bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3079: Epstein Barr virus-encoded LMP1 reprograms glucose metabolism to enhance cell motility in nasopharyngeal epithelial cell
Authors: Zhang Jun , Lin Weitao , Tsang Chi Man , Liu Teng Fei , Tang Wing Chong , Yip Yim Ling , Deng Wen , Jia Lin , Tsao Sai Wah 
Published: August 2018

Abstract
How oncogenic virus rewires glucose flux to regulate cell motility is not well-understood. Epstein-Barr virus (EBV) infection of preinvasive nasopharyngeal epithelium is believed to be an essential initiation event during nasopharyngeal carcinoma pathogenesis. Here we demonstrate that EBV-encoded LMP1 enhances glycolysis thereby accelerating cell mobility of nasopharyngeal epithelial (NPE) cells. Activation of IGF1/mTORC2/AKT/PDHE1α signaling which mediates Histone 3 acetylation is involved in cell motility in EBV-infected NPE cells. Blocking the glucose uptake by pharmacological inhibitors effectively suppress glycolysis as well as the cell motility, linking the glucose metabolism to cell movement. We further show that mTORC2/AKT mediated phosphorylation of pyruvate decarboxylase kinase 1 (PDHK1) and its substrate, pyruvate decarboxylase E1α (PDHE1α) component plays a significant role in cell motility. PDHE1α knockdown effectively blocks LMP1-induced cell motility while overexpression of its phosphomimetic mutant S293A but not S293D inhibits LMP1-induced cell motility, supporting the involvement of PDHE1α in enhanced cell motility is depended on Ser293 phosphorylation. Furthermore, PDHE1α translocation into nucleus enhances Histone 3 acetylation and its binding to the promoter region of snail to enhance cell motility. Finally, we find that LMP1 increases the mRNA expression and the secretion of the ligand IGF1, which promotes phosphorylation of IGF1R as the key regulator for LMP1-induced mTORC2/AKT activation. In summary, this study provides evidences of involvement of EBV infection in metabolic reprogramming of NPE cells to promote cell motility involving activation of mTORC2/AKT/PDHE1α.
Acknowledgment: This project was supported by funding from the Research Grants Council, Hong Kong: General Research Fund (17120814, 17161116, 17111516, 171110315), Area of Excellence (AoE/M-06/08), Theme-Based Research Scheme (T12-401/13-R), Collaborative Research Fund (Project reference: C7027-16G); Health and Medical Research Fund of Hong Kong (12110782, 13120872, 04151726); and CRCG, University of Hong Kong, Hong Kong.
Citation Format: Jun Zhang, Weitao Lin, Chi Man Tsang, Teng Fei Liu, Wing Chong Tang, Yim Ling Yip, Wen Deng, Lin Jia, Sai Wah Tsao. Epstein Barr virus-encoded LMP1 reprograms glucose metabolism to enhance cell motility in nasopharyngeal epithelial cell [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 3079.
Abstract 3084: Epstein Barr virus-encoded LMP1 activates the mTORC2 signaling pathway to reprogram glucose metabolism in nasopharyngeal epithelial cell
Authors: Zhang Jun , Lin Weitao , Tsang Chi-Man , Liu Teng Fei , Tang W C. , Yip Tim Ling , Deng Wen , Jia Lin , Tsao Sai-Wah 
Published: August 2018

Abstract
Epstein-Barr virus (EBV) infection of preinvasive nasopharyngeal epithelium is believed to be an essential initiation event during nasopharyngeal carcinoma pathogenesis, but the underlying mechanisms are largely undefined. Here we demonstrate that EBV-encoded LMP1 reprograms the glucose metabolism from oxidative phosphorylation to glycolysis of nasopharyngeal epithelial (NPE) is a major process for NPC pathogenesis. RNA-seq analysis indicates that EBV infection reprograms the glucose metabolism from glycolysis and oxidative phosphorylation and enhances the metabolic associated pathways. Our study show EBV encoded LMP1 is important for this event, EBV infection and LMP1 expression enhance the extracellular acidification rate and decrease the oxygen consumption rate in NPE cells. We further show that activation of mTORC2/AKT signaling is involved in this metabolic reprogramming in EBV-infected NPE cells. Genetic or pharmacologic inhibition of the mTORC2/AKT signaling blocks the LMP1-induced glycolysis. In summary, this study provides evidences of involvement of EBV infection in metabolic reprogramming of NPE cells. Acknowledgment: This project was supported by funding from the Research Grants Council, Hong Kong: General Research Fund (17120814, 17161116, 17111516, 171110315), Area of Excellence (AoE/M-06/08), Theme-Based Research Scheme (T12-401/13-R), Collaborative Research Fund (Project reference: C7027-16G); Health and Medical Research Fund of Hong Kong (12110782, 13120872, 04151726); and CRCG, University of Hong Kong, Hong Kong.
Citation Format: Jun Zhang, Weitao Lin, Chi-Man Tsang, Teng Fei Liu, W C. Tang, Tim Ling Yip, Wen Deng, Lin Jia, Sai-Wah Tsao. Epstein Barr virus-encoded LMP1 activates the mTORC2 signaling pathway to reprogram glucose metabolism in nasopharyngeal epithelial cell [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 3084.
Abstract 3086: CPAP enhances diethylnitrosamine-induced hepatocarcinogenesis via STAT3 pathway
Authors: Hung Liang-Yi 
Published: August 2018

Abstract
Chronic and persistent inflammation is a well-known carcinogenesis promoter. Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCC arises in the context of chronic inflammation and hepatic injury. Both NF-κB and STAT3 are important regulators for inflammation. Our previous studies indicated that CPAP (centrosomal P4.1-associated protein), a centrosomal protein that majorly participates in centrosome functions, is overexpressed in HCC and can increase TNFα-mediated NF-κB activation and IL-6-induced STAT3 activation. A hepatocyte-specific CPAP-expressing transgenic mouse was generated to investigate the physiological role of CPAP in hepatocarcinogenesis. An obvious inflammatory cell accumulation and fatty change were shown in the CPAP transgenic (Tg) mouse liver. The ALT level as well as the expression of inflammatory genes, such as IL-6, IL1β and TNF-α in CPAP Tg mouse are higher than in the wild type (WT) mouse. By high-dose and short-term diethylnitrosamine (DEN) treatment, the ALT level, pro-inflammatory genes and STAT3 activation are increased in CPAP Tg mouse; low-dose and long-term DEN treatment induces more severe liver tumor formation in CPAP Tg mouse than in WT mouse. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via activating the STAT3 pathway.
Citation Format: Liang-Yi Hung. CPAP enhances diethylnitrosamine-induced hepatocarcinogenesis via STAT3 pathway [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 3086.
Abstract 3090: Phenol modifying influence on genotoxic effect in organism during peroral combined administration with benzo[a]pyrene
Authors: Ostash Olga , Chernichenko Igor , Balenko Nina , Vinarska Elena , Grigorenko Lyudmila , Lukyanchuk Svetlana , Shvager Oksana 
Published: August 2018

