bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2207: High-risk human papillomavirus detection in head and neck cancers using saliva
Authors: Tang Kai D , Perry Chris , Punyadeera Chamindie 
Published: August 2018

Abstract
Human papillomavirus (HPV), a virus vital to the etiology of cervical cancer, is strongly associated with the development of head and neck cancer. Therefore, it is pivotal to develop a noninvasive and cost-effective approach for detecting oral HPV. Accumulating evidence suggested the usefulness of salivary oral rinse as a diagnostic fluid to detect oral HPV DNA within a clinical setting. However, there is little known about the HPV DNA prevalence and type distribution in unstimulated whole mouth saliva (UWMS). In the current study, we show a positive correlation of HPV-16 E2 (r = 0.95, p &lt; 0.0001) and E6/7 (r = 0.93, p &lt; 0.0001) relative copy number as well as high-risk HPV genotypes (HPV 16, 18 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and fold change difference between the relative copy numbers of E2 and E6/7 (r = 0.46, p &lt; 0.0098) in both salivary oral rinse and UWMS samples collected from OPC patients. More importantly, in line with the previous study, among HPV-16 positive head and neck cancer cases, most often a mixed HPV-16 form (episomal and integrated) was found in both saliva sampling methods. In conclusion, regardless of the sampling method, detection of HPV in saliva is an attractive, noninvasive method that could change the need for invasive biopsies in head and neck cancer patients.
Citation Format: Kai D Tang, Chris Perry, Chamindie Punyadeera. High-risk human papillomavirus detection in head and neck cancers using saliva [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 2207.
Abstract 2220: Autoantibody detection of high-grade serous ovarian cancer with paraneoplastic antigens
Authors: Hurley Laura C. , Levin Nancy K. , Chatterjee Madhumita , Tainsky Michael A. 
Published: August 2018

Abstract
Improved early detection methods for ovarian cancer are necessary as the majority of cases present at late stage metastatic disease with a poor prognosis. Early stages of tumor development initiate an immune response, eliciting antibodies that target tumor associated antigens. Paraneoplastic neurological syndromes are rare autoimmune disorders that develop when the unregulated immune response against a tumor also targets healthy cells, due to shared tumor antigen expression with nervous system and muscle tissue. As these syndromes generally precede detection of a tumor, paraneoplastic antibodies are previously unexplored candidate biomarkers for early diagnosis of ovarian cancer. We have detected paraneoplastic antibodies in serum samples from patients with high-grade serous ovarian cancer (HGSOC) that did not present with paraneoplastic neurological syndrome symptoms using paraneoplastic diagnostic line blots. Ovarian cancer specific epitopes discovered previously in our laboratory by phage-display biopanning were evaluated for both homology to paraneoplastic antigens and for reactivity with paraneoplastic neurological syndrome patient sera. Western blot screening revealed a panel of paraneoplastic antigens that distinguished HGSOC patient sera autoantibody reactivity from healthy and benign sera. An indirect ELISA for measuring patient serum autoantibody reactivity was developed and correlated with western blot results. A panel consisting of 8 antigens: 5 paraneoplastic antigens, 2 well-characterized tumor associated antigens, and a non-reactive control was selected for screening on ELISA against patient serum samples representing each group of HGSOC early stage, HGSOC late stage, healthy, and benign. Biomarkers identified can contribute to an autoantibody diagnostic panel for early clinical diagnosis of ovarian cancer, which would allow for timely therapeutic intervention with potential to improve patient outcome.
Citation Format: Laura C. Hurley, Nancy K. Levin, Madhumita Chatterjee, Michael A. Tainsky. Autoantibody detection of high-grade serous ovarian cancer with paraneoplastic antigens [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 2220.
Abstract 2229: Mammography assessment of microcalcifications using a pixel detector system
Authors: Bernal Carlos Ávila , Roque Gerardo , Rueda Roberto , Racedo Jorge 
Published: August 2018

