bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A88: Genome-wide association study identifies variants in several loci associated with circulating vitamin E levels
Authors: Major Jacqueline M. , Yu Kai , Zhang Hong , Wheeler William , Cornelis Marilyn , Yeager Meredith , Snyder Kirk , Hunter David , Chanock Stephen , Kraft Peter , Albanes Demetrius 
Published: January 2011

Abstract
Background: Observed associations between vitamin E status and certain cancers (e.g., lung, prostate, colorectal, cervical and ovarian) suggest a protective relation may exist, with many studies focusing on the antioxidant and antiproliferative properties of alpha-tocopherol. Recent findings suggest that gamma-tocopherol may play a similar role that is independent of alpha-tocopherol. The purpose of this study was to identify genetic variants associated with circulating levels of alpha- and gamma-tocopherol. This is the first genome-wide association study (GWAS) to examine these two nutritional phenotypes.
Methods: Prior to analysis, tocopherol levels were log-transformed to normalize the distributions. General linear models were used to relate the log-transformed outcomes to a SNP by assuming an additive mode of inheritance. Analyses were adjusted for the effects of age, cancer status, body mass index, and cholesterol (because it is well established that vitamin E levels are affected by circulating lipids).
Results: Based on the combined data from the two adult cohorts (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) cohorts) comprising 5,006 men of European descent, we found evidence of novel loci associated with circulating vitamin E, including BUD13 (rs964184, P=3.5 x 10-10), CYP4F2 (rs2108622, P=7.8 x 10-9), and SCARB1 (rs11057830, P=3.0 x 10-7), all of which meet genome-wide level of significance for their association with alpha-tocopherol. Our three identified single nucleotide polymorphisms (SNPs) have previously been reported to be associated with HDL cholesterol and triglycerides, which are involved in vitamin E transport. We further replicated the most significant findings in an independent data set of 2,769 women, with combined meta-analysis significance of P=1.1 x 10-12 (BUD13, rs964184), P=1.1 x 10-9 (CYP4F2, rs2108622), and P=3.5 x 10-8 (SCARB1, rs11057830). The genome-wide significant associations for gamma-tocopherol levels and SNPs in four gene regions did not replicate, however.
Conclusion: Our findings reveal specific, previously unknown proteins related to vitamin E biochemical status that add to our understanding of this membrane-integrated micronutrient and that can be investigated with respect to cancer and other disease phenotypes.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A88.
Abstract A9: UDP-glucuronosyltransferase 2B7 (UGT2B7) inhibits melanoma invasiveness
Authors: Dellinger Ryan W. , Matundan Harry H. , West Alisa L. , Meyskens Frank L. 
Published: January 2011

Abstract
The UDP-glucuronosyltransferase (UGT) family of enzymes catalyzes the glucuronidation of a variety of endogenous compounds such as bilirubin and steroid hormones, as well as xenobiotics including chemotherapeutic agents and environmental carcinogens. Glucuronidation of these substrates inactivates them by making them more hydrophilic and easily excreted. UGTs are expressed primarily in the liver, but are also expressed in several extrahepatic tissues including prostate, breast, colon, lung, brain, kidney, bladder, and ovary. However, there have been no reports measuring UGTs in melanocytes or melanoma.
We screened several primary melanocyte cultures from neonatal foreskin as well as several primary and metastatic melanoma cell lines for UGT expression by RT-PCR. Three UGT family members, UGT2B7, UGT2B10, and UGT2B15, were found to be expressed in melanocytes. Interestingly, of all the melanoma cell lines screened only WM115, a primary melanoma, had UGT expression. Again, only UGT2B7, UGT2B10, and UGT2B15 were detected. UGT expression was not detected in another primary melanoma cell line, WM3211, or in any metastatic melanoma cell line assayed suggesting that loss of UGT expression occurs during melanoma progression.
Knockdown of UGT2B7 in WM115 cells using shRNA resulted in a 2.6-fold increase in invasiveness as measured by migration through Matrigel. Conversely, stable expression of UGT2B7 in the metastatic melanoma cell line SKmel28 (which lacks UGT expression) resulted in dramatic reduction of invasiveness. Furthermore, treatment of SKmel28 cells stably expressing UGT2B7 with β-estradiol (a competitive inhibitor of UGT2B7) restored invasiveness of this cell line to parental levels. Thus, glucuronidation prevents invasiveness in melanoma.
Taken together, we hypothesize that the observed loss of UGT expression is required for melanoma progression and that preventing the loss of UGT expression may be a viable strategy for melanoma chemoprevention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A9.
Abstract A93: Lapatinib suppresses RTK-mediated signaling through multiple signaling pathways in the chemically induced ER+ model of mammary cancer
Authors: Grubbs Clinton J. , Li Jixia , Cho Yeon-Yong , Ericson Marna , Lubet Ronald , Bode Ann 
Published: January 2011

