bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4165: Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion.
Authors: Han Hye Sook , Yun Jieun , Lee Ok-Jun 
Published: August 2014

Abstract
Circulating cell-free microRNAs (miRNAs) have been identified as potential noninvasive biomarkers in cancer. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE). We have also analyzed the expression of carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1, which are the most commonly used tumor markers in pleural effusion. Cell-free miRNA expression was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (10 BPEs and 10 LA-MPEs). The PANArrayTM miRNA expression profiling kit (PANAGENE, INC. Daejeon, Korea) was used to identify candidate miRNAs in the discovery set. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA-MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs, CEA, and CYFRA 21-1. Microarray profiling showed that miR-198 was significantly downregulated in LA-MPE compared with BPE (P = 0.002). The miRNA microarray analysis results were confirmed by qRT-PCR (P &lt; 0.001) using the validation set. miR-198 showed an AUC of 0.887, with a sensitivity of 71.1% and a specificity of 95.2%. The AUC for CEA was 0.898, with a sensitivity of 78.4% and a specificity of 97.5%. The AUC for CYFRA 21-1 was 0.836, with a sensitivity of 78.4% and a specificity of 82.5%. The diagnostic performance of miR-198 was comparable with that of CEA, but better than that of CYFRA 21-1. The AUC for all three markers combined was 0.926 (95% confidence interval, 0.843-0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study shows that expression of miR-198 was significantly downregulated in LA-MPE compared with BPE, and combination of cell-free miR-198, CEA and CYFRA 21-1 can be used to differentiate LA-MPE from BPE with a high degree of accuracy. These results suggest that miR-198 in pleural effusions may be a potential diagnostic biomarker for discriminating between BPE and LA-MPE.
Citation Format: Hye Sook Han, Jieun Yun, Ok-Jun Lee. Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion. [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 4165. doi:10.1158/1538-7445.AM2013-4165
Abstract 4167: Target mRNA analysis for miR-125a-5p in cervical carcinoma cells.
Authors: Martinez Acuna Natalia , Benitez Hess Maria L. , Alvarez Salas Luis M. 
Published: August 2014

Abstract
It has been firmly established that high-risk human papillomavirus (HPV) infection is associated with the appearance and persistence of anogenital dysplasia. However, only a small fraction of HPV-infected patients ever develop cervical cancer. Therefore, other factors must contribute for the development of a malignant phenotype in HPV-infected cells. Aberrant microRNA (miRNA) expression is nowadays recognized as a key factor for the development of several pathologies including cancer. Several studies on the miR-125a-5p function have suggested a tumor suppressor role in diverse cell types. Our previous results shown that miR-125a-5p induced cell-cycle arrest, proliferation inhibition and apoptosis in cervical carcinoma cells. Nevertheless, miR-125a-5p role and mRNA targets in cervical cancer are not fully established in cervical cancer. RT-qPCR analysis of miR-125a-5p expression showed differential expression on immortal and tumor cervical cell lines suggesting a role in malignant progression. To probe for possible miR-125a-5p targets we performed in silico analyses using several miRNA target analysis tools and validated the results with a panel of cervical immortal and tumor cell lines. The bio-informatics analysis showed Mark1, bcl-2 and vEGF genes as possible targets for miR-125a-5p. Further RT-qPCR and immunoblot analysis indicated an inverse correlation of miR125a-5p and MARK1 expression in tumor lines but not in immortal lines irrespective of the HPV content. Interestingly, transfection of a pre-miR-125a-5p mimic in C33-A cells (lacking HPV and with low endogenous miR-125a-5p levels), resulted in specific down-regulation of MARK1 and VEGF. Therefore, we suggest a potential role for miR-125a-5p in cervical carcinogenesis through the regulation of MARK1.
Citation Format: Natalia Martinez Acuna, Maria L. Benitez Hess, Luis M. Alvarez Salas. Target mRNA analysis for miR-125a-5p in cervical carcinoma 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 4167. doi:10.1158/1538-7445.AM2013-4167
Abstract 4168: The role of miRNA-125a-Fyn interplay in prostate cancer tumorigenesis.
Authors: Ninio Many Lihi , Ben-Aharon Irit , Zilber Sofia , Levy Mattan , Stemmer Salomon M. , Shalgi Ruth 
Published: August 2014

Abstract
Background: The SRC-family of kinases (SFKs) has been broadly implicated in the pathogenesis of prostate cancer. Fyn, a member of the SFKs, mediates mitogenic signals and regulates proliferation, adhesion and motility. Cumulative data indicate that Fyn serves as a proto-oncogene and is known to be over-expressed in several types of malignancies. MicroRNAs are noncoding RNAs that are aberrantly expressed in cancer and seem to influence tumor behavior and progression. In a previous study performed in human embryonic kidney (HEK 293T) cells, we have validated the binding specificity of miR-125a-3p and Fyn 3’UTR using Luciferase assay and established the regulation of Fyn expression and signaling by miR-125a-3p. In the current study we aimed to characterize the interplay between miRNA-125a-3p and Fyn in prostate cancer. Methods: Prostate cancer (PC3) cell line, were transiently transfected with empty miR-vec (control) or with miR-125a-3p and their cell cycle and apoptotic rate were measured by fluorescence activated cell sorting (FACS). The migration ability was measured by transwell assay and scratch assay. Proliferation was assessed by MTT assay. Quantitative PCR and western blot analysis were implicated to determine the effect of miR-125a-3p on Fyn expression as well as on the activation state of its downstream effectors/proteins FAK, Akt and paxillin. Extraction of miRNA from formalin fixed paraffin-embedded (FFPE) cancerous and matched adjacent prostate tissues was performed with miRNeasy FFPE Kit on a cohort of 20 human prostate cancer specimens.
Results: Overexpression of miR-125a-3p in PC3 cells reduced significantly the expression of Fyn mRNA and protein and led to impaired cell viability to an arrest at the G2/M phase of the cell cycle. Moreover, overexpressing of miR-125a-3p reduced the activity of FAK, Akt and paxillin and the secretion of VEGF to the culture media. In miRNA125a-3p-overexpressing PC3 cells the migration was compromised by 50% and cell viability decreased by 50%. Moreover, we observed an inverse correlation between the expression of miR-125a-3p and the Gleason score of tissue samples obtained from patients diagnosed with prostate cancer, whereas the expression of miR-125a-3p was extremely reduced in Gleason score higher than 8.
Conclusions: Our study indicates miR-125a-3p signature in cellular pathways accounted for cell viability and migration of prostate cancer cells. The interplay between miR-125a-3p and Fyn may represent a new plausible therapeutic target in prostate cancer.
Citation Format: Lihi Ninio Many, Irit Ben-Aharon, Sofia Zilber, Mattan Levy, Salomon M. Stemmer, Ruth Shalgi. The role of miRNA-125a-Fyn interplay in prostate cancer tumorigenesis. [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 4168. doi:10.1158/1538-7445.AM2013-4168
Abstract 4177: Detection of mir-449 and mir-let-7g expression in Taiwan paired hepatocellular carcinoma.
Authors: Zhang Yu-Jing , Wu Hui-Chen , Shen Jing , Yu Ming-Whei , Santella Regina M. 
Published: August 2014

Abstract
Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal human malignancies. In recent decades, it has been increasing in Western, developed countries such as the United States. MicroRNAs (miR) regulate genes involved in diverse biological functions and alterations in miR expression have been linked to the pathogenesis of many malignancies. Some previous studies have reported that miR-449 and miR-let-7g have tumor suppressor functions, but other studies indicate that miR-449 may have more variable functions. In the present study, miR-449 and miR-let-7g expression were measured in 36 Taiwanese paired HCC tumor/adjacent tissues using formalin fixed paraffin embedded samples with real-time RT-PCR. The mean log levels of miR-449 expression in tumor and adjacent non-tumor tissues are -1.14 and -2.65, respectively (p=0.02); for miR-let-7g, the mean log levels of tumor and adjacent non-tumor expression are 5.40 and 5.49 respectively (p=0.87). The relationship between exposure to chemical carcinogens as indicated by levels of polycyclic aromatic hydrocarbon (PAH)-DNA adducts and miR expression was also investigated. The mean log levels of miR449 in tumor tissues with high, moderate and low PAH-DNA adduct levels are -2.27, -2.22 and -0.43, respectively (p=0.02). The log levels of miR449 in tumors with and without cirrhosis are 0.02 and -1.42, respectively (p=0.02). These findings suggest that chemical carcinogen exposure and cirrhosis status may affect miR449 expression in HCC. Larger sample sizes and studies on the underlying mechanisms of miR449 and mir-let-7g expression in HCC are needed.
Citation Format: Yu-Jing Zhang, Hui-Chen Wu, Jing Shen, Ming-Whei Yu, Regina M. Santella. Detection of mir-449 and mir-let-7g expression in Taiwan paired hepatocellular 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 4177. doi:10.1158/1538-7445.AM2013-4177
Abstract 4191: MiR-20a inhibits thyroid cancer cell growth and invasion through LIMK1.
Authors: Xiong Yin , Zhang Lisa , Kebebew Electron 
Published: August 2014

