bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PL02-01: Advancing cancer diagnostics with artificial intelligence
Authors: Hipp Jason D. , Stumpe Martin 
Published: August 2018

Abstract
Rendering cancer diagnoses from tissues is a highly complex process that requires many years of expert training. It involves challenging tasks for pathologists, such as identifying rare events in very large images (e.g., micrometastases in lymph nodes) or classifying subtle differences between normal vs tumor or among similar-looking tumors that have very different treatment plans. These tasks are typically more challenging for human cognition, and, consequently, over- and underdiagnoses are not uncommon, resulting in nonoptimal treatment selection. Deep learning, a type of machine intelligence, has been successfully applied to solve similar identification and classification problems for Gmail, Google Maps, Google Photos, Google Translate, etc., and may have the potential to solve these similar challenges in the practice of pathology and help improve patient's diagnoses. This talk will begin by providing a brief background on deep learning and how it has been utilized at Google for health care and non-health care applications. The latter half of the talk will discuss the potential of deep learning to improve the accuracy and efficiency of the pathology workflow while highlighting recent advances towards that goal.
Citation Format: Jason D. Hipp, Martin Stumpe. Advancing cancer diagnostics with artificial intelligence [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 PL02-01.
Abstract PL02-04: Decoding patient genomes through the hierarchical pathway architecture of the cancer cell
Authors: Ideker Trey 
Published: August 2018

Abstract
Although cancer is governed by complex molecular systems, the composition and modular organization of these systems remains poorly understood. I will describe efforts by the Cancer Cell Map Initiative (CCMI) to generate large protein interaction maps of tumor cells, which we are integrating with existing molecular and structural data to assemble a comprehensive multiscale map of cancer cell biology. The current draft map contains a hierarchy of ~250 systems covering both known hallmarks and unexpected components. Integration with tumor mutation profiles suggests that the modules under strongest selective pressure in cancer are often not genes, but extend upwards in scale to include protein complexes, broad cellular processes, and organelles. This observation suggests a classification of cancer based on convergence of mutations at key bottlenecks in the hierarchy of cellular systems.
Citation Format: Trey Ideker. Decoding patient genomes through the hierarchical pathway architecture of the cancer cell [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 PL02-04.
Abstract PL04-04: Oncohistones in cancer: How to turn a cell's symphony into non harmonic rap
Authors: Jabado Nada 
Published: August 2018

Abstract
Recent studies have shown that chromatin-associated proteins and transcription factors have more somatic alterations than any other class of oncoproteins in childhood CNS tumors. Different Histone H3 genes (H3F3A, Hist3.1B) and variants (K27, G34, K36) can be affected with remarkable specific association between tumor location and type as well as the particular H3 residue or variant that is mutated. We have shown a high prevalence of H3 mutations in pediatric and young adult High Grade Astrocytoma, in sarcomas such as Giant Cell Tumors of the bone and chondroblastomas, and most recently, in Head and Neck Squamous Cell Carcinomas. These ground-breaking discoveries of oncohistones implicate a direct effect of epigenetic misregulation in oncogenesis. Here, we describe these epigenetic misfits and our knowledge of their effects, along with novel tools needed to study them. We will also discuss how we are harnessing synergies between the approaches of cancer genomics and chemical biology to help make sense of the pathogenesis of oncohistones and describe how oncohistones are promoting global redistribution of important epigenetic marks, seemingly hijacking our epigenome.
Citation Format: Nada Jabado. Oncohistones in cancer: How to turn a cell's symphony into non harmonic rap [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 PL04-04.
Abstract SY18-03: Cross-presenting DC in the TME
Authors: Krummel Matthew F. 
Published: August 2018

Abstract
The immune response to tumors is malleable as we have learned from the various success of immunotherapies, across a diversity of tumor types. What are the foundations for a solid immune response, particularly one executed by T cells? Imaging and single-cell approaches provide key insights into immune cell types that can be unleashed on tumors, identifying both their identity and the immune interactions that are to be fostered. In considering this, we consider the concepts of seeking "allies" for tumor therapies as well as for understanding the balance of push/pull signals that likely contribute to determine the consensus immune response.We discuss a few of these with particular emphasis on the diversity of the innate immune system and how its component parts can contribute toward antitumor immunity.
Citation Format: Matthew F. Krummel. Cross-presenting DC in the TME [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 SY18-03.
Abstract SY24-01: Genomic biomarkers for radiation resistance and targeted radiosensitizers
Authors: Willers Henning 
Published: August 2018

