bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3011: The role of peroxidasin in human prostate cancer.
Authors: Woods Keith 
Published: August 2014

Abstract
Peroxidasin is a peroxidase associated with kidney disease and its function is not totally known. Peroxidasin was identified first in the common fruit fly, or Drosophilia, where its function has not been identified, but is expressed in different stages of development. When peroxidasin was identified in the human system, it was found in colon cancer cell lines as the product of a p-53 response gene. It was originally called melanoma gene 50 because it was speculated to be a potent-melanoma associated antigen. In previous studies, we have found using real-time PCR array, that peroxidasin is up regulated 300-fold in ARCaP prostate cancer cell line overexpressing Snail transcription factor. Snail is the transcriptional factor that is involved in Epithelial-Mesenchymal Transition, or EMT, which is associated with increased migration and metastasis. Snail down-regulates cell-cell association genes like E-cadherin and up-regulates mesenchymal genes like vimentin. We hypothesized that the enzyme, peroxidasin, will be one of the causes for increased cellular migration and increased tumor progression in aggressive prostate cancer. By using Western Blot, immunofluorescence and immunohistochemical analyses, peroxidasin presence was examined in normal prostate epithelial tissue, prostate cancer patient tissue, non-metastatic and metastatic prostate cancer cell lines. We also utilized LNCaP and ARCaP prostate cancer cell lines that were modified to over-express Snail to better ascertain the regulation of peroxidasin by Snail in these cell lines. So far, we have found that peroxidasin is increased in prostate cancer patient tissue as compared to normal epithelial tissue. Peroxidasin is also expressed at varying levels in prostate cancer cell lines. LNCaP and ARCaP Snail-transfected cells also expressed more peroxidasin as compared to empty vector Neo control cells. Migration, invasion, and adhesion assays will be performed to examine the role of peroxidasin in these biological pathways. Based on the results, future studies will focus on the migration of prostate cancer cells towards nerve cells and if peroxidasin presence is significant to this process. Overall, we have shown that peroxidasin is highly expressed in prostate cancer and its expression is mediated by Snail transcription factor.
Supported by grants P20MD002285-01 & G12RR003062-22.
Citation Format: Keith Woods. The role of peroxidasin in human prostate cancer. [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 3011. doi:10.1158/1538-7445.AM2013-3011
Abstract 3018: Identification of genes up-and down-regulated by dermcidin in G-361 malignant melanoma cell line.
Authors: Belizario Jose E. , Perez Marcela 
Published: August 2014

Abstract
Dermcidin (DCD) is a human gene mapped to chromosome 12q13 region, only identified in primates and humans, and normally expressed in the eccrine glands of skin and brain. Several studies have confirmed DCD-derived peptides contribute to innate and immune surveillance and in the oncogenic processes of breast, prostate and skin cancers, as revealed by its role as a growth factor and cell survival. We have further explored DCD function and its tumorigenic potential on skin melanocytes by specifically knocking down its expression in G-361 malignant melanoma cells via expressing constitutively short hairpin RNA against DCD mRNA. Biological and biochemical assays showed that the "knockdown" in the expression of DCD in two cell clones decreased significantly the in vitro growth in cell culture and tumor formation in nude mice. Similar results were obtained treating nude mice bearing G-361 melanoma xenografts with rabbit polyclonal antibodies against DCD protein (1 mg/Kg, i.p., once week, and one month). Here, we present a summary of a DNA microarray-based study that identified the genes that are up- and down-regulated in a G-361 pLKO control clone and a clone expressing constitutively short hairpin RNA against DCD mRNA. A total of 213 genes were differentially and repeatedly expressed in the G-361-DCD-RNAi clone IBC-I (&gt;3-fold change and P &lt; 0.005). Relative to pLKO vector control data profiling, 99 genes were up-regulated and 120 genes were down-regulated. Next, we validated various genes by real time-PCR. Systematic functional analysis of the differentially expressed genes using DAVID platform revealed significant enrichment for U1-U5 spliceosomal complex genes (SNORs) required for post-transcriptional processing of rRNA, mRNA and tRNA as well as small nucleolar RNA and non-coding RNAs (ncRNAs). Further studies are on way to prove the functional connections among ncRNAs in DCD-induced the development and progression of melanoma malignancy.
Citation Format: Jose E. Belizario, Marcela Perez. Identification of genes up-and down-regulated by dermcidin in G-361 malignant melanoma cell line. [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 3018. doi:10.1158/1538-7445.AM2013-3018
Abstract 3024: FGFR1 amplification is linked to the squamous cell carcinoma subtype in esophageal carcinoma.
Authors: von Loga Katharina , Kohlhaussen Jule , Marx Andreas H. , Sauter Guido , Grob Tobias , Quaas Alexander 
Published: August 2014

Abstract
Introduction
Stimulation of Fibroblast-growth-factor-receptor-1 (FGFR1) plays an important role in cell differentiation and cell growth. Amplification of the FGFR1 gene was described in various cancer types. Clinical phase I trials are currently performed to address the potential applicability of anti-FGFR1-drugs in squamous cell carcinoma of the lung. Prevalence and clinical significance of FGFR1 amplification are unknown in esophageal carcinoma.
Material and Methods
In this study, six hundred formalin-fixed paraffin-embedded tissue samples from patients with esophageal carcinoma were analysed, including 346 patients with adenocarcinoma and 254 patients with squamous cell carcinoma. Dual-labeling Fluorescence in situ hybridization (FISH) was applied using probes for FGFR1 and centromere 8. The initial analysis was in a tissue microarray (TMA) format. All available tumor blocks from amplified tumors were subsequently analysed for heterogeneity on large sections. When available, lymph node metastases and tumor-adjacent dysplasia were also analysed on large sections from these tumors,
Results
FGFR1 amplification was more frequently seen in squamous cell carcinoma (9.4% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308). High polysomy was found in an additional 5.9% of squamous cell carcinoma and 0.6% of adenocarcinoma. FGFR1 amplification was significantly associated with histologic grade (p=0.02) but was unrelated to tumor type, pT, pN, pM, UICC stage and survival. FGFR1 amplification was homogeneous across the tumor in most cases. FGFR1 heterogeneity was observed in only 3 of 24 cases. FGFR1 amplification was similarly observed in the primary tumor and in 6 cases each of lymph node metastases and dysplasia.
Summary
In conclusion, FGFR1 amplification in squamous cell carcinoma of the esophagus occurs at similar frequencies as in squamous cell carcinoma of the lung. The high homogeneity of FGFR1 in the primary tumor and the lack of discordant results in dysplasia argue for FGFR1 amplification, representing an early alteration in a subgroup of esophageal cancers. The high homogeneity of FGFR1 amplification provides further arguments for FGFR1 representing an interesting drug target in these cancers.
Citation Format: Katharina von Loga, Jule Kohlhaussen, Andreas H. Marx, Guido Sauter, Tobias Grob, Alexander Quaas. FGFR1 amplification is linked to the squamous cell carcinoma subtype in esophageal carcinoma. [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 3024. doi:10.1158/1538-7445.AM2013-3024
Abstract 3026: Targeting aberrantly activated AREG-EGFR signaling in CRTC1-MAML2-positive mucoepidermoid carcinoma.
Authors: Chen Zirong , Gu Yumei , Hu Chengbin , Li Jian-Liang , Lin Shuibin , Shen Huangxuan , Cao Chunxia , Chen Jie , Li Jiancheng , Ha Patick K. , Kaye Federic J. , Griffin James D. , Wu Lizi 
Published: August 2014

