bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4907: The Emerging technology of Yb2Ti2O7 electrolyte-insulator-semiconductor biosensors for rapid screening of targeted mutation
Authors: Cheng Han Jhou , Shin Hsun Kao , Sow Neng Pang , Tung Ming Pan , Wen Hui Weng 
Published: August 2015

Abstract
Genetic mutations play an important role in the development of most cancers; thus, they have become key targets of investigation in the discovery of new biomarkers to help with cancer diagnostic and prognostic prediction, as well as monitor the development of drug resistance in cancer cells. We have now developed a technique by designing several probes that contain with different types of mutations, including substitution, insertion and deletion mutations for 6 or 12 bps (Table 1). Following this, we then mapped a colorectal cancer wild type KRAS cell line Caco2. To screen for different types of gene alterations,an electrolyte-insulator-semiconductor (EIS) device, incorporating a high-κ Yb2Ti2O7 sensing membrane deposited on Si substrates through co-sputtering to screen the genetic mutations, was made. X-ray diffraction and X-ray photoelectron spectroscopy were used to explore the structural features of these films annealed at various temperatures. The Yb2Ti2O7 EIS device, which annealed at 900 °C, exhibited a higher sensitivity of 59.4 mV/pH (in the solutions from pH = 2 to pH = 12), a lower hysteresis voltage of 1.6 mV (in the pH = 7→4→7→10→7), and a smaller drift rate of 0.16 mV/h (in the pH = 7 buffer solution) than those of the other annealing temperatures. We successfully demonstrated that high-κYb2Ti2O7 EIS devices with DNA-immobilized alginate films were able to screen all the designed mutation probes in Caco2 cells, and there was clear distinction from wild type based lines. In addition, even the substitution mutations were presented high resolution. Current measurement system provides a simple and inexpensive method for rapid and accurate detection of genetic changes in target genes; therefore it provided the high potential to serve as a diagnosis tool in clinical practice in the future.
Table 1.Design oligonucleotide probes.Oligonucleotide probessequencesTest 1wild type 24 bp5′-taggcaagagtgccttgacgatac-3′deletion 12 bp5′-taggca…………cgatac-3′deletion 6 bp5′-taggcaaga……tgacgatac-3′Test 2wild type 24 bp5′-ataggtgattttggtctagctaca-3′substitution 1 bp5′-ataggtgatttAggtctagctaca-3′insertion 6 bp5′-ataggtgattttGGGAACggtctagctaca-3′
Citation Format: Jhou Cheng Han, Kao Shin Hsun, Pang Sow Neng, Pan Tung Ming, Weng Wen Hui. The Emerging technology of Yb2Ti2O7 electrolyte-insulator-semiconductor biosensors for rapid screening of targeted mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4907. doi:10.1158/1538-7445.AM2015-4907
Abstract 4919: Tumor heterogeneity represented in human cancer cell lines
Authors: Volpe Lysa-Anne , Foulke John , Jackson Michael , Chen Luping , Randle David H. , Gitschier Hannah J. , Gardner Kelly , Tian Fang 
Published: August 2015

