bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2878: Targeting the CXCL5-CXCR2-CREB signaling axis suppresses growth, survival, and invasion of lung adenocarcinoma.
Authors: Park Hee Sun , Lee Jong Woo , Saintigny Pierre , Kurie Jonathan M. , Herbst Roy S. , Koo Jaseok Peter 
Published: August 2014

Abstract
The role of chemokines and chemokine receptors has been evolving in cancer. Besides their functions in the immune system, they also play a critical role in tumor initiation, promotion and progression. Since the tumor microenvironment play a critical role in cancer development and progression, the immune components of the tumor microenvironment have gained attention in the recent decades for its critical role in tumorigenesis and tumor control. Recent studies have clearly demonstrated the importance of CXCR2 in the development of lung cancer. Our recent studies showed that CXCR2 expression in tumor cells was associated with poor prognosis in non-small cell lung cancer (NSCLC) patients (n=262). Analysis of gene expression profiles from the National Cancer Institute (NCI) Director's Challenge Cohort of in lung adenocarcinoma patients (n=442) revealed that overexpression of CXCR2 ligands and CXCR2 genes was clustered together in approximately 25% of lung adenocarcinoma patients. Expression of CXCR2 and its associated ligand gene cluster in tumor cells was associated with poor prognosis, smoking status, and poor histologic differentiation. Furthermore, CXCL5 was involved as an potent angiogenic factor in NSCLC. The objective of the current study was to establish the role of the CXCL5/CXCR2 axis in tumor growth and invasion and to determine its related molecular mechanisms. In the study, CXCL5 activated the CREB transcription factor via the pERK1/2-p90Rsk-pCREB signaling pathway. In addition, inhibitors of CXCR2 and downstream signal transduction molecules blocked the activation of pERK1/2-pRsk-pCREB signaling molecules. Blockade of the CXCR2 receptor, CXCR2-dependent signal molecules, or CREB resulted in suppression of NSCLC cell growth, survival and invasion. These results suggest that the CXCL5-CXCR2-CREB signaling axis may be a source of potential therapeutic targets in lung adenocarcinoma.
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Citation Format: Hee Sun Park, Jong Woo Lee, Pierre Saintigny, Jonathan M. Kurie, Roy S. Herbst, Jaseok Peter Koo. Targeting the CXCL5-CXCR2-CREB signaling axis suppresses growth, survival, and invasion of lung adenocarcinoma. [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 2878. doi:10.1158/1538-7445.AM2013-2878
Abstract 2881: E-FABP protects host from tumor development.
Authors: Zhang Yuwen , Rao Enyu , Li Bing 
Published: August 2014

Abstract
Epidermal fatty acid-binding protein (E-FABP) is constitutively expressed in many immune cells, including dendritic cells, macrophages and T lymphocytes. However, the role of E-FABP in host immunity against tumor and cancer development is unknown. We hypothesize that E-FABP plays an essential role in host immune responses to ward off tumor challenges. Here we utilize a murine breast cancer model and E-FABP knockout mice to study the function of E-FABP in host immune responses to tumor challenges. It is found that implanted breast cancer cells develops much faster into tumor in E-FABP knockout mice than in wild type ones. It is also discovered that, when compared to wild type mice, F4/80+CD11c+ macrophages in tumor stroma from E-FABP knockout mice show a defective protective immune response to breast cancer cells. Moreover, tumors in E-FABP knockout mice contained much lower numbers of NK cells, CD8+ and CD4+ T cells than those in WT mice. All these results suggest E-FABP protects host from tumor development, implicating a significant role of E-FABP in host immunity against tumor formation.
Citation Format: Yuwen Zhang, Enyu Rao, Bing Li. E-FABP protects host from tumor development. [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 2881. doi:10.1158/1538-7445.AM2013-2881
Abstract 2886: Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of Chronic Lymphocytic Leukemia B cells.
Authors: Palomba M. Lia , Piersanti Kelly , Ziegler Carly G. K. , Cotari Jesse , Balderas Robert , Malek Sami N. , Seymour Erlene , Zelenetz Andrew D. , van den Brink Marcel R. M. , Altan-Bonnet Gregoire 
Published: August 2014

