tbuckley/cabot-search huggingface dataset:
Abstract 2542: c-Jun and FOXO1 play key roles in the overexpression of oncogenic PKC-ι in human prostate and melanoma cell lines
Authors: Andre H. Apostolatos, Wishrawana S. Ratnayake, Anisul Islam, Christopher Apostolatos, Tracess Smalley, Mildred Acevedo-Duncan
Journal: Cancer Research (2018)

Abstract Protein Kinase C-ι (PKC-ι) is an anti-apoptotic oncogene overexpressed in multiple cancers including prostate, melanoma, ovarian, breast, and glioma. We have previously shown that PKC-ι is part of a cycle that helps cancer cells avoid senescence by releasing the transcription factor NF-kB. Additionally, PKC-ι has an anti-apoptotic effect while promoting epithelial-mesenchymal transition in melanoma {Ratnayake, et al. Int. J. Oncol. 51(5), (2017), 1370-1382}. PKC-ι is activated externally by factors like loss of PTEN and TGFβ stimulation. However treatment with PKC-ι specific inhibitors downregulate expression of both PKC-ι and phosphorylated PKC-ι, suggesting PKC-ι plays a role in regulating its own expression. A previous study showed the ELK1 transcription factor to be a regulator of PKC-ι (Gustafson, et al. J. Biol. Chem 279(10), (2003), 9400-8}. In this study, transcription factors c-Jun, ISGF3, PAX3, EGR1, and FOXO1 which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC-ι regulation in prostate cancer cell lines (DU145 and PC3) and melanoma cell lines (SK-MEL-2 and MeWo). Each transcription factor was systematically silenced. Western blots revealed that treatment with either c-Jun or FOXO1 siRNA significantly altered expression of PKC-ι. Results showed c-Jun followed by FOXO1 are the two major transcription factors which involve in PKC-ι expression in prostate cells compared to FOXO1 in melanoma cells. This suggests that these transcription factors act as activators that regulate PKC-ι expression and can be downstream targets of PKC-ι. We found that regulation of PKC-ι expression was governed mainly through NF-κB pathway. siRNA knockdown of NF-κB p65 and application of NF-κB inhibitors confirmed the above observation. We have also used immuno-paired-antibody detection assay to determine which pathways were affected with PKC-ι inhibitor treatments other than NF-κB pathway. qPCR and microarray were performed to analyze the transcriptome of treated cells to match protein levels with mRNA levels. We have analyzed multiple targets both up and downstream of PKC-ι to determine the mechanism of PKC-ι self-regulation. Overall results suggest that PKC-ι inhibition downregulates its own expression making it a novel target in prostate and melanoma cancer treatment. Citation Format: Andre H. Apostolatos, Wishrawana S. Ratnayake, Anisul Islam, Christopher Apostolatos, Tracess Smalley, Mildred Acevedo-Duncan. c-Jun and FOXO1 play key roles in the overexpression of oncogenic PKC-ι in human prostate and melanoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2542.
Abstract 2274: Cancer genomics visualization and interpretation using UCSC Xena
Authors: Mary Goldman, Brian Craft, Jingchun Zhu, David Haussler
Journal: Cancer Research (2018)

Abstract The UCSC Xena platform (http://xena.ucsc.edu/) allows biologists and bioinformaticians to securely analyze and visualize functional genomics data. Our unique Visual Spreadsheet shows multiple data types side by side enabling discovery of correlations across and within genes and genomic regions. Dynamic Kaplan-Meier survival analysis assesses survival stratification in addition to scatter plots, bar graphs, and boxplots all shown with statistical tests. In addition to the commonly available SNPs, INDELs, CNV, and gene expression datasets, we support DNA methylation, exon-, transcript-, miRNA-, lncRNA-expression and structural variants. We also support clinical data such as phenotypes, subtype classifications and biomarkers. Our new whole genome views allow users to easily visualize non-coding regions for both copy number variation and somatic mutations. All of our data is available for download via our python API or through AWS S3 buckets. Our expanding public Xena Data Hubs currently host 1500+ datasets from more than 35 cancer types, as well as Pan-Cancer datasets. In addition to serving seminal cancer genomic datasets to the scientific community, including the latest from the GDC, TCGA, TARGET, and ICGC, we also host 'normal tissue' datasets from GTEx. A recompute of TCGA, TARGET and GTEx datasets through the same bioinformatics pipeline allows users to compare expression between tumor and normal tissues. In addition to exploring these public datasets, the UCSC Xena Browser can easily display an investigator's genomic and clinical data on their own Xena Hub. By empowering users to install and load data into their own hub, our architecture ensures that the investigator's data remains private. The lightweight Xena Data Hubs are straightforward to install on Windows, Mac and Linux operating systems and loading data is easy using either our application or command line interface. Citation Format: Mary Goldman, Brian Craft, Jingchun Zhu, David Haussler. Cancer genomics visualization and interpretation using UCSC Xena [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2274.
A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma
Authors: Olumide B. Gbolahan, Ryan F. Porter, John T. Salter, Constantin Yiannoutsos, Matthew Burns, E. Gabriella Chiorean, Patrick. J. Loehrer
Journal: Journal of Thoracic Oncology (2018)
Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy
Authors: Kris M. Mahadeo, Sajad J. Khazal, Hisham Abdel-Azim, Julie C. Fitzgerald, Agne Taraseviciute, Catherine M. Bollard, Priti Tewari, Christine Duncan, Chani Traube, David McCall, Marie E. Steiner, Ira M. Cheifetz, Leslie E. Lehmann, Rodrigo Mejia, John M. Slopis, Rajinder Bajwa, Partow Kebriaei, Paul L. Martin, Jerelyn Moffet, Jennifer McArthur, Demetrios Petropoulos, Joan O’Hanlon Curry, Sarah Featherston, Jessica Foglesong, Basirat Shoberu, Alison Gulbis, Maria E. Mireles, Lisa Hafemeister, Cathy Nguyen, Neena Kapoor, Katayoun Rezvani, Sattva S. Neelapu, Elizabeth J. Shpall
Journal: Nature Reviews Clinical Oncology (2018)

