bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ED05-02: Targeting estrogen receptors for breast cancer prevention
Authors: Ford Leslie G. , Dunn Barbara K. 
Published: May 2019

Abstract
Before “targeted” therapy was part of the oncology lexicon, the estrogen receptor (ER) was already a much touted target of drug development for breast cancer treatment and prevention. Selective estrogen receptor modulators (SERMs) were developed for the purpose of binding to the ER. Tamoxifen, the first SERM studied for breast cancer treatment and prevention, inhibits the action of the ER in the breast. In the 1980s it elicited improvements in overall and disease-free survival in women with breast cancer and was subsequently tested with a primary endpoint of breast cancer prevention in high-risk women. The Breast Cancer Prevention Trial demonstrated a 49% reduction in new breast cancers in high-risk women, leading to FDA approval of tamoxifen for this purpose in 1998. The was the first FDA approval of an agent for a cancer prevention indication. Subsequently a series of SERMs have been developed for osteoporosis, most notably raloxifene. The Study of Tamoxifen and Raloxifene showed the two SERMs to be equivalent in terms of their ability to target the ER and prevent ER-positive breast cancer, with raloxifene exhibiting overall less toxicity. This agent, already approved for osteoporosis treatment and prevention, was approved for breast cancer prevention in postmenopausal women in 2007. More recently, meta-analyses of these and other studies comparing SERMs to placebo in a variety of disease settings have consistently shown benefits for breast cancer prevention in the SERM arm. The latest approach to targeting the estrogenic effect on breast cancer development involves inhibition of estrogen production, as opposed to estrogen action. The aromatase inhibitors (AIs) prevent the enzyme, aromatase, from converting androgens to estrogens. In postmenopausal women, in whom the majority of AI studies have been carried out, the inhibition of estrogen production is almost complete. The Mammary Prevention 3 trial showed that the AI exemestane decreased the incidence of breast cancer by up to 70% compared to placebo, with different toxicities than tamoxifen. The International Breast Cancer Intervention Study II, which is comparing the AI anastrozole to placebo in high-risk postmenopausal women, is still ongoing. Both the SERM and AI classes of targeted breast cancer prevention agents are effective in preventing ER-positive breast cancers, leaving an urgent need to develop drugs to prevent ER-negative breast cancers.
Citation Format: Leslie G. Ford, Barbara K. Dunn. Targeting estrogen receptors for breast cancer prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED05-02.
Abstract PL02-03: Changing landscape of environmental carcinogenesis in Qidong, China: Lessons for prevention
Authors: Kensler Thomas W. , Chen Jian-Guo , Chen Tao-Yang , Egner Patricia , Ng Derek , Munoz Alvaro , Groopman John 
Published: May 2019

Abstract
Residents of Qidong, China, located at the mouth of the Yangtze River, are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic and environmental factors. As tracked by their cancer registry, there are extraordinary changes in the China age-standardized incidence rates for the two leading cancer killers in the Qidong region: one going down and the other one up, liver and lung cancer respectively. In endemic areas such as Qidong, liver cancer arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Agricultural and economic reforms in the 1980s promoted a switch from maize to rice as the dietary staple, with concomitant &gt;40-fold decreases in aflatoxin exposure over this period as measured by aflatoxin-albumin adducts in archived serum samples. Universal, subsidized vaccination against HBV was initiated in the early 2000s and likely does not account for the 45% drop in liver cancer incidence over the past quarter century, but augurs well for the future. Age standardized incidence rates for lung cancer, by contrast, have tripled in men over this period, reflecting the high prevalence of smoking (~60%) in adult males and increasing numbers of cigarettes smoked. Women in Qidong, on the other hand rarely smoke. Nonetheless, their rates of lung cancer incidence have doubled over the past decade only, perhaps related to changing patterns of exposures to indoor and outdoor air pollution. Approaches to modulate the impact of these exposures through chemopreventive interventions will be presented. Both primary and secondary prevention strategies appear to offer opportunities for risk reduction in this shifting landscape of exposures to environmental carcinogens.
Citation Format: Thomas W. Kensler, Jian-Guo Chen, Tao-Yang Chen, Patricia Egner, Derek Ng, Alvaro Munoz, John Groopman. Changing landscape of environmental carcinogenesis in Qidong, China: Lessons for prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL02-03.
Abstract PL04-03: Working in innovative settings to enhance reach and improve population-based physical activity levels
Authors: Linnan Laura 
Published: May 2019

