bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3148: Mapping mobile DNAs in human cancer cell lines.
Authors: Zampella John G. , Yang Wan Rho , Rodric Nemanja , Huang Cheng Ran Lisa , Welch Jane , Gnanakkan Veena P. , Cornish Toby C. , Boeke Jef D. , Burns Kathleen H. 
Published: August 2014

Abstract
Genomic instability represented by genetic and epigenetic changes is a hallmark of oncogenesis and tumor progression. The study of genomic instability using conventional methods has necessarily been restricted to regions of unique DNA and excludes repetitive DNA sequences. Repeat elements derived from mobile DNAs comprise a large portion of the human genome and are known sources of genetic variation in humans. Active transposable elements (TE) have recently been shown to cause genetic heterogeneity in tumors through somatic insertions. The functional impact of inherited and somatically acquired TE in cancer development and progression remains unproven. To begin to understand the roles of these mobile DNA elements in transformed cells, we used a novel genomic method to map TEs in a panel of well-characterized human cancer cell lines. Using transposon insertion profiling (TIP)-chip we discover transposition competent families of L1 and Alu TEs. This technique recovered many known reference and polymorphic insertions, novel polymorphisms shared by unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. Insertions were discovered in several important oncogenes such as KRAS, ALK and BRAF. Most insertions discovered were intronic or intergenic, however 16 TEs were putative exonic. Analysis of the novel and polymorphic insertions revealed a relative enrichment of L1 and Alu insertions in cancer gene loci that are mutated in human cancers or implicated in tumor development in forward genetic screens (p=7.74e-10). We also report associations of individual insertion sites with cellular phenotypes, including DNA methylation status, RNA and protein expression, and drug sensitivities. Epigenetic, gene expression and gene pathway associations were evaluated to delineate local (cis) from pathway (trans) effects. We identified several examples of cis effects of TEs on gene structure as well as nearly 250 curated proliferation pathways affected by a TE insertion. These data suggest that TE insertions may function locally to alter genomic structure or act more globally in concert with other genetic mechanisms to promote the development and progression of several common tumor types.
Citation Format: John G. Zampella, Wan Rho Yang, Nemanja Rodric, Cheng Ran Lisa Huang, Jane Welch, Veena P. Gnanakkan, Toby C. Cornish, Jef D. Boeke, Kathleen H. Burns. Mapping mobile DNAs in human cancer cell lines. [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 3148. doi:10.1158/1538-7445.AM2013-3148
Abstract 3149: Genetic alteration of lung adenocarcinomas with micropapillary component.
Authors: Furukawa Masashi , Toyooka Shinichi , Yamamoto Hiromasa , Tada Ryuhei , Hashida Shinsuke , Shien Kazuhiko , Soh Junichi , Asano Hiroaki , Tsukuda Kazunori , Ouchida Mamoru , Ichimura Kouichi , Miyoshi Shinichiro 
Published: August 2014

Abstract
Purpose: Adenocarcinoma with micropapillary component (AMPC) is known as one of aggressive subtypes among lung adenocarcinoma. The molecular profiles of AMPC have not been well characterized from the view point of difference from other adenocarcinomas. In this study, we analyzed molecular alterations of AMPC to investigate its molecular pathogenesis. Methods: We reviewed pathological reports of patients who underwent surgical resection for lung cancers between April 2004 and May 2012. Twenty-eight patients were recorded to possess micropapillary component among 674 patients diagnosed as lung adenocarcinoma. A total of 52 resected lung adenocarcinomas without micropapillary component were selected in the same period so as to adjust age, sex, and smoking status to those of the patients with micropapillary component. Mutational status was determined by the following two methods: SNaPshot assay based on multiplex PCR, primer extension, and capillary electrophoresis that was designed to assess for 38 somatic mutations in eight genes (AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3CA, and PTEN), and a PCR-based sizing assay that assesses for EGFR exon 19 deletions, EGFR exon 20 insertions, and HER2 exon 20 insertions. EML4-ALK fusion was screened by ALK immunohistochemistry and confirmed using reverse transcriptional PCR assay and break-apart FISH assay.Results: As for genetic alterations, 13 (46.4%) of 28 lung adenocarcinomas with micropapillary component harbored mutually exclusive mutations: 9 (32.1%) EGFR mutation, 1 (3.3%) KRAS mutation and 3 (9.9%) EML4-ALK fusion. Adenocarcinomas without micropapillary component harbored 11 (21.2%) EGFR mutations and 8 (15.3%) KRAS mutations in a mutually exclusive manner, but had no EML4-ALK fusion genes. There were no mutations in AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3CA, PTEN and HER2 genes in the both groups. EML4-ALK fusions appeared to occur significantly more frequent in AMPC than in control cases (P = 0.039).Conclusion: Although the size of our study was small, our study suggests the molecular pathogenesis of AMPC may be different from other adenocarcinoma, associated with its unique character among lung adenocarcinomas.
