bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5117: Comprehensive structural analysis of cancer genomes by genome mapping
Authors: Lam Ernest , Delpu Yannick 
Published: August 2019

Abstract
Tumors are often comprised of heterogeneous populations of cells, with certain cancer-driving mutations at low allele fractions in early stages of cancer development. Effective detection of such variants is critical for diagnosis and targeted treatment. However, typical short sequence reads are limited in their ability to span across repetitive regions of the genome and to facilitate structural variant (SV) analysis. Based on specific labeling and mapping of ultra-high molecular weight (UHMW) DNA, we developed a single-molecule platform that has the potential to detect disease-relevant SVs and give a high-resolution view of tumor heterogeneity.
We developed a DNA isolation and sample preparation workflow that preserves the DNA integrity and conserves structural variation information from blood, cells and preserved tissue. Single molecules are labeled at specific motifs and analyzed in massively parallel nanochannels. The single-molecule maps are used in a bioinformatics pipeline that effectively detects structural variants at low allele fractions. It includes single-molecule based SV calling and fractional copy number analysis. Preliminary analyses using simulated and well-characterized cancer samples showed high sensitivity for variants of different types at as low as 5% allele fractions. The candidate variants are then annotated and further prioritized based on control data and publicly available annotations. The data are imported into a graphical user interface tool that includes new visualization tools (such as Circos diagrams) for real-time interactive visualization and curation.
Bionano offers sample preparation, DNA imaging and genomic data analysis technologies combined into one streamlined workflow that enables high-throughput genome mapping on the Bionano Saphyr system. Together, these components allows for efficient analysis of any genome of interest.
Citation Format: Ernest Lam, Yannick Delpu. Comprehensive structural analysis of cancer genomes by genome mapping [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5117.
Abstract 513: Investigating the expression of indolamine deoxygenase I (IDO1) and other immune markers in tissue microarrays
Authors: Cerezo Ana , Hoyo Gloria Martinez-del , Peregrina Sandra , Mondejar Tamara , Caleiras Eduardo , Gonzalez Patricia , Lospitao Eva , Hernandez-Tiedra Sonia , Diezma Laura , Casas Estela , Dorsey Frank , Benhadji Karim , Gilmour Raymond , Geeganage Sandaruwan , Velasco Susana 
Published: August 2019

Abstract
Purpose of the study: To gain insight to the proportion of solid tumors that express IDO1, CD73 and PD-L1 in lung cancer, colon adenocarcinoma, renal cell carcinoma (RCC) and melanoma, and the correlation between expression of these immune checkpoints and immune cell infiltration within the tumor.
Experimental procedures: Using a battery of properly validated antibodies, we have performed an in situ analysis of IDO1, CD73 and PD-L1 expression by immunohistochemistry in a panel of colon cancer (n=68), lung cancer (n=36), RCC (n=67) and melanoma (n=48) tissue microarray samples. Tumor infiltrating T cells, CD3+ and CD8+, were also detected by IHC and counted in serial sections for each sample. We search for a possible a correlation between the expression of these immunosuppressor proteins and the number of infiltrating CD3+ and CD8+ T cells as well as their expression in the different tumor components: tumor cells, stroma and endothelium.
Results: Our IHC analysis allowed us to classify the analyzed samples into two main groups: those with expression of IDO1, CD73 and PD-L1, which were also the ones with a high presence of immune cells within the tumors, “hot tumors”, and those that showed to be negative for all three proteins, and that correlated with lower infiltration of T cells, “cold tumors”. We also analyzed the location of the proteins within the tumors, and found an effect between endothelial expression of Ido1 and reduced infiltration in lung and RCC tumors.
Conclusions: The response to combined immune checkpoint and IDO1 therapy could depend on the proper stratification of patients; therefore, it is of significant interest to determine the proportion of solid tumors that express IDO1, CD73 and PD-L1, and the correlation of the expression of these three immune check points to immune cell infiltration within the tumor. Thus, proper patient stratification based on the expression of these immune checkpoints may improve the efficacy of IDO1 inhibitor based immune therapies.
Citation Format: Ana Cerezo, Gloria Martinez-del Hoyo, Sandra Peregrina, Tamara Mondejar, Eduardo Caleiras, Patricia Gonzalez, Eva Lospitao, Sonia Hernandez-Tiedra, Laura Diezma, Estela Casas, Frank Dorsey, Karim Benhadji, Raymond Gilmour, Sandaruwan Geeganage, Susana Velasco. Investigating the expression of indolamine deoxygenase I (IDO1) and other immune markers in tissue microarrays [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 513.
Abstract 5145: A new discovering motif on SOS1 PR domain clues Grb2-SOS1 association
Authors: Liao Tsung-Jen , Jang Hyunbum , Nussinov Ruth , Fushman David 
Published: August 2019