Abstract
Physically active individuals accrue a wide range of health benefits including reduced risk of cardiovascular disease, stroke, diabetes and metabolic syndrome, certain types of cancer; as well as improving mental health, mood, bone and muscular strength, and reduced risk of falls. However, less than half of US adults (age 18+) meet the national Surgeon General recommendations of at least 150 minutes of moderate physical activity, including 2 days of strength training, each week. Certain subgroups of the population, Blacks, Hispanics, lower education and income levels, and those living in rural locations, are more likely to not meet the guidelines. In addition, 33.9% of the US population are considered “inactive” (e.g. less than 10 minutes of activity/week)….and inactive subgroups are also quite similar to those who do not meet physical activity guidelines. To address key health and cancer disparities, we must consider intervention strategies that improve reach and effectiveness within these subgroups. This presentation will share examples of working within innovative settings to improve physical activity levels, as well as decrease inactivity. We will introduce constructs of the RE-AIM framework to guide this discussion.
Citation Format: Laura Linnan. Working in innovative settings to enhance reach and improve population-based physical activity levels. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL04-03.
Abstract PL05-01: Inflammatory mediators, tumor microenvironment, and progression of colorectal cancer
Authors: DuBois Raymond N. 
Published: May 2019

Abstract
Population studies and experimental observations indicate that chronic inflammation and diet are risk factors for colorectal cancer (CRC). The mechanisms by which these factors contribute to the development of cancer are poorly understood. A large body of work has shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk for developing colorectal cancer (CRC) by up to 40-50%. NSAIDs exert some of their anti-inflammatory and anti-tumor effects by targeting cyclooxygenase enzymes (COX-1 and COX-2). Prostaglandin E2 (PGE2) is a pro-inflammatory mediator that promotes colorectal cancer progression. The aim of our present study was to determine the underlying mechanisms by which PGE2 affects progression of CRC.
We have found a novel function of pro-inflammatory PGE2 in regulating DNA methylation in colorectal cancer. Our in vitro and in vivo studies demonstrated that PGE2 treatment silenced certain tumor suppressors and DNA repair genes such as CDKN2B (p15), CNR1, MGMT, and MLH1 by enhancing CpG island methylation of their promoter via inducing DNMT1 and DNMT3B expression. We also found that a demethylating agent inhibited the effect of PGE2 on promoting tumor growth in a mouse model of colorectal cancer, indicating that PGE2 accelerates tumor growth via regulating DNA methylation. Furthermore, combined treatment of Apcmin/+ mice with inhibitors of COX-2 and DNA methylation has more effectively anti-tumor effects than either single agent alone. To further determine the clinical relevance of our in vitro and in vivo results, we examine the relationship between COX-2 expression, PGE2 levels, DNMT1/3b expression, CpG island methylation status and expression of these tumor suppressors and DNA repair genes in human colorectal carcinomas. The levels of COX-2 and PGE2 positively correlated with DNMT1 and DNMT3B expression in these human colorectal cancer specimens. Importantly, the PGE2 levels as well as COX-2, DNMT1, and DNMT3B expression are also positively associated with the CpG island methylation in the promoters of these tumor suppressors and DNA repair genes. We also observed a specific type of immune cells (MDSCs) attracted to the tumor microenvironment by the presence of PGE2.
Citation Format: Raymond N. DuBois. Inflammatory mediators, tumor microenvironment, and progression of colorectal cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL05-01.
Abstract PP01-01: Chemoprevention of Cancer: Past, Present, and Future
Authors: Sporn Michael B. 
Published: May 2019

