bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1356: Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients
Authors: Mukasa Akitake , Aihara Koki , Gotoh Kengo , Saito Kuniaki , Nagae Genta , Tsuji Shingo , Tatuno Kenji , Yamamoto Shogo , Takayanagi Shunsaku , Narita Yoshitaka , Shibui Soichiro , Aburatani Hiroyuki , Saito Nobuhito 
Published: May 2015

Abstract
Introduction. Mutations in the H3F3A gene, which encodes histone H3.3, were recently reported in cases of pediatric glioblastoma. H3F3A K27M mutations occur in gliomas that arise at midline locations, including the pons, thalamus, and spine; moreover, this particular mutation is found mainly in tumors in children and adolescents. In this study, we aimed to determine the association between H3F3A mutations and adult thalamic glioma.
Methods. Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 years; range, 17 - 46), and seven were from patients more than 50 years of age. Additionally, for 14 of the 20 gliomas, 639 genes_including cancer-related genes and chromatin-modifier genes_were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome.
Results. The H3F3A K27M mutation was present in 10 of (91%) of the 11 younger patients, and absent from all seven older patients. Additionally, H3F3A K27M was not detected in the two diffuse astrocytomas. By additional sequencing, recurrent mutations were identified in TP53, ATRX, NF1, and EGFR. In addition, a KDM6A mutation was found in one case of diffuse astrocytoma and a CREBBP mutation was identified in one case of glioblastoma with the H3F3A K27M mutation. Gliomas with H3F3A K27M from pediatric or young-adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas.
Conclusion. We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently have the H3F3A K27M mutation.
Citation Format: Akitake Mukasa, Koki Aihara, Kengo Gotoh, Kuniaki Saito, Genta Nagae, Shingo Tsuji, Kenji Tatuno, Shogo Yamamoto, Shunsaku Takayanagi, Yoshitaka Narita, Soichiro Shibui, Hiroyuki Aburatani, Nobuhito Saito. Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1356. doi:10.1158/1538-7445.AM2014-1356
Abstract 1375: Epigenetic changes associated with resistance to sunitinib in human clear cell renal cell carcinoma models
Authors: ADELAIYE REMI , Miles Kiersten Marie , Ciamporcero Eric , Conroy Dylan , Ramakrishnan Swathi , Orillion Ashley , Ku Sheng Y. , Elbanna May , shen Li , Chintala Sreenivasulu , Pili Roberto 
Published: May 2015

Abstract
Background: Sunitinib is first-line therapy for patients with advanced clear cell renal cell carcinoma (ccRCC). Despite the clinical efficacy of sunitinib, in the majority of patients the disease eventually develops resistance and progresses. Epigenetic modifications of histone protein in chromatins have been shown to play a role in the regulation of gene transcription patterns in cells primarily by the catalytic activity of histone methyltransferase. EZH2 has been shown to contribute to tumor angiogenesis by inactivating anti-angiogenic factors via methylation at their promoter region. In this study, we examined epigenetic changes that may be associated with response and the resistant phenotype. Methods: Human ccRCC xenograft models RP-01 (isolated from a skin metastasis in a patient with sporadic ccRCC) and RP-02 (isolated from a skin metastasis in a patient with hereditary ccRCC) were implanted (∼1mm pieces) subcutaneously into SCID mice and were randomly assigned into two groups (sunitinib and vehicle). Mice were treated 5 days/week with sunitinib at 40mg/kg. Tumor volumes and body weights were assessed weekly by caliper measurements and weigh scale, respectively. Tumor tissues and blood were collected prior treatments and when tumors became resistant to treatment. Tissues collected were used for immunohistochemistry studies and RNA analysis. Results: Our results showed that RP-01 and RP-02 tumors, although initially responsive to treatment at 40 mg/kg, eventually became resistant to treatment. Immunohistochemistry analysis of RP-01 tumor samples indicated tumors to be hypo-vasculature when responding to sunitinib, but then became hyper-vascularized at point of resistance by CD31 staining. Analysis also revealed an associated increase in the expression of the methyltransferase EZH2 when tumors became resistant to sunitinib. However, there was no change in the expression levels of its EZH2 associated histone make H3K27me3. In addition, we noticed an increase in the levels of H3k9me2 and H3k4me2 in tumors resistant to sunitinib as compared to controls. Conclusion: Overall, our results suggest the potential role of epigenetic changes that that may be associated with sunitinib-induced resistance in ccRCC
Citation Format: REMI ADELAIYE, Kiersten Marie Miles, Eric Ciamporcero, Dylan Conroy, Swathi Ramakrishnan, Ashley Orillion, Sheng Yu Ku, May Elbanna, Li shen, Sreenivasulu Chintala, Roberto Pili. Epigenetic changes associated with resistance to sunitinib in human clear cell renal cell carcinoma models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1375. doi:10.1158/1538-7445.AM2014-1375
Abstract 1380: Genome-wide fingerprinting of regulatory chromatin to evaluate the tissue specific origins of high-grade serous ovarian cancer
Authors: Shen Howard C. , Coetzee Simon , Hazelett Dennis J. , Coetzee Gerhard A. , Noushmehr Houtan , Gayther Simon A. 
Published: May 2015

Abstract
The normal precursor tissue origins of high grade serous epithelial ovarian cancers (HSOC) are likely to be the fallopian tube epithelium (FTE) and/or the ovarian surface epithelium (OSE). To address this hypothesis, we used FAIRE-seq and ChIP-seq to evaluate the genome wide regulatory profiles of both tissue types and compared these profiles to well characterized HSOC cell lines (CaOV3 and UWB1.289). This analysis provided, for the first time, global high-resolution annotation of open chromatin and histone H3K27 acetylation and H3K4 monomethylation marks for these tissues types, which are consistent with sites of transcriptional regulation. Using these data, we identified over 10,000 non-promoter associated FAIRE/ChIP signal sites that represent candidate functional enhancers. The regulatory features provided a cell type-specific fingerprint for each cell type. While there were many similarities between OSE and FTE compared to other normal cell types, we also were also able to use these profiles to functionally distinguish OSE from FTE. When we compared profiles of HSOC cells, we observed stronger similarities in the regulatory chromatin landscape between FTE and HSOC cell types than between OSE and FTE. Supervised pathway analysis of genes located closest to putative enhancer sites provided additional evidence of signaling pathways that may underlie the neoplastic initiation and progression from normal tissue to HSOC phenotypes. Our results demonstrate the utility of this approach for identifying precursor tissue types for HSOC and other cancers based on the cell type specific chromatin datasets.
Citation Format: Howard C. Shen, Simon Coetzee, Dennis J. Hazelett, Gerhard A. Coetzee, Houtan Noushmehr, Simon A. Gayther. Genome-wide fingerprinting of regulatory chromatin to evaluate the tissue specific origins of high-grade serous ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1380. doi:10.1158/1538-7445.AM2014-1380
Abstract 14: Drug sensitivity of vascularized tumor tissue in vitro
Authors: Ehsan Seema M. , Inoue Masahiro , Waterman Marian L. , Hughes Christopher C. , George Steven C. 
Published: May 2015

Abstract
While there have been significant advances in using 3D culture systems to recapitulate physiological aspects of the tumor microenvironment, few systems are able to capture the full range of authentic, complex in vivo processes such as neovascularization and metastasis. Furthermore, these systems generally utilize established cell lines which compromise the clinical relevance. The goal of this study was to create a 3D in vitro model of patient-specific vascularized tumor tissue that could be used to evaluate the sensitivity to F-fluoruracil (5-FU). Colon cancer cells isolated directly from patient biopsies and endothelial colony forming cell-derived endothelial cells (EC) from cord blood were combined to form multicellular spheroids, and then embedded in a fibrin gel containing normal stromal cells (primary human lung fibroblasts). After 7 days in culture, these “prevascularized tumors” (PVTs) exhibited robust sprouting angiogenesis into the surrounding matrix, and also formed a distinct and contiguous vessel network within the spheroid itself. Network formation and branching of the sprouting vessels was comparable to those generated by co-culture spheroids of EC and cells from the colon cancer cell line SW620. These spheroids in particular demonstrated intravasation of single cells within the lumens of the vessel networks. This phenomenon was enhanced in low oxygen, and abrogated by silencing the transcription factor Slug. Thus, this phenomena is consistent with endothelial-mesenchymal transition. The PVTs have furthermore been used to distinguish the effects of EC on SW620 viability in response to 5-FU. Spheroids composed of EC and SW620 cells demonstrated decreased sensitivity to low dosage 5-FU treatment compared to spheroids composed of SW620 cells only, implicating potential EC-induced drug resistance. Our results demonstrate the utility of a 3D model system of the tumor microenvironment that may be used to study intravasation, microvessel formation, and sensitivity to anti-cancer drugs.
Citation Format: Seema M. Ehsan, Masahiro Inoue, Marian L. Waterman, Christopher CW Hughes, Steven C. George. Drug sensitivity of vascularized tumor tissue in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 14. doi:10.1158/1538-7445.AM2014-14
Abstract 1402: Regulation of Id2 In the proliferation of glioma-initiating neural progenitor cells
Authors: Sullivan Jaclyn , Havrda Matthew , Paolella Brenton , Kettenbach Arminja , Gerber Scott , Israel Mark A. 
Published: May 2015

