bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD09-04: Weight Loss in Postmenopausal Women Is Associated with Modulation of Serum and Tissue Based Risk Biomarkers
Authors: Fabian CJ , Kimler BF , Phillips TA , Zalles CM , Klemp JR , Malone LM , Hursting SD. 
Published: April 2011

Abstract
Background
In a pilot study, a structured program of reduced energy diet, physical activity, and weekly group behavioral intervention with other high risk women was successful at producing a median 11% weight loss with at least a 5% weight loss in 88% of subjects. We evaluated the association of weight loss with changes in serum and breast tissue risk and mechanisms of action biomarkers. Methods
High risk postmenopausal women with BMI &gt;25 kg/m2 had breast tissue harvested by random periareolar fine needle aspiration (RPFNA) before and after a 6-month energy balance intervention. Specimens were evaluated for biomarkers including cytomorphology, proliferation (immunocytochemical Ki-67), gene expression by RT-qPCR, and expression of cytokines and adpokines by Luminex assay. Fasting serum was assayed for insulin, glucose, adiponectin, leptin, high sensitivity CRP, IL-6, prolactin, SHBG, estradiol and testosterone using ELISA or Luminex.
Results
For 24 biomarker evaluable subjects, 21 had &gt;5% weight loss (median = 11%). Cytologic atypia was present in 10/24 at baseline and 4/24 at 6 months (p=0.034). For 20 subjects with sufficient cells for assessment of Ki-67 at both times, median baseline Ki-67 was 0.7% and off study 0.3%, with a median change of -0.2% (p=0.19). Statistically significant changes (≥0.003; Wilcoxon) were observed for serum levels of adiponectin, adiponectin:leptin ratio, and SHBG (increases); and leptin, bioavailable estradiol and hsCRP (decreases). Reduction was also observed for insulin (p=0.018) and bioavailable testosterone (p=0.033). These results were duplicated (p≥0.014) by Luminex for adiponectin, leptin, adiponectin: leptin ratio, and insulin; plus hepatocyte growth factor (HGF, decrease). Also, an increase in the adiponectin:leptin ratio was observed for the RPFNA specimens (p=0.012). Gene expression (RT-qPCR) of pS2 was significantly modified (decrease, p=0.035). Further, the weight loss (expressed as relative change) was highly statistically correlated with change (relative) in serum leptin, adiponectin:leptin ratio, SHGB, and free estradiol; as well as with relative change in adiponectin:leptin ratio in RPFNA specimens. Conclusion
Weight loss in high risk postmenopausal women is accompanied by significant modulation of numerous serum and breast tissue-based biomarkers. For several risk and response biomarkers there is a significant correlation between change in the biomarker and the weight loss achieved. This suggests the possibility of identifying mechanisms of action and signaling pathways for dietary/energy balance interventions that may reduce risk for development of breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-04.
Abstract PD09-06: Obesity Promotes Breast Cancer Progression and Tamoxifen Resistance Via Cross-Talk between Growth Factor and Estrogen Signaling Pathways
Authors: Bowers LW , Cavazos DA , De Angel RE , Price RS , Hursting SD , Brenner AJ , deGraffenried LA. 
Published: April 2011

