bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1404: Role of catechol-O-methyltransferase gene in prostate cancer
Authors: Maekawa Shigekatsu , Kato Taku , Hashimoto Yutaka , Shiina Marisa , Wong Ryan K. , Shahryari Varahram , Yamamura Soichiro , Majid Sahana , Saini Sharanjot , Tabatabai Laura Z. , Homma Yukio , Dahiya Rajvir , Tanaka Yuichiro 
Published: August 2018

Abstract
Prostate cancer is one of the most common malignancies and ranks the second most common cause of cancer-related deaths in men in the United States. Catechol-O-methyltransferase (COMT) is a phase II enzyme that detoxifies various catechol compounds that are reactive toward DNA and damaging to the cell. Studies have shown COMT to play a protective role against cancers such as renal and breast, but their effect on prostate is not well understood. In this study, the biological properties and function of COMT in prostate cancer were studied. Expression of COMT was initially measured in normal/benign and cancerous prostate tissues by immunohistochemistry, and cell lines by real-time PCR and western blotting. Cancerous cells displaying the lowest levels was then transfected with COMT. Gene effect on various cellular properties such as cell proliferation, migration, invasion and apoptosis, as well as growth in athymic nude mice were determined. COMT protein expression was lower in cancer regions compared to benign and normal regions of prostate tissues. Cancerous DU145 and DuPro cells also had reduced mRNA levels of COMT but with undetectable protein levels. Interestingly, re-expressing COMT in DU145 and DuPro cells led to decreased cell proliferation, migration, wound healing ability and invasion, and increased apoptosis compared to vector control. COMT also inhibited cell tumor formation in animal models. As a possible target, the TNFRSF11B gene was upregulated due to COMT. These results demonstrate COMT to protect against prostate cancer progression and to have a functional role by affecting apoptosis. COMT may thus be a potential biomarker or therapeutic target for prostate cancer.
Citation Format: Shigekatsu Maekawa, Taku Kato, Yutaka Hashimoto, Marisa Shiina, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Sahana Majid, Sharanjot Saini, Laura Z. Tabatabai, Yukio Homma, Rajvir Dahiya, Yuichiro Tanaka. Role of catechol-O-methyltransferase gene in prostate 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 1404.
Abstract 1412: Comprehensive characterization of clock genes in human cancers
Authors: Ye Youqiong , Xiang Yu , Takahashi Joseph , Mills Gordon , Yoo Seung-Hee , Han Leng 
Published: August 2018

Abstract
Cancer chronotherapy has been considered to optimize the balance of anti-tumor effects and toxicity. To develop cancer chronotherapy, the first crucial step is to understand the significant roles of clock genes in cancer. Circadian machinery is controlled by two main transcription auto-regulatory feedback loops, which including 14 core circadian genes. Core clock genes have at least one paralog gene may be functionally redundant in circadian regulation. Dysregulation of circadian genes promotes tumorigenesis through mechanisms that include the cell cycle, DNA damage and metabolism. However, there has been no comprehensive analysis to characterize the roles of circadian genes and circadian rhythms in tumorigenesis and to assess their potential utility in cancer chronotherapy. We determined genetic and epigenetic alterations of clock genes in human cancer, and explore clock gene clinical effect through integrative analysis, based on The Cancer Genome Atlas (TCGA) profiles contained DNA, RNA, protein, epigenetic levels and clinical data. Our results suggested several clock genes may function as oncogene, such as ARNTL2, NR1D1, and NPAS2, while several other clock genes may function as tumor suppressors, such as PERs, CRYs, RORs. We revealed disruption and reprogramming of circadian rhythms across patient samples by showing significantly reduced number of genes correlated to clock genes. We further showed that transcriptional dysregulation of clock genes is strongly associated with patient survival, tumor stage and subtype. Taken together, our results provide the comprehensive analysis of clock system across different cancer types and expected outcomes will lay the groundwork for the future development of cancer chronotherapy.
Citation Format: Youqiong Ye, Yu Xiang, Joseph Takahashi, Gordon Mills, Seung-Hee Yoo, Leng Han. Comprehensive characterization of clock genes in human cancers [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 1412.
Abstract 1414: Germline cancer predisposition gene mutations among patients with early onset rectal cancer
Authors: Beltrami Caroline , Alvim Luisa Matos , Kupper Bruna Elisa , Petersen Annabeth , Jørgensen Mads , Junior Samuel Aguiar , Rogatto Silvia Regina 
Published: August 2018

