bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1842: Identifying long noncoding RNAs in breast cancer microarrays.
Authors: Jia Hui , Lipovich Leonard , Ju Donghong , Kosir Mary A. 
Published: August 2014

Abstract
Long noncoding RNAs (lncRNA) are powerful regulators of gene expression. The emerging role of long noncoding RNAs (lncRNA) is facilitated by the development of new technologies such as tilling array and next generation sequencing. In this study, our research focused on lncRNA's regulatory mechanisms in breast cancer.
Methods: The Gencode v7 lncRNA and FANTOM5 lncRNA datasets were integrated as our lncRNA transcriptome. The expression profile was from four publications of microarray analysis in breast cancer. First, we checked the Affymetrix probe dataset U133 plus with our lncRNA transcriptome. If a probe was on the same strand and 100% fell into the exonic region of one lncRNA transcript, then the probe could this lncRNA. We integrated all lncRNAs from our transcriptome which matched the probes from the supplementary data of four papers and selected those occurred more than once.
Results: There were 23 nonredundant lncRNA candidates identified. Among those 23 candidates, PTENP1 was identified. PTENP1 is the pseudogene of tumor suppressor gene PTEN. The 3’UTR can bind the same miRNAs as the related protein-coding gene, PTEN. This suggests that pseudogenes may have a biological function as ‘decoys’, sequestering miRNAs and thereby affecting their regulation of expressed genes. Another candidate identified was ENST00000415285.1, which is the antisense gene of FGF14. FGF14 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including tumor growth and invasion.
ENST00000415285.1 is up-regulated in breast cancer, while the expression level of FGF14 is unknown, so further research is necessary to predict the possible mechanism of regulation to FGF14.
Conclusion: LncRNAs are identified in datasets for breast cancer that may elucidate further regulatory mechanisms driving the pathogenesis of breast cancer.
Citation Format: Hui Jia, Leonard Lipovich, Donghong Ju, Mary A. Kosir. Identifying long noncoding RNAs in breast cancer microarrays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1842. doi:10.1158/1538-7445.AM2013-1842
Abstract 1861: Autophagy and cell death in breast cancer cells following oxidative stress by mitoquinone.
Authors: Gonzalez-Berrios Yanira , Aryal Baikuntha P. , Chehab Leena M. , Rao Ashutosh 
Published: August 2014

Abstract
Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone agent, selectively killed breast cancer cells compared to healthy cells mammary epithelial cells. While mitoquinone treatment led to irreversible loss in clonogenicity, the exact mechanism by which this agent was cytotoxic was unknown. We demonstrated that mitoquinone, although a synthetic derivative of the antioxidant ubiquinone, generated superoxide in MDA-MB-231 cells. Investigation into the cytotoxicity mechanism of MitoQ showed that a greater number of cells undergo autophagy than apoptosis. Drug treatment increased protein levels of the autophagosome-associated light chain 3 (LC3-II) that is responsible for the formation and nucleation of the autophagy bodies. Autophagy was confirmed by ultrastructural analysis using electron microscopy. However, the relationship between mitoquinone-induced oxidative stress and autophagy as a primary cellular response was not clear. We found that MitoQ induces Atg7-dependent but Beclin-1-independent cellular autophagy. Cancer cells and mouse embryonic fibroblast (MEF) lacking the autophagy related gene 7 (Atg7) had lower levels of autophagy after MitoQ treatment than Atg7 wild-type counterparts. In addition, we observed higher levels of oxidation in Atg7 deficient cells. Keap1, an oxidative stress sensor protein that regulates an antioxidant response via the transcription factor Nrf2, underwent oxidation and degradation in drug-treated cells. However, in Atg7 deficient cells Keap1 degradation decreased, suggesting Atg7-dependent Keap1 degradation. Conversely, knockdown of Keap1 decreased autophagy levels, but had no apparent effect on apoptosis. In vivo studies using spontaneously hypertensive rats implanted with a tumor confirmed that treatment with MitoQ reduced tumor size and increase autophagy in tumor cells. We established the anti-tumor activity of Mito-Q in breast cancer cell lines and in an animal model. We also provided preliminary evidence for an Atg7- and Keap1- dependent autophagy as one of the mechanisms that respond to the oxidative stress by Mito-Q.
Citation Format: Yanira Gonzalez-Berrios, Baikuntha P. Aryal, Leena M. Chehab, Ashutosh Rao. Autophagy and cell death in breast cancer cells following oxidative stress by mitoquinone. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1861. doi:10.1158/1538-7445.AM2013-1861
Abstract 1865: Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression.
Authors: Kim Jin Young , Shin So Jin , Park Keon Uk , Jeon Young June , Cho Chi Heum , Ha Eunyoung 
Published: August 2014

