabled the use of these complementary analyses, thereby achieving a more complete understanding of compound sensitivity in solid tumors and illustrating how spheroids can be utilized to screen for novel cancer therapeutics.
Citation Format: Michael Kowalski, Vipat Raksakulthai, Kristin Prasauckas, Tara Jones-Roe. Automation-enabled 3D tumor chemosensitivity screening by imaging and flow cytometry analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4265.
Abstract 4270: UMR957: a new osteogenic osteosarcoma cell-line derived from an osteoprotegerin null mutant mouse
Authors: Navet Benjamin , Amiaud Jérome , Charrier Céline , Quillard Thibaut , Brounais-Le Royer Bénédicte , Heymann Dominique , Lezot. Frederic P.R. 
Published: July 2016

Abstract
Background: Mouse osteosarcoma cell-lines enabling in vivo studies in syngeneic mouse strains are rare but important for preclinical studies. Existing cell-lines when injected are mainly osteolytic with a moderate tumor osteoid tissue formation. There is a crucial need for new cell-lines with higher osteogenic characteristic.
Methods: A female osteoprotegerin null mutant mouse, breed in the animal house of the Faculty of Medicine from the University of Nantes (France), spontaneously developed an osteosarcoma on the left tibia. The mouse was sacrificed, a biopsy was place in culture for further in vitro and in vivo (injections) studies and the tumor was analyzed using μ-CT, μ-radiography, classical histology and immunohistochemistry.
Results: μ-CT and μ-radiography analyses evidenced that the tumor developed in the Opg-/- mouse was highly osteogenic with an important tumor osteoid tissue that colonized most of the surrounding soft tissues. A total destruction of the tibia was observed. Histology and immunohistochemistry confirmed the presence of an osteosarcoma with an important expression of most bone markers as Osterix. An important vascularization was evidenced in the tumor as the presence of numerous TRAP positive cells. Monocyte/macrophage and T-lymphocyte cells were also present in this tumor. From the biopsy a cell-line was obtained and named UMR957. This cell-line evidenced all markers of the osteoblast cell. When injected in the tibia vicinity of either naïve C57BL/6J, Nude or Opg-/- mouse a highly osteogenic osteosarcoma was observed with similar features to the initial tumor.
Conclusions: A new mouse osteosarcoma cell-line was obtained from a spontaneous tumor developed in an Opg-/- mouse. This cell-line when injected in syngeneic mouse recapitulates all features of the initial tumor more particularly its massive osteoid tissue formation.
Citation Format: Benjamin Navet, Jérome Amiaud, Céline Charrier, Thibaut Quillard, Bénédicte Brounais-Le Royer, Dominique Heymann, Frederic P.R. Lezot. UMR957: a new osteogenic osteosarcoma cell-line derived from an osteoprotegerin null mutant mouse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4270.
Abstract 4281: Mitochondrial DNA copy number, urinary isoprostanes and colorectal cancer risk
Authors: Thyagarajan Bharat , Wang Renwei , Koh Woon-Puay , Barcelo Helene , Adams-Haduch Jennifer , Guan Weihua , Bostick Roberd M. , Yuan Jian-Min , Gross Myron D. 