Citation Format: Masashi Furukawa, Shinichi Toyooka, Hiromasa Yamamoto, Ryuhei Tada, Shinsuke Hashida, Kazuhiko Shien, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Mamoru Ouchida, Kouichi Ichimura, Shinichiro Miyoshi. Genetic alteration of lung adenocarcinomas with micropapillary component. [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 3149. doi:10.1158/1538-7445.AM2013-3149
Abstract 3167: Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations.
Authors: Lorber Thomas , Dietsche Tanja , Gsponer Joël , Rufle Alexander , Barret Michael , Sommer Lukas , Glatz Katharina , Ruiz Christian , Bubendorf Lukas 
Published: August 2014

Abstract
1) Background
Melanoma is a heterogeneous disease and even though consistent genetic patterns among different subtypes have been revealed, clinical trials have failed to significantly improve survival. However, most of the genomic studies do not take into consideration the underlying genomic heterogeneity. In this study, we used genomic profiling of sorted clonal tumor populations in order to investigate the genomic heterogeneity and the clonal evolution in malignant melanoma.
2) Methods
Multiple biopsies from melanoma patients were subjected to flow-sorting based on DNA content. The tumor specific marker SOX10 was used as an additional parameter to exclude contribution of normal tissue. Resulting clonal tumor populations were genomically characterized by usage of high resolution aCGH. A TMA was constructed for validation of the findings.
3) Results
DNA content based flow sorting of small human melanoma biopsies was successfully implemented and revealed the co-existence of distinct clonal populations (diploid as well as aneuploid) within these samples. The use of the additional marker SOX10 allowed us to uncover and sort pure diploid tumor populations from diploid fractions admixed with normal cells. These findings were confirmed by aCGH.
4) Conclusions
Human malignant melanoma is composed of different clonal populations with population-specific genomic aberrations. The use of SOX10 allowed unraveling of pure tumor populations within the diploid peaks, which would have been obscured by the use of DNA content alone. Further genomic analyses of these sorted clonal tumor populations are fundamental for the understanding of the genomic heterogeneity and its potential impact on metastasis and therapy response in malignant melanoma.
Citation Format: Thomas Lorber, Tanja Dietsche, Joël Gsponer, Alexander Rufle, Michael Barret, Lukas Sommer, Katharina Glatz, Christian Ruiz, Lukas Bubendorf. Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations. [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 3167. doi:10.1158/1538-7445.AM2013-3167
Abstract 3180: In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner.
