bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3945: Association of inflammation-related microRNA gene expression in inflammatory bowel disease and IBD-associated colon cancer
Authors: Schetter Aaron J. , Welsh Judith A. , Bowman Elise D. , Harris Curtis C. 
Published: August 2014

Abstract
Introduction: There is an undeniable link between chronic inflammation and cancer. Inflammatory bowel disease (i.e. ulcerative colitis [UC] and Crohn's disease [CD]) are conditions that lead to chronic inflammation of the colon and increased risk of colon cancer. Indentifying factors that contribute to inflammatory bowel disease (IBD) and IBD-associated cancers may allow for the development of therapeutic and preventive strategies for these diseases. Altered expression of microRNAs may contribute to these diseases.
Methods: We examined the expression of 29 specific microRNAs by Taqman-based quantitative RTPCR using the Fluidigm 96.96 dynamic array system. The 29 microRNAs were selected based on a combination of our own preliminary microarray data on inflammatory bowel disease and published literature on microRNAs involved in inflammation or inflammatory bowel disease. RNA was extracted from colon tissues of 34 patients with CD, 33 patients with UC, 64 sporadic colon cancer patients, 14 patients with IBD-associated colon cancer and 18 patients with adenomas. We identified microRNAs associated with gross inflammation in UC and CD patients. We also compared microRNA expression profiles of sporadic tumors with IBD-associated tumors.
Results: The expression of 18 microRNAs were significantly altered in gross inflammation of CD and 19 microRNAs were altered in gross inflammation of UC. In general, the expression patterns were similar comparing UC and Crohn's tissues, but 3 microRNAs were significantly different between the two diseases. Fifteen microRNAs were altered in sporadic colon cancer. The microRNA expression patterns of IBD-associated tumors were quite different from the expression patterns of sporadic colon tumors.
Summary: We find evidence supporting that the chronic inflammation of both ulcerative colitis and Crohn's disease leads to a systematic change in microRNA expression patterns. Altered expression of microRNA may be in part responsible for the phenotypic affects of gross inflammation. The expression of miR-21, miR-135b and miR-192 were altered in similar ways in colon tumors as they were in chronic inflammation, suggesting that alteration of these specific microRNAs may in part be responsible for the elevated risk of cancer in these populations. We also find that sporadic tumors have different expression profiles that IBD-associated tumor, suggesting that the different etiology of these tumors results in different microRNA transcriptomic expression patterns.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2011-3945
Abstract 3951: The ERG 3′-UTR is a target of miR-145 and expression patterns of ERG isoforms are altered in prostate cancer
Authors: Wach Sven , Hart Martin , Nolte Elke , Szczyrba Jaroslaw , Wullich Bernd , Graesser Friedrich 
Published: August 2014

Abstract
Background: Prostate cancer is a leading cause of tumor mortality. In order to identify the underlying mechanisms we have analyzed microRNA (miRNA) expression profiles of primary prostate cancers and non-cancer prostate tissue. Using database analysis, we sought to identify regulatory targets of aberrantly expressed miRNAs.
Material and Methods: We performed comparative miRNA expression profiling using deep sequencing of cDNA libraries and microarray analyses. Potential target genes of deregulated miRNAs were identified by database analysis and subsequently validated in vitro using reporter gene constructs. The abundance of ERG as one of the identified target genes was assessed by Western blotting using a self-generated polyclonal antiserum.
Results: One of the miRNAs consistently deregulated in primary prostate cancer samples was miR-145 which was down regulated more than 1.5-fold in deep sequencing and 1.44-fold in microarray experiments (p&lt;0.001, ANOVA). Independent target prediction databases (including miRanda, Targetscan and PicTar) indicated that the 3’ untranslated region (3’-UTR) of the ERG gene is a regulative target for miR-145. This prediction could be confirmed using a luciferase reporter gene vector containing the ERG 3’-UTR. Co-expression of the reporter gene construct with miR-145 resulted in a reduction of reporter gene activity while mutation of the miRNA binding site caused a loss of responsiveness to the respective miRNA. We generated a polyclonal antiserum directed against the 100 C-terminal amino acids of the longest ERG isoform and discovered that transient expression of miR-145 reduced the amount of ERG protein by 26% in the HEK293 cell line. Western blots of 26 corresponding pairs of prostate cancer and nonmalignant tissue samples showed, that ERG protein is overexpressed in the majority of cancer samples and that the relative abundance of several identified isoforms of ERG is altered in cancer samples. As expected, miR-145 expression was reduced in 24 of the 26 tumor samples.
Conclusion: Our findings demonstrate that the 3’-UTR of ERG is one regulative target of miR-145, which is commonly deregulated in prostate cancer. The ERG gene is commonly overexpressed in prostate cancer and the relative abundance of ERG isoforms is altered in samples of primary prostate cancers. This is the first report to show that ERG is a target of miR-145.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3951. doi:10.1158/1538-7445.AM2011-3951
Abstract 4043: Characterization of the enzymatic activity, biochemical requirements and inhibition of deubiquitinating enzymes, a novel oncology target class
Authors: Wrigley Jonathan D. , Eckersley Kay , Plant Helen , Preston Marian , Millard Lindsey , Hardern Ian , Nowak Thorsten , Simpson Peter B. , Andrews David , Hudson Kevin 
Published: August 2014

Abstract
Deubiquitinating enzymes (DUBs) represent promising opportunities for therapeutic intervention in oncology, and this study reports key information about the catalytic activity, assaying and inhibition of this novel enzyme class. The DUBs are proteases responsible for the cleavage of Ubiquitin from substrate molecules, and the resulting effects on the levels or activity of the substrates has been shown to play key roles in a range of cellular processes.
Here we have utilized a range of in vitro and cellular assays of DUB activity to characterize various DUB enzymes, generate high throughput screens and profile DUB inhibition by hit molecules, to further our understanding in this area.
The characterization of different DUBs has enabled us to highlight both differences and similarities in their behavior and requirements, particularly with respect to protein subunits, reducing conditions, and activity against different substrates. Profiling of small-molecule hits targeting these enzymes, under various in vitro conditions, and also in a cellular environment, has not only yielded information on the compounds, but has also demonstrated key considerations about the inhibition of these cysteine proteases.
Together these findings further our knowledge of this novel target class, as well as providing valuable information to aid the hunt for therapeutic agents modulating these enzymes in a range of oncology settings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4043. doi:10.1158/1538-7445.AM2011-4043
Abstract 4050: Quantitation of sirtuin activity with a one-step luminescent assay
Authors: Kirkland Thomas A. , Evans Nathan , Niles Andrew L. 
Published: August 2014

Abstract
The Sirtuin family of histone/protein deacetylating enzymes has gained considerable interest both for their recognized importance in processes such as gene silencing and expression and in cellular metabolism. This has led to identification of these enzymes as important actors in diverse pathologies including diabetes, Alzheimer's disease and oncology. We have developed a convenient and sensitive screening methodology to detect and measure both inhibitors and activators of sirtuin activity. Here we describe a one-step, homogeneous luminescent assay for the detection of activity for multiple sirtuin isotypes. The reagent formulation contains a pro-luminescent sirtuin peptide substrate, NAD+, ATP, thermostable luciferase, and a developer enzyme that cleaves deacetylated lysine residues. The addition of an active sirtuin enzyme source leads to a robust luminescent signal within minutes with “glow-type” characteristics lasting for several hours. Data will be presented showing characterization of the assay using a diverse assortment of established sirtuin inhibitors, followed by suitability for screening in 384-well formats and the incorporation of a control substrate to identify false positives.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4050. doi:10.1158/1538-7445.AM2011-4050
Abstract 4066: Combination metformin and ODC siRNA inhibit human melanoma proliferation and migration
Authors: Hsueh Eddy C. , Zhang Yanping , Peng Guangyong 
Published: August 2014

