bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2446: 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation
Authors: Jeong Jinseon , Kim Yong Jae , Shin Su-Hyun , Lee Do Young , Moon Byoung-Gon , Sohn Ki-Young , Yoon Sun Young , Kim Jae Wha 
Published: August 2018

Abstract
Neutrophils are the most abundant leukocyte in circulation and are the first responder to foreign particles and/or injury. Some chemotherapeutics are known to induce depletion of blood neutrophils as its high cytotoxicity. However, it is also possible that circulating neutrophils undergo extravasation in response to chemotactic gradients induced by anticancer agents. Here, we found that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation via the inhibition of neutrophil-attracting chemokine expression in macrophages using in vivo and in vitro approaches. First, we observed that there were increased neutrophils infiltrated into the peritoneal cavity following gemcitabine treatment in 4T1 tumor-bearing mice. In addition, gemcitabine increased MIP-2 mRNA expression in the peritoneal cells as well as in other tissues of the mice. Likewise, gemcitabine induced the migration of circulating neutrophils into the peritoneal cavity in normal mice, and PLAG effectively decreased neutrophil migration by inhibiting the expression of adhesion molecules. Inhibition of CXCR2 by its antagonist, reparixin, abrogated gemcitabine-induced neutrophil migration, indicating that chemokines produced by gemcitabine mainly support neutrophil activation. In vitro experiments demonstrated that PLAG inhibited NADPH oxidase (NOX)-mediated reactive oxygen species production induced by gemcitabine, which is upstream of MIP-2 and/or CXCL8. Importantly, PLAG downregulated gemcitabine-induced membrane translocation of the cytosolic NOX subunit, Rac1, and phosphorylation of p47phox. We also demonstrated that 1-palmitoyl-2-linoleic-3-hydroxyl-rac-glycerol (PLH), the natural form of diacylglycerol, has no effects on gemcitabine-induced CXCL8 production and dHL-60 migration, suggesting that an acetyl group at the third position of the glycerol backbone may have a key role in the regulation of neutrophil activation. Altogether, this study suggests the potential of PLAG as a therapeutic strategy to modulate chemotherapy-induced neutrophil activation for cancer patients undergoing chemotherapeutic treatment.
Citation Format: Jinseon Jeong, Yong Jae Kim, Su-Hyun Shin, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2446.
Abstract 2448: Chemotherapy drug-induced AXL activation and cell survival signaling via reactive oxygen species that can be inhibited to enhance drug efficacy in mesothelioma
Authors: Oien Derek B. , Garay Tamás , Eckstein Sarah , Chien Jeremy 
Published: August 2018

Abstract
Cellular oxidative stress is characterized by elevated reactive oxygen species (ROS), and is a frequent phenotype of cancer cells. The consequences of ROS are complex, where ROS can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. On the other hand, a current chemotherapy regime for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS induced by cisplatin and pemetrexed may promote cell survival signaling pathways, which ultimately may contribute to chemotherapy resistance. In The Cancer Genome Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma compared to other cancer samples. We showed that ROS induce the phosphorylation of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31 mesothelioma cells. We also showed that cisplatin and pemetrexed induce the phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N-acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed when cells were pretreated with BGB324 before adding chemotherapy. These results demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking AXL activation enhances the efficacy of cisplatin and pemetrexed. These results suggest AXL inhibition may represent an effective strategy to enhance the efficacy of chemotherapy in mesothelioma. We further hypothesize AXL signaling may be part of an adaptive response to chemotherapeutic agents, providing transient resistance to cisplatin and pemetrexed that may ultimately contribute to acquired chemotherapy resistance.
Citation Format: Derek B. Oien, Tamás Garay, Sarah Eckstein, Jeremy Chien. Chemotherapy drug-induced AXL activation and cell survival signaling via reactive oxygen species that can be inhibited to enhance drug efficacy in mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2448.
Abstract 2453: Eradication of neuroblastoma by suppressing the expression of a single noncoding RNA
Authors: Tee Andrew E. , Liu Pei Y. , Milazzo Giorgio , Hannan Kate M. , Maag Jesper , Bartonicek Nenad , Song Renhua , Jiang Chen C. , Zhang Xu D. , Norris Murray D. , Haber Michelle , Marshall Glenn M. , Li Jinyan , Vandesompele Jo , Mattick John S. , Mestdagh Pieter , Perini Giovanni , Hannan Ross D. , Dinger Marcel E. , Liu Tao 
Published: August 2018

