bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B5: Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study
Authors: Stolzenberg-Solomon Rachael Z. , Schairer Catherine , Hollenbeck Albert , Silverman Debra T. 
Published: June 2012

Abstract
Background: Adiposity at older age is positively associated with pancreatic cancer in many studies; however its association at younger ages and weight gain across a lifetime has not been examined extensively particular in cohort studies.
Methods: We prospectively analyzed the association between body mass index (BMI) at different ages (18, 35, 50, and &gt; 50 years), BMI gain, and first age of overweight or obesity and exocrine pancreatic cancer in the NIH-AARP Diet and Health Study, a large cohort of men and women aged 50–71 who completed questionnaires at baseline (1995–1996) and six months later that ascertained height and weight history. During follow-up though 2006, 2120 and 1204 pancreatic cancer cases were identified in the baseline cohort among participants &gt; 50 years (n=501,702) and sub-cohort who completed the second questionnaire (n=273,977), respectively. Hazards Ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazards with adjustment for smoking, sex, energy and total fat. Statistical tests were two sided.
Results: Compared to normal weight, overweight (body mass index, BMI &gt;25.0–30 kg/m2) or obesity (BMI &gt; 30 kg/m2) at ages 18, 35, 50 or &gt; 50 years was significantly associated with elevated pancreatic cancer risk with HR ranging from 1.18 to 1.25. Adiposity gain (per 5 kg/m2) from early adulthood to older age was significantly associated with pancreatic cancer especially among never smokers (HR=1.12, 95% CI 1.04–1.21). The etiologic fraction of pancreatic cancer explained by overweight or obesity at any age in our population was 13% overall.
Conclusion: Overweight or obesity at any age is associated with a greater pancreatic cancer risk. Prevention of weight gain might prevent pancreatic cancer.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B5.
Abstract B55: Dietary cadmium intake and risk of invasive breast cancer in the VITAL cohort
Authors: Adams Scott V. , Newcomb Polly A. , White Emily 
Published: June 2012

Abstract
Background: Evidence from two retrospective case-control studies suggests that cadmium is associated with risk of breast cancer. The primary routes of cadmium exposure in the general population are smoking cigarettes and eating certain foods including vegetables, grains, and seafood. To our knowledge, no reports from prospective epidemiological studies of cadmium and breast cancer risk have been published.
Methods: Dietary cadmium consumption was estimated for peri- or post-menopausal women in the VITamins And Lifestyle (VITAL) cohort by combining baseline food frequency questionnaire (FFQ) responses and US Food and Drug Administration Total Diet Study market basket survey data on the cadmium content of foods. Women reporting a personal history of breast cancer prior to enrollment in the study were excluded. The outcome of incident, invasive breast cancer was ascertained through linkage to the western Washington State Surveillance, Epidemiology, and End Results cancer registry. Women were censored at the earliest of diagnosis of in situ breast cancer, moving out of the catchment area, death, or withdrawal from the study. Multivariable adjusted Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for invasive breast cancer with increasing estimated dietary cadmium intake, adjusted for cigarette smoking history, total energy intake, total servings of vegetables and potatoes, and established breast cancer risk factors.
Results: During an average of 6 years of follow-up, 794 invasive breast cancers were registered among 31,630 women included in analysis. No evidence of an association between dietary cadmium and invasive breast cancer risk was observed in the entire analytical cohort (aHR (95% CI) comparing highest to lowest quartile dietary cadmium: 0.94 (0.63–1.38) P-trend=0.4). Similar results were obtained in analysis restricted to never-users of hormone therapy, or never-smokers. Because cadmium may compete for binding sites with zinc, we examined the interaction between dietary cadmium and estimated total intake of zinc from diet, supplements, and multivitamins; no evidence of effect modification was observed.
Conclusions: This study does not provide evidence in support of the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake was a limitation of the study that could have obscured an association.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B55.
Abstract B61: Postpartum mammary gland involution drives DCIS progression through collagen and COX-2, identifying a target for intervention
Authors: Lyons Traci R. , O'Brien Jenean , Conklin Matthew , Keely Patricia , Borges Virginia , Schedin Pepper 
Published: June 2012

