bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2347: PSA splice variants and their expression in prostate cancer
Authors: Yang Alice S. , Alahapperuma Thushari , Mubiru James N. , Garcia-Forey Magdalena , Shade Robert E. 
Published: May 2015

Abstract
Introduction
Prostate cancer (PCa) is the second most common cancer in American men, resulting in 32,000 deaths annually. Challenges for the management of PCa include the inability to distinguish indolent from aggressive and untreatable castration-resistant PCa. These challenges can be addressed by understanding the molecular basis of cancer initiation and progression. Prostate specific antigen (PSA) is widely used for screening, diagnosing and monitoring of PCa, although it is also elevated in other disorders and therefore lacks specificity and sensitivity. Alternative splicing is a common mechanism used in nature to enhance protein diversity. Alternative splicing of the PSA gene produces at least 15 transcripts of 0.7-6.1 kb (Heuzé-Vourc'h et al 2003). Several variants of PSA have been reported and are shown to be differentially expressed in PCa compared to normal prostates or to benign prostatic hyperplasia (BPH).
Here we describe the identification of four variants of PSA with the potential to improve on the specificity of the PSA test.
Material and Methods
Human prostate cDNAs were from cryopreserved prostate tissues collected after radical prostatectomies and have been described previously (Mubiru et al. 2004). PCR was carried out using primers that amplify the complete PSA mRNA and also those specific for the most common splice variant (Heuzé-Vourc'h et al. 2001). The PCR products were inserted into the PCR2.1-TOPO vector (Life Technologies) and sequenced.
Results
We identified four novel splice variants of the PSA gene.
Novel PSA Splice VariantsTypeNameContaining Exons (Ex) and Introns (In)Molecular Weight (Da)pIPSA mRNAPSAEx3del246Ex1, Ex2, Partial Ex38,5949.61PSA mRNAPSA25RVEx1, Partial In111,1815.55PSA mRNAPSA Yang 28Ex1, Ex2, Ex514,1539.59PSA mRNAPSA Yang 21Ex1, Ex2, Partial Ex3, Ex4, Ex523,6986.64
Results also indicate that some transcripts are differentially expressed in tumors compared to non-tumors.
References
1.Mubiru JN, et al. (2004). Gene 327: 89-98.
2.Heuzé-Vourc'h N, et al. (2003) Eur J Biochem 270: 706-714.
3.Heuzé-Vourc'h N, et al. (2001) Eur J Biochem 268: 4408-4413.
Citation Format: Alice S. Yang, Thushari Alahapperuma, James N. Mubiru, Magdalena Garcia-Forey, Robert E. Shade. PSA splice variants and their expression in prostate 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 2347. doi:10.1158/1538-7445.AM2014-2347
Abstract 2350: Inhibition of Gli1 as a novel therapeutic target for lung squamous cell carcinoma
Authors: Shao Chunli 
Published: May 2015

