bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4368: The clinicopathological significance of glutathione S-transferase P1 hypermethylation in breast cancer, a meta-analysis and literature review
Authors: Liu Mingli 
Published: July 2017

Abstract
Background: Glutathione S-transferase P1 (GSTP1) has been reported to function as a tumor suppressor gene in various types of human cancers including breast cancer (BC). However, the association and clinicopathological significance between GSTP1 hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate clinicopathological significance of GSTP1 methylation in BC.
Method: A detailed literature search was made in PubMed, EMBASE, Web of Science and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds Ratios (OR) with 95% corresponding confidence intervals (CIs) were calculated. A total of twenty four relevant articles were available for meta-analysis.
Results: The frequency of GSTP1 hypermethylation was significantly increased in BC than in benign breast disease, the pooled OR was 7.09, p&lt;0.00001. The rate of GSTP1 hypermethylation was significantly different between early stage I/II and later stage III/IV, OR was 2.05, p&lt;0.0001. In addition, the rate of GSTP1 hypermethylation was also significantly different regarding the node involvement status. The rate of GSTP1 hypermethylation in node positive BC was higher than that in node negative BC, OR was 1.77, p=0.006. However, GSTP1 hypermethylation was not significantly associated with ER, PR and HER2 status.
Conclusion: In summary, our meta-analysis indicated that the frequency of GSTP1 hypermethylation was significantly increased in BC than in benign breast disease. The rate of GSTP1 hypermethylation in late stages of BC was higher than that in early stages. Our data suggested that GSTP1 hypermethylation could be a risk factor and a diagnostic biomarker of BC carcinogenesis. GSTP1 hypermethylation may have a role in the progression of BC. GSTP1 is a potential drug target for development of demethylation treatment for patients with BC.
Note: This abstract was not presented at the meeting.
Citation Format: Mingli Liu. The clinicopathological significance of glutathione S-transferase P1 hypermethylation in breast cancer, a meta-analysis and literature review [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 4368. doi:10.1158/1538-7445.AM2017-4368
Abstract 4383: Novel fusion transcripts in colorectal cancer patients revealed by next-generation RNA sequencing
Authors: Choi Yuri , Kwon Chae Hwa , Park Hye Ji , Won Yeo-Jin , Park Do Youn 
Published: July 2017

Abstract
Although colorectal cancer (CRC) is the third most common type of cancer in the world, there is an insufficient research on molecular targets for prevention and therapies of CRC. Gene fusions are associated with tumorigenesis and tumor activation, and could be a standard to distinguish tumor heterogeneity for personalized therapy. In the present study, we performed next-generation RNA sequencing (150 tumor and 50 matched normal tissues) in order to discover novel fusion transcripts in CRC. A total 25 transcript candidates were detected by GFP, deFuse, and FusionMap algorithms. Among the candidates, 6 fusion transcripts were selected (B4GALT1-BAG1, GTF3A-CDK8, NAGLU-IKZF3, RNF121-FOLR2, STRN-ALK, and TAF4-NDRG3) after analyzing expression and function of the acceptor genes. All of them were validated by sanger-sequencing and were not found in another cohort. Overexpression of these fusion genes, except B4GALT1-BAG1, increased proliferation of CRC cells. In addition, overexpression of NAGLU-IKZF3 enhanced migration of CRC cells. These results reveal novel fusion transcripts and their tumorigenic effects in CRC. Ultimately, it could illuminate a genomic-driven strategy to develop personalized medicine.
Key words: fusion transcript, colorectal cancer, RNA-seq
Citation Format: Yuri Choi, Chae Hwa Kwon, Hye Ji Park, Yeo-Jin Won, Do Youn Park. Novel fusion transcripts in colorectal cancer patients revealed by next-generation RNA sequencing [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 4383. doi:10.1158/1538-7445.AM2017-4383
Abstract 4384: Targeted sequencing reveals distinct and rare pathogenic variants in Caucasians with colorectal cancer
Authors: Mokarram Pooneh , Varma Sudhir , Azimi Hamed , Olumi Hasti , Safarpour Ali reza , Nickerson Michael , Brim Hassan , Ashktorab Hassan 
Published: July 2017

Abstract
PURPOSE: Next-generation sequencing (NGS) is currently used to establish mutational profiles in many multigene diseases such as colorectal cancer (CRC) which is on the rise in many parts of the developing World including in the Middle East. Little is known about its genetic hallmarks in these populations. AIM: To identify variants in 15 CRC-associated genes in patients of Iranian descent.
METHODS: CRC specimens from 63 patients were used to establish the variants’ profile on an Ion Torrent platform by targeted exome sequencing. To rule out technical artifacts, the variants were validated in 13 of these samples using an Illumina NGS platform. Validated variants were annotated and compared to variants from publically available databases. An in-silico functional analysis was performed. MSI status of the analyzed samples was established. RESULTS: There were 51 validated variants distributed on 12 genes: 22% MSH3 (n=11/51), 10% MSH6 (n=5/51), 8% AMER1 (n=4/51), 20% APC (n=10/51), 2% BRAF (n=1/51), 2% KRAS (n=1/51), 12% PIK3CA (n=6/51), 8% TGFβR2A (n=4/51), 2% SMAD4 (n=1/51), 4% SOX9 (n=2/51), 6% TCF7L2 (n=3/51), and 6% TP53 (n=3/51). Most known and distinct variants were in mismatch repair genes (MMR, 32%) and APC (20%). Among oncogenes, PIK3CA was the top target (12%). MSH3 variants were more frequent and predominantly homozygous in the analyzed population.
CONCLUSION: These results illustrate for the first time CRC mutational profile in Iranian patients. MSH3, MSH6, APC and PIK3CA genes seem to play a bigger role in the path to cancer in this population. This is especially true for MSH3 variants that were very frequent and predominantly homozygous as these will associate with the EMAST phenotype that has prognostic implications. These findings will potentially lead to informed genetic diagnosis protocol and targeted therapeutic strategies.
Citation Format: Pooneh Mokarram, Sudhir Varma, Hamed Azimi, Hasti Olumi, Ali reza Safarpour, Michael Nickerson, Hassan Brim, Hassan Ashktorab. Targeted sequencing reveals distinct and rare pathogenic variants in Caucasians with colorectal 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 4384. doi:10.1158/1538-7445.AM2017-4384
Abstract 439: Metabolic flux analysis reveals targets to sensitize chemoresistance in acute myeloid leukemia induced by mesenchymal stromal cell-derived exosomes
Authors: Achreja Abhinav , Zhao Hongyun , Zhu Ziwen , Gerszberg Jonathan , Konopleva Marina Y. , Andreeff Michael , Nagrath Deepak 
Published: July 2017

Abstract
The tumor microenvironment has a pleiotropic role in supporting cancer cell growth, metastasis and drug resistance. Exosomes from mesenchymal stromal cells (MSC) were found to regulate metabolism of acute myeloid leukemia (AML) cells that led to a chemoresistant phenotype. Exosomes carry a host of proteins, nucleotides and metabolites that can induce metabolic reprogramming recipient cells via direct supply of metabolite cargo or through signaling. We utilized 13C tracer techniques and two metabolic flux analysis techniques to reveal the mechanism of metabolic reprogramming induced by MSC-derived exosomes. First, 13C metabolic flux analysis was used to quantify intracellular fluxes of central carbon, amino acids and fatty acid metabolism in AML cells cultured with and without exosomes in media with 13C substrates. Second, we employed a novel technique, exosome-mediated metabolic flux analysis (Exo-MFA), to estimate direct support provided by metabolite supply from exosome cargo by introducing 13C-labeled exosomes. The combined analysis dissected the metabolite supply from exosome cargo from the overall reprogramming of metabolic pathways due to exosomes. Our results revealed key metabolic pathways that could be targeted to inhibit exosome-induced reprogramming to reverse the chemoresistant phenotype.
Citation Format: Abhinav Achreja, Hongyun Zhao, Ziwen Zhu, Jonathan Gerszberg, Marina Y. Konopleva, Michael Andreeff, Deepak Nagrath. Metabolic flux analysis reveals targets to sensitize chemoresistance in acute myeloid leukemia induced by mesenchymal stromal cell-derived exosomes [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 439. doi:10.1158/1538-7445.AM2017-439
Abstract 4394: Whole-genome, virome, and immuno-genome of liver cancer indicate its genomic feature associated with virus infection and inflammation
Authors: Nakagawa Hidewaki 
Published: July 2017