Abstract
Preclinical and clinical development of molecular targeted drugs with radiation therapy (RT) +/- chemotherapy is of critical importance to the field. However, a huge body of preclinical drug/RT studies has not translated into an adequate number of successful radiation oncology trials. Major contributing factors likely include poor reproducibility of preclinical data, over-reliance on tumor growth delay but not long-term local tumor control experiments, and insufficient preclinical modeling of genomic heterogeneity that influences the treatment sensitivity of tumors in the clinic. There exists an urgent need to overcome these barriers to successful clinical translation of targeted radiosensitizers. Our efforts to establish high-throughput screening of targeted radiosensitizers and identify genomic biomarkers of radiosensitization will be presented. The key underlying concept is that short-term, nonclonogenic assays are suitable for capturing the relative change in radiation sensitivity that is induced by a targeted drug, and thus can serve as surrogate endpoints for the “gold standard” clonogenic survival assay. Through the use of a large number of annotated cancer cell lines, high-throughput platforms can model clinically relevant genomic heterogeneity across and within different tumor types. Moreover, these platforms facilitate the inclusion of patient-derived organoid tumor model,s which are likely better suited to mimic in vivo growth conditions than historical 2D monolayer cultures. Examples of biomarker-correlated radiosensitization effects in 2D as well as 3D settings will be shown. In particular, novel therapeutic targets associated with mutated KRAS will be highlighted. To this end, our recent in vitro, in vivo, and clinical data have established KRAS mutation as a biomarker of radiation resistance, especially when accompanied by co-mutation in TP53. The radiation resistance of KRAS mutant cancers constitutes an unmet clinical need. Taken together, by leveraging large panels of genomically characterized preclinical tumor models (2D or 3D) for testing the radiosensitizing properties of novel or repurposed agents, we may ultimately identify biomarker-directed combinatorial approaches that have a higher likelihood of leading to successful radiation therapy clinical trials than past studies.
Citation Format: Henning Willers. Genomic biomarkers for radiation resistance and targeted radiosensitizers [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 SY24-01.
Abstract SY25-01: Genome regulation by long noncoding RNAs
Authors: Chang Howard Y. 
Published: August 2018

Abstract
The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provides an important new perspective on the centrality of RNA in gene regulation. I will discuss genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in human diseases.
Citation Format: Howard Y. Chang. Genome regulation by long noncoding RNAs [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 SY25-01.
Abstract SY26-03: Dual targeting of senescence and tumor immunity for cancer therapy
Authors: Alimonti Andrea 
Published: August 2018

Abstract
Senescence induction in cancer works as a potent weapon to eradicate tumorigenesis. Therapies that enhance senescence not only promote a stable cell growth arrest but also work as a strong stimulus for the activation of the tumor immune response. However, cancer cells bypass senescence by either acquiring new genetic alterations or by disrupting the tumor immune response. Here, I will discuss the identification of oncogenic pathways that bypass Pten-loss-induced cellular senescence, thereby promoting prostate cancer progression and metastasis. Next, I will present evidence demonstrating that both tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) control senescence induction in chemotherapy-treated prostate cancers and that immunotherapies that interfere with either MDSCs' recruitment or the polarization of TAMs promote senescence in advanced PTEN-deficient prostate cancer.
Citation Format: Andrea Alimonti. Dual targeting of senescence and tumor immunity for cancer therapy [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 SY26-03.
Abstract SY29-01: Role of nitrogen metabolism in obesity-associated pancreatic cancer
Authors: Kalaany Nada Y. 
Published: August 2018