Abstract
Grb2 is an adaptor protein that recruits Ras-specific guanine nucleotide exchange factor (GEF), such as Son of sevenless 1 (SOS1), to the plasma membrane. SOS1 exchanges GDP by GTP, activating Ras. Grb2 consists of an SH2 domain in the middle and flanks nSH3/cSH3 domains at both ends. Both nSH3/cSH3 domains bind to SOS1’s C-terminal proline rich (PR) domain and have the preference for interacting with the PXXPXR motif. Our NMR data suggest that the arginine residue, followed by prolines in the PXXPXR motif, is responsible for the SH3-SOS1 association, yielding large chemical shift perturbations (CSPs) on the binding interface of SH3. The SOS1’s PR motif, PVPPPVPPRRRP, exhibits the strongest binding affinity to both SH3 domains. Using comprehensive techniques involving molecular dynamics (MD) simulation and NMR measurement, we uncover a new SOS1’s PR motifs, PKLPPKTYKREH, which shows strong binding to cSH3 but exhibits very weak affinity to nSH3. Unlike the arginine residue in the PXXPXR motif, the lysine residue in the PXXPPKXXKR motif induces weak interaction with cSH3. However, high affinity interaction is mainly derived from the hydrophobic interaction between the PXXP motif and cSH3, indicating the different binding modes of interaction. Our results suggest that Grb2 nSH3/cSH3 bind to SOS1 at distinct locations and provide atomic detailed models of Grb2-SOS1 association. Recent Grb2 targeted therapy reveals that peptide inhibitors, which interrupt Grb2-SOS1 interaction, effectively prevent the migration of breast cancer cell. The mechanism of Grb2-SOS1 interaction may enlighten the promising drug treatment development.
Citation Format: Tsung-Jen Liao, Hyunbum Jang, Ruth Nussinov, David Fushman. A new discovering motif on SOS1 PR domain clues Grb2-SOS1 association [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5145.
Abstract 5232: PES1 is highly expressed and its biological function in gastrointestinal tumor
Authors: Feng Qin , Lian Shenyi , Wang Ping , Wang Yue , Li Zhongwu , Shou Chengchao , Ren Tingting , Lin Dongmei 
Published: August 2019

Abstract
Nucleolus, one of the most important organelles in cell nuclear of eukaryotic cells, is made of rRNA, rDNA and nucleoproteins. Its main function is rRNA synthetic. PES1 is part of nucleolar protein, and was identified in the mutational study of the embryonic development of Zebrafish. Its main biological functions include forming nucleolus, promoting cell proliferation and regulating cell cycle. A few researches indicate the close relationship between PES1 and tumorigenesis.
The purpose of this study is to explore the role of PES1 in tumorigenesis and the possible mechanism. Three specific monoclonal antibodies against PES1 were made through hybridoma technique. Using these antibodies, it is found that PES1 had significantly higher expression in gastric and colon carcinoma than in tumor-adjacent and -distant tissues. Immunohistochemical assay on gastric carcinoma specimens and colon carcinoma specimens indicated that PES1 had significantly higher expression in carcinoma than in tumor-adjacent tissues. Moreover, we demonstrated the localization of PES1 was changed from nucleolus to nucleoplasm significantly under the stimulation of chemotherapeutic drugs and UV. The phenomenon of PES1 translocation in nucleus was weaken in drug-resistant cancer cell lines. These results suggest that the translocation of PES1 in nucleus might be related to DNA damage repair and drug resistance mechanism of cancer cells.
In summary, PES1 expression is significantly higher in gastric and colon carcinoma tissue. And dynamic changes of PES1 localization in the cell nucleus is an important biological function and is worth further research.
Note: This abstract was not presented at the meeting.
Citation Format: Qin Feng, Shenyi Lian, Ping Wang, Yue Wang, Zhongwu Li, Chengchao Shou, Tingting Ren, Dongmei Lin. PES1 is highly expressed and its biological function in gastrointestinal tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5232.
Abstract 5236: A qualitative change in transcriptome during MDCKII 3D epithelial morphogenesis is linked to intracellular trafficking
Authors: Wang Tianfang , Zhao Shaying , Cheng Shi-Yuan 
Published: August 2019

Abstract
The majority of human cancers are derived from epithelial tissues. Understanding epithelial morphogenesis is hence important in cancer research. Madin-Darby canine kidney II (MDCKII) cells, cultured in 3D and 2D conditions, are used extensively as a model for studying cell polarity, epithelial morphogenesis and carcinogenesis. Like other cell differentiation systems, gene expression plays a key role in MDCKII epithelial morphogenesis.
To better understand the change in the transcriptome, we performed a time course RNA-seq analysis of MDCKII 3D cytogenesis, along with fully polarized 2D cells for comparison. Surprisingly, our study reveals that the change is not linear, but rather clearly biphasic. Specifically, about 3,000 genes are significantly up- or down-regulated between 24 hour and day 3 after seeding, when the lumen is forming, compared to &lt; 120 such genes during other time intervals. Because previous studies have shown that Rab11-coordinated intracellular trafficking plays an essential role in MDCKII lumen formation, we hypothesize this qualitative change in the transcriptome is linked to intracellular trafficking. To test this hypothesis, we used knockdown clones of AVL9 and DENND5A, both interacting with Rab11 and participating in trafficking. Knockdown cells have altered cell polarity and defective trafficking, but not as significant changes in transcriptome as wild type cells, supporting our hypothesis. We then focused on β-catenin to better understand the mechanism. Our study reveals that in wild type cells, following the first cell division, β-catenin is depleted from the nucleus and enriched in cell-cell junction. This results in MYC transcriptional silencing (supported by ATAC-seq analysis), which in turn initiated down-regulation of numerous MYC target genes. These observations are however not observed in knockdown cells.
Our study supports the qualitative change (“switch on-off”) model, rather than the quantitative (gradual) change model, in transcriptome remodeling during epithelial cell differentiation. Moreover, our work supports that intracellular trafficking likely initiates this quantitative change in transcriptome.
Citation Format: Tianfang Wang, Shaying Zhao, Shi-Yuan Cheng. A qualitative change in transcriptome during MDCKII 3D epithelial morphogenesis is linked to intracellular trafficking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5236.
Abstract 5242: To investigate the molecular mechanism and therapeutic roles of PSF-1 in leukemia
Authors: Hsieh Han-Yun , Jia Wei-Zhen , Takakura Nobuyuki 
Published: August 2019

