bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B21: The effect of mutant Kras associated changes in redox signaling in pancreatic neoplasia.
Authors: Schultz Michelle A. , Shah Rital , DeCant Brian , Mascarinas Windel E. , Bentrem David , Grippo Paul 
Published: October 2015

Abstract
Recent studies have suggested that mutant Kras associated activation of the Nrf2 pathway may have a significant role in pancreatic cancer (PaCa) tumorigenesis. Nrf2 regulates a battery of antioxidant genes, including peroxiredoxin-1 (Prdx-1), that are responsible for maintaining redox homeostasis in the cell. While ROS detoxification may have significant roles in cancer, several non-classical mechanisms of redox signaling associated with protein oxidation and phosphorylation are also important in tumorigenesis. Prdx-1 can regulate transcription as a cofactor in multiple oxidation states, represses tumorigenesis in its reduced state, and can act as a nuclear chaperone in elevated states of oxidation and when phosphorylated. We are therefore investigating the role of Prdx-1 and its oxidation states in oncogenic signaling pathways in mutant Kras models of pancreatic tumorigenesis and neoplasia. Our data suggests that throughout tumor progression, Prdx-1 is differentially regulated and that its localization changes. In vitro, neoplastic and tumorigenic pancreatic cell lines have more total prdx-1 expression and oxidized Prdx-1 expression than non-tumorigenic cell lines. Moreover, cells that have mutant Kras were associated with higher levels of protein oxidation than those with wildtype Kras expression. Interestingly, mutant Kras was also associated with differences in pERK interaction with Prdx-1, which was also differentially regulated by NOX inhibitors and fatty acids that control pancreatic neoplasia. In addition, AKT, ERK , and FOXO3a phosphorylation were also differntially modified by DPI treatment and fatty acid treatment in wildtype and mutant Kras normal, neoplastic, and tumorigenic cell lines. We therefore conclude that mutant Kras is associated with elevated levels of Prdx-1 oxidation and that Kras mediated activation of ERK could be associated with changes in Prdx-1 signaling in pancreatic neoplasia.
Citation Format: Michelle A. Schultz, Rital Shah, Brian DeCant, Windel E. Mascarinas, David Bentrem, Paul Grippo. The effect of mutant Kras associated changes in redox signaling in pancreatic neoplasia.. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B21.
Abstract B25: Association of down-regulation of miR-193b and up-regulation of miR-196a with prognosis in gastric cancer
Authors: Sun Wenjie , Mu Yongping , Su Xiulan 
Published: October 2015

Abstract
Dysregulated expression of microRNAs (miRNAs) is confirmed to be closely associated with tumor development, progression, and carcinogenesis. The purpose of the present study was to determine the miRNA expression proﬁle of gastric cancer and to explore the relationship between aberrant miRNA expression and prognosis of gastric cancer in Chinese patients. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be present at significantly different expression levels in tissues from gastric cancer compared to those matched adjacent non-tumor tissues (ANTTs). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was then employed to characterize the expression patterns of miR-193b and miR-196a in total 96 snap frozen clinical gastric samples including 48 gastric cancer tissues and 48 paired ANTTs. The association between miRNA expression and clinical-pathological characteristics of patients was analyzed by binary logistic regression. We found that down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (P &lt; 0.05), while up-expression of miR-196a was significantly correlated with poor differentiation (P = 0.022). Moreover, down-expression of miR-193b elevated cancer risk in UICC stage (adjusted odds ratio = 8.69; 95% confidence interval = 1.06-56.91; P = 0.043;). A Kaplan-Meier survival curve indicated that the patients with high fold change of down-regulated miR-193b had a significantly shorter survival time (n = 19; median survival = 29 months) compared to patients with low fold change of down-regulated miR-193b (n = 29; median survival = 54 months) (P = 0.001). Overall survival time of patients with low fold change of up-regulated miR-196a (n = 27; median survival = 52 months) was longer than that of patients with high fold change (n = 21; median survival = 46 months) (P = 0.003). Thus, miR-193b and miR-196a may be applied as novel and promising prognostic factors in gastric cancer.
Note: This abstract was not presented at the conference.
Citation Format: Wenjie Sun, Yongping Mu, Xiulan Su. Association of down-regulation of miR-193b and up-regulation of miR-196a with prognosis in gastric cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B25.
Abstract B36: Pyruvate kinase M2 regulates adipocyte differentiation and the expression of enzymes involved in glucose metabolism
Authors: Kimura Tetsuo , Bhardwaj Priya , Falcone Domenick J. , Dannenberg Andrew J. , Subbaramaiah Kotha 
Published: October 2015