Abstract
Background: Although the incidence rates of rectal cancer (ReCa) have been increasing, the mechanisms or mutations involved in the development of the disease are poorly explored, especially in younger patients. To date, rectal tumors from young patients show molecular, clinical and pathological differences compared with colorectal cancer from older patients. Few studies have reported the presence of a hereditary factor involved in the risk of developing ReCa in a set of patients even in the absence of family history of cancer.
Patients and Method: Twenty-seven ReCa younger patients (&lt;40 years old) were screened for germline alterations in DNA from blood samples. The family history and clinical-pathological findings were assessed from the medical records from all subjects. DNA library was performed from SureSelectQXT Library Prep kit (Agilent, Santa Clara, CA) and next-generation sequencing was applied using a multigenic panel with 105 cancer-related genes (SureSelectXT Custom Panel; Agilent, Santa Clara). The generated sequences were aligned to human genome (hg19) and reported as pathogenic, likely pathogenic, variant of uncertain significance (VUS), benign and likely benign according to the American College of Medical Genetics and Genomics guidelines. Sanger sequencing was used to confirm the pathogenic variants.
Results: Two patients carried out high penetrance genes associated with colorectal cancer, MUTYH biallelic and BMPR1A. MTHFR and MUTYH variants were found in two patients. POT1 (melanoma predisposition), MEN1 (high penetrance) and ATM (moderate penetrance) variants were found in three additional ReCa patients. Three patients carried out likely pathogenic varaints (BMPR1A, CHEK2 and RAD51D genes). Four of ten patients with pathogenic variants had no family history of cancer.
Conclusion: Pathogenic (7/27) and likely pathogenic (3/27) variants were found in 37% of ReCa patients younger than 40 years old affecting genes with high or moderate penetrance. Our data suggest that genetic testing using a multigene panel and genetic counseling should be offered for younger patients with rectal cancer.
Citation Format: Caroline Beltrami, Luisa Matos Alvim, Bruna Elisa Kupper, Annabeth Petersen, Mads Jørgensen, Samuel Aguiar Junior, Silvia Regina Rogatto. Germline cancer predisposition gene mutations among patients with early onset rectal 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 1414.
Abstract 1415: Target sequencing of tumor driver genes in lung adenocarcinoma tissues
Authors: Zhu Jiawei , Feng Lin , Xiao Ting 
Published: August 2018

Abstract
Background and objective As the main histological subtype of lung cancer, lung adenocarcinoma (ADC) contributes to a cancer-related death in the word. With the development of high-throughput genomic analysis, whole-genome sequencing provides a new opportunity to identify genetic mutations that drive the origination, growth, and spread of cancer. The aim of this study is to detect the mutated genes in lung adenocarcinoma tissues and to analyze its clinical significance, based on 483 tumor driver gene sequence of ADC samples.
Methods We obtained 40 pairs of samples from ADC tumors and matched normal adjacent tissue, which included female (58%), male (43%), people over 60 years old (63%), stage I (40%), stage II (20%), stage III (38%), and stage IV (3%). Based on the Illumina HiSeq2500 sequencing technology platform, small fragment library was built, high coverage of the target area was captured by NovoP products (Agilent sure select XT Custom 0.5-2.9Mb kit, contains 483 tumor related target gene probe). DNA samples was examined by Paired-End sequencing; sequencing data of 40 cases of tumor samples was obtained. We analyzed the sequencing results of lung adenocarcinoma tumor and matched normal adjacent tissues by using bioinformatics analysis methods, and sought for somatic mutations in lung adenocarcinoma tumor and matched normal adjacent tissues.
Results There were 31 ADC samples had reliable exons mutations in the target area, totally 142 (102 genes) mutation positions, including non-synonymous mutations (65%), synonymous mutations (26%), and terminating translation mutation (8%). Totally 116 mutation positions (81.69%) were located in the target capture area. Gene mutations were more frequent in smoking and aged patients. Top ten mutation frequency genes were TP53, EGFR, PIK3CA, ATN1, ATXN1, ABL1, ALK, EGF, EPHA3, and KRAS. And compared to The Cancer Genome Atlas (TCGA) data, the mutation frequency of EGFR was significantly higher in our research.
Conclusion These data provided evidence for the further determination of the molecular mechanism and molecular typing of lung adenocarcinoma. Mutation frequency of TP53, EGFR and PIK3CA in lung adenocarcinoma tissue was the highest.
Citation Format: Jiawei Zhu, Lin Feng, Ting Xiao. Target sequencing of tumor driver genes in lung adenocarcinoma tissues [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 1415.
Abstract 1416: Pan-cancer mutual vulnerability and viability
Authors: Yeerna Huwate , Kim William , Hahn William C. , Mesirov Jill , Tamayo Pablo 
Published: August 2018

Abstract
We used a skew-distribution-based statistical methodology to fit parametric models of cell-viability profiles from genome-wide RNAi-gene knockdowns. We identify the subset of genes with the highest degree of skewness that represent most oncogenes and tumor suppressors. We decomposed those genes using matrix decomposition in order to define mutual vulnerabilities. The resulting matrix decomposition components represent coordinated patterns of gene dependency shared by many genes in many cell lines across cancer types. We identify the most salient mutual vulnerabilities, generate a comprehensive catalog of them, and annotate them based on their association with a variety of genomic features including: gene, protein, and pathway expression, mutational landscape, copy number alterations, promoter methylations, metabolites, miRNAs, and drug sensitivities. We also generate an Onco-GPS (Oncogenic Positioning System) Map that provides a summary and visual representation of the mutual vulnerabilities and their components, and allow us to compare them with their counterparts in Pan-Cancer transcriptional and drug sensitivity spaces.
Citation Format: Huwate Yeerna, William Kim, William C. Hahn, Jill Mesirov, Pablo Tamayo. Pan-cancer mutual vulnerability and viability [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 1416.
Abstract 1422: NEBNext Direct® Custom Ready myeloid genes for NGS target enrichment
Authors: Adams Scott M. , Patel Kruti M. , Emerman Amy B. , Bowman Sarah K. , Elfe Charles D. , Mauceli Evan , Barry Andrew , Davis Theodore , Hendrickson Cynthia L. 
Published: August 2018