Abstract
Recently, DNA replication protein PSF-1 gets more and more attention on the research field, PSF-1 not only plays the critical role in normal cell DNA replication but also involves in cancer cell proliferation and anti-apoptosis. PSF1 highly expressed in many types of cancers, such as non-small lung cancer, breast cancer, and colon carcinoma. However, the role and mechanism of PSF1 in leukemia are still uncleared. Compared to the human normal peripheral blood mononuclear cells (PBMCs), the expression level of PSF1 was significantly increased in several types of leukemia, including acute and chronic type leukemia. We also found that PSF1 participate in leukemic cell proliferation and anti-apoptosis. Since PSF1 presents in many types of leukemia, PSF-1 might act as a potential therapeutic target of pan-leukemia. However, in order to enhance the therapeutic effect of leukemia, against its recurrence and metastasis, leukemic stem cells (LSCs) become the novel therapeutic research target. Previous studies indicated that PSF-1 is essential for stem cell proliferation. Based on the study, we selected PSF-1 as the candidate. In this research, we would like to investigate the role of PSF-1 in leukemia and its cancer stem cell niche. Further to establish the new therapeutic method of LSC-specific clinical treatment.
Citation Format: Han-Yun Hsieh, Wei-Zhen Jia, Nobuyuki Takakura. To investigate the molecular mechanism and therapeutic roles of PSF-1 in leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5242.
Abstract 5247: Overexpression of methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) in bladder cancer: A potential therapeutic target
Authors: Eich Marie-Lisa , Pena Maria D. Rodriguez , Chandrashekar Darshan S. , Gordetsky Jennifer B. , Netto George J. , Varambally Sooryanarayana 
Published: August 2019

Abstract
Introduction: Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1L) is a mitochondrial enzyme involved in the folate cycle by catalyzing the reaction of formyl-tetrahydrofolate to format and tetrahydrofolate (THF). THF is crucial for de novo purine and thymidylate synthesis and is also involved in the regeneration of methionine. Cancer cells rely on purines derived from the de novo pathway for the nucleotides whereas normal cells favor the salvage pathway. Thus, MTHFD1L could be a valuable therapeutic target for anticancer drug design. This study aimed to examine MTHFD1L expression in bladder cancer (BLCA).
Material and Methods: Applying the publicly available cancer transcriptome database UALCAN, we searched for overexpressed genes in bladder cancer associated with survival probability. These in silico analyses indicated a high expression of MTHFD1L in bladder cancer. Furthermore, MTHFD1L expression was analyzed in different molecular subtypes, stage and race groups. Survival probability in MTHFD1L low-and high-expressing tumors was also assessed using UALCAN. Additionally, by searching the publicly available data base Human Protein Atlas we analyzed MTHFD1L immunostaining patterns in bladder cancer.
Results: We analyzed data for 19 normal bladder tissues and 408 primary bladder cancers from the TCGA dataset. MTHFD1L was significantly (p&lt;0.0001) overexpressed in tumorous tissue compared to normal. This overexpression was observed independent of stage, race and age. Furthermore, we found a higher number of MTHFD1L mRNA transcripts in tumors belonging to the basal/squamous and in the neuronal TCGA subtype. Kaplan-Meier survival analysis indicated a poorer survival in patients with high MTHFD1L expression (p=0.05). Evaluation of immunohistochemistry staining pattern in bladder cancer using the Human Protein Atlas database showed a differential expression among human bladder cancer tissues. We are performing in vitro studies to evaluate the role of MTHFD1L in bladder cancer initiation and progression.
Conclusions: Our preliminary findings on MTHFD1L suggest that its overexpression is associated with poor patient survival in bladder cancer. These results suggest that MTHFD1L could be important in the biology of BLCA and a potential target for therapy. Future studies will investigate the functional significance of MTHFD1L and its regulation in bladder cancer.
Citation Format: Marie-Lisa Eich, Maria D. Rodriguez Pena, Darshan S. Chandrashekar, Jennifer B. Gordetsky, George J. Netto, Sooryanarayana Varambally. Overexpression of methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) in bladder cancer: A potential therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5247.
Abstract 5257: Activation of the oncogene ERG by the Ras/ERK and PI3K/AKT pathways
Authors: Strittmatter Brady G. , Hollenhorst Peter 
Published: August 2019

