bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PREDICTION OF FAT PERCENTAGE IN THE LONGISSIMUS DORSI MUSCLE IN FED BEEF USING NUCLEAR MAGNETIC RESONANCE
Authors: GARCIA L.G. , LAWRENCE T.E. , MONTGOMERY T.H. , PARKER D.B. , BROWN M.S. 
Published: September 2006

ABSTRACT The objective of this study was to develop predictive equations to estimate the percentage of crude fat in beef longissimus dorsi muscles from subjective marbling evaluations or objective visual evaluations. Forty beef ribs and loins representing four U.S. Department of Agriculture (USDA) quality grades – USDA Prime (n = 10); USDA Premium Choice [upper 2/3 of Choice] (n = 10); USDA Low Choice (n = 10); and USDA Select (n = 10) – were fabricated into 3.17‐cm transverse slices for subjective and objective visual evaluations. Additional 0.63‐cm slices were removed for crude fat analysis. Mean crude fat percentages were as follows: USDA Prime = 11.90, USDA Premium Choice = 9.78, USDA Low Choice = 7.08 and USDA Select = 5.29. Regression analysis indicated that crude fat can be estimated with the following equation using a subjective marbling score: = (–0.58) + 0.17 × marbling score (R2 = 0.55); furthermore, crude fat = (3.47) + 0.73 × objective visual percent fat (R2 = 0.54).
Immunohistochemical Expressions of Ki-67, Cyclin D1, β-Catenin, Cyclooxygenase-2, and Epidermal Growth Factor Receptor in Human Colorectal Adenoma: A Validation Study of Tissue Microarrays
Authors: Su Yinghao , Shrubsole Martha J. , Ness Reid M. , Cai Qiuyin , Kataoka Nobuhiko , Washington Kay , Zheng Wei 
Published: September 2006

Abstract
Background: Tissue microarray (TMA) holds promise as a high-throughput method for the analysis of biomarkers in tissue specimens. The validity and reliability of this method, however, may vary for different biomarkers in different tissue specimens.
Objectives: In this study, we evaluated the validity and reliability of using TMA to assess biomarkers in colorectal adenomas.
Methods: Sixty-three consecutive patients with colorectal adenomas were recruited in this study. Two TMA blocks were constructed using four punches from each adenoma (one periphery, one deep, and two middle zones). The immunostaining of five markers (Ki-67, cyclin D1, β-catenin, cyclooxygenase-2, and epidermal growth factor receptor) was analyzed, and the concordance between data obtained from TMAs and standard whole-tissue sections was evaluated by Spearman's correlation and kappa analysis.
Results: Colorectal adenoma exhibited zonal, heterogeneous expression patterns for all five markers. The concordance rates for the semiquantitative evaluation of markers between data from TMAs and whole sections ranged from 87% to 93% with corresponding kappa statistics of 77% to 90%. In addition, both quantitative and semiquantitative methods were used to score TMA sections, and good correlations between these two methods were shown for all five markers with intraclass correlation coefficients ranging from 0.5 to 0.8.
Conclusion: Our study indicates that TMA can be used to reliably assess the expression levels of Ki-67, cyclin D1, β-catenin, cyclooxygenase-2, and epidermal growth factor receptor in colorectal adenoma tissues. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1719–26)
Estrogens, Enzyme Variants, and Breast Cancer: A Risk Model
Authors: Crooke Philip S. , Ritchie Marylyn D. , Hachey David L. , Dawling Sheila , Roodi Nady , Parl Fritz F. 
Published: September 2006