Abstract
Epidemiological studies indicate that obesity increases the risk of breast cancer by approximately 50% in postmenopausal women. This population most commonly develops estrogen receptor (ER) alpha positive breast cancer, suggesting that elevated estrogen synthesis by the adipose tissue and local mammary epithelia is the primary mediator of breast tumorigenesis in obese postmenopausal women. However, the specific mechanisms by which obesity promotes the development of postmenopausal breast cancer remain unclear. In vitro and animal studies have indicated that obesity-associated growth factor and cytokine signaling also play a role in breast tumorigenesis. Specifically, obesity is accompanied by elevated levels of insulin, insulin-like growth factor 1 (IGF-1), and leptin, and these all have significant tumorigenic effects in the breast.
In the current study, we utilize an in vitro model of obesity to examine the effects of elevated circulating hormones and growth factors on breast cancer cells. C57BL/6 mice were randomized at six weeks of age to either a 60% fat diet to induce obesity or a 10% fat diet to produce a lean comparison and maintained on these diets for 12 weeks prior to sacrifice. Sera was obtained from the mice at the time of euthanasia and used to treat ER alpha positive MCF-7 breast cancer cells at a concentration of 2% in serum-free media. Preliminary data indicates that sera from the obese mice induces 31% greater proliferation of MCF-7 cells in comparison to sera from lean animals (p=0.0025). This proliferation is mediated primarily via a phosphoinositide 3-kinase (PI3K) pathway, as evidenced by the ability of LY294002, a PI3K inhibitor, to neutralize the proliferative effect of the obese sera. The addition of LY294002 to MCF-7 cells treated with 2% obese sera decreased proliferation by 43% (p=0.0083). Intriguingly, tamoxifen did not significantly affect proliferation in the cells treated with obese sera (p=0.2425), suggesting that obesity may induce tamoxifen resistance.
Consequently, we hypothesize that obesity promotes breast cancer progression and tamoxifen resistance via cross-talk between growth factor and ER alpha signaling pathways. Further studies will be conducted to examine the pathways through which circulating factors mediate obesity-induced breast cancer progression. These will include measurement of the expression and activation of ER alpha, Akt, Erk1/2, IGF-1 receptor, and other proteins in MCF-7 cells in response to treatment with sera from obese and lean mice. By improving our understanding of the mechanisms linking obesity and post-menopausal breast cancer risk, we ultimately hope to develop a rational and effective chemopreventive regimen for this population.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-06.
Abstract PD09-08: Obesity in Long-Term Disease Free Survivors of Invasive Breast Cancer
Authors: Bahadur S , Roques-Davis R , Shi R , Burton G , Quispe D. 
Published: April 2011

Abstract
Background: As the number of breast cancer survivors increases due to improvements in screening and treatment for breast cancer, there is a particular interest in identifying lifestyle factors associated with long-term survival. Obesity may be one of the modifiable risk factors that can play a role in the outcome of breast cancer patients however studies shown controversial results. Besides, little is known about the role of obesity in long-term survivors. The objective of this study is to examine the role of obesity in breast cancer patients who remained disease free at least 5 years after diagnosis.
Methods: We reviewed the medical records of all women with invasive breast cancer diagnosed at LSUHSC between 1980 and 2005. The patients with stage IV breast cancer at diagnosis were excluded from the analysis. For this study we selected patients whom were disease free at least five years after the breast cancer diagnosis. We classified our patients by body mass index (BMI) at the time of breast cancer diagnosis into: normal weight (BMI &lt;25 kg/m2), overweight (BMI 25-29 kg/m2), and obese (BMI &gt;30 kg/m2). Data on demographics clinical characteristics, tumor characteristic, breast cancer therapy, and relapse were analyzed within BMI classes. Results: A total of 967 patients were diagnosed with invasive breast cancer between 1980 and 2005. Out of those 49% were African American, 29% were overweight, and 49% were obese. From this population 597 (62%) patients were disease free more than 5y: 217 (49%) obese, 113 (26%) overweight, 112 (25%) normal weight. Obese breast cancer survivors in comparison to overweight and normal weight survivors were more likely to: be African American (61%, P&lt;0.01), received Medicaid coverage (14.2%, p=0.05) and to have lower rates of mastectomy (p=0.017). There was not difference in tumor characteristics (ER status, Nodal status, Tumor size) and adjuvant treatment (chemotherapy, radiotherapy and hormonal therapy) between obese and non-obese patients. One hundred and ten patients (19%) developed a recurrence 5 years after diagnosis (48 obese and 33 overweight): 65 local (48 obese and 33 overweight) and 45 systemic (21 obese and 10 overweight).
Discussion: Our study has some limitations typical of retrospective studies and the generalization of the results may be limited. Our analysis suggests that in long-term disease free survivors obesity and race might be associated. To further clarify the role of obesity in long-term breast cancer survivors prospective studies with long term follow up are warranted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-08.
Abstract PL3-1: The Upside of Irrationality
Authors: D Ariely 
Published: April 2011

Abstract
Dan will discuss some of the challenges and underlying benefits of irrationalities in our day-to-day life. Using behavioral economic principles as a starting point, Dan will look at how these irrationalities affect our day-to-day behaviors both in the workplace and in our personal lives.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PL3-1.
Abstract S2-6: Aromatase Inhibitors and Risk of Myocardial Infarction, Stroke and Fracture
Authors: Ligibel JA , O'Malley A , Fisher M , Daniel G , Winer EP , Keating NL. 
Published: April 2011