Published: July 2016

Abstract
Previous epidemiological studies on mitochondrial DNA (mtDNA) copy number and risk of colorectal cancer have yielded mixed results. One study reported a positive association, another reported an inverse association, and a third, a U-shaped association of mtDNA copy number with colorectal cancer risk. Since oxidative stress is one of the proposed underlying mechanisms that may link mtDNA copy number variation to colorectal cancer risk, we conducted a matched case-control study of incident colorectal cancer nested within the Singapore Chinese Health Study. Pre-diagnostic blood and urine samples were obtained from 448 colorectal cancer cases and 869 age- and sex-matched controls. The mtDNA copy number in peripheral white cells was measured using real time PCR and urinary F2-isoprostanes were quantified using a liquid chromatography mass spectrometry based method. Conditional logistic regression was used to estimate associations of mtDNA copy number and urinary F2-isoprostanes with incident colorectal cancer. The odds ratios (OR) and 95% confidence intervals (95% CI) for those in the highest relative to those in the lowest quartiles of relative mtDNA copy numbers and urinary F2-isoprostanes were 1.02 (95% CI 0.72 - 1.43; p for trend = 0.56) and 1.11 (95% CI 0.78-1.59; p for trend = 0.35) respectively. Urinary F2-isoprostanes levels were not associated with the mtDNA copy number among the controls (r = 0.03; p = 0.33). The results of this prospective study suggest that white blood cell mtDNA copy number or urinary levels of F2-isoprostanes in biospecimens collected several years prior to the diagnosis of colorectal cancer may not be associated with risk of developing colorectal cancer.
Citation Format: Bharat Thyagarajan, Renwei Wang, Woon-Puay Koh, Helene Barcelo, Jennifer Adams-Haduch, Weihua Guan, Roberd M. Bostick, Jian-Min Yuan, Myron D. Gross. Mitochondrial DNA copy number, urinary isoprostanes and colorectal cancer risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4281.
Abstract 4285: Intra-individual variation in circulating miRNA expression levels in human plasma samples
Authors: Wu Jie , Cai Hui , Xiang Yong-Bing , Matthews Charles , Ye Fei , Zheng Wei , Cai Qiuyin , Shu Xiao-Ou 
Published: July 2016

Abstract
Circulating miRNAs as possible non-invasive biomarkers for disease risk assessment and cancer early diagnosis has attracted increasing interest. Little information, however, is available regarding the intra-individual variation of circulating miRNA levels. We measured miRNA expression in repeated plasma samples that were collected 6 to 12 months apart from 53 healthy individuals participating in a sub-study nested in the Shanghai Women's and Shanghai Men's Health Studies. Total RNA, including miRNA, was isolated from plasma using Qiagen's miRNeasy Serum/Plasma Kit. Three synthetic spike-in RNA oligos (osa-miR414, cel-miR248, and ath-miR159a) were added to control for variances in the starting material and the efficiency of RNA extraction. NanoString's Human v2 miRNA Expression Assay, which includes CodeSets of probes specific for 800 common human miRNAs, was used for the miRNA assays. The derived miRNA counts were first corrected by subtracting the background counts and then were normalized by using the average count from three spike-in oligos and
the top fifty miRNAs that gave most significant hybridization signals. The intra-individual variation was evaluated by an intra-class correlation coefficient (ICC). A total of 185 miRNAs were detected in at least 10% of samples. The detectable rate varied for each miRNA, with 69 and 44 miRNAs being detected in 50% and 75% of samples, respectively. The median ICC was 0.46 for all of the 185 detectable miRNAs. Among them, 41% (75 miRNAs) had an ICC ≥0.5, and 42 miRNAs had an ICC ≥0.6. The ICC is higher for miRNAs with higher expression levels and higher detection rates, when compared to their counterparts with lower expression or detection rates. In summary, we found that 185 miRNAs were expressed in at least 10% of plasma samples, and 69 miRNAs in 50% of samples from healthy Chinese men and women, and that 75 of these miRNAs had an ICC ≥0.5. These results suggest that common circulating miRNAs can serve as reliable biomarkers for epidemiological and clinical research.
Citation Format: Jie Wu, Hui Cai, Yong-Bing Xiang, Charles Matthews, Fei Ye, Wei Zheng, Qiuyin Cai, Xiao-Ou Shu. Intra-individual variation in circulating miRNA expression levels in human plasma samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4285.
Abstract 4288: Association between tumor necrosis factor alpha -308 G/A polymorphism and risk of bladder cancer in Asian population: a meta-analysis
Authors: Kao Wei-Tang , Tung Min-Che , Hsueh Kuan-Chun , Wang Yuan-Hung , Wu Chia-Chang 
Published: July 2016

Abstract
Previous studies have investigated the association between TNF-α-308 G/A polymorphism and bladder cancer risk in various populations. However, these findings remain inconclusive. Therefore, we performed a meta-analysis to explore the relationship between TNF-α-308 G/A polymorphism and bladder cancer risk. A literature search in PubMed was performed to select eligible studies regarding the association between TNF-α-308 G/A polymorphism and bladder cancer risk. The strength of risk under fixed- and random- effects models were estimated using the odds ratios (ORs) with 95% confidence intervals (CIs). We identified 7 case-control studies including 1153 cases and 1587 controls were included in the present meta-analysis. Compared with subjects carrying the G/G genotype of TNF-α-308 G/A polymorphism, those with the A/A and G/A genotypes had non-significant bladder cancer risks under the fixed effects model (OR = 1.037) and the random effects model (OR = 1.012). In the recessive model, subjects with the A/A genotype had an increased bladder cancer risk (OR = 1.875) compared with those carrying the G/A and G/G genotypes of TNF-α-308 G/A polymorphism. The major finding of this meta-analysis suggest that TNF-α-308 G/A polymorphism is correlated with the risk of bladder cancer in Asian population under the recessive model. We should further investigate the joint effects of environmental risk factors and TNF-α-308 G/A polymorphism on bladder cancer risk.
Citation Format: Wei-Tang Kao, Min-Che Tung, Kuan-Chun Hsueh, Yuan-Hung Wang, Chia-Chang Wu. Association between tumor necrosis factor alpha -308 G/A polymorphism and risk of bladder cancer in Asian population: a meta-analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4288.
Abstract 4292: Mitochodrial D-loop polymorphisms are associated with colorectal adenoma risk
Authors: Thyagarajan Bharat , Guan Weihua , Fedirko Veronika , Barcelo Helene , Gross Myron D. , Goodman Michael , Bostick Roberd M. 
Published: July 2016

Abstract
Somatic mutational events in the mitochondria have been detected in adenomatous polyps. However, the contribution of germline variation in the mitochondrial DNA towards risk of colorectal adenomas, well recognized precursor lesions to colorectal cancer, has not been evaluated previously. Hence, we evaluated associations of mitochondrial polymorphisms in the D-loop and non-D loop regions with incident colorectal adenoma in three pooled colonoscopy-based case-control studies (n = 327 colorectal adenoma cases and 420 controls) that used identical methods for case ascertainment and risk factor determination. We sequenced a 1,124 bp fragment to comprehensively identify all genetic variation in the mitochondrial D-loop region, and used the Sequenom platform to genotype 64 previously described tagSNPs in the non-D loop region. We used multivariate unconditional logistic regression to analyze the association between the mitochondrial polymorphisms and colorectal adenoma risk after adjustment for potential confounders. We identified 320 germline mutations in the D-loop region; 30 (9%) had a minor allele frequency (MAF) ≥ 5%. Most of the mutations clustered in the hypervariable regions HV1 (n = 124; 39%) and HV2 (n = 111; 35%) of the D-loop region. Among the nine common polymorphisms (MAF ≥ 5%) in the HV1 region, four polymorphisms (mt16069, mt16278, mt16294, and mt16296) were statistically significantly directly associated with colorectal adenoma risk (odds ratios [OR]: 1.76 - 2.66; p-values: 0.001 - 0.04). In addition, the polyC tract in the HV1 region was inversely associated with colorectal adenoma risk (OR: 0.90; p = 0.03). None of the other polymorphisms in the mitochondrial D-loop region tract was associated with colorectal adenoma risk. After correction for multiple comparisons, none of the mitochondrial tagSNPs in the non-D loop region was associated with colorectal adenoma risk. These findings suggest that polymorphisms in the HV1 region of the mitochondrial D-loop may be associated with colorectal adenoma risk and support further investigation in future studies.