Abstract
Comprehensive genetic evaluation of patients with blood cancer can be imperative for identifying and classifying myeloid malignancies in a patient. Since liquid tumors comprise of highly variable percentages of normal cells or multiple tumor clones, this type of screening is critical for early stage disease patients where a cytogenetic profile informs diagnosis or disease stratification, prognosis, and treatment options. For patients with late-stage disease, genetic testing can assist in choosing options for alternative treatments, including targeted therapies. Thus, next generation sequencing technologies are needed that can provide the sensitivity and specificity to identify these genetic complexities. Here we introduce a selection of over 50 genes from the NEBNext Direct® Custom Ready gene catalog that are known to be involved in myeloid malignancies. The NEBNext Direct® technology uses a novel approach to selectively enrich nucleic acid targets, and rapid customized panels can be generated by combining one to several hundred genes from the Custom Ready catalog. Unlike alternative hybridization methods, NEBNext Direct® does not require upfront library preparation. The approach rapidly hybridizes both strands of genomic DNA to biotinylated baits, captures the targets on streptavidin beads, enzymatically removes off-target sequence, and directly converts captured molecules into Illumina-compatible sequencing libraries in a single day protocol. A 12-base unique molecular identifier (UMI) tags each individual molecule prior to the final PCR amplification to enable identification of PCR duplicates, and an 8-base barcode is added to each library during PCR for high-throughput pooling. With 100ng of DNA input the panel provides highly uniform coverage and approximately 95% of sequence reads map to the targeted myeloid genes. The NEBNext Direct® Custom Ready myeloid genes demonstrate a high-throughput and cost-effective approach for the rapid and sensitive analysis of exon coding regions (~200kb) for over 50 oncogenic genes important in the pathogenesis of these types of blood disorders. These gene mutations are powerful prognostic markers that can be used as a guide for effective patient management.
Citation Format: Scott M. Adams, Kruti M. Patel, Amy B. Emerman, Sarah K. Bowman, Charles D. Elfe, Evan Mauceli, Andrew Barry, Theodore Davis, Cynthia L. Hendrickson. NEBNext Direct® Custom Ready myeloid genes for NGS target enrichment [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 1422.
Abstract 1433: Estrogen-related receptor alpha (ERRα) functions to promote prostate cancer cell stemness via its transcriptional regulation of ZIP1 and ACON2 to enhance oxidative phosphorylation
Authors: Ma Taiyang , Xu Zhenyu , Wang Yuliang , Wang Zhu , Gao Weijie , You Wenxin , Chan Leung Franky 
Published: August 2018

Abstract
Accumulating evidences suggest that cancer stem-like cells (CSCs) play critical roles in cancer relapse and metastasis, likely due to their strong self-renewal capacity and chemo-radiotherapy resistance. Recent advances also indicate that the energy metabolism status of the CSCs differs greatly from the bulk cancer cells, and that such energy metabolism shift may favor the maintenance of cancer cell stemness. Estrogen-related receptor alpha (ERRα, NR3B1) is a key energy metabolism regulator. In this study, we aim to characterize its role in the energy metabolism regulation in prostate cancer stem-like cells (PCSCs). By analyzing the oxygen consumption and extracellular acidification rates using the Seahorse XF Analyzer, we revealed that the PCSCs, isolated from prostate cancer cell lines (LNCaP, DU145 and PC3) by low attachment 3D-culture, exhibited lower aerobic glycolysis but higher oxidative phosphorylation status. Expression analyses by qPCR and Western blot showed that the isolated PCSCs expressed higher levels of ERRα. Further functional studies showed that overexpression of ERRα could promote the oxidative phosphorylation but lower the glycolysis status, and also enhance the 3-D spheroid formation capacity (stemness) of prostate cancer cells (LNCaP, DU145 and PC3), whereas its knockdown could reverse the effects. Furthermore, we identified by combined chromatin immunoprecipitation (ChIP) and PCR analysis that ERRα could directly regulate two key energy metabolic genes ACON2 (a rate limiting enzyme in TCA cycle) and ZIP1 (a zinc transporter) in PCSCs. Western blot analysis showed that ERRα could up-regulate the ACON2 but repress the ZIP1 expression, whereas its knockdown reverse the expressions of these two proteins in prostate cancer cells. Together, our results show that ERRα can promote the stemness of prostate cancer cells and enhance the cellular energy metabolism towards oxidative phosphorylation in PCSCs via its transcriptional regulation of ACON2 and ZIP1 genes.This study is supported by a General Research Fund from the Research Grants Council of Hong Kong (project code 14107116).
Citation Format: Taiyang Ma, Zhenyu Xu, Yuliang Wang, Zhu Wang, Weijie Gao, Wenxin You, Leung Franky Chan. Estrogen-related receptor alpha (ERRα) functions to promote prostate cancer cell stemness via its transcriptional regulation of ZIP1 and ACON2 to enhance oxidative phosphorylation [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 1433.
Abstract 1435: Investigation of phosphoserine aminotransferase 1: Its role in breast cancer progression
Authors: Metcalf Stephanie , Kruer Traci , Wittliff James , Klinge Carolyn , Clem Brian F. 
Published: August 2018