Authors: Saginc Gaye , Ukil Leena , Woo Xingyi , Menghi Francesca , Bertrand Denis , Lee Charlie Wah Heng , Inaki Koichiro , Liu Edison Tak Bun 
Published: August 2014

Abstract
The molecular complexity of cancer still remains as the limiting factor for developing efficient therapies with minimal side effects. However, scientists succeeded in determining common alterations in most human cancer types. Each of these alterations results from disruption of an anti-cancer regulation mechanism and/or activation of cancer-promoting networks by genetic and epigenetic changes. As a consequence, cancer cells become capable of mimicking stem cells’ ability to proliferate indefinitely while maintaining their cellular identity, or to self-renew, which is crucial for any type of stem cell. Indeed, some of the networks which are deregulated in cancer normally regulate self-renewal in stem cells. However, self-renewal is tightly regulated in stem cells, while cancer cells manage to escape the internal and external regulation mechanisms. Hence, cancer cells differ from stem cells by displaying disruptions in feedback mechanism controlling the rate of cell division, aberrant differentiation programs and error-prone replication, so they become invasive and even metastatic. We hypothesize that the stemness regulatory “cassette” that serves limitless replicative potential and undifferentiated state is a measure of cancer virulence and progression. We believe that this gene cassette is established through different mechanisms in each cell type, so it can be separated from invasion and instability in a precise and defined manner. To test our hypotheses, we set up a system reconstruction model consisting of induced pluripotent cells and transformed cells as stem and cancer cell models respectively, and their source of primary mouse embryonic fibroblast cells. From this model system, we created a system's map for transformation using differential expression patterns from whole genome expression arrays. We discovered gene networks that are common between stem and cancer cells, but different from their primary cells of origin. We also found deregulated/activated cassettes which are unique for cancer cells and which are hardwired by genomic rearrangements (copy number and structural variations) identified by DNA paired end tag (DNA-PET) sequencing and single nucleotide variations using RNA sequencing. We are now investigating the role of candidate genes selected from this analysis in cancer and stem cell maintenance through a high content siRNA screening.
Citation Format: Gaye Saginc, Leena Ukil, Xingyi Woo, Francesca Menghi, Denis Bertrand, Charlie Wah Heng Lee, Koichiro Inaki, Edison Tak Bun Liu. In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner. [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 3180. doi:10.1158/1538-7445.AM2013-3180
Abstract 3193: NPV-LDE-225 (Erismodegib) inhibits human prostate cancer stem cell growth in NOD/SCID IL2Rγ null mice by regulating Bmi-1 and microRNA-128.
Authors: Nanta Rajesh , Shankar Sharmila , Srivastava Rakesh K. 
Published: August 2014

Abstract
Prostate cancer stem cells (CSCs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. It is now clear that CSCs are involved in tumor growth and recurrence, and resistance to conventional treatments. Thus, the strategy that suppresses stemness and consequently tumorigenic potential of CSCs could be considered for the management of prostate cancer. The objectives of this study were to examine the molecular mechanisms by which NPV-LDE-225 / Erismodegib (smoothened inhibitor) regulates stem cell characteristics in prostate cancer. Effects of NPV-LDE-225 on CSC's viability, sphere formation, apoptosis, transcriptional activity, and epithelial-mesenchymal transition (EMT) were measured. NPV-LDE-225 inhibited cell viability and spheroid formation, and induced apoptosis by activation of caspase-3 and cleavage of PARP. NPV-LDE-225 induced expression of Bax and Bak, and inhibited the expression of Bcl-2, Bcl-XL, XIAP, cIAP1, cIAP2 and survivin. NPV-LDE-225 inhibited Gli transcriptional activity, Gli-DNA interaction, and the expression of Gli1, Gli2, Patched1 and Patched 2 in prostate CSCs. Interestingly, NPV-LDE-225 induced PDCD4 and apoptosis and inhibited cell viability by suppressing miR-21. Furthermore, NPV-LDE-225 inhibited pluripotency maintaining factors Nanog, Oct4, cMyc and Sox-2. The inhibition of Bmi-1 by NPV-LDE-225 was regulated by up-regulation of miR-128. NPV-LDE-225 suppressed EMT by up-regulating E-cadherin and inhibiting N-cadherin, Snail, Slug and Zeb1 through regulating miR-200 family. Finally, NPV-LDE-225 inhibited CSC tumor growth which was associated with the suppression of Gli1, Gli2, Patched-1, Patched-2, Cyclin D1 and PCNA, and cleaved caspase-3 and PARP in tumor tissues derived from NOD/SCID IL2Rγ null mice. Overall, our findings suggest that inhibition of the Shh signaling pathway in CSCs is a potential therapeutic strategy for prostate cancer.
