bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 417: SMAD3 upregulation is a novel biomarker of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer.
Authors: Yamazaki Ken , Masugi Yohei , Effendi Kathryn , Sakamoto Michiie 
Published: August 2014

Abstract
Pancreatic cancer has one of the worst survival rates among all cancers. Features like epithelial-mesenchymal transition (EMT) are often seen in pancreatic tumors and correlate with poor prognosis. The purpose of this study was to identify factors involved in EMT in pancreatic cancer that may serve as prognostic indicators. Gene-expression profiling identified overexpression of SMAD3 in pancreatic cancer with high-grade solitary cell infiltration, one of the EMT-like features. SMAD3 expression was then evaluated through immunohistochemical analysis using clinical specimens. SMAD3 was accumulated in the nuclei of tumor cells (positive rate ranging from 0% to 75%), but was not detected in most of the epithelial cells in the pancreatic duct. Upregulated SMAD3 (≥15% positive in nuclei of tumor cells) correlated with malignant characteristics, such as higher tumor grade (P = 0.001) and lymph node metastasis (P &lt;0.001), as well as with EMT-like features, such as reduced E-cadherin (P = 0.013) and elevated vimentin (P = 0.032). SMAD3 knockdown in pancreatic cancer cells resulted in increased E-cadherin expression, decreased vimentin expression and decreased cell motility. The suppressed EMT-like features by SMAD3 knockdown were observed even in SMAD4-inactivated pancreatic cancer cells, suggesting that SMAD3 is involved in EMT induction, regardless of SMAD4 status. In clinical cases, SMAD3 upregulation and EMT-like features correlated with shorter survival time. Moreover, SMAD3 and E-cadherin were identified as independent prognostic factors by multivariate analysis, and the group of patients with both upregulated SMAD3 and reduced E-cadherin had the least favorable prognosis compared with other groups. Taken together, SMAD3 seems to play an important role in malignant progression of pancreatic cancer, and may provide a potential biomarker for poor prognosis of pancreatic cancer.
Citation Format: Ken Yamazaki, Yohei Masugi, Kathryn Effendi, Michiie Sakamoto. SMAD3 upregulation is a novel biomarker of poor prognosis and epithelial-mesenchymal transition in pancreatic 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 417. doi:10.1158/1538-7445.AM2013-417
Abstract 4172: MiR-215 expression in tumor tissue and in vitro effects of its replacement in colorectal cancer.
Authors: Faltejskova Petra , Svoboda Marek , Mlcochova Jitka , Srutova Klara , Fabian Pavel , Vyzula Rostislav , Slaby Ondrej 
Published: August 2014

Abstract
Background: MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumor suppressors.
Methods: We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoral tissues and identified 42 differentially expressed miRNAs. One of the most significantly altered miRNAs was miR-215, significantly down-regulated in tumor tissue. We chose miR-215 for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro functional studies on DLD1, HCT116 and HT29 cell lines.
Results: MiR-215 was proved to be significantly decreased in CRC tumor tissues (p&lt;0.0001) and to be negatively correlated with clinical stage (p&lt;0.0001) and tumor grade (p=0.04). In vitro analyses showed that ectopic expression of miR 215 decreases viability in DLD1 (p=0.05) and HCT116 (p=0,05) cells, increases apoptosis in HCT116 (p=0.005), promotes cell cycle arrest (inhibited G1/S transition) in HCT-116 colon cancer cells (p=0.01) and decreases migration in DLD1 (p=0.05) and HT-29 cells (p=0.05). We further confirmed transcription factor HOXB9 as direct target of miR-215 on the mRNA and protein level.
Conclusions: These findings indicate that miR 215 play an important role in CRC as tumor suppressor and contributes to CRC pathogenesis.
Supported by Internal Grant Agency of Czech Ministry of Health, grant numbers: NT13549-4/2012 a NT13860 4/2012.
Citation Format: Petra Faltejskova, Marek Svoboda, Jitka Mlcochova, Klara Srutova, Pavel Fabian, Rostislav Vyzula, Ondrej Slaby. MiR-215 expression in tumor tissue and in vitro effects of its replacement in colorectal 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 4172. doi:10.1158/1538-7445.AM2013-4172
Abstract 4173: MicroRNA expression of non-terminal respiratory unit type lung adenocarcinoma.
Authors: Kim Mi Hyun , Lee Min Ki , Shin Dong Hoon , Lee Chang Hun 
Published: August 2014