Abstract
The TMPRSS2-ERG re-arrangement occurs in ~50% of prostate cancers and results in androgen driven aberrant expression of the transcription factor ERG. ERG acts as an oncogene in the prostate and activates a transcriptional program which results in cell migration, epithelial to mesenchymal transition, and tumorigenesis. Activation of both the Ras/ERK and PI3K/AKT signaling pathways has been demonstrated to be necessary for transcription of ERG target genes and is required for ERG mediated phenotypes in the prostate, however, the exact mechanism of this requirement is not known. Recently, our lab demonstrated that ERK1/2 phosphorylation of ERG abrogates ERG’s interaction with the co-repressor EZH2 and the PRC2 and is necessary for ERG-mediated transcription of genes involved in cell migration. It has been demonstrated that ERG also requires activation of the PI3K/AKT pathway for ERG-mediated tumorigenesis in the prostate, however how the Ras/ERK and PI3K/AKT pathways cooperate in transcription of ERG target genes and ERG mediated phenotypes is not well understood. Here we use genomic and transcriptomic approaches to demonstrate that Ras/ERK and PI3K/AKT pathway requirements for ERG function differ between distinct ERG-mediated mediated gene expression programs which correlate with distinct phenotypic outputs. Overall, our results demonstrate how the Ras/ERK and PI3K/AKT pathways contribute to ERG mediated tumorigenesis in the prostate and point the way towards new therapeutic targets.
Citation Format: Brady G. Strittmatter, Peter Hollenhorst. Activation of the oncogene ERG by the Ras/ERK and PI3K/AKT pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5257.
Abstract 5274: Multi-omics integration analysis robustly predicts high grade patient survival and identified altered fatty acid metabolism in high grade bladder cancer
Authors: Vantaku Venkata Rao , Dong Jianrong , Ambati Chandrashekar R , Perera Dimuthu , Donepudi Sri Ramya , Amara Chandra Sekhar , Putluri Vasanta , Shankar Ravi Shiva , Robertson Matthew J , Piyarathna Danthasinghe Waduge Badrajee , Villanueva Mariana , Rundstedt Friedrich-Carl von , Karanam Balasubramanyam , Ballester Leomar Y , Terris Martha K. , Lerner Seth P. , Andrea Apolo B , Villanueva Hugo , Sikora Andrew , Lotan Yair , Sreekumar Arun , Coarfa Cristian , Putluri Nagireddy 
Published: August 2019

Abstract
Cancer metabolism varies depending on tumor grade. Currently, there is an absence of integration of multi-omics data to predict Bladder cancer (BLCA) survival. We aimed to identify a metabolic signature in high-grade BLCA by integration of unbiased metabolomics, lipidomics and transcriptomics to predict patient survival and to discover novel therapeutic targets. In the current study, using a robust mass spectrometry platform, we conducted global unbiased metabolic and lipid profiling analysis. We identified 518 differential metabolites and 19 lipids of various classes using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively, between low-grade and high-grade BLCA then mapped them to associated genes. Pathway analysis revealed a unique set of biochemical pathways highly deregulated in high-grade BLCA. Integromics analysis identified a molecular gene signature associated with patient poor survival. Importantly, low expression of fatty acid associated enzymes in high-grade tumors was associated with low fatty acid β- oxidation and acyl carnitines in high-grade BLCA and confirmed using tissue microarray. Our key finding is that impaired fatty acid β-oxidation (FAO) by downregulation of fatty acid associate enzymes suggests a crucial role in the progression of low grade to high grade BLCA. Using a metabolic-centered multi-omics based integrative analysis provided a system-level perspective of BLCA that would facilitate the development of novel therapeutics for high-grade BLCA.
Note: This abstract was not presented at the meeting.
Citation Format: Venkata Rao Vantaku, Jianrong Dong, Chandrashekar R Ambati, Dimuthu Perera, Sri Ramya Donepudi, Chandra Sekhar Amara, Vasanta Putluri, Ravi Shiva Shankar, Matthew J Robertson, Danthasinghe Waduge Badrajee Piyarathna, Mariana Villanueva, Friedrich-Carl von Rundstedt, Balasubramanyam Karanam, Leomar Y Ballester, Martha K. Terris, Seth P. Lerner, Apolo B Andrea, Hugo Villanueva, Andrew Sikora, Yair Lotan, Arun Sreekumar, Cristian Coarfa, Nagireddy Putluri. Multi-omics integration analysis robustly predicts high grade patient survival and identified altered fatty acid metabolism in high grade bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5274.