Abstract
Oxidative metabolites of estrogens have been implicated in the development of breast cancer, yet relatively little is known about the metabolism of estrogens in the normal breast. We developed a mathematical model of mammary estrogen metabolism based on the conversion of 17β-estradiol (E2) by the enzymes cytochrome P450 (CYP) 1A1 and CYP1B1, catechol-O-methyltransferase (COMT), and glutathione S-transferase P1 into eight metabolites [i.e., two catechol estrogens, 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2); three methoxyestrogens, 2-methoxyestradiol, 2-hydroxy-3-methoxyestradiol, and 4-methoxyestradiol; and three glutathione (SG)-estrogen conjugates, 2-OHE2-1-SG, 2-OHE2-4-SG, and 4-OHE2-2-SG]. When used with experimentally determined rate constants with purified enzymes, the model provides for a kinetic analysis of the entire metabolic pathway. The predicted concentration of each metabolite during a 30-minute reaction agreed well with the experimentally derived results. The model also enables simulation for the transient quinones, E2-2,3-quinone (E2-2,3-Q) and E2-3,4-quinone (E2-3,4-Q), which are not amenable to direct quantitation. Using experimentally derived rate constants for genetic variants of CYP1A1, CYP1B1, and COMT, we used the model to simulate the kinetic effect of enzyme polymorphisms on the pathway and identified those haplotypes generating the largest amounts of catechols and quinones. Application of the model to a breast cancer case-control population identified a subset of women with an increased risk of breast cancer based on their enzyme haplotypes and consequent E2-3,4-Q production. This in silico model integrates both kinetic and genomic data to yield a comprehensive view of estrogen metabolomics in the breast. The model offers the opportunity to combine metabolic, genetic, and lifetime exposure data in assessing estrogens as a breast cancer risk factor. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1620–9)
Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies
Authors: Lim Unhee , Subar Amy F. , Mouw Traci , Hartge Patricia , Morton Lindsay M. , Stolzenberg-Solomon Rachael , Campbell David , Hollenbeck Albert R. , Schatzkin Arthur 
Published: September 2006

Abstract
Background: In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener.
Objective: We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer).
Methods: We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes.
Results: During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for ≥600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for ≥400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women.
Conclusions: Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1654–9)
Polymorphisms in Nucleotide Excision Repair Genes and DNA Repair Capacity Phenotype in Sisters Discordant for Breast Cancer
Authors: Shen Jing , Desai Manisha , Agrawal Meenakshi , Kennedy David O. , Senie Ruby T. , Santella Regina M. , Terry Mary Beth 
Published: September 2006

AbstractInterindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro–induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T&gt;C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C&gt;A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T&gt;C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1614–20)
Effect of a 12-Month Exercise Intervention on Patterns of Cellular Proliferation in Colonic Crypts: A Randomized Controlled Trial
Authors: McTiernan Anne , Yasui Yutaka , Sorensen Bess , Irwin Melinda L. , Morgan Angela , Rudolph Rebecca E. , Surawicz Christina , Lampe Johanna W. , Ayub Kamran , Potter John D. , Lampe Paul D. 
Published: September 2006

AbstractBackground: Colon crypt architecture and proliferation may be appropriate biomarkers for testing prevention interventions. A hypothesized mechanism for exercise-induced colon cancer risk reduction might be through alterations in colon crypt cell architecture and proliferation.Methods: Healthy, sedentary participants with a colonoscopy within the previous 3 years were recruited through gastroenterology practices and media. We randomly assigned 100 women and 102 men, ages 40 to 75 years, to a control group or a 12-month exercise intervention of moderate-to-vigorous aerobic exercise, 60 minutes per day, 6 days per week, and assessed change in number and relative position of Ki67-stained cells in colon mucosal crypts.Results: Exercisers did a mean 370 min/wk (men) and 295 min/wk (women) of exercise (seven dropped the intervention). In men, the mean height of Ki67-positive nuclei relative to total crypt height was related to amount of exercise, with changes from baseline of 0.0% (controls), +0.3% (exercisers &lt;250 min/wk), −1.7% (exercisers 250-300 min/wk), and −2.4% (exercisers &gt;300 min/wk; Ptrend = 0.03). In male exercisers whose cardiopulmonary fitness (VO2max) increased &gt;5%, the mean height of Ki67-positive nuclei decreased by 2% versus 0.9% in other exercisers, and versus no change in controls (Ptrend = 0.05). Similar trends were observed in other proliferation markers. In women, increased amount of exercise or VO2max did not result in notable changes in proliferation markers.Conclusions: A 12-month moderate-to-vigorous intensity aerobic exercise intervention resulted in significant decreases in colon crypt cell proliferation indices in men who exercised a mean of ≥250 min/wk or whose VO2max increased by ≥5%. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1588–97)
PGR+331 A/G and Increased Risk of Epithelial Ovarian Cancer
Authors: Risch Harvey A. , Bale Allen E. , Beck Patricia A. , Zheng Wenxin 
Published: September 2006

