bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA32: Metabolic syndrome and breast cancer risk among black women: An exercise intervention
Authors: Adams-Campbell Lucile L. 
Published: December 2017

Abstract
Breast cancer rates, which are increasing worldwide, parallel the increases in lifestyle diseases including Type 2 diabetes, obesity, and metabolic syndrome (MetS). MetS represents a cluster of risk factors associated with increased risk of cardiovascular diseases, and includes several components individually related to breast cancer etiology, i.e., central obesity, hypertension, hyperglycemia, and low high-density lipoprotein cholesterol. Among Black women who have high rates of MetS and breast cancer mortality, it is hypothesized that lifestyle interventions on MetS may improve the MetS profile and reduce breast cancer risk. In the present randomized controlled trial (RCT) we compared two exercise interventions: a supervised facility-based and a home-based exercise intervention to a control group in Black women with MetS who are at increased risk for breast cancer (based on the CARE model). This 6-month three-arm RCT assesses the impact of the exercise interventions on biomarkers related to obesity, insulin-related pathways, inflammation, and hormones. The specific aim of the proposed study is to compare the impact of a supervised facility-based and a home-based exercise intervention on obesity, metabolic syndrome and known breast cancer biomarkers in postmenopausal Black women with MetS who are at increased risk of breast cancer. There was a total of N=213 women randomized to the 3 arms of the RCT comprising 73, 69, and 71 women in the supervised, home-based, and control groups. The data reveal that the home-based intervention arm results have more favorable changes in metabolic components compared to the supervised and control groups. These findings appear to have broad public health utility in addressing lifestyle interventions among Black women, with a successful home-based intervention.
Citation Format: Lucile L. Adams-Campbell. Metabolic syndrome and breast cancer risk among black women: An exercise intervention [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA32.
Abstract IA5: Aspirin for precision chemoprevention of colorectal cancer
Authors: Chan Andrew T. 
Published: December 2017

Abstract
Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. These studies have been complemented by compelling data from randomized controlled trials (RCTs). Five placebo-controlled RCTs among individuals with a history of colorectal adenoma or cancer showed that aspirin reduced the risk of recurrent adenomas, the precursors of the vast majority of cancers. Data from long-term follow-up of the CAPP2 trial, a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and the Women's Health Study, a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated that randomized aspirin treatment was associated with a lower risk of colorectal cancer. Finally, secondary analyses of RCTs of aspirin for cardiovascular prevention have shown that aspirin reduces incidence of and mortality from colorectal cancer. As a reflection of the strength of the evidence, the U.S. Preventive Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin in 2016. The USPSTF now recommends low-dose aspirin (81 mg/day) for chronic disease prophylaxis, including colorectal cancer prevention, among U.S. adults between ages 50-59, and possibly ages 60-69, with a greater than 10% ten-year risk of cardiovascular events. The new USPSTF recommendation represents a significant milestone for the field of preventive medicine. With the exception of tamoxifen for women at high-risk for breast cancer, this is the first medication broadly recommended for cancer prevention by the USPSTF. Despite this advance, wider scale efforts to implement aspirin chemoprevention are limited by concerns about risk-benefit profile in view of the established association of aspirin with gastrointestinal bleeding. In concert with broader efforts to tailor prevention strategies, our group has led several studies into the mechanistic basis of aspirin's anti-cancer effect that has led to the development of intratumoral, colonic, germline, and circulating molecular correlates of outcomes. Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles. In this presentation, we will review the evidence supporting a role for aspirin in the prevention of colorectal cancer, with a focus on novel methods for molecular risk stratification. Such a precision chemoprevention strategy could play a role in global efforts for chronic disease prevention and control.
Citation Format: Andrew T. Chan. Aspirin for precision chemoprevention of colorectal cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA5.
Abstract B12: Analysis of Lipid Metabolism and Gene Expression in Hepatocellular Carcinoma Reveals Mitochondrial Function as a Potential Target for Combinatorial Treatment
Authors: Zarrinpar Ali , Palumbo Tiziana , Barupal Dinesh 
Published: December 2017

Abstract
Background: Hepatocellular carcinoma (HCC), the most common malignant liver tumor, is a heterogeneous disease with little efficacious chemotherapy. Lipid metabolic dysfunction is integral to the pathogenesis of HCC, but the underlying mechanisms remain poorly understood. HCC cell lines and patient tumors can be classified into hepatocyte and hepatoblast subtypes based on gene expression patterns, with the hepatoblast type being more aggressive.
Methods: We characterized the RNA expression profiles of 20 HCC cell lines (13 hepatoblast and 7 hepatocyte type) and 1 normal immortalized liver cell line. We also characterized the steady state concentrations of hundred of metabolites of these cells lines. In addition, to find the specific small molecules to inhibit their growth we tested a panel of metabolic pathway inhibitors for activity against these cell lines.
Results: There are significant differences between the transcriptional profiles of the two subtypes of HCC, as well as between HCC cell lines and the normal liver cell line. The most important determinants of these differences are in lipid metabolic pathways. Analysis of the microarray data, corroborated by real time quantitative PCR analysis showed significant difference between transcript levels of ACOX1, ACOX2, FASN, SCD1, and SCAP, as well as in fatty acid transport proteins (FATPs, SLC27As) and elongation enzymes (ELOVL). Metabolomic studies show that not only are there differences between the steady state amounts of long chain and very long chain fatty acids among the groups, but there are also differences in the levels of acyl-carnitines. These differences indicate that there is variability in their reliance on mitochondrial oxidative respiration. Accordingly, there are significant differences between the sensitivity of the HCC cell lines to oligomycin compared with a normal liver cell line.
Conclusion: These data point to the importance of lipid metabolic and mitochondrial oxidative dysfunction in the pathogenesis of hepatocellular carcinoma. We anticipate combining the inhibition of oxidative phosphorylation with the standard of care treatment consisting of sorafenib to allow for a much lower and better tolerated dose of both drugs while maintaining anti-tumor efficacy.
Citation Format: Ali Zarrinpar, Tiziana Palumbo, Dinesh Barupal. Analysis of Lipid Metabolism and Gene Expression in Hepatocellular Carcinoma Reveals Mitochondrial Function as a Potential Target for Combinatorial Treatment [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B12.
Abstract PR02: Synthetic lethality screen identifies novel druggable targets in the MYC pathway
Authors: Li Yulin , Deutzmann Anja , Bell John , Ji Hanlee , Felsher Dean 
Published: December 2017

Abstract
The MYC oncogene is frequently overexpressed in human cancers. However, targeting MYC directly has proven to be extremely difficult and MYC itself is currently considered undruggable. We sought to identify alternative genetic vulnerabilities of MYC-driven cancer by using CRISPR-based genome-wide synthetic lethality screens. The library screens were performed in a MYC-driven cancer cell line derived from our transgenic mouse model of hepatocellular carcinoma. In this cancer cell line, the level of MYC is regulated by the Tet-Off transgenic system. Using lentiviral infection, the Cas9 nuclease was delivered into the cells, followed by the CRISPR library with 130,000 guide RNAs to knock out each gene in the mouse genome. Comparison of the clonal dropouts under high MYC versus low MYC conditions lead to the identification of specific target genes that are essential to tumors with high MYC expression. Preliminary pathway analysis of our screening hits has revealed the functional landscape of the MYC oncogene. We found that several pathways that are essential for MYC function converge on RNA metabolism. Furthermore, we have identified and tested druggable targets that can be translated into therapeutics for MYC-driven cancers.
Citation Format: Yulin Li, Anja Deutzmann, John Bell, Hanlee Ji, Dean Felsher. Synthetic lethality screen identifies novel druggable targets in the MYC pathway [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr PR02.
Abstract 45: Development of a molecular diagnostic tool for more precise diagnosis of oral squamous cell carcinoma
Authors: Jacobsen Martha Rolland , Dongre Harsh , Ahmed Israa , Tuljaurkar Vidisha , Pai Prathamesh S. , Patil Asawari , Sapkota Dipak , Johannessen Anne Christine , Filipovic Nenad , Vaidya Milind , Sawant Sharda , Costea Daniela Elena 
Published: December 2017

Abstract
Expression of cancer-associated biomarkers represents a great potential for a more precise diagnosis for patient stratification and more personalized treatment of oral squamous cell carcinoma (OSCC). The aim of this study was to develop an immunohistochemistry-based malignancy index diagnostic system (IHC-MIDS) based on the expression of a panel of several molecules expressed by different tumor components and involved in different oncogenic pathways. IHC was performed on paraffin embedded formalin fixed tissue samples from 102 patients for the following biomarkers: p16, p53, ki67, p75NTR, LoxL4, aSMA, Foxp3, CD68, CD 163, CD80, FVIII and D2-40. The stained tissues were scanned and quantified using Immage J open source software. An IHC-MIDS score was developed using correlation-based feature selection algorithm. IHC-MIDS was able to stratify OSCC lesions for several clinical pathological features, including the risk of recurrence. This study shows that a scoring system based on expression of a panel of biomarkers is more precise than the use of a single biomarker and that it can be used for risk stratification of OSCC lesions in order to guide further management.
Citation Format: Martha Rolland Jacobsen, Harsh Dongre, Israa Ahmed, Vidisha Tuljaurkar, Prathamesh S. Pai, Asawari Patil, Dipak Sapkota, Anne Christine Johannessen, Nenad Filipovic, Milind Vaidya, Sharda Sawant, Daniela Elena Costea. Development of a molecular diagnostic tool for more precise diagnosis of oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 45.
Abstract 70: PARP1 as a potential therapeutic target in Merkel cell carcinoma
Authors: Ferrarotto Renata , Su Shirley , Diao Lixia , Eterovic A Karina , Prieto Victor , Morrison William , Wang Jing , Glisson Bonnie , Kies Merrill , Bell Diana 
Published: December 2017

Abstract
Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Patients with incurable disease are treated with the same chemotherapy agents utilized in small-cell lung cancer (SCLC) achieving similar responses. Overexpression of PARP1 is common in SCLC and promising antitumor activity of PARP inhibitors is being demonstrated in early clinical trials. Furthermore, PARP inhibitors are active in a subset of tumors harboring mutations in DNA-damage repair (DDR) genes and benefit correlates to response to platinum. Based on its similarities with SCLC, its association with DNA damage by UV light, and its sensitivity to platin, our study explores PARP1 as a therapeutic target in MCC.
Methods: We evaluated the prevalence of PARP1 expression by immunohistochemistry in 19 MCC. Polyoma virus (MCPyV) status was evaluated by staining with anti-MCPyV antibody in the tissue specimens. Exome-sequencing of 263 genes was performed in 14 patients' samples using next-generation sequencing. Only mutations predicted to impair protein function in 17 genes related to DDR or mismatch repair were included in our analysis. Fisher's exact test was used for statistical significance.
Results: The majority of MCC express PARP1 (84%), suggesting underlying defects in DNA damage repair. Approximately half of the tumors (47%) were associated with MCPyV. There was no statistical correlation between PARP1 expression and MCPyV status or primary site of disease. Mutations in genes predicted to impair DDR was identified in 9 samples (64%), occurred exclusively in head and neck primaries, and correlated with mutations in TP53 or RB1 (P=0.03). Mutations in ARID1A predictive to be loss-of-function and potentially confer sensitivity to PARP inhibitors were found in 36% of the patients, exclusively in MCPyV negative samples (P=0.003). Mutations in TP53 and/or RB1 were more frequent in MCPyV negative tumors (P=0.03).
Conclusions: In spite of the small sample size, the high prevalence of PARP1 expression in MCC samples, similarly to SCLC, suggests that patients with MCC might also benefit from PARP1 inhibitors. Furthermore, the frequent mutations in genes involved in DNA-damage repair and ARID1A, particularly in the MCPyV negative cases, merits further characterization. Taken together, we believe clinical trials with PARP inhibitors in MCC patients should be considered.
Citation Format: Renata Ferrarotto, Shirley Su, Lixia Diao, A Karina Eterovic, Victor Prieto, William Morrison, Jing Wang, Bonnie Glisson, Merrill Kies, Diana Bell. PARP1 as a potential therapeutic target in Merkel cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 70.
Abstract IA03: Detection of tumor DNA in the saliva and plasma of patients with HNSCC
Authors: Agrawal Nishant 
Published: December 2017

Abstract
To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.
Citation Format: Nishant Agrawal. Detection of tumor DNA in the saliva and plasma of patients with HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA03.
Alligator Song
Authors: Vander Meer Elizabeth 
Published: December 2017

Abstract
Alligators were perceived as dangerous by early settlers in Florida, and they also reflected the untamed and potentially untameable Florida wilderness. By the 20th century, alligator farms capitalized on the thrill of alligator encounters in controlled theme park experiences. Alligators are tamed in the current farm context and valued increasingly for the products that can be derived from their bodies. This anthrozoological investigation of perceptions of Florida alligators explores how farms define alligators and why visitors might accept these particular constructed images of alligators, concluding with a wider view to consider these perceptions of farmed animals in relation to the idea of the nuisance alligator. The discussion is framed by multi-species studies that rest on notions of embodiment and attentiveness, which in this case push the importance of alligator experience and agency to the foreground.
Lay Buddhists and Moral Activism in Contemporary China (当代中国的佛教居士与道德能动主义)
Authors: Fisher Gareth 
Published: December 2017