Abstract
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDAC remain unknown. Here we show that obesity-driven PDAC exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDAC. In vivo infusion of 15N-glutamine in obese mouse models of PDAC demonstrates enhanced nitrogen flux into the urea cycle, and infusion of 15N-arginine shows that Arg2 loss causes significant ammonia accumulation that results from the shunting of arginine catabolism into alternative nitrogen repositories. Furthermore, analysis of PDAC patient tumors indicates that ARG2 levels correlate with body mass index (BMI). The specific dependency of PDAC on ARG2 rather than the principal hepatic ureagenic enzyme ARG1 opens a therapeutic window for obesity-associated pancreatic cancer.
Citation Format: Nada Y. Kalaany. Role of nitrogen metabolism in obesity-associated pancreatic 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 SY29-01.
Abstract A29: Investigation of RECQL variants in European and African American breast cancer cohorts
Authors: Chandler Madison R. , Bergstresser Sydney , Huskey Anna LW , Stallworth Elizabeth , Davis Amber , Dean Holly , Johnson Brandon , Merner Nancy D. 
Published: August 2018

Abstract
Although an average woman in the United States can have a 12.5% lifetime risk of developing breast cancer (BC), inherited genetic risk variants can greatly influence a woman’s overall lifetime risk. Genes that harbor BC risk variants are referred to as BC susceptibility genes. Unfortunately, mutations in known BC susceptibility genes only explain approximately 35% of hereditary BC cases, leaving a large portion, approximately 65%, genetically unexplained. With the introduction of next-generation sequencing, several attempts have been carried out to identify additional hereditary BC susceptibility genes using whole-exome sequencing. The majority of these studies were relatively unsuccessful; however, Cybulski et al. (2015) successfully associated two rare truncation variants in RECQL, p.K555delinsMYKLIHYSFR and p.R215*, in a Polish and French-Canadian cohort, respectively. Subsequently, two additional studies were carried out in northern and southern regions of China, which also confirmed that overtly deleterious coding mutations in RECQL are associated with familial BC. Herein, we investigated RECQL variants in BC-affected African Americans (AAs) and European Americans (EAs). To our knowledge, this study represents the first attempt to identify an association between RECQL variants and BC cases in the United States. We initially screened all RECQL coding exons using polymerase chain reaction and Sanger sequencing in 49 BC cases (19 AAs and 30 EAs) from Alabama. Primarily synonymous variants were detected in both ethnicities; thus, in order to further investigate the role of RECQL synonymous variants in BC risk, we analyzed RECQL in blood-derived exomes of 168 and 580 BC-affected AAs and EAs, respectively, from The Cancer Genome Atlas (TCGA) project using an in-house bioinformatics pipeline. A case-control analysis revealed that all rare synonymous variants detected in EA BC cases were associated with BC, and p.S64= was significantly associated in both ethnicities. Interestingly, only one truncation variant was detected (p.Y492*) in all 748 BC cases analyzed. Unlike previous findings, this preliminary analysis suggests that rare RECQL synonymous variants may also increase an individual’s lifetime risk of developing BC; further investigation is warranted.
Citation Format: Madison R. Chandler, Sydney Bergstresser, Anna LW Huskey, Elizabeth Stallworth, Amber Davis, Holly Dean, Brandon Johnson, Nancy D. Merner. Investigation of RECQL variants in European and African American breast cancer cohorts [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A29.
Abstract 51: The eukaryotic translation initiation factor 4H regulates proliferation, migration, and invasion in cancer cells
Authors: Singh Manohar , Trivedi Rachana , Mishra Durga Prasad 
Published: August 2018