Abstract
Activation of receptor tyrosine kinases (RTKs) plays a key role in the prognosis of mammary cancer. EGFR and HER2 are validated therapeutic targets. Lapatinib is a small molecule dual RTK inhibitor that targets EGFR and HER2. Identifying the protein targets involved in the effects of lapatinib and other RTK inhibitors might help determine why preventive efficacy varies. In this study, female Sprague-Dawley rats (50 days old) were given methylnitrosourea (MNU) by IV injection through the jugular vein (75 mg/kg BW). The rats developed multiple ER+ tumors. Two different approaches were taken to evaluate the efficacy of lapatinib as either a chemopreventive or chemotherapeutic drug. First, we demonstrated that treatment with lapatinib beginning 5 days after MNU was highly effective in preventing tumor development. In addition, we treated rats with palpable mammary tumors with lapatinib (75mg/KgBW/day). In some of the tumor bearing animals, treatment proceeded for 42 days, and therapeutic results were obtained. In a separate group, rats bearing tumors were treated for 5 days, and the resulting lesions examined for biomarkers modulation. Lapatinib caused a marked inhibition of mammary cancers, and effectively suppressed the abundance of both HER2, phosphorylated HER2 (Tyr1221, Tyr1222) and phosphorylated EGFR (Tyr1173, Tyr1110) compared to tumors from untreated control rats. Protein array analyses allowed parallel determination of the effect of lapatinib on the relative levels of protein phosphorylation and apoptosis. Interestingly, unlike Gefitinib (Iressa), which appears to target EGFR signaling mediated primarily through the ERK MAP kinases, lapatinib seems to suppress EGFR/HER2 signaling primarily through Src-related proteins, Lyn and Lck, Akt and GSK3. The complete signaling cascade involves a number of signaling molecules potentially leading to impaired proliferation, apoptosis or cell cycle arrest.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A93.
Abstract A98: Prevention of gastrointestinal adenomas in the ApcMin mouse by high-fiber rice bran
Authors: Jones Donald JL , Horner-Glister Emma , Norris Leonie , Gescher Andreas , Sale Stewart 
Published: January 2011

Abstract
Consumption of dietary bran has been considered to be beneficial to health. It has also been linked to a lower risk of developing malignancies, most notably, colorectal cancer. Rice bran (containing 23-35% dietary fiber) at 30% in the diet interfered with adenoma development in the ApcMin mouse, a preclinical model of colorectal cancer (Verschoyle et al., Br J Cancer 2007). Here we used a high fiber rice bran extract (Nutracea, USA), with a fiber content of 40-50% to explore whether an increase in fiber imparts higher efficacy in the ApcMin mouse. The bran was mixed in with the diet at three concentrations: 5, 15 and 30% (n=19-22 per group) and administered to ApcMin mice from 4 weeks of age until termination of study at 16 weeks. Adenoma numbers were reduced by 12, 26, 74 % and adenoma burden by 30, 26 and 84 %, respectively, in the treatment groups in comparison to control mice, with reduction being significant only at the highest dose (p&lt;0.05). The high fiber rice bran seems to be more efficacious than the rice bran used in the previous study in which 30% rice bran reduced adenoma numbers by 51% (Verschoyle et al., Br J Cancer 2007). Plasma samples from each experimental group were collected and undergo proteomic analysis using liquid chromatography-mass spectrometry to identify potential biomarkers of efficacy. This study highlights the potential health benefit of high-fiber rice bran, but further investigations are warranted to better understand the role of fiber in colorectal cancer prevention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A98.
Abstract A99: Evaluation of the effects of naproxen in human colon polyp cells using gene expression and pathway analysis
Authors: Elmore Eugene , Steele Vernon E. , Redpath John L. 
Published: January 2011