Abstract
Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 gene fusion, encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a highly specific genetic alteration in more than 50% of mucoepidermoid carcinoma (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth ad survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and the in vivo. CRTC1-MAML2 induced the up-regulation of the EGFR ligand AREG by co-activating the transcription factor CREB and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with unresectable CRTC1-MAML2-positive MEC.
Citation Format: Zirong Chen, Yumei Gu, Chengbin Hu, Jian-Liang Li, Shuibin Lin, Huangxuan Shen, Chunxia Cao, Jie Chen, Jiancheng Li, Patick K. Ha, Federic J. Kaye, James D. Griffin, Lizi Wu. Targeting aberrantly activated AREG-EGFR signaling in CRTC1-MAML2-positive mucoepidermoid carcinoma. [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 3026. doi:10.1158/1538-7445.AM2013-3026
Abstract 304: Reactive oxygen species induce prostate cancer cells via activation of the IL6/STAT3 pathway.
Authors: Qu Yi , Liu Runhui , Zhang Jigang , Popa Mihaela , Hua Yaping , Lin Biaoyang , McCormack Emmet , Zhang Weidong , Oyan Anne Margrete , Kalland Karl-Henning , Ke Xisong 
Published: August 2014

Abstract
Background: Previously we have established a stepwise prostate carcinogenesis model including human primary prostate epithelial EP156T cells, non-malignant mesenchymal EPT1 cells and pre-malignant EPT2-D5 cells. Aims and methods: To further achieve malignant cells, EPT2-D5 cells were grown in protein-free medium and the tumorigenesis was tested in vivo. Results: 1) Lots of spheres were generated in monolayer culture of D5 cells in protein free medium. The sphere forming cells were named D5HS. 2) Different from EPT2-D5 cells, D5HS formed large subcutaneous tumors (EPT3) and metastasis (EPT3M) in SCID mice. 3) Gene expression profiling showed inflammation signatures in D5HS. 4) Cellular Reactive Oxygen Species Detection Assay (DCFDA) showed high reactive oxygen species (ROS) in D5HS, and ELISA and Western blotting showed high secreted IL6 and high STAT3 expression in D5HS. 5) Blocking of ROS or STAT3 signaling reduced the sphere formation. 6) Immunohistochemistry staining showed high pSTAT3 level in the EPT3 tumor. Conclusions: Reactive oxygen species induce prostate cancer cells via activation of the IL6/STAT3 pathway.
Citation Format: Yi Qu, Runhui Liu, Jigang Zhang, Mihaela Popa, Yaping Hua, Biaoyang Lin, Emmet McCormack, Weidong Zhang, Anne Margrete Oyan, Karl-Henning Kalland, Xisong Ke. Reactive oxygen species induce prostate cancer cells via activation of the IL6/STAT3 pathway. [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 304. doi:10.1158/1538-7445.AM2013-304
Abstract 3047: The PML isoform IV is a negative regulator of nuclear EGFR's transcriptional activity in lung cancer.
Authors: Kuo Hong-Yi , Chen Yi-Chen , Chang Hsiang-Yi , Jeng Jen-Chong , Lin Erh-Hsuan , Pan Chih-Ming , Wang Mong-Lien , Chou Yu-Ting , Shih Hsiu-Ming , Wu Cheng-Wen 
Published: August 2014

Abstract
EGF receptor (EGFR) is a membrane-bound receptor tyrosine kinase which can transduce intracellular signals responsible for cell proliferation. It is frequently overexpressed and/or constitutively activated in non-small cell lung cancer (NSCLC) and thus is considered as a major cause of this disease. Recently, EGFR has been found in the nucleus where the nuclear EGFR (nEGFR) can function as a transcription factor activating the transcription of genes such as cyclin D1 gene (CCND1) which is essential for cell proliferation. Nevertheless, how nEGFR's transcriptional activity is regulated remains unclear. Promyelocytic leukemia protein (PML) is a tumor suppressor which is lost in various cancers including lung cancer. However, the role of PML in the suppression of lung cancer growth is still unclear. When we investigated the role of PML in the regulation of lung cancer cell growth, we found that PML isoform IV (PMLIV) preferentially represses the growth of lung cancer cells bearing constitutively active EGFR. Besides, when growing in the EGFR activating conditions, the growth of EGFR wild-type bearing A549 cells has been repressed by PMIV overexpression. We also found that PMLIV has protein-protein interactions with nEGFR and represses the transcription of nEGFR target genes. We showed that PMLIV is recruited by nEGFR to the target promoters and reduces the promoter histone acetylation level via HDAC1. Together, our results suggest that PMLIV interacts with nEGFR upon EGFR activation and represses the transcription of nEGFR target genes such as CCND1 and thus leading to inhibition of the lung cancer cell growth.
Citation Format: Hong-Yi Kuo, Yi-Chen Chen, Hsiang-Yi Chang, Jen-Chong Jeng, Erh-Hsuan Lin, Chih-Ming Pan, Mong-Lien Wang, Yu-Ting Chou, Hsiu-Ming Shih, Cheng-Wen Wu. The PML isoform IV is a negative regulator of nuclear EGFR's transcriptional activity in lung cancer. [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 3047. doi:10.1158/1538-7445.AM2013-3047
Abstract 3060: MicroRNA expression profiling in African American and Caucasian prostate cancer.
Authors: Theodore Shaniece , Davis Melissa , Rhim Jhong , Grizzle William , Turner Timothy , Yates Clayton 
Published: August 2014

Abstract
PURPOSE: African American men have almost twice the incidence and death rates related to prostate cancer compared to Caucasian men. Several studies have suggested that some of these differences may be attributed to the elevated expression of different genes. Recently, a new class of genetic regulators has emerged known as microRNAs. Many reports have found microRNAs to be implicated in cell growth, cell differentiation and the onset of many diseases including prostate cancer. We sought to investigate whether microRNAs are differentially expressed in African American and Caucasian prostate samples.
METHODS: We analyzed the expression of over 300 microRNAs in 11 African American and Caucasian cell lines utilizing Affymetrix Microarray Chip. Validations of the most significant miRNAs were done by qRT-PCR. Methylation analysis of miR-152 promoter region was carried out by performing bisulfite modification and DNA sequencing. Characterization of the miRNA was carried out by performing MTT assay, Flow Cytometry, Western Blot, and Imunoflourescence.
RESULTS: We identified 15 microRNAs that were differentially expressed between the African American and Caucasian cell lines. Further validations led to the identification of miR-152 which is significantly expressed among both groups. Bisulfite modification and DNA sequencing revealed that miR-152 is methylated in aggressive prostate cancer cell lines. 5-Aza-2’/TSA treatment restored miR-152 levels in these cell lines. MiR-152 is responsible for inhibiting DNA methyltransferase 1, Rictor and TGF-β. Our results showed that miR-152 reduced cellular proliferation in PC-3, DU-145 and LNCaP prostate cancer cell lines. In addition, miR-152 initiated G2-M cell cycle arrest. Expression of miR-152 in 40 normal-tumor paired prostate tissue samples indicated that its expression was down-regulated in 67% of tumor samples. Analysis of African American and Caucasian prostate normal-tumor paired sample revealed that both normal and tumor prostate samples had lower miR-152 expression in the African American prostate samples compared to the Caucasian prostate samples.
CONCLUSION: These results give evidence that microRNAs may play a role in the advance progression seen in prostate cancer in African Americans. Future studies will focus on validating these results in larger patient sample sizes. Research supported by G12 RR03059-21A1(NIH/RCMI), and CA118623 (NIH/NCI).
Citation Format: Shaniece Theodore, Melissa Davis, Jhong Rhim, William Grizzle, Timothy Turner, Clayton Yates. MicroRNA expression profiling in African American and Caucasian prostate cancer. [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 3060. doi:10.1158/1538-7445.AM2013-3060
Abstract 3064: Epstein-Barr virus encoded BART microRNAs facilitate nasopharyngeal carcinoma development and progression via deregulation of Wnt signaling.
Authors: Wong Alissa Michelle G. , Chen Jinna , Ma Stephanie , Tsang Janice Wing Hang , Guan Xin Yuan 
Published: August 2014