Abstract
Background: Dysregulated translation during protein synthesis is a hallmark of multiple human cancers. However, the precise mechanisms remain to be understood. Protein translation of oncogenic mRNAs is highly upregulated in cancer cells and these cells are very sensitive to therapeutic strategies/agents targeting translation inhibition. In this study we investigated the role of translation initiation factor eIF4H in proliferation and survival of cancer cells.
Methods: We selected the breast cancer cell line MDA-MB 231 and the CML cell line K562 for our study. We silenced eIF4H by shRNA and cell proliferation were analyzed by MTT assay and flowcytometry. Expression of antiapoptotic and proproliferative proteins were analyzed by Western blotting and for analysis of mRNA expression real-time PCR was used. Effect of eIF4H silencing on cell migration and invasion was analyzed by migration and invasion assays, respectively.
Results: Using 2D Gel based proteomics we targeted the translational machinery in chronic myeloid leukemia cell line K562 and identified eIF4H as a critical regulator of carcinogenesis. The eIF4H expression was found to be overexpressed in a variety of cancer cell line vis-à-vis the normal nontransformed cells. Similarly, the real-time PCR analysis showed eIF4H overexpression in chronic myeloid leukemia clinical samples compared to that of the healthy controls. The pharmacologic inhibition of eIF4H induced downregulation of its regulatory proteins cMYC, cyclin D1, and antiapoptotic proteins in breast cancer cell line MDAMB-231 and CML cell line K562 cells. The genomic inhibition of eIF4H decreased cell migration and invasion in vitro in MDA-MB 231 cell line and it also inhibits proliferation of both cell lines. Furthermore, the p65-dependent transcriptional activation of eIF4H was observed to be associated with this process.
Conclusion: Our results demonstrate that eIF4H plays an important role in the proliferation, migration, and invasion of cancer cells. Silencing of eIF4H markedly decreased expression of antiapoptotic and proproliferative proteins. Collectively, our findings suggest that eIF4H may have translational relevance as a therapeutic target in cancer therapy.
Citation Format: Manohar Singh, Rachana Trivedi, Durga Prasad Mishra. The eukaryotic translation initiation factor 4H regulates proliferation, migration, and invasion in cancer cells [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 51.
Abstract IA12: The role of malignant RNA editing in leukemia stem cell generation
Authors: Jamieson Catriona H. M. 
Published: August 2018

Abstract
Deregulation of RNA processing contributes to cancer progression and drug resistance. As a major driver of coding and noncoding transcriptomic diversity, adenosine deaminase associated with RNA1 (ADAR1) induces hydrolytic deamination of adenosines (A) to inosines (I) in response to proinflammatory cytokines elicited by viral infection or malignant microenvironments. Recently, we and other groups demonstrated that enhanced A-to-I RNA editing promotes therapeutic resistance of many cancers, including myeloproliferative neoplasms (MPN). As a paradigm for dissecting the molecular evolution of cancer, MPNs are initiated in hematopoietic stem cells (HSCs) by BCR-ABL1, JAK2 V617F or CALR mutation expression and transform to acute myeloid leukemia (AML) as a result of malignant reprogramming of progenitors into self-renewing leukemia stem cells (LSCs). With regard to the role of noncoding RNA editing in LSC evolution, ADAR1 enhances self-renewal of preleukemic progenitors in CML by impairing let-7 microRNA (miRNA) biogenesis. Moreover, ADAR1 editase activity suppresses the expression of miRNAs that regulate cell cycle, cancer progression, p53 stabilization, and WNT signaling. In addition to noncoding transcript deregulation, A-to-I editing is also observed in coding regions of stem cell regulatory transcripts, such as the sonic hedgehog transcriptional activator GLI1, and induces mis-splicing of GSK3β, thereby enhancing β-catenin activation. In summary, RNA editing research will inform the development of clinically tractable strategies for predicting and preventing LSC generation.
Citation Format: Catriona H. M. Jamieson. The role of malignant RNA editing in leukemia stem cell generation [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr IA12.
Abstract IA25: Epigenetic regulation of cancer immune surveillance processes
Authors: Johnstone Ricky W. 
Published: August 2018

Abstract
Altered expression, function, or localization of epigenetic enzymes and/or their partner proteins can play a crucial role in cancer onset and progression. Histone writers and erasers that regulate histone acetylation or methylation, or histone readers that recognize specific histone marks, play important roles in tightly regulating gene expression through the remodeling of chromatin and these proteins are promising targets for therapeutic interventions intended to reverse aberrant epigenetic states associated with cancer. The effects of HDAC inhibitors (HDACi) and BET bromodomain inhibitors (BETi) on tumor cell growth and survival have been well documented. However, HDACi and BETi also have immunomodulatory properties that could be important for antitumor responses and could be harnessed to enhance the activities of other anticancer agents. I will present data showing that HDACi and BETi can activate different components of the innate and adaptive immune response through effects on both the target tumor cells and on immune cells. These properties are important for the antitumor effects of HDACi and BETi and can be exploited to devise novel combination regimes involving epigenetic regulators and immune modulators.
Citation Format: Ricky W. Johnstone. Epigenetic regulation of cancer immune surveillance processes [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr IA25.