The last few decades have seen the rise of grassroots groups of lay Buddhists in post-Mao China who, through the composition, exchange, and discussion of Buddhist-themed media, foster moral discourses that critique what they perceive as the materialistic direction of contemporary Chinese society. Disseminated at legal but unregulated spaces within Buddhist temples, these discourses empower the economically marginalized lay practitioners who gather there and provide them with new purpose in life. Practitioners are also able to transmit these moral discourses through networks to other temple spaces. However, they do not yet possess the means to use them to influence the social direction of Chinese society at large. This is due to (1) political restrictions against the circulation of religious-themed materials outside of approved religious activity sites; (2) economic obstacles faced by the practitioners who seek to spread anti-materialistic messages; (3) a lack of organizational cohesiveness among the practitioners; and (4) the influence on practitioners of doctrines within Buddhism that caution against proselytizing to those who do not already possess a pre-fated bond with the Buddha and his teachings. As a result, lay Buddhists do not as yet constitute a social movement in the way the term is conventionally used by sociologists.佛教居士组成的草根社会团体在毛时代之后的几十年快速发展。通过书写、交流与讨论与佛教主题相关的文献，他们促进形成了一套批判当前中国社会拜金主义倾向的道德话语。这套话语在合法且相对自由的佛教寺院中传播，鼓励了经济窘迫的信徒，帮助他们获得新的生活目的。这一道德话语也借由信徒进一步传播给其他的寺院。但是因为以下原因，这些草根团体无力影响中国社会的整体方向：1)宗教政策限制了宗教思想在寺庙以外的传播；2)信徒的经济地位较低，难以宣传反对拜金主义的话语；3)信徒中间缺乏组织凝聚力；4)反对向那些与佛陀无缘的人宣传佛家思想的信条。因此到目前为止，佛教居士团体还没有形成社会学意义上的社会运动。
Local and External Moisture Sources for the Arctic Warming over the Barents–Kara Seas
Authors: Zhong Linhao , Hua Lijuan , Luo Dehai 
Published: December 2017

Water vapor is critical to Arctic sea ice loss and surface air warming, particularly in winter. Whether the local process or poleward transport from lower latitudes can explain the Arctic warming is still a controversial issue. In this work, a hydrological tool, a dynamical recycling model (DRM) based on time-backward Lagrangian moisture tracking, is applied to quantitatively evaluate the relative contributions of local evaporation and external sources to Barents–Kara Seas (BKS) moisture in winter during 1979–2015. On average, the local and external moistures explain 35.4% and 57.3% of BKS moisture, respectively. The BKS, Norwegian Sea, and midlatitude North Atlantic are the three major sources and show significant increasing trends of moisture contribution. The local moisture contribution correlates weakly to downward infrared radiation (IR) but significantly to sea ice variation, which suggests that the recent-decade increase of local moisture contribution is only a manifestation of sea ice melting. In contrast, the external moisture contribution significantly correlates to both downward IR and sea ice variation, thus suggesting that meridional moisture transport mainly explains the recent BKS warming. The moisture contributions due to different sources are governed by distinct circulation patterns. The negative Arctic Oscillation–like pattern suppresses external moisture but favors local evaporation. In the case of dominant external moisture, a well-organized wave train spanning from across the midlatitude Atlantic to mid–high-latitude Eurasia has the mid–high-latitude components similar to a positive-phase North Atlantic Oscillation with a Ural blocking to the east. Moreover, the meridional shift of the wave train pathway and the spatial scale of the wave train anomalies determine the transport passage and strength of the major external moisture sources.
Effects of Projected Changes in Wind, Atmospheric Temperature, and Freshwater Inflow on the Ross Sea
Authors: Dinniman Michael S. , Klinck John M. , Hofmann Eileen E. , Smith Walker O. 
Published: December 2017

Abstract
A 5-km horizontal resolution regional ocean–sea ice–ice shelf model of the Ross Sea is used to examine the effects of changes in wind strength, air temperature, and increased meltwater input on the formation of high-salinity shelf water (HSSW), on-shelf transport and vertical mixing of Circumpolar Deep Water (CDW) and its transformation into modified CDW (MCDW), and basal melt of the Ross Ice Shelf (RIS). A 20% increase in wind speed, with no other atmospheric changes, reduced summer sea ice minimum area by 20%, opposite the observed trend of the past three decades. Increased winds with spatially uniform, reduced atmospheric temperatures increased summer sea ice concentrations, on-shelf transport of CDW, vertical mixing of MCDW, HSSW volume, and (albeit small) RIS basal melt. Winds and atmospheric temperatures from the SRES A1B scenario forcing of the MPI ECHAM5 model decreased on-shelf transport of CDW and vertical mixing of MCDW for 2046–61 and 2085–2100 relative to the end of the twentieth century. The RIS basal melt increased slightly by 2046–61 (9%) and 2085–2100 (13%). Advection of lower-salinity water onto the continental shelf did not significantly affect sea ice extent for the 2046–61 or 2085–2100 simulations. However, freshening reduces on-shelf transport of CDW, vertical mixing of MCDW, and the volume of HSSW produced. The reduced vertical mixing of MCDW, while partially balanced by the reduced on-shelf transport of CDW, enhances the RIS basal melt rate relative to the twentieth-century simulation for 2046–61 (13%) and 2085–2100 (17%).