Abstract
Epstein-Barr Virus (EBV) encoded BamHI Rightward Transcript (BART) microRNAs are frequently upregulated in Nasopharyngeal Carcinoma (NPC) specimens as previously reported by our group and also several others. However, very few studies have linked the potential role of these BARTs with commonly deregulated signaling pathways in NPC, particularly Wnt Signaling. Herein, we demonstrate that functional clustering of overexpressed BART microRNA target genes confer high enrichment within the Wnt signaling pathway, whereby BARTs 6-3p, 7, 14, 17-5p and 19-3p appear to extensively target key Wnt inhibitors such as WIF1, GSK3B, APC (forms destruction complex), BTRCP (Ubiquitin mediated proteolysis of B-catenin) and NLK (interfere with B-catenin/TCF/LEF binding). Although these 5 candidate BARTs were able to enhance TCF/LEF activity to induce downstream factors (e.g. CMYC, CCND1, MMP7, OCT4, SLUG), the extent and underlying mechanisms of Wnt activation conferred by these BARTs are not entirely the same. BARTs 17-5p and 19-3p can efficiently activate Wnt signaling marked by significantly enhanced levels of total and active B-catenin via post-translational downregulation of GSK3B, APC, BTRC and NLK. Meanwhile, the more conservative increase in active B-catenin and TCF/LEF activity induced by BARTs 6-3p, 7 and 14 could be attributable to their inability to inhibit the ubiquitin mediated proteolysis effects of B-TRC, despite partial downregulation of GSK3B and NLK. Upon demonstrating the wide influence of BART19-3p in Wnt deregulation, in vitro and in vivo functional assays also demonstrate the ability of BART19-3p to acquire oncogenic properties associated with Wnt activation (e.g. enhanced proliferation, invasion, EMT and stemness).
Citation Format: Alissa Michelle G. Wong, Jinna Chen, Stephanie Ma, Janice Wing Hang Tsang, Xin Yuan Guan. Epstein-Barr virus encoded BART microRNAs facilitate nasopharyngeal carcinoma development and progression via deregulation of Wnt signaling. [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 3064. doi:10.1158/1538-7445.AM2013-3064
Abstract 3095: Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer.
Authors: Hirata Hiroshi , Ueno Koji , Shahryari Varahram , Tanaka Yuichiro , Tabatabai Z. Laura , Hinoda Yuji , Dahiya Rajvir 
Published: August 2014

Abstract
Abstract
Introduction and Objective: Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-182-5p in bladder cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in BC. Methods: Initially we found that miR-182-5p expression was significantly higher in bladder cancer compared to normal tissues and high miR-182-5p expression was associated with shorter overall survival in BC patients. To study the functional significance of miR-182-5p, we over-expressed miR-182-5p with miR-182-5p precursor. Results: Cell proliferation, migration and invasion abilities were increased in BC cells. However cell apoptosis was inhibited by miR-182-5p. We also identified Smad4 and RECK as potential target genes of miR-182-5p using several algorithms. 3’UTR luciferase activity of these target genes was significantly decreased and protein expression of these target genes was significantly up-regulated in miR-182-5p inhibitor transfected bladder cancer cells. MiR-182-5p also increased nuclear beta-catenin expression and while Smad4 repressed nuclear beta-catenin expression. Conclusions: Our data suggests that miR-182-5p plays an important role as an oncogene by knocking down RECK and Smad4, resulting in activation of the Wnt-beta-catenin signaling pathway in bladder cancer.
Source of Funding: Grants RO1CA138642, RO1CA130860, RO1CA160079, VA Research Enhancement Award Program (REAP) and Merit Review grants
Citation Format: Hiroshi Hirata, Koji Ueno, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya. Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer. [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 3095. doi:10.1158/1538-7445.AM2013-3095