Abstract
We will summarize highlights of new concepts relating to chemoprevention of cancer during a long career of research on this topic. Particular emphasis will be placed on the following topics: carcinogenesis as a chronic disease process, the question of whether asymptomatic people are truly healthy, the use of drugs both singly and in combination for chemoprevention of cancer, tumor cell heterogeneity, the importance of the use of multifunctional drugs for chemoprevention, and the application of drugs developed in cancer studies for diseases other than cancer.
Citation Format: Michael B. Sporn. Chemoprevention of Cancer: Past, Present, and Future. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PP01-01.
Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review
Authors: Woodcock Eric A. , Hillmer Ansel T. , Mason Graeme F. , Cosgrove Kelly P. 
Published: May 2019

There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification of <i>myo-</i>inositol levels is a putative glial marker found in astrocytes. Neuroinflammatory responses are initiated and maintained by microglia and astrocytes, and thus represent important imaging markers. The goal of this review is to summarize neuroimaging findings from the substance use literature that report data using these markers and discuss possible mechanisms of action. The extant literature indicates abused substances exert diverse and complex neuroimmune effects. Moreover, drug effects may change across addiction stages, i.e. the neuroimmune effects of acute drug administration may differ from chronic use. This burgeoning field has considerable potential to improve our understanding and treatment of SUDs. Future research is needed to determine how targeting the neuroimmune system may improve treatment outcomes.
Rapid Successful Reperfusion of Basilar Artery Occlusion Strokes With Pretreatment Diffusion‐Weighted Imaging Posterior‐Circulation ASPECTS <8 Is Associated With Good Outcome
Authors: Guillaume Morgan , Lapergue Bertrand , Gory Benjamin , Labreuche Julien , Consoli Arturo , Mione Gioia , Humbertjean Lisa , Lacour Jean‐Christophe , Mazighi Mikael , Piotin Michel , Blanc Raphaël , Richard Sébastien ,   the Endovascular Treatment in Ischemic Stroke (ETIS) Investigators, Decroix Jean‐Pierre , Wang Adrien , Evrard Serge , Tchikviladzé Maya , Bourdain Frederic , Rodesh Georges , Coskun Oguzhan , Di Maria Federico , Pico Fernando , Rakotoharinandrasana Haja , Tassan Philippe , Poll Roxanna , Corabianu Ovide , de Broucker Thomas , Smadja Didier , Redjem Hocine , Ciccio Gabriele , Smadja Stanislas , Alamowitch Sonia , Fahed Robert , Desilles Jean‐Philippe , Obadia Mickael , Fisselier Matthieu , Sabben Candice , Ille Olivier , Manchon Eric , Garcia Pierre‐Yves , Turjman Francis , Riva Roberto , Labeyrie Paul‐Emile , Bracard Serge , Anxionnat René , Braun Marc , Schmitt Emmanuelle , Planel Sophie , Derelle Anne‐Laure , Tonnelet Romain , Liao Liang 
Published: May 2019

Background
The association between time to reperfusion and clinical outcome is well known in anterior circulation strokes, whereas the impact of main time metrics remains unknown in posterior circulation strokes. We investigated the clinical effect of different time intervals from symptom onset to reperfusion on the 90‐day clinical outcome in acute ischemic stroke patients with basilar artery occlusion, and especially in the subset population presenting a low stroke volume on baseline diffusion‐weighted imaging.

