bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A4: Protection against radiation-induced carcinogenesis
Authors: Mitchell James B. , Anver Miriam , Sowers Anastasia , Figueroa Maria , Thetford Angela , Krishna Murali C. , Albert Paul S. , Cook John A. 
Published: January 2011

Abstract
The rationale of this study stems from the concern of radiation-induced second malignancies after a course of definitive radiation therapy or the possibility of a terrorist-mediated nuclear attack resulting in large populations of people exposed to non-lethal radiation doses, which would substantially increase the risk for cancer induction post-exposure. Currently, there are no safe and effective interventions to reduce this risk to humans. Previous studies have shown that chronic administration of Tempol (nitroxide antioxidant) in the diet of mice results in decreased weight and spontaneous tumorigenesis, and increased tumor latency (Mitchell JB, et al., Free Radic Biol Med 34:93-102, 2003). In the current study we tested the hypothesis that Tempol (TP) administered in the diet of mice would reduce radiation-induced cancer when given after the radiation exposure. Total body radiation (3 Gy) was administered to female C3H and CBA mice. Along with various control groups, immediately after radiation one group of animals from each strain was placed on a TP diet. Food consumption and animal weights were monitored throughout the study. Animals were followed for their entire lifespan (&gt;1300 mice). The endpoint for the study was tumor formation or until the animal reached a humane endpoint at which time the animal was euthanized and evaluated for the presence of tumor (pathology evaluated on all animals). TP food supplementation after radiation: a) did not alter food consumption compared to animals on a control food diet, b) compared to animals on control food diet, the TP diet resulted in decreased weights in both mouse strains (40% for C3H and 20% for CBA), and c) TP food supplementation post-radiation significantly enhanced the survival of both mouse stains. Median survival values for 0 Gy, 3 Gy, 0 Gy TP, and 3 Gy TP for C3H mice was 706, 434, 764, and 670 days, respectively. For CBA mice median survival values for 0 Gy, 3 Gy, 0 Gy TP, and 3 Gy TP for C3H mice was 901, 660, 939, and 782 days, respectively. The incidence of hematopoietic neoplasms (predominantly lymphomas) was significantly reduced in both mouse strains by TP treatment and both the onset and incidence of solid neoplasms was significantly reduced in CBA mice treated with TP. These results encourage more research on nitroxide-based antioxidants in the chemoprevention of cancer to elucidate the mechanism(s) involved.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A4.
Abstract A52: Koetjapic acid suppresses angiogenesis causing inhibition in VEGF expression
Authors: Shah Amin Malik , Majid Abdul , Nassar Zeyad D. , Aisheh Abdelrahim A. , Alrokayyan Salman A. , Abu-Salah Khalid M. 
Published: January 2011

Abstract
Koetjapic acid is a naturally occurring ichthyotoxic compound which can be isolated from the stem bark of Sandricum keotjape. This is a large tree species that can be found widely in Malaysia and other tropical countries in Southeast Asia. In our studies, we found koetjapic acid to be strongly antiangiogenic causing significant inhibition in endothelial tube formation. The compound inhibited VEGFA expression and caused retardation in cell migration. Keotjapic acid also suppressed the activity of Hif-1a and up regulates TGFβ and NFκB activity. This suggests the potential use of Keotjapic acid to target ailments that is angiogenesis dependent.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A52.
Abstract A53: Antiangiogenic activity of GER, a derivative of sweet leaf tea extract, is mediated by the downregulation of bFGF and VEGF
Authors: Yang Peiying , Cartwright Carrie , Liu Dong , Liu Zhijun 
Published: January 2011

Abstract
Mounting evidence indicates that angiogenesis is essential for the proliferation and survival of number of malignant diseases, thus inhibition of angiogenesis might be an effective therapeutic strategy. Antiangiogenic agent that targets both bFGF and VEGF (VEGFR) are considered to be effective adjuncts to the treatment of solid tumors or cancer preventive. Chinese sweet leaf tea, a hot water extract of Rubus suavissimus S. Lee (Rosaceae) (RUS) has been reported to have antiangiogenic activities evidenced by its ability to inhibit the angiogenic initiation and growth of human placental vein tissue (Liu et al., Phytother, Res. 20: 806-813, 2006) and experimental corneal neovascularization (Hakan, O.F., et al, Pharmaceu. Biol. 45: 44-47, 2007). We reported that this particular extract has the ability to inhibit the endothelial tubule formation, migration, and VEGF (VEGFR) of the HUVEC cells (Proc. Am. Assoc. Cancer Res, 1432, 2009). Here we investigated the anti-angiogenic activity of GER, a combination of gallic acid, ellagic acid, and rubusoside purified from the RUS and the relevant molecular mechanisms using HUVEC cells. Our preliminary data demonstrated that GER (5 to 25 µg/ml) markedly inhibited migration of HUVEC cells compared to the vehicle control. This inhibitory effect was concentration-dependent. At a similar concentration, the endothelial tubule formation was almost completely inhibited. When HUVEC cells were treated with GER (5 to 20 µg/ml), the expression of both bFGF and VEGF were markedly inhibited even at the lowest starting concentration. These inhibitory effects were also concentration-dependent. To further confirm the involvement of VEGF pathway in GER-induced anti-angiogenic activity, the protein level of tyrosine kinase receptor VEGFR2 (Flk-1/KDR) was examined. Intriguingly, the expression of Flk-1 was significantly suppressed in HUVEC cells treated with GER (40 µg/ml) by 54.1% ± 2.3% in comparison to that of vehicle control. In contrast, VEGFR2 kinase activity and protein levels of VEGFR1 remained unchanged compared to that of the vehicle control. These results suggest that GER derived from the sweet leaf tea extract may be completely responsible for the observed anti-angiogenic effect of the sweet leaf tea reported previously by down-regulating proangiogenic factors bFGF and VEGF. The chemopreventive effect of GER and its parent extract RUS on the development of human pancreatic carcinoma (L3.6pl cells) in mouse orthotopic model is currently under investigation and will be reported. This study was supported by NIH grant 1R21 AT002882-01A2.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A53.
Abstract A57: Breast adipocytes bioactivate Vitamin D3 and regulate hormone-induced epithelial cell growth
Authors: Zinser Glendon M. , Kashinkunti Soumya , Niehaus Matt 
Published: January 2011

Abstract
Vitamin D3, a nutritionally modulated hormone, participates as a negative growth regulator of mammary gland development and transformation. However, the mechanism behind breast specific vitamin D3 synthesis, metabolism, and signaling to maintain glandular homeostasis and inhibit the onset of mammary transformation remains unknown. Our objective was to test the concept that vitamin D3 signaling in mammary adipose tissue contributes to the negative growth regulation of mammary epithelial cells. We hypothesized that the mammary adipose tissue bioactivates 25-hydroxyvitamin D3 [25(OH)D3] to the active metabolite, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], and induces adipocyte Vitamin D3 Receptor (VDR) signaling along with paracrine secretion of 1,25(OH)2D3 to surrounding mammary epithelial cells to regulate growth of normal and transformed breast epithelial cells. We utilized mammary glands from VDR knockout (KO) and wild type (WT) mice for various procedures including ex vivo co-cultures with mammary epithelium and adipocytes, gene and protein expression assays, immunohistochemistry, and whole mount analysis. We discovered that breast adipocytes express essential signaling components of the vitamin D3 endocrine system and have the ability to bioactivate 25(OH)D3 to 1,25(OH)2D3 inducing mammary specific vitamin D3-responsive gene expression. Breast adipocytes likely participate to maintain localized vitamin D3 homeostasis and contribute to 1,25(OH)2D3-induced growth regulation of mammary epithelial cells in response to various hormonal stimulations, modulating mammary development and differentiation. Thus, our work suggests that breast adipose tissue serves as a vital endocrine mediator of Vitamin D3 signaling and offers a possible mechanism by which elevated 25(OH)D3 serum concentrations reduce the susceptibility to breast cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A57.
Abstract A58: Activation of diverse signaling pathways in pancreatic cancer revealed by phosphoproteomics
Authors: Kim Min-Sik , Kuppireddy Sarada Vineela , Zhong Jun , Jacob Harrys KC , Marimuthu Arivusudar , Kashyap Manoj Kumar , Pandey Akhilesh 
Published: January 2011

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Based on genomic studies, a number of genes that have somatic mutations including CDKN2A, SMAD4, TP53 and KRAS have been identified in pancreatic cancers. Recently, a comprehensive genomic analysis was performed in a panel of 14 primary pancreatic cancer cell lines and 10 xenografts, in which ∼1,500 somatic alterations were identified and a core set of 12 signaling pathways were defined.
In this study, we characterized the 14 primary pancreatic cancer cell lines whose genomes have been sequenced. From Western blots using anti-phosphotyrosine antibodies, we observed a heterogeneous pattern of tyrosine phosphorylation in these cell lines, indicating that different tyrosine kinases were likely activated in different cells. Phosphotyrosine-containing peptides were enriched by immunoprecipitation by anti-phosphotyrosine antibodies. The enriched phosphopeptides were analyzed on a high resolution Fourier transform mass spectrometer coupled to nanoflow reverse phase liquid chromatography.
Our preliminary data indicates that the approach used in this study is suitable for the global profiling of tyrosine kinase pathways that are abnormally activated in pancreatic cancers. For example, lymphocyte-specific protein tyrosine kinase and spleen tyrosine kinase were observed to be activated in one of pancreatic cancer cell lines (Panc 8.13), while insulin receptor was activated in different cell lines (Panc 198).
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A58.
Abstract A59: Prospective analysis of the association between use of statins or other lipid-lowering agents and colorectal cancer risk
Authors: Simon Michael S. , Rosenberg Carol A. , Rodabough Rebecca A. , Greenland Philip , Ockene Ira S. , Hemant Roy K. , Lane Dorothy S. , Cauley Jane A. , Khandekar Janardan D. 
Published: January 2011

Abstract
Background: Experimental and epidemiologic data suggest that 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have antitumor activity against colorectal cancer (CRC). We utilized data from the population-based Women's Health Initiative (WHI) cohort to assess whether statins are associated with a decreased risk of CRC.
Methods: The study population included 159,219 postmenopausal women ages 50-79 at baseline, in which 2,000 cases of CRC were identified over an average of 10.7 (2.9) years of follow-up. All cases of CRC were confirmed by review of medical records and pathology reports. Participants were asked to bring all current medications to their screening interviews and clinic staff entered information on statin use and other lipid lowering medications into the WHI database. Self- and interviewer-administered questionnaires were used to collect information on other CRC risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses investigated the association of any statin use, type of statin, statin potency, and duration of use with CRC. Statistical tests were two-sided.
Results: Statins were used by 12,030 (7.6%) women in the cohort. The annualized rate of CRC was 0.13% among statin users and 0.12% among nonusers. The multivariable adjusted HR for statin users compared with nonusers was 0.99 (95% CI=0.83 to 1.20, p=0.95). There was no trend in risk of CRC by duration of statin use, with HR = 0.91 (95% CI=0.66 to 1.27) for &lt; 1 years of use, HR = 1.28 (95% CI=0.97 to 1.68) for 1- &lt; 3 years of use, and HR =0.79 (95% CI=0.56 to 1.11) for &gt; 3 years of use. There was no relationship between type of statin use, statin potency (low, medium and high), or use of other lipid-lowering medications and CRC risk. In addition there was no relationship between statin use and tumor location (proximal, distal and rectal), or clinical features (tumor stage, grade or histology).
Conclusions: Statin use was not associated with a decrease in CRC risk in the WHI cohort.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A59.
Abstract A65: Gene-based test for lung cancer risk motivates smoking cessation in randomly selected smokers
Authors: Hopkins Raewyn J. , Young Robert P. , Hay Bryan A. , Gamble Gregory D. 
Published: January 2011