Abstract
Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. To assess the aberrant behavior of BCR signaling in CLL B cells, we developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled the complex nature of BCR signaling using Partial Least Squares Regression (PLSR) to gain new insights into the strongest predictors of discrimination between CLL and normal B cells. We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pBLNK, ppERK) phosphoresponses. Furthermore, PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as key to the pathogenic properties of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Single-cell multidimensional analysis of BCR signaling permitted focused study of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness.
Citation Format: M. Lia Palomba, Kelly Piersanti, Carly G. K. Ziegler, Jesse Cotari, Robert Balderas, Sami N. Malek, Erlene Seymour, Andrew D. Zelenetz, Marcel R. M. van den Brink, Gregoire Altan-Bonnet. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of Chronic Lymphocytic Leukemia B 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 2886. doi:10.1158/1538-7445.AM2013-2886
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2894: Integrated bioinformatic analysis to elucidate molecular mechanisms associated with reversal of osteosarcoma malignancy induced by CD99.
Authors: Sciandra Marika , Grilli Andrea , Marino Maria Teresa , Manara Maria Cristina , Picci Piero , Scotlandi Katia 
Published: August 2014

Abstract
Introduction: CD99 is a transmembrane glycoprotein which is physiologically involved in several biological processes, such as cell migration, adhesion, and differentiation. High levels of CD99 have been reported in mesenchymal stem cells and osteoblasts. In contrast, the molecule has been shown to be absent in osteosarcoma (OS), in which it acts as a tumour suppressor. The molecular mechanisms responsible for its functions are however still poorly defined. In this study we used bioinformatic studies to integrate gene expression and miRNA data to identify crucial mediators.
Methods: Forced expression of CD99 was stably induced in Saos-2 OS cell line. Microarray analyses of gene or miRNA expression were performed and integrated by using different bioinformatic approaches. TargetScan, Miranda, Diana-microT and PicTar prediction databases were used to identify miRNA targets.
Results: CD99-overexpressing cells displayed a massive down-regulation of gene expression. Only 19 probes were found to be significantly up-regulated in CD99 transfectants compared to parental cells. In contrast, 231 probes were found to be down-regulated, thus suggesting gene modulation by epigenetic mechanisms. We thus examined miRNA profile of these cells. A significant up-regulation of miR-1225-3p, miR-1238, miR-1305, miR-191*, miR-34a, and miR-425* was observed in CD99 overexpressing cells. Enrichment analyses pointed out an involvement of TGFβ signalling. Interestingly, SMAD-2 and -4, which emerged as targets of miR-34a, were among the main down-modulated genes. miR34 mimics confirmed the association between miR34a and SMAD-4. Functional studies are on-going to establish associations with osteosarcoma malignancy.
Conclusions: Besides inhibiting osteosarcoma malignancy, CD99 expression in osteosarcoma cells determines massive gene expression repression, likely due to changes in miRNA profile. Up-regulation of miR-34a together with down-regulation of TGFβ signalling mediators seem to be critical players.
Studies are granted by AIRC 10452 and Ministry Health RF-2009 to KS.
Citation Format: Marika Sciandra, Andrea Grilli, Maria Teresa Marino, Maria Cristina Manara, Piero Picci, Katia Scotlandi. Integrated bioinformatic analysis to elucidate molecular mechanisms associated with reversal of osteosarcoma malignancy induced by CD99. [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 2894. doi:10.1158/1538-7445.AM2013-2894
Abstract 2901: An integrated matrix factorization algorithm for DNA methylation and gene expression identi es HNSCC clinical subtypes and GLI1 signaling speci c to HPV-negative HNSCC.
Authors: Fertig Elana J. , Markovic Ana , Danilova Ludmila V. , Gaykalova Daria A. , Cope Leslie , Chung Christine H. , Califano Joseph A. , Ochs Michael F. 
Published: August 2014

Abstract
Global methylation changes occur heterogeneously in primary head and neck squamous cell carcinoma (HNSCC). To infer methylation-driven changes in expression in subtypes of HNSCC, we integrated global gene expression and DNA methylation measurements in 44 HNSCC and 25 normal samples using a matrix factorization algorithm. This algorithm incorporated novel models to transform methylation and expression measurements to a common scale. Although unsupervised, this integrated matrix factorization inferred patterns common to gene expression and methylation data that differentiate clinical subtypes within the 44 HNSCC samples, including notably HPV status and tumor site. Informatic analysis of the genes associated with these patterns identified specific pathway activity related to HPV status. This algorithm uniquely linked DNA methylation changes and reactivation of genes in the Hedgehog pathway predominantly in HPV-negative samples. We further examined the pathway by determining expression levels of GLI1, one of the downstream target genes of the Hedgehog pathway, in two independent cohorts. We confirmed that GLI1 expression was higher in tumors compared to normal samples and HPV-negative tumors had higher GLI1 expression compared to HPV-positive tumors, suggesting that increased expression of GLI1 plays a role in HPV-negative HNSCC.
Citation Format: Elana J. Fertig, Ana Markovic, Ludmila V. Danilova, Daria A. Gaykalova, Leslie Cope, Christine H. Chung, Joseph A. Califano, Michael F. Ochs. An integrated matrix factorization algorithm for DNA methylation and gene expression identi es HNSCC clinical subtypes and GLI1 signaling speci c to HPV-negative HNSCC. [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 2901. doi:10.1158/1538-7445.AM2013-2901
Abstract 2902: Global bioinformatic analysis for transcription factor genomic binding sites from ChIP-sequencing.
Authors: Fu Junjiang 
Published: August 2014

Abstract
The technique for Chromatin Immunoprecipitation (ChIP) combining with high-throughput DNA sequencing (ChIP-seq), is better than the ChIP-on-chip, which might reveal interactions between proteins and DNAs by the new generation sequencing technology. ChIP-seq can accurately reveal all possible binding sites in the whole cellular genome of the transcription factors or interesting proteins. TWIST, an important transcription factor which has a highly conserved, basic helix - loop - helix (bHLH) domain, can bind with DNA motif CANNTG (E-box). However, ChIP-seq will generate millions of data and the exactly E-boxes of TWIST in the whole genome is unknown. In this study, we performed the global bioinformatic analysis for transcription factor TWIST genomic binding sites from ChIP-seq result in cell lines. MACS software was used to identify TWIST binding sites from ChIP-seq data. MEME, a motif discovery tool, was used to search for statistically over-represented motifs in and near TWIST-occupied regions. There are 26,229 binding sites and 90,659 E-boxes in whole genome, and 42,390 E-boxes within the peak of 100bp in the binding sites. The majority of ChIP-seq signals could be parsimoniously explained by a CABVTG motif within ±200bp of ChIP summit and, of these, CAGCTG is most prevalent. Specifically, the characteristics of E-box mainly are CACATG, CATATG, CAGATG, CAGCTG and CACCTG. The CAGCTG is most prevalent E-box with 9% in total, and most E-boxes located within ±200bp of ChIP summit with more than 70% in total. Additionally, further analysis in chromosome 6 revealed 1936 binding sites and 6,437 E-boxes. We defined 88 genes in which binding sites located at promoter region in chromosome 6. Through gene function prediction, they are divided into three clusters. Some genes from the clusters function as tumor development and necrosis, which will provide us the clues for studying TWIST net work regulation and signal pathways in cancer biology. Therefore, our results showed that bioinformatics analysis from high resolution ChIP-seq data may be used to drive effective discovery and dissect all of binding sites for transcript factors, including TWIST, in silico.
This work was supported by NSFC (30371493, 81172049). We thank Drs. R Chen, J Xu and Ms. J Cheng.
Citation Format: Junjiang Fu. Global bioinformatic analysis for transcription factor genomic binding sites from ChIP-sequencing. [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 2902. doi:10.1158/1538-7445.AM2013-2902
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2914: To study DNA repair function of two closely related human lung adenocarcinoma cell lines, CL1-0 and CL1-5.
Authors: Wu Feng- Chang , Lin Yu-Fen , Lai Liang-Chuan , Chuang Eric Y , Tsai Mong-Hsun 
Published: August 2014