Abstract
Background: Lung adenocarcinomas can be classified into two major subtypes, terminal respiratory unit (TRU) type and non-TRU type. We previously reported that non-TRU type adenocarcinoma has unique clinical and morphological features compared with TRU type adenocarcinoma. In brief, among 36 cases of non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.
Objectives: We investigated whether microRNA (miRNA) expression profiles can differentiate between non-TRU type and TRU type lung adenocarcinoma.
Methods: MiRNA expression in lung adenocarcinoma with non-TRU and TRU type was analyzed by microarray analysis with 1205 human and 144 human viral miRNAs.
Results: Eight pairs of lung adenocarcinomas and corresponding noncancerous lung tissues (4 for non-TRU type and 4 for TRU type) were analyzed by microarray analysis. Initially, 44 miRNAs showed statistical differences in expression between lung cancer tissues and corresponding noncancerous tissues. Comparison analyses between non-TRU type and TRU type revealed 30 miRNAs with statistically different expression. Particularly, hsa-mir-494 and ebv-mir-BART19 were upregulated with more than 5-fold difference as compared with TRU type adenocarcinoma. Similarly, hsa-mir-551b was downregulated at more than 5-fold as compared with TRU type adenocarcinoma. Only 2 miRNAs (hsa-mir-1 and hsa-mir-133b) were shared in both non-TRU and TRU type of adenocarcinoma.
Conclusion: We demonstrated that non-TRU type adenocarcinoma showed different miRNAs expression patterns compared with TRU type adenocarcinoma, suggesting different carcinogenic pathways for these tumors. Further studies are required for validation the results from microarray analysis.
Citation Format: Mi Hyun Kim, Min Ki Lee, Dong Hoon Shin, Chang Hun Lee. MicroRNA expression of non-terminal respiratory unit type lung adenocarcinoma. [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 4173. doi:10.1158/1538-7445.AM2013-4173
Abstract 4174: miR-17-92 as a therapeutic target in gastric cancer.
Authors: park Dong M. , Lee Seok C. , Kim Hark K. 
Published: August 2014

Abstract
We previously reported that 82 gastric cancer patients overexpress miR-17-5p, compared with healthy volunteers [median tumor/normal ratio, 1.6; false discovery rate&lt;0.001]. Although 13q31.3 amplification has been reported in gastric cancer, the exact frequency of MIR17HG gene amplification in gastric cancer has not been systematically investigated. Using combined CGH and expression array analyses, we identified genomic abnormalities associated with miR-17-5p expression. No copy number alteration of MIR17HG was identified among the 32 study patients. Median or higher levels of miR-17-5p expression in gastric cancer patients were associated with copy number gain and overexpression of known oncogenes such as MYC and FGFR2. Based on mRNA expression microarray, genes differentially expressed between the high miR-17-expressing tumors and healthy volunteers were significantly enriched in MYC target genes (LS P value, 0.007). MYC knockdown in SNU-16 gastric cancer cells significantly decreased miR-17-92 expression. Although transcriptional activation, rather than gene amplification, was identified as the primary mechanism underlying miR-17-92 overexpression in gastric cancer, miR-17-5p inhibition led to suppressed monolayer and anchorage-independent growth and increased G1/S phase ratio in KATO-III cells which harbor FGFR2 gene amplification. Hence, miR-17-92 may serve as a therapeutic target in gastric cancer (supported by the Proteogenomic Research Program through the National Research Foundation of Korea funded by the Korean Ministry of Education, Science and Technology; and by Korean National Cancer Center Grant 121005).
Citation Format: Dong M. park, Seok C. Lee, Hark K. Kim. miR-17-92 as a therapeutic target in 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 4174. doi:10.1158/1538-7445.AM2013-4174
Abstract 4175: Characterization of hsa-miR-135b in human neuroblastoma cell line SK-N-BE(2).
Authors: Castillo Chelsea A. , Chang Judy C. , Hung Jaclyn Y. 
Published: August 2014