Citation Format: Bharat Thyagarajan, Weihua Guan, Veronika Fedirko, Helene Barcelo, Myron D. Gross, Michael Goodman, Roberd M. Bostick. Mitochodrial D-loop polymorphisms are associated with colorectal adenoma risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4292.
Abstract 4299: Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh
Authors: Zhang Chenan , Kibriya Muhammad , Jasmine Farzana , Roy Shantanu , Ahsan Habibul , Pierce Brandon L. 
Published: July 2016

Abstract
Chronic exposure to arsenic, a human carcinogen, has been shown in epidemiologic studies to increase the risk of arsenical skin lesions (keratosis and melanosis) as well as cancer (including non-melanoma skin cancer). Recent studies suggest that the mechanism of arsenic's toxicity may be related to telomere dysfunction, including altered telomere length (TL), and differential expression of genes involved in telomere maintenance. However, prior studies of arsenic exposure, TL, and skin lesion tend to be small and cross-sectional in nature. In this study, we investigated the association between arsenic exposure and TL (measured by qPCR as T/S ratio), as well as TL and subsequent risk of skin lesion in individuals who are exposed to naturally contaminated drinking water with a wide range of arsenic levels in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000-2009). In all laboratory analyses, we attempted to randomize samples across plate positions, and in statistical analyses, we controlled for any residual confounding by plate or plate position. All TL data generated showed a strong inverse association with age. In a random sample of the baseline cohort (n = 649), we observed a positive association between water arsenic levels and TL (Ptrend = 0.035), with beta estimates of 0.001, 0.023, and 0.025 for water arsenic levels of 10.1-50ug/L, 50.1-150ug/L and 150+ug/L, respectively, compared to &lt;10ug/L. However the association was not replicated in an independent random sample (n = 1181, Ptrend = 0.176) with beta estimates of 0.007, -0.004, and -0.017. In a nested case-control study comparing skin lesion incident cases diagnosed across a nine year period with sex- and age-matched controls (448 cases and 462 controls), we observed higher incident skin lesion risk with shorter TL (Ptrend = 4.6E-5), with odds ratios of 3.05, 1.30, and 1.21 for the first (shortest), second, and third TL quartiles compared to the longest. Our findings show that arsenic exposure is not strongly associated with TL, indicating that TL is likely not the main mode of action for arsenic's carcinogenic toxicity. However, TL is inversely associated with skin lesion risk, suggesting that short TL may be a biomarker of susceptibility for arsenical skin lesions independent of arsenic exposure.
Citation Format: Chenan Zhang, Muhammad Kibriya, Farzana Jasmine, Shantanu Roy, Habibul Ahsan, Brandon L. Pierce. Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4299.
Abstract 4309: Rare protein truncating and missense variants in ATM, CHEK2, PALB2, but not XRCC2, confer increased breast cancer risks
Authors: Decker Brennan , Allen Jamie , Luccarini Craig , Pooley Karen A. , Pharoah Paul PD , Dunning Alison M. , Easton Douglas F. 
Published: July 2016

Abstract
Breast cancer (BC) is the most common malignancy in women and has a major heritable component that is driven by both common SNPs and rarer variants in susceptibility genes. However, the risks associated with most rare susceptibility alleles are not well estimated. We sequenced the coding regions of ATM, CHEK2, PALB2, and XRCC2 in 13,087 BC cases and 5,488 controls from East Anglia to characterize their role in BC risk in the largest sequencing study of these genes to date.
We performed multiplexed microfluidic PCR target enrichment of 221 amplicons, covering 99.3% of the coding bases. Amplified DNA was barcoded, pooled, and sequenced on the Illumina HiSeq2000. Reads were demultiplexed, trimmed, and aligned to the hg19 reference sequence. Variants were called with GATK UnifiedGenotyper and filtered for missing data. Retained variants were annotated with CADD and VEP. Truncating variants, missense alleles, and other functional variant groups were assessed for association with BC risk using logistic regression.