Abstract
EGFR has been found frequently mutated in human cancers, and more than 10% lung cancer patients associated with EGFR mutation. In addition, several critical mutations within the EGFR have been shown as gain of function mutations or can cause drug resistance to the EGFR inhibitors. A panel of ATCC tumor cell lines has been characterized for EGFR mutation and EGFR signaling pathway. Particularly, lung cell line NCI-H1975, which contains both drug sensitive mutation EGFR p.L858R and drug resistant mutation p.T790M, has displayed a resistance to EGFR inhibitor.Overall, NCI-H1975 cell line can be used as a nice model to study drug resistance, as well as to screen novel EGFR inhibitors that overcome the p.T790M-mediated resistance. Moreover, we have used next generation sequencing to analyze the mutation allelic frequency of both mutations, and observed tumor heterogeneity within this cell line. Impact of cell passage numbers on the mutation allele frequency of the cell line was also examined. Furthermore, a novel single cell western blot assay has been used to analyze the EGFR mutation, EGFR protein expression and downstream signaling within individual cells of three lung cancer cell lines at the single cell level. Collectively, NCI-H1975 cell line represents the acquired drug resistance found in clinical cancer patients, and this study demonstrates the tumor heterogeneity represented in human cell lines.
Citation Format: Lysa-Anne Volpe, John Foulke, Michael Jackson, Luping Chen, David H. Randle, Hannah J. Gitschier, Kelly Gardner, Fang Tian. Tumor heterogeneity represented in human cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4919. doi:10.1158/1538-7445.AM2015-4919
Abstract 492: Epigenetic suppression of miRNA-203 promotes Ewing sarcoma malignancy
Authors: Hensel Tim , Heid Esther , Plehm Stephanie , Burdach Stefan , Richter Günther H. 
Published: August 2015

Abstract
Ewing sarcoma (ES), a malignancy of bone and soft tissue that affects children and young adults, is characterized by early metastasis to lung and bone and by oncogenic ews/ets translocations. We previously observed the histone methyltransferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be regulated by EWS-FLI1 and highly increased in ES. We hypothesized non-coding RNAs to contribute to epigenetic processes and malignancy of ES. Here we show by ChIP on chip analysis that EZH2 occupies promoter regions of putative tumor suppressor miRNAs, oncogenic miRNAs and differentiation-associated miRNAs in ES and investigated their functional relevance by miRNA mimic, RNA interference, and functional assays. We show that hsa-miR-203a-3p (miR-203), a promoter of epidermal differentiation and trigger to exit cell cycle, was found epigenetic silenced in ES. We not only observed miR-203 up-regulation in different ES lines after EZH2 knock down or treatment with the EZH2 inhibitors GSK126 but also after histone de-acetylase inhibition (HDACi) via Trichostatin A (TSA) as well as MS-275. Similarly, treatment of ES lines with the DNA-methylation inhibitor 5′-azacytidine resulted in a strong up-regulation of miR-203 in ES. On the other hand, de-regulated expression of miR-203 after transient transfection with a miR-203-mimic identified a feed back loop resulting in a down-regulation of EWS-FLI1 and EZH2 in ES cell lines as compared to controls. In functional assays we observed that an increased expression of miR-203 suppressed contact dependent as well as independent growth in ES. In addition, in vitro invasiveness was strongly impaired after over-expression of miR-203. Taken together, we demonstrate the essential need for epigenetic suppression of miR-203 expression in ES that otherwise would suppress critical features of ES malignancy such as contact independent growth and invasiveness of ES. These results further provide a rationale for epigenetic combination therapy directed to reverse miR-203 suppression.
Citation Format: Tim Hensel, Esther Heid, Stephanie Plehm, Stefan Burdach, Günther H. Richter. Epigenetic suppression of miRNA-203 promotes Ewing sarcoma malignancy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 492. doi:10.1158/1538-7445.AM2015-492
Abstract 4942: Activation of Phosphatase toward the Retinoblastoma protein in breast and colorectal cancer cell spheroids
Authors: Egger Jacklynn , Antonucci Lisa , Lane Maria , Krucher Nancy A. 
Published: August 2015