Abstract
Ciglitazone is a kind of thiazolidinedione and a potent, selective peroxisome proliferator-activated receptor γ (PPAR γ) ligand and it is active in vivo as an anti-hyperglycemic agent in the murine model. Glucose metabolism plays a key role in the maintenance of energy homeostasis in organisms and changes in cellular glucose uptake rate are found in malignant diseases. Significant increase in glucose consumption can be found in many malignant conditions and research so far has focused on its apoptotic and inhibition of proliferation properties but their role in cell death is unclear. We show that ciglitazone inhibits glucose uptake in ovarian cancer cell through GLUT-1 expression. In this study, we investigated the effect of ciglitazone to GLUT-1 expression and cell proliferation. We further demonstrate that ciglitazone pretreated tumor cell was increased apoptosis dose dependent manner and siGLUT-1 treated tumor cell showed increased apoptosis. Interestingly, not only cancer cell line but also in vivo state, ciglitazone could decrease tumor mass.
Specificity protein (Sp) is highly expressed in tissues of prostate cancer, breast carcinomas and lung cancer when compared to normal tissues or cells. Previous studies showed that Sp1 plays an important role in carcinogenesis and metastasis of several human tumor types by regulating growth-related signal transduction, cell cycle control molecules, apoptosis, oncogenes, tumor suppressor genes. In this study there was no relation with apoptosis and SP1 expression. We demonstreated that ciglitazone inhibit glucose uptake in ovarian cancer cell lines and the relationship between ciglitazone and GLUT-1 in ciglitazone induced cell death.
Citation Format: Jin Young Kim, So Jin Shin, Keon Uk Park, Young June Jeon, Chi Heum Cho, Eunyoung Ha. Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1865. doi:10.1158/1538-7445.AM2013-1865
Abstract 1866: Stable isotope resolved metabolomics of colorectal cancer cells treated with inhibitor of monocarboxylate transporter-1.
Authors: Tan Bo , Kuo Ming-Shang , Breyer Matthew D. , Liu Ling , Zhao Yang 
Published: August 2014

Abstract
The rationale of this cell based study was to examine the metabolic effects of a synthetic monocarboxylate transporter 1 (MCT1) inhibitor (AR-C155858) on multiple cellular metabolites in colorectal tumor cells using [1,2,3,4,5,6-13C6]-D-glucose or [1,2,3,4,5-13C5]-D-glutamine as the single precursor metabolic tracer. DiFi colorectal cancer cells were cultured for 24 hrs in the presence of 0.1% DMSO (vehicle control) or 100 nM of MCT-1 inhibitor. Intracellular glycolysis intermediates measured by liquid chromatography/mass spectrometry (LC/MS) included phosphoenolpyruvate (PEP), phosphoglycerate (PG), fructose 1,6 bisphosphate (FBP), Glucose-6-phosphate (G6P), Gluconate-6-phosphate, glyceraldehydes 3-phosphate (G3P), ribose-5-phosphate (R5P), seduheptulose-7-phosphate (S7P), pyruvate, and lactate. TCA cycle intermediates measured included malate, α-ketoglutarate, succinate, fumarate, and citrate. Both glutamine and glutamate were also measured. Increases in PEP, PG3, G6P, Gluconate-6-phosphate, G3P, S7P, pyruvate, and lactate were induced by MCT1 inhibitor when traced with 13C6 glucose. When traced with 13C5 glutamine, PEP, G6P, S7P, pyruvate, and lactate were increased by MCT1 inhibitor. In contrast, decreases in α-ketoglutarate and glutamate were seen with both tracers.
Citation Format: Bo Tan, Ming-Shang Kuo, Matthew D. Breyer, Ling Liu, Yang Zhao. Stable isotope resolved metabolomics of colorectal cancer cells treated with inhibitor of monocarboxylate transporter-1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1866. doi:10.1158/1538-7445.AM2013-1866
Abstract 1867: Metabolomic discrimination of undifferentiated and differentiated gastric cancer.
Authors: Kami Kenjiro , Fujimori Tamaki , Terashima Masanori , Kusuhara Masatoshi , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Yamamoto Hiroyuki , Ohashi Yoshiaki 
Published: August 2014