Abstract
Breast cancer is a major public health problem being the most frequently diagnosed malignancy and the second leading cause of dead from cancer among women in the United States. In 2015, there were expected around 231,840 new cases of invasive breast cancer, as well as 60,290 cases of in situ breast cancer, and 40,290 deaths. Worldwide, it represents 23% of the total cases diagnosed of cancer and 14% of the cancer deaths in female. Diagnosing breast cancer before it has the potential to invade surrounding tissue and metastasize can increase the chance of survival, reduce poor prognosis and the need of aggressive treatment. This is one of the main goals of early diagnosis that advocates mammography, the clinical examination and the breast self-examination as screening modalities for breast cancer. Recently, other technologies have been proposed like ultrasound and magnetic resonance imaging (MRI). Although these screening methods have reduced the relative risk of death, they have some limitations in some population groups. The aim of this work is adapting and testing a semiconductor pixel detector, Timepix in a custom-swine breast phantom to evaluate its technical feasibility to introduce this technology in a clinical setting for mammography assessment based on microcalcification detection. Swine model is commonly used in medical research based on anatomical and histopathological characteristics closely resemble those of humans, and this is an advantage over the wax-based phantoms that contains aluminum oxide (Al2O3) specks, nylon fibers and other inclusions to mimic microcalcifications and histopathological structures. The Timepix detector was used together with a Tungsten microfocus X-ray to detect hydroxyapatite crystals mimicking malignant microcalcifications with sizes ranged between 153-827μm, embedded into the swine phantom. To compare the detection performance in the swine phantom, a commercial phantom has been used (Model 015 CIRS Inc., Norfolk, VA, US). Both phantoms were tested on a clinical mammography system (Selenia Dimensions AWS 5000 ET19) and by using the experimental setup with the Timepix. This approach has potential to be used for mammography screening in different population groups based on its performance in microcalcifications detection. The results are highly relevant for further studies of the feasibility of pixel detectors for risk assessment and early diagnosis of breast cancer.
Citation Format: Carlos Ávila Bernal, Gerardo Roque, Roberto Rueda, Jorge Racedo. Mammography assessment of microcalcifications using a pixel detector system [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 2229.
Abstract 2237: Diclofenac as a dual inhibitor of cyclooxygenase and aldo-keto-reductase 1B10 inhibits pancreatitis-enhanced carcinogenesis in LSL-Kras
G12D
-Pdx-1-Cremice
Authors: Liao Jie , Sun Leyu , Li Haonan , Xia Rong , You Xiaoming , Xu Dandan , Yang Guang-Yu 
Published: August 2018

Abstract
Diclofenac is one of non-steroid anti-inflammatory drugs and is recently identified as a competitive inhibitor of aldo-keto reductase family 1B10 (AKR1B10). AKR1B10 is an NADPH-dependent enzyme that exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl involved in protein prenylation (such as for Kras) and plays an oncogenic role in pancreatic carcinogenesis. In the present study, we determined the chemopreventive effects and mechanism of diclofenac on inhibiting pancreatitis-carcinogenesis in LSL-KrasG12D/Pdx1-Cre mice (called Pankras mice), particularly on Kras prenylation. Pancreatitis was induced by single i.p. injection of Cearulein (250ug/Kg body weight) for 5-week old mice, and one week after caerulein treatment, Pankras mice were fed an AIN-93M diet or a diet with 5 or 20ppm diclofenac (n=12 mice/group) for 7 months. The results showed that Diclofenac significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III and to invasive carcinoma was significantly suppressed and the tumor incidence significantly reduced to 50% and 17% in the mice treated with either 5ppm or 20 diclofenac compared to 86% in Pankras mice. Inhibition of membrane-bound mutant Kras (prenylated) and its transmitted phosphorylation of mitogen-activated protein kinase's kinase/extracellular signal-regulated kinases were demonstrated in pancreatic tissues by western blot assay. Analysis of the eicosanoid profile revealed a significant reduction of prostaglandin E2. These results indicate that diclofenac is a highly potential agent for preventing chronic pancreatitis and carcinogenesis, mainly via targeting mutant Kras and inflammation (Supported by NIH R01 CA164041).
Citation Format: Jie Liao, Leyu Sun, Haonan Li, Rong Xia, Xiaoming You, Dandan Xu, Guang-Yu Yang. Diclofenac as a dual inhibitor of cyclooxygenase and aldo-keto-reductase 1B10 inhibits pancreatitis-enhanced carcinogenesis in LSL-KrasG12D-Pdx-1-Cremice [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 2237.
Abstract 2243: Cell-phone radiofrequency enhances angiogenesis and stimulates cell invasion of human head and neck cancer cells
Authors: Moustafa Ala-Eddin Al 
Published: August 2018

Abstract
Today, cell-phone is the most widespread technology globally. It has been suggested that cell-phone radiofrequency (RF) use may increase the risk of human brain and probably head cancers. However, the outcome of cell phone RF on head and neck (HN) cancer progression has not been explored yet. Thus, first we examined the outcome of cell-phone RF on angiogenesis using the chorioallantoic membrane (CAM) of the chicken embryo as a model. Then we investigated the effect of cell-phone RF on cell invasion and colony formation in soft agar of two human HN cancer cell lines. Our data revealed that cell-phone RF promotes angiogenesis of the CAM. In addition, cell-phone RF enhances cell invasion and colony formation of human HN cancer cells; this is accompanied by a down-regulation of E-cadherin expression. Regarding the mechanism of cell-phone RF on angiogenesis, cell invasion and colony formation, we found that cell-phone RF activates Erk1 and Erk2 in our experimental models which could be the main pathway behind these events. These data suggest that cell-phone RF enhances HN cancer progression by stimulating angiogenesis, cell invasion and tumor formation via Erk1 and Erk2.
Citation Format: Ala-Eddin Al Moustafa. Cell-phone radiofrequency enhances angiogenesis and stimulates cell invasion of human head and neck cancer cells [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 2243.
Abstract 2274: Cancer genomics visualization and interpretation using UCSC Xena
Authors: Goldman Mary , Craft Brian , Zhu Jingchun , Haussler David 
Published: August 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.
Abstract 2280: Systematic analysis of causal noncoding mutations in pediatric B-cell acute lymphoblastic leukemia
Authors: He Bing , Gao Peng , Ding Yang , Chen Chia-Hui , Kim Hannah , Hunger Stephen P. , Tasian Sarah K. , Tan Kai 
Published: August 2018

Abstract
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent childhood hematological malignancy and the leading cause of childhood cancer-related mortality. To date, the molecular pathogenesis of B-ALL has not been completely defined, limiting our ability to develop targeted therapies. Despite great advances in identifying mutations in cancer patients, the functional consequences of noncoding mutations are still difficult to interpret. Transcriptional enhancers are key determinants of tissue-specific gene expression. Several recent studies have reported novel mutations in cancer genome that disrupt enhance function and thus expression of their target genes. However, systematic detection of noncoding mutations that perturb either enhancer sequence or enhancer-promoter (EP) interaction is still challenging. Such analysis can help to identify novel driver mutations and improve our understanding of the disease.
Here we introduce a novel algorithm for identifying causal mutations that disrupt enhancer function and target gene expression in B-ALL. The algorithm takes as input
whole genome sequencing (WGS) and RNA-Seq data to predict causal noncoding mutations. We apply the algorithm to analyze data from 163 B-ALL patients and identify 332 noncoding mutations that disrupt EP interactions and gene expression. Our analysis recapitulate previously known translocations such as t(14;X) that leads to CRLF2 overexpression, as well as novel causal translocations that leads to deregulation of TMEM106A and MIR663B. Systematic analysis of the identified mutations indicated that SNVs in enhancer region have a higher variant allele frequency (VAF), suggesting enhancer mutations likely occur earlier than coding mutations during oncogenesis. In addition, pathway analysis show that the majority (57%) of mutations perturbing metabolic pathways are noncoding mutations. Further analysis and experimental follow-up of the predicted noncoding mutations may reveal novel insights into the pathogenesis of B-cell ALL.
Citation Format: Bing He, Peng Gao, Yang Ding, Chia-Hui Chen, Hannah Kim, Stephen P. Hunger, Sarah K. Tasian, Kai Tan. Systematic analysis of causal noncoding mutations in pediatric B-cell acute lymphoblastic leukemia [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 2280.
Abstract 2294: Customizable weighted DNA copy-number networks inform oncogenic pathway alterations and chemoresistance risk
Authors: Delaney Joe Ryan , Stupack Dwayne G. 
Published: August 2018

Abstract
Cancer is driven by mutations of many types: single nucleotide variants, insertion-deletion events within coding exons, and prolific DNA copy-number alterations (CNAs). CNAs have been often viewed as a passenger event due to seemingly inconsistent patterns between tumors and a large fraction of the genome altered, preventing traditional statistical analysis. Here, we present a tool which incorporates phenotypic data including haploinsufficiency and triploproficiency of genes and protein-protein interaction studies, which enables the identification of consistently altered pathways in cancer. This tool, HAPTRIG (for HAPloinsufficient and TRIplosensitive Gene) can be used with RNA, log2 CNA, absolute CNA data, or any other normalized gene-level data. As part of the pathway scoring process, control CNA networks are generated to provide a permuted-genome control, enabling detection of alterations in very heterogeneous cancer backgrounds. The customizable gene-scores which build these networks allow prioritization of altered network hubs: single genes which have exceptional influence within an altered pathway, facilitating hypothesis-testing in cell and animal models. A beta-version was validated in a recent publication from our lab to better predict tumor suppressor genes and oncogenes than Gene Set Enrichment Analysis, and additionally identified targetable pathway hubs which improved murine treatment in ovarian cancer chemo-resistant models. However, its applicability was limited in the beta. Now HAPTRIG can work with any user-supplied human dataset, not just TCGA samples, is an order of magnitude faster, able to run in parallel processors for unlimited speed improvement, and can produce pan-pathway outputs. The tool can use expected background rates from permuted data or compare to a second control dataset, which can be used to compare altered CNA pathways in tumor subtypes or unusual alterations of RNA compared to CNAs, among many other possibilities. We provide this tool for free community use online and in App form, so molecular biologists without bioinformatics training may produce well-informed hypotheses. We find that altered CNA pathways can predict chemoresistance risk groups within tumor types. A tumor suppressor gene hub was found to accelerate tumorigenesis upon deletion in a spontaneous mouse model. Overall, HAPTRIG represents a user-friendly tool to better understand a whole new landscape of tumor mutations: that of copy number alterations.
Citation Format: Joe Ryan Delaney, Dwayne G. Stupack. Customizable weighted DNA copy-number networks inform oncogenic pathway alterations and chemoresistance risk [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 2294.
Abstract 2304: In vivo E2F reporting reveals efficacious schedules of MEK1/2-CDK4/6 targeting and mTOR-S6 resistance mechanisms
Authors: Teh Jessica , Cheng Phil F. , Purwin Timothy J. , Nikbakht Neda , Patel Prem , Chervoneva Inna , Keibler Ines , Kim HooKim , Davies Michael A. , Kwong Lawrence N. , Levesque Mitch P. , Dummer Reinhard , Aplin Andrew E. 
Published: August 2018

