bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2803: The NCI mouse repository: Cancer models and miRNA-ES cell resource
Authors: Awasthi Parirokh , Debra Fitzgerald , Stephen Jones N. 
Published: July 2017

Abstract
The NCI Mouse Repository, located at the Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland, is an NCI-funded resource of approximately 150 genetically-engineered mouse cancer models and associated strains, including mice bearing conditional and point-mutant alleles in cancer-related genes. In addition, the Repository houses a unique collection of over 1500 different mouse ES cell clones bearing conditionally-activated miRNA transgenes to facilitate in vivo exploration of miRNA functions. The NCI Mouse Repository makes strains and mESCs available to all members of the scientific community (academic, non-profit, and commercial). The mouse models and ES cell clones are cryo-archived and distributed as frozen germplasm or cells.
Requests may be placed through the NCI Mouse Repository website (https://ncifrederick.cancer.gov/Lasp/MouseRepository/Default.aspx). In addition to the request form, this website includes detailed description for each strain accepted into the Repository and the associated publications provided by the donating scientist. The miR-harboring ESCs, originally generated at the Cold Spring Harbor Laboratories for the NCI, are described in full detail and include validation data for each miRNA ES cell clone. These resources are available for nominal cost to NCI, NIH, and other US government-funded investigators, as well as to Investigators at non-profit organizations.
Citation Format: Parirokh Awasthi, Fitzgerald Debra, Jones N. Stephen. The NCI mouse repository: Cancer models and miRNA-ES cell resource [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2803. doi:10.1158/1538-7445.AM2017-2803
Abstract 2816: The Jackson Laboratory Repository: Mouse models for cancer research
Authors: Boswell Deborah , Rockwood Stephen , Sasner Michael , Team The JAX Repository 
Published: July 2017

Abstract
The mouse is a well-established model organism for research of the biology, prevention, diagnosis, and treatment of cancer. Among the advantages of this valuable biomedical research tool are a relatively short reproductive cycle, an accelerated lifespan, and the ease of genetic manipulation and modification. Serving as a resource to the scientific community, the JAX Repository collection encompasses over 10,000 mouse strains and acquires hundreds of new models each year. Some of these new models are highlighted in this poster. Many of these strains have applications for modeling human cancer, including genetically engineered mouse models for specific cancers and xenograft models. Research tool strains, such as cas9-expressing (CRISPR) lines, a suite of immunodeficient mice, and recombinase expressing strains, are available to investigators to generate customized mutant lines for specialized purposes. JAX offers supplementary research tools that include specialized strain platforms and other useful resources. The JAX patient-derived xenograft (PDX) cancer model resource leverages the immunodeficient NSG strain for tumor engraftment.
The Repository maintains a searchable online resource to find mice (www.jaxmice.jax.org) and an Oncology Therapeutic Area page (www.jax.org/jax-mice-and-services/solutions-by-therapeutic-area/oncology) as a launch pad to featured JAX strains and resources related to oncology research.
The Repository has a rigorous quality control program that inspects and confirms expected mutation identity and genetic background. JAX mouse lines are also screened for alleles (GFP, cre, lacZ, etc.) that may contaminate strains in mouse lines shared between labs—an underappreciated problem that may contribute to inconsistencies of reproducibility. In addition, the Reproductive Sciences group at JAX safeguards each strain by cryopreservation, and can create cohorts for studies rapidly using IVF technology. Researchers can submit their strains to be considered for inclusion in the Repository by using the on-line form available at The Jackson Laboratory website: www.jax.org/donate-a-mouse.
The Jackson Laboratory Repository is supported by the NIH, The Howard Hughes Medical Institute, and other private charitable foundations.
Citation Format: Deborah Boswell, Stephen Rockwood, Michael Sasner, The JAX Repository Team. The Jackson Laboratory Repository: Mouse models for cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2816. doi:10.1158/1538-7445.AM2017-2816
Abstract 2832: Class I histone deacetylase inhibitors impair tumor growth and metastatic programs
Authors: Krämer Oliver H. , Kiweler Nicole 
Published: July 2017

