bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4252: Regulation of the oncogene ZNF217 by localization in breast cancer
Authors: Messana Matthew J. , Yang Chao , Littlepage Laurie E. 
Published: May 2015

Abstract
Poor prognosis in breast cancer patients occurs when malignant tumors adapt to environmental insults, become resistant to chemotherapy, evade immune surveillance and metastasize to other tissues. Tumors are thought to arise from individual cells with multiple mutations, including amplification of genomic regions that provide a growth advantage. A region on human chromosome 20 called 20q13 is increased in ∼25% of early stage human breast cancers and correlates with poor prognosis in patients. We have studied a novel oncogene ZNF217 within this region. ZNF217 is key in promoting breast cancer: it is not only a prognostic indicator of breast cancer progression in patients who have the worst prognosis but also is itself a drug target and/or a marker of patient response to therapy. We find that ZNF217 protein is expressed most strongly in a small subset of cells within normal mammary epithelium and localizes predominantly in the nucleus of mammary epithelial cells. In contrast, the localization of ZNF217 is heterogeneous in breast tumors, with localization in both the nucleus and cytoplasm. Moreover, a truncated form of the protein localizes exclusively in the cytoplasm. We hypothesize that ZNF217 cytoplasmic localization affects ZNF217 function during cancer progression and can be used to predict poor prognosis in breast cancer patients. Thus, our first aim is to identify the regions of ZNF217 that are required for ZNF217 localization in the nucleus and cytoplasm. Second, we will utilize integrated biological approaches to determine the consequences of mislocalization of ZNF217 on cancer progression. We will determine which regions of ZNF217 are required for oncogenesis by overexpressing ZNF217 truncations in mammary epithelial cells and using these cells in a variety of assays that model steps in cancer progression_assays that have previously shown that ZNF217 promotes cancer progression. If our data shows that the cytoplasmic ZNF217 is implicated in oncogenesis, further studies will be required to identify the mechanisms by which ZNF217 is truncated in cells. Hopefully, this will aid in the development of innovative cancer diagnostics and therapeutics for breast cancer and other cancers.
Citation Format: Matthew J. Messana, Chao Yang, Laurie E. Littlepage. Regulation of the oncogene ZNF217 by localization in breast 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 4252. doi:10.1158/1538-7445.AM2014-4252
Abstract 4254: ESE1 binds to beta catenin and modulates its expression
Authors: Yang Xu-yu , Kim Kui Jin , Shao Hong Jun , Lee Seong-Ho 
Published: May 2015

Abstract
ESE-1 is an epithelium-specific transcription factor that functions in the differentiation of intestinal epithelial cells. ESE-1's structure predicts its interaction with a number of other proteins with various cellular functions. Previously we have shown that tolfenamic acid (TA) could induce nuclear translocation of ESE1 in colorectal cancer cells, and plays a critical role in the activation of apoptosis. Here we show that β-catenin, an important protein regulating cell-cell adhesion and gene transcription, binds and colocalizes with ESE-1 in cell cytoplasm. The binding sites were mapped to carboxy terminus ESE-1, which includes the ETS domain, and N-terminus of β-catenin, which contains several important phosphorylation sites. C-terminus of ESE1 also binds to α-catenin, and ESE1/ β-catenin interaction was abrogated with suppression of either β-catenin or α-catenin in HEK293 cells by si RNA treatment; moreover, suppression of both α-catenin and β-catenin further impaired ESE1/ β-catenin binding. Furthermore, knockdown of endogenous ESE1 significantly decreased β-catenin level in HCT116 cells. Current data support a role of ESE1 in the regulation of β-catenin function in colon cancer.
Citation Format: Xu-yu Yang, Kui Jin Kim, Hong Jun Shao, Seong-Ho Lee. ESE1 binds to beta catenin and modulates its expression. [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 4254. doi:10.1158/1538-7445.AM2014-4254
Abstract 426: Transcriptional regulation of dnmt1 by E2F1 in melanoma progression
Authors: SILVA CAMILA T. DA , Molognoni Fernanda , Melo Fabiana H. M. de , Jasiulionis Miriam Galvonas 
Published: May 2015

Abstract
Melanoma is the most aggressive skin cancer due to its high resistance to currently available therapy. Like other kinds of cancer, melanoma presents changes in DNA methylation and epigenetic machinery such as Dnmt1, however it is still unclear why tumor cells acquire these epigenetic alterations. The aim of this study was to analyze the mechanisms involved in Dnmt1 transcriptional regulation by the transcription factor E2F1 in melanoma progression. The cell model used in this study was previously developed in our laboratory, submitting non-tumorigenic murine melanocytes (melan-a) to successive cycles of anchorage blockade. A linear cell model for melanoma was obtained consisting in pre-malignant (1C and 4C), tumorigenic non-metastatic (4C11-) and metastatic (4C11+) cell lines. Bioinformatics data show the existence of four transcripts for Dnmt1 in mice. The transcripts 1 and 2 have the same promoter, and the transcripts 3 and 4 share a different promoter. Real time PCR showed the absence of transcript 3 in all cell lines analyzed. The transcript 4 was present in all lineages, but no significant change in its expression was observed in any one compared to melan- a melanocytes. Transcripts 1 and 2 are present and their levels are increased in 1C, 4C, 4C11- and 4C11+ compared to melan-a cells. Chromatin immunoprecipitation (ChIP) showed increased binding of E2F1 in Dnmt1 promoter in 1C, 4C, 4C11- and 4C11+ compared to melan-a cells. Interestingly, the intensity of binding was stronger in the first promoter, which regulates transcripts 1 and 2, than in the second promoter, which regulates transcripts 3 and 4. These results show for the first time that E2F1 may have an important role in the transcription regulation of Dnmt1 during melanoma progression. Additionally, we observed the increase in superoxide anion (O2.-) in 1C compared to melan-a cells. Recently published data from our group showed that depleting O2.- with MnTBAP scavenger during melan-a anchorage blockade cycles, the malignant transformation is drastically compromised. Here, we showed that 1C cells treated with MnTBAP do not have Dnmt1 mRNA and protein increase compared to melan-a cells. Furthermore, E2F1 levels seem to be regulated by O2.- in 1C cells, indicating that O2.- can be a possible mediator for E2F1 regulation and Dnmt1 transcriptional regulation in melanoma progression. Together, these data suggest an important role of oxidative stress and epigenetic mechanisms in the first steps of melanoma progression. Supported by FAPESP and CNPq.
Citation Format: CAMILA T. DA SILVA, Fernanda Molognoni, Fabiana H. M. de Melo, Miriam Galvonas Jasiulionis. Transcriptional regulation of dnmt1 by E2F1 in melanoma progression. [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 426. doi:10.1158/1538-7445.AM2014-426
Abstract 4265: The landscape of somatic hypermutation in human cancer
Authors: Chapman Jocelyn S. , Chang Matthew T. , Asthana Saurabh , Lall Kriti , Schultz Nikolaus , Taylor Barry S. 
Published: May 2015

Abstract
Somatic hypermutation is present in the tumor genomes of a subset of human cancers. Nevertheless, the extent as well as the biological and clinical impact of hypermutation in cancer patients is unknown. Moreover, in an age of precision oncology, there is a pressing need to understand the catastrophic mutational burden of sporadically hypermutated tumors to ensure an accurate clinical interpretation of candidate actionable lesions thereby facilitating genomically driven oncology in these patients. To explore these questions, we assembled a curated repository of cancer genome data consisting of the sequenced tumor exomes and whole genomes of 10,852 patients representing 36 tumor types from 90 unique cohorts. Through integrative genomic analyses of mutational and DNA copy number profile data, we identified 395 hypermutated tumors, representing ∼3.6% of all cancers. Of these, 47% of patient tumors possessed somatic hypermutation that could not be explained by an established exogenous mutagen, environmental exposure, or known defect in DNA repair. Our analysis of this unknown class of hypermutated cancers revealed six distinct mutational signatures, which may be associated with specific mechanisms driving hypermutation. From allelic abundance data, the temporal sequence of multiple mutational processes accumulated over the lifespan of a tumor was apparent. Our analyses also revealed that despite a high mutational burden, abnormalities cluster to reveal biologic and therapeutic dependencies. Overall, we exploit big data to explore uncommon cancer phenotypes like somatic hypermutation, bridging the gap between complex mutational landscapes and rational therapeutic choices for molecularly defined cancer patients.
Citation Format: Jocelyn S. Chapman, Matthew T. Chang, Saurabh Asthana, Kriti Lall, Nikolaus Schultz, Barry S. Taylor. The landscape of somatic hypermutation in human 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 4265. doi:10.1158/1538-7445.AM2014-4265
Abstract 4274: High fidelity copy number analysis of formalin-fixed and paraffin-embedded tissues using Affymetrix CytoScan HD chip
Authors: Luo Jian-Hua , Michalopoulos Amantha , Ding Ying , Yu Yan P. 
Published: May 2015

Abstract
Detection of human genome copy number variation (CNV) is one of the most important analyses in diagnosing human malignancies. Genome CNV detection in formalin-fixed and paraffin-embedded (FFPE) tissues remains challenging task. Here, we report that a modified method to analyze CNV in FFPE tissues using Affymetrix Cytoscan HD chips. Our analysis showed a 91% overlap in CNV detection between FFPE and the karyotype analysis on 8 cases of lymphoma samples. The CNV overlap between frozen and the matched FFPE tissues reached 93.8%. When the analyses were restricted to regions containing genes, 87.1% concordance between FFPE and fresh frozen tissues was found. The results suggest that the modified method using Affymetrix Cytoscan HD chip represents a significant improvement over most of the previous methods in terms of accuracy in detecting CNV in FFPE tissues. This FFPE methodology may hold promise for wide application of CNV analysis on clinical samples.
Citation Format: Jian-Hua Luo, Amantha Michalopoulos, Ying Ding, Yan P. Yu. High fidelity copy number analysis of formalin-fixed and paraffin-embedded tissues using Affymetrix CytoScan HD chip. [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 4274. doi:10.1158/1538-7445.AM2014-4274
Abstract 4278: International Cancer Genome Consortium (ICGC)
Authors: Hudson Thomas J. , Jennings Jennifer L. 
Published: May 2015

Abstract
The International Cancer Genome Consortium (ICGC) was established to bring together researchers from around the globe to comprehensively analyze the genomic, transcriptomic, and epigenomic changes in 50 different tumor types or subtypes that are of clinical and societal importance across the globe (International network of cancer genome projects. Nature 464, 993-998 (15 April 2010)).
As of December 2013, the ICGC has received commitments from researchers and funding organizations in Asia, Australia, Europe, North America, and South America for 69 project teams in 17 jurisdictions to study more than 25,000 tumor genomes.
Over 27,552 tumors that meet ICGC requirements for consent have been obtained, and research pathologists have approved over 24,160 samples with project-confirmed diagnosis as meeting ICGC standards.
Processed data is available via the Data Coordination Centre (http://dcc.icgc.org) based at the Ontario Institute for Cancer Research and is updated bimonthly. The latest data release (Version 14) in September 2013 includes datasets from 8532 donors participating in 41 ICGC project teams. The ICGC Data Portal has been improved to provide enhanced support to the research community browsing this vast dataset.
ICGC researchers plan to undertake a suite of studies called the Pan-Cancer Analysis Project (PCAP). The analyses will begin in early 2014 using whole genome sequencing (WGS) datasets from approximately 2,000 matched tumour-normal specimen pairs representing more than a dozen different tumour types. It is expected that this effort will lead to the identification of driver mutations outside coding regions including those that affect cis-regulatory regions and non-coding RNAs, and identification of gene regulatory pathways altered by non-coding mutations. Because the projected size of the pan-cancer dataset, i.e. 4,000 WGS, is very large, PCAP will need to use a compute cloud environment (involving multiple computing centers in the USA, Europe, and Asia) that will meet technical requirements of the project and the bioethical framework of ICGC and its member projects.
More information can be found on www.icgc.org.
Citation Format: Thomas J. Hudson, Jennifer L. Jennings. International Cancer Genome Consortium (ICGC). [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 4278. doi:10.1158/1538-7445.AM2014-4278
Abstract 4291: A novel image-based cytometry method for autophagy detection in living cells
Authors: Chan Leo Li-Ying , Shen Dee , Wilkinson Alisha R. , Patton Wayne , Lai Ning , Chan Eric , Kuksin Dmitry , Lin Bo , Qiu Jean 
Published: May 2015

Abstract
Autophagy is an important cellular catabolic process that plays a variety of important roles, including maintenance of the amino acid pool during starvation, recycling of damaged proteins and organelles, and clearance of intracellular microbes. Currently employed autophagy detection methods include fluorescence microscopy, biochemical measurement, SDS-PAGE, and Western blotting, but they are time-consuming, labor-intensive, and require much experience for accurate interpretation. More recently, development of novel fluorescent probes have allowed the investigation of autophagy via standard flow cytometry. However, flow cytometers remain relatively expensive and require a considerable amount of maintenance. Previously, image-based cytometry has been shown to perform automated fluorescence-based cellular analysis comparable to flow cytometry. In this study, we developed a novel method using the Cellometer image-based cytometer in combination with Cyto-ID® Green dye for autophagy detection in live cells. The method is compared to flow cytometry by measuring macroautophagy in nutrient-starved Jurkat cells. Results demonstrate similar trends of autophagic response, but different magnitude of fluorescence signal increases, which may arise from different analysis approaches characteristic of the two instrument platforms. The possibility of using this method for drug discovery applications is also demonstrated through the measurement of dose-response kinetics upon induction of autophagy with rapamycin and tamoxifen. The described image-based cytometry/fluorescent dye method should serve as a useful addition to the current arsenal of techniques available in support of autophagy-based drug discovery relating to various pathological disorders.
Citation Format: Leo Li-Ying Chan, Dee Shen, Alisha R. Wilkinson, Wayne Patton, Ning Lai, Eric Chan, Dmitry Kuksin, Bo Lin, Jean Qiu. A novel image-based cytometry method for autophagy detection in living cells. [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 4291. doi:10.1158/1538-7445.AM2014-4291
Abstract 4313: Efficacy of fluorescence-guided surgery on primary human osteosarcoma
Authors: Miwa Shinji , Hiroshima Yukihiko , Yano Shuya , Matsumoto Yasunori , Uehara Fuminari , Yamamoto Mako , Kimura Hiroaki , Hayashi Katsuhiro , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: May 2015

Abstract
We investigated the effectiveness of fluorescence-guided surgery (FGS) to improve outcomes in an orthotopic mouse model of human osteosarcoma. 143B-RFP human osteosarcoma cells were injected into the intramedullary cavity of the tibia in 32 nude mice. Two weeks after the implantation, 16 mice underwent FGS, and the other 16 mice underwent bright-light surgery (BLS). Half of the BLS and FGS mice (8 mice in each group) underwent adjuvant chemotherapy with cisplatin. Weekly imaging of the mice was performed and RFP-expressing areas were recorded. The fluorescent area of residual tumor after BLS and FGS were 10.2 ± 2.4 mm2 and 0.1 ± 0.1 mm2, respectively (P &lt; 0.001). The residual tumor grew after BLS and BLS+CDDP. In contrast, the FGS mice and the FGS+CDDP mice had almost no tumor growth. Disease-free survival (DFS) in the BLS-, the BLS+CDDP-, the FGS-, and the FGS+CDDP-treated mice was 12.5%, 37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had significantly higher DFS rate than the BLS-treated mice (P = 0.021), and the FGS+CDDP-treated mice had significantly higher DFS rate than the BLS+CDDP-treated mice (P = 0.043). Although chemotherapy significantly reduced multiple metastases (P = 0.033), there was no significant correlation between FGS and lung metastasis. Our study showed that FGS significantly reduced the recurrence of the tumor, but did not reduce lung metastasis. To reduce tumor recurrence and multiple metastases, the combination of FGS and chemotherapy may be necessary in the clinic.
Citation Format: Shinji Miwa, Yukihiko Hiroshima, Shuya Yano, Yasunori Matsumoto, Fuminari Uehara, Mako Yamamoto, Hiroaki Kimura, Katsuhiro Hayashi, Hiroyuki Tsuchiya, Robert M. Hoffman. Efficacy of fluorescence-guided surgery on primary human osteosarcoma. [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 4313. doi:10.1158/1538-7445.AM2014-4313
Abstract 4331: Lowering glucose increases nutlin-3 toxicity against melanomas irrespective of BRAF,NRAS or p53 mutations
Authors: Rieber Manuel , Chavez-Perez Valery , Strasberg-Rieber Mary 
Published: May 2015