Methods and Results

We studied patients included in the prospective, multicenter, observational
ETIS
(Endovascular Treatment in Ischemic Stroke) registry who had had basal artery occlusion and had achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b‐3). Three time intervals (onset to reperfusion, onset to imaging, and imaging to reperfusion) were considered in all patients and separately in patients with pc‐
ASPECTS
(posterior‐circulation Alberta Stroke Program Early Computed Tomography Score) <8 and ≥8 on baseline diffusion‐weighted imaging. The primary end point was good outcome defined as 90‐day modified Rankin Scale scores of 0 to 2. Among the 95 included patients, 38 (40%) achieved a good outcome. In all patients, no significant association was found between the different time intervals and outcome. In patients evaluated with diffusion‐weighted imaging (n=61) at baseline, a significant negative association was found between imaging‐to‐reperfusion time for patients with pc‐
ASPECTS
<8 (adjusted odds ratio=0.4 per 30‐minute increase; 95% CI 0.18‐0.85;
P
=0.02) compared with those with pc‐
ASPECTS
≥8.

Conclusions

In patients with basilar artery occlusion and pc‐
ASPECTS
<8 at baseline diffusion‐weighted imaging, clinical outcome is highly dependent on the time from imaging to reperfusion, which suggests that rapid endovascular reperfusion should be performed after imaging in these patients.
Increased Complement 3 With Suppression of miR‐145 Induces the Synthetic Phenotype in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats
Authors: Chen Lan , Fukuda Noboru , Otsuki Tomoyasu , Tanaka Sho , Nakamura Yoshihiro , Kobayashi Hiroki , Matsumoto Taro , Abe Masanori 
Published: May 2019

Background

We previously reported that vascular smooth muscle cells (
VSMC
s) from spontaneously hypertensive rats (
SHR
s) show the increased expression of complement 3 (C3) and the synthetic phenotype. We targeted the
SHR
C3 gene (C3 knockout [C3
KO] SHRs
) by the zinc finger gene editing method. In the current study, we investigated the mechanisms underlying the increased expression of C3 and the role of endogenous C3 in the synthetic phenotype of
SHR VSMC
s in comparison to cells from Wistar‐Kyoto (
WKY)
rats and C3
KO SHR
s.

Methods and Results

Nonmuscle myosin heavy chain staining of aortas from
SHR
s at 1 day after birth was stronger in comparison to
WKY
rats and C3
KO SHR
s.
DNA
synthesis in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. Immunohistochemical staining of renin and liver X receptor α in
VSMC
s from
SHR
s was stronger in comparison to
WKY
rats and C3
KO SHR
s. The expression of renin, Krüppel‐like factor 5, and liver X receptor α proteins in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of synthetic phenotype markers osteopontin, matrix gla, and
l
‐caldesmon, growth factors transforming growth factor‐β1 and platelet‐derived growth factor‐A, transcription factors Krüppel‐like factor 5 and liver X receptor α, and angiotensinogen
mRNA
s in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of miR‐145
mRNA
in
VSMC
s from
SHR
s was suppressed in comparison to cells from
WKY
rats. miR‐145 inhibitor significantly increased the expression of C3 in
VSMC
s from
WKY
rats, but not in cells from
SHR
s.

Conclusions

These findings indicate that the increased C3 with the suppression of miR‐145 induces the synthetic phenotype through Krüppel‐like factor 5 and the activation of the renin‐angiotensin system through liver X receptor α in
VSMC
s from
SHR
s.
A Nonlinear Theory of Atmospheric Blocking: A Potential Vorticity Gradient View
Authors: Luo Dehai , Zhang Wenqi , Zhong Linhao , Dai Aiguo 
Published: May 2019