Abstract
Targeting cyclin dependent kinases 4 and 6 (CDK4/6) represents a viable therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor in different genetic subsets of melanoma. However, continuous dosing of MEK inhibitor (MEKi) plus CDK4/6 inhibitor (CDK4/6i) elicits toxicities in patients. Utilizing an in vivo E2F reporter system, we analyzed the efficacy of MEKi plus CDK4/6i schedules in a quantitative and temporal manner. Continuous MEKi with intermittent CDK4/6i led to more complete responses as compared to either continuous CDK4/6i with intermittent MEKi or intermittent dosing of both drugs. Nevertheless, some tumors acquired resistance. Phospho-proteomic analysis of resistant tumors revealed increased phosphorylation of ribosomal S6 protein (RPS6). These data were supported by staining of patient biopsies from clinical trials, which also indicated that high phospho S6 levels may serve as a predictor of response to CDK4/6i plus targeted inhibitors. Enhanced phospho S6 provided a therapeutic window for the mTORC1/2 inhibitor, AZD2014, in MEKi plus CDK4/6i-resistant tumors. Mechanistically, aberrant regulation of NRAS was associated with resistance and sufficient to mediate resistance. This study highlights the use of an in vivo reporter model for optimization of schedules and supports targeting the mTORC1/2-S6 pathway as a salvage option to overcome MEKi plus CDK4/6i resistance.
Citation Format: Jessica Teh, Phil F. Cheng, Timothy J. Purwin, Neda Nikbakht, Prem Patel, Inna Chervoneva, Ines Keibler, HooKim Kim, Michael A. Davies, Lawrence N. Kwong, Mitch P. Levesque, Reinhard Dummer, Andrew E. Aplin. In vivo E2F reporting reveals efficacious schedules of MEK1/2-CDK4/6 targeting and mTOR-S6 resistance mechanisms [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 2304.
Abstract 2321: Molecular crosstalk between ferroptosis and apoptosis: Emerging role of ER stress-induced p53-independent PUMA expression
Authors: Lee Young-Sun , Hong Se Hoon , Lee Dae-Hee , Jo Min J. , Jeong Yoo A. , Kwon William T. , Choudry Haroon A. , Bartlett David L. , Lee Yong J. 
Published: August 2018

Abstract
Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and BxPC-3 and human colorectal cancer HCT116 cells were treated with ferroptotic agents such as erastin and artesunate (ART) in combination with the apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed synergistic interaction of erastin or ART with TRAIL as determined by cell death assay, caspase activation, poly [ADP-ribose] polymerase 1 (PARP-1) cleavage, flow cytometry analysis, and lipid peroxidation assay. Moreover, erastin and ART induced endoplasmic reticulum (ER) stress and promoted p53 upregulated modulator of apoptosis (PUMA) expression via C/EBP-homologous protein (CHOP). Synergy of erastin/ART and TRAIL was abolished in PUMA-deficient HCT116 cells and CHOP-deficient mouse embryonic fibroblasts, but not in p53-deficient HCT116 cells. The results suggest the involvement of the p53-independent CHOP/PUMA axis in response to ferroptosis inducers, which may play a key role in ferroptotic agent-mediated sensitization to TRAIL-induced apoptosis.
Citation Format: Young-Sun Lee, Se Hoon Hong, Dae-Hee Lee, Min J. Jo, Yoo A. Jeong, William T. Kwon, Haroon A. Choudry, David L. Bartlett, Yong J. Lee. Molecular crosstalk between ferroptosis and apoptosis: Emerging role of ER stress-induced p53-independent PUMA expression [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 2321.