Abstract
Purpose: It is clear that Hedgehog (Hh) signaling pathway can promote small cell lung cancer development but is not sufficient to drive tumor formation. However, the functional role of Hh pathway in non-small cell lung cancer remains unclear. We found that Gli1, a transcription factor of Hh pathway, is highly expressed in lung squamous cell carcinoma (SSC). The purpose of our study is to identify the functional importance of Gli1 in lung SCC.
Methods: We performed a genome-wide gene expression analysis to examine Hh pathway component expression in 275 lung cancer patient specimens. qRT-PCR and western blot were used to validate their expression in SCC lines. To further explore its biological function in lung SCC we manipulated Gli1 expression genetically or pharmacologically followed by colony formation and tumor formation assays.
Results: Microarray analysis revealed that Gli1, Gli2, Gli3, and Smoothened are significantly upregulated in lung SCC compared to lung adenocarcinoma (AD). Consistently we found the increased expression of Glis in lung SCC lines relative to AD lines by real-time PCR and western blot. Knocking down Gli1 by siRNA decreased liquid colony formation ability and Gli1-luciferase reporter activity in SCC lines. A significant reduction of cell proliferation and liquid colony formation was observed in shGli1 expressing SCC cells compared to control cells. Gli1 specific inhibitor GANT61 strongly inhibited SCC cell proliferation through inducing cell apoptosis. However, Gli1 expression or transcriptional activity is not regulated by classical Hh pathway upstream regulators in lung SCC. We found that blocking PI3K or ERK pathways by pharmacological inhibitors significantly reduced Gli1 expression and cell survival. In addition, TGF-β stimulation promoted Gli1 expression and transcriptional activity in SCC cells.
Conclusions: Our data suggest that Hh pathway downstream factor Gli1 expression is essential for cell proliferation and colony formation in lung SCC. Gli1 is not regulated by canonical Hh pathway regulators, whereas PI3K, ERK, and TGF pathways are involved in its regulation. Blocking Gli1 function is a novel therapeutic strategy for lung SCC treatment.
Citation Format: Chunli Shao. Inhibition of Gli1 as a novel therapeutic target for lung squamous cell carcinoma. [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 2350. doi:10.1158/1538-7445.AM2014-2350
Abstract 2366: Transcriptome analysis of human metastasis prostate cancer cells deciphers new function of Esrrb
Authors: Lu Yuan , Li Jilong , Cheng Jianlin , Lubahn Dennis B. 
Published: May 2015

Abstract
Orphan nuclear receptor family member, Estrogen Related Receptor β (esrrb) became a research hot topic in recent years. Although the function of esrrb is relatively well studied in stem cells and early embryonic development, little is known about its function in cancer. Esrrb is reported to arrest prostate cancer cell cell-cycle by upregulating p21. Here we investigate the transcriptome alteration induced by esrrb expression and its synthetic ligand DY131 in a human prostate cancer cell line. We distinguished 205 qualified differentially expressed (DE) genes regulated by esrrb alone, and 3202 genes with DY131 treatment with esrrb expression, indicating esrrb has both ligand independent and ligand dependent activity. From the esrrb-regulated transcriptome, we established a hypothetical esrrb transcription regulation model in prostate cancer cells by matching the DNA motif recognized by transcriptional factors (TFs) to the promoter sequences of differentially expressed genes. We found esrrb-regulated gene expression is mediated by TAGLN, HOXB2 and HOXB8 from our model. Our findings potentially provide multiple markers to characterize esrrb's function in prostate cancer.
Citation Format: Yuan Lu, Jilong Li, Jianlin Cheng, Dennis B. Lubahn. Transcriptome analysis of human metastasis prostate cancer cells deciphers new function of Esrrb. [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 2366. doi:10.1158/1538-7445.AM2014-2366
Abstract 2369: Molecular biological characterization of newly established epithelial ovarian cancer (EOC) cell lines : The cyclin-dependent kinase 1 pathway
Authors: yang wookyeom , Cho hanbyoul , Shin hayeon , Lee eunju , Kwon hyunja , Kim sol , Kim jaehoon 
Published: May 2015

Abstract
Background
Gene expression pattern analysis comparing normal cells with cancer cells are performed by many competitors in the worldwide lab. Cancer has many different species in itself due to its individual differences, variations and heterogeneity. Therefore, it is necessary to spend more time in gene expression pattern analysis using microarray or whole genome sequencing. The purpose of this study was to identify genes and proteins that are highly differentially expressed in newly established epithelial ovarian cancer (EOC) cell lines, and to use this knowledge for the development of novel diagnostic and prognostic markers for EOC. We further performed the validation studies of several candidate genes.
Results
Comparison of gene expression patterns using microarray analysis enabled us to identify 84 genes that were commonly up-regulated and 132 genes that were down-regulated in cancer cell lines (up; &gt; 2-fold, down; &lt; 3-fold, P &lt; 0.05). In 2-DE and MALDI-TOF/PMF, 31 up-regulated spots that had at least two-fold differences between the 3 EOC cell lines and HOSE cells used as controls were observed. 15 up-regulated genes in cell cycle related genes and 9 down-regulated genes in apoptosis related confirmed gene expression using quantitative RT-PCR. Pathway analysis was validated in cell cycle related genes in six EOC cell lines.
Conclusions
The data shows the aberrant expression of several cell cycle related genes in EOC and that Cyclin-dependent kinase 1 (CDK1) pathway may play a significant role in ovarian carcinogenesis, implying that CDK1 pathway could be used as a novel therapeutic target for ovarian cancer treatment.
Citation Format: wookyeom yang, hanbyoul Cho, hayeon Shin, eunju Lee, hyunja Kwon, sol Kim, jaehoon Kim. Molecular biological characterization of newly established epithelial ovarian cancer (EOC) cell lines : The cyclin-dependent kinase 1 pathway. [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 2369. doi:10.1158/1538-7445.AM2014-2369
Abstract 2372: Detecting driver genes based on tumor whole-exome sequencing studies
Authors: Hua Xing , Landi Teresa Maria , Shi Jianxin 
Published: May 2015

