bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3963: MicroRNA-124 and microRNA-1, commonly lost in glioma, coordinately target sphingosine kinase-1 in glioma cells
Authors: Godlewski Jakub A. , Bronisz Agnieszka , Van Brocklyn James , Wang Yan , Lawler Sean , Chiocca E. Antonio 
Published: August 2014

Abstract
Glioma (Glioblastoma multiforme, GBM) is the most common and the most aggressive form of brain tumor. As its Latin name implies, glioma is characterized by enormous heterogeneity and many different genes and cellular pathways responsible for glioma genesis and progression have been described. One of them is Sphingosine Kinase-1 (SPHK-1), a bona fide oncogene in glioma, whose marked up-regulation of expression and activity is responsible for the poor patient outcome due to escalating proliferation and invasiveness of glioma cells.
MicroRNAs are short, non-coding regulators of the gene expression and deregulation of their expression is a frequent event in the formation and progression of many malignancies including glioma. Among these deregulated microRNAs, microRNA-124 is the most downregulated microRNA. It has been shown to promote neuronal differentiation and inhibit glioma cell proliferation and to target CDK6. Here we show that microRNA-1 is also severely downregulated in glioma patients and that it acts coordinately with microRNA-124 to target SPHK-1. We show that both microRNAs directly target the SPHK-1 3’UTR and that such targeting results in the decrease of both SPHK-1 expression and activity. We also demonstrate that overexpression of both microRNA-124 and microRNA-1 causes a significant increase in the frequency of apoptotic cells and marked decrease in glioma cell proliferation and invasiveness.
Additionally, we show that microRNA-1 directly targets another glioma oncogene – Annexin2A (ANXA2). Targeting of ANXA2 by microRNA-1 impairs glioma cell-cell adhesion and glioma spheroid formation, which effect can be partially rescued by the overexpression of ANXA2 with a mutated microRNA-1 target site but not by wild type ANXA2.
Our results provide another target of therapeutic importance for microRNA-124 in glioma cells. Here we show that microRNA-124, along with microRNA-1 can exert profound effect on glioma cells by inhibiting expression and activity of SPHK1 and that additional effects caused by microRNA-1 are likely mediated through targeting ANXA2.
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 3963. doi:10.1158/1538-7445.AM2011-3963
Abstract 4045: c-Met inhibition synergistically enhances death receptor-induced apoptosis via upregulation of DR5 in papillary thyroid cancer
Authors: Bavi Prashant , Bu Rong , Hussain Azhar R. , Ahmed Maqbool , Thangavel Saravanan , Al-Sobhi Saif , Al-Nuaim Abdulrahman , Amin Tarek , Ahmed Mohammed , Uddin Shahab , Al-Kuraya Khawla S. 
Published: August 2014

Abstract
The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in variety of human malignancies. Previously we have shown that c-Met was overexpressed in Middle Eastern Papillary Thyroid Cancer (PTC) and significantly associated with poor prognoses. In this study, we investigated the functional link between c-Met/AKT signaling pathway and Dearth Receptor 5 (DR5) in a large cohort of PTC patient samples, a panel of PTC cell lines, and xenografts in a NUDE mouse model by using tissue microarray, MTT, flow cytometry and DNA fragmentation assays and western blotting. Immunohistochemistry staining showed a significant association of p-Met with DR5 in PTC patient samples. The PHA665752, an inhibitor of c-met tyrosine kinase, inhibited cell proliferation and induced apoptosis in a dose dependent manner in all cell lines studied. PHA665752 treatment resulted in dephosphorylation of c-Met, AKT and its downstream effector molecules FOXO1, GSK-3 and pBad. Additionally, treatment of PTC cell lines with PHA665752 resulted in activation of caspases-9 and 3, cleavage PARP and apoptosis. Moreover, HGF, a ligand of c-Met, stimulated the growth of all PTC cell lines via activation of c-MET and AKT. In addition, pre-treatment of PTC cell line with PHA665752 abrogated the HGF stimulated growth and activation of c-met and AKT further suggesting the critical role of c-met and AKT pathway in PTC pathogenesis. Furthermore, c-Met inhibitor PHA665752 up-regulated DR5 expression in PTC cell line cells, and synergistically potentiated death receptor-induced apoptosis with TRAIL. Finally, co-treatment with PHA665752 and TRAIL causes more pronounced effect on PTC xenograft tumor growth in NUDE mice. Our data suggest that c-Met/HGF pathway may be a potential target for therapeutic intervention for treatment of PTC with c-Met inhibitor alone or in combination of conventionally therapeutic agents.
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 4045. doi:10.1158/1538-7445.AM2011-4045
Abstract 4047: TRIM32 facilitates cell growth, migration and anti-apoptosis
Authors: Kano Satoshi , Hatakeyama Shigetsugu , Fukuda Satoshi , Hatakeyama Hiromitsu 
Published: August 2014

Abstract
Introduction: Tripartite motif (TRIM) proteins are characterized by the presence of a RING finger, one or two zinc-binding motifs named B-boxes and an associated coiled-coil region. Most TRIM proteins have been reported to have a role in the ubiquitination process. Furthermore, several TRIM family members are involved in various cellular processes such as transcriptional regulation, cell growth, apoptosis, development and oncogenesis. TRIM32 also has a RING-finger domain and functions as an E3-ubiquitin ligase. In the previous study, it has been reported that TRIM32 protein expression is elevated in a mouse skin carcinogenesis model and in human skin squamous cell carcinoma and TRIM32 mRNA expression is elevated in human head and neck squamous cell carcinoma. However, the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we studied the function of TRIM32 in the progression of carcinogenesis.
Methods: We established the cell lines overexpressed TRIM32 wild type and the deletion mutant of the RING-finger domain by the infection of retrovirus vectors. Using these cell lines, we analyzed the effect of TRIM32 on cell growth, transforming activity, cell motility and apoptosis induced by cisplatin. Additionally, we investigated whether siRNA for TRIM32 effects on these functions. Furthermore, we examined the expression level of TRIM32 protein in oral carcinoma samples using immunohistochemical method and analyzed the relationship between TRIM32 and clinical presentation.
Results: Overexpression of TRIM32 promoted cell growth, transforming activity and cell motility, whereas a dominant negative mutant of TRIM32 lacking the RING-finger domain inhibited these effects. In addition, we found that TRIM32 suppressed apoptosis induced by cisplatin in HEp2 cell lines, originating from human laryngeal squamous cell carcinoma. In contrast, siRNA for TRIM32 suppressed cell proliferation, cell motility and anti-apoptosis. In clinical research, a high-expression group of TRIM32 presented more advanced stage (clinical stage, T stage and neck lymph node metastasis) than a low-expression group.
Conclusions: In this study, our experimental results in vitro were supported by clinical research. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis and resistance to anti-cancer drugs.
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 4047. doi:10.1158/1538-7445.AM2011-4047
Abstract 4048: Histological image profiling identifies aggressive glioblastoma phenotype with poorer survival
Authors: Liu Yuexin , Shmulevich Ilya , Fuller Gregory , Zhang Wei 
Published: August 2014