Abstract
In the modern world in different spheres of life, people experience a load of the complex of numerous chemical compounds of different types, which have a wide range of biological effects - from toxic ones to mutagenic and carcinogenic. For instance, people suffer from the growth of cancer, which is one of the direct consequences of the impact of environmental pollution by chemical compounds. It has now been proved that the development of cancer is determined not only by the initiating effect of chemical carcinogens, but also by the modifying effect of the concomitant toxic compounds. The aim of this work was experimental study of the role of toxic substances (phenol) in the modification of the evidence of genotoxic and immunological changes in organism in the early stages of carcinogenic activity (benzo[a]pyrene).The studies were conducted with random-bred white male mice. Peroral administration was applied to animals taken benzo[a]pyrene (day-dose 0.1mg), benzo[a]pyrene - phenol (day-dose 0.1; 0.002 mg). Genotoxic changes in forestomach were assessed with the help of micronuclear test. The carcinogenic effect (forestomach papillomas) and common regularities of genotoxical and immunological changes in relation to carcinogenesis and their dose and treatment duration dependence under benzo[a]pyrene (day-dose 0,1mg), benzo[a]pyrene and phenol (day-dose 0,1; 0,002 mg) complexes oral administration in random-bred white mice were established. The noted regularities conducted in interrelation and identical directivity of mutagenic (increasing of micronucleus incidence) and immunological (reducing the relative number of T-lymphocytes) indexes changes in relation to carcinogenesis, presence of reliable cross-correlation connections between them in the end of the first months. Besides, the modifying effect of phenol on the carcinogenesis that appeared by increasing of micronucleus incidence, immunosuppression and index of forestomach papillomas multiplicity was determined. The findings detect the presence of cancer risk from the action of carcinogenic and toxic substances, the formation of which begins in the early period (at the end of the first month) and manifests itself as a genotoxic effect in combination with immunosuppression, which must be taken into account in the hygienic assessment of the state of the environment.
Citation Format: Olga Ostash, Igor Chernichenko, Nina Balenko, Elena Vinarska, Lyudmila Grigorenko, Svetlana Lukyanchuk, Oksana Shvager. Phenol modifying influence on genotoxic effect in organism during peroral combined administration with benzo[a]pyrene [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 3090.
Abstract 3110: Heterokaryon formation and nuclear fusion of hybridizing cancer cells visualized in real time by color-coded imaging
Authors: Suetsugu Atsushi , Matsumoto Takuro , Hasegawa Kousuke , Nakamura Miki , Kunisada Takahiro , Shimizu Masahito , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M. 
Published: August 2018

Abstract
Background: Fusion of cancer cells has been studied for over half a century. However, the steps involved after initial fusion between cells, such as heterokaryon formation and nuclear fusion, have been difficult to observe in real time. In order to be able to visualize these steps, we have established cancer-cell sublines from the human HT-1080 fibrosarcoma, one expressing green fluorescent protein (GFP) linked to histone H2B in the nucleus and a red fluorescent protein (RFP) in the cytoplasm and the other subline expressing RFP in the nucleus (mCherry) linked to histone H2B and GFP in the cytoplasm.
Materials and Methods: The two reciprocal color-coded sublines of HT-1080 cells were fused using the Sendai virus. The fused cells were cultured on plastic and observed using an Olympus FV1000 confocal microscope.
Results: Multi-nucleate (heterokaryotic) cancer cells, in addition to hybrid cancer cells with a single fused nucleus undergoing mitosis, were observed by confocal microcopy. Red, green, orange and yellow nuclei were observed in cells. The orange and yellow nuclei indicate nuclear fusion. Red and green nuclei remained unfused.
Conclusion: Cell fusion with subsequent heterokaryon formation followed by nuclear hybridization may be an important natural phenomenon between cancer cells that may make them more malignant. The ability to image the complex processes following cell fusion using reciprocal color-coded cancer cells will allow greater understanding of the genetic basis of malignancy.
Citation Format: Atsushi Suetsugu, Takuro Matsumoto, Kousuke Hasegawa, Miki Nakamura, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Michael Bouvet, Robert M. Hoffman. Heterokaryon formation and nuclear fusion of hybridizing cancer cells visualized in real time by color-coded imaging [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 3110.
Abstract 3111: Expansion of mouse prostate epithelial stem cells in serum-free ProstaCult Organoid Growth Medium
Authors: Stingl John , Rowbotham David , Thomas Terry E. , Eaves Allen C. , Louis Sharon A. 
Published: August 2018