Abstract
Prognosis of young women's breast cancer is influenced by reproductive history. Women diagnosed within five years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. We propose that breast involution following pregnancy accounts for the poor prognosis of breast cancers diagnosed postpartum. Our ‘involution hypothesis’ states that the physiologically normal microenvironment of the postpartum involuting gland is tumor promotional; however, testing the involution hypothesis has been limited by lack of pre-clinical models. We developed a mouse xenograft model of PABC that isolates postpartum mammary gland involution as a driving force for breast cancer progression and metastasis. In this model, human breast cancer cells are injected into actively involuting mouse mammary glands and nulliparous controls. Results from this model indicate that tumor cells exposed to the collagen rich involuting mammary microenvironment form larger tumors characterized by abundant fibrillar collagen, high COX-2 expression, and an invasive phenotype. In culture, these tumor cells are invasive in a collagen/COX-2-dependent manner. Importantly, in the involuting mammary gland, inhibition of COX-2 with celecoxib or ibuprofen reduced the collagen fibrillogenesis associated with involution, as well as tumor growth and lung infiltration. These anti-tumor effects were observed without blocking apoptosis of secretory mammary epithelial cells, which is required to remodel the gland to a non-secretory state, and is a requisite for advancing this strategy to clinical trial. The question of whether an NSAID based intervention study could be aimed at recently pregnant women at high risk for breast cancer remains to be determined, but is an extremely desirable objective given that there are more than 6 million pregnancies in the US per year. In summary, these data support further research to determine whether women at high-risk for postpartum breast cancer would benefit from treatment with NSAIDs during postpartum involution.
This work was funded by DOD, Komen, and ACS.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B61.
Abstract B72: Resolvin D1, derived from n-3 polyunsaturated fatty acid, stimulates efferocytosis and protects macrophages from oxidative stress-induced apoptosis
Authors: Lee Ha-Na , Kundu Joydeb Kumar , Shin Jun-Wan , Cha Young-Nam , Surh Young-Joon 
Published: June 2012

Abstract
Phagocytosis of apoptotic neutrophils by macrophages, called efferocytosis, is critical to resolution of inflammation as this process prevents the exposure of surrounding tissues at the inflammatory site to the toxic contents of lytic cells. Docosahexaenoic acid (DHA)-derived resolvin D1 (RvD1), endogenously generated during resolution of inflammation, is known to stimulate efferocytosis, but little is known about the mechanism of its action. In the present study, we found that lipopolysaccharide (LPS; 200 g/ml) suppressed efferocytosis by murine macrophage-like RAW264.7 cells, and RvD1 (50 nM) restored the phagocytic ability of these cells by down-regulating TNF-α expression. The inhibitory effect of RvD1 on LPS-induced TNF-α expression was associated with enhanced nuclear localization of p50/p50 homodimer and concomitant reduction in the nuclear levels of p65/p50 heterodimer. siRNA knockdown of NF-κB p50 abolished RvD1-mediated suppression of TNF-α expression and resulted in impaired efferocytosis, suggesting that the replacement of p65/p50 with p50/p50 homodimer is an essential event for RvD1-mediated stimulation of efferocytosis. In a murine peritonitis model, intraperitoneal administration of RvD1 (300 ng) abrogated zymosan A (30 mg/kg)-induced TNF-α production, thereby reactivating efferocytosis. In addition, RvD1 protected RAW264.7 cells from oxidative stress-induced apoptosis during efferocytosis. The generation of reactive oxygen species after efferocytosis was markedly blocked in RvD1-exposed macrophages. Moreover, RvD1 upregulated the anti-apoptotic Bcl-2 and Bcl-xL expression and downregulated the proapoptotic Bax and Bad expression. In conclusion, RvD1 expedites resolution of inflammation through stimulating efferocytosis while preserving viability of macrophage during efferocytosis. These findings account, at least in part, for the chemopreventive effects of DHA on inflammation-associated carcinogenesis.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B72.
Abstract B73: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair
Authors: Seo Young Rok 
Published: June 2012

Abstract
Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53-wild type cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53-wild type RKO cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating cell nucleus antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B73.
Abstract B74: EGCG inhibits cancer invasion by regulating tumor-stromal crosstalk in oral squamous cell carcinoma
Authors: Bae Jung Yoon , Moon Sook , Kim Eun Kyoung , Kim Jin 
Published: June 2012

Abstract
Introduction: Epigallocatechin-3-O-gallate (EGCG), a major constituent polyphenol of green tea, has been shown to have suppressive effects on the invasion of various cancer cells, whereas the exact mechanisms have not yet been fully elucidated. In this study, the effects of EGCG on the invasion of oral squamous cell carcinoma (OSCC) were investigated where the new perspective focused on tumor-stromal crosstalk was emphasized, unlikely other previous studies focused on cancer cell mainly.
Materials and Methods: OSCC were cultured with or without carcinoma-associated fibroblasts (CAF) in the dose dependent treatment of EGCG. In order to investigate the invasiveness, invasion assay and zymography were examined. Based on our previous study found that several cytokines are concerned with tumor-stromal crosstalk in invasion of OSCC, RT-PCR and ELISA assay were employed to examine the influence of EGCG on the expression levels of cytokines.
Results: The invasiveness of OSCC was reduced by EGCG treatment, and the 50% reduction was demonstrated at the half concentration of EGCG (25 μM) in co-cultured group with CAF, compared to OSCC mono-cultured (50 μM). Zymography showed that EGCG treatment reduced MMP-9 expression in co-cultured condition. In addition, EGCG resulted in a noticeable decrease in the expression of cytokines, especially GRO-α/CXCL1, concerned with tumor-stromal crosstalk in invasion of OSCC.
Conclusions: In this study, inhibitory effect of EGCG on cancer invasion was found at which its concentration is lower than previously known. Taking these results into consideration, EGCG may play an effective role in preventing invasion of OSCC by regulating tumor-stromal crosstalk.
Acknowledgement: This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0029702).
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B74.
Abstract B75: Resveratrol and its analogues as chemopreventive and anticancer agents in prostate cancer: Epigenetic mechanisms of action
Authors: Dias Steven J. , Li Kun , Dhar Swati , Ivanovic Marina , Rimando Agnes M. , Levenson Anait S. 
Published: June 2012