Abstract
Cultures of human colon polyp cells were treated with naproxen to determine its potential efficacy as a chemopreventive agent for colon cancer. The exposures and naproxen concentration used were selected to be similar to the anticipated exposures that would be used in a clinical trial. We treated the human precancerous colon polyp cell line, VACO-235, with naproxen at a clinically achievable concentration of 1 µg/mL. The exposure was continuous over 96 hr with treatment media replenishment every 24 hr. This treatment allowed the naproxen induced changes in the cultures to reach a steady state prior to the assessing gene expression levels. For the gene expression analysis, five separate cultures were used to generate five arrays for the control and treated cultures. Gene expression was assessed using Human gene 1.0 ST arrays from Affymetrix (Santa Clara, CA). The quality of the data from each array was assessed using the manufacturer's software and no outliers were found. Gene expression was assessed using JMP Genomics 4.1 (Cary, NC). The relative gene expression in naproxen treated cultures was compared to the matched controls. Pathway analysis was done using Ariadne Genomics, Pathway Studio 7.1 (Rockville, MD). The data were evaluated using pathway analysis to identify pathway specific changes that were relevant to regulation of growth, metabolism, cell cycle regulation, and cancer. Of the forty-one functional classes and cellular processes associated with the notch pathway, thirty-two showed reduced gene expression or function. In the growth factor receptor pathway associated with AP-1, CREB/CREBBP/ELK-SRF/Myc signaling, thirty-eight of forty-five genes, transcription factors, or functional classes were reduced in expression. Naproxen showed inhibition of genes related to transcription of oncogenes including Ras, Fos, Myc, Jun, Vav1, ELK1, ELK4, multiple map kinases, and TGFBR1 signaling. The data suggest that 96 hr continuous exposure to naproxen at a relevant human serum level was sufficient to reduce the expression of genes in pathways that relate to cancer and growth in the Human colon polyp cells. Supported by NCI contract #N01-CN-43300.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A99.
Abstract B11: Risk of fracture and androgen deprivation therapy
Authors: Shao Joni Y. , Moore Dirk F. , Shih Weichung , Lin Yong , Lu-Yao Grace L. 
Published: January 2011

Abstract
Background: Extended use of androgen deprivation therapy (ADT) is common among elderly men; however, the associated long-term toxic effects have not been well documented.
Methods: We conducted a population based cohort study by analyzing a total of 46,587 men diagnosed with localized prostate cancer and survived at least 5 years after diagnosis in the Surveillance, Epidemiology, and End Results (SEER) -Medicare program to estimate the risk of fracture among men who received long-term ADT.
Results: More than 46% of ADT users received more than 25 months of treatment. The hazard ratio (HR) of hospitalized fracture was 1.47 (95 percent confidence interval, 1.29 to 1.67) among men receiving 36 or more doses of Gonadotropin-releasing hormone (Gn-RH) agonist. Men treated with ADT were associated with a 57.8% increase in the risk of multiple fractures after the first 24 months of treatment. Older age, higher comorbidity, history of fracture and stoke were independently associated with increased fracture risk. Men who were 75 years of age or older and received GnRH agonist for more than 24 months were associated with a 3.63 times risk of having fracture, compared with those aged 66 to 74 and have ADT shorter than 24 months.
Conclusion: Men who are older and with comorbidity are more likely to received long-term ADT than attempted curative treatment. However, those men are also at substantial risk of fracture. The increased risk of fracture along with ADT should be carefully evaluated before initiating a treatment.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B11.
Abstract B14: Psychosocial correlates to intention to participate in CRC screening among an urban sample of nonscreened African Americans
Authors: Lawsin Catalina , DuHamel Katherine , Jandorf Lina 
Published: January 2011