Abstract
Randomized trials have demonstrated that aromatase inhibitors (AI's) are more effective than tamoxifen in preventing breast cancer recurrence. Since many women with early stage disease have a modest risk of recurrence, it is important to consider carefully the potential side effects of treatments in this setting. Trials have suggested increased risk of fracture is the only serious side effect of AI's, but study participants are often healthier than the general population, and little is known about toxicities of AI's in nontrial populations. We sought to evaluate the association between use of AI's and the incidence of myocardial infarction (MI), stroke, and fracture in community-based populations.
Methods: Using encounter and pharmacy data from WellPoint plans in the HealthCore Integrated Research Database, 44,463 women aged ≥50 years with at least 2 diagnosis codes for breast cancer between 2001 and 2007 were identified and followed through the end of 2008. We used propensity score methods to identify matched controls from a cohort of 88,101 women aged ≥50 years enrolled in WellPoint plans who had no diagnosis codes for breast cancer. We identified receipt of aromatase inhibitors and tamoxifen and used Cox proportional hazards models with time-varying treatment variables to assess whether treatment with aromatase inhibitors or tamoxifen was associated with MI, stroke, and fracture among women with breast cancer and to assess the association of breast cancer with the outcomes of interest.
Results: Among 44,049 breast cancer patients and 44,049 matched controls, the average age was 67 and 87% of cases and controls had no baseline comorbidities. After a median follow-up of 899 days for cases and 1004 for controls, 1.3% of women had an MI, 2.9% an ischemic stroke, 1.5% a hip fracture and 9.5% any fracture. Breast cancer patients treated with AI's had a significantly lower adjusted hazard of ischemic stroke and a significantly higher adjusted hazard of fracture compared with breast cancer patients not receiving an AI or tamoxifen.
Table. Adjusted hazard ratio (95% CI) associated with breast cancer and hormonal therapy
Treatment with AI or tamoxifen was not associated with MI or any fracture. Patients treated with tamoxifen had a significantly lower adjusted hazard of stroke and hip fracture compared with breast cancer patients not receiving hormonal therapy.
Conclusion: The side effect profile of AI's in this community-based population was similar to that seen in clinical trials and suggests that these drugs are associated with few serious side effects.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-6.
Abstract S6-1: Menopausal Hormone Therapy Influence on Cancer Incidence and Related Cancer Mortality in the Women's Health Initiative Randomized Trials
Authors: Chlebowski RT 
Published: April 2011

Abstract
The Women's Health Initiative (WHI) has conducted two phase III randomized placebo controlled trials evaluating menopausal hormone therapy. Conjugated equine estrogen 0.625 mg daily plus medroxyprogesterone acetate 2.5 mg daily (E+P) was evaluated in 16,608 postmenopausal women with no prior hysterectomy and conjugated equine estrogen alone 0.625 mg daily (E alone) was evaluated in 10,738 postmenopausal women with prior hysterectomy. Previous analyses suggested differences in E+P vs E alone influence on incidence and related mortality of several cancers. More recent analyses after additional follow-up clarify these issues and suggest a unifying hypothesis regarding hormone therapy influence on cancer. In cross study comparisons using multivariate Cox regression models statistically significant differences between the two WHI trials regarding E+P vs E alone influence on breast cancer incidence (P=0.01), colorectal cancer incidence (P=0.004) and deaths from non-small cell lung cancer (P=0.03) are seen. In addition, E+P, but not E alone, had a greater adverse influence on mortality attributed to breast cancer, colorectal cancer, and NSCLC then on the incidence of these cancers. Results are summarized below.
Menopausal Hormone Therapy Influence on Incidence and Related Mortality of Selected Cancer
Chlebowski JAMA 2003;289:3243, Chlebowski NEJM 2004;350:991, Stefanick JAMA 2006;242:1048, Ritenbaugh Cancer Epi Bio Prev 2008;17:2609, Prentice Cancer Epi Bio Prev 2009;18:1531, Chlebowski NEJM 2009;360:573, Chlebowski Gynecologic Oncology 2010;117:394; abst, Chlebowski Proc ASCO 2010;abst 1705 As estrogen plus progestin simulates angiogenesis, these findings suggest an hypothesis that, in addition to its influence on cancer incidence, combined E+P use, thru angiogenesis stimulation or other mechanisms, broadly enhances growth of already established cancers, differentially impacting cancer-related survival across several cancer categories.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-1.
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Authors: Tworkoski Kathryn , Singhal Garima , Szpakowski Sebastian , Zito Christina Ivins , Bacchiocchi Antonella , Muthusamy Viswanathan , Bosenberg Marcus , Krauthammer Michael , Halaban Ruth , Stern David F. 
Published: April 2011