Abstract
Personalized risk assessment has been successfully used in coronary heart disease prevention to motivate lifestyle change and target drug therapy. In the Tension, Trigger and Treatment (3Ts) paradigm of smoking cessation, smokers quit smoking when the perceived harms outweigh benefits (or when motivational tension outweighs optimistic bias). Using a gene-based test for lung cancer risk, recently validated in a prospective study, we examined the effect of risk assessment on smoker's attitudes and actions to quitting. In this pilot study, 28 smokers were randomly recruited from a hospital database (eligibility: ≥40 years old, current smoker, and 20+ pack year smoking history). Through a telephone questionnaire, baseline smoking history and recent quit attempts were documented. Smokers were also offered a gene-based risk test for lung cancer risk. 25 (90%) accepted and were followed. On visit 1, smokers were counseled, consented and a cheek swab was taken for genotyping. On visit 2, the lung cancer risk test result was given along with materials on smoking cessation services and medications.
Based on a telephone questionnaire at 6 months after genetic testing (n=25) we found the following; 32% had quit smoking while 48% had reduced their smoking consumption (overall 80% had taken positive steps toward reducing smoking), 48% had used a smoking cessation service or product and only 4% of smokers appeared less committed to quitting. Quit rates were comparable in moderate- and high-risk groups.
We conclude from this pilot study that personalized risk assessment using a gene-based test of lung cancer susceptibility appears to confer a positive effect on quitting smoking. The quit rates achieved in this study occurred in randomly selected smokers and compares favorably with other approaches. We suggest that the risk test provides a teachable moment and enhances motivational tension towards quitting.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A65.
Abstract A67: Phase IIA trial testing erlotinib as an intervention against intraductal papillary mucinous neoplasms
Authors: Lipkin Steven M. , Lee John , Imagawa David , Zell Jason , Wong Vanessa , Gonzalez Rachel , Della'Zanna Gary , Richmond Ellen , Rodriguez Luz , Meyskens Frank 
Published: January 2011

Abstract
Intraductal papillary mucinous neoplasms (IPMNs) account for about 7% of clinically diagnosed pancreatic neoplasm and up to 50% of all incidentally detected pancreatic cysts. Described by Oshi et al in 1982, the incidence of these mucin-producing epithelial tumors of the exocrine pancreas has been increasing. Furthermore, IPMNs are thought to be direct precursors of pancreatic ductal carcinoma (PDA), which is among the most lethal human cancers. Many of the IPMNs are detected occur in nonsurgical candidates. Those surgically resected, a significant proportion develops PDA in the pancreatic remnant and die of disseminated disease. There is currently no chemotherapy specifically approved for treating IPMNs. Erlotinib (Tarceva, OSI-774) is an anti epidermal growth factor receptor (EGFR) orally active antitumor agent for treatment of solid tumors that is used in combination with chemotherapy to treat pancreatic adenocarcinoma.
A single arm, presurgical phase IIa trial using 100mg erlotinib in IPMNs patients (7-28 days prior to surgery) was conducted. Pre and post-erlotinib IPMN tissues were compared for a reduction in the EGF regulated biomarker Mucin 5AC (MUC 5AC) as the primary outcome. Secondary outcomes included clinical regression of IPMNs and quantification of the concentration of erlotinib in pancreatic tissue. Six IPMN patients were enrolled and pancreatic surgical specimens consistently showed decreased MUC5AC with erlotinib treatment. Additionally, one patient had a clinical complete response by CT criteria. No unanticipated safety issues were observed in trial participants. Overall, these preliminary results suggest erlotinib and other EGFR antagonists should be examined further for anti-IPMN activity.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A67.
Abstract A68: Randomized presurgical trial of finasteride vs. flutamide vs. placebo in prostate cancer
Authors: Zanardi Silvia , Maffezzini Massimo , Puntoni Matteo , Montironi Rodolfo , Johansson Harriet , Campora Sara , Vagge Alessandra , Rondanina Gabriella , Bandelloni Roberto , Turbino Laura , Mori Marco , Hurle Rodolfo , Decobelli Ottavio , Carmignani Giorgio , Santinelli Alfredo , Mazzucchelli Roberta , Bartels Peter H. , DeCensi Andrea 
Published: January 2011

Abstract
This abstract is being presented as a short talk in Concurrent Session 5. A full abstract is printed in the Proffered Abstracts section (PR-03) of the Conference Proceedings.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A68.
Abstract A73: Randomized placebo-controlled trial of pioglitazone for oral premalignant lesions: A cross-consortium collaborative study in progress
Authors: Boyle Jay O. , Ondrey Frank G. , Brown Powel H. , Bailey Howard H. , Kim KyungMann , El-Naggar Adel K. , Szabo Eva M. 
Published: January 2011

Abstract
This abstract is being presented as a short talk in Concurrent Session 14. A full abstract is printed in the Proffered Abstracts section (PR-10) of the Conference Proceedings.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A73.
Abstract A75: Nonsteroidal anti-inflammatory drugs (NSAIDs) and colorectal cancer risk in the National Institutes of Health-AARP Diet and Health Study
Authors: Ruder Elizabeth H. , Laiyemo Adeyinka O. , Graubard Barry I. , Hollenbeck Albert R. , Schatzkin Arthur , Cross Amanda J. 
Published: January 2011