Abstract
(a) introductory sentence indicating the purposes of the study
Metastasis formation is associated with poor patient prognosis. Epithelial-mesenchymal and mesenchymal-epithelial (EMT/MET) transition cycles are key for the formation, survival, and homing of metastatic cells. Inhibitors against epigenetic modulators of the histone deacetylase family (HDACi) are promising, clinically tested epigenetic drugs that may combat cancer proliferation and spread.
(b) brief description of pertinent experimental procedures
We chose a systems toxicology approach to analyze the relevance of HDACs and their inhibitors for metastatic cell growth. We combined in vivo tests with morphological, cellular, functional, and global proteomic analyses. This strategy follows the 3R principle by Russel and Burch. Of the four classes of HDACs (I-IV), the class I subgroup is most important for tumorigenesis. We therefore analyzed how the pharmacological inhibition of class I HDACs affects the growth and spreading of syngeneic kidney cancer cells into the lungs of BALB/c mice and how such drugs affect tumor cell growth, apoptosis, migration, and gene expression patterns controlling EMT/MET in transformed kidney and breast cells. Furthermore, we investigated how the genetic elimination of HDACs affects cancer cell growth and EMT/MET. We used flow cytometry, immunoblot, immunofluorescence, qPCR, proteomics on a global scale, RNAi against the class I HDACs HDAC1/HDAC2, and in vivo tumor analyses.
(c) summary of the new, unpublished data
Both the inhibition as well as the elimination of HDAC1/HDAC2 evokes growth arrest, morphological alterations, and apoptosis. HDACi block tumor cell migration, integrin-dependent cell adhesion, and EMT induced by the cytokine TGF-β. Global proteomics and qPCR analyses illustrate that HDACi disrupt EMT/MET cycles and metastatic spread. Moreover, these assays reveal pathways through which HDACi propel cancer cell apoptosis.
(d) statement of the conclusions
Class I HDACi can modulate the EMT/MET balance that is required for the detrimental process of metastasis. Hence, HDACi should be considered further as clinical treatment option.
Citation Format: Oliver H. Krämer, Nicole Kiweler. Class I histone deacetylase inhibitors impair tumor growth and metastatic programs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2832. doi:10.1158/1538-7445.AM2017-2832
Abstract 2836: Mitochondrial genomic backgrounds differentially affect nuclear DNA methylation and gene expression
Authors: Vivian Carolyn J. , Brinker Amanda E. , Graw Stefan , Koestler Devin C. , Legendre Christophe , Gooden Gerald C. , Salhia Bodour , Welch Danny R. 
Published: July 2017

Abstract
Accumulating data implicate mitochondrial genetics and metabolism as contributors to metastatic efficiency. With only 13 proteins encoded by the mtDNA genome, the mechanism(s) by which the coordination of multiple genes involved in metastasis could occur is unclear. We hypothesized that mitochondrial DNA (mtDNA) polymorphisms would differentially regulate nuclear DNA (nDNA) methylation and gene expression. To test the hypotheses, we created Mitochondrial Nuclear Exchange (MNX) mice, by transferring an oocyte nucleus from strainx into an enucleated oocyte from strainy. The mice show that mammary tumor formation and metastasis are regulated by inherited mitochondrial polymorphisms (PMID: 26471915). Age-matched, male mouse brains were collected and pooled from four litter mates representing each of the wild-type and MNX mice (8 groups). Genome-wide nDNA methylation (Mouse methyl-Seq) and gene expression (RNA-Seq) were measured and results validated in independent replicate samples. Significant, selective and reproducible differential DNA methylation and gene expression were observed and validated between strains having identical nDNA, but different mtDNA. While the signal(s) from mitochondria altering methylation is not fully defined, the findings support the hypothesis and demonstrate how mitochondrial genetic alterations could be one of several quantitative trait loci involved in complex phenotypes, such as metastasis. The results also suggest that mtDNA polymorphisms could serve as predictive biomarkers for cancer aggressiveness. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Biomedical Research Training Program, Kansas Bioscience Authority, CA134981, P30-CA168524.
Citation Format: Carolyn J. Vivian, Amanda E. Brinker, Stefan Graw, Devin C. Koestler, Christophe Legendre, Gerald C. Gooden, Bodour Salhia, Danny R. Welch. Mitochondrial genomic backgrounds differentially affect nuclear DNA methylation and gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2836. doi:10.1158/1538-7445.AM2017-2836
Abstract 2841: Investigating drivers of disease progression in invasive lobular carcinoma
Authors: Tasdemir Nilgun , Sikora Matthew , Li Zhu , Levine Kevin , Basudan Ahmed , Luthra Soumya , Elishaev Esther , Chandran Uma , Tseng George C. , Jankowitz Rachel , Dabbs David J. , McAuliffe Priscilla , Davidson Nancy E. , Oesterreich Steffi 
Published: July 2017