Abstract
There are more than 14,000 new cases of malignant high grade glioma diagnosed each year in the US, and although surgical resection, radiation, and cytotoxic therapies are available, these current treatment methods are not curative. Inhibitor of DNA Binding 2 (Id2), a helix-loop-helix (HLH) protein, functions as a dominant negative inhibitor of basic helix-loop-helix (bHLH) transcription factors and is highly expressed in glioma. Recent data from our laboratory defines a critical role for Id2 in the pathogenesis of a subset of glioma known as proneural glioma. Id2 protein function has been characterized in neural progenitor cells (NPCs) where it acts to suppress differentiation and enhance cell cycle progression. These are two key characteristics that are shared with glioma-derived stem cells. We have identified three phosphorylation sites on Id2 in proliferating NPCs using mass spectrometry, and prepared altered Id2 molecules that cannot be phosphorylated at each of these sites. Id2-/- NPCs expressing WT and phosphorylation-site-ablated Id2 have been prepared to examine the role of Id2 phosphorylation in mediating its interactions with binding partners and in modulating the rate of proteasome-dependent degradation. We found an increased level of Id2 in NPCs expressing a mutant form of Id2 that cannot by phosphorylated when compared with NPCs expressing WT Id2. Moreover, the level of WT Id2 protein decreases when NPCs exit the cell cycle; however, unphosphorylated Id2 resists this degradation and exhibits a longer half-life. Stable isotope labeling by amino acids in cell culture (SILAC) experiments revealed that unphosphorylated Id2 molecules bind significantly less than WT Id2 to several anaphase promoting complex (APC) subunits. These findings suggested a possible mechanism for phosphorylation-dependent proteasome-mediated degradation of Id2 in NPCs. Understanding the effect of Id2 phosphorylation in modulating steady state levels of this important protein will inform future studies designed to identify pathways of interest in the transformation of NPCs and the malignant progression of NPC-initiated glioma. This work was supported in part by the Theodora B. Betz Foundation.
Citation Format: Jaclyn Sullivan, Matthew Havrda, Brenton Paolella, Arminja Kettenbach, Scott Gerber, Mark A. Israel. Regulation of Id2 In the proliferation of glioma-initiating neural progenitor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1402. doi:10.1158/1538-7445.AM2014-1402
Abstract 1413: RUNX3 plays an oncogenic role in Ewing sarcoma cells
Authors: Bledsoe Krista L. , McGee-Lawrence Meghan E. , Camilleri Emily T. , Oliveira Andre M. , Wijnen Andre J. van , Westendorf Jennifer J. 
Published: May 2015

Abstract
Ewing sarcomas are aggressive, poorly differentiated pediatric tumors of bone and soft tissue. Ewing sarcoma affects one to three people per million every year and is the second most common pediatric bone malignancy after osteosarcoma. Approximately 85% of Ewing sarcomas harbor the EWS-FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS-FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS-FLI binds the osteogenic transcription factor RUNX2, and prevents osteoblast differentiation. RUNX3 is highly homologous to RUNX2 and participates in the mesenchymal-derived bone formation. RUNX3 has been described as both a tumor suppressor and an oncogene in different tumor types.
In this study, we investigated the role of RUNX3 in Ewing Sarcoma. RUNX3 was detected in all Ewing sarcoma cells examined (7/7 cell lines, and 4/4 primary tumors), whereas RUNX2 was detected in only 73% of these specimens. Immunoprecipitation experiments revealed that RUNX3 binds to EWS-FLI via its Runt domain, which is &gt;91% identical to the Runt domain in RUNX2. The interaction between RUNX3 and EWS-FLI in cell nuclei was confirmed by immunofluorescence. Moreover, EWS-FLI interactions prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2.
To determine the role of RUNX3 in Ewing sarcoma cell growth, we stably suppressed RUNX3 expression in the Ewing sarcoma cell line A673 with shRNAs. In anchorage independent growth assays in soft agar, RUNX3-deficient A673 cells formed smaller colonies than cells expressing scrambled shRNAs. Consistent with the smaller colonies, RUNX3 suppressed cells had increased expression of the cyclin dependent kinase inhibitor p21. Taken together, these results suggest and oncogenic role for RUNX3 in Ewing sarcoma.
Citation Format: Krista L. Bledsoe, Meghan E. McGee-Lawrence, Emily T. Camilleri, Andre M. Oliveira, Andre J. van Wijnen, Jennifer J. Westendorf. RUNX3 plays an oncogenic role in Ewing sarcoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1413. doi:10.1158/1538-7445.AM2014-1413
Abstract 1415: Prostate cancer: An integrated evaluation of metabolomics, transcriptomics, and proteomics expression data
Authors: Rennefahrt Ulrike , Meyer Hellmuth-A. , Kamlage Beate , Reszka Regina , Schatz Philipp , Stephan Carsten , Jung Klaus , Dietrich Dimo , Kristiansen Glen 
Published: May 2015

