bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3011: Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma
Authors: Deng Yang , Tu Huakang , Pierzynski Jeanne A. , Miller Ethan , Huang Maosheng , Gu Xiangjun , Chang David W. , Ye Yuanqing , Hildebrandt Michelle A. , Klein Alison P. , Lippman Scott M. , Wu Xifeng 
Published: August 2018

Abstract
Background Quality of life (QOL) is impaired in pancreatic cancer patients. Our aim was to investigate the determinants and prognostic value of QOL after diagnosis in a hospital-based cohort of racially/ethnically diverse patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods QOL was prospectively assessed using the Short Form-12 version 1 in 2478 PDAC patients. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were categorized into tertiles based on their distribution. Ordered logistic regression was adopted to compare the risk of having lower PCS and MCS by patient sociodemographic and clinical characteristics. The association of PCS and MCS with mortality was assessed by Cox regression. Results Compared with non-Hispanic whites, Hispanics were at significantly higher risk of having lower PCS (odds ratio [95%CI], 1.69 [1.26-2.26]; P &lt; .001) and lower MCS (1.66 [1.24-2.23]; P &lt; .001). Patients diagnosed with stage III (1.80 [1.10-2.94]; P = .02) and stage IV (2.32 [1.50-3.59]; P &lt; .001) were more likely to have lower PCS than were patients diagnosed with stage I. Other determinants included sex, age, drinking, smoking, education level, and comorbidities. The low tertile of PCS (hazard ratio [95%CI], 1.94 [1.72-2.18]; P &lt; .001) and MCS (1.42 [1.26-1.59]; P &lt; .001) were each related to poor prognosis. Similar results were found for non-Hispanic Whites as compared to African Americans/Hispanics/others. Conclusion QOL after diagnosis is a significant prognostic indicator for patients with PDAC, and multiple factors determine QOL, suggesting possible means of intervention to improve QOL and outcomes of PDAC patients.
Citation Format: Yang Deng, Huakang Tu, Jeanne A. Pierzynski, Ethan Miller, Maosheng Huang, Xiangjun Gu, David W. Chang, Yuanqing Ye, Michelle A. Hildebrandt, Alison P. Klein, Scott M. Lippman, Xifeng Wu. Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma [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 3011.
Abstract 3015: Precise investigation of cancer stem cells in mouse glioblastoma
Authors: Xie Xuanhua P. , Laks Dan R. , Sun Daochun , Poran Asaf , Laughney Ashley M. , Belenguer German , Massague Joan , Zhou Xiuping , Farinas Isabel , Elemento Olivier , Parada Luis F. 
Published: August 2018

Abstract
In this study, we employ mouse models to investigate features and roles of cancer stem cells (CSCs) in glioblastoma (GBM). A nestin-TK-GFP transgene is firstly used to label CSCs in a fully penetrant mouse model of GBM (M7: hGFAP-Cre; Nf1fl/+; p53fl/fl; Ptenfl/+). Food-mediated ganciclovir (GCV) delivery kills proliferative transgene positive cells and significantly prolongs the lives of the transgene bearing mice. Isolation and transplantation of the tumor cells indicates the GFP+ cells are more tumorigenic than the GFP- cells. We then generate and characterize a novel transgene (CGD: nestin-CreERT2-H2BeGFP-hDTR) that labels all the neural stem/progenitor cells in the subventricular zone (SVZ). This transgene efficiently promotes brain tumors by eliminating tumor suppressor genes (CGD-M4: CGD; Nf1fl/+; p53fl/+; Ptenfl/+) in the corresponding cells. The CGD-GFP+ tumor cells are quiescent in vivo, yet form more spheres in vitro than the GFP- cells. The GFP+ cells are competent to develop tumors in a serial transplantation assay and constantly maintain a quiescent subpopulation pool in the newly formed tumors. Diphtheria toxin treatment ablates the CGD-GFP+ tumor cells and greatly reduces the tumor bulk. Temozolomide, the conventional chemotherapy for human GBM patients, benefits only mice transplanted with GFP- but not CGD-GFP+ tumor cells. Our study demonstrates the essential role of CSCs in GBM initiation, recurrence, and drug resistance. Further analysis of the CGD-GFP+ cells might delineate novel treatments for this deadly disease.
Citation Format: Xuanhua P. Xie, Dan R. Laks, Daochun Sun, Asaf Poran, Ashley M. Laughney, German Belenguer, Joan Massague, Xiuping Zhou, Isabel Farinas, Olivier Elemento, Luis F. Parada. Precise investigation of cancer stem cells in mouse glioblastoma [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 3015.
Abstract 3058: Data and resource sharing: Advancing our understanding of glioblastoma
Authors: Luchman Hema A. , Coutinho Fiona , Weiss Samuel , Consortium Stand Up to Cancer Stem Cell Dream Team , Dirks Peter 
Published: August 2018

Abstract
Glioblastoma multiforme (GBM), characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity, remains incurable. GBM has a median survival of only 12-15 months post-surgery in adults even with standard of care chemotherapy and radiation. Through a collaborative pan-Canadian Stand up to Cancer (SU2C) Stem Cell Dream Team effort, our group is focusing on brain tumour stem cells (BTSCs), a subpopulation of cells within tumours, which are hypothesized to drive tumour growth, relapse, and resistance to conventional chemotherapies. We are completing large-scