1,721,076 research outputs found
Abstract 4130: Characterization of URST1 as a prognostic biomarker and therapeutic target for lung cancer
No full textAbstract
Lung cancer is the most frequent cause of cancer deaths worldwide and its overall prognosis remains poor. Therefore, next generation of biomarkers and therapeutic strategies for lung cancer are eagerly awaited. We selected genes that were overexpressed in the majority of lung cancer using our gene expression profile database. During this process, we identified URST1 (Up-regulated in solid tumor 1) as a candidate. Immunohistochemical staining showed that URST1 expression was observed in the majority of non-small cell lung cancer (NSCLC) patients (P = 0.0013 by log rank test). Multivariate analysis revealed high level of URST1 expression was an independent prognostic factor for NSCLC patients. Moreover, reduction of URST1 by siRNA or treatment with URST1 inhibitor significantly suppressed lung cancer cell growth probably through cell cycle arrest at G2/M. Exposure of cancer cells to URST1 inhibitor significantly suppressed These data suggest that URST1 is a possible prognostic biomarker and therapeutic target for lung cancer.
Citation Format: Atsushi Takano, Yohei Miyagi, Yataro Daigo. Characterization of URST1 as a prognostic biomarker and therapeutic target for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4130. doi:10.1158/1538-7445.AM2017-4130</jats:p
Abstract 4453: Identification and characterization of oncogenic kinase LASK2 as a diagnostic and therapeutic target for lung cancer
No full textAbstract
Lung cancer is the leading cause of cancer deaths worldwide. Since the number of patients responding well to standard therapies is still limited, further development of new anti-cancer agents with minimum risk of adverse event is urgently awaited. To screen oncoantigens which could be used for the development of new diagnostic biomarkers and molecular targeted drugs, we have established a screening system as follows; i) To identify overexpressed genes in 120 lung cancers by genome-wide screening using the microarray representing 27,648 genes and pure populations of tumor cells taken from cancer tissues by laser microdissection, ii) To verify the genes for their very low or absent expression in normal tissues by northern-blotting, iii) To validate the clinicopathological significance of their expression with tissue microarray covering hundreds of archived lung cancers, iv) To verify whether the target genes are essential for the growth or survival of lung cancer cells by RNAi and cell growth assays. During this process, we selected dozens of druggable oncogenes with various enzymatic activities, and identified overexpression of protein kinase LASK2 (lung cancer-associated kinase 2) in the majority of lung cancers, but not in normal tissues except testis. Immunocytochemical analysis found LASK2 to be mainly localized in the cytoplasm and nucleus of lung cancer cells. Immunohistochemical analysis revealed that strong LASK2 expression was an independent prognostic factor for non-small cell lung cancer (NSCLC) (P&lt;0.0001). Suppression of LASK2 expression with its specific siRNAs caused growth inhibition of lung cancer cells. The enhanced cellular proliferation by introduction of LASK2 in mammalian cells also supported its oncogenic function. Since LASK2 plays a significant role in the cell proliferation and malignant nature of lung cancers, LASK2 is likely to be a prognostic biomarker and a potential therapeutic target for developing new anti-cancer drugs.
Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Identification and characterization of oncogenic kinase LASK2 as a diagnostic and therapeutic target for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4453. doi:10.1158/1538-7445.AM2017-4453</jats:p
Abstract 3708: RAS-MAPK signal is required for enhanced PD-L1 expression in human lung cancers
No full textAbstract
Ectopic programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancers (NSCLCs) is related to immune evasion by cancer, and it is a molecular target of immune checkpoint therapies. Since the precise mechanisms responsible for ectopic PD-L1 expression remains obscure, we analyzed the molecular mechanisms of ectopic PD-L1 expression in human lung cancers, focusing on the MAPK signal. Because we found a higher frequency of EGFR/KRAS mutations in NSCLC cell lines with high PD-L1 expression (p &lt; 0.001), we evaluated the relationships between downstream signals and PD-L1 expression, particularly in three KRAS-mutant adenocarcinoma cell lines. The MEK inhibitor U0126 (20 μM) significantly decreased the surface PD-L1 levels by 50-60% compared with dimethyl sulfoxide (p &lt; 0.0001). Phorbol 12-myristate 13-acetate stimulation (100 nM, 15 min) increased (p &lt; 0.05) and two ERK2 siRNAs as well as KRAS siRNAs decreased (p &lt; 0.05) PD-L1 expression. Post-transcriptional mechanism by miR-200s appears not to be in general under the downstream of MAPK in the PD-L1 expression. The transcriptional activity of the potential AP-1 site (+4785 to +5056 from the transcription start site) in the PD-L1 gene was demonstrated by luciferase assays, which was inhibited by U0126. The chromatin immunoprecipitation assay demonstrated the binding of cJUN to the AP-1 site. Two STAT3 siRNAs decreased PD-L1 expression by 10-32% in two of the three KRAS-mutant lung adenocarcinoma cell lines (p &lt; 0.05), while the PI3K inhibitor LY294002 (40 μM) did not change the expression level. Supervised cluster analysis and gene set enrichment analysis between the PD-L1-high and -low NSCLCs revealed a correlation between PD-L1 expression and genes/pathways related to cell motility/adhesion. These results indicate that MAPK signaling is the dominant downstream signal responsible for ectopic PD-L1 expression at a transcriptional level, in which STAT3 is also involved to some extent. Furthermore, MAPK signaling may control the expression of PD-L1 and several genes related to enhanced cell motility. Our findings suggest that MAPK is important for determining PD-L1 expression, which could be useful for targeted therapies against lung cancers.
Citation Format: Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Yataro Daigo. RAS-MAPK signal is required for enhanced PD-L1 expression in human lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3708. doi:10.1158/1538-7445.AM2017-3708</jats:p
Abstract 3115: Characterization of CDCA1 protein as a novel prognostic biomarker and therapeutic target for oral cancer
No full textAbstract
Oral cavity carcinoma (OCC) is one of the most common causes of cancer-related death worldwide. Current therapies for OCC still show poor clinical outcome with five-year survival rate of less than 63%. Therefore, next generation biomarkers and therapeutic strategies for OCC are eagerly awaited. We selected genes that were specifically overexpressed in the majority of OCC using our gene expression profile database, and identified cell division cycle associated 1 (CDCA1) that appeared to encode nuclear protein as a candidate. Immunohistochemical analysis using tissue microarray covering 99 OCC tissues detected that CDCA1 protein was expressed in 67 cases of 99 OCC tissues (68%), but not in normal oral epithelia. In addition, high levels of CDCA1 protein expression was significantly associated with poor prognosis for OCC patients (P = 0.0244 by log-rank test). Furthermore, knockdown of CDCA1 expression by siRNAs significantly inhibited the growth of tumor cells. Moreover, flow cytometric analysis, multiple apoptosis assays, and live cell imaging experiment revealed that CDCA1 could be important for the growth and survival of OCC cells, probably through the regulation of mitotic prophase and/or apoptosis. Our findings suggest that CDCA1 is likely to be a novel prognostic biomarker and a therapeutic target for OCC patients.
Citation Format: Thang Manh Phung, Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yoshinori Murakami, Yataro Daigo. Characterization of CDCA1 protein as a novel prognostic biomarker and therapeutic target for oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3115. doi:10.1158/1538-7445.AM2017-3115</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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