bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A2-30: A new fluorescence-based andrographolide exhibits anticancer activity
Authors: Hsu Ya-Hsin , Hsu Yu-Ling , Liu Sheng-Hung , Liao Hsin-Chia , Lee Po-Xuan , Lin Chao-Hsiung , Lo Lee-Chiang , Fu Shu-ling 
Published: November 2015

Abstract
Andrographolide is a lactone diterpenoid compound isolated from the medicinal plant Andrographis paniculata. The anticancer activity of andrographolide has been previously demonstrated both in vitro and in vivo. We recently synthesized an andrographolide derivative, ANDRO-FL, in which a fluorescent chemical structure was covalently conjugated to andrographolide. We found that ANDRO-FL exhibited potent anticancer activity: ANDRO-FL reduced the viability of various types of cancer cells; ANDRO-FL suppressed the migration activity of melanoma cells; ANDRO-FL treatment induced the cleavage of heat shock 90 protein (Hsp90) as well as the downregulation of Hsp90 client oncoproteins such as v-Src and Bcr-abl. Notably, in all aforementioned experiments, ANDRO-FL showed stronger inhibitory effects than andrographolide. The kinetics and distribution of ANDRO-FL in cancer cells were further examined using fluorescence microscopy. The fluorescent signals could be detected within the cells in five minutes after ANDRO-FL treatment and the intensity increased as incubation time increased. Furthermore, the fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. In vitro binding assays demonstrated that ANDRO-FL could covalently bind to several known target proteins of andrographolide, including NF-kB, GST and hnRNP K. In summary, our data indicate that ANDRO-FL is a promising anticancer compound. Moreover, with comparable anticancer profile to andrographolide, Andro-FL can serve an effective tool to further explore the molecular targets underlying the anticancer mechanism of andrographolide. The in vivo anticancer activity of ANDRO-FL is currently under investigation.
Citation Format: Ya-Hsin Hsu, Yu-Ling Hsu, Sheng-Hung Liu, Hsin-Chia Liao, Po-Xuan Lee, Chao-Hsiung Lin, Lee-Chiang Lo, Shu-ling Fu. A new fluorescence-based andrographolide exhibits anticancer activity. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-30.
Abstract A2-31: Chemical proteomics approach reveals a monoacylglycerol lipase-dependent migration suppression of melanoma cells by andrographolide
Authors: Hsu Ya-Hsin , Huang Ting-Yun , Lo Lee-Chiang , Fu Shu-Ling , Lin Chao-Hsiung 
Published: November 2015

Abstract
Andrographolide is the major chemical component of an herbal plant, Andrographis paniculata, and has been reported to exhibit anti-cancer activity. We had previously demonstrated that andrographolide can suppress the migration and invasion of a highly metastatic melanoma cell, B16F10, but the molecular target and regulatory mechanism underlying this phenomenon remain unknown. A chemical proteomics approach using serine hydrolase activity probes and mass spectrometry-based identification was carried out to reveal that monoacylglycerol lipase (MAGL) of lipid metabolism is involved in the andrographolide-mediated suppression of B16F10 cell migration. MAGL has been reported to be elevated in aggressive cancers and associated with tumor metastasis. We observed that the hydrolase activity of MAGL in B16F10 cells was decreased upon andrographolide treatment but not in the poorly metastatic B16F1 cells. In addition, a known MAGL-specific inhibitor (JZL184) was used to demonstrate that suppression of MAGL enzyme activity could reduce B16F10 migration. Notably, overexpression of MAGL in B16F10 cells abrogated the andrographolide-mediated suppression of B16F10 migration, but such overexpression could not rescue the JZL184-mediated suppression. Further analysis showed a downregulation of MAGL mRNA levels in B16F10 cells upon treatment of andrographolide. With the use of an IKK inhibitor (Bay11-7082), the NF-kB signaling pathway is shown to be involved in the andrographolide-mediated suppression of MAGL expression. Taken together, we herein demonstrate that andrographolide suppresses melanoma cell migration via transcriptional downregulation of monoacylglycerol lipase, providing a new anti-cancer mechanism of andrographolide and a basis for further development of potent derivatives.
Citation Format: Ya-Hsin Hsu, Ting-Yun Huang, Lee-Chiang Lo, Shu-Ling Fu, Chao-Hsiung Lin. Chemical proteomics approach reveals a monoacylglycerol lipase-dependent migration suppression of melanoma cells by andrographolide. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-31.
Abstract A2-41: The Amplinome™ Test – A droplet digital PCR (ddPCR) based pan-cancer test to assess gene amplification status in solid tumors
Authors: Wong Amy , Pecson Jennifer , Putcha Girish , Nadauld Lincoln , So Austin P. 
Published: November 2015

Abstract
Gene amplifications constitute &gt;30% of all actionable mutation types present in cancer. However, despite their prevalence and the availability of targeted drug therapies, the development of molecular assays to detect gene amplifications has been limited by technical challenges such as limited DNA quantity and tumor heterogeneity. To address this, we describe the Amplinome™ test, a test that leverages the high precision and accuracy of droplet digital PCR (ddPCR) to determine the amplification status of 12 commonly amplified genes targeted by FDA approved drugs.
Twelve taqman assays were designed to target AURKA, BRAF, CDK4, CDK6, EGFR, ERBB2/HER2, ERBB3/HER3, FGFR1, JAK2, MET, SRC, and VEGFA, and duplexed with the reference gene RNaseP (Epoch, Bothell, WA). Each duplexed assay was then assembled with 2 μL of purified DNA and analyzed via ddPCR (Bio-rad QX-200 ddPCR Platform, Hercules CA). Genes were identified as “amplified” if the observed target:reference ratio was &gt;1.48 (p &lt; 0.005), which adjusts the ASCO-CAP threshold of 2.2 recommended for HER2 amplification for a minimum tumor content of 40%.
The Amplinome test identified 29 of 49 patients having actionable amplifications in at least one of the 12 assayed genes. In contrast, only 6 of 49 patients were identified as having amplifications in these genes through a commercially available sequencing test. An overall concordance rate of 90% (532/588 calls) between the two tests was observed. Discordant calls (56/588) arose from amplifications identified by the Amplinome test but not sequencing (55/56). One discordant call (HER3) was identified as amplified via sequencing, but confirmed to be unamplified via FISH.
The observed 10-fold increase in sensitivity versus a sequencing-based clinical test suggests that the prevalence of actionable amplifications may be significantly underestimated in cancer. This sensitivity, combined with its ability to provide results within an actionable timeframe (&lt;1 week), the underlines the potential value of Amplinome™ test in providing treatment options for oncologists and their patients.
Citation Format: Amy Wong, Jennifer Pecson, Girish Putcha, Lincoln Nadauld, Austin P. So. The Amplinome™ Test – A droplet digital PCR (ddPCR) based pan-cancer test to assess gene amplification status in solid tumors. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-41.
Abstract A2-45: R2: Accessible web-based genomics analysis and visualization platform for biomedical researchers
Authors: Koster Jan , Molenaar Jan J. , Versteeg Rogier 
Published: November 2015

Abstract
In this era of explosive high throughput (HT) genomics data generation, there is a growing need for accessible software solutions that can help unlock biological/clinical characteristics from such data. With the biomedical researcher (with limited or no bioinformatics skills) in mind, we developed a comprehensive web-based system called R2 (http://r2.amc.nl). R2 aids in the analysis and visualization of private/shielded as well as public high throughput data and their associated annotated features.
The R2 platform consists of a database storing both publicly accessible as well as shielded datasets with unified gene annotation, supplemented with a large suite of tools that can be used on these data, and their associated annotation. As such the user experiences the same look & feel throughout the mining process.
In the public section, R2 hosts over 60,000 HT samples. Next to gene expression (microarray and RNA-seq), the platform is also being employed in the integration, analysis and visualization of other data types, such as aCGH, SNP, ChIP, methylation, miRNA, and NGS whole genome sequencing information.
R2 contains an expanding set of interactive analyses which are heavily inter-connected, allowing users to quickly hop from one view (representation of the data) to another. Analyses include, correlation, differential expression, gene sets, gene ontology, transcription factor binding sites, PCA, kmeans, Kaplan Meier scans, signature creation etc. Visualizations include, various gene oriented plots, heatmaps, circos, embedded genome browser, Venn, etc.
Many parts of the R2 platform are publicly accessible through the http://r2.amc.nl portal. The R2 gene expression analysis tools have thus far been used in more than 180 peer-reviewed scientific publications including journals as Nature, Nature Genetics and Cell. R2 also supports restricted / shielded use and is used in many (inter)national collaborative efforts involving unpublished datasets. The webservers have been serving over 900.000 pages over the past 12 months (Nov 2014).
Citation Format: Jan Koster, Jan J. Molenaar, Rogier Versteeg. R2: Accessible web-based genomics analysis and visualization platform for biomedical researchers. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-45.
Abstract A2-46: Melanoma Profiler web tool for integrative genomic analysis of melanoma
Authors: Qaadri Kashef , Stones-Havas Steven , Ammundsen Brett , Trevarton Alexander , Print Cristin 
Published: November 2015

Abstract
Despite ongoing research, metastatic melanoma five-year survival rates remain low and treatment options limited. Researchers can access a rapidly growing amount of molecular and clinical information about melanoma that may be critical to understanding this disease and making clinically relevant treatment decisions. However, this information is becoming difficult to collate and clinically interpret due to its dispersed nature. Presented here is Melanoma Profiler, a new cloud-based web application for clinically relevant metastatic melanoma genomic research. It performs a tumor/normal comparative variant analysis, comparing proband modified genes and pathways to those in a curated set of characterized melanoma tumor samples. To provide clinical decision support, modified genes and pathways are cross-referenced with clinical and molecular data. These data are incorporated from publicly available sources, including: associations between gene expression and patient survival, data concerning drug targets, biomarkers, and druggability as well as past clinical trials. The resultant MelanomaDB cross-reference database integrates data from cutting edge research on a continuous basis. The interface is presented in two tiers: a front-panel summary tier and an evidential detail tier. For the busy clinician, immediately presented in the summary view is a dynamic report clearly highlighting the relevant actionable information, potential drug targets, and a summary of affected genes and pathways. For researchers that wish to dig deeper, they may browse annotated pathway data, and view a comprehensive comparative summary of affected genes in waterfall and heatmap reports. Melanoma Profiler is a free research tool hosted by Biomatters, produced in collaboration with the University of Auckland, New Zealand. A recent Frontiers in Oncology methods article describing the research behind the application can be found at http://bit.ly/1bUilqS. The Melanoma Profiler web application can be found at https://apps.biomatters.com/melanoma-profiler/.
Citation Format: Kashef Qaadri, Steven Stones-Havas, Brett Ammundsen, Alexander Trevarton, Cristin Print. Melanoma Profiler web tool for integrative genomic analysis of melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-46.
Abstract A2-49: Integrated Omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact
Authors: Moran Michael F. , Kislinger Thomas , Li Lei , Ignatchenko Vladimir , Wei Yuhong , To Christine , Taylor Paul , Tong Jiefei , Pham Nhu An , Pintilie Melania , Muthuswamy Lakshmi , Shepherd Frances A. , Tsao Ming Sound 
Published: November 2015

Abstract
Cancer results from processes prone to selective pressure and dysregulation acting along the sequence-to-phenotype continuum DNA→RNA→Protein→Disease. An Omics Array integrating DNA gene copy number, mRNA transcriptome, and quantified proteome was assembled into a genetic map representing non-small cell lung carcinoma (NSCLC). Data were collected from patient-matched normal lung, primary tumors, and patient tumor-derived xenograft (PDX) tumors. Dysregulated proteins not previously implicated as cancer drivers were found encoded throughout the genome including but not limited to regions of recurrent DNA amplification/deletion in NSCLC. Unsupervised clustering revealed signatures comprising metabolism proteins particularly highly recapitulated between matched primary and PDX tumors, and which distinguished between the major NSCLC histological subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Interrogation of The Cancer Genome Atlas (TCGA) revealed sizeable cohorts of NSCLC patients with DNA alterations in genes encoding the metabolism proteome signatures, and accompanied by differences in survival. Similar to the proteome signatures from which they were extrapolated, the gene mutation signatures with prognostic impact discriminated between the lung ADC and SCC subtypes. Serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in serine/glycine and folate-dependent one-carbon metabolism, is upregulated in the proteomes of NSCLC primary and PDX tumours, and is implicated as a driver of recurrent chromosome 12q14.1 amplification in NSCLC. SHMT2, along with other enzymes implicated as anti-folate targets, is also part of a metabolism signature associated with poor outcome in lung ADC. The interrogation of cancer genomes and proteomes for alterations that are related products of selective pressures driving the cancer phenotype may be a general approach to uncover and group together cryptic, polygenic cancer drivers, which might represent new anti-cancer therapeutic targets.
Note: This abstract was not presented at the conference.
Citation Format: Michael F. Moran, Thomas Kislinger, Lei Li, Vladimir Ignatchenko, Yuhong Wei, Christine To, Paul Taylor, Jiefei Tong, Nhu An Pham, Melania Pintilie, Lakshmi Muthuswamy, Frances A. Shepherd, Ming Sound Tsao. Integrated Omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-49.
Abstract A2-53: Integrative systems analyses reveal addiction of HER2+ breast cancers to ERAD for survival
Authors: Singh Navneet , Joshi Rashika , Komurov Kakajan 
Published: November 2015