In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.
Methadone maintenance treatment and mortality in people with criminal convictions: A population-based retrospective cohort study from Canada
Authors: Angela Russolillo, Akm Moniruzzaman, Julian M. Somers
Journal: PLoS Medicine (2018)

Background Individuals with criminal histories have high rates of opioid dependence and mortality. Excess mortality is largely attributable to overdose deaths. Methadone maintenance treatment (MMT) is one of the best evidence-based opioid substitution treatments (OSTs), but there is uncertainty about whether methadone treatment reduces the risk of mortality among convicted offenders over extended follow-up periods. The objective of this study was to investigate the association between adherence to MMT and overdose fatality as well as other causes of mortality. Methods and findings We conducted a retrospective cohort study involving linked population-level administrative data among individuals in British Columbia (BC), Canada with a history of conviction and who filled a methadone prescription between January 1, 1998 and March 31, 2015. Participants were followed from the date of first-dispensed methadone prescription until censoring (date of death or March 31, 2015). Methadone was divided into medicated (methadone was dispensed) and nonmedicated (methadone was not dispensed) periods and analysed as a time-varying exposure. Hazard ratios (HRs) with 95% CIs were estimated using multivariable Cox regression to examine mortality during the study period. All-cause and cause-specific mortality rates were compared during medicated and nonmedicated methadone periods. Participants (n = 14,530) had a mean age of 34.5 years, were 71.4% male, and had a median follow-up of 6.9 years. A total of 1,275 participants died during the observation period. The overall all-cause mortality rate was 11.2 per 1,000 person-years (PYs). Participants were significantly less likely to die from both nonexternal (adjusted HR [AHR] 0.27 [95% CI 0.23–0.33]) and external (AHR 0.41 [95% CI 0.33–0.51]) causes during medicated periods, independent of sociodemographic, criminological, and health-related factors. Death due to infectious diseases was 5 times lower (AHR 0.20 [95% CI 0.13–0.30]), and accidental poisoning (overdose) deaths were nearly 3 times lower (AHR 0.39 [95% CI 0.30–0.50]) during medicated periods. A competing risk regression demonstrated a similar pattern of results. The use of a Canadian offender population may limit generalizability of results. Furthermore, our observation period represents community-based methadone prescribing and may omit prescriptions administered during hospital separations. Therefore, the magnitude of the protective effects of methadone from nonexternal causes of death should be interpreted with caution. Conclusions Adherence to methadone was associated with significantly lower rates of death in a population-level cohort of Canadian convicted offenders. Achieving higher rates of adherence may reduce overdose deaths and other causes of mortality among offenders and similarly marginalized populations. Our findings warrant examination in other study centres in response to the crisis of opiate-involved deaths.
Abstract 79: Restart a Heart Day: The Danish Way 2013 and Strategy for 2014
Authors: GretheThomas, MereteKabel, JesperKjærgaard, FreddyLippert
Journal: Circulation (2014)

Purpose of the Study: The first European Restart a Heart Day was held on October 16th 2013, with the purpose of creating awareness of OHCA and the importance of bystander CPR. Material and methods: The goal was to provide Danes with knowledge of CPR, the use of AEDs and www.hjertestarter.dk. Additionally, Danes were encouraged to take an ERC-approved CPR-AED course. The combination of research presentation and citizen engagement provided the background for the strategic planning of the day. www.hjertestarterdagen.dk was created to enable Danes to view upcoming free events with CPR and AED demonstrations. Pamphlets and posters were made available free of charge for organizers to market the events. Furthermore, a nationwide competition encouraged Danes to locate AEDs not yet registered in the national network for public use. An updated publication of the Danish Cardiac Arrest Registry served as a communicative icebreaker toward the media. Figure 1. This astonishing development was highlighted to motivate mo...
Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders
Authors: BenoitDrolet, GuyRousseau, PascalDaleau, RenéCardinal, JacquesTurgeon
Journal: Circulation (2000)

Background—Several cases of QT prolongation and ventricular tachyarrhythmia have been reported with domperidone, a gastrokinetic and antiemetic agent available worldwide but still under investigation in the United States. Although electrolyte disturbances such as hypokalemia could account for some of these events, we hypothesized that domperidone may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. Methods and Results—Studies were undertaken in 9 isolated guinea pig hearts, which demonstrated reverse use–dependent prolongation of cardiac repolarization by 100 nmol/L domperidone. Action potential duration increased 27% from baseline with domperidone (from 114±3 to 145±2 ms) during pacing at a cycle length of 250 ms, and a 9% increase (from 97±2 to 106±3 ms) was seen with pacing at a cycle length of 150 ms. Experiments in human ether-a-go-go–related gene (HERG)-transfected Chinese hamster ovary cells (n=32) demonstrated a concentration-dependent block of the rapid c...
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Authors: Silvia S. Kang, Mark T.W. Ebbert, Kelsey E. Baker, Casey Cook, Xuewei Wang, Jonathon P. Sens, Jeanne-Pierre Kocher, Leonard Petrucelli, John D. Fryer
Journal: The Journal of Experimental Medicine (2018)

Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.
Abstract 4352: High caveolin-1 expression in African American women with early-stage triple-negative breast cancer
Authors: Lisa L. Baumbach-Reardon, Julie Getz, Mary E. Ahearn, John Carpten, Mark Pegram
Journal: Cancer Research (2018)

Abstract In the U.S., the incidence rates of breast cancer (BC) among Caucasian (CA) women are lower than those of African American (AA); however, AA women have a significantly higher mortality rate. It is imperative that we continue to investigate the underlying molecular biology that may contribute to the cause of health disparities between AA and CA with TNBC. In this study, gene expression profiling, using the Almac BC DSA Research Tool, was performed on archived FFPE samples, obtained from CA and AA women diagnosed with early-stage (Node 0) TNBC. Unsupervised hierarchical clustering revealed a pattern of differential gene expression in the AA cohort compared to CA. Using a subtyping Tool for TNBC, we found a distinct distribution pattern of TNBC molecular subtypes in the AA cohort, which was very different than the CA cohort: basal-like (14%), immunomodulatory (43%) and mesenchymal (43%). Gene expression analyses, comparing the AA and CA cohort (fold change &amp;gt; 2.0, p-value &amp;lt;.05), resulted in 190 differentially expressed genes (DEG). Pathway enrichment analysis conducted in MetaCore GeneGo revealed that the DEGs were over-represented in cytoskeletal remodeling, cell adhesion, tight junctions, and immune response in the AA TNBC cohort. Furthermore, several genes in the Wnt/β-catenin pathways were overexpressed in the top 10 enrichment pathways. We validated our results using RT-qPCR and identified Caveolin-1 (CAV1) as being significantly expressed in the AA-TNBC cohort (p-value 1.22 x 10-05). An independent cohort of FFPE samples, from AA and CA women with early stage TNBC, was used to create a tissue microarray (TMA). Immunohistochemistry results showed no difference in subcelluar localization of Cav1 between the AA and CA cohorts; however, the AA cohort had significantly higher levels of Cav1 staining (p-value 0.04). Additionally, using RT-qPCR, we demonstrated that CAV1 mRNA was significantly higher in the AA TNBC cohort (p-value 0.48). Furthermore, endogenous Cav1 was shown to be highly expressed in a cell line panel of TNBC, in particular, those of the mesenchymal and basal-like molecular subtypes. Finally, using siRNA, we demonstrated that CAV1 silencing resulted in a significant decrease in cell proliferation for each of the TNBC cell lines while it showed no effect on the luminal ER+ cell lines. Our combined study results suggest that CAV1 overexpression may be a biologic contributor to the observed health disparity between AA women and CA diagnosed with early-stage TNBC. Citation Format: Lisa L. Baumbach-Reardon, Julie Getz, Mary E. Ahearn, John Carpten, Mark Pegram. High caveolin-1 expression in African American women with early-stage triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4352.
Abstract MP94: Impact of a 12-Weeks Supervised Physical Activity Program After Bariatric Surgery on Body Composition and on Abdominal and Mid-Thigh Body Fat Distribution Changes; a Randomized Study
Authors: AudreyAuclair, JanyHarvey, AlexandreSanctuaire, SimonMarceau, LaurentBiertho, SimonBiron, Frederic-SimonHould, StefaneLebel, OdetteLescelleur, PaulPoirier
Journal: Circulation (2015)