Abstract
Background and Aims: Prolonged nonsteroidal anti-inflammatory drug (NSAID) use has been associated with lower colorectal cancer risk; however, little is known about the association of NSAID use within colorectal subsites or among individuals with a family history of colon cancer. This study assessed NSAID use and colorectal adenocarcinoma by subsite, including subanalysis of individuals with a family history of colon cancer.
Methods: Using Cox proportional hazard regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between NSAID use and colorectal cancer incidence among 301,240 participants; of whom 26,994 individuals reported having a first degree relative with history of colon cancer. We accrued 3,894 colorectal cancer cases during 10 years of follow-up; 372 cases had a first degree relative with colon cancer.
Results: Use of aspirin or non-aspirin NSAIDs (yes versus no) reduced colorectal cancer risk (HR=0.91, 95% CI: 0.85, 0.98; HR=0.82, 95% CI: 0.77, 0.87, respectively); these risks were lowered with increasing frequency of use (HR=0.86, 95% CI: 0.79, 0.94; HR=0.71, 95% CI: 0.63, 0.80 for daily use compared to non-users of aspirin or non-aspirin NSAIDs, respectively). Participants with a first degree relative with colon cancer who used non-aspirin NSAIDs daily had reduced colon cancer risk specifically (HR: 0.49, 95% CI: 0.29, 0.82).
Conclusions: NSAID use reduced colorectal cancer risk; the magnitude of this association varied with NSAID type and tumor location. Daily non-aspirin NSAID use was associated with a 50% lower risk of colon cancer in those with a first degree relative with this malignancy.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A75.
Abstract A83: A prospective study of dietary vitamin D intake and total all-cause mortality and cancer mortality in men and women
Authors: Murphy Neil , Michaud Dominique , Vineis Paolo , Gallo Valentina , Riboli Elio 
Published: January 2011

Abstract
Introduction: Recent research investigating the vitamin D-cancer hypothesis has generally focused on outcomes of cancer incidence, with few studies examining the effects of vitamin D on mortality. Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we analysed the relationships between dietary vitamin D consumption and total all-cause mortality and cancer specific mortality.
Methods: Vitamin D intakes were estimated from dietary questionnaires administered at recruitment. Risk estimates for total all-cause mortality and cancer specific mortality were obtained by using Cox proportional hazards models, stratified by age at recruitment and study centre, and adjusted for smoking status, body mass index, physical activity, and intakes of total energy, alcohol, calcium, saturated fat, cholesterol and vegetables. Our main analysis included all participants. In secondary analyses, we excluded individuals who reported previous chronic disease at baseline (stroke, cancer, and myocardial infarction).
Results: After a mean follow-up of 9.7 years there were 21,345 all-cause deaths and 8,332 cancer-related deaths among the 475,862 participants. For total all-cause mortality, no associations were observed when the highest intake quintile of vitamin D was compared against the lowest in men (HR 0.88, 95% CI: 0.75-1.04; P-trend 0.13) and women (HR 0.99, 95% CI: 0.87-1.12; P-trend 0.83). For total cancer mortality, a statistically significant 23% reduction in risk was observed among men in the highest vitamin D intake quartile compared with the lowest (HR 0.77, 95% CI: 0.60-0.99). No association was observed for total cancer mortality amongst women (Q5 vs. Q1 HR 1.04, 95% CI: 0.88-1.23). For male colorectal cancer mortality, a reduced risk was observed when participants in the highest intake quartile were compared with those in the lowest intake quartile (HR 0.50, 95% CI: 0.19-1.30; P-trend 0.05). No significant associations were observed for vitamin D intake and colorectal cancer mortality amongst women. Results from the secondary analyses (i.e., excluding existing conditions at baseline) were generally similar to the primary analysis; however the association for colorectal cancer risk amongst men was slightly stronger and statistically significant (HR 0.30, 95% CI: 0.10-0.94; P-trend &lt;0.01).
Conclusion: Results from this large prospective study suggest that higher dietary vitamin D intakes may reduce the risk of overall cancer mortality and colorectal cancer mortality in men.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A83.