Abstract
Clinicopathological characteristics of gastric cancer patients strongly depend on histological type. In contrast with gene and protein expressions, metabolic properties of undifferentiated (UT) and differentiated (DT) gastric cancer have been largely unknown. Here, we conducted comparative metabolome analyses in UT and DT cell lines, uncovering characteristic differences between the levels of metabolites involved in energy metabolism. The metabolomic profile of DT cell lines was featured by its considerably high glycolytic intermediate, nucleotide, and glutathione levels, which highlight hallmarks of cancer metabolism represented by the Warburg effect and hyperactive nucleotide syntheses. In contrast, UT cell lines rather showed relatively low energy and redox statuses. We further confirmed the trends by measuring 392 metabolites of paired non-tumor and tumor gastric tissues obtained pairwise from 27 gastric cancer patients in order to metabolomically characterize non-tumors, UT (n=18), and DT (n=9) tumors. The results not only distinguished the profile of non-tumors from tumors, especially of DT, but also reaffirmed the distinctions between UT and DT tumors. Taken together, UT and DT cancers were metabolomically characterized both in vitro and in vivo; DT exhibited more typical cancer metabolic profiles than UT, whereas low glutathione ratios in UT imply their vulnerability to oxidative stress, which thus could be useful for developing more subtype-specific cancer therapeutics.
Citation Format: Kenjiro Kami, Tamaki Fujimori, Masanori Terashima, Masatoshi Kusuhara, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Hiroyuki Yamamoto, Yoshiaki Ohashi. Metabolomic discrimination of undifferentiated and differentiated gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1867. doi:10.1158/1538-7445.AM2013-1867
Abstract 189: Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice.
Authors: Shimizu Masahito , Terakura Daishi , Kochi Takahiro , Ohno Tomohiko , Kubota Masaya , Shirakami Yohei , Tanaka Takuji , Moriwaki Hisataka 
Published: August 2014

Abstract
Obesity and its associated disorders, such as non-alcoholic steatohepatitis, increase the risk of hepatocellular carcinoma (HCC). Branched-chain amino acids (BCAA), which improves protein malnutrition in patients with liver cirrhosis, reduces the risk of HCC in these patients with obesity. In the present study, the effects of BCAA supplementation on the spontaneous development of hepatic premalignant lesions, foci of cellular alteration (FCA), in db/db obese mice were examined. Male db/db mice were given a basal diet containing 3.0% of either BCAA or casein, a nitrogen content-matched control of BCAA, for 36 weeks. At sacrifice, supplementation with BCAA significantly inhibited the development of FCA when compared to casein supplementation by inhibiting cell proliferation, but inducing apoptosis. BCAA supplementation increased the expression levels of PPAR-γ, p21CIP1, and p27KIP1 mRNA and decreased the levels of c-fos and cyclin D1 mRNA in the liver. BCAA supplementation also reduced both the amount of hepatic triglyceride accumulation and the expression of IL-6, IL-1β, IL-18, and TNF-α mRNA in the liver. Increased macrophage infiltration was inhibited and the expression of IL-6, TNF-α, and MCP-1 mRNA in the white adipose tissue (WAT) were each decreased by BCAA supplementation. BCAA supplementation also reduced adipocyte size, while increasing the expression of PPAR-α, PPAR-γ, and adiponectin mRNA in the WAT compared to casein supplementation. These findings indicate that BCAA supplementation inhibits the early phase of obesity-related liver tumorigenesis by attenuating chronic inflammation in both the liver and WAT. BCAA supplementation may be useful in the chemoprevention of liver tumorigenesis in obese individuals.
Citation Format: Masahito Shimizu, Daishi Terakura, Takahiro Kochi, Tomohiko Ohno, Masaya Kubota, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki. Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 189. doi:10.1158/1538-7445.AM2013-189
Abstract 1894: The lipogenic phenotype of HER2/neu-positive breast cancer cells.
Authors: Baumann Jan M. , Kourtidis Antonis , Conklin Douglas S. 
Published: August 2014