Abstract
Background: MicroRNAs (miRs) are an abundant class of small (∼22 nucleotides), non-coding, single-strand RNAs (ncRNA) that negatively regulate gene expression at a post-transcriptional level. miRs are thought to act by inhibiting the translation of messenger RNAs (mRNAs) into protein in addition to promoting mRNA degradation. These regulatory ncRNAs play an important role in the control of many biological processes and their deregulation has been implicated in a variety of pathological conditions, including many cancers. Emerging evidence supports the concept that in many cancer types a pool of cancer cells responsible for cancer maintenance and long-term remission failure exhibit stem-like properties. Using a high throughput miR microfluidic card assay qRT-PCR approach, we identified 26 miRs (23 up-regulated and 3 down regulated) as stem-like associated miRs in six pediatric cancer cell lines, including neuroblastoma cell line SK-N-BE(2). hsa-miR-135b was one of the miRs that was up-regulated. The purpose of this study was to characterize the functional consequences of hsa-miR-135b silencing in the SK-N-BE(2) cell line.
Methods: hsa-miR-135b expression was knocked down (KD) using Lipofectamine® transfection reagent and a stable cell line was generated in the presence of puromycin. Cell cycle distribution as well as the effect of inhibition on the ability to form neurospheres (read-out for self-renewal) was determined. To investigate the effect on anchorage-independent growth, the ability of the KD cells to form colonies in soft agar was measured. Cell capacity for invasion was tested using basement membrane matrix invasion culture system. Western blot analysis was performed on the components of the Wnt/****B-catenin signaling pathways.
Results: Our results indicated that inhibition of hsa-miR-135b impaired sphere formation (read-out for self renewal) as well as growth of colonies on a semi-solid culture media. No significant difference in cell cycle distribution was observed between control and hsa-miR-135b KD cells.
Conclusion: Our findings suggest that in our model system, hsa-miR-135b likely plays a role in the maintenance of cancer stem cells and tumor progression. Therefore, it is a promising therapeutic target in neuroblastoma patients.
Citation Format: Chelsea A. Castillo, Judy C. Chang, Jaclyn Y. Hung. Characterization of hsa-miR-135b in human neuroblastoma cell line SK-N-BE(2). [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 4175. doi:10.1158/1538-7445.AM2013-4175
Abstract 4187: Regulation of NRSF/REST by miR-217; Implications during pancreatic acinar ductal trans-differentiation.
Authors: Azevedo-Pouly Ana Clara P. , Jiang Jinmai , Sutaria Dhruvitkumar , Schmittgen Thomas 
Published: August 2014