Abstract
Metformin can exert an antiproliferative effect on human tumor cells through the AMP-activated kinase (AMPK) pathway. Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis pathway in cancer cell proliferation and tumor progression. We hypothesized that the combination of Metformin and small interfering RNA (siRNA) against ODC could inhibit human melanoma cell growth and migration in vitro.
Human melanoma cell line cells (SK-MEL23, MEL1861, MEL938, MEL3910, and MEL888) were evaluated. ODC siRNA and contol siRNA were transfected into the human melanoma cells using lipofectamine per manufacturer's instructions (Santa CruZ. CA). Transfected cell were then treated with 1uM, 2uM, 5uM Metformin and assess for cell proliferation and migration assay at various time points up to 72 hours. Cell proliferation assay was performed in triplicates using Cell Titer Blue Assay system according to manufacturer's protocol (Promega). Migration was assessed by creating an artificial homogenous wound onto a cell culture monolayer with a sterile plastic 10µl micropipette tip. Migration of cells into the wound was observed and photographed up to 48 hours. A total of three areas were selected randomly from each well and the cells in three wells of each group were quantified. All Data were presented as means ± SD for the three separate experiments. For comparison between groups, the student's t test was used and p&lt; 0.05 was considered to be statically significant.
Human melanoma cells were infected with ODC siRNA or control siRNA. On quantitative RT-PCR and Western blot analysis, &gt;95% suppression of ODC expression was achieved. The siRNA-ODC significantly inhibited cells growth up to 50% at 72 hour (P&lt;0.01). Inhibition of melanoma cell proliferation was also observed with Metformin in a dose-dependent fashion in all 5 melanoma cell line cells. Combination of ODC siRNA and Metformin significantly inhibited cell growth compared to ODC siRNA or MF alone (P&lt;0.01) in all 5 melanoma cell line cells. The addition of Metformin to siRNA-ODC also significantly inhibited melanoma migration in the wounding assay model.
Metformin treatment and inhibition of ODC expression can have anti-proliferative effect on human melanoma cells. The combination also retard melanoma cell migration in a wounding model. The combination of Metformin and ODC inhibition may be a novel treatment strategy for human melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4066. doi:10.1158/1538-7445.AM2011-4066
Abstract 4113: Kinase activity based biomarkers: Identification of prognostic and erlotinib response prediction markers in NSCLC patients
Authors: Ruijtenbeek Rob , Thijssen Victor , Schaake Eva , Houkes Liesbeth , de Wijn Rik , van de Heuvel Michel , van Suylen Robert-Jan , van Pel Rene , Nederlof Petra , Hilhorst Riet , Dingemans Anne-Marie , Klomp Houke 
Published: August 2014

Abstract
Background: Reliable diagnostic tests are needed to identify early stage non-small cell lung carcinoma (NSCLC) patients with poor prognosis. Concomitantly there is a clear need for tests that enable the selection of patients who will benefit from targeted therapy with kinase inhibitors. We evaluated kinase activity profiles in two groups of early stage NSCLC patients, either for prognosis of long- or short-term survival, or for predicting erlotinib drug response.
Method: Retrospective studies were performed on fresh frozen resection material of two groups of early stage NSCLC patients. The first group consisted of 48 short- and long-term survivors who underwent a complete surgical resection (5+ years follow-up). The second group consisted of 14 NSCLC patients who received 3 weeks of neo-adjuvant treatment with erlotinib prior to complete surgical resection. Response evaluation to neo-adjuvant treatment was based on histopathological examination of the surgical specimens. For both studies, kinase activity profiles of lysed cryosections of tumour tissues were generated in the presence and absence of protein tyrosine kinase inhibitors on PamChip® peptide micro-arrays, comprising 144 tyrosine containing peptides, derived from known phosphorylation sites of human proteins. Partial least square discriminant analysis was used to construct prediction models. ClustalW alignment algorithms were used to investigate the most informative phosphorylation sites.
Results: Kinase activity profiles obtained in the absence of inhibitor did not distinguish between subgroups (long- versus short-term survival, responder or non-responder to TKI), whereas ratios of inhibited versus non-inhibited signals resulted in distinct classifiers predicting survival for the first group, and response for the second group. Multivariate unsupervised analysis with leave-one-out cross-validation resulted in an error rate for survival prediction of 29%. In the drug response prediction 13 out of 14 patients were correctly classified.
Conclusion: This is the first study to show that kinase activity profiles of tumour tissue exposed to a kinase inhibitor can be used to identify NSCLC patients likely to respond to erlotinib treatment. Furthermore, based on kinase activity profiles of early stage NSCLC tumours, a prognostic classifier, for a set of 48 patients, was obtained.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4113. doi:10.1158/1538-7445.AM2011-4113
Abstract 4115: Prediction of drug sensitivity based on correlation of molecular and genetic signatures between lung tumor cell lines and tumor tissue samples from NSCLC cancer patients
Authors: Gong Hua C. , Beer David , Singh Sharat , Webster Edvelyn , Meyer Gary 
Published: August 2014

Abstract
To establish transition of preclinical response profiles to the subsequent clinical treatment, we profiled pathway activation and genomic signature in tumor cell lines and human tumor tissues. This profiling has allowed us to define molecular pathways and these models may serve as an excellent platform to evaluate the efficacy of targeted therapies. We profiled pathway activation, mutation status, and clinical histology of a panel of representative lung tumor cell lines and 50 human lung adenocarcinoma samples. We cluster patients samples with corresponding tumor cell lines based on such signature and predicted treatment options for the patients based on response to selected candidate treatment of the cell lines. Subsets of patients were identified as candidates to treatment with inhibitors of EGFR, cMET, IGFR, MEK, and PI3K/mTOR. EGF pathways in EGFR mutant cell lines NCI-H1975, HCC827 and NCI-H1650 are highly activated, and those cells were sensitive to inhibitors blocking EGFR signaling. A group of patients were identified to share the similar profiles, and we predict those are candidates for EGFRi therapies. While H1973 is a cMET amplified line with cMET and EGFR activated, patients sharing this genotype may respond to cMET inhibitor treatment. IGF1R expressing A549 and NCI-H358 cells were sensitive to IGF1R inhibition, the patients sharing the similar profile may be candidates to this class of therapies. PI3K/mTOR inhibitor, BEZ 235, effectively inhibited tumor cell growth in most of the cell lines except NCI-H1993 and NCI-H358 cells; while MEK inhibitor PD-325901 was less active in blocking growth of k-RAS mutant cell lines NCI-H460, NCI-H1734, NCI-H358 and A549. Patients with a similar signature may benefit from those treatments. By combining pathway biomarker, mutation status, and clinical features, we were able to cluster clinical patient samples to the lung tumor cell lines and propose treatment options for the patients based on their signature overlap.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4115. doi:10.1158/1538-7445.AM2011-4115
Abstract 4116: Predictive biomarkers for the PI3 kinase inhibitor GDC-0941 in NSCLC
Authors: Spoerke Jill , O'Brien Carol , Boyd Zach , Mohan Sankar , Pandita Ajay , Berry Leanne , Fridlyand Jane , Friedman Lori , Hampton Garret , Amler Lukas , Lackner Mark 
Published: August 2014

Abstract
The class I phosphatidylinositol 3’ kinase (PI3K) plays a major role in proliferation and survival in a wide variety of human cancers. A key factor in successful development of drugs targeting the PI3K pathway is likely to be the identification of responsive patient populations with predictive diagnostic biomarkers. GDC-0941 is a pan-inhibitor of all 4 isoforms of class 1 PI3K that is currently undergoing testing in the clinic. We were interested in the predictive value of candidate biomarkers in NSCLC to help inform clinical trial biomarker strategies in this indication. We assembled a focused panel of cell lines with key alterations in the PI3K pathway isolated from other genetic events to the extent possible. The approach involved pharmacogenomic and proteomic profiling. We found that models harboring key pathway alterations were exquisitely sensitive to GDC-0941. In particular, cell lines with EGFR mutations, PIK3CA mutations or amplification were the most sensitive. Inhibition of PI3K in mechanism of action studies showed effects consistent with induction of apoptosis, cell cycle arrest, and impairment of translation in models with these key alterations. In addition, gene expression changes of genes downstream of PI3K were seen upon treatment with GDC-0941 in sensitive cell lines but not those that were resistant. We extended these studies to NSCLC tumor samples and evaluated the prevalence of important pathway alterations, including PTEN loss, PIK3CA amplification, LKB1 loss in tumors representing distinct histopathological subtypes. We find that certain candidate biomarkers show subtype specific associations, and will discuss the implications for the development of PI3K-targeting agents in NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4116. doi:10.1158/1538-7445.AM2011-4116
Abstract 4117: A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA in lung cancer patients
Authors: Aragane Naoko , Nakamura Tomomi , Iwanaga Kentaro , Sato Akemi , Komiya Kazutoshi , Abe Tomonori , Ureshino Norio , Hayashi Shinichiro , Hosomi Toshiya , Hirai Mitsuharu , Sueoka Eisaburo , Kimura Shinya 
Published: August 2014

Abstract
Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) have great response to lung adenocarinoma with EGFR activating mutations, acquired resistance eventually developed. The half of these patients has the gatekeeper T790M mutation of EGFR in lung cancer tissue. A non-invasive mutation detection system is desired considering the difficulty in obtaining tissue specimens during disease progression_the majority of lung cancer recurrences occur in distant sites. We report a novel non-invasive monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect the mutation using plasma DNA. The MBP-QP method is combined with mutated biased PCR and genotyping based on the analysis of a melting curve of probe DNA which is bound to the target mutated site using a fluorescence quenching probe. The detection limit was 2 copies of control plasmid, and 0.2 ng of genomic DNA isolated from a lung caner cell line harboring T790M. 0.3 % mutant plasmid could be detected in the mixture of plasmids inserted with EGFR exon 20 with or without T790M. With this method, T790M mutations were detected in plasma DNA of 50% of patients who acquired resistance, but not in primary EGFR-TKI non-responders, patients responding to treatment, or patients not treated with EGFR-TKI, which is consistent with the clinical course. The non-invasive MBP-QP method enabled us to monitor T790M repeatedly and will be useful for determining appropriate lung cancer treatment strategies in practice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4117. doi:10.1158/1538-7445.AM2011-4117