Abstract
The number of overweight and obese individuals continues to increase in both the U.S. and worldwide. This increase has led to a significant increase in obesity-related medical problems including diabetes mellitus, cardiovascular disease and cancer. In obesity, the differentiation of adipocytes is suppressed. Although adipocyte differentiation is associated with changes in glucose metabolism, little is known about the potential of enzymes involved in glucose metabolism to modulate this process. Pyruvate kinase (PK) mediates the rate-limiting step of glycolysis. The M2 isoform of PK (PKM2) is expressed in adipocytes but its role in adipogenesis is unknown. Here we demonstrate that PKM2 regulates the differentiation of both human and mouse adipocytes. Silencing of PKM2 in preadipocytes led to increased lipid accumulation, enhanced expression of markers (FABP4, PPARgamma, C/EBPBeta) of adipocyte differentiation and caused a shift in the pattern of enzymes involved in glucose metabolism favoring the TCA cycle. Overexpression of PKM2 suppressed adipocyte differentiation. In obesity, increased numbers of macrophages are found in adipose tissue and are believed to contribute to insulin resistance. Interestingly, we found that activated macrophages produce factors that inhibit adipocyte differentiation leading to increased levels of enzymes involved in aerobic glycolysis including PKM2. Given its importance in regulating adipocyte differentiation, we investigated the mechanism by which PKM2 expression was regulated. The HIF-1alpha - c-Myc - HnRNPA1 pathway induced PKM2 in preadipocytes. The redox sensor CtBP1 was found to be a negative regulator of this pathway. Taken together, these results provide evidence that PKM2 is not only expressed in adipose tissue but is also a determinant of adipocyte differentiation. Whether pharmacologically targeting PKM2 will impact on obesity or its consequences warrants further investigation.
Citation Format: Tetsuo Kimura, Priya Bhardwaj, Domenick J. Falcone, Andrew J. Dannenberg, Kotha Subbaramaiah. Pyruvate kinase M2 regulates adipocyte differentiation and the expression of enzymes involved in glucose metabolism. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B36.
Abstract B54: Current intervention strategies in the NCI PREVENT Cancer Preclinical Drug Development Program
Authors: Shoemaker Robert H. , Dunn Barbara K. , Suen Chen , Boring Dan L. , Klein Brian D. , Miller Mark S. , Steele Vernon E. 
Published: October 2015

Abstract
Chemoprevention research in the Division of Cancer Prevention (DCP) was re-structured in 2011 creating the PREVENT Cancer Preclinical Drug Development Program. This Program provides for peer-review of proposals from the general research community for development of small molecules or biologicals, including vaccines, for cancer prevention or biomarkers to facilitate clinical evaluation of prevention strategies. The process for applying to the Prevent Program is described at: http://prevention.cancer.gov/programs-resources/programs/prevent. Applications are submitted twice yearly and reviewed by a panel of experts from the extramural community and NIH Scientists outside DCP and scored for scientific merit, feasibility, etc. Top scoring applications undergo secondary review and prioritization by a panel of DCP and other NIH scientists. Applications with potential for near-term clinical translation are given highest priority. Approved projects are implemented as Task Orders via a system of contracts with academic and nonprofit, independent research institutions that provide the full range of preclinical studies, including good laboratory practice toxicology, needed to support Investigational New Drug Applications. Twenty-five Task Orders addressing a range of intervention strategies have been awarded in the first two years of the Program. Small molecules targeting classic aspects of inflammation as well as newer molecular-targeted agents (n=16) are under study. Pharmacodynamic assays are coupled to efficacy studies. Immunoprevention strategies targeting tumor-associated antigens as well as antigens from cancer-associated infectious agents (n=6) are being pursued. Preliminary data from current projects will be presented. The PREVENT Cancer Program has engaged a broad cross-section of investigators, supporting preclinical development of agents addressing a wide variety of cancer prevention strategies.
Citation Format: Robert H. Shoemaker, Barbara K. Dunn, Chen Suen, Dan L. Boring, Brian D. Klein, Mark S. Miller, Vernon E. Steele. Current intervention strategies in the NCI PREVENT Cancer Preclinical Drug Development Program. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B54.
Abstract CN01-01: Big challenges of big data: Biomedical science in the petabyte era
Authors: Shyr Yu 
Published: October 2015