Abstract
Nutritional chemoprevention is a promising approach for prostate cancer (PCa) management. Resveratrol (Res), found in plants, has antioxidant, cardioprotective, anti-inflammatory and anticancer properties. Res may be considered as both a chemopreventive and chemotherapeutic agent on the basis of molecular and preclinical studies. We propose to investigate novel epigenetic mechanisms of the chemopreventive and anticancer effects of Res. We discovered that Res down-regulates metastasis-associated protein 1 (MTA1) by causing its proteasomal degradation. MTA1 levels correlate with cancer aggressiveness and metastases and, as a part of the nucleosome remodeling deacetylation (NuRD) complex, MTA1 plays a role in chromatin remodeling and transcriptional repression.
We hypothesize that MTA1 nuclear overexpression promotes PCa progression and metastasis by enhancing MTA1/HDAC1/NuRD deacetylation activity. We further hypothesize that Res, as a potent inhibitor of MTA1, exerts its anticancer effects, at least in part, through blocking MTA1/HDAC1/NuRD-mediated deacetylation. We propose: (1) determine the effects of Res on MTA1-mediated epigenetic modifications of PTEN and HIF-1α. We will use PCa cells with silenced MTA1 (shRNA-mediated knockdown) to examine the acetylation state of PTEN and HIF-1α in the presence or absence of Res. Transcriptional activation/repression of downstream signaling (PI3K/Akt) or target genes (VEGF) will be used as readouts. (2) evaluate MTA1-associated epigenetic anticancer effects of Res analogues in PCa. We will compare biopotency of natural and synthetic Res analogues in inhibiting MTA1, cell proliferation, invasion and migration in vitro. (3) evaluate MTA1-mediated Res chemopreventive and therapeutic efficacy in PCa mouse models. a. we will use orthotopic PCa xenografts to evaluate MTA1-mediated effects of Res on PCa initiation, progression and metastasis; b. we will evaluate Res chemopreventive and therapeutic effects using autochthonous, prostate-specific Pten −/− mouse model.
Our study is the first to identify MTA1 as a specific molecular target of Res, further defining a novel epigenetic mechanism of Res anticancer activity as an HDAC inhibitor. The mechanism-based studies will significantly contribute to a better understanding of the role of MTA1 as an upstream epigenetic regulator of tumor suppressors and oncogenes. The results from this study will aid the development of preventive and curative strategies based on Res, its potent analogues, and synergy with other “epigenetic” agents. Our preclinical studies will provide a powerful base for initiating clinical trials in men.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B75.
Abstract CN03-03: Chemoprevention of lung cancer by metformin
Authors: Dennis Phillip A. 
Published: June 2012

Abstract
Metformin is the most widely prescribed drug for type II diabetes. Diabetics maintained on metformin have decreased incidence of several types of cancer, including lung cancer, compared to diabetics maintained on other anti-diabetic drugs. This retrospective analysis has raised the possibility that metformin might be an effective chemopreventive agent. In diabetics, metformin decreases hepatic gluconeogenesis and decreases circulating levels of IGF-I and insulin. In certain tissues such as liver, muscle, and fat, metformin activates AMP-activated kinase and inhibits mTOR, a kinase whose activity is required for lung tumorigenesis in several mouse models. We previously showed that metformin in the drinking water inhibits tobacco carcinogen-induced lung tumorigenesis in a mouse model of lung cancer. Inhibition of tumorigenesis occurred at steady state levels of metformin easily achieved in humans, and the mechanism of action in lung tissues appeared independent of AMPK but dependent upon inhibition of IGF-I receptor-mediated signaling. This presentation will describe the efficacy of metformin in other mouse models of lung cancer, identify additional tissue-specific biomarkers for metformin that might have predictive value, and discuss the design of clinical prevention trials with metformin.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN03-03.
Abstract CN07-03: IL6 and AKT as targets for chemoprevention
Authors: Ibarra-Drendall Catherine , Ford Anne , Tolbert Nora , Frye Endya , Lee Laurie , Broadwater Gloria , Barry William , Petricoin Emanuel , Liota Lance , Seewaldt Victoria 
Published: June 2012