Abstract
15 - 30 % of all breast cancer cases are classified as HER2/neu-positive, a very aggressive form of breast cancer that correlates with a poor prognosis, reduced survival time and increased incidence of metastasis. Kourtidis et al. (2010) have recently shown that the HER2-positive breast cancer cell line BT474 relies on a unique Warburg-like metabolism for survival and aggressive behavior. These cells are dependent on fatty acid synthesis, presumably as a means to regenerate NAD+ for aerobic glycolysis. The nuclear receptors NR1D1 and PPARγ enable these cells to upregulate de novo fatty acid synthesis while avoiding palmitate-induced lipotoxicity by storing neutral fats (TAGs). The cells show markedly increased levels of stored fats compared to other breast cancer cell lines and disruption of the synthetic process results in apoptosis of BT474 cells. Metabolomic analysis of NR1D1 overexpressing cells compared to normal cells reveals profound differences in their metabolite profiles. This metabolic phenotype is operating at its limits in HER2-positive cells, as addition of exogenous palmitate results in cell death, whereas HER2-normal cells are not affected by this treatment. Microarray analysis suggests that palmitate induces an ER-stress response in the HER2-positive cells, ultimately resulting in cell death. Preliminary results suggest that this response is CHOP-dependent. Combination treatments with palmitate and HER2-targeted therapeutic compounds show synergistic effects and markedly increase the cytotoxic effects of either compound alone. The uptake of exogenous fatty acids as well as the de novo fatty acid synthesis are dependent on the essential co-factor coenzyme A (CoA), which is generated from the precursor pantothenate (vitamin B5). Based on our genomic analysis we predicted that HER2-positive breast cancer cells are more sensitive to changes in intracellular CoA levels. Our results show that HER2-positive breast cancer cells are sensitive to shRNA-mediated knockdown of coenzyme A pathway enzymes whereas MCF-7 cells are not. We observe the same pattern of sensitivity using the competitive CoA pathway inhibitor homopantothenate. Interestingly, limiting the supply of CoA in HER2-positive cells reduces the toxicity of exogenous palmitate.
Our data suggest that HER2-positive breast cancer cells are metabolically different from other breast cancer cell lines and that these differences offer new possibilities for therapeutic applications.
Citation Format: Jan M. Baumann, Antonis Kourtidis, Douglas S. Conklin. The lipogenic phenotype of HER2/neu-positive breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1894. doi:10.1158/1538-7445.AM2013-1894
Abstract 1906: Differential downstream effects of nicotinamide adenine dinucleotide (NAD) salvage pathway-inhibition in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).
Authors: Gehrke Iris , Poeppl Armando , Johnston James , Gibson Spencer B. , Banerji Versha 
Published: August 2014