Abstract
Liver cancer is prevalent worldwide, mainly associated with virus infection and chronic inflammation, but its underlying molecular mechanism is quite heterogeneous. We performed virome and immuno-genomic analyses, in addition to whole-genome landscape of somatic alterations and transcriptome in 300 liver cancers. Our whole-genome analysis elucidated point mutations in non-coding regions, structural variations, and virus integrations (HBV and AAV), in addition to coding mutations. We discovered novel recurrently mutated coding and non-coding regions, such as NEAT1/MALAT1 lincRNAs, promoters, CTCF-binding sites, and novel regulatory regions, and known cancer genes (CDKN2A, APC, TERT) and novel cancer genes (ASH1L, NCOR1, MACROD2) that were recurrently affected by SVs. For virome analysis, we performed ultra-deep sequencing after capturing HBV sequences from DNAs of 100 liver cancers or adjacent HBV-infected liver tissues, which demonstrated genome-wide HBV-integrations (1794 sites) in liver cancers and infected liver tissues and eliminated pathological mechanism of viral integration. We also generated immuno-genomic profiles of these liver cancers, including HLA genotypes and mutations, neo-antigen presentation, immune signatures, and TCR repertories, which suggested some distinct immunological features and underlying molecular pathways of liver cancer associated with inflammation. These trans-omics data demonstrated comprehensive and distinct immuno-genomic feature of virus-related liver cancer, as well as its distinct whole-genome profiles, and can help to understand the molecular and microenvironment pathways underlying carcinogenesis and treatment response of liver cancer.
Citation Format: Hidewaki Nakagawa. Whole-genome, virome, and immuno-genome of liver cancer indicate its genomic feature associated with virus infection and inflammation [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 4394. doi:10.1158/1538-7445.AM2017-4394
Abstract 440: The oncogenic activity of a pro-oxidant intracellular milieu is associated with redox dependent activation of NF-kB
Authors: Yee Michelle Y. , Chong Stephen J. , Pervaiz Shazib 
Published: July 2017

Abstract
Evidence over the years has highlighted that intracellular redox status plays a critical role in determining cell fate. To date, we have shown that a pro-oxidant milieu, specifically a mild elevation of intracellular superoxide, promotes cancer cell survival and chemoresistance. To that end, we demonstrated in vitro that elevated superoxide, upon silencing of superoxide dismutase (SOD1), resulted in sustained phosphorylation of Bcl-2 at serine 70, thereby stabilizing its anti-apoptotic activity. These findings were corroborated by the abundance of Serine 70 Bcl2-phosphorylation and low SOD1 expression in lysates of patients with aggressive lymphomas and/or disease with poor prognosis. In addition to the anti-apoptotic protein Bcl-2, the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB)- mediated signaling was also shown to be modulated by intracellular redox milieu. As constitutive activation of NF-κB has been reported in various human tumors, which is often associated with malignant progression and chemotherapeutic resistance, here we set out to investigate whether a pro-oxidant environment, specifically the upregulation of intracellular superoxide, was associated with the induction of NF-κB transcriptional activity. Indeed, we demonstrate that elevated intracellular superoxide via the pharmacological inhibition and genetic silencing of SOD1 results in enhanced activation of canonical NF-κB signalling. This is accompanied by increased p65 nuclear localization and transcription of NF-κB regulated genes, which potentially confer survival advantages to tumour cells upon chemotherapeutic treatments. Considering the association between NF-kB activation, chronic inflammation and the process of carcinogenesis, these preliminary data provide a novel mechanism of activation of this master transcriptional factor with potential therapeutic implications.
Citation Format: Michelle Y. Yee, Stephen J. Chong, Shazib Pervaiz. The oncogenic activity of a pro-oxidant intracellular milieu is associated with redox dependent activation of NF-kB [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 440. doi:10.1158/1538-7445.AM2017-440
Abstract 441: GOT1 regulates anaplerotic glutamine metabolism under chronic acidosis stress in pancreatic cancer
Authors: Abrego Jaime , Gunda Venugopal , Vernucci Enza , Shukla Surendra , King Ryan J. , Dasgupta Aneesha , Chaika Nina , Singh Pankaj Kumar 
Published: July 2017

Abstract
Epithelial-cell derived tumors exhibit the Warburg effect that is characterized by an increased rate of glycolysis and lactate release, as well as, reduced oxidative metabolism. It is known that these metabolic alterations of cancer cells result in a tumor microenvironment with a lower pH than that of the plasma. However, little is known regarding the physiology and metabolism of cancer cells enduring chronic acidosis. Here, we cultured pancreatic cancer cells in chronic acidosis, i.e. pH 6.9 to 7.0, and observed a shift from glycolytic metabolism to oxidative metabolism that also results in reduced cell growth and increased intracellular ROS levels. We identified that this is due to an increase in glutamine uptake and increased expression of the transaminase enzyme GOT1 that enhances glutamine metabolism. Survival in low pH is reduced upon depletion of GOT1 due to further increased intracellular ROS levels. Thus, GOT1 plays an important role in energy metabolism and ROS balance in chronic acidosis stress. Our studies suggest the therapeutic potential of targeting anaplerotic glutamine metabolism in pancreatic cancer.
Citation Format: Jaime Abrego, Venugopal Gunda, Enza Vernucci, Surendra Shukla, Ryan J. King, Aneesha Dasgupta, Nina Chaika, Pankaj Kumar Singh. GOT1 regulates anaplerotic glutamine metabolism under chronic acidosis stress in pancreatic 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 441. doi:10.1158/1538-7445.AM2017-441
Abstract 4417: The role of EBV infection in aerobic glycolysis in nasopharyngeal carcinoma
Authors: Tsao George S. , Zhang Jun , Xia Lin , Tsang C , Lin Weitao , Yip Y , Deng W , Lo K , Lung M 
Published: July 2017

Abstract
Accumulating evidence indicates that oncogenic viral protein exerts a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a trans-membrane protein with potent cell signaling properties and has tumorigenic transformation property. Activation of NF-κB is a major signaling pathway mediating many downstream transformation properties of LMP1. Here we report that activation of mTORC1 by LMP1 is a key modulator for activation of NF-κB signaling to mediate aerobic glycolysis. NF-κB activation is involved for LMP1-induced upregulation of glucose transptor-1 (Glut-1) transcription and growth of nasopharyngeal carcinoma (NPC) cells. Collectively, blocking the activity of mTORC1 signaling effectively suppressed LMP1-induced NF-κB activation and Glut-1 transcription. Interfering NF-κB signaling has no effect on mTORC1 activity but effectively altered Glut-1 transcription. Luciferase promoter assay of Glut-1 also confirmed that Glut-1 is a direct target gene of NF-κB signaling. Furthermore, we demonstrated that the LMP1 C-terminal activating region (CTAR) 2 is the key domain involved in mTORC1 activation, mainly through IKKβ-mediated phosphorylation of TSC2 at Ser939. Depletion of Glut-1 effectively led to suppression of aerobic glycolysis, inhibition of cell proliferation, colony formation, and attenuation of tumorigenic growth property of LMP1-expressing nasopharyngeal epithelial (NPE) cells. These findings suggest that targeting the signaling axis of mTORC1/NF-κB/Glut-1 represents a novel therapeutic target against NPC.
Acknowledgement: 96 800x600 This project was supported by the General Research Fund (HKU 779810M, 17120814 and 17161116), CRF equipment grant (1061402980, Health and Medical Research Fund of Hong Kong (12110782), AoE grant (AoE/M-06/08) and TBRS grant (T12-401/13-R). We thank Prof. Dongyan Jin (Department of Biochemistry, The University of Hong Kong) for the kind gifts of IKK related plasmids and Prof. Zhenguo Wu (Division of Life Science, The Hong Kong University of Science and Technology) for the discussion and interpretation of the data. We also thank Mr. Tony Chan for his technical support.
Note: This abstract was not presented at the meeting.
Citation Format: George S. Tsao, Jun Zhang, Lin Xia, C Tsang, Weitao Lin, Y Yip, W Deng, K Lo, M Lung. The role of EBV infection in aerobic glycolysis in nasopharyngeal carcinoma [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 4417. doi:10.1158/1538-7445.AM2017-4417
Abstract 4427: An integrated analysis package of miRNA and mRNA expression dataAn integrated analysis package of miRNA and mRNA expression data
Authors: Wang Ti-Tai 
Published: July 2017

Abstract
MicroRNAs(miRNAs) are small and non-coding RNAs that can regulate gene expression by binding on the 3’UTR of target mRNAs and inhibiting mRNAs to translate protein, or even promoting mRNAs degradation. In various complex disease and pathological conditions, we can identify dysregulated which are the causative factors. Therefore, it is an essential approach to explore the interactions between miRNA and gene in certain diseases, such as cancers. However, challenge arises when we are trying to validate the interactions by doing bench experiments. The numbers of miRNA-gene interactions are too large to be validated. Currently, most prediction algorithms only provide its own result and low consistency rates across independent methods have been reported. Therefore, it is necessary to develop a systematic method to perform a comprehensive analysis by using the expression profiles from genes and miRNAs concurrently. To address these issues, we developed an R package named as anamiR. AnamiR is able to perform an integrated analysis of mRNA and miRNA with the phenotype information. The analysis procedures are briefly summarized as the follows. Initially, differential expression analysis would be applied to the raw data. Subsequently, the anamiR package can identify significant pairs of miRNAs and genes if their Pearson correlation coefficients are lower than the pre-defined threshold. Next, the significant pairs were compared to the embedded database in anamiR, which included two validated and several predicting miRNA-gene databases. Lastly, functional analysis is also available in this package to characterize the biological functions and signaling pathways of dysregulated miRNAs and genes. A breast cancer dataset was analyzed by using anamiR, which identified nine miRNA-gene interactions for deeper studying. Among these interactions, there are two miRNAs and nine genes included. miR-497-5p and miR-204-5p which both were mentioned in breast cancer frequently, are found by anamiR. The anamiR package is freely available at Bioconductor.
Citation Format: Ti-Tai Wang. An integrated analysis package of miRNA and mRNA expression dataAn integrated analysis package of miRNA and mRNA expression data [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 4427. doi:10.1158/1538-7445.AM2017-4427