Abstract
Background: Currently we lack adequate prevention strategies for triple-negative breast cancer; progress in designing targeted strategies is limited by a lack of knowledge of the biology of cancer initiation. The origins of triple-negative breast cancer in premenopausal women are poorly understood. Importantly, we do not understand whether the molecular pathways that underlie the aggressive behavior of triple-negative breast cancer can be detected in premalignant breast lesions. Growing evidence indicates that early mammary carcinogenesis is regulated by integrated signaling networks and not by isolated genes. Interleukin-6 (IL6) plays a role in stem cell regeneration, promotes epithelial to mesenchymal transition (EMT), and high IL6 serum levels predict a poor outcome in premenopausal women with triple-negative breast cancer.
Methods and Results: We used Reverse-Phase Protein Microarray (RPPM) profiling to test for activation of phosphoprotein signaling in premalignant Random Periareolar Fine Needle Aspiration (RPFNA) mammary epithelial cytology from 65 high-risk African American women. Unsupervised hierarchical clustering of RPPM proteomic analysis RPFNA aspirates identified three activated ER− signaling pathways including co-activation of Akt/mTOR/PI3K and IL6/pStat3/vimentin. Analysis of interstitial breast tissue demonstrated that high interstitial IL6/VEGF cytokine production predicted high epithelial expression of pStat3/vimentin. Based on these observations we are currently launching a prevention trial to target Akt/mTor using metformin 500 mg bid.
Conclusion: This is the first demonstration that Akt/mTor and IL6/Stat3/vimentin signaling is activated in pre-cancerous mammary epithelial cells from high-risk premenopausal women. Currently we are testing whether trials are on-going to test whether metformin can inhibit activation of mammary epithelial Akt/mTor and perhaps IL6/Stat3/vimentin signaling.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN07-03.
Abstract CN08-02: Psychological stress and disease progression
Authors: Andersen Barbara L. 
Published: June 2012

Abstract
A randomized clinical trial was designed to test the hypothesis that cancer patients coping with a cancer diagnosis but receiving a psychological intervention would have reduced risk for disease progression (1994). Patients (N=227) surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychological and behavioral measures, had a health evaluation, and a 60 mL blood sample was drawn. Patients were randomized to Psychological Intervention or Assessment only arms. The intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment. Earlier papers (2004, 2007) showed that, compared to the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. T cell blastogenesis was also enhanced. An interim paper (2007) clarified treatment mechanisms in the Intervention arm. First, patients were satisfied with the intervention, but it was group cohesion that related to better outcomes. Second, offering patients a stress conceptualization (Selye) and teaching them multiple coping strategies related to better health. Third, three relationships between treatment utilization and outcomes are noted: 1) Relaxation training was associated with both distress reduction and symptom lowering. 2) Patients' use of assertive communication with health care providers was associated with better health outcomes. 3) Intervention strategy use was also associated with fewer signs/symptoms and cancer treatment toxicities. After a median of 11 years follow-up, recurrence occurred for 62 of 212 (29%) women and death for 54 of 227 (24%). Intent to treat hazard analyses showed, as predicted, Intervention arm patients had a reduced risk of recurrence [Hazard Ratio (HR)=0.55, P=.034] and breast cancer death (HR=0.44, P=.016). Follow up papers (2009) have examined the covariation of inflammation and distress during the period of intervention delivery (2009) and in the months prior to recurrence diagnosis (2008). Learning Objective 1: Show that a randomized clinical trial has produced evidence that a behavioral intervention can reduce fatal and nonfatal regional breast cancer recurrence. Learning Objective 2: Demonstrate that patients' use of assertive communication with health care providers was associated with better health outcomes.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN08-02.
Abstract ED05-02: Building a tobacco-free world: Engaging youth and young adults
Authors: Vallone Donna 
Published: June 2012

Abstract
A recent study by Christakis and Fowler (2008) found that when one or two people in a social network stop smoking, others in that network also tend to stop as well—highlighting both the importance of social networks and the potential to virally spread behavior change. Dr. Donna Vallone will discuss research related to prompting online social engagement and participation in the EX community, a component of the web-based smoking cessation program, www.becomeanex.org. Evidence suggests that these online social networks can provide social support to online smokers interested in quitting—a critical component of cessation treatment outlined in the US Clinical Guidelines for Smoking Cessation. Social media applications of EX on Facebook, Twitter and other channels will also be discussed.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED05-02.