Abstract
African Americans have the highest mortality rates for colorectal cancer (CRC) in the United States. Unfortunately, this disparity may be related to underscreening. While a variety of psychosocial factors have been shown to contribute to their low CRC screening rates as compared to African Americans’ screening rates for other cancers, the construct of tolerance for ambiguity (TFA) has yet to be examined in the context of CRC screening. TFA describes the level of uncertainty an individual can manage and has been shown to influence decision making, such that individuals with a higher tolerance are more likely to enter ambiguous situations. This study sought to examine the role of TFA as a possible barrier to screening amongst a group of African American individuals (N= 93) who have yet to participate in CRC screening in an urban outpatient clinic. Participants ranged in ages between 50 and 87 (mean age = 56, SD = 6.693) and were from lower socioeconomic backgrounds (63% earned less than $15,000 per year and 27% completed less than 11 years of schooling). Correlational analysis between TFA, screening intention in the next year, and psychosocial factors previously shown to influence decision to screen including: knowledge of screening, perceived risk, collectivism, and worry was conducted. Contrary to hypothesis, TFA was not shown to be significantly associated with intent to screen. Instead, among the psychosocial factors, knowledge of screening demonstrated the strongest relationship with intention to have a colonoscopy in the next year (P&lt; 0.01). However, TFA was shown to be significantly related to higher collectivism (P&lt; 0.01) and education levels (P&lt; 0.04). TFA does not appear to be a primary barrier to screening, however warrants further examination as to how it contributes or possibly overlaps with other psychosocial factors. Results suggest that amid this sample of African American non-screeners, providing adequate information regarding the need for screening remains an important factor that may improve screening rates, particularly among those from lower socio-economic backgrounds. Acknowledgement of funding: NCI: CA104130-01
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B14.
Abstract B17: A novel cancer prevention management strategy at the Comprehensive Cancer Center Freiburg (CCCF), Germany
Authors: Leifert Jens A. , Schulz Cornelia , Jaehne Andreas , Elze Mirjam , Balmford James , Opitz Oliver 
Published: January 2011

Abstract
Background: Smoking is a significant risk factor for cancer. Over 90% of smokers consider quitting, but the majority does not use professional support, thus foregoing substantially higher chances of success (tenfold higher 1-year abstinence-rate). Hospitalized patients are especially receptive to cessation advice, but structured counseling of smoking in-patients is rarely available.
The aim of the project at the Comprehensive Cancer Center Freiburg (CCCF)/University Medical Center Freiburg (UMCF) is to establish a Cancer Prevention Management Team (CPMT) dedicated to identify smoking patients, motivate them to quit and link them to appropriate smoking cessation programs offered by external providers.
Methods: The CPMT was implemented as a structure to identify smoking patients to provide them with intensive counseling based on Motivational Interviewing, to enhance their motivation to quit and to refer them to suitable cessation programs. Enrolled patients (treatment arm) were referred to at least one form of cessation treatment (structured multicomponent program: individual/group setting, use of self-help materials, nicotine replacement therapy (NRT)) and received continued weekly telephone support by the CPMT. Enrolled patients who were unwilling to use any cessation therapy were followed up only (observation arm).
Results: CPMT structures and a screening system for smoking patients have been successfully implemented in 24 departments of the UMCF (1.113 hospital beds) organized in 60 wards and 10 outpatient departments. A network of 52 regional providers of evidence based cessation programs has been established. Within the first 15 months 703 smoking patients were counselled; 371 (52%) patients agreed to participate in the study. Out of these, 337 patients were included in the treatment arm, 34 patients were included in the observation arm of the program. The majority of the patients were suffering from patients (36%) or cardiovascular disease (19%).
Abstinence rates after 3 months (n=122) were 34.4% overall, counting patients with lost contact (n=24) as smokers. Among patients in the treatment arm, abstinence rates were higher in patients using behavioural therapy (BT) (44.0%) compared to patients not using BT (41.1%).
Conclusion: A Cancer Prevention Management Team is a highly efficient structure in large hospitals to screen patients for smoking status and motivate them to enter into a cessation program. Quit rates after 3 months were high, considering that all of these patients were treated in-hospital for severe illnesses and none of the patients had an initial intention to quit when entering the hospital.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B17.
Abstract B2: Conceptual barriers in cancer prevention research
Authors: Aktipis C. Athena , Johnson Kathryn , Dong Elizabeth , Kwan Virgina S. Y. , Neuberg Steven L. , Maley Carlo C. 
Published: January 2011