Abstract
Exogenous agents and endogenous processes, such as reactive oxygen species (ROS) can induce base oxidation and DNA lesions. One of the most severe DNA lesions is the double-strand break (DSB). There are several repair systems to fix the resulting DNA lesions to prevent error copies of genetic information to be carried to daughter cells. Oxidative stress is an important factor to induce DNA damage during normal cellular metabolism. In this study, we wanted to use lung cancer cells, CL1-0 and CL1-5 cells, which have differential invasiveness ability to characterize DNA repair function. Hydrogen peroxide (H2O2) was treated in lung adenocarcinoma cells to induced DNA DSB. By using immunoflurecence microscope, we found that CL1-5 had more gamma-H2AX foci (DNA DSB marker) and ROS accumulation than CL1-0 post both 1 mM and 5 mM H2O2 treatment. Moreover, CL1-0 had a tight G2/M checkpoint and has a longer G2 arrest after H2O2 treatment, but not found in CL1-5. In addition, increasing sub-G1 population (apoptotic cells) was found in H2O2-treated CL1-5 but less in CL1-0. Furthermore, phosphorylated-Akt (S473) was decreased in CL1-5, In contrast, phosphorylated-ATM (S1981) and Chk2 were increased after 5 mM H2O2 treatment for 90 min. In addition, the level of GSH was persistently lower at the steady state and post H2O2 treatment in CL1-5 by LC-MS/MS analysis. Besides, the apoptotic cells were decreased but no differences in CL1-0 while supplement reduced-GSH before H2O2 treatment. We therefore hypothesize that there are different processes on dealing with ROS scavenging post oxidative stress between CL1-0 and CL1-5. Taken together, using hydrogen peroxide for treating two lung cancer cell lines seem to have different DNA repair function to regulate cellular function. In the following experiments, the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase as well as glutathione peroxidase (GPx) post oxidative stress in CL1-0 and CL1-5 will be determined. Moreover, we will examine the level of GSH in different tumor cell lines to investigate whether GSH involved in tumor invasion ability.
Citation Format: Feng- Chang Wu, Yu-Fen Lin, Liang-Chuan Lai, Eric Y Chuang, Mong-Hsun Tsai. To study DNA repair function of two closely related human lung adenocarcinoma cell lines, CL1-0 and CL1-5. [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 2914. doi:10.1158/1538-7445.AM2013-2914
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2916: NOXX: Friend or foe for cellular proliferation.
Authors: Dho So Hee , Kim Ji Young , Kim Chang-Jin , Nauseef William M. , Choi So-Young , Lee Kwang-Pyo , Kwon Ki-Sun 
Published: August 2014

Abstract
Reactive oxygen species (ROS) are signaling molecules that determine cellular fate. In tumor progression, ROS have been suggested to function as a dual cell controller. They could induce cellular proliferation in low levels while inhibiting cellular proliferation in high levels. ROS can be produced by NOXX, a member of NADPH oxidase family. Here, we present that an increase in NOXX levels by activation of STAT5 are critical in tumor progression by comparing the NOXX levels of breast and lung tumor tissues to those of normal tissues. Consistently, depletion of NOXX causes tumor suppression of lung and breast cancer cells, and expression of NOXX induces proliferation of normal lung cells. Notably, we found that cisplatin, an antineoplastic agent, increases NOXX activity and inhibits cellular proliferation. Specifically, cisplatin activates NOXX to induce a high level of ROS in multiple ways through (i) an increase in NOXX levels, (ii) an increase in levels of c-abl which is an activator of NOXX, and (iii) a release of Ca2+, the other activator of NOXX. Together, NOXX is a double-edged sword for tumorigenesis in lung and breast cancers by modulating ROS levels, and will be a promising target for cancer therapy.
Citation Format: So Hee Dho, Ji Young Kim, Chang-Jin Kim, William M. Nauseef, So-Young Choi, Kwang-Pyo Lee, Ki-Sun Kwon. NOXX: Friend or foe for cellular proliferation. [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 2916. doi:10.1158/1538-7445.AM2013-2916
Abstract 2920: Effect of nitric oxide on invasiveness and metabolism of cancer cells.
Authors: Caneba Christine A. , Marini Juan , Nagrath Deepak 
Published: August 2014