Abstract
There have been conflicting reports regarding the function of miR-20a in a variety of cancers. In this study, we evaluated the expression and function of miR-20a in thyroid cancer tissue and cell lines in vitro and in vivo. We found miR-20a was significantly downregulated in undifferentiated and aggressive thyroid cancer (p&lt;0.05). Ectopic overexpression of miR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p &lt; 0.01) and in vivo (p &lt; 0.01), tumor spheroid formation (p &lt; 0.05), and invasion (p &lt; 0.05) in multiple thyroid cancer cell lines. We performed integrated transcriptome analysis with and without miR-20a overexpression and target prediction analysis, and identified LIMK1 as a target of miR-20a. Luciferase assay demonstrated that LIMK1 was a direct target of miR-20a and that direct knockdown of LIMK1 recapitulated the effects of miR-20a in multiple thyroid cancer lines. Our findings suggest that miR-20a has a tumor suppressive function in thyroid cancer which is mediated through LIMK1 and that loss of miR-20a expression may be involved in thyroid cancer progression.
Citation Format: Yin Xiong, Lisa Zhang, Electron Kebebew. MiR-20a inhibits thyroid cancer cell growth and invasion through LIMK1. [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 4191. doi:10.1158/1538-7445.AM2013-4191
Abstract 4197: Function of microRNA-143 and its potential of prognostic factor in scirrhous type gastric cancer.
Authors: Naito Yutaka , Sakamoto Naoya , Uraoka Naohiro , Sentani Kazuhiro , Oue Naohide , Yashiro Masakazu , Hirakawa Kosei , Yasui Wataru 
Published: August 2014

Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide. Scirrhous type GC is highly metastatic and characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs), small non-coding RNA of 19-25 nucleotides, play a part in crucial biological processes and also have an important role in cancer development and progression. In the present study, we show that microRNA-143 (miR-143) is expressed at higher level in diffuse type GC than in intestinal type GC by microRNA microarray analysis. We investigated whether miR-143 is useful as a diagnostic marker of scirrhous type GC. Quantitative RT-PCR analysis revealed that miR-143 expression was low in GC in comparison with adjacent non-tumorous mucosa. Expression levels of miR-143 were higher in scirrhous type GC than those in other types of GC. Treatment of 5-aza-2′-deoxycytidine retrieved miR-143 expression, suggesting that miR-143 might be repressed by DNA methylation. Quantitative RT-PCR and in situ hybridization analysis showed that miR-143 is expressed at higher level in normal fibroblast and cancer associated fibroblast cell lines than in GC cell lines, indicating that major source of miR-143 in cancer tissue is stromal fibroblasts rather than cancer cells. miR-143 knock down by RNAi repressed collagen type III expression in normal fibroblast and cancer associated fibroblast cell lines. Furthermore, TGF-β treatment induced expression of miR-143 and collagen type III mRNA, and this induction of collagen type III mRNA was repressed by miR-143 knock down. We also studied the relation of miR-143 expression with GC patient prognosis (n=68). High miR-143 expression was associated with worse prognosis (P=0.0141). These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and miR-143 expression is a prognostic marker of GC.
Citation Format: Yutaka Naito, Naoya Sakamoto, Naohiro Uraoka, Kazuhiro Sentani, Naohide Oue, Masakazu Yashiro, Kosei Hirakawa, Wataru Yasui. Function of microRNA-143 and its potential of prognostic factor in scirrhous type gastric 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 4197. doi:10.1158/1538-7445.AM2013-4197
Abstract 4201: miR-124 suppresses colorectal tumor progression in a mouse xenograft model via targeting KITENIN.
Authors: Park So-Yeon , Bae Jeong A , Yoon Somy , Kim Hangun , Kim Kyung Keun 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are increasingly implicated in modulating the progression of various cancers. Although there is emerging evidences that some miRNAs can function as oncogenes or tumour suppressors, the regulation of colorectal cancer (CRC) progression by miRNA is not fully understood. KITENIN (KAI1 C-terminal interacting tetraspanin, Vangl1) is not only a major component of PCP pathway but also a functional protein promoting CRC cell motility and invasiveness. Previously, we observed that KITENIN acts as a metastasis-enhancing protein in a mouse model of colon cancer and that KITENIN is highly expressed in sporadic human CRC tissues. But the underlying regulation mechanisms of aberrant expression of KITENIN in CRC are not clearly understood. Here we tried to identify the miRNAs, which modulate the expression of KITENIN, using luciferase assay and with computational prediction of miRNA targeting KITENIN. We identified several miRNAs and one of them is miR-124. miR-124 negatively regulated KITENIN expression through binding to the 3′-untranslated region of KITENIN. We further examined whether increased expression of miR-124 affects colorectal tumor progression via targeting KITENIN. Ectopic expression of miR-124 was found to suppress the migration and invasiveness of various CRC cells. miR-124 also inhibited tumor growth in a mouse xenograft model. These findings provide the experimental evidence to a possible therapeutic effect of miR-124 on suppressing colorectal tumor progression and identification of miR-124-mediated regulation of KITENIN might provide a promising therapeutic target in treating CRC.
Citation Format: So-Yeon Park, Jeong A Bae, Somy Yoon, Hangun Kim, Kyung Keun Kim. miR-124 suppresses colorectal tumor progression in a mouse xenograft model via targeting KITENIN. [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 4201. doi:10.1158/1538-7445.AM2013-4201
Abstract 4226: PIK3CA mutation detection in clinical samples using PNA mediated real-time PCR clamping assay..
Authors: Kim Hysun , Choi Jae Jin , Park Heekyung 
Published: August 2014

