bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5091: Aneuploidy is in stomatin overexpressed cells
Authors: Lee Jui-Hao , Lin Chi-Hung 
Published: May 2015

Abstract
A 31.5 kDa membrane associated protein which is highly abundant in the lipid rafts is stomatin. Human gene expression profile from UCSC Genome Bioinformatics databank indicates that stomatin is major in the peripheral blood, adipose tissue, muscle, and bone marrow. In the beginning, stomatin was thought to be involved in the disease OHSt (overhydrated hereditary stomatocytosis), and therefore named stomatin. However, later studies did not reveal mechanistic role of stomatin in mediating OHSt by evaluating stomatin gene deleted mice; the function of stomatin is therefore remained unclear. In this study, we found that overexpression of stomatin was able to induce the multinucleated cell formation. Our data also demonstrated that stomatin made in the cytoplasm could be transported outside of the cell and released to the culture medium. While adding the culture medium or condition medium to the cells, which did not contain exogenous stomatin, these cells were also triggered to undergo formation of multinucleated cells. Additionally, the stomatin induced multinucleated cells presented aneuploidy and abnormal centrosome number. Possible mechanisms underlying functions of stomatin that induce multinucleated cells are investigated.
Note: This abstract was not presented at the meeting.
Citation Format: Jui-Hao Lee, Chi-Hung Lin. Aneuploidy is in stomatin overexpressed 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 5091. doi:10.1158/1538-7445.AM2014-5091
Abstract 5097: Co-targeting of convergent, switchable nucleotide biosynthetic pathways induces synthetic lethality in leukemia
Authors: Radu Caius G. , Nathanson David A. , Czernin Johannes 
Published: May 2015

Abstract
Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine triphosphate (dCTP) can be produced by the de novo pathway (DNP) via ribonucleotide reductase, and/or by the nucleoside salvage pathway (NSP) via deoxycytidine kinase (dCK). The NSP's role in supporting tumor DNA replication is unknown. Here we show that survival of acute lymphoblastic leukemia cells upon inhibition of DNP-dependent dCTP production requires a functional NSP. Thus, DNP inhibition triggers a compensatory switch to NSP-mediated dCTP production. This metabolic switch can be imaged by positron emission tomography, thereby providing a non-invasive method for monitoring pharmacological targeting of the DNP. Blocking both DNP dCTP production using thymidine and the switch to NSP using a new dCK inhibitor induces replication stress overload and synthetic lethality in leukemia cells, without significant host toxicity. This co-targeting therapy may be broadly applicable against other malignancies characterized by high levels of replication stress.
Citation Format: Caius G. Radu, David A. Nathanson, Johannes Czernin. Co-targeting of convergent, switchable nucleotide biosynthetic pathways induces synthetic lethality in leukemia. [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 5097. doi:10.1158/1538-7445.AM2014-5097
Abstract 512: Cell-based analysis of oxidative stress, lipid peroxidation and lipid peroxidation-derived protein modifications using fluorescence microscopy
Authors: Mandavilli Bhaskar S. , Aggeler Robert 
Published: May 2015