Abstract
Growing prostate epithelial cells as organoids in a three-dimensional (3D) cell culture environment represents a more physiological model system than conventional 2D adherent cell culture systems for studying many different aspects of prostate epithelial cell biology. Two types of prostate epithelial organoids have been previously described: large hollow cystic organoids, and smaller solid organoids (Karthaus et al, Cell 2014). Both types of organoids are composed of androgen receptor (AR)-expressing luminal cells and keratin (K) 5-expressing basal cells, but only vary in the proportion of each cell type, with the cystic organoids enriched for luminal cells and solid organoids enriched for basal cells. We are currently developing ProstaCult™ Organoid Growth Medium, a serum-free medium for the long-term propagation of both types of organoids from mouse prostate tissue. To initiate the cultures, mouse prostates are enzymatically dissociated sequentially in collagenase type II, trypsin and dispase to generate a single cell suspension, and 5x103 the liberated cells are then embedded in Corning® Matrigel® and cultured in ProstaCult™ Organoid Growth Medium. Approximately 10±2% (mean±sem; n=6) of the seeded cells will proliferate and generate approximately equivalent numbers of cystic and solid organoids, which can be dissociated and passaged every 7 days as a single cell suspension. Typical total epithelial cell expansion observed during media development ranges from 21-240-fold per passage for a minimum of 4 passages. Experiments are ongoing to determine the long-term passageability of organoids maintained in ProstaCult™ Organoid Growth Medium. Organoids that are generated at multiple passages are composed of a polarized epithelium with AR+K18+ luminal cells and K5+ basal cells. These results demonstrate that ProstaCult™ Organoid Growth Medium efficiently generates and expands prostate epithelial organoids.
Citation Format: John Stingl, David Rowbotham, Terry E. Thomas, Allen C. Eaves, Sharon A. Louis. Expansion of mouse prostate epithelial stem cells in serum-free ProstaCult Organoid Growth Medium [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 3111.
Abstract 3112: Distinct oncogenic events induce different DNA methylation and copy number changes in human mammary epithelial cells
Authors: manoir Stan P. du , Fonti Claire , Saumet Anne , Abi-Khalil Amanda , Orsetti Béatrice , Elouan Cleroux , Bender Ambre , Dumas Michael , Colinge Jacques , Weber Michael , Theillet Charles 
Published: August 2018

Abstract
Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. Molecular subtypes may originate from different cell lineages in the mammary gland, but also from the early activation of oncogenes that may drive the establishment of these molecular subtypes. However, in the natural history of human cancer, it is difficult to discriminate between these two factors : cell lineage and initial oncogenic alterations. In this work, we designed an experimental strategy aiming at determining whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. We show that initial activation of CCNE1, WNT1 and RASv12 in shp53 immortalized HMECs results in different and reproducible profiles of mRNA and miR expression, copy number alterations (CNA) and DNA methylation modifications. Interestingly, first the extend of CNA measured as fraction of the genome altered was lower in HMECs transformed by RAS than CCNE1 and WNT1 transformed HMECs revealing a lower genetic instability. This was confirmed by less numerous γH2Ax and 53BP1 nuclear foci in HMECs transformed by RAS. Second, HMECs transformed by RAS bore specific profiles of CNAs and DNA methylation, clearly distinct of those shown by CCNE1 and WNT1 transformed HMECs. Genes differentially expressed in the RAS and the CCNE1/WNT1 clusters and included in CNAs or with variable CpG methylation were mostly different, depicting the activation of distinct signaling pathways in these two clusters. These data indicate that early activation of distinct oncogenic pathways may leads to adaptive events resulting in specific pattern of CNAs and DNA methylation changes. We postulated that the early activation of oncogenes may be an important determinant of the establishment of breast cancer molecular subtypes along with cell lineage origin.
Citation Format: Stan P. du manoir, Claire Fonti, Anne Saumet, Amanda Abi-Khalil, Béatrice Orsetti, Cleroux Elouan, Ambre Bender, Michael Dumas, Jacques Colinge, Michael Weber, Charles Theillet. Distinct oncogenic events induce different DNA methylation and copy number changes in human mammary epithelial cells [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 3112.
Abstract 3114: In vitro culture system for circulating tumor cell
Authors: Yin-Ju Chen , Lu Long-Sheng , Lee Hsin-Lun , Ting Lai-Lei , Chiou Jeng-Fong 
Published: August 2018