Abstract
Nitric oxide synthase (NOS) expression has been shown to be upregulated in cancer cells compared to normal cells. The resulting increased nitric oxide (NO) production changes the metastatic ability of cancer cells. The link between NOS expression, NO production, apoptosis, and drug resistance in ovarian cancer is beginning to be studied. However, the effect of NO on metabolism and invasiveness of ovarian cancer cells is not known. Here, using gas chromatography - mass spectroscopy based isotope analysis we show that highly-invasive ovarian cancer cells convert arginine to citrulline via the nitric oxide pathway as opposed to less-invasive ovarian cancer cells. We hypothesize that NO is important for the proliferation, migration, invasion, and drug resistance in highly-invasive ovarian cancer cells as opposed to less-invasive ovarian cancer cells, and that these changes in metastatic behavior are linked to changes in metabolism. We show that L-NG-Nitroarginine Methyl Ester (L-NAME), an inhibitor of NOS, decreases NO production and thus decreases proliferation, migration, and invasion of ovarian cancer cells, as well as decreases drug resistance. Using metabolic assays, we show that NO affects the glucose consumption, lactate secretion, and pyruvate uptake, and provides us with clues regarding the effect of NO on glycolytic activity of highly-invasive and less-invasive ovarian cancer cells. Lastly, we show that NO affects oxygen consumption rate in these cells, and thus oxidative phosphorylation. Our findings are the first to link NO production and invasiveness with metabolism in ovarian cancer cells.
Citation Format: Christine A. Caneba, Juan Marini, Deepak Nagrath. Effect of nitric oxide on invasiveness and metabolism of 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 2920. doi:10.1158/1538-7445.AM2013-2920
Abstract 2925: p90RSK2 coordinates pro-apoptotic and anti-apoptotic signaling pathways to protect cancer cells from anoikis.
Authors: Jin Lingtao , Li Dan , Lee Jongseok , Alesi Gina N. , Fan Jun , Kang Hee-Bum , Wang Dongsheng , Fu Haian , Taunton Jack , Boggon Titus J. , Tucker Meghan , Gu Ting-Lei , Chen Zhuo G. , Shin Dong M. , Khuri Fadlo R. , Kang Sumin 
Published: August 2014

Abstract
How invasive and metastatic tumor cells evade from anoikis induction remains unclear. We found that knockdown of RSK2 sensitizes diverse cancer cells to anoikis induction, which is mediated through phosphorylation targets, including apoptosis signal-regulating kinase 1 (ASK1) and cAMP response element-binding (CREB). We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109 and T1326 through novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding. Moreover, RSK2-CREB signaling pathway provides anti-anoikis protection by regulating gene expression of protein effectors that are involved in cell death regulation, including anti-apoptotic protein tyrosine kinase 6 (PTK6) and pro-apoptotic inhibitor of growth protein 3 (ING3). PTK6 overexpression or ING3 knockdown in addition to ASK1 knockdown further rescued the increased sensitivity to anoikis induction in RSK2 knockdown cells. These data together suggest that RSK2 functions as a signal integrator to provide anti-anoikis protection to cancer cells in both transcription-independent and -dependent manners, in part by signaling through ASK1 and CREB, and contributes to cancer cell invasion and tumor metastasis.
Citation Format: Lingtao Jin, Dan Li, Jongseok Lee, Gina N. Alesi, Jun Fan, Hee-Bum Kang, Dongsheng Wang, Haian Fu, Jack Taunton, Titus J. Boggon, Meghan Tucker, Ting-Lei Gu, Zhuo G. Chen, Dong M. Shin, Fadlo R. Khuri, Sumin Kang. p90RSK2 coordinates pro-apoptotic and anti-apoptotic signaling pathways to protect cancer cells from anoikis. [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 2925. doi:10.1158/1538-7445.AM2013-2925