Abstract
Invasive lobular carcinoma (ILC) is the second most common type of breast cancer following invasive ductal carcinoma (IDC) and accounts for 10-15% of all cases. Unlike the masses or lumps formed by IDCs, ILCs grow as small, dis-cohesive cells in a single-file pattern within dense layers of extracellular matrix. Paradoxically, while patients with ILC display favorable prognostic and predictive factors (ER+, PR+, HER2-, low Ki67), their long-term response to endocrine therapy is worse than patients with IDC. Despite such histological and clinical differences, ILC has remained a gravely understudied subtype of breast cancer. Thus, there is urgent need to investigate molecular drivers of ILC progression in order to develop more effective therapeutic strategies and improve patient outcome. To this end, we used the Nanostring platform to measure the expression of 577 copy number variation-associated genes in 131 primary ILC tumors and identified two candidate drivers that exhibit higher expression in tumors from patients with recurrent versus non-current disease: CTTN (cortical actin binding protein) and QSOX1 (quiescin sulfhydryl oxidase). In follow-up studies, we observed high CTTN and QSOX1 expression in human ILC cell lines, tumors and patient-derived xenografts. In addition, QSOX1 expression was further increased in ILC ovarian metastases compared to their matched primary tumors. In functional in vitro studies, RNAi-mediated inhibition of CTTN led to decreased adhesion and haptotaxis to Collagen I, while QSOX1 knockdown diminished the growth of human ILC cell lines. We are currently assessing the in vivo therapeutic utility of CTTN and QSOX1 inhibition in tumor growth and metastasis using human ILC cell line and patient-derived xenograft mouse models. This study greatly advances our understanding of ILC disease mechanisms and identifies novel therapeutic targets towards improving the clinical outcome of patients with this understudied subtype of breast cancer.
Citation Format: Nilgun Tasdemir, Matthew Sikora, Zhu Li, Kevin Levine, Ahmed Basudan, Soumya Luthra, Esther Elishaev, Uma Chandran, George C. Tseng, Rachel Jankowitz, David J. Dabbs, Priscilla McAuliffe, Nancy E. Davidson, Steffi Oesterreich. Investigating drivers of disease progression in invasive lobular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2841. doi:10.1158/1538-7445.AM2017-2841
Abstract 2844: Identification of genes associated with pancreatic cancer metastasis by genome-wide CRISPR Cas9 screening
Authors: Li Youjia , Feng Huiyi , Liu Guangjie , Wong Chi Hin , Li Chi Han , Chen Yangchao 
Published: July 2017