Abstract
BACKGROUND: Melanomas are commonly characterized by mutually exclusive BRAF V600Emutations (∼60%) or NRASQ61 mutations (∼15%). Although targeted therapy with vemurafenib is initially efficient in melanoma with BRAF mutations, tumor recurrence occurs including emergence of resistant melanoma cells with secondary N-RASQ61K mutations. Recently it was demonstrated that nutlin-3, an HDM2 antagonist capable of restoring p53 tumor suppressor function synergized with vemurafenib against BRAF V600E wt p53 melanomas. Although nutlin-3 was initially believed to be non-genotoxic, it can originate p53 mutations which are infrequent in primary melanomas.
OBJECTIVES: Since tumor growth increases metabolic demand and glucose consumption, we investigated whether lowering glucose with glycolytic inhibitors increases nutlin-3 toxicity against melanomas irrespective of BRAF, NRAS or p53 status. EXPERIMENTAL: Metabolic activity/proliferation of melanoma cells harbouring BRAF, NRAS or p53 mutations was quantitated by fluorometric studies, crystal violet staining was used to determine differential cell survival, and mechanisms of cell death were studied by protein array immune blotting.
RESULTS: Restricting glucose increases nutlin-3 toxicity against wt p53 melanoma cells harbouring BRAF or NRAS, even if the latter have p53 mutations. Responses occur through mechanisms dependent and independent of p53 serine 15-phosphorylation and p21/CIP1/CDNK1A.
CONCLUSION: Elimination of melanoma cells irrespective of their BRAF, NRAS or p53 mutational status may be helped by joint use of glucose-lowering agents together with nutlin-3.
Citation Format: Manuel Rieber, Valery Chavez-Perez, Mary Strasberg-Rieber. Lowering glucose increases nutlin-3 toxicity against melanomas irrespective of BRAF,NRAS or p53 mutations. [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 4331. doi:10.1158/1538-7445.AM2014-4331
Abstract 4363: Macrophage migration inhibitory factor (MIF) and miR-301b interactively enhance disease aggressiveness by targeting NR3C2 in human pancreatic cancer
Authors: Yang Shouhui , He Peijun , Wang Jian , Schetter Aaron , Funamizu Naotake , Yanaga Katsuhiko , Gaedcke Jochen , Ghadimi B. Michael , Gaida Matthias M. , Ried Thomas , Hanna Nader , Alexander H. Richard , Hussain S. Perwez 
Published: May 2015

Abstract
MIF is a pleiotropic cytokine, which plays a role in inflammatory and immune responses and is implicated in tumorigenesis. Our previous study showed that MIF enhances tumor aggressiveness and predicts outcome in patients with pancreatic ductal adenocarcinoma (PDAC). Aberrant microRNA (miRNA) expression is a common feature in cancer and cytokine responsive miRNAs are recently described as critical effectors in tumor progression. We have investigated MIF-associated miRNAs and their interactive roles in the progression of human pancreatic cancer. Global analysis of miRNA expression revealed 38 differentially expressed miRNAs in MIF-high as compared with MIF-low cases of PDAC based on the median value. Kaplan-Meier survival analysis showed that a higher expression of miR-301b in tumors was associated with poorer survival (p=0.008, N=37), which was further validated in an independent cohort of PDAC patients (p=0.021, N=42). Additionally, MIF expression positively correlated with miR-301b and mediated its expression in several human pancreatic cancer cells. Mechanistic analysis revealed that miR-301b promotes pancreatic cancer cell migration and invasion. Furthermore, nuclear receptor subfamily group c member 2 (NR3C2) was identified as a functional target of miR-301b. NR3C2 inhibited tumor migration and invasion and a higher expression of NR3C2 predicted better survival in pancreatic cancer patients. Further in vivo studies showed a significant decrease in NR3C2 in MIF-overexpressing orthotopic xenograft as compared to control. Taken together, our results demonstrate that MIF and miR-301b interactively contribute to pancreatic cancer progression by targeting NR3C2. This novel MIF-miR-301b-NR3C2 axis may provide potential targets for improving disease outcome in pancreatic cancer.
Citation Format: Shouhui Yang, Peijun He, Jian Wang, Aaron Schetter, Naotake Funamizu, Katsuhiko Yanaga, Jochen Gaedcke, B. Michael Ghadimi, Matthias M. Gaida, Thomas Ried, Nader Hanna, H. Richard Alexander, S. Perwez Hussain. Macrophage migration inhibitory factor (MIF) and miR-301b interactively enhance disease aggressiveness by targeting NR3C2 in human pancreatic 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 4363. doi:10.1158/1538-7445.AM2014-4363