Abstract
Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) represent the two most common hematologic malignancies in western countries. Up to date both diseases are mainly treated palliatively rather than curatively which reinforces the need for new treatment options. Targeting metabolism-associated pathways is a novel route for treatment of hematologic malignancies. Nicotinamide adenine dinucleotide (NAD) is not only a central molecule for metabolic processes such as ATP-generation, but is also involved in several other cancer-relevant events. The NAD-dependent enzyme Sirtuin 1 (Sirt1) has been described to function as an oncogene. Further, the rate-limiting enzyme for NAD-generation via salvage-pathways nicotinamide phosphoribosyltransferase (NAMPT) is upregulated in several cancers, making it an attractive metabolism-associated drug target.
We used the NAMPT-inhibitor FK866 to treat the MM-cell line IM9 and the CLL-like cell lines JVM3 and Mec2 as well as primary CLL-cells. Cellular energy status was assessed by means of ATP content and functioned as a measure of viability. Sirt1 levels were assessed by immunoblotting.
The MM-cell line IM9 was highly sensitive to FK866 with regard to ATP-reduction (50% reduction at 51.7nM). Also the tested CLL-like cell lines JVM3 and Mec2 were sensitive to FK866 with 50% reduction of ATP content at 76.6nM and 51.1nM, respectively. Primary CLL cells showed very heterogenous response. Some samples were highly sensitive with 50% reduction of ATP-content at 21.6nM, while others were completely resistant. We could not detect any correlation to available clinical data such as ZAP70 status or white blood cell counts. All three cell lines were positive for Sirt1. While the two CLL-like cell lines Mec2 and JVM3 showed a concentration-dependent downregulation of Sirt1 upon FK866 treatment for 72h, Sirt1 levels remained stable in the MM-cell line IM9. Primary CLL-cells showed various baseline levels of Sirt1 and a concentration-dependent downregulation upon FK866 treatment.
We conclude that FK866 activity in CLL-like cell lines involves downregulation of the NAD-dependent oncogene Sirt1, while FK866 activity in the MM-cell line IM9 is Sirt1-independent. In primary CLL-cells Sirt1 baseline levels may predict responsiveness to FK866 treatment.
Citation Format: Iris Gehrke, Armando Poeppl, James Johnston, Spencer B. Gibson, Versha Banerji. Differential downstream effects of nicotinamide adenine dinucleotide (NAD) salvage pathway-inhibition in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1906. doi:10.1158/1538-7445.AM2013-1906
Abstract 1910: 3′UTR poly(T/U) tract deletions and altered expression of EWSR1 are a hallmark of mismatch repair-deficient cancers.
Authors: Piscuoglio Salvatore , Kishore Shivendra , Kovac Michal , Gylling Annette , Wenzel Friedel , Trapani Francesca , Altermatt Hans Joerg , Mele Valentina , Marra Giancarlo , Peltomaki Päivi , Terracciano Luigi , Zavolan Mihaela , Heinimann Karl 
Published: August 2014

Abstract
Background: Microsatellite instability (MSI), the genome-wide accumulation of DNA replication errors, is the hallmark lesion of DNA mismatch repair (MMR) deficient cancers, present in Lynch syndrome (LS)-related and 10-20% of sporadic colorectal (CRC), gastric and endometrial cancers. MSI testing is widely used to guide clinical management but the functional significance of MSI at distinct genic loci remains largely elusive. Here, we characterize a novel MSI target locus consisting of a mononucleotide (T/U)16 tract located in the 3’untranslated region (UTR) of the Ewing sarcoma break point region 1 (EWSR1) gene (EWS16T).
Methods: The diagnostic accuracy of EWS16T to identify MMR-deficient cancers was determined by analyzing 319 cancers (240 colorectal, 72 gastric, 7 endometrial) from two different populations. The functional consequences of EWS16T contractions were assessed in vitro (siRNA-mediated poly(A) site selection and pull-down assays) and in vivo (mRNA and protein expression by qPCR and tissue microarray analysis).
Results: The EWS16T locus discriminates MMR-proficient (n=128) from deficient (n=191) cancers with perfect diagnostic sensitivity (100%) and specificity (100%). Biochemical analyses indicate that EWS16T contractions alter poly(A) site selection by promoting SFPQ-mediated distal poly(A) site usage in EWSR1 pre-mRNAs and result in decreased mRNA as well as EWS protein expression. In contrast to their MMR-proficient counterparts (n=64), MMR-deficient, LS-related CRC (n=94) display altered subcellular localization of EWS (p&lt;0.001).
Conclusions: The EWS16T locus represents a novel, quasi-monomorphic MSI target locus to accurately identify both hereditary and sporadic MMR-deficient cancers. Contractions therein affect multiple regulatory mechanisms implicating the RNA-/DNA-binding Ewing sarcoma protein in MSI-associated colorectal tumorigenesis.
Citation Format: Salvatore Piscuoglio, Shivendra Kishore, Michal Kovac, Annette Gylling, Friedel Wenzel, Francesca Trapani, Hans Joerg Altermatt, Valentina Mele, Giancarlo Marra, Päivi Peltomaki, Luigi Terracciano, Mihaela Zavolan, Karl Heinimann. 3′UTR poly(T/U) tract deletions and altered expression of EWSR1 are a hallmark of mismatch repair-deficient cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1910. doi:10.1158/1538-7445.AM2013-1910