Abstract
Background
Metabolite profiling research offers a deeper insight into biochemical changes in cancer metabolism. Moreover the integrated analysis of transcription, metabolomics and proteomics data can improve the understanding of the underlying biological processes.Material and Methods
A set of 254 metabolites was determined by gas chromatography/liquid chromatography-mass spectrometry in matched malignant and non-malignant prostatectomy samples from 95 prostate cancer (PCa) patients. Transcription profiling data obtained from 15 PCa patients by means of Affymetrix U133 arrays was analysed together with public GEO expression data. Expression levels of selected proteins were determined by means of immunohistochemistry and tissue micro array technology in 41 matched frozen tissue samples.
The association with clinicopathological variables and clinical outcome was tested. Transcription and metabolomics data were statistically analysed (ANOVA, Mann-Whitney U test) and significant differentially regulated metabolites/genes/proteins were selected.Results
Differentially regulated metabolites/genes discrimination between malignant and non-malignant tissues was used for network analysis. Enriched pathways which are involved in PCa progression or recurrence such as carbohydrate and fatty acid metabolism were identified. The role of fatty acid metabolism in PCa was analysed in more detail. Several fatty acids such as cerebronic acid, 2-hydroxybehenic acid, tricosanoic acid showed higher concentrations in malignant than in non-malignant tissues. This finding is in concordance to the observed higher mRNA and protein expression level of fatty acid synthase (FASN) in PCa. In contrast to normal prostate tissue, where protein expression level of FASN was correlated to the level of measured metabolites we found in malignant tissues a deregulation of the corresponding pathway. Conclusion
Our integrated analysis of transcription, metabolite and proteomics data confirms and extends the role of several biological pathways which are involved in PCa progression
Citation Format: Ulrike Rennefahrt, Hellmuth-A. Meyer, Beate Kamlage, Regina Reszka, Philipp Schatz, Carsten Stephan, Klaus Jung, Dimo Dietrich, Glen Kristiansen. Prostate cancer: An integrated evaluation of metabolomics, transcriptomics, and proteomics expression data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1415. doi:10.1158/1538-7445.AM2014-1415
Abstract 1429: Bioluminescent methods for investigating metabolic pathways
Authors: Leippe Donna , Sobol Mary , Vidugiriene Jolanta , Zhou Wenhui , Vidugiris Gediminas , Good Troy , Bernad Laurent , Meisenheimer Poncho , Cali James 
Published: May 2015

Abstract
Cancer cells are dependent on metabolic pathways that have been altered to support unique requirements for cancer cell growth and survival. The central role of these pathways makes them attractive targets for new treatment approaches. Rapid and sensitive assays, amenable to high-throughput screening, are needed to study the enzymes, metabolites and cofactors involved in cancer cell metabolic pathways. We developed a bioluminescent technology to address these needs and monitor changes in the fundamental metabolic co-factors nicotinamide adenine dinucleotides and key metabolites such as lactate.
The bioluminescent method uses a novel proluciferin substrate for the enzyme diaphorase. Luciferin is produced in the presence of NAD(P)H, resulting in a luciferase-generated light signal proportional to the starting NAD(P)H concentration. This is a versatile technology for measuring dinucleotide concentrations, enzyme activity and also metabolite levels. When lactate dehydrogenase is included in the reaction, the cellular metabolite lactate, an indicator of glycolytic rate, can be measured. NAD, NADP, NADH and NADPH can be measured in enzyme reactions or in biological samples, such as cells and tissues, with the use of NAD- and NADP-specific cycling enzymes.
Total NAD+NADH or NADP+NADPH levels in cultured cells were rapidly monitored using a one-reagent addition, in-well plate protocol without the need for cell processing. Additionally, the levels of individual dinucleotides and their ratios were determined from cell and tissue samples using a streamlined in-well acid and base-treatment protocol. The effects of small molecules on cellular dinucleotide levels can be quickly assessed, as demonstrated with FK866, an inhibitor of NAD biosynthesis.
Advantages of the bioluminescent approach over other detection methods include higher sensitivity (LOD ≤ 50 nM), larger maximum signal windows (S/B &gt; 100) and compatibility with automated, high-throughput protocols (Z' &gt; 0.8). By providing these features, the bioluminescent assays should be useful tools for facilitating the study of cancer cell metabolic pathways and the development of therapeutics that target these pathways.
Citation Format: Donna Leippe, Mary Sobol, Jolanta Vidugiriene, Wenhui Zhou, Gediminas Vidugiris, Troy Good, Laurent Bernad, Poncho Meisenheimer, James Cali. Bioluminescent methods for investigating metabolic pathways. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1429. doi:10.1158/1538-7445.AM2014-1429