Abstract
Pancreatic ductal adenocarcinoma is believed to arise from exocrine acinar cells following trans-differentiation to cells with a more epithelial phenotype. A pancreas enriched cluster of miRNAs (miR-216a/b-217) is located on chromosomes 2 and 11 in humans and mice, respectively. These miRNAs are significantly reduced in patient's tumor specimens and during tumor progression in a transgenic mouse model of pancreatic ductal adenocarcinoma. To investigate a role for miR-216/-217 during acinar ductal trans-differentiation, we used a model by which primary mouse pancreatic acini trans-differentiate into epithelial-like cells when cultured on matrigel. Over a 4 day culture period, the acini develop an epithelial morphology and display reduced mRNA expression of the acinar marker amylase, increased expression of the epithelial marker cytokeratin-19 (KRT19) and reduced expression miR-216/-217. Forced expression of miR-217 using a lentiviral vector (LV) decreased KRT19 mRNA expression compared to the empty vector control treated cells on day 4 of the trans-differentiation. To implicate miR-217 targets in regulating acinar trans-differentiation, we considered REST/NRSF, a transcriptional repressor of neuronal genes in non-neuronal tissues. REST mRNA expression increased during the 4 day trans-differentiation implying regulation of REST by miR-217. Regulation of REST by miR-217 was validated using a luciferase assay and western blotting. Furthermore, two REST target genes were upregulated by the miR-217 LV on day 4 of the trans-differentiation. Studies are ongoing to determine if this increase in expression results from miR-217 suppressing REST protein levels. Additionally, miR-217 LV infection of 3 pancreas cancer cell lines reduced REST protein and caused significant cell death. Our current focus is to establish a link between miR-217 suppression of REST and cell death. We report a connection between reduced miR-217 in several pancreas model systems. We hypothesize a novel role for REST in pancreas homeostasis and cancer.
Citation Format: Ana Clara P. Azevedo-Pouly, Jinmai Jiang, Dhruvitkumar Sutaria, Thomas Schmittgen. Regulation of NRSF/REST by miR-217; Implications during pancreatic acinar ductal trans-differentiation. [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 4187. doi:10.1158/1538-7445.AM2013-4187
Abstract 4194: The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell carcinoma .
Authors: Yang Pei-Wen , Hsieh Ching-Yueh , Huang Yu-Ting , Huang Ya-Chuan , Chiang Tzu-Hsuan , Lee Jang-Ming 
Published: August 2014

Abstract
PURPOSE: To investigate the effect of the single nucleotide polymorphisms (SNPs) in microRNA-related genes on the prognosis of patients with esophageal squamous cell carcinoma (ESCC).
PATIENTS AND METHODS: A total of 504 patients with a diagnosis of ESCC were enrolled in the study. The genotypes of miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the clinical outcome of patients, which was first evaluated in a randomly assigned training set (n=129) and subsequently verified by a replication set (n= 375).
RESULTS: In training group, the heterozygous CG genotype of mir-608 rs4919510 was associated with reduced risk for adverse clinical outcomes (HR [95% CI] =0.47 [0.27-0.82] for death; HR [95% CI] =0.47 [0.29-0.77] for recurrence). In contrast, both homozygous CC and GG genotypes showed unfavorable for prognosis. The associations were confirmed in an independent replication group (GG+CC vs. CG, HR [95% CI] =1.36 [1.07-1.73], P=0.013 for death; HR [95% CI] = 1.26 [1.00-1.59], P=0.048 for recurrence). The prognostic effect was more pronounced among patients with advanced tumor stages and in those treated with concurrent neoadjuvant chemo- radiotherapy (CCRT). Functional relevance of rs4919510 was correlated with the serum IL-6 levels. GG variant was significantly associated with IL-6 over-expression in advanced ESCC patients.
CONCLUSION: The hereditary genetic variants in mir-608 can serve as an independent predictor for the clinical outcome of ESCC patients. The prognostic effect of rs4919510 may be partially mediated by impairing the ability in regulating IL-6 expression.
Citation Format: Pei-Wen Yang, Ching-Yueh Hsieh, Yu-Ting Huang, Ya-Chuan Huang, Tzu-Hsuan Chiang, Jang-Ming Lee. The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell 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 4194. doi:10.1158/1538-7445.AM2013-4194
Abstract 4200: Effects of microRNA-100 on cell proliferation and apoptosis is associated with dysregulation of Plk1 in hepatocellular carcinoma cells.
Authors: Zhu Wuling , Fan Binglin , zhang Hongge , Ji Xiaohui , Yang Wancai , Yang Wancai 
Published: August 2014

Abstract
The microRNAs (miRNAs) are a family of small non-coding RNAs that negatively regulate gene expression by degrading mRNA and by inhibiting translation of protein. Numerous studies have demonstrated the critical roles of miRNA in physiological and pathological procedures, including cell proliferation, differentiation and apoptosis, and in carcinogenesis. Recent studies have particularly reported that miR-100 is aberrantly expressed in multiple cancers, including colorectal, lung, prostate, ovarian, thyroid, pancreatic, liver, breast, cervical and nasopharyngeal cancers. It has also been reported that reduction of miRNA-100 is associated with poor prognosis. But the effects of miRNA-100 on human hepatocellular carcinoma cells and its potential mechanisms are largely unknown. In the present study, we transfected miRNA-100 analogue into human hepatocellular carcinoma cell line HepG2 cell, employed quantitative RT-PCR, immunoblotting, immunofluorescence, flow cytometry and other approaches, and found that the expression of miRNA-100 was markedly lower but polo-like kinase 1 (Plk1) was higher in the HCC cell line and fetal liver, compared to those in the normal hepatocytes and adult liver, respectively. Moreover, increasing miRNA-100 expression in HepG2 cells inhibited cell proliferation, caused cell cycle arrest and promoted apoptosis. Mechanistic and correlation studies revealed that the anti-cancer effects of miRNA-100 were associated with downregulation of Plk1 expression at mRNA and protein levels. Factually, bioinformatic analysis has predicted that Plk1 could be a target of miRNA-100. In conclusion, our results have shown that miRNA-100 has a tumor suppressor function in human hepatocellular carcinoma cells, which may be associated with downregulation of Plk1, and implicate the potential application of miR-100 in connection with Plk1 for targeted gene therapy of hepatocellular carcinoma.
Citation Format: Wuling Zhu, Binglin Fan, Hongge zhang, Xiaohui Ji, Wancai Yang, Wancai Yang. Effects of microRNA-100 on cell proliferation and apoptosis is associated with dysregulation of Plk1 in hepatocellular 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 4200. doi:10.1158/1538-7445.AM2013-4200
Abstract 4205: Simultaneous high resolution fluorescence imaging of cellular DNA and RNA enabled by complex oligonucleotide libraries in various sample types.
Authors: Ach Robert A. , Tsang Peter , Scheffer-Wong Alicia , Bruhn Laurakay , Powell Weston , LaSalle Janine , Yamada Alice 
Published: August 2014

Abstract
Fluorescence in situ Hybridization (FISH) is a powerful technique for determining the structure, organization, and localization of specific nucleic acid sequences within individual cells. However, the use of FISH has often been dependent upon access to cloned template DNA for the generation of probes, which can be difficult if clones for specific regions are unavailable, or if the genomic region of interest contains repetitive and/or other problematic sequences. We have leveraged our ability to chemically synthesize DNA in massively parallel reactions to produce libraries of oligonucleotides up to 200 bases in length that can be used for the generation of FISH probes. The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to avoid repetitive elements or regions homologous to other non-targeted loci. Using oligonucleotide library-derived FISH probes on DNA, human genomic regions as small as 1.8 kb and as large as whole chromosomes can be visualized in both metaphase and interphase cells using the same simple assay protocol. Because of the inherent flexibility in our probe design methods, we readily visualized regions rich in repeats and/or GC content. We have also used these oligonucleotide library-derived FISH probes to detect the localization of a variety of both coding and non-coding RNAs in fixed cells, using both conventional fluorescence and structured illumination microscopy. Simultaneous hybridization of FISH probes labeled with different fluorophores enables visualization of multiple sequences at once. Using probes designed specifically to transcribed vs. non-transcribed regions, we have been able to simultaneously detect DNA and RNA from the same locus in the same FISH assay. We have successfully used this technique in several types of fixed tissue culture cells as well as in formalin-fixed paraffin-embedded tissue sections. Our oligo FISH methods are readily compatible with the co-detection of cellular proteins by immunocytochemistry. The ability to generate high performance FISH probes using chemically synthesized oligo libraries that can work flexibly with co-detection of other molecules yields a valuable tool for studies of how localization of specific nucleic acids impacts biological function.
Citation Format: Robert A. Ach, Peter Tsang, Alicia Scheffer-Wong, Laurakay Bruhn, Weston Powell, Janine LaSalle, Alice Yamada. Simultaneous high resolution fluorescence imaging of cellular DNA and RNA enabled by complex oligonucleotide libraries in various sample types. [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 4205. doi:10.1158/1538-7445.AM2013-4205