Abstract
N-Myc gene amplification occurs in one quarter of human neuroblastoma tissues, and is a marker for poor patient prognosis. We performed RNA sequencing experiments, and identified 5 transcripts, including RP1NB1, which were most considerably differentially expressed between N-Myc gene amplified and nonamplified human neuroblastoma cell lines. Affymetrix microarray studies revealed that DEPD was one of the few genes considerably downregulated in neuroblastoma cells after RP1NB1 depletion. Chromatin immunoprecipitation assays showed that knocking down RP1NB1 expression reduced histone H3 lysine 4 trimethylation, a marker for active gene transcription, at the DEPD gene promoter. Luciferase assays demonstrated that knocking down RP1NB1 decreased DEPD gene promoter activity. Depletion of RP1NB1 or DEPD with two independent siRNAs or shRNAs significantly reduced ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, N-Myc protein stabilization, neuroblastoma cell proliferation and survival. Clonogenic assays showed that knocking down RP1NB1 with doxycycline completely abolished colony formation capacity of neuroblastoma cells stably transfected with doxycycline-inducible RP1NB1 shRNAs. Importantly, treatment with doxycycline in mice xenografted with neuroblastoma cells stably transfected with doxycycline-inducible RP1NB1 shRNA led to tumor eradication. In human neuroblastoma tissues from 600 neuroblastoma patients, high levels of RP1NB1 gene expression correlated with DEPD gene expression and poor patient prognosis. In conclusion, this study identifies the novel long noncoding RNA RP1NB1 as an important regulator of N-Myc protein stability and neuroblastoma tumorigenesis.
Citation Format: Andrew E. Tee, Pei Y. Liu, Giorgio Milazzo, Kate M. Hannan, Jesper Maag, Nenad Bartonicek, Renhua Song, Chen C. Jiang, Xu D. Zhang, Murray D. Norris, Michelle Haber, Glenn M. Marshall, Jinyan Li, Jo Vandesompele, John S. Mattick, Pieter Mestdagh, Giovanni Perini, Ross D. Hannan, Marcel E. Dinger, Tao Liu. Eradication of neuroblastoma by suppressing the expression of a single noncoding RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2453.
Abstract 2458: The androgen receptor-regulated lncRNA landscape reveals a role for ARlnc1 in prostate cancer progression
Authors: Zhang Yajia , Pitchiaya Sethuramasundaram , Cieślik Marcin , Niknafs Yashar S. , Tien Jean C. , Hosono Yasuyuki , Wang Lisha , Qiao Yuanyuan , Cao Xuhong , Ljungman Mats , Jiang Hui , Mehra Rohit , Guo Shuling , Malik Rohit , Chinnaiyan Arul M. 
Published: August 2018

Abstract
The androgen receptor (AR) signaling plays a key role in the development of the normal prostate as well as prostate cancer. While substantial efforts have been undertaken to study AR-regulated protein-coding genes in primary prostate cancer and castration-resistant prostate cancer, few studies have investigated the role of long noncoding RNAs. In this study, we employed transcriptome sequencing to delineate long noncoding RNAs (lncRNAs) associated with AR signaling in prostate cancer progression. ARlnc1 (AR-regulated lncRNA 1) was identified as being the top AR-induced, cancer-associated lncRNA in an integrative analysis of prostate cancer cell lines and tissues. Not only was ARlnc1 induced by AR, but ARlnc1 also was shown to sustain AR signaling by stabilizing the AR transcript via interaction with the AR 3' UTR. Knockdown of ARlnc1 suppressed AR expression, global AR signaling, and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARlnc1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression, and identifies ARlnc1 as a novel therapeutic target.
Citation Format: Yajia Zhang, Sethuramasundaram Pitchiaya, Marcin Cieślik, Yashar S. Niknafs, Jean C. Tien, Yasuyuki Hosono, Lisha Wang, Yuanyuan Qiao, Xuhong Cao, Mats Ljungman, Hui Jiang, Rohit Mehra, Shuling Guo, Rohit Malik, Arul M. Chinnaiyan. The androgen receptor-regulated lncRNA landscape reveals a role for ARlnc1 in prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2458.
Abstract 2461: Prognostic impact of telomeric repeat containing RNA expression on long-term oncologic outcomes in colorectal cancer
Authors: Bae SungUk , Jeong Woon Kyung , Bae Seong Kyu , Lee Jae-Ho 
Published: August 2018

Abstract
Purpose: Telomere shortening is associated with colorectal carcinogenesis and transcription from subtelomeres produces telomeric repeat containing RNA (TERRA), a natural inhibitor of telomerase activity (TA). Previous studies on TERRA expression demonstrated downregulation in advanced stages of human tumors.
Materials and Methods: We evaluated the 2p TERRA expression and telomere length using quantitative real-time PCR in 60 patients who underwent surgical resection for colorectal cancer between June 2008 and November 2010.
Results: Patients were grouped according to 2p TERRA expression, with 27 (45%) and 33 (55%) in the low and high TERRA expression groups, respectively. The median follow-up period was 80 months (range 2-103). 2p TERRA expression was marginally significantly associated with preoperative CEA (P = 0.082) and significantly associated with telomere length (P &lt; 0.05). Five-year overall survival rates in the high 2p TERRA expression group and the low expression group were 73.6% and 78.2%, respectively (p = 0.322), and five-year disease-free survival rates in the high 2p TERRA expression group and the low expression group were 66.1% and 75.1%, respectively (p = 0.317).
Conclusions: 2p TERRA expression was marginally significantly associated with preoperative CEA and significantly associated with telomere length; however, it was not prognostic on long-term oncologic outcomes in colorectal cancer.
Citation Format: SungUk Bae, Woon Kyung Jeong, Seong Kyu Bae, Jae-Ho Lee. Prognostic impact of telomeric repeat containing RNA expression on long-term oncologic outcomes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2461.
Abstract 2462: Epstein-Barr virus-encoded microRNAs regulate the expression of BRCA1 in nasopharyngeal carcinoma
Authors: Lam Ka-Hei , Lung Raymond Wai-Ming , Hau Pok-Man , Yip Kevin Yuk-Lap , Tsao George Sai-Wah , Yu Ken Hung-On , Tong Joanna Hung-Man , Lo Kwok-Wai , To Ka-Fai 
Published: August 2018

Abstract
Nasopharyngeal carcinoma (NPC) is an aggressive epithelial malignancy and is endemic in southern China and Southeast Asia. It is well-known to be associated with Epstein-Barr virus (EBV) infection. The miRNAs derived from EBV BamH1-A rightward transcripts (miR-BARTs) are abundantly expressed in NPC and have been suggested that can contribute to cancer development by regulating several gene expression. In this study, we established comprehensive expression profile of miRNAs in an EBV positive NPC cell line and 5 xenografts by small RNA sequencing. By using the prediction algorithm of miRanda and RNAhybrid, in silico analysis identified that several abundantly expressed miRNAs from viral and cellular genomes could negatively regulate BRCA1 expression via the 3' untranslated region (3'UTR). Notably, the regulatory role of miR-BART17-5p, miR-BART19-3p, miR182-5p on endogenous BRCA1 expression was demonstrated by transient transfection assays in HeLa cells and the direct recognitions were verified by luciferase reporter assays, while the downregulation of BRCA1 in primary NPCs was substantiated in the immunohistochemical (IHC) staining in a cohort of 61 histologically normal nasopharyngeal (NP) and 37 primary NPC cases (p&lt;0.001). Taken togethher, we showed that the highly expressed miRNAs could work co-operatively to modulate BRCA1 activity. It has been reported that BRCA1 deficient tumor cells are defective in repairing the DNA double-strand breaks (DSBs) via error-free homologous recombination (HR). The impaired DSB repair by EBV latent infection may induce genome instability during NPC tumorigenesis and also contribute to sensitizing the tumor cells to ionizing radiation and DNA-damaging agent treatments.
Acknowledgement:
Theme-based Research Scheme (T12-401/13-R) and GRF (14104415, 14138016), Research Grant Council, Hong Kong
Citation Format: Ka-Hei Lam, Raymond Wai-Ming Lung, Pok-Man Hau, Kevin Yuk-Lap Yip, George Sai-Wah Tsao, Ken Hung-On Yu, Joanna Hung-Man Tong, Kwok-Wai Lo, Ka-Fai To. Epstein-Barr virus-encoded microRNAs regulate the expression of BRCA1 in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2462.
Abstract 2464: Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction
Authors: Kajino Taisuke , Shimamura Teppei , Gong Shuyi , Yanagisawa Kiyoshi , Nakatochi Masahiro , Griesing Sebastian , Shimada Yukako , Kano Keiko , Suzuki Motoshi , Miyano Satoru , Takahashi Takashi 
Published: August 2018

Abstract
Long non-coding RNAs (lncRNAs), longer than 200 nucleotides in length, function in a wide range of processes by diverse mechanisms. lncRNAs are attracting research interest in the field of cancer research though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. In order to search for MYC-modulating lncRNA, we performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity despite its low levels of expression and cell cycle progression. A proteomic search for MYMLR-binding proteins identified PCBP2, which transcriptionally regulates MYC expression in cooperation with MYMLR. Mechanistically, MYMLR places a 557-kb upstream enhancer region to make the MYC promoter and enhancer regions reside in the proximity. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC, and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes in cancer development.
Citation Format: Taisuke Kajino, Teppei Shimamura, Shuyi Gong, Kiyoshi Yanagisawa, Masahiro Nakatochi, Sebastian Griesing, Yukako Shimada, Keiko Kano, Motoshi Suzuki, Satoru Miyano, Takashi Takahashi. Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2464.
Abstract 2475: Long noncoding RNA NNT-AS1 sponges miR-424 to promote the progression and metastasis of gastric cancer
Authors: Chen Beibei , Zhao Qingfang , Guan Lulu , Lv Huifang , Bie Liangyu , Huang Jinxi , Li Jitian , Zhang Jianying , Chen Xiaobing 
Published: August 2018

Abstract
Background: Long noncoding RNAs (lncRNAs) have been illustrated to function as important regulator in carcinogenesis and cancer progression. However, the roles of lncRNA NNT-AS1 in gastric cancer remain unclear. In present study, we investigate the expression level of NNT-AS1 in gastric cancer tissue and the role on gastric cancer cells tumorigenesis.
Methods: NNT-AS1 expression level was measured using RT-PCR. The prognosis and survival rate of gastric cancer patients with high/low expression of NNT-AS1 was tracked and analyzed. Cellular experiments were performed to test the role of NNT-AS1 on gastric cancer phenotype, including proliferation analysis, transwell assay, EMT-related marker blots and xenograft mice assay. Bioinformatics online program and luciferase assay were performed to predict and verify the potential miRNAs targeting NNT-AS1.
Results: NNT-AS1 expression level was significantly upregulated in 55 cases of gastric cancer tissue samples compared with adjacent normal tissue. Besides, the aberrantly enhanced NNT-AS1 expression predicted poor prognosis and lower survival rate. In vitro, NNT-AS1 knockdown suppressed the gastric cancer cells proliferation, invasion and EMT-related marker (N-cadherin and vimentin) expression. In vivo, lentivirus mediated NNT-AS1 silencing decreased the tumor growth. MiR-503 was verified to be the target miRNA of NNT-AS1 using bioinformatics online program and luciferase assay. Furthermore, miR-424 could reverse the role of NNT-AS1 on gastric cancer cells.
Conclusion: In conclusion, our study indicates that NNT-AS1 sponges miR-424 to facilitate gastric cancer cells invasion and metastasis, revealing the oncogenic role of NNT-AS1 on gastric cancer cells.
Citation Format: Beibei Chen, Qingfang Zhao, Lulu Guan, Huifang Lv, Liangyu Bie, Jinxi Huang, Jitian Li, Jianying Zhang, Xiaobing Chen. Long noncoding RNA NNT-AS1 sponges miR-424 to promote the progression and metastasis of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2475.
Abstract 2480: Olig2-dependent reciprocal shift in PDGF and EGF receptor signaling regulates tumor phenotype and mitotic growth in malignant glioma
Authors: Lu Fanghui , Xin Mei , Lu Qing Richard 
Published: August 2018

Abstract
Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Diverse molecular characteristics in gliomas represent a significant hurdle for effective therapy. We uncover that a population of Olig2+ cells function as glioma-propagating cells and is critical for tumor initiation of primary gliomas in mice. Elimination of Olig2+ mitotic progenitors blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate. Genome occupancy and expression profiling analyses reveal that OLIG2 directly activates cell proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrocyte precursor-correlated proneural toward an astrocyte-associated gene expression pattern, manifest in downregulation of PDGF receptor-alpha and reciprocal upregulation of EGFR. Olig2 deletion further sensitizes glioma cells to EGFR inhibitors and extends animal lifespans. Our observations reveal that OLIG2 is a molecular arbiter of tumor phenotype plasticity that may underlie drug resistance, suggesting new strategies for enhancing EGFR drug sensitivity in glioma treatment.
Citation Format: Fanghui Lu, Mei Xin, Qing Richard Lu. Olig2-dependent reciprocal shift in PDGF and EGF receptor signaling regulates tumor phenotype and mitotic growth in malignant glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2480.
Abstract 2481: Loss of FUBP1 impairs terminal neuronal differentiation and predisposes neural progenitors for transformation
Authors: Hwang Inah , Cao Dongqing , Kim Do-Yeon , Zhang Tuo , Hu Jian , Yao Yu , Paik Jihye 
Published: August 2018

Abstract
Loss of terminal differentiation capacity through genetic mutations is a selected genetic event in tumorigenesis. 1p19q co-deletion associated recurrent mutations of far upstream element-binding protein 1 (FUBP1) have been reported from genomic analysis of low- grade oligodendroglioma. It is frequently overexpressed in many human cancers and strongly correlated with disease progression. However, left unanswered is how FUBP1 serves uniquely as a tumor suppressor in the central nervous system. Here we show that expression of FUBP1 is dynamically regulated during neurogenesis, marking specific stages of neuronal differentiation. Loss of FUBP1 in neural stem/progenitor cells (NPC) increased the number of cells fail to terminally differentiate. Knockdown of FUBP1 further blocks differentiation and promotes tumorigenesis collaboratively with the expression of neomorphic isocitrate dehydrorgenase 1 mutant IDH1R132H. Mechanistically FUBP1 is necessary for mini exon 8a splicing of neurospecific isoform of histone demethylase LSD1 (nLSD1). It binds to intron 8 of LSD1 together with a neuron-specific splicing complex containing NOVA1 and 2 and works synergistically with SRRM4 for the inclusion of mini exon 8a. The expression level of nLSD1 is decreased upon loss of FUBP1 in neural progenitors, impairing the terminal neuronal differentiation and maturation. Reinforcing nLSD1 expression in FUBP1-downregulated NPC restores terminal differentiation, establishing nLSD1 as an obligatory effector of FUBP1-dependent neuronal differentiation. Together, these findings establish a direct role for FUBP1 in neuronal differentiation and also uncover the mechanism for its tumor suppressor function in the nervous system.
Citation Format: Inah Hwang, Dongqing Cao, Do-Yeon Kim, Tuo Zhang, Jian Hu, Yu Yao, Jihye Paik. Loss of FUBP1 impairs terminal neuronal differentiation and predisposes neural progenitors for transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2481.