Abstract
Driver somatic mutations confer a selective growth advantage to tumors while passenger mutations do not. Genes carrying driver mutations are detected in whole-exome sequencing (WES) studies if their non-synonymous mutations are significantly more frequent than their silent mutations, adjusting for the heterogeneous mutation rates across genomic locations, subjects and mutation types. Typical tumor WES studies (∼100-300 tumor samples) lack statistical power, and thus can identify only small numbers of candidate driver genes and possibly miss the well-established ones. The best algorithm to detect driver genes to date is MutSigCV. For each target gene, MutSigCV identifies its “bagel”, a set of genes predicted to have similar background mutation rates to the target gene and use the “bagels” to estimate the background mutation rate. Based on the identified “bagels”, we developed a novel statistical method implementing a series of algorithms to improve the statistical power while maintaining the type-I error rate. First, we developed a statistical framework for testing the selective growth advantage of each mutation type and appropriately integrating evidence of growth advantage across mutation types to achieve robust power. We then extended the algorithm to consider spatial clustering information. This substantially improves the statistical power when non-silent mutations are clustered into a few short regions or nucleotides. We applied this novel method to TCGA melanoma WES including 271 tumor samples. Without modeling spatial clustering information, over 30 candidate driver genes, including BRAF, NRAS, PTEN, TP53, PPP6C and CDKN2A were detected controlling FDR=0.01. Modeling spatial information of somatic mutations detected additional rarely mutated genes, including DISP1 (P=1.3×10-20, involved in cellular proliferation and differentiation that leads to normal development of embryonic structures), IDH1 (P=1.0×10-8, previously identified in relation to gliobalstoma and acute myeloid leukemia), MAP2K1 (P=5×10-18, a member of the mitogen-activated protein kinases that also include BRAF, MEK and other important players in melanoma), INTS8 (P=7.7×10-15, an integrator of small nuclear RNA processing), and STK19 (P=1.2×10-10, encoding a serine/threonine kinase, previously identified in melanoma). Finally, we developed methods to simultaneously analyze multiple cancers to improve the power for genes mutated in more than one cancer type, which will be illustrated by analyzing 12 major cancers in TCGA. Our method will provide an important tool for improving driver gene mutation detection in cancer.
Citation Format: Xing Hua, Teresa Maria Landi, Jianxin Shi. Detecting driver genes based on tumor whole-exome sequencing studies. [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 2372. doi:10.1158/1538-7445.AM2014-2372
Abstract 2384: Time-lapse imaging of response to DNA damage occuring during mitosis
Authors: Miwa Shinji , Yano Shuya , Yamamoto Mako , Hiroshima Yukihiko , Uehara Fuminari , Matsumoto Yasunori , Kimura Hiroaki , Hayashi Katsuhiro , Efimova Elena V. , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: May 2015

Abstract
The DNA damage response protein 53BP1 forming foci when double-stranded breaks occur in DNA. In this study, the response to DNA damage during mitosis was visualized using fluorescent protein-based real-time imaging of 53BP1 linked to GFP (GFP-53BP1) focus formation by the fusion protein in the MiaPaCa2 Tet-On Advanced cell line. The MiaPaCa2Tet-On GFP-53BP1 cells were cultured in 35 mm dishes for 48 h. 53BP1 foci were observed every 30 minutes with the FluoView FV1000 confocal laser microscope (Olympus Corp., Tokyo, Japan). The increased expression of GFP-53BP1 was observed during mitosis in MiaPaCa2Tet-On GFP-53BP1 cells without any treatment Mitotic changes were observed 1.09 ± 0.10 times in each cell during over 24 h. Apoptotic changes were observed in 7.3 ± 3.3% of the cells during the 24 h. During the time-lapse imaging, focus formation of GFP-53BP1 was observed in 11.4 ± 2.1% of the mitotic cells during over 24 h. Non-mitotic cells did not have an increase in GFP-53BP1 focus formation. This study indicates that DNA strand breaks occur during mitosis and can be repaired, at least to some extent.
Citation Format: Shinji Miwa, Shuya Yano, Mako Yamamoto, Yukihiko Hiroshima, Fuminari Uehara, Yasunori Matsumoto, Hiroaki Kimura, Katsuhiro Hayashi, Elena V. Efimova, Hiroyuki Tsuchiya, Robert M. Hoffman. Time-lapse imaging of response to DNA damage occuring during mitosis. [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 2384. doi:10.1158/1538-7445.AM2014-2384
Abstract 2396: Widespread occurrence of extrachromosomal microDNAs in normal and cancerous vertebrate tissues and cell lines
Authors: Dillon Laura , Kumar Pankaj , Shibata Yoshiyuki , Dutta Anindya 
Published: May 2015

Abstract
MicroDNAs are small (&lt;400 base pairs in length) single- or double-stranded extrachromosomal circular DNAs that are derived by excision from tens of thousands of sites within the mammalian genome. Thus far, microDNAs have been detected in several mouse tissues, mouse and human cell lines, and both normal and malignant cells. Here, we examine the properties of microDNAs across ten tissue types (brain, heart, lung, liver, thymus, spleen, kidney, skeletal muscle, testis and sperm) from normal adult mice, chicken cell lines and human cancer cell lines. We observed microDNAs in all tissue types, originating from thousands of unique genomic loci. As was previously described, these microDNAs are small circles (100 to 400 base pairs), possess a high GC content and are enriched in genic regions. Hot spots of microDNA generation were noted across all tissue types and correlate with high gene density and GC content. Previously, we suggested that the release of microDNAs leaves behind microdeletions within the source genomic loci, resulting in somatically mosaic cells. Our results confirm this possibility by demonstrating that microDNAs are universally present across cell and tissue types in vertebrates. Interestingly, we found altered distribution patterns in the human cancer cell lines. In addition, short (2-15 bp) direct repeats that usually flank the genomic loci yielding microDNAs lead us to hypothesize that DNA damage repair pathways may be involved in microDNA generation. A survey of microDNAs in cell lines defective in proteins required for many DNA repair pathways revealed that the homologous recombination and non-homologous end joining pathways are dispensable for microDNA formation. However, deletion of two proteins, MSH3 and AID, resulted in a significant increase of microDNA originating from CpG islands. These observations combined with those in the cancer cell lines suggest that perturbation of normal cellular processes can alter the generation of microDNA.
Citation Format: Laura Dillon, Pankaj Kumar, Yoshiyuki Shibata, Anindya Dutta. Widespread occurrence of extrachromosomal microDNAs in normal and cancerous vertebrate tissues and cell lines. [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 2396. doi:10.1158/1538-7445.AM2014-2396
Abstract 2404: Cumulative dosage effect of TSGs and OGs drives aneuploidy patterns in cancer
Authors: Davoli Teresa , Xu Andrew Wei , Mengwasser Kristen E. , Sack Laura M. , Yoon John C. , Park Peter J. , Elledge Stephen J. 
Published: May 2015