Citation Format: Rajesh Nanta, Sharmila Shankar, Rakesh K. Srivastava. NPV-LDE-225 (Erismodegib) inhibits human prostate cancer stem cell growth in NOD/SCID IL2Rγ null mice by regulating Bmi-1 and microRNA-128. [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 3193. doi:10.1158/1538-7445.AM2013-3193
Abstract 3198: The RNA-binding protein Musashi-1 stabilizes TAC1 mRNA in breast cancer cells.
Authors: Nahas George R. , Murthy Raghav G. , Greco Steven J. , Rameshwar Pranela 
Published: August 2014

Abstract
Breast cancer (BC) remains a major public health challenge in the United States. Prognosis for metastatic cancer is poor with nearly all deaths from BC due to metastatic disease. Upon discovery in bone, the five year survival rate of BC patients is approximately eight percent. The tachykinin gene, TAC1, has been implicated in facilitating metastasis of BC to the bone marrow. The predominant product of TAC1 is the neuropeptide, substance P (SP). We have previously demonstrated that in non-malignant cells, TAC1 translation is suppressed by miRNAs. Stimulation with specific cytokines decreased these miRNA to allow synthesis of SP. BC cells (BCCs) lack endogenous expression of the TAC1-specific miRNA, which is consistent with the increased levels of SP in these cells. Herein the present study investigated the translational control of TAC1 mRNA in BCCs. Cytoplasmic extracts from BCCs showed an increase in TAC1 translation and stabilization of its mRNA. These findings led us to bioinformatic analyses of the secondary structure of TAC1 mRNA, which predicted candidate interacting sites in Exons 3 and 7. These predictions were further refined by results from an RNA shift assay that indicated an RNA-binding protein specifically targeting Exon 7. Through western blots and proteomic analysis we identified the RNA-binding protein, Musashi-1 (Msi1), as a putative candidate. Identity was confirmed by RNA supershift assay utilizing an antibody specific for Msi1. Gain-of-function and reporter gene assays utilizing the Msi1 expression vector co-transfected with a luciferase reporter gene linked to the 3′UTR of TAC1, including Exon 7, confirmed a stabilizing role for Msi1 in TAC1 mRNA regulation, concomitant with an increase in substance P. In summary, we identified Msi1 as a novel binding protein for the oncogenic TAC1 mRNA. These findings have implications for the identification of novel targets to treat BC.
Citation Format: George R. Nahas, Raghav G. Murthy, Steven J. Greco, Pranela Rameshwar. The RNA-binding protein Musashi-1 stabilizes TAC1 mRNA in 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 3198. doi:10.1158/1538-7445.AM2013-3198
Abstract 3201: PTBP1 stability is increased in ovarian and breast cancer cell lines compared to matched controls.
Authors: Arslan Ahmet Dirim , Asztalos Szilard , Stampfer Martha , Tonetti Debra , He Xiaolong , Beck William T. 
Published: August 2014

Abstract
PTBP1 (polypyrimidine tract-binding) protein is a splicing factor that is frequently upregulated in ovarian and breast tumors. Knockdown (KD) of PTBP1 expression by shRNA impairs ovarian tumor cell growth in vivo and in vitro, as well as colony formation and invasiveness in vitro (He et al, Oncogene 26:4961-8, 2007). We have also found that PTBP1 is progressively upregulated in immortalized human mammary epithelial cells (HMECs) and human ovarian surface epithelial (HOSE) cells, correlating with their transformation state. These results prompted us to determine the factors that play a role in the upregulation of PTBP1 protein expression. We first asked whether the increased PTBP1 protein in human ovarian and breast cell lines is accompanied by proportional increases of PTBP1 mRNA. We found that there was a discordance between PTBP1 mRNA and protein levels, as measured by RT-PCR and western blot, in these cancer cell lines in relation to the control cells (finite lifespan HMEC or HOSE, respectively). Accordingly, we attempted to understand the basis for this discrepancy, and measured PTBP1 protein half-life. We treated A2780 (ovarian cancer), MCF7 (breast cancer) cells, and “finite lifespan” HMEC (184A1) with cycloheximide to terminate protein synthesis and followed the fate of PTBP1 protein over time by western blot. We found that the half-life of PTBP1 protein is ∼3-5 h in the HMECs with finite lifespan, whereas it ranges from ∼9-12h in human epithelial ovarian and breast cancer cells. These results demonstrate that PTBP1 expression is regulated in part by events that control the stability of the protein and suggest that the normal regulation of PTBP1 protein turnover is altered in cancer cell lines. Bioinformatics analysis identified one possible SUMO-binding motif site within the PTBP1 protein (SUMOsp 2.0 - SUMOylation Site Prediction, http://sumosp.biocuckoo.org/), suggesting that SUMOylation may play a role in PTBP1 stability; we are currently examining this possibility. Findings presented herein will enhance our understanding of the regulation of PTBP1 expression and the mechanisms underlying its variation in protein and mRNA levels in ovarian and breast tumors.