Abstract
Pancreatic cancer is an extremely lethal cancer with a 5-year survival rate of 7%. One major reason why pancreatic cancer is hard to treat is its metastasis nature. Genes that related to the tumorigenesis and progression of pancreatic cancer were identified after decades of efforts. Several researches had revealed that pancreatic cancer originated from the successive accumulation of gene mutations, especially KRAS2, CNKD2A, TP53 and SMAD4. However, little is known about genes that regulate pancreatic cancer metastasis. Here we used a genome wide CRISPR Cas9 screening to identify the gene(s) associated with the metastasis of pancreatic cancer. We transduced pancreatic cancer cell line with lentivirus-based genome wide CRISPR sgRNA library to establish mutated cell library, and orthotopically injected the cell library into nude mice and waited for primary tumor growth and metastasis, then collected primary and metastatic tumors after several months. By next generation sequencing and analysis, we identified some gene candidates which may play important roles on pancreatic cancer metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Youjia Li, Huiyi Feng, Guangjie Liu, Chi Hin Wong, Chi Han Li, Yangchao Chen. Identification of genes associated with pancreatic cancer metastasis by genome-wide CRISPR Cas9 screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2844. doi:10.1158/1538-7445.AM2017-2844
Abstract 2847: Loss of heterozygosity (LOH) within the hypoxia inducible factor 3A (HIF3A) locus in liver metastasis (LM) from primary colorectal cancer (CRC)
Authors: Kitajima Takahito , Koi Minoru , Worix Alexander , Carethers John M. 
Published: July 2017

Abstract
Background and Aims: HIF3α is a hypoxia-regulated transcription factor that represses the effects of HIF1α and HIF2α under hypoxia at transcriptional and posttranslational levels. We previously found that LOH at the HIF3A locus is frequent in LM (59%) and the expression of HIF3A protein is reduced in LM compared to primary CRC. At present, the smallest overlapping LOH (SOL-LOH) region has been mapped to the intron 8 of the HIF3A, spanning from 46,312,911 to 46,315,651 on chromosome 19 in LMs. This genomic region contains multiple FOXA1 binding sites embedded in the two DNase I hypersensitive sites (UCSC Genome Browser, https://genome.UCSC.edu). About 30% of the human population carries a deletion within our SOL-LOH region (1000 Genomes Consortium: esv3644527, Chr19: 46,314,109-46,315,478). In this study, we determined whether esv3644527 deletion affects on the expressions of HIF3A, HIF2A, HIF1A and their target genes under normoxic and hypoxic conditions.
Methods: For LOH mapping, 75 resected LMs derived from primary CRC were analyzed for LOH using 8 polymorphic markers. We obtained three EBV-transformed B cell lines with heterozygous esv3644527 deletion and the one with the homozygous deletion from the Coriell Institute. The expression levels of 23 genes related to HIF pathways were determined by qRT-PCR.
Results and Discussion: The expression levels of HIF3A mRNA were too low to compare among these B cell lines by qRT-PCR. However, the expression levels of HIF2A and its target gene, angiopoietin 2 (ANGPT2), are significantly elevated in B cells with a homozygous deletion compared to B cells with a heterozygous deletion under both normoxic and hypoxic conditions. These observations are compatible with the results obtained from a previous study where pulmonary endothelial cells from HIF3A-knockout mice expressed elevated levels of HIF2A and ANGPT2 (Kobayashi-S et al., Genes Cells, 2015, 20:224-241), suggesting that deletion of the FOXA1 sites present in this region may regulate the HIF3A expression.
Conclusions: Our results show that about 60% of LMs exhibit LOH in the 2.7 Kb region surrounding intron 8 of the HIF3A locus. Deletion within this region may lead to upregulation of HIF2A and ANGPT2 by negatively regulating HIF3A expression. To prove our hypothesis, colon cancer cell lines with deleted FOXA1 sites will be assessed.
Citation Format: Takahito Kitajima, Minoru Koi, Alexander Worix, John M. Carethers. Loss of heterozygosity (LOH) within the hypoxia inducible factor 3A (HIF3A) locus in liver metastasis (LM) from primary colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2847. doi:10.1158/1538-7445.AM2017-2847
Abstract 2848: Identifying and targeting competing endogenous RNA (ceRNAs) networks to inhibit lung metastasis in triple negative breast cancer
Authors: Ersan Pelin , Tokat Unal , Eyupoglu Erol , Raza Umar , Riazalhosseini Yasser , Alkan Can , Thieffry Denis , Gautheret Daniel , Sahin Ozgur 
Published: July 2017