AbstractChildbearing and use of oral contraceptives are known to lower the risk of ovarian cancer, and it has been suggested that progesterone or progestin exposures play a role in these associations. The effects of progesterone may be mediated in part through the progesterone receptor, which exists in two functionally distinct protein isoforms, hPR-A and hPR-B. It is known that individuals carrying the A allele of the progesterone receptor gene (PGR) polymorphism, +331 A/G (rs10895068), have greater production of the hPR-B receptor isoform. We therefore examined the association between PGR +331 A/G genotype and risk of ovarian cancer in a population-based study of 490 cases and 534 controls in the state of Connecticut. Adjusted for various reproductive and other factors, a statistically significant increased risk was seen for carriage of the A allele compared with GG genotype [odds ratio (OR), 1.68; 95% confidence interval (95% CI), 1.09-2.59]. When subjects were considered separately according to menopausal status, no increased risk with the A allele was seen for premenopausal women (OR, 0.96; 95% CI, 0.46-2.02) but significantly increased risk was found for postmenopausal women (OR, 2.31; 95% CI, 1.31-4.06). Similar increased risks particularly among postmenopausal women were seen for all histologic tumor types. These findings have been observed before for breast and endometrial cancer, although not for ovary, but still suggest that an hPR-B mechanism may be involved in ovarian neoplasia. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1738–41)
Folate Metabolism Polymorphisms Influence Risk of Colorectal Adenoma Recurrence
Authors: Hubner Richard A. , Muir Kenneth R. , Liu Jo-Fen , Sellick Gabrielle S. , Logan Richard F.A. , Grainge Matthew , Armitage Nicholas , Chau Ian , Houlston Richard S. ,   The United Kingdom Colorectal Adenoma Prevention Consortium
Published: September 2006

AbstractFolate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G&gt;C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1607–13)
Establishing a Cancer Center Data Bank and Biorepository for Multidisciplinary Research
Authors: Ambrosone Christine B. , Nesline Mary K. , Davis Warren 
Published: September 2006

Abstract
The establishment of a biorepository with linkage to clinical and epidemiologic data will provide an invaluable resource for cancer research, including studies of cancer etiology, progression, and prognosis, as well as development of biomarkers for early detection. Developing an infrastructure for a biorepository linked to clinical, pathologic, and epidemiologic data requires significant efforts in strategic planning for efficient means to ascertain, identify, and consent participants, as well as guidelines for blood collection, processing, and storage while maintaining participant privacy rights. In this report, we present an approach to developing a Data Bank and Biorepository at our own institution, with discussion of elements to be considered when establishing such a bank. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1575–7)
Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer
Authors: Choi Kang Hyun , Park Min Woo , Lee Seung Yeon , Jeon Mi-Ya , Kim Mee Young , Lee Hee Kyu , Yu Jaehoon , Kim Hong-Jin , Han Kyungsook , Lee Heviran , Park Keerang , Park Woong June , Jeong Sunjoo 
Published: September 2006

AbstractT-cell factor (TCF)-1 protein forms the transcriptional complex with β-catenin and regulates the expression of diverse target genes during early development and carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA-binding domain of TCF-1 and have shown that it interfered with binding of TCF-1 to its specific DNA recognition sequences in vitro. As an approach to modulate the transcription by TCF/β-catenin complex in the cells, we have developed the RNA expression vector for stable expression of RNA aptamer inside of the mammalian cells. High level of RNA was expressed as an intramer in the fusion with the stable RNA transcript. The RNA intramer inhibited TCF/β-catenin transcription activity as shown by luciferase assay. It also modulated the expression of TCF/β-catenin target genes, such as cyclin D1 and matrix metalloproteinase-7, as predicted to be as an effective inhibitor of the TCF function. In addition, it efficiently reduced the growth rate and tumorigenic potential of HCT116 colon cancer cells. Such RNA intramer could lead to valuable gene therapeutics for TCF/β-catenin-mediated carcinogenesis. [Mol Cancer Ther 2006;5(9):2428–34]
Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding
Authors: Jones Dylan T. , Harris Adrian L. 
Published: September 2006