Bariatric surgery is the most effective long-term treatment for the management of severe obesity. Weight loss induced by bariatric surgery is characterize by a greater reduction of fat mass but also by a reduction of muscle mass. So far, there is a lack of data regarding the effect of physical activity after bariatric surgery on changes in weight and muscle mass. The purpose of this study was to measure the impact of supervised physical activity program, between months 3 to 6 after bariatric surgery, on body composition and on abdominal and mid-thigh body fat distribution. Patients were randomized either in a supervised physical activity program group (exercise group) or either usual care without personalized physical activity follow-up group (control group). For all patients, anthropometric measurements (waist circumference and bioimpedance analysis) and computed tomography scan (CT scan) at the abdomen and mid-thigh levels were performed before, at 3 and 6 months after bariatric surgery (sleeve gastrect...
Abstract 897: A novel fusion gene responsible for colon cancer drug resistance
Authors: Jingwu Xie, Dongsheng Gu, Ruolan Song
Journal: Cancer Research (2018)

Abstract Colorectal cancer is a leading cause of cancer-related mortality worldwide. Patients with advanced colorectal cancer eventually succumb to the disease, despite the fact that some patients respond initially to therapies (chemotherapy and targeted therapy). Thus, identifying molecular mechanisms responsible for drug resistance will help design novel strategies to treat colorectal cancer. In this study, we identified a novel mechanism by which colorectal cancer cells acquired 5-FU resistance. Through exome sequencing, we discovered a novel fusion gene common in 5-FU-resistant colorectal cancer cells. This fusion gene, once ectopically expressed in the sensitive cancer cells, promotes drug resistance to 5-FU treatment. Further analyses have revealed a signaling network linking this fusion gene to drug resistance. Taken together, we have revealed a novel mechanism for drug resistance in colorectal cancer, which may be a novel target to overcome drug resistance in colorectal cancer. Citation Format: Jingwu Xie, Dongsheng Gu, Ruolan Song. A novel fusion gene responsible for colon cancer drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 897.
Abstract 5279: Prevalence and correlates of perceived harmfulness and addictiveness to traditional and alternative tobacco products among US adults
Authors: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Ahmad M. Al-Taee, Gebran W. Khneizer, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs
Journal: Cancer Research (2018)

Abstract Purpose: Beliefs about addictiveness and harmfulness of tobacco products are associated with intentions to use them. This study aimed to (1) evaluate perceived harmfulness and addictiveness patterns towards multiple tobacco products and (2) examine sociodemographic variables that influence those perceptions. Methods: Weighted multivariate ordinal logistic regression analyses were performed on 5,474 US adults aged ≥18 years who participated in the 2015 and 2017 cycles of the Health Information National Trends Survey-FDA. The two primary outcomes were perceived harmfulness and addictiveness of traditional (cigarette, cigar, and pipe filled with tobacco) vs alternative tobacco (e-cigarette, hookah, and “roll your own” cigarettes). All models were adjusted for age, gender, race/ethnicity, education, household income, census region, and smoking status. Results: Overall, 7.9% of adults in the U.S. perceived alternative tobacco as “not harmful at all” compared to 2.4% for the traditional products. Similarly, 16.2% of adults perceived alternative tobacco as “not addictive at all” compared to 13.6% for the traditional products. Beliefs about the harmfulness and addictiveness of traditional and alternative tobacco products differed by sociodemographic characteristics and smoking status: Those who believed traditional and alternative tobacco products are more harmful were more likely to be female, older (compared with those aged 18-34), Black (compared with White), former or never smokers (compared with current smokers), and adults living in West (compared with Northeast). Similarly, those who believed traditional and alternative tobacco products are more addictive were more likely to be female, older, Black, and adults living in West. However, no association between smoking status and perceived addictiveness was noted. Conclusion: Adults in U.S. perceive tobacco harmfulness and addictiveness differently based on their sociodemographic characteristics and smoking status. These findings are potential areas for targeted behavioral interventions to increase individuals' perceived risk of harm and addiction to all forms of tobacco products in the United States. Citation Format: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Ahmad M. Al-Taee, Gebran W. Khneizer, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs. Prevalence and correlates of perceived harmfulness and addictiveness to traditional and alternative tobacco products among US adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5279.