Abstract
Next-generation sequencing technologies (NGS) have exploded in popularity in recent years thanks to their ability to produce an enormous volume of data quickly and at relatively low cost compared to traditional sequencing methods such as Sanger sequencing. The emergence of NGS has pushed forward the goal of personalized medicine, but looking at the entire scope of a study from experimental design to data analysis to the ultimate goal of dose selection based on a patient's genome reveals many more challenges. Sample size for RNA-seq studies has been a persistent problem that has only recently received attention. Sequencing data analysis packages are numerous and constantly in development, but without a clear gold standard, they can be more overwhelming than helpful. Finally, this genomic information must be seamlessly integrated with clinical information for the knowledge to be useable by practitioners before the goal of personalized medicine can become a reality.
Citation Format: Yu Shyr. Big challenges of big data: Biomedical science in the petabyte era. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN01-01.
Abstract CN07-02: Obesity, inflammation, and breast cancer
Authors: Dannenberg Andrew J. 
Published: October 2015

Abstract
Obesity is a risk factor for the development of several malignancies including hormone receptor–positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. Chronic inflammation increases the risk of multiple tumor types. A link between obesity, breast inflammation and hormone receptor-positive breast cancer was previously unknown. Obesity causes subclinical inflammation in visceral and subcutaneous white adipose tissue, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We found increased numbers of CLS, activation of the NF-kappaB transcription factor, increased levels of pro-inflammatory mediators and elevated aromatase levels in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity-inflammation-aromatase axis is important for breast carcinogenesis. Importantly, these findings have now been translated to women. Breast tissue was obtained from women who underwent surgery. CLS of the breast (CLS-B) were found in approximately 50% of patient samples. The severity of breast inflammation correlated with both body mass index and adipocyte size. Menopause is an independent determinant of CLS-B. Consistent with our preclinical findings, increased NF-κB binding activity, increased levels of pro-inflammatory mediators and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity-inflammation-aromatase axis is present in the breast tissue of most overweight and obese women and is likely to contribute to the increased risk of hormone receptor-positive breast cancer. The discovery of the connection between obesity, breast inflammation and changes in the expression of genes linked to breast cancer provides a mechanistic rationale for the development of behavioral, dietary and pharmacological strategies to reduce the risk of breast cancer. Non-invasive biomarkers of adipose inflammation are needed to both identify at-risk individuals and monitor the efficacy of interventions aimed at attenuating inflamed adipose tissue. Recent progress in the development of blood biomarkers of breast adipose inflammation will be reviewed.
Citation Format: Andrew J. Dannenberg. Obesity, inflammation, and breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN07-02.
Abstract CN11-02: Impact for the menopausal transition on skeletal and breast health
Authors: Cauley Jane A. 
Published: October 2015

Abstract
Women spend about one-third of their lifespan in the postmenopausal period. Menopause represents a vulnerable time in a woman's life for a number of reason, in particular, for her skeletal health. Estrogen deficiency associated with menopause increases bone remodeling leading to an imbalance between bone formation and bone resorption. The Study of Women's Health Across the Nation (SWAN) is an ongoing multicenter study designed to investigate a broad range physiological, psychosocial and social issues for women at midlife. The long range goal was to distinguish ovarian aging from chronological aging. Skeletal health was a particular focus of SWAN. At baseline, all 3302 women were age 42-52 years and pre- or early perimenopausal, having had a menstrual period within 3-months of study entry. A 10-year longitudinal analysis was conducted in a subset of 242 African American, 384 Caucasian, 117 Chinese and 119 Japanese women for whom a final menstrual period (FMP) could be defined. Bone loss was not evident during the pretransmenopausal state (between 5-years and 1-year prior to the FMP). Bone mineral density (BMD) loss began 1-year prior to FMP and slowed 2 years after FMP. Cumulative loss was greatest in Asian women and slowest in African American women. The 10-year cumulative loss of lumbar spine BMD was 10.6%, most of which was lost in the transmenopause period.
This menopause associated estrogen deficiency might also influence breast density, a major risk factor for breast cancer. An ancillary study to SWAN focused on breast density: 1007 women from 3 sites were included. Mammograms that were taken 2-years before baseline up to 2-years after the 6th annual follow-up visit were retrospectively obtained and graded for breast density. Findings from the SWAN breast density include the observation that greater parity and younger age at first birth were inversely associated with breast density and may support a mechanism for parity and breast cancer through breast density. Smokers had lower breast density supporting an anti-estrogenic effect on breast tissue. The percentage of breast density decreased with increasing body mass index over time.
In conclusion, the SWAN study provides important insights into menopausal health.
Citation Format: Jane A. Cauley. Impact for the menopausal transition on skeletal and breast health. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN11-02.
Abstract PR09: Intermittent dosing regimens maintain efficacy of several cancer preventing drugs
Authors: Steele Vernon E. , Grubbs Clinton J. , Lubet Ronald A. 
Published: October 2015

Abstract
Many potential chemopreventive drugs have adverse effects on human subjects when given daily. One strategy to alleviate these adverse events is to give the drugs on an intermittent dosing schedule. Such intermittent dosing has proven effective in other settings to reduce toxicity with limited effect on efficacy. Two animal models were used: the rat methylnitrosourea (MNU) - induced mammary cancer model and the rat hydroxy-butyl(butyl)-nitrosamine (OH-BBN) -induced urinary bladder cancer model. For the mammary study female Sprague-Dawley rats were given 75 mg of MNU/kg body weight at 50 days of age and five days later the EGFR inhibitors, Erlotinib, Gefitinib or Lapatinib were administered either daily or once a week at two dose levels. Multiplicity of ER-positive mammary cancers was followed weekly for four months. For the urinary bladder study female Fischer 344 rats were given 150 mg OH-BBN/gavage twice weekly beginning at 56 days of age and continuing for 8 weeks. Two weeks after the last OH-BBN treatment the rats were given naproxen either daily, one week on/one week off, or 3 weeks on/3 weeks off. Bladders were excised after 8 months of naproxen treatment and bladders with tumors were excised and weighed. EGFR inhibitors and the NSAID, Naproxen, have similar efficacy when given intermittently compared to daily. The EGFR antagonists, Erlotinib and Lapatinib, decreased mammary cancer multiplicity by 90% given daily and 75 % given weekly. The NSAID, naproxen, decreased large bladder cancers by about 65-80% given either daily, one week on/one week off or 3 weeks on/3 weeks off. Therefore intermittent dosing can be used for agents in two different mechanistic classes in animal mammary and bladder cancer models to lower toxicity, yet show little reduction in chemoprevention efficacy compared to daily dosing. Intermittent dosing schedules in the clinic should reduce EGFR mediated rash and NSAID induced gastric toxicity clinically while retaining efficacy.
Citation Format: Vernon E. Steele, Clinton J. Grubbs, Ronald A. Lubet. Intermittent dosing regimens maintain efficacy of several cancer preventing drugs. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR09.
T-cell–based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition
Authors: Houot Roch , Schultz Liora Michal , Marabelle Aurélien , Kohrt Holbrook 
Published: October 2015

Abstract
Tumor immunotherapy has had demonstrable efficacy in patients with cancer. The most promising results have been with T-cell–based therapies. These include adoptive cell transfer of tumor-infiltrating lymphocytes, genetically engineered T cells, and immune checkpoint inhibitor antibodies. In this review, we describe the different T-cell–based strategies currently in clinical trials and put their applications, present and future, into perspective. Cancer Immunol Res; 3(10); 1115–22. ©2015 AACR.
Dose–Response Relationship Between Physical Activity and Risk of Heart Failure
Authors: Pandey Ambarish , Garg Sushil , Khunger Monica , Darden Douglas , Ayers Colby , Kumbhani Dharam J. , Mayo Helen G. , de Lemos James A. , Berry Jarett D. 
Published: October 2015

Background—
Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose–response association between PA and HF risk has not been reported previously.

Methods and Results—
Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose–response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]–min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67–0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87–0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77–0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58–0.73) the minimum guideline-recommended levels.

Conclusions—
There is an inverse dose–response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.
A Local Meshless Method for Approximating 3D Wind Fields
Authors: Pepper Darrell W. , Waters Jiajia 
Published: October 2015

AbstractAn efficient, mesh-free numerical method has been developed for creating 3D wind fields using data from meteorological towers. Node points are placed within a region of interest, generally based upon topological features. Since meshless methods do not require connective mesh generation, storage is greatly reduced, permitting implementation of the code using MATLAB on a personal computer. Utilizing locally collocated nodes and radial basis functions, a 3D wind can be quickly created that satisfies mass consistency. The meshless method yields close approximations to results obtained with mesh-dependent finite-difference, finite-volume, and finite-element techniques.