Abstract
In this paper, an extended nonlinear multiscale interaction model of blocking events in the equivalent barotropic atmosphere is used to investigate the effect of a slowly varying zonal wind in the meridional direction on dipole blocking that is regarded as a nonlinear Rossby wave packet. It is shown that the meridional gradient of potential vorticity (PVy=∂PV/∂y) prior to the blocking onset, which is related to the background zonal wind and its nonuniform meridional shear, can significantly affect the lifetime, intensity, and north–south asymmetry of dipole blocking, while the blocking dipole itself is driven by preexisting incident synoptic-scale eddies. The magnitude of the background PVy determines the energy dispersion and nonlinearity of blocking. It is revealed that a small background PVy is a prerequisite for strong and long-lived eddy-driven blocking that behaves as a persistent meandering westerly jet stream, while the blocking establishment further reduces the PVy within the blocking region, resulting in a positive feedback between blocking and PVy. When the core of the background westerly jet shifts from higher to lower latitudes, the blocking shows a northwest–southeast-oriented dipole with a strong anticyclonic anomaly to the northwest and a weak cyclonic anomaly to the southeast as its northern pole moves westward more rapidly and has weaker energy dispersion and stronger nonlinearity than its southern pole because of the smaller PVy in higher latitudes. The opposite is true when the background jet shifts toward higher latitudes. The asymmetry of dipole blocking vanishes when the background jet shows a symmetric double-peak structure. Thus, a small prior PVy is a favorable precursor for the occurrence of long-lived and large-amplitude blocking.
Small-Scale Potential Vorticity in the Upper-Ocean Thermocline
Authors: Lien Ren-Chieh , Sanford Thomas B. 
Published: May 2019

AbstractTwenty Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats in the upper-ocean thermocline of the summer Sargasso Sea observed the temporal and vertical variations of Ertel potential vorticity (PV) at 7–70-m vertical scale, averaged over O(4–8)-km horizontal scale. PV is dominated by its linear components—vertical vorticity and vortex stretching, each with an rms value of ~0.15f. In the internal wave frequency band, they are coherent and in phase, as expected for linear internal waves. Packets of strong, >0.2f, vertical vorticity and vortex stretching balance closely with a small net rms PV. The PV spectrum peaks at the highest resolvable vertical wavenumber, ~0.1 cpm. The PV frequency spectrum has a red spectral shape, a −1 spectral slope in the internal wave frequency band, and a small peak at the inertial frequency. PV measured at near-inertial frequencies is partially attributed to the non-Lagrangian nature of float measurements. Measurement errors and the vortical mode also contribute to PV in the internal wave frequency band. The vortical mode Burger number, computed using time rates of change of vertical vorticity and vortex stretching, is 0.2–0.4, implying a horizontal kinetic energy to available potential energy ratio of ~0.1. The vortical mode energy frequency spectrum is 1–2 decades less than the observed energy spectrum. Vortical mode energy is likely underestimated because its energy at vertical scales > 70 m was not measured. The vortical mode to total energy ratio increases with vertical wavenumber, implying its importance at small vertical scales.
What Is the Impact of Additional Tropical Observations on a Modern Data Assimilation System?
Authors: Slivinski Laura C. , Compo Gilbert P. , Whitaker Jeffrey S. , Sardeshmukh Prashant D. , Wang Jih-Wang A. , Friedman Kate , McColl Chesley 
Published: May 2019

Abstract
Given the network of satellite and aircraft observations around the globe, do additional in situ observations impact analyses within a global forecast system? Despite the dense observational network at many levels in the tropical troposphere, assimilating additional sounding observations taken in the eastern tropical Pacific Ocean during the 2016 El Niño Rapid Response (ENRR) locally improves wind, temperature, and humidity 6-h forecasts using a modern assimilation system. Fields from a 50-km reanalysis that assimilates all available observations, including those taken during the ENRR, are compared with those from an otherwise-identical reanalysis that denies all ENRR observations. These observations reveal a bias in the 200-hPa divergence of the assimilating model during a strong El Niño. While the existing observational network partially corrects this bias, the ENRR observations provide a stronger mean correction in the analysis. Significant improvements in the mean-square fit of the first-guess fields to the assimilated ENRR observations demonstrate that they are valuable within the existing network. The effects of the ENRR observations are pronounced in levels of the troposphere that are sparsely observed, particularly 500–800 hPa. Assimilating ENRR observations has mixed effects on the mean-square difference with nearby non-ENRR observations. Using a similar system but with a higher-resolution forecast model yields comparable results to the lower-resolution system. These findings imply a limited improvement in large-scale forecast variability from additional in situ observations, but significant improvements in local 6-h forecasts.