Abstract
Excessive phosphorylation of the Retinoblastoma protein is found in most cancer tumor types. Several cyclin dependent kinase (cdk) inhibitors are in development or in clinical trials at the present time. Our previous studies have focused on the regulation of Rb phosphorylation by the phosphatase, PP1. Specificity toward substrates is imparted onto PP1 by many different interacting proteins. In proliferating cells, PP1 is associated with a regulatory protein called PNUTS (Phosphatase Nuclear Targeting Subunit). Our previous experiments have shown that PNUTS inhibits PP1 activity toward specific Rb phosphorylation sites. Further we have demonstrated that siRNA mediated knockdown of PNUTS in several cancer cell types (colon, breast, ovarian) leads to an increase in Rb specific PP1 activity, Rb dephosphorylation on several sites, and a dramatic induction of apoptosis. Furthermore, the ability of PNUTS siRNA to induce apoptosis was shown to be dependent on Rb expression. Interestingly, further studies showed that PNUTS knockdown had no effect on non-transformed breast and colorectal cells, in which Rb is not hyperphosphorylated. Thus we have developed a method to activate the Rb phosphatase in cells by knockdown of the PP1 binding protein, PNUTS. The current study was undertaken to analyze the effect of PNUTS knockdown in cancer cells grown in three-dimensional spheroids grown by incubation of cells in hanging drop plates. The effect of PNUTS knockdown on Rb phosphorylation, cell proliferation and cell viability using this model system will be presented.
Citation Format: Jacklynn Egger, Lisa Antonucci, Maria Lane, Nancy A. Krucher. Activation of Phosphatase toward the Retinoblastoma protein in breast and colorectal cancer cell spheroids. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4942. doi:10.1158/1538-7445.AM2015-4942
Abstract 4949: HAS2 is a critical effector for AGL mediated regulation of tumor growth
Authors: Guin Sunny , Ru Yuanbin , Lew Carolyn R. , Agarwal Neeraj , Owens Charles , Theodorescu Dan 
Published: August 2015

Abstract
In bladder cancer, reduced levels of Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL), an enzyme involved in glycogenolysis and mutated in glycogen storage disease type III, enhances proliferation in vitro and tumor growth in vivo. To identify how reduced levels of AGL promote bladder cancer growth, we gene expression profiled two bladder cancer cell lines with and without siRNA mediated AGL depletion. This identified that hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis, is upregulated with AGL depletion. We validated this finding in several additional bladder cancer cell lines and also found that HA levels were 2-fold higher bladder cancer cells with low AGL compared to control. Interestingly, siRNA induced knockdown of HAS2 preferentially reduced monolayer, anchorage independent and xenograft growth in bladder cancer cells with low AGL. 4-Methylumbelliferone (4-MU), an inhibitor of HA synthesis, had similar effects. Analysis of human bladder cancer tissues showed that AGL and HAS2 mRNA expression are negatively correlated in 5/8 patient datasets (N = 725). Bladder cancer patients with high HAS2 and low AGL expression had worse survival than patients with the reciprocal relationship between these two genes suggesting that HAS2 is a driver of bladder tumor growth with AGL loss establish the HAS2/HA axis as a major driver and target of therapy in bladder tumors with low AGL.
Citation Format: Sunny Guin, Yuanbin Ru, Carolyn R. Lew, Neeraj Agarwal, Charles Owens, Dan Theodorescu. HAS2 is a critical effector for AGL mediated regulation of tumor growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4949. doi:10.1158/1538-7445.AM2015-4949
Abstract 4962: Inhibition of TGF-β-RUNX3 signaling by activated Shh is correlated with the development of TGF-β resistance in gastric cancer cells
Authors: Park Seong Hye , Kim Jung Lim , Kim Bo Ram , Na Yoo Jin , Oh Sang Cheul 
Published: August 2015