Abstract
Therapies directed against receptor tyrosine kinases are effective in many cancer subtypes, including lung and breast cancer. We used a phosphoproteomic platform to identify active receptor tyrosine kinases that might represent therapeutic targets in a panel of 25 melanoma cell strains. We detected activated receptors including TYRO3, AXL, MERTK, EPHB2, MET, IGF1R, EGFR, KIT, HER3, and HER4. Statistical analysis of receptor tyrosine kinase activation as well as ligand and receptor expression indicates that some receptors, such as FGFR3, may be activated via autocrine circuits. Short hairpin RNA knockdown targeting three of the active kinases identified in the screen, AXL, HER3, and IGF1R, inhibited the proliferation of melanoma cells and knockdown of active AXL also reduced melanoma cell migration. The changes in cellular phenotype observed on AXL knockdown seem to be modulated via the STAT3 signaling pathway, whereas the IGF1R-dependent alterations seem to be regulated by the AKT signaling pathway. Ultimately, this study identifies several novel targets for therapeutic intervention in melanoma. Mol Cancer Res; 9(6); 801–12. ©2011 AACR.
Pharmacodynamic Evaluation of Pantoprazole Therapy on Clopidogrel Effects
Authors: Ferreiro José Luis , Ueno Masafumi , Tomasello Salvatore D. , Capodanno Davide , Desai Bhaloo , Dharmashankar Kodlipet , Seecheran Naveen , Kodali Murali K. , Darlington Andrew , Pham John-Paul , Tello-Montoliu Antonio , Charlton Ronald K. , Bass Theodore A. , Angiolillo Dominick J. 
Published: April 2011

Background—
Safety concerns have recently emerged based on a drug interaction between clopidogrel and proton pump inhibitors leading to reduced pharmacodynamic effects. However, whether such drug interaction is a class effect or a drug effect and if this can be modulated by timing of drug administration remains a matter of debate. The aim of this study was to assess the impact of high-dose pantoprazole therapy, a proton pump inhibitor with low potential to interfere with clopidogrel metabolism, administered concomitantly or staggered, on clopidogrel-mediated pharmacodynamic effects.

Methods and Results—

This was a prospective, randomized, crossover study conducted in 20 healthy volunteers. Subjects were randomly assigned to receive pantoprazole (80 mg daily) administered concomitantly (CONC) or staggered by 8 to 12 hours (STAG) for 1 week on a background of clopidogrel therapy (600-mg loading dose followed by a 75-mg maintenance dose during all phases) in a crossover fashion with a 2- to 4-week washout period between treatments. All subjects had a 1-week treatment phase with a clopidogrel-only regimen with a 2- to 4-week washout period from randomization sequence. Platelet function was assessed by flow cytometric analysis of the status of phosphorylation of the vasodilator-stimulated phosphoprotein, light transmittance aggregometry after adenosine diphosphate stimuli, and VerifyNow P2Y
12
system at 3 time points: baseline, 24 hours after loading dose, and 1 week after maintenance dose. The primary end point was the comparison of P2Y
12
reactivity index assessed by vasodilator-stimulated phosphoprotein at 1 week. After 1 week, there were no significant difference in P2Y
12
reactivity index between the CONC and STAG regimens (least-squares mean±SEM, 56.0±3.9% versus 56.1±3.9%;
P
=0.974), as well as when compared with the clopidogrel-only regimen (61.0±3.9%;
P
=0.100 versus CONC and
P
=0.107 versus STAG). Further, no differences were observed at baseline and 24 hours between regimens. Concordant results were obtained by light transmittance aggregometry and VerifyNow P2Y
12
assays.

Conclusions—
Pantoprazole therapy used at high doses is not associated with modulation of the pharmacodynamic effects of clopidogrel, irrespective of timing of drug administration.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01170533.
Direct Costs of Patients With Stroke Can Be Continuously Monitored on a National Level
Authors: Meretoja Atte , Kaste Markku , Roine Risto O. , Juntunen Merja , Linna Miika , Hillbom Matti , Marttila Reijo , Erilä Terttu , Rissanen Aimo , Sivenius Juhani , Häkkinen Unto 
Published: April 2011

Background and Purpose—
Treatment of stroke consumes a significant portion of all healthcare expenditure. We developed a system for monitoring costs from individual patient data on a national level in Finland.