Abstract
Neoplastic progression is an evolutionary process and cancer prevention is successful to the extent that it can impact that process, reducing the likelihood that premalignant cells will evolve invasive or metastatic phenotypes. Despite the centrality of somatic evolution in cancer progression, evolutionary tools and analyses have rarely been applied to the development and implementation of interventions to reduce cancer incidence. Conceptual barriers such as cognitive biases, misperceptions about the nature of cancer, or the use of misleading metaphors may interfere with the effective incorporation of evolutionary principles into cancer prevention and treatment. We analyzed cancer articles for evidence of several biases that are likely to interfere with evolutionary thinking and conducted surveys to measure these cognitive biases. We found evidence for several biases, including a failure to recognize the mutability of neoplasms. Further, our surveys indicated that respondents favor metaphors for cancer (as an invading enemy or parasite) that may bias towards overly aggressive interventions. By identifying cognitive barriers to the penetration of evolutionary principles in cancer research and prevention, we will be able to more effectively offset these biases and expand the conceptual framing of cancer so as to facilitate cancer prevention research, improve patient management and prevent over-treatment.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B2.
Abstract B20: Identification of age-dependent biomarkers for early detection of breast cancer using metabolite profiling: A multisite study
Authors: Asiago Vincent M. , Shanaiah Narasimhamurthy , Gowda Nagana G. , Owusu-Sarfo Kwadwo , Alvarado leiddy , Liu Lingyang , Heiligstedt Heather , Raftery Daniel 
Published: January 2011

Abstract
This abstact is being presented as a short talk in Concurrent Session 9. A full abstract is printed in the Proffered Abstracts section (PR-06) of the Conference Proceedings.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B20.
Abstract B33: Serum hormone concentrations in women who yield breast nipple aspirate fluid (NAF) and those who do not
Authors: Khan Seema A. , Chatterton Robert T. , Heinz Richard , Fought Angela , Kmiecik Thomas , McGathey Claire , Scholtens Denise 
Published: January 2011

Abstract
Objective: Determine whether differences in serum hormone concentrations explain the lack of NAF yield among women participating in a study of NAF hormone concentrations in breast cancer cases and screening controls.
Methods: 80 NAF yielders (Y) and 80 non-yielders (NY) were randomly selected from women who had completed participation in an ongoing case-control study, equally divided by menopausal status and case-control status (only the contralateral breast was aspirated in cases). Average age of premenopausal women was 45.95 years and of postmenopausal women was 57.54 years. The percentage of African American and Caucasian subjects was similar among those who yielded NAF and those who did not. Serum was collected on the same day that nipple aspiration was attempted and the serum was assayed for estradiol, progesterone, and FSH by standard immunoassays. Hormonal concentrations were compared among 80 subjects who produced &gt;2 microliters of NAF and 80 who did not. Wilcoxon tests were used to compare rank distributions of the values for yielders and non-yielders within each menopausal and case/control category.
Results: Hormonal data were analyzed in quintiles with the following comparisons: premenopausal cases Y vs NY; postmenopausal cases Y vs NY; premenopausal controls N vs NY; postmenopausal controls N vs NY. Among premenopausal cases estradiol was significantly greater at the P = 0.0067 level among those who did not produce NAF. This remained significant after correction for multiple comparisons. The difference remained significant after combining cases and controls at the P = 0.021 level. The other comparisons were not significant. Analyses of progesterone and FSH yielded no significant differences.
Discussion: The inhibition of breast fluid accumulation by estradiol is consistent with the effect of ovarian steroids on milk secretion observed after parturition. The observation that this effect was greater in cases is interesting and will be investigated further to ascertain whether other factors associated with breast cancer may play a role in the observed inhibition.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B33.