bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5274: Expression of selected miRNA and miRNA processing genes in oral precancer and cancer tissues.
Authors: Roy Bidyut , Roy Roshni , De Sarkar Navonil , Paul Ranjan Rashni 
Published: August 2014

Abstract
Introduction: Oral leukoplakia is a premalignant lesion that long has been considered to confer increased risk for the development of Oral Cancer which is highly prevalent in India. Oral lichen planus (OLP) on the other hand is a chronic inflammatory disease whose malignant potential is debatable. Since not all oral precancerous lesions progress to oral cancer, molecular markers like miRNA expression could be used to diagnose and predict progression of disease that cannot be detected histopathologically.
Objective: Study of intra- and inter-variation in the expression of a few microRNAs (26a1, 423, 34b, 29a, 193a, 137 and 205) and microRNA processing (XPO5, GEMIN3 and RAN) genes in the three disease types, namely, oral cancer, leukoplakia and lichen planus.
Methodology: Total RNA was extracted from paired disease and normal tissues from 15 oral cancer, 19 leukoplakia and 19 OLP patients. Expression of microRNAs and microRNA processing genes were studied using TaqMan assay. Subsequent statistical analyses were performed for interpretation of expression data.
Results: Expression of mir 26a-1 and mir 137 genes was dysregulated &gt;2 folds in 70% of the cancer samples while expression of remaining microRNAs and mir-processing genes were deregulated in a few samples. In leukoplakia, expression of mir-26a-1 was dysregulated &gt;2 folds in 50% of the samples while dysregulation in expression of the remaining miRNAs was observed in 1/3rd of the patients. In OLP, there was an interesting trend of unidirectional up or down regulation in the expression of mir26a-1, mir29a, mir-34b and mir-137 genes. We also observed that the average expression of miRNA genes differed among the three patient groups.
Conclusion: Deregulation in microRNA expression could not be correlated with individual's tobacco habits. Variation in expression of microRNA as well as miRNA processing genes was observed within individuals of the same patient group (i.e. cancer or leukoplakia or lichen planus) and between any two patients groups. There was correlation in expression of microRNAs which probably explains the unidirectional increase or decrease of miR expression in OLP. Finally, the mean expression level in the three types of disease tissues differed significantly. But expression of more miRNA genes in more samples would be necessary for molecular markers.
Citation Format: Bidyut Roy, Roshni Roy, Navonil De Sarkar, Ranjan Rashni Paul. Expression of selected miRNA and miRNA processing genes in oral precancer and cancer tissues. [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 5274. doi:10.1158/1538-7445.AM2013-5274
Abstract 5285: miRNA expression pattern for predicting prognosis of ovarian serous carcinoma.
Authors: Cui Shiying , Zhang Xinchen , Yu Xiaotang , Ding Yanfang , Zhao Jinyao , Zhao Henan , Wang Chang 
Published: August 2014

Abstract
Objective: One of the best prognosis predictors for patients with epithelial ovarian cancer is clinic pathological stage at diagnosis. The goal of this study is to develop and validate a gene expression profile that can predict prognosis to ovarian serous carcinoma (OSC) at early and advanced stages.
Methods/materials: To identify a unique miRNAs pattern that involved in the progression of OSC at earlier and later stages, miRNA microarray was performed by using 38 China tumor-bank specimens with OSC at stage I and III in a retrospective analysis. The expression of dysregulated miRNAs were validated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in external cohort OSC at stage I and stage III. Kaplan-Meier analysis was further performed to analysis the correlation between the expression of key microRNAs and prognosis.
Results: Of the 768 miRNAs analyzed from microarray, 26 miRNAs were significantly either up or down-regulated with 2 fold difference at least in OSC at stage I compared to III. qRT-PCR results confirmed that 19 miRNAs were significantly down-regulated and 7 was up-regulated in OSC at stage III compared to stage I, which is consistent with the results of microarray. Downregulation of 5 miRNAs was significantly associated with poor disease-specific survival (P&lt;0.05). The patient survival rate of miRNAs high-expression group was 77.8% higher than the low-expression group 33.3%. The different expression patterns of key miRNAs in OSC at stage I versus III were further validated by in situ hybridization.
Conclusions: Our results suggest that miRNA plays an important role in the progression of OSC and 5 miRNAs may be considered as the novel candidates of clinic biomarkers for predicting OSC outcome.
Citation Format: Shiying Cui, Xinchen Zhang, Xiaotang Yu, Yanfang Ding, Jinyao Zhao, Henan Zhao, Chang Wang. miRNA expression pattern for predicting prognosis of ovarian serous 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 5285. doi:10.1158/1538-7445.AM2013-5285
Abstract 5286: A genetic selection system for microRNA targets identification and validation.
Authors: Zhou Nanjiang , Mo Yin-Yuan 
Published: August 2014