Methods—
Multiple national administrative registers were linked to gain episode-of-care data on all hospital-treated patients with incident stroke over the years 1999 to 2007 (n=94 316). Inpatient and specialist outpatient costs were evaluated with a cost database, long-term care costs with fixed prices, and medication costs with true retail prices.

Results—
For the patients of Year 2007, the mean 1-year costs after an ischemic stroke were $29 580, after an intracerebral hemorrhage $36 220, and after a subarachnoid hemorrhage $42 570, valued in Year 2008 US dollars. Only part of these costs are attributable to stroke, because the annual costs prior to stroke were significant, $8900 before ischemic stroke, $7600 before intracerebral hemorrhage, and $4200 before subarachnoid hemorrhage. Older patients with ischemic stroke, and, among patients with ischemic stroke and subarachnoid hemorrhage, women, incurred higher costs. The mean estimated lifetime costs were $130 000 after ischemic stroke or intracerebral hemorrhage and $80 000 after subarachnoid hemorrhage. Annually $1.6 billion is spent in the care of Finnish patients with stroke, which equals to 7% of the national healthcare expenditure, or 0.6% of the gross domestic product. Costs of patients with stroke are increasing with prolonged survival and the aging population.

Conclusions—
Treatment of patients with stroke is a large national investment. Setting up a nationwide system for continuous monitoring of stroke costs is feasible. Cost data should optimally be evaluated in conjunction with effectiveness and performance indicators.
Water Mass Exchange in the Southern Ocean in Coupled Climate Models
Authors: Downes Stephanie M. , Gnanadesikan Anand , Griffies Stephen M. , Sarmiento Jorge L. 
Published: April 2011

Abstract
The authors estimate water mass transformation rates resulting from surface buoyancy fluxes and interior diapycnal fluxes in the region south of 30°S in the Estimating the Circulation and Climate of the Ocean (ECCO) model-based state estimation and three free-running coupled climate models. The meridional transport of deep and intermediate waters across 30°S agrees well between models and observationally based estimates in the Atlantic Ocean but not in the Indian and Pacific, where the model-based estimates are much smaller. Associated with this, in the models about half the southward-flowing deep water is converted into lighter waters and half is converted to denser bottom waters, whereas the observationally based estimates convert most of the inflowing deep water to bottom waters. In the models, both Antarctic Intermediate Water (AAIW) and Antarctic Bottom Water (AABW) are formed primarily via an interior diapycnal transformation rather than being transformed at the surface via heat or freshwater fluxes. Given the small vertical diffusivity specified in the models in this region, the authors conclude that other processes such as cabbeling and thermobaricity must be playing an important role in water mass transformation. Finally, in the models, the largest contribution of the surface buoyancy fluxes in the Southern Ocean is to convert Upper Circumpolar Deep Water (UCDW) and AAIW into lighter Subantarctic Mode Water (SAMW).
Performance of a Dynamic Initialization Scheme in the Coupled Ocean–Atmosphere Mesoscale Prediction System for Tropical Cyclones (COAMPS-TC)
Authors: Hendricks Eric A. , Peng Melinda S. , Ge Xuyang , Li Tim 
Published: April 2011

Abstract
A dynamic initialization scheme for tropical cyclone structure and intensity in numerical prediction systems is described and tested. The procedure involves the removal of the analyzed vortex and, then, insertion of a new vortex that is dynamically initialized to the observed surface pressure into the numerical model initial conditions. This new vortex has the potential to be more balanced, and to have a more realistic boundary layer structure than by adding synthetic data in the data assimilation procedure to initialize the tropical cyclone in a model. The dynamic initialization scheme was tested on multiple tropical cyclones during 2008 and 2009 in the North Atlantic and western North Pacific Ocean basins using the Naval Research Laboratory’s tropical cyclone version of the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS-TC). The use of this initialization procedure yielded significant improvements in intensity forecasts, with no degradation in track performance. Mean absolute errors in the maximum sustained surface wind were reduced by approximately 5 kt for all lead times up to 72 h.