Abstract
Three members of the Runt-related (RUNX) family of genes, RUNX1, RUNX2, and RUNX3 transcription factors, are known as developmental regulators important in the inception and progression of a variety of human cancers. RUNX3 is a tumor suppressor in gastric cancer, and its expression is frequently inactivated by DNA methylation or its protein mislocalized in many cancer types, including gastric and breast cancer. In this study hypothesized that the relationship between Shh signaling and RUNX3 may be involved in the development of TGF-β resistance.
Here, we was investigated a role and mechanism for RUNX3 reported a functionally important component in transforming growth factor-beta (TGF-beta) mediated signaling pathway. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay that treat TGF-b in SHH overexpressed gastric cancer cell. The result showed that inhibit the proliferation by TGF-beta treatment in the control cells in a dose-dependent pattern but did not, SHH overexpressing gastric cancer cells. RT-PCR analysis showed that the expression of Runx3 in SHH overexpressing cells with TGF-beta. RUNX3 mRNA level not affected in control and SHH overexpressing cellls. When Shh overexpressing cells were treated with the proteasome inhiitors, MG132, level of Runx3 was decrease. RUNX3 are known to be primarily localized to the nucleus. Immunofluorescence indicate translocation of Runx3 from the nuleus to the cytoplasm in SHH overexpressing cells. On the other hand, treatment with SHH blocking antibody inhibited the moved from the nucleus to the cytoplasm in SHH overexpressing cells. These results indicate that suppression of TGF-β-RUNX3 signaling by activated Shh is correlated with the development of TGF-β resistance in gastric cancer.
Citation Format: Seong Hye Park, Jung Lim Kim, Bo Ram Kim, Yoo Jin Na, Sang Cheul Oh. Inhibition of TGF-β-RUNX3 signaling by activated Shh is correlated with the development of TGF-β resistance in gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4962. doi:10.1158/1538-7445.AM2015-4962
Abstract 4963: Prognostic significance of the expression of nuclear EIF5A2 in human melanoma
Authors: Khosravi Shahram , Martinka Magdalena , Ong Christopher J 
Published: August 2015

Abstract
Eukaryotic translation initiation factor 5A2 (EIF5A2) is an oncogene that is upregulated in several different cancers. We previously showed that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with melanoma patient survival. In this study, we used immunohistochemistry and tissue microarray (TMA) using a large number of melanocytic lesions (n = 459) to examine the expression profile of nuclear EIF5A2 in melanoma progression in addition to the correlation between nuclear EIF5A2 expression and melanoma patient survival. We found that nuclear EIF5A2 expression was significantly upregulated in primary melanomas compared with normal nevi and dysplastic nevi, as well as in metastatic melanomas compared with primary melanomas, normal nevi and dysplastic nevi. Nuclear EIF5A2 expression had a significant inverse correlation with overall and disease-specific 5-year survival of all and primary melanoma patients. Nuclear EIF5A2 expression was also significantly correlated with melanoma thickness and AJCC stages, suggesting the possible role of nuclear EIF5A2 in melanoma cell invasion. We then investigated the correlation between the expression of nuclear EIF5A2 and MMP-2 which is one of the important factors for promoting cancer cell invasion. Nuclear EIF5A2 expression and strong MMP-2 expression were directly correlated as well, and their concurrent expression was significantly associated with worse overall and disease-specific 5-year survival of all and primary melanoma patients. We also studied the correlation between nuclear and cytoplasmic EIF5A2 expression and found that they were significantly correlated, and simultaneous expression of both was significantly associated with poor overall and diseases-specific 5-year survival of all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear expression of EIF5A2 was an adverse independent prognostic factor for melanoma patients. In conclusion, we for the first time demonstrated the nuclear expression of EIF5A2 as an independent prognostic marker in melanoma and its role in melanoma progression and patient survival. As a result, nuclear EIF5A2 may have the potential to serve as a therapeutic marker for melanoma.
Citation Format: Shahram Khosravi, Magdalena Martinka, Christopher J Ong. Prognostic significance of the expression of nuclear EIF5A2 in human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4963. doi:10.1158/1538-7445.AM2015-4963
Abstract 4967: The BAP1 deubiquitinase promotes triple-negative breast cancer partially by stabilizing the KLF5 transcription factor
Authors: Chen Ceshi , Qin Junying , Zhou Zhongmei 
Published: August 2015