Truncating variants in ATM, CHEK2, and PALB2 increased overall BC risk, whereas XRCC2 variants did not (Table 1). The estimated relative risk was higher for PALB2 than ATM or CHEK2. While 88% of CHEK2 variant alleles were attributable to CHEK2*1100delC, other truncating alleles appeared to confer similar risks. CHEK2 truncating alleles were more strongly associated with risk of estrogen receptor (ER) positive disease than ER negative or triple negative disease. In contrast, PALB2 protein-truncating variants conferred similar relative risks for all subtypes. Analysis of rare missense variants suggested that specific subset of alleles in ATM (P = 0.012), CHEK2 (P = 0.009), and PALB2 (P = 0.017) may contribute to risk. Localization within known functional domains were a predictor of association among these variants.
These results confirm that truncating variants in ATM, CHEK2, and PALB2 are associated with moderate BC risks, and exclude a large effect on risk from XRCC2 variants. Truncating Variant RiskATMATMCHEK2CHEK2PALB2PALB2XRCC2XRCC2ORP-ValueORP-ValueORP-ValueORP-ValueSEARCH Cases3.262.11E-053.345.18E-115.424.45E-080.940.9232ER Positive3.191.04E-043.719.11E-124.322.73E-050.870.8419ER Negative1.280.67431.560.23655.583.62E-040.880.9102Triple Negative2.850.14880.420.32217.500.0022NANA
Citation Format: Brennan Decker, Jamie Allen, Craig Luccarini, Karen A. Pooley, Paul PD Pharoah, Alison M. Dunning, Douglas F. Easton. Rare protein truncating and missense variants in ATM, CHEK2, PALB2, but not XRCC2, confer increased breast cancer risks. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4309.
Abstract 4318: Reversal of BRCA-1 CpG hyperthylation by genistein and (-)-epigallocatechin-3-gallate in human breast cancer cells with activated AhR
Authors: Selmin Ornella I. , Papoutsis Andreas J. , Romagnolo Donato F. 
Published: July 2016

Abstract
Sporadic breast cancers, which represent the vast majority (∼90%) of breast tumor cases, do not have mutations in the tumor suppressor gene, BRCA-1 but have absent or markedly reduced levels of BRCA-1 similar to those observed in hereditary BRCA-1 tumors. Therefore, understanding the non-mutational mechanisms that contribute to repression of BRCA-1 has important implications for the prevention of both hereditary and sporadic breast tumors. Agonists of the aromatic hydrocarbon receptor (AhR) are ubiquitous in the environment and include dietary compounds, metabolites of fatty acids, industrial pollution, and photoproducts generated in the skin from ultraviolet radiation. In cultured estrogen-receptor (ER)α-positive MCF-7 breast cancer cells, we found that activation of the AhR with the prototype ligand 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) repressed by 50% estradiol-induced BRCA-1 expression. Conversely, the post-treatment with the soy isoflavone genistein and tea (-)-epigallocatechin-3-gallate (EGCG) at physiological doses (1 μM) rescued within 24 to 48 h BRCA-1 expression to levels ∼2.0 to 3.0-fold higher than those measured in cells treated with estradiol alone. Genistein and EGCG reversed BRCA-1 promoter hypermethylation in AhR-activated MCF-7 cells. In ERα-negative and AhR-overexpressing UACC-3199 breast cancer cells, genistein (1 μM) reactivated BRCA-1 expression. The post-treatment of AhR-activated MCF-7 cells with genistein and EGCG antagonized the recruitment of DNA-methyl transferase-1 (DNMT-1) enzyme to the BRCA-1 promoter. These results suggest the involvement of epigenetic mechanisms in the repression of BRCA-1 and reversal effects of genistein and EGCG against breast tumorigenesis associated with activation of the AhR.
Citation Format: Ornella I. Selmin, Andreas J. Papoutsis, Donato F. Romagnolo. Reversal of BRCA-1 CpG hyperthylation by genistein and (-)-epigallocatechin-3-gallate in human breast cancer cells with activated AhR. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4318.