Abstract
Introduction: Triple negative breast cancer (TNBC), the most aggressive breast cancer subtype, has high incidence rate of lung metastasis. Not only protein coding transcripts, but also non-coding transcriptome, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have active roles in cancer progression and metastasis. Additionally, lncRNAs can act as sponges for miRNAs. Here, we aimed i) to construct the first mRNA-miRNA-lncRNA competing endogenous RNA (ceRNA) network controlling metastasis in TNBC, and ii) to prevent lung metastasis by targeting identified central candidate genes.
Material/Method: We established primary tumor and human-in-mouse (HIM) and mouse-in-mouse (MIM) lung metastasis models using TNBC cell lines in nude and Balb/c mice, respectively. We visualized both primary and metastatic tumors using in vivo imaging system, harvested tumors and performed both RNA and small RNA sequencing. We obtained differentially expressed miRNAs, mRNAs and lncRNAs between primary and metastatic tumors. Using several bioinformatics tools, we did enrichment analyses, miRNA target predictions, and network construction. Identified central lncRNAs were overexpressed or knocked down and will be tested in in vitro and vivo metastasis-related assays.
Results and Conclusions: We obtained 45 and 91 miRNAs which were differentially expressed between primary and metastatic tumors in HIM and MIM models, respectively. A miRNA family with an established role in metastasis as well as several other miRNAs was identified as highly differentially expressed in the same direction in both models. Moreover, 1127 and 3350 mRNAs, and 85 and 111 lncRNAs were differentially expressed in HIM and MIM models, respectively. Metastasis-related processes based on differentially expressed mRNAs were enriched in the data. We then integrated these three layers of data, functional enrichments, pathway maps and target predictions to construct the first ceRNA network controlling lung metastasis in TNBCs. Currently, we are testing the functional roles of candidate lncRNAs in in vitro and in vivo metastasis assays. Ultimately, our study will uncover novel lncRNAs that can be used as potential targets and/or biomarkers in breast-to-lung metastasis.
Funding: This study is supported by TUBITAK-CNRS Bilateral Grant with project number 214S364.
Citation Format: Pelin Ersan, Unal Tokat, Erol Eyupoglu, Umar Raza, Yasser Riazalhosseini, Can Alkan, Denis Thieffry, Daniel Gautheret, Ozgur Sahin. Identifying and targeting competing endogenous RNA (ceRNAs) networks to inhibit lung metastasis in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2848. doi:10.1158/1538-7445.AM2017-2848
Abstract 2849: Identification of active enhancers as potential biomarkers of aggressive colorectal cancer
Authors: Wang Zhiquan 
Published: July 2017

Abstract
Colorectal cancer is the third most common cancer and second leading cause of cancer-related deaths in the United States. Tumor metastasis is the primary cause of mortality. Even with aggressive surgical and therapeutic management approaches, more than one third of patients will develop metastatic disease. Understanding the molecular changes that drive tumor cells to the metastatic state is key to developing targeted therapies and identifying early-stage markers for progression. To identify changes that promote cell invasiveness, a hallmark of tumor progression, we exposed the pre-metastatic SW-480 colorectal cancer cell line to multiple rounds of selection for the capacity to invade through a synthetic extra-cellular matrix. Following repeated selection, invasiveness increased by more than 10-fold. Epithelial markers, such as E-cadherin, were repressed and markers commonly associated with tumor cells that have undergone epithelial-mesenchymal transition, such as N-cadherin and Vimentin, were upregulated. Likewise, invasive cells showed increased affinity for ECM components. Paired ChIP-seq and RNA-seq revealed likely roles for epigenetic alterations in driving gene expression changes. Furthermore, the epigenetic changes followed ordered patterns of activation and inactivation, suggesting that these epigenetic signatures may provide insight into early mechanisms associated with epithelial-mesenchymal transition. Collectively, our data suggest that early epigenetic markers may be better early predictors of colorectal cancer aggressiveness than gene expression patterns and support the use of this in vitro metastasis model to study the molecular mechanisms of cancer progression.
Citation Format: Zhiquan Wang. Identification of active enhancers as potential biomarkers of aggressive colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2849. doi:10.1158/1538-7445.AM2017-2849