Abstract
The stratification of glioblastoma (GBM) patients into clinically relevant subtypes is an essential step in the direction of personalized genomic medicine. In contrast to currently employed time- and cost-intensive genomic methodologies, we describe here a novel cost-effective approach capable of detecting predictors of invasive disease in GBM based on profiling of histological images. Unsupervised statistical analysis of imaging feature data first distinguishes two major clusters with strikingly different phenotypes. The subsequent Kaplan-Meier survival analysis of these two clusters shows that patients who had tumors in cluster 2 (which we refer to as aggressive subtype for the purpose of clarity) had poorer overall survival. Among the differentially varied features, the aspect ratio parameter, which is a strong indicator of cell movement, exhibits larger values in the aggressive subtype, suggesting greater invasiveness of this subset. Based on the initial dataset, a predictive model comprised of informative features was constructed using a weighted voting algorithm. Cross-validation of this sample set revealed a predictive accuracy of over 90% in correctly classifying these two groups, with specificity of ∼94% and sensitivity of ∼90% as determined by the receiver operating characteristic curves method. In a manner similar to gene biomarkers, some of imaging features can be used as diagnostic and prognostic factors in GBM. To identify the molecular events underlying the identified phenotypes, we performed genome-wide expression data analysis of the same sample set. Among the marker genes identified as overexpressed in the aggressive subtype were CHI3L1, CD44 and TNFRSF1A, which have been previously associated with poorer survival in GBM. In addition, pathway analysis of differentially-expressed genes indicates significant activation of the glioma invasiveness signaling and NF-κB signaling pathways; most of the altered genes in both pathways are more highly expressed in the aggressive GBM subtype and are thus potentially linked to the poorer survival of this group. Our novel approach has the potential to unify the imaging and genomic dimensions of GBM for clinical stratification.
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 4048. doi:10.1158/1538-7445.AM2011-4048
Abstract 4049: AP2A1 is required for UV-induced EGFR nuclear translocation
Authors: Hsu Sheng-Chieh 
Published: August 2014

Abstract
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved in cell proliferation, differentiation and survival. Aberrant expression and activation of EGFR have shown to cause various types of human and frequently associated with poor prognosis, metastasis and chemoresistance. Interestingly, this cell membrane receptor, which has been extensively studied, not only transduces signals from the cell membrane, but can also translocate into the nucleus and play a role in gene regulation, DNA repair and chemoresistance. Nuclear translocation of EGFR could be induced by ligand-dependent and ligand-independent manners including ionizing radiation (IR), cisplatin and UV treatment. However, the molecular mechanisms of EGFR nuclear translocation induced by DNA damage agents remain unclear. Here, we identify EGFR interacts with AP2A1 upon UV treatment using proteomic approach. The AP2A1 is the alpha 1 adaptin subunit of the adaptor protein 2 (AP2) complex found in clathrin coated vesicles. Knock-down AP2A1 expression inhibits the UV-induced EGFR nuclear translocation. Thus, we demonstrate here AP2A1 is required for UV-induced EGFR nuclear translocation.
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 4049. doi:10.1158/1538-7445.AM2011-4049
Abstract 4054: Cell viability, apoptosis and ploidy analyses on a multi-laser, versatile flow cytometry analyzer – the EclipseTM
Authors: Song Yong 
Published: August 2014

Abstract
Cell viability, apoptosis and ploidy analyses are essential tools in cancer research involving in vitro and in vivo studies. Assays for cell count and viability, apoptosis and cell cycle analysis are described in this report. Jurkat or Chinese hamster ovary cells were treated with various reagents such as anti-CD95, taxol, or brefaldin A to induce apoptosis. Apoptotic cells were labeled with Avenxin-V conjugated with Pacific Blue or FITC to determine externalization of phosphatidylserine to the cell surface. In combination with cell impermeant dyes, such as 7-aminoactinomycin D (7-AAD) or propidium iodide (PI), live, early apoptotic and late apoptotic/dead cells were labeled and analyzed on an Eclipse equipped with the 405 and 488 lasers. The iCyt® Eclipse TM is a compact bench top flow cytometry analyzer with an autoloader that supports a wide variety of multi-well plate and test tube formats. The system can be equipped with up to 4 lasers (405, 488, 561 and 642nm) and provides simultaneous detection of 5 colors, forward scatter, side scatter, electronic volume (EV) and cell concentration. The EV parameter enables accurate cell volume (size) measurement and allows normalization of fluorescent intensity on a per volume or surface area basis. Apoptotic cells were also detected with a phycoerythrin-labeled anti-active caspase 3 antibody after fixation and permeabilization. Cell cycle analysis with G0/G1, S and G2/M phase statistics plus cell size was achieved by labeling cells with 4′,6-diamidino-2-phenylindole (DAPI) in a cell permeabilization solution and analyzing on the Eclipse. Together with its intuitive software, the Eclipse flow cytometry analyzer provides a rapid, accurate and cost effective tool for most flow cytometry applications such as cell viability, apoptosis and cell cycle analysis.
Note: For research use only. Not for use in diagnostic procedures.
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 4054. doi:10.1158/1538-7445.AM2011-4054
Abstract 4110: NanoString multiple target profiling identifies AEG-1 as an essential predictor of erlotinib outcome in EGFR-mutant non-small cell lung cancer (NSCLC)
Authors: Taron Miquel , Benlloch Susana , Rosell Rafael , Sanchez Jose Javier , Costa Carlota , Santarpia Mariacarmela , Viteri Santiago , Gasco Amaya , Massuti Bartomeu , Gimenez-Capitan Ana 
Published: August 2014