AbstractHypoxia-inducible factor-α (Hif-α) plays an important role in tumor growth by increasing resistance to apoptosis and the production of angiogenic factors, such as vascular endothelial growth factor (VEGF). Therefore, Hif-α is an attractive target for development of novel cancer therapeutics. We have generated Chinese hamster ovary cells, which stably express luciferase reporter construct under the control of a hypoxia response element to screen 15,000 compounds. We identified 40 compounds that inhibited hypoxic up-regulation of luciferase, and the top 30 compounds were further screened in a secondary assay using MDA-468 breast cancer cell line. Eight compounds were shown to inhibit VEGF expression in hypoxic cells at subtoxic concentrations. Three top putative Hif inhibitors, DJ12, DJ15, and DJ30, were chosen for further analysis. Transient transfection of cells with hypoxia-regulated luciferase reporter plasmids further validated that these compounds inhibit hypoxia up-regulated genes. All three compounds failed to inhibit Hif-1α protein levels but they did inhibit induction of downstream targets of Hif-α under hypoxia. Two of the three compounds were cell type specific, whereas compound DJ12 inhibited VEGF at subtoxic levels in breast cancer cell lines MDA-468 and ZR-75, melanoma cell line MDA-435, and pVHL mutant renal cancer cell lines RCC4 and 786-0. Compound DJ12 down-regulated mRNA of downstream targets of Hif-α, and significantly inhibited Hif-1α transactivation activity by blocking Hif-1α hypoxia response element-DNA binding. Our cell-based approach and deconvolution of the inhibitory effect of DJ12 has identified a novel compound that targets the hypoxia pathway by inhibiting Hif-α–inducible transcription. [Mol Cancer Ther 2006;5(9):2193–202]
Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells
Authors: Hrzenjak Andelko , Moinfar Farid , Kremser Marie-Luise , Strohmeier Bettina , Staber Philipp B. , Zatloukal Kurt , Denk Helmut 
Published: September 2006

Abstract
Covalent modifications of histone proteins, in particular deacetylation of lysine residues, are important for the regulation of gene transcription both in normal and malignant cells. These processes are controlled by histone acetyltransferases and histone deacetylases (HDAC) and have up to now not been described in solid mesenchymal tumors. The present study shows differences in the HDAC1 and HDAC2 expression in endometrial stromal sarcomas (ESS) and a cognate cell line (ESS-1) compared with nonneoplastic endometrial stroma. We show for the first time that HDAC2 expression is consistently increased in ESS. In contrast, HDAC1 expression is generally lower than HDAC2 both in nonneoplastic stroma and in ESS, suggesting that these two proteins, although closely related, are regulated in different ways. In vitro experiments with an ESS cell line showed that valproate, an inhibitor of the class I HDACs, led to significant HDAC2 decrease and to cell differentiation. HDAC2 inhibition in ESS-1 cells caused significant changes in the cell cycle by inhibiting G1-S transition and influencing expression of p21WAF1 and cyclin D1. Moreover, in ESS-1 cells, increased expression of the p21WAF1 was associated with reduction of HDAC2 expression after transfection with small interfering RNA directed against HDAC2. Our results suggest that HDAC2 might be considered as potential drug target in the therapy of ESS and that HDAC inhibitors should be further evaluated in clinical trials in ESS. [Mol Cancer Ther 2006;5(9):2203–10]
Intracellular inhibition of carboxylesterases by benzil: modulation of CPT-11 cytotoxicity
Authors: Hyatt Janice L. , Tsurkan Lyudmila , Wierdl Monika , Edwards Carol C. , Danks Mary K. , Potter Philip M. 
Published: September 2006

AbstractCarboxylesterases are ubiquitous proteins responsible for the detoxification of xenobiotics. However, these enzymes also activate prodrugs, such as the anticancer agents capecitabine and CPT-11. As a consequence, overexpression of carboxylesterases within tumor cells sensitizes these cells to CPT-11. We have recently identified two classes of carboxylesterase inhibitors based on either a benzil (diphenylethane-1,2-dione) or a benzene sulfonamide scaffold and showed that these compounds inhibit carboxylesterases with Kis in the low nanomolar range. Because both classes of inhibitors show reversible enzyme inhibition, conventional in vitro biochemical assays would not accurately reflect the in situ levels of carboxylesterase activity or inhibition. Therefore, we have developed a novel assay for the determination of intracellular carboxylesterase activity using 4-methylumbelliferone as a substrate. These studies show that benzil and a dimethylbenzil analogue efficiently enter cells and inhibit human intestinal carboxylesterase and rabbit liver carboxylesterase intracellularly. This inhibition results in reduced cytotoxicity to CPT-11 due to the lack of carboxylesterase-mediated conversion of the prodrug to SN-38. These results suggest that intracellular modulation of carboxylesterase activity with benzil or its analogues may be applied to minimize the toxicity of normal cells to CPT-11. [Mol Cancer Ther 2006;5(9):2281–8]