Abstract
The transcription factor KLF5 is highly expressed in basal triple-negative breast cancer (TNBC) and promotes breast cancer cell proliferation, survival and tumor growth. However, the mechanism by which KLF5 is regulated in breast cancer remains unclear. In this study, we performed a genome-wide siRNA library screening against deubiquitinases (DUBs) and identified BAP1 as a bona fide KLF5 DUB. BAP1 interacts with KLF5 directly and stabilizes KLF5 via deubiquitination. KLF5 is in the BAP1/HCF-1 complex, and this newly identified complex promotes cell cycle progression partially by inhibiting p27 gene expression. Furthermore, BAP1 knockdown inhibits tumorigenicity and lung metastasis, which can be partially rescued by ectopic KLF5 expression. Collectively, our findings not only identified BAP1 as the first DUB for KLF5 but also revealed a critical mechanism for KLF5 expression regulation in TNBC. BAP1 could be a potential therapeutic target for TNBC and other cancers.
Citation Format: Ceshi Chen, Junying Qin, Zhongmei Zhou. The BAP1 deubiquitinase promotes triple-negative breast cancer partially by stabilizing the KLF5 transcription factor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4967. doi:10.1158/1538-7445.AM2015-4967
Abstract 4968: microRNA-mediated silencing of COP1 and altered ubiquitination of key oncogenic transcription factors promote cancer stem cell (CSC) phenotype and prostate cancer progression
Authors: Dallavalle Cecilia , Albino Domenico , Civenni Gianluca , Curti Laura , Ostano Paola , Mello-Grand Maurizia , Garcia-Escudero Ramon , Chiorino Giovanna , Catapano Carlo V. , Carbone Giuseppina M. R. 
Published: August 2015

Abstract
Mutations and deletions of ubiquitin ligase complex proteins are emerging as important mechanisms driving tumorigenesis. In this study we report an alternative mechanism, depending on microRNA-mediated post-transcriptional silencing, leading to altered ubiquitination of key oncogenic proteins and induction of tumorigenic and CSC properties in prostate epithelial cells (PrECs). We found that increased expression of miR-424 promotes malignant transformation of normal PrECs by targeting the E3 ubiquitin ligase COP1. miR-424 was upregulated in primary prostate cancers and prevalently in ERG negative tumors. Bioinformatics and functional analysis demonstrated that miR-424 targeted COP1 mRNA in PrECs drastically reducing its protein level. Moreover, miR-424 and COP1 expression were inversely correlated in prostate tumors and associated with enrichment of CSC features. Functionally, over-expression of miR-424 or knockdown of COP1 in PrECs increased anchorage-independent growth, cell migration and prostatosphere formation under CSC selective conditions. Consistently, inhibition of miR-424 or over-expression of COP1 prevented these phenotypic changes in normal PrECs and prostate cancer cell lines. Moreover, COP1 knockdown reproduced closely the effects of miR-424 upregulation in PrECs. Mechanistically, we found that silencing of COP1 by miR-424 resulted in reduced turnover and increased level of several oncogenic transcription factors, including known COP1 substrates like c-JUN and ETV1. Furthermore, we identified STAT3 as a novel substrate of the miR-424/COP1 axis. Consistently, miR-424 upregulation and COP1 silencing increased STAT3 protein level and enhanced basal and cytokine induced STAT3 activity in PrECs and prostate cancer cells. These effects were blocked by miR-424 inhibition and COP1 overexpression. These results establish the miR-424/COP1 axis as a relevant oncogenic pathway acting through deregulation of key transcription factors and with important prognostic and therapeutic implications.
Citation Format: Cecilia Dallavalle, Domenico Albino, Gianluca Civenni, Laura Curti, Paola Ostano, Maurizia Mello-Grand, Ramon Garcia-Escudero, Giovanna Chiorino, Carlo V. Catapano, Giuseppina M. R. Carbone. microRNA-mediated silencing of COP1 and altered ubiquitination of key oncogenic transcription factors promote cancer stem cell (CSC) phenotype and prostate cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4968. doi:10.1158/1538-7445.AM2015-4968