Abstract
Background: Low BRCA1 mRNA expression significantly prolongs progression-free survival (PFS) to erlotinib in EGFR-mutant NSCLC patients (p). In order to explore other genes potentially involved in erlotinib resistance, we used NanoString, an integrated digital technology, to examine expression levels of 48 genes in a single reaction. Several genes involved in homologous recombination repair were included in the 48-gene assessment, including the E3 ubiquitin ligases RNF8, RNF168 and RAP80.
Methods: CodeSets (Reporter and Capture probe sets) for 48 genes were custom-designed by NanoString Technologies. 100ng of total RNA for each sample was mixed with the reagents and hybridized at 65° overnight. Samples were processed and analyzed with the nCounter Prep Station (NanoString Technologies). Data analysis was performed adjusting the expression values according to positive control values and normalizing the data according to housekeeping genes.
Results: In 43 EGFR-mutant NSCLC p treated with erlotinib, response rate was 67.6%, PFS was 16 months (m), median survival (MS) was 29 m. Three genes were significantly associated with PFS: PIAS1, DBC1 and AEG-1. Median PFS was not reached in p with low levels of AEG-1, while it was 18 m for p with intermediate levels and 5 m for p with high levels (P=0.002). In the multivariate analysis, the hazard ratio for high levels of AEG-1 was 14 (P&lt;0.001).
Conclusions: AEG-1 activates the NF-κB and PI3K/Akt pathways, induces the transcription factor LSF, which upregulates TS, ALDH3A1 and Met, conferring resistance to several cytotoxic drugs. AEG-1 mRNA expression predicts outcome to erlotinib-treated EGFR-mutant NSCLC p and could have important implications for the optimal management of 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 4110. doi:10.1158/1538-7445.AM2011-4110
Abstract 4111: EGFR gene mutation as a predictive marker of the response to pemetrexed-based chemotherapy in non-small cell lung cancer
Authors: Nobuyuki Koyama , Sadakata Rinako , Miyazawa Hitoshi , Hagiwara Koichi , Kobayashi Kunihiko 
Published: August 2014

Abstract
[Background] Pemetrexed (PEM) is an antimetabolite that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, and one of standard anti-cancer agents against non-small cell lung cancer (NSCLC), particularly non-squamous cell carcinoma, whereas there is insufficient evidence for clinical practice. [Methods] We retrospectively studied 111 NSCLC cases treated with PEM-based chemotherapy in our institute to analyze the correlation of clinicopathological characteristics with the therapeutic effect of PEM. Furthermore, the validation of identified factors from the analysis was also conducted, using in vitro assays. [Results] The therapeutic effect of PEM plus carboplatin was comparable to that of PEM plus cisplatin from χ2 test. Kaplan-Meier survival analysis and logrank test showed that in the patients receiving PEM-based chemotherapy, epidermal growth factor receptor (EGFR) gene mutation was significantly correlated with the therapeutic effect and progression free survival but not overall survival. From IC50 of PEM, NSCLC cells with mutant EGFR were significantly sensitive to those with wild-type EGFR. [Conclusion] EGFR gene mutation can be a predictive marker of the response to PEM-based chemotherapy.
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 4111. doi:10.1158/1538-7445.AM2011-4111
Abstract 4112: De novo EGFR T790M mutation modifies outcome to second-line erlotinib in non-small cell lung cancer (NSCLC) according to metastatic site and upfront chemotherapy
Authors: Rosell Rafael , Molina Miguel Angel , Sanchez Jose Javier , Taron Miquel , Benlloch Susana , Moran Teresa , Carcereny Enric , Cardenal Felipe , Massuti Bartomeu , Magri Ignacio 
Published: August 2014

Abstract
EGFR T790M mutation is associated with shorter progression-free survival (PFS) (12 months [m] vs 18 m; P=0.02). We hypothesized that the site of metastases (mets) and/or prior chemotherapy could also influence outcome in these p.
Methods: The T790M mutation was assessed in 129 advanced NSCLC p by TaqMan assay in the presence of a peptide-nucleic acid designed to inhibit the amplification of the wild-type allele.
Results: De novo T790M mutations were identified in 35% (45 of 129) of EGFR-mutant p before receiving erlotinib. The T790M mutation was detected more frequently in p with bone mets (35.6% vs 16.7%; P=0.03). PFS was 20 m for 58 p with a deletion in EGFR exon 19 (del 19) but without the T790M mutation vs 12 m for 23 p with both del 19 and the T790M mutation (P=0.03), but with no difference in MS between these two groups (31 m vs 29 m; P=0.56). PFS was 15 m for 26 p with the L858R mutation but without the T790M mutation vs 16 m for 22 p with both the L858R and T790M mutations (P=0.83), with no difference in MS between these two groups (27 m vs 21 m; P=0.81). When p with T790M were divided according to the presence of brain mets, PFS was 1 m for 4 p with brain mets vs 13 m for 41 p without brain mets (P=0.002), while MS was 6 m for p with brain mets vs 36 m for those without (P=0.009). No effect on PFS or MS was observed in p with the T790M mutation according to lung, liver, pleura or bone mets. In the multivariate analysis, the presence of the T790M mutation did not increase the risk of short MS (HR, 1.3; P=0.49), while having received prior chemotherapy was associated with longer MS (HR, 0.48; P=0.02).
Conclusions: The de novo T790M mutation is a marker for poor prognosis in p with brain mets. Upfront chemotherapy can play a role in the management of NSCLC p with the de novo T790M mutation.
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 4112. doi:10.1158/1538-7445.AM2011-4112
Abstract 4118: Expression of CD133 as a prognostic marker of non-small cell lung cancers
Authors: Mizugaki Hidenori , Konishi Jun Sakakibara , Kikuchi Junko , Kikuchi Eiki , Moriya Jun , Kubota Kanako , Kinoshita Ichiro , Oizumi Satoshi , Akita Hirotoshi Dosaka , Matsuno Yoshihiro , Nishimura Masaharu 
Published: August 2014

Abstract
[Background] CD133 is a membrance glycoprotein with five transmembrance loops. Previous reports have suggested that CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal abilities has biological features as a cancer stem cell. In addition, it has been reported that the presence of CD133-positive cells was associated with a significantly poorer prognosis compared with the CD133-negative cells in some solid tumors, including colon cancer, hepatocellular carcinoma and glioma. However, little is known about the relationship between the expression of CD133 and clinical and clinicopathological characteristics in lung cancer.
[Aim and Method] We conducted immunohistochemical assessment of 161 surgically resected non-small cell lung cancers (NSCLCs) at Hokkaido University Hospital between 1982 and 1994 to evaluate the correlation between CD133 expression and various features, including clinical and clinicopathological characteristics.
[Results] Normal alveoli were used as negative controls and Bowman's capsule basement membrane as positive controls. CD133 expression was significantly correlated with advanced p-Stage (p=0.040). The Kaplan-Meier method demonstrated that NSCLC patients with CD133 expression in tumor cells showed poor prognosis compared to those without CD133 expression in p-Stage II, III and IV (p=0.0098). CD133 expression alone was an independent factor for unfavorable prognostic in those patients (Hazard Ratio=3.157, p=0.015).
[Conclusion] CD133 expression was correlated with p-Stage and was an independent factor for unfavorable prognosis in patients with p-Stage II, III and IV NSCLCs. CD133 expression may be a novel prognostic marker for NSCLCs.
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 4118. doi:10.1158/1538-7445.AM2011-4118