Abstract
Somatic mutations in the PIK3CA gene have been frequently found in various human cancers, and their presence correlates to therapy response. These somatic mutations within the PIK3CA gene are localized in exon 9 and 20.
We have developed a highly sensitive and simple method to detect 13 mutations in exons 9 and 20 of PIK3CA using PNA-mediated real-time PCR clamping, PNAClampTM.
PNAClampTM is based on unique properties of PNA probes that PNA oligomers are not recognized by DNA serving as sequence-selective clamps during
PCR amplification. This method can also detect 13 mutations through only three tube reactions each with 10 ng of the target DNA.
PNAClampTM is simple and reliable with a detection limit of approximately 3% mutant alleles using 10 to 50 ng of normal DNA as a template. The turnaround time for performing this assay was only 2 hours. Furthermore, while direct sequencing method will detect most of PIK3CA samples as having E545A mutation, due to homology in exon 9 in PIK3CA gene, highly specific PNAClampTM Method have overcome this perceived problem.
In clinical studies with breast cancer patients in Korea, PIK3CA mutations were detected utilizing PNAClampTM in 60 (35.7 %) of clinical samples, and the results were compared with direct sequencing method. Among 168 patients, 6 (3.6
%) had mutations in codon 542, 23 (13.7 %) had mutations in codon 545 and 31 (18.5
%) had mutations in codon 1047.
To confirm these results, the same clinical samples were analyzed with a sequencing assay. Consistent results were obtained from 137 (81.5 %) of the 168 clinical samples between PNAClampTM and the sequencing assay. The results not in agreement with the sequencing numbered 21 (12.5 %) samples. Ten samples did not react by direct sequencing due to quality problems with the target DNA. The remaining samples were initially determined as the wild type by direct sequencing, but they were found to be PIK3CA mutant using PNAClampTM.
This result was likely due to the high sensitivity of PNAClampTM.
PNAClampTM is a rapid, sensitive and easy to perform tool that can be used for the detection of PIK3CA mutations in the clinical field.
[j1]Check this - original was unclear. Is this what you mean?
Citation Format: Hysun Kim, Jae Jin Choi, Heekyung Park. PIK3CA mutation detection in clinical samples using PNA mediated real-time PCR clamping assay. [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 4226. doi:10.1158/1538-7445.AM2013-4226
Abstract 4237: Isoenzyme-selective HDAC activity assays.
Authors: Kupcho Kevin R. , Evans Nathan J. , Niles Andrew L. , Lazar Dan F. , Kirkland Thomas A. 
Published: August 2014

Abstract
Histone deacetylases (HDACs) are the family of enzymes which catalyze removal of acetyl groups from lysine residues on both histone and non-histone proteins. The lysine acetylation state of histones is an important post-translational modification which affects both chromatin structure and gene transcription. Thus, by deacetylating the amino-terminal tails of histones, HDACs have a profound effect on numerous and diverse cellular functions including cell proliferation. Given this important regulatory role, as well as evidence for significant HDAC involvement in the modulation of cancer, rapid advancement has been made in the development of broad-spectrum HDAC inhibitors. Recently, there has been an increased focus on the development of isoenzyme-specific HDAC inhibitors which may lead to improved therapy, including better efficacy and reduced off target effects. To enable selective HDAC studies, we developed assays that selectively measure specific isoenzyme activities in cells, extracts, or recombinant proteins. The assays use a homogeneous luminescent approach with a single reagent addition that is amenable to HTS. Isoenzyme-selective, luminogenic acetylated peptide substrates provide the basis for HDAC isoenzyme selectivity. Peptide deacetylation is measured by exposure to developer and a luciferin detection reagent. In addition to isoenzyme specificity, the assays show approximately 100-fold or better enhanced sensitivity over fluorescence methods and the versatility necessary for both biochemical and cell-based formats.
Citation Format: Kevin R. Kupcho, Nathan J. Evans, Andrew L. Niles, Dan F. Lazar, Thomas A. Kirkland. Isoenzyme-selective HDAC activity assays. [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 4237. doi:10.1158/1538-7445.AM2013-4237