Abstract
Oxidative stress plays an important role in the progression of several diseases including inflammation, atherosclerosis, aging and age-related degenerative disorders. Reactive oxygen species damage membrane bound lipids resulting in lipid peroxidation-derived protein modifications. Cell-based measurements of oxidative stress, lipid peroxidation and protein carbonylation by traditional fluorescence microscopy provide a powerful platform to quantitate oxidative stress and lipid peroxidation. Here, we used three different approaches to measure oxidative stress and lipid peroxidation in cells by fluorescence microscopy. 1) Two new fluorogenic probes, CellROX™ Orange and CellROX ™ Green Reagents to measure oxidative stress in cells, 2) Image-iT® Lipid Peroxidation Kit for a ratiometric determination of lipid peroxidation in live cells 3) Click-iT® Lipid Peroxidation Imaging Kit, a click chemistry-based approach which utilizes incorporation of an alkyne-modified unsaturated fatty acid analog, linoleamide, into the cellular membranes. The resulting oxidation products, like 9, 12-dioxo-10(E) dodecenoic acid (DODE) can readily modify proteins and these modifications were readily detected in fixed cells by the copper-catalyzed click reaction using fluorescent azides. Using these approaches, we measured oxidative stress and lipid peroxidation caused by several oxidants in cells. Increases in oxidative stress, lipid peroxidation, and protein modifications were assessed by high content imaging and analysis as well as traditional fluorescence microscopy. In the models tested, at least 2-3 fold increases were observed compared to controls was and responses were successfully inhibited by antioxidants. The three strategies described here provide powerful new tools for the assessment of oxidative stress in cells and convey distinct advantages over existing cell-based methods.
Citation Format: Bhaskar S. Mandavilli, Robert Aggeler. Cell-based analysis of oxidative stress, lipid peroxidation and lipid peroxidation-derived protein modifications using fluorescence microscopy. [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 512. doi:10.1158/1538-7445.AM2014-512
Abstract 5159: The histone methyltransferase SUV39H2 is a novel target of anticancer therapy
Authors: Sone Kembun , Nakamura Yusuke , Hamamoto Ryuji 
Published: May 2015

Abstract
Besides genetic disorders, dysregulation of epigenetic machinery has been proved to play a crucial role in human carcinogenesis, and the histone methylation/demethylation process has been considered as one of key regulators for this event. In this study, we demonstrate that one of the HMTs, suppressor of variegation 3-9 homolog 2 (SUV39H2), plays pivotal roles in human carcinogenesis. Quantitative real-time PCR revealed that SUV39H2 is aberrantly overexpressed in lung cancer, bladder cancer and multiple myeloma compared with their corresponding normal tissues, and immunohistochemical analysis revealed its positive staining in 251 out of 392 lung cancer cases and 16 of 29 bladder cancer cases, while no significant staining was observed in various normal tissues we examined. cDNA microarray analysis using a number of clinical tissues also confirms overexpression of SUV39H2 in various types of cancer. SUV39H2-specific small interfering RNAs significantly knocked down its expression, and caused the G1 arrest as well as suppression of cancer cell growth. Since SUV39H2 expression was undetectable in the normal tissues, SUV39H2 is considered to be an ideal target for development of tumor-specific therapeutics.
Citation Format: Kembun Sone, Yusuke Nakamura, Ryuji Hamamoto. The histone methyltransferase SUV39H2 is a novel target of anticancer therapy. [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 5159. doi:10.1158/1538-7445.AM2014-5159
Abstract 5161: The development of therapeutic inhibitors of the KDM5 histone demethylases
Authors: Hudlebusch Heidi R. , Heinemann Bo , Nielsen Jesper M. , Kleine-Kohlbrecher Daniela , Hauge Camilla , Boesen Thomas , Labelle Marc , Gerlach Lars-Ole , Staller Peter , Birk Peter 
Published: May 2015

Abstract
Histone methyl marks contribute to the regulation of chromatin architecture and of DNA-based processes such as replication, repair and gene transcription. There is increasing evidence for alterations in histone methylation patterns in cancer and other human diseases. Importantly, aberrant methylation can contribute to deregulated gene expression and thereby to excessive proliferation, survival and metastasis of cancer cells.
Histone methyl transferases and demethylases establish a dynamic equilibrium of histone modifications, and the expression and activity of several members of these enzyme families are deregulated in human cancer. The jumonji C-domain histone H3K4me3/2 demethylase KDM5B/PLU1/JARID1B as well as its close relative KDM5A/JARID1A are potential oncogenes. Both proteins are overexpressed in human tumors and the gene encoding KDM5B is e.g. amplified in invasive breast cancer cells. Results obtained with RNA interference and targeted deletions in mice have provided additional support for a critical role of KDM5 demethylases in cancer cells.
EpiTherapeutics is developing novel cancer drugs targeting the enzymatic activity of histone demethylases. Here we present our recent progress in obtaining selective, potent, and cell-permeable inhibitors of the KDM5 demethylases. Biochemical and cellular activities, pharmacological data, and in vivo antitumor activity will be discussed.
Citation Format: Heidi R. Hudlebusch, Bo Heinemann, Jesper M. Nielsen, Daniela Kleine-Kohlbrecher, Camilla Hauge, Thomas Boesen, Marc Labelle, Lars-Ole Gerlach, Peter Staller, Peter Birk. The development of therapeutic inhibitors of the KDM5 histone demethylases. [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 5161. doi:10.1158/1538-7445.AM2014-5161
Abstract 5175: Re-analysis of breast invasive carcinoma (BRCA) TCGA copy number data improves tumor profiles
Authors: Culot Louis J. , O'Hara Andrea , Keshavan Raja , Che Zhiwei , Shams Soheil 
Published: May 2015

Abstract
Using the copy number and SNP- probes available in the TCGA level 1 data, reprocessed tumor profiles were more consistent with a control set in terms of median number of copy number events, sample ploidy, and breakpoint genes than the published “level 3” TCGA data. Probe-level data were analyzed using Nexus Copy Number SNP-FASST2 (a multi-state HMM algorithm that uses both SNP and copy number probes in making state assignments), with systematic correction applied to correct for GC biases. Additionally we performed manual baseline adjustment to correct for sample ploidy based on whole-genome B-alelle frequency data for each sample. The median number of copy number events in the TCGA data set was reduced from 377 (in the level 3 set) to 193, with a corresponding reduction in variance, and in line with our control samples (median CN changes of 173 and 142). After manual inspection, more than 15% of the TCGA BRCA samples available at level 3 were found to have incorrect baseline ploidy assignments. The resultant reanalyzed data set, along with associated clinical annotations for each sample, is available through Nexus DB repository to the general scientific community and should provide greater utility for further research.
Citation Format: Louis J. Culot, Andrea O'Hara, Raja Keshavan, Zhiwei Che, Soheil Shams. Re-analysis of breast invasive carcinoma (BRCA) TCGA copy number data improves tumor profiles. [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 5175. doi:10.1158/1538-7445.AM2014-5175
Abstract 5189: RNA editing in rhoq promotes invasion potential in colorectal cancer
Authors: Kim Hwang-Phill , Han Sae-Won , Lee Kyung-Hun , Park Kyu Joo , Seo Jeong-Sun , Kim Jong-Il , Kim Tae-You 
Published: May 2015

Abstract
RNA editing can increase RNA sequence variation without alteration of DNA sequence. By comparing whole genome and transcriptome sequence data of a rectal cancer, we have found a novel tumor specific RNA editing in RHOQ. The A-to-I editing results in substitution of sparagine with serine at residue 136. We observed higher level of the RHOQ RNA editing in tumor compared with normal tissue in colorectal cancer. The degree of RNA editing was associated with RhoQ activity in colorectal cancer cell lines. RhoQ N136S amino acid substitution increased RhoQ activity, actin cytoskeletal reorganization, and invasion potential. KRAS mutation further increased the invasion potential of RhoQ N136S in vitro. Among colorectal cancer patients, recurrence was more frequently observed in patients with tumors having edited RHOQ and mutant KRAS. Collectively, we show that RNA editing is another mechanism of sequence alteration contributing to colorectal cancer progression.
Citation Format: Hwang-Phill Kim, Sae-Won Han, Kyung-Hun Lee, Kyu Joo Park, Jeong-Sun Seo, Jong-Il Kim, Tae-You Kim. RNA editing in rhoq promotes invasion potential in colorectal 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 5189. doi:10.1158/1538-7445.AM2014-5189
Abstract 5208: MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1
Authors: Xu Qing-Fu , Pang Jesse Chung-sean , Yang Hui , Lv Sheng-Qing , Ohgaki Hiroko 
Published: May 2015

Abstract
Medulloblastoma (WHO grade IV) is the most frequent malignant CNS tumor in children. MicroRNAs (miRNAs, miRs) are small non-coding RNAs that target protein-coding mRNAs that play roles in a variety of cellular processes through regulating multiple target genes. In the present study, we analyzed miR-22 expression and its effect on cell proliferation and apoptosis in medulloblastomas. Quantitative RT-PCR revealed significantly lower expression of miR-22 in 19/25 (76%) medulloblastomas, D341, DAOY and ONS-76 medulloblastoma cells and primary cultured medulloblastomas cells, compared to normal cerebellum. Forced expression of miR-22 by lentiviral vector transfection reduced cell proliferation and induced apoptosis in DAOY and ONS-76 cells. DAOY cells with miR-22 overexpression in nude mice yielded tumors smaller than those originated from control DAOY cells. Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles; PAPST1 being the most significantly (10-fold) down-regulated gene. Quantitative RT-PCR revealed PAPST1 up-regulation in 18/25 (72%) medulloblastomas. Furthermore, the results of luciferase reporter assay in ONS-76 cells suggested that miR-22 directly targets the PAPST1 gene. Thus, frequently down-regulated miR-22 expression is associated with cell proliferation in medulloblastomas, at least in part via PAPST1, which is a novel target of miR-22.
Citation Format: Qing-Fu Xu, Jesse Chung-sean Pang, Hui Yang, Sheng-Qing Lv, Hiroko Ohgaki. MiR-22 is frequently down-regulated in medulloblastomas, and inhibits cell proliferation via the novel target PAPST1. [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 5208. doi:10.1158/1538-7445.AM2014-5208
Abstract 5214: miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland and plays a role in breast cancer development
Authors: Navas David Llobet , Barrueco Ruth Rodriguez , Silva Jose 
Published: May 2015

Abstract
The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy and tumorigenesis. Importantly, miR-424(322)/503 loci is deleted in 20% of basal and luminal B tumors. Through the generation of a knock-out mouse model, we found that regression of the secretory acini of the mammary gland was compromised in the absence of miR-424(322)/503. Mechanistically, we show that miR-424(322)/503 orchestrates cell life and death decisions by targeting CDC25A, BCL-2 and IGF1R. Furthermore, we demonstrate that the expression of this miR-cluster is regulated by TGF-β, a well characterized regulator of mammary involution. Overall, our data suggest a model where activation of the TGF-β pathway after weaning induces the transcription of the miR-424(322)/503 which in turn downregulates the expression of key genes. Here, we unveil a previously unknown, multilayered-regulation of epithelial tissue remodeling coordinated by the microRNA cluster miR-424(322)/503.
Note: This abstract was not presented at the meeting.
Citation Format: David Llobet Navas, Ruth Rodriguez Barrueco, Jose Silva. miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland and plays a role in breast cancer development. [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 5214. doi:10.1158/1538-7445.AM2014-5214
Abstract 522: Revealing the complexity of cancer associated small non-coding RNAs by next generation sequencing (NGS) and low-density array
Authors: Montani Francesca , Marzi Matteo , Carletti Rose Mary , Fiore Pier Paolo Di , Nicassio Francesco 
Published: May 2015