Abstract
Circulating tumor cells (CTCs) detection could be considered a real-time “liquid biopsy” approach and contains several advantages such as being minimally invasive, easy and safe to perform, multiple samples can be taken over time, better prognosis to indicate an elevated risk of metastases, improved therapy monitoring, and providing live disease status information. CTC analysis is a promising new diagnostic field for estimating the risk for metastatic relapse and metastatic progression in patients with cancer. However, the number of CTCs is very low so the establishment of cell culture from CTCs becomes the most challenging over the past year. In this study, we development a cost-effective and reproducible in vitro system for primary CTC cultures or established cell lines from CTCs. 8 CTC cell lines were generated from patients including breast cancer, small cell lung cancer, pancreatic cancer and expanded for more than one year. These cell lines exhibit the tissue-specific markers and also correlated with clinical treatment response from patients. This system provides an opportunity for broad applications of CTCs for personalized oncology and advancing precision medicine.
Citation Format: Chen Yin-Ju, Long-Sheng Lu, Hsin-Lun Lee, Lai-Lei Ting, Jeng-Fong Chiou. In vitro culture system for circulating tumor cell [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 3114.
Abstract 3117: Full spectrum of in vitro disease models with optimized CRISPR-Cas9 gene editing in difficult-to-transfect blood-lineage cells
Authors: Jin Huanyu , Yu Zhongsheng , Pak Vladimir , Zhang Yin , Tummala Padmaja , Rajeswaran Pavithra , Nguyen Diana , Maleszewska Monika , Li Jinling , Cao Charles , Chen-Tsai Ruby Yanru 
Published: August 2018

Abstract
CRISPR/Cas9 technology is a powerful tool for gene editing in mammalian cells. However, the efficiency of gene editing in certain types of cells, especially suspension cells such as several blood-lineage cell lines, is extremely low. This is due to a variety of factors including low transfection efficiency of CRISPR/Cas9 reagents, cytotoxicity, and low or undesired gRNA and Cas9 activities in the cell lines. By optimizing the protocol and transfection conditions, we were able to successfully generate a spectrum of gene modifications in blood-lineage cells. Here, we describe techniques optimized for genome editing in some difficult-to-transfect blood-lineage cell lines and the types of modifications achieved: (1) For leukemia cell lines such as KG-1 and MOLM-13 cells, we compared DNA-based versus RNP-based Cas9 delivery efficiency, and found that plasmid-based Cas9 transfection resulted in cytotoxicity. In contrast, the RNP-based route demonstrated significantly lower cytotoxicity and higher efficiency of gene editing. Furthermore, we found that the application of a DNA-dependent protein kinase inhibitor dramatically enhanced the homology directed repair (HDR) in these cell lines; (2) For T lymphocyte cell lines such as Jurkat cells, we could efficiently delete a targeted 5kb regulatory region of a critical gene. We were also able to sequentially knockout (KO) two genes (double KO) in Jurkat cells using a Cas9-plasmid protocol; (3) In the case of the lymphoblastic cell line T2, we successfully created a large fragment knock-in, as well as a gene knockout cell line model, through DNA-based CRISPR/Cas9 delivery. Our studies demonstrate that for CRISPR/Cas9 genome editing in blood-lineage cells, different cell lines may require different approaches or modified protocols to deliver the CRISPR/Cas9 components for efficient and successful modifications of the targeted genes.
Citation Format: Huanyu Jin, Zhongsheng Yu, Vladimir Pak, Yin Zhang, Padmaja Tummala, Pavithra Rajeswaran, Diana Nguyen, Monika Maleszewska, Jinling Li, Charles Cao, Ruby Yanru Chen-Tsai. Full spectrum of in vitro disease models with optimized CRISPR-Cas9 gene editing in difficult-to-transfect blood-lineage cells [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 3117.