Abstract
ERBB2/HER2-positive breast cancers are associated with poor prognosis; and resistance to HER2-targeted therapy is one of the significant clinical challenges. Trastuzumab and lapatinib are two agents that target the HER2 protein in the clinic and constitute the standard of care for HER2+ breast cancers (BCs). However, the clinical benefits of HER2-targeted therapies are limited due to significant de novo (&gt;60%) and acquired resistance (~100%) to these agents during prolonged phases of treatment. No treatment options exist for metastatic HER2+ BCs that have progressed on HER2-targeted therapy. Therefore, targeting of non-oncogenic vulnerabilities is a promising therapeutic approach in tumors that are resistant to oncogene-targeted therapy.
Using an evolutionary selection criterion, we computationally interrogated targetable non-oncogenic vulnerabilities in ERBB2/HER2+ breast cancers, which suffer from a high rate of de novo and acquired resistance to HER2-targeted therapy. We found that the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway is induced in HER2+ breast cancers, partly due to adaptive genomic rearrangements, to counter ER stress caused by increased proteotoxic burden due to heightened HER2/mTOR activity. Genetic and pharmacologic targeting of ERAD lead to irrecoverable ER stress and selectively killed HER2+ breast cancer cells, including those that are resistant to conventional therapy. Cell death due to ERAD inhibition was executed by the IRE1α/JNK pathway, which was suppressed in HER2+ breast cancers due to the activation of JNK phosphatases. Accordingly, inhibiting ERAD in combination with JNK phosphatases synergized in killing HER2+, but not HER2-, breast cancer cells. Our study supports exploiting oncogenic proteotoxicity as a novel therapeutic approach for therapy-refractory breast cancers, and presents an integrated strategy to identify non-oncogenic vulnerabilities in cancers.
Citation Format: Navneet Singh, Rashika Joshi, Kakajan Komurov. Integrative systems analyses reveal addiction of HER2+ breast cancers to ERAD for survival. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-53.
Abstract A2-67: Live cell imaging of ERK reveals unique inhibitor-specific adaptive responses
Authors: Gillies Taryn E. , Distor Kevin , Sànchez Marta Minguet , Pargett Michael , Albeck John 
Published: November 2015

Abstract
Defects in cell-to-cell signaling pathways can result in developmental abnormalities as well as cancer. The Ras/MAPK pathway is a central regulator of gene expression, cellular proliferation, and differentiation that is frequently de-regulated in cancer. While this pathway is a promising target for cancer therapeutics, a major obstacle is the tendency of the pathway to become re-activated via feedback within hours following inhibition. This adaptive response is important because the timing and duration of Ras/MAPK activity are known to determine the resulting cellular response and gene expression pattern. We have developed a new live-cell reporter, EKAR3, that allows ERK activity to be monitored with high temporal precision and resolution of heterogeneous individual cell behavior. To track the detailed pattern of adaptation to Ras/MAPK pathway inhibitors, we imaged over 10,000 individual cells responding to specific inhibitors of EGFR, Raf, MEK, and ERK. ERK activity was immediately reduced upon inhibition, but returned after a period of time ranging from 1-12 hours, depending on the inhibitor and its concentration. Strikingly, different inhibitors were found to induce distinct ERK recovery patterns, ranging from frequent, high-amplitude pulses to extended steady-state activity. We then statistically analyzed the effect of these differential ERK responses on cell behavior to dissect elements of the temporal signal relevant for information transmission in the cell. Our results indicate that, at the level of individual cells, targeted inhibitors induce kinetically distinct adaptive responses, which are likely to determine their effectiveness in controlling different aspects of cellular proliferation, survival, and migration.
Citation Format: Taryn E. Gillies, Kevin Distor, Marta Minguet Sànchez, Michael Pargett, John Albeck. Live cell imaging of ERK reveals unique inhibitor-specific adaptive responses. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-67.
Abstract IA04: Clinical decision support in the era of genome informed cancer medicine
Authors: Levy Mia 
Published: November 2015

Abstract
The emergence of high throughput genomic testing of tumors presents both an opportunity and challenge for use in clinical decision making across the continuum of cancer care. A tsunami of molecular data is now reaching the clinic with variable levels of evidence with respect to clinical validity and clinical utility. Not surprising, a large knowledge gap remains for oncologists who try to apply this new data for clinical decisions at the point of care. In order to address this knowledge gap, we have developed My Cancer Genome (MCG), a publically available website with the mission to curate and disseminate knowledge regarding the clinical significance of genomic alterations in cancer. My cancer genome contains content curated by domain experts on the prognostic and therapeutic implications of genomic alterations in cancers, including experimental therapeutics and active clinical trials. In addition to being publically available via MyCancerGenome.org, the content has also been integrated into a decision support tool for interpretation and reporting of results for tumor next generation sequencing via a commercial partner. Opportunities to scale resources like MCG continue to present opportunities and challenges to the cancer community. Data driven approaches where we learn from the experience of all cancer patients will be needed to help realize the promise of precision cancer medicine.
Citation Format: Mia Levy. Clinical decision support in the era of genome informed cancer medicine. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA04.