(Support in part by NCI grants R01 CA40570 and R01 CA138762 [to WTB], by OCRF [to XH], and by UIC.)
Citation Format: Ahmet Dirim Arslan, Szilard Asztalos, Martha Stampfer, Debra Tonetti, Xiaolong He, William T. Beck. PTBP1 stability is increased in ovarian and breast cancer cell lines compared to matched controls. [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 3201. doi:10.1158/1538-7445.AM2013-3201
Abstract 3207: Application of an antibody-free, highly sensitive PRISM-SRM proteomics approach for monitoring low abundance proteins and protein isoforms in cell lines and tumor tissue.
Authors: He Jintang , Sun Xuefei , Shi Tujin , Schepmoes Athena , Fillmore Thomas , Petyuk Vladislav , Xie Fang , Gritsenko Marina , Yang Feng , Kitabayashi Naoki , Chae Sung Suk , Rubin Mark , Siddiqui Javed , Wei John , Chinnaiyan Arul , Qian Wei-Jun , Smith Richard , Kagan Jacob , Srivastava Sudhir , Liu Tao , Rodland Karin , Camp David 
Published: August 2014

Abstract
Stable-isotope dilution coupled to targeted mass spectrometry, applying selected reaction monitoring (SRM), provides good selectivity, reproducibility, and sensitivity rendering it highly suitable for robust and high-throughput protein quantification. Historically, SRM sensitivity for measuring protein concentration in biofluids such as blood plasma has been limited to the low μg/mL level. Application of front-end sample preparation methods such as immunoaffinity depletion and strong cation exchange (SCX) chromatographic fractionation has improved the SRM detection limit to low ng/mL level. The ability to detect and quantify low abundance proteins present in blood plasma/serum at sub-ng/mL levels, however, relies on the availability of specific affinity reagents (e.g., antibodies that have the associated disadvantage of an expensive, lengthy, and high failure rate de novo process).
To address this limitation, we have recently developed an antibody-free, targeted quantification capability that enables protein quantification of prostate-specific antigen and other exogenous proteins at 50-100 pg/mL levels in plasma/serum. Unlike the traditional SCX fractionation approach where all resulting fractions are analyzed by the second dimension LC-SRM, this new capability, PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing), uses high resolution.
Citation Format: Jintang He, Xuefei Sun, Tujin Shi, Athena Schepmoes, Thomas Fillmore, Vladislav Petyuk, Fang Xie, Marina Gritsenko, Feng Yang, Naoki Kitabayashi, Sung Suk Chae, Mark Rubin, Javed Siddiqui, John Wei, Arul Chinnaiyan, Wei-Jun Qian, Richard Smith, Jacob Kagan, Sudhir Srivastava, Tao Liu, Karin Rodland, David Camp. Application of an antibody-free, highly sensitive PRISM-SRM proteomics approach for monitoring low abundance proteins and protein isoforms in cell lines and tumor tissue. [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 3207. doi:10.1158/1538-7445.AM2013-3207