Abstract
Background. The recent development of high-throughput sequencing technologies (Next Generation Sequencing - NGS) provided instruments to reveal the complexity of nucleic acids, highlighting the existence of numerous species of non-coding RNAs (ncRNAs) that play a significant regulatory role in complex organisms, impacting on both physiology and disease. In particular, microRNAs (miRNAs) have been proposed as “next-generation” markers for their ability to unambiguously distinguish cellular states, including SCs, progenitors and differentiated cells, as well as tumour types, even among closely related cancers or in different biological fluids. However, a comprehensive approach for the identification and characterization of small non-coding RNAs from pathological samples (blood, FFPE, primary cultures) has not been established nor compared with current available methodologies (i.e. QPCR).
Aim: Our aim is to develop a simultaneous and comparative protocol for the analysis of small non-coding RNAs from pathological samples, which encompasses both high-throughput QPCR and sequencing analysis in order to reveal the complexity of cancer associated small ncRNAs.
Results: An optimized protocol to analyse small ncRNAs from different pathological samples has been developed and compared with high-throughput QPCR. Both platforms resulted as highly efficient and quantitative, although NGS manages to score many molecules and RNA species that could not be analysed by current QPCR platforms, thus revealing a major complexity of cancer associated non-coding RNAs.
Conclusion: We propose that the combined use of NGS and QPCR platforms would allow a wider and more detailed analysis of ncRNAs, expanding our ability to fish out robust and efficient molecular markers for diagnostic (early detection), prognostic or therapeutic use.
Note: This abstract was not presented at the meeting.
Citation Format: Francesca Montani, Matteo Marzi, Rose Mary Carletti, Pier Paolo Di Fiore, Francesco Nicassio. Revealing the complexity of cancer associated small non-coding RNAs by next generation sequencing (NGS) and low-density array. [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 522. doi:10.1158/1538-7445.AM2014-522
Abstract 5229: Profiling of circulating miRNAs is a critical prognostic biomarker tool for high-risk neuroblastoma
Authors: Ramraj Satish Kumar , Pandian Vijayabaskar , Khan Faizan H. , Aravindan Sheeja , Herman Terence S. , Natarajan Mohan , Aravindan Natarajan 
Published: May 2015

Abstract
Circulating miRNAs has momentous clinical relevance and has been correlated with disease progression in many solid tumors. In this study, we investigated the circulating miRNAs' variations exploiting unique mouse models of non-metastatic favorable and high-risk, aggressive human neuroblastoma. Conditioned serum samples from animals bearing favorable or high-risk disease were examined for alterations in circulating miRNAs using whole genome human miRNA profiling approach. Serum from sham mice were used as mouse-background false-positive controls. Data after chip-to-chip normalization and mouse background subtraction were compared by adopting favorable-to-high-risk animal(s) crisscross analysis. Compared to favorable neuroblastoma, miRNA profiling revealed a significant (&gt;2 fold) upregulation of 33 miRNAs and complete suppression of 42 miRNAs in animals with high-risk NB. Preferential exclusion of mouse miRNA with sequence homology blast revealed 11 (off 33 upregulated) unique human miRNA including miR-1261, miR-1268, miR-1280, miR-1304, miR-1308, miR-1908, miR-198, miR-513a-5p, miR-513b, miR-548h, miR-580. Consistently, homology blasting identified 13 (off 42 downregulated) miRNAs including, miR-1206, miR-548a-5p, miR-548f, miR-576-5p, miR-600, miR-639, miR-640, miR-641, miR-647, miR-662, miR-886-3p, miR-887, miR-888. Expression pattern of select miRNAs were validated using QPCR. Target analysis for these miRNAs revealed a signature pattern, mostly pertaining to stemness and tumor progression flow-through signaling viz., NKX3.2, MEGF10, GRB10, GPX8, ZEB1, SIX-1, ZIC2, MMP-2, SMAD4, KRAS, NFkB1, CD24, CD44. Together, these data identifies unique circulating miRNA signature of high-risk neuroblastoma and further implies that these miRNAs may play functional role in the progression of the disease.
Citation Format: Satish Kumar Ramraj, Vijayabaskar Pandian, Faizan H. Khan, Sheeja Aravindan, Terence S. Herman, Mohan Natarajan, Natarajan Aravindan. Profiling of circulating miRNAs is a critical prognostic biomarker tool for high-risk neuroblastoma. [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 5229. doi:10.1158/1538-7445.AM2014-5229