Abstract
Metastasis and endocrine resistance are two factors that complicate therapeutic intervention in breast cancer patients and lead to poorer overall survival. Metastasis is known to be responsible for 90% of cancer related deaths, and is especially prevalent in triple negative breast cancer (TNBC); while endocrine resistance can affect up to 50% of patients diagnosed with estrogen receptor positive breast cancer (ER+BC). Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step within de novo serine biosynthesis and increased expression of enzymes in this pathway have been linked to progression of breast cancer and poor clinical outcomes. Within our preliminary retrospective analysis of human breast cancer patients, we identified an inverse association with elevated transcript levels and poorer distant metastasis free survival, which, coupled to a previously reported correlation of PSAT1 with response to endocrine therapy in patients with ER+BC, we postulate that PSAT1 contributes to breast cancer progression through promotion of metastasis and/or endocrine resistance. To initially determine relevance for PSAT1, immunohistochemistry was performed to determine PSAT1 expression in human breast cancer patients. We found that PSAT1 expression is increased through breast cancer progression, with highest levels observed within metastatic conditions. To investigate the metastatic contribution of PSAT1, we silenced PSAT1 expression within the triple negative breast cancer cell line (TNBC), MDA-MB-231. While suppression of PSAT1 had no effect on proliferation, there was a significant decrease in the motility and invasion of these cells. In addition, decreased PSAT1 substantially inhibited tumor nodule formation following tail-vein injections of MDA-MB-231 cells in vivo. To investigate PSAT1's role in endocrine resistance, we used parental MCF-7 cells and an endocrine-resistant derivative cell lines and found that resistant cells exhibited higher PSAT1 expression compared to parental MCF-7 cells. Lastly, suppression of PSAT1 trended to sensitize the resistant cells to 4-hydroxytamoxifen treatment. Taken together, these data indicate that PSAT1 may contribute to the progression of human breast cancer via either metastasis or endocrine resistance or both and could potentially serve as a viable target for new therapies.
Citation Format: Stephanie Metcalf, Traci Kruer, James Wittliff, Carolyn Klinge, Brian F. Clem. Investigation of phosphoserine aminotransferase 1: Its role in breast 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 1435.
Abstract 1445: Metastasis-resistant fatty liver induced by a choline-deficient diet
Authors: Nakamura Miki , Suetsugu Atsushi , Satake Tomoyuki , Hasegawa Kosuke , Shimizu Masahito , Saji Shigetoyo , Moriwaki Hisataka , Hoffman Robert M. 
Published: August 2018

Abstract
Background: Fatty liver disease is increasing worldwide. The differences of the liver metastasis between fatty liver and normal liver remain unclear. We established the EL4-RFP lymphoma models in mice with fatty liver induced by a choline-deficient-diet (CDD) comparing the frequency of liver-metastasis of this tumor in mice with fatty and normal livers.
Material and method: C57BL/6-GFP transgenic mice were fed with a CDD in order to establish a fatty liver model. EL4-RFP malignant lymphoma cells were injected in the spleen of fatty-liver mice and normal mice. Using the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope, metastases in mice with fatty liver or normal liver were imaged.
Results: EL4-RFP tumors were observed to metastasize to the liver and bone marrow as well as form ascites. Fewer metastases in the fatty liver were observed than in the normal liver. Similarly, fewer cancer-associated fibroblasts (CAFs) were observed in the fatty liver.
Conclusion: The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty liver. The fatty liver may not be a suitable environment for CAFs which may be due to re-programmed methionine metabolism which may have occurred during the time the animals were on the CDD.
Citation Format: Miki Nakamura, Atsushi Suetsugu, Tomoyuki Satake, Kosuke Hasegawa, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M. Hoffman. Metastasis-resistant fatty liver induced by a choline-deficient diet [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 1445.