Abstract
Since Boveri's postulates in 1914, aneuploidy has been recognized as a hallmark of human cancer. However, no comprehensive theory exists to explain the patterns of aneuploidy and its role in tumor evolution. Recurrent gains or losses of specific chromosomes have been observed in cancer, but it is not clear whether a recurrent pattern of aneuploidy exists among cancer karyotypes and whether the recurrent patterns just happen to occur more frequently or are specifically selected during tumor evolution.
We have developed the Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method for the prediction of tumor suppressor genes (TSGs) and oncogenes (OGs) through the analysis of the pattern of somatic mutations in cancer (Davoli et al., Cell, 2013). By analyzing &gt;8200 tumor-normal pairs from more than 20 tumor types we provide statistical evidence suggesting that many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. The TUSON Explorer analysis on the entire dataset has identified new potential TSGs such as RASA1, TP53BP1, USP28 and OGs such as PPP2R1A and PPP6C. The TUSON Explorer was also applied to individual tumor types, leading to the identification of new potential tissue-specific drivers.
In addition, we have integrated our prediction of TSGs and OGs with information of copy number alterations. We found that the distribution on chromosome and the potency of TSGs and OGs can predict the frequency of arm-level and chromosome-level deletions and amplification. For example, the density and potency of TSGs strongly positively and negatively correlated with the frequency of arm and chromosome deletion and amplification, respectively (r value=∼0.6, p&lt;10-4). The opposite behavior is seen for the OG density and potency. We find that by combining the TSG, OG and essential gene density and potency in a unified score, we can predict a high fraction of the recurrent arm and chromosome deletions and amplifications (r value= ∼0.8, p&lt;10-9). We propose that it is the decrease or increase in the gene dosage of cancer drivers and essential genes in deletion and amplification to determine the recurrent patterns of aneuploidy selected during tumor evolution. In this view the aneuploidy state of tumor cells, first recognized by Bovery exactly a century ago, represents a driving force during the evolution of human cancer.
Citation Format: Teresa Davoli, Andrew Wei Xu, Kristen E. Mengwasser, Laura M. Sack, John C. Yoon, Peter J. Park, Stephen J. Elledge. Cumulative dosage effect of TSGs and OGs drives aneuploidy patterns in 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 2404. doi:10.1158/1538-7445.AM2014-2404
Abstract 2421: Small molecule inhibitors of DNA glycosylases as potential drugs in cancer therapy
Authors: Dizdaroglu Miral , Jaruga Pawel 
Published: May 2015

Abstract
DNA glycosylases are required to initiate the DNA base excision repair pathway of lesions that are formed by DNA damage. Recently, several DNA glycosylases including NEIL1, OGG1 and NTH1 were identified as potential targets in combination chemotherapeutic strategies for cancer treatment. The potential therapeutic benefit for the inhibition of DNA glycosylases was validated by demonstrating synthetic lethality with drugs that are commonly used to limit DNA replication through dNTP pool depletion. Additionally, NEIL1-associated synthetic lethality has been achieved in combination with Fanconi anemia, group G. In this work, we designed experimental strategies to discover small molecule inhibitors of NEIL1, with subsequent analyses of the specificity of those molecules for other DNA glycosylases. Using NEIL1 as the proof-of-principle DNA glycosylase, we developed a fluorescence-based assay that utilizes incision of site-specifically modified oligodeoxynucleotides to detect enzymatic activity. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of purine-derived lesions. We also applied gas chromatography/isotope-dilution tandem mass spectrometry for the measurement of the effect of preferred small molecule inhibitors on activities of the DNA glycosylases NEIL1, OGG1 and NTH1. The release of modified bases, which are known substrates of these enzymes, was measured in the presence and absence of the inhibitors. These data revealed that several of the purine analogs were general glycosylase inhibitors with one compound being the most effective inhibitor for all three enzymes. However, there were significance differences in inhibition of enzymatic activities among these three DNA glycosylases. Overall, this work forms the foundation for the future discovery of DNA repair inhibitors as drugs in cancer therapy for the entire family of DNA glycosylases.
Citation Format: Miral Dizdaroglu, Pawel Jaruga. Small molecule inhibitors of DNA glycosylases as potential drugs in cancer 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 2421. doi:10.1158/1538-7445.AM2014-2421