Abstract
Overwhelming evidence has indicated that microRNAs can play a fundamental role in regulation of diverse cellular functions and dysregulation of microRNA expression could lead to a variety of disorders including human cancer. Although significant progress has been made in the past years in discovery of microRNAs and their biogenesis, and their role in many cellular phenotypes, it is not fully understood how microRNAs exert their cellular functions because a single microRNA can have hundreds of targets. Hence, identification of microRNA targets is a critical step toward understanding of molecular mechanisms of microRNA-mediated gene expression in normal and disease processes. Here we reported a selection system for microRNA target identification and validation. We used Sleeping Beauty (SB) transposon system to generate selection vectors. The first generation of SB-based vector is named pSSMT-5/6 which carries tetO-EF1a promoter driving GFP/or mCherry-T2A-Pu and tetR-Krab under CMV promoter. We examined the feasibility of these new constructs in 293T and HeLa cells. Using GFP or m-Cherry along with Pu (puromycin resistance) as a reporter, we found that the construct carrying either a given UTR or microRNA sponge provides a significant selection advantage over the vector alone. For example, we cloned 6 different UTRs into the construct and identified 3 of them, CDH1, p53 and p27, revealed stronger mCherry signals and are more resistant to puromycin. Thus, we will test our microRNA library to identify microRNAs capable of targeting these genes (i.e., one known UTR construct against the microRNA library). Together, these results suggest that this system provides proof of principle. In the future, we will generate a UTR library so that we will be able to test for an individual microRNA against the UTR library to identify its biologically relevant targets.
Citation Format: Nanjiang Zhou, Yin-Yuan Mo. A genetic selection system for microRNA targets identification and validation. [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 5286. doi:10.1158/1538-7445.AM2013-5286
Abstract 529: Giα proteins are a differential mediator of activation of RTK signaling in normal and breast cancer cells.
Authors: Wang Zhanwei , Dela-Cruz Rica , Jiang meisheng , Chu Wen-Ming 
Published: August 2014

Abstract
In classic view, inhibitory heterotrimeric G protein alpha subunits 1, 2, and 3 (Gi1α, Gi2α and Gi3α) couple to Giα protein-coupled receptors (GiPCR) and then transduce signals from GiPCRs to downstream pathways in hormone and chemo-attractant signaling. Recent genetic evidence demonstrates that Giα proteins are crucial to embryo development and growth as well as tumorigenesis. However, the molecular mechanism underlying the implication of Giα proteins in this physiological and pathological process is largely unknown.
Here we report that Giα proteins differentially regulate receptor tyrosine kinases (RTKs)-mediated activation of growth factor signaling. Gi1α and Gi3α double deficient (Gi1/3 DKO) mouse embryonic fibroblasts (MEFs), in which Gi2α expression is also lower than that in wild type cells, exhibited a clear defect in ERK1/2 activation by EGF, HB-EGF, insulin and IGF-I, but not aFGF, bFGF or high dose of serum (FBS). Further, Gi1/3 DKO MEFs were largely defective in Akt-mTORC1 activation by aFGF, bFGF, EGF, HB-EGF, serum, but not IGF-1 and insulin. The defect in Akt or ERK1/2 activation in Giα deficient MEFs was rescued upon reintroduction of Gi1α and Gi3α proteins. Interestingly, Giα deficiency impaired activation of Akt-mTROC1 and ERK1/2 by PDGF at a low, but not a high dose. Using a RNA interference strategy, we showed that knockdown of Giα proteins in either wt MEFs or triple negative breast cancer cells (MDA-MB231-D3H2-LN) led to a defect in Akt-mTROC1 and ERK1/2 activation, which is similar to that in Giα deficient cells in response to EGF, bFGF or IGF-1.
Additional experimental analysis revealed that Giα proteins formed a complex with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells in response to EGF, bFGF, or IGF-1. Gi1/3 DKO MEFs showed a defect in EGF- and IGF-1-induced interaction of Gab1 with SHP2, which is required for ERK1/2 activation by EGF and IGF-1, and a defect in bFGF-induced interaction of Grb2 with Gab1, which is required for Akt-mTORC1 activation by aFGF and bFGF. Finally, knockdown of Giα proteins impaired in vitro growth and invasion of breast cancer cells in response to bFGF, EGF, and IGF-1.
Thus, Giα proteins are a differential mediator of RTK signaling in normal and breast cancer cells.
Citation Format: Zhanwei Wang, Rica Dela-Cruz, meisheng Jiang, Wen-Ming Chu. Giα proteins are a differential mediator of activation of RTK signaling in normal and breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 529. doi:10.1158/1538-7445.AM2013-529
Abstract 5295: Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting PDPN gene.
Authors: Chen Wantao 
Published: August 2014

Abstract
Head and neck squamous cell carcinoma (HNSCC) is characterised by an elevated capacity for cell invasion and lymph node metastasis. The cause remains to be determined. Recent studies suggest that microRNAs can regulate the evolution of malignant behaviours by regulating multiple target genes. In this study, we first confirmed that miR-363 is down-regulated in HNSCC tissues with lymph node metastasis and cell lines with highly invasive capacity. We also found that podoplanin (PDPN) is up-regulated in the metastatic HNSCC tissues, and ectopic over-expression of miR-363 suppressed the metastatic behaviour of HNSCC cells by directly targeting PDPN. These data support a key role of miR-363-PDPN in head and neck cancer metastasis by regulating cellular invasion and migration.
Citation Format: Wantao Chen. Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting PDPN gene. [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 5295. doi:10.1158/1538-7445.AM2013-5295
Abstract 5298: Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients.
Authors: Yu Jing , Dong Ningning , Yan Ying , Shao Bin , Di Lijun , Song Guohong , Che Li , Jia Jun , Jiang Hanfang , Liang Xu , Zhu Yulin , Wang Chaoying , Zahng Jie , Zhu Budong , Zhou Xinna , Wang Xiaoli , Yang Huabing , Ren Jun , Lyerly Herbert Kim 
Published: August 2014

Abstract
The successful predictively treatment of metastatic breast cancer (MBC) remains a major challenge. Until now there is no definite marker to distinguish responder from non-responder and more and more important, metastasis occurred within different organs lead to serious variations of overall survival. In this study, paclitaxel and anthracyclines pretreated153 patients with MBC received 606 cycles of docetaxel plus thiotepa. 65 of 153 patients were concurrently diagnosed as MBC involved liver metastasis (LM). Among 153 patients, the response were 1 complete response (CR) (0.7%), 25 partial responses (PR) (16.3%), 73 stable diseases (SD) (47.7%), 46 progressive diseases (PD) (30.1%) and 8 unevaluable(5.2%). For LM patients, the localized liver response were 2 CR (3.1%), 20 PR (30.8%), 16 SD (24.6%), 22 PD (33.8%),5 unevaluable (7.7%). Median PFS and OS for both entire and LM subgroup were 6.5 (95% CI, 5.6 to 7.4) versus 4.2 (95%CI, 2.3-6.1), and 20.0 (95% CI, 15.6 to 24.4) versus 14.2 (95%CI, 9.5-18.9) months respectively. 79 SNPs in CYP450, whose minor allele frequency were ≥ 10% were genotyped. There was no significant difference of SNPs in therapeutic responses, PFS or OS. Of importance, there were two distinctive SNPs, rs2277119 and rs4646487 *2/*3 alleles, which tended to have the better liver metastases response than *1 when choosing a false discovery rate as 12%. It seemed that docetaxel plus thiotepa might be regarded as an active specific regimen for MBC with liver metastasis. The generation of conceptually specific chemotherapy targeting the organ with cancer metastasis should be considered in the future.
Citation Format: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly. Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients. [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 5298. doi:10.1158/1538-7445.AM2013-5298
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5310: Activation of FGFR3 by genomic fusion in urothelial carcinoma of the bladder.
Authors: Williams Sarah V. , Hurst Carolyn D. , Knowles Margaret A. 
Published: August 2014

Abstract
FGFR3 is frequently activated by mutation in urothelial carcinoma of the bladder. We demonstrate here a further method of activation, by gene fusion following chromosomal re-arrangement. Four fusions with transforming acid coiled-coil 3 (TACC3) resulting from 4p16.3 re-arrangement were identified. A fifth fusion following t(4;7) was with BAI1-associated protein 2-like 1 (BAIAP2L1), also known as IRTKS (Insulin Receptor Kinase Substrate) on chromosome 7. The FGFR3-TACC3 fusions involve four different genomic re-arrangements resulting in three different transcripts. The fusion proteins show constitutive phosphorylation, activation of the MAPK pathway and transform NIH-3T3 cells. All have lost the final exon of FGFR3, which includes the PLCγ1 binding site. Thus PLCγ1 pathway activation and known PLCγ1-induced effects in normal urothelial cells were not induced. The FGFR3-BAIAP2L1 fusion retains most of BAIAP2L1 including the IRSp53/MIM domain (IMD) that mediates actin binding and Rac interaction, while the FGFR3-TACC3 fusions all retain the TACC domain that mediates microtubule binding. As cells containing these fusion genes are highly sensitive to FGFR-selective agents, detection of fusion genes may be useful in selecting patients for targeted therapy.
Citation Format: Sarah V. Williams, Carolyn D. Hurst, Margaret A. Knowles. Activation of FGFR3 by genomic fusion in urothelial carcinoma of the bladder. [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 5310. doi:10.1158/1538-7445.AM2013-5310
Abstract 5314: Calcium mediated growth control in normal and transformed colon cells: A possible role of the calcium sensing receptor.
Authors: Aggarwal Abhishek , Höbaus Julia , Fetahu Irfete Sh. , Mesteri Ildikó , Kállay Enikö 
Published: August 2014

Abstract
Introduction: Calcium (Ca2+) plays an important role in regulating proliferation of colonic epithelium. Epidemiological studies suggest an inverse correlation between dietary Ca2+ intake and colorectal cancer (CRC) risk. However in CRC, transformed cells lose their sensitivity to the tumour inhibiting effects of Ca2+. We have shown that the extracellular calcium-sensing receptor (CaSR) expression is lost in CRC and therefore hypothesized that the CaSR mediates the effect of Ca2+ in regulating proliferation.
Methods: We investigated the expression of the CaSR and of a cluster of genes responsible for ‘triggering off’ proliferation (CDT1, CDC6, CDC45, MCM2-7, Geminin, known as replication licensing genes) at mRNA level by qRT-PCR in CRC samples and in their respective ‘normal’ adjacent mucosa (n=57). To study the effect of Ca2+ in normal colon physiology, we fed male and female C57BL/6 mice with a diet containing high (0.9%) or low (0.1%) levels of Ca2+ and assessed the influence of dietary Ca2+ on proliferation (immunohistochemistry staining and mRNA expression) and CaSR mRNA expression.
Results and Discussion: In tumours we found the expression of CaSR significantly downregulated when compared with respective adjacent mucosa (p&lt;0.001). All genes involved in replication licensing are significantly higher expressed (p&lt;0.001) in these samples. Our data suggest that the loss of CaSR gives the tumour cells growth advantage. In the tumour samples we found negative correlation between CaSR and licensing factors (CDC45 (p&lt;0.05, ρ=−0.265) and MCM6 (p&lt;0.05, ρ=−0.262) reaching significance). Surprisingly, CaSR showed positive correlation with the licensing factors in the ‘normal’ mucosa (CDT1 (p&lt;0.05, ρ=0.269), MCM2 (p&lt;0.003, ρ=0.382) and MCM5 (p&lt;0.001, ρ=0.490) reaching significance). These results are similar to our observation in the mouse study, where low dietary Ca2+ enlarged the proliferative zone of the crypts with no significant change in CaSR expression.
Conclusion: We conclude that the CaSR might regulate the calcium-dependent inhibition of proliferation in normal colonocytes. Upregulation of CaSR is probably a defence mechanism of the normal colon to control epithelial growth and counteract hyper-proliferative signals. This control mechanism is lost in cancer where CaSR expression is downregulated.
Citation Format: Abhishek Aggarwal, Julia Höbaus, Irfete Sh. Fetahu, Ildikó Mesteri, Enikö Kállay. Calcium mediated growth control in normal and transformed colon cells: A possible role of the calcium sensing receptor. [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 5314. doi:10.1158/1538-7445.AM2013-5314
Abstract 5317: Evidence for intracellular calcium-regulated secretion in gastrointestinal stromal tumor.
Authors: Berglund Erik , Berglund David , Akcakaya Pinar , Ghaderi Mehran , Dare Elisabetta , Berggren Per-Olof , Aspinwall Craig A. , Lui Weng-Onn , Zedenius Jan , Larsson Catharina , Bränström Robert 
Published: August 2014

Abstract
Gastrointestinal stromal tumors (GISTs) are considered to originate from the electrically active pacemaker cells of the gut. Despite the presence of synaptic like vesicles and proteins involved in exocytosis and secretory response in other cell types, it still remains unclear if GIST cells have a regulated secretion. A GIST tumor cell line (GIST882) was used as a model cell system, and stimulus-secretion coupling was investigated performing measurements of intracellular Ca2+, confocal microscopy, flow cytometry and an ATP-based assay to measure secretory response. We demonstrate that GIST cells have an intracellular signaling pathway downstream regulating cell secretion observed as an ATP release. Cell membrane integrity was preserved showing that ATP is released and not related to cell membrane rupture or cell death. The stimulus-secretion signal transduction is, at least partly, dependent on Ca2+ influx, since exclusion of extracellular Ca2+ diminishes the secretory response. We conclude that measurements of the secretory response in GIST by using ATP as a marker may be a useful tool in dissecting the signal transduction pathway, identification of secretory substances and in the development of drugs.
Citation Format: Erik Berglund, David Berglund, Pinar Akcakaya, Mehran Ghaderi, Elisabetta Dare, Per-Olof Berggren, Craig A. Aspinwall, Weng-Onn Lui, Jan Zedenius, Catharina Larsson, Robert Bränström. Evidence for intracellular calcium-regulated secretion in gastrointestinal stromal tumor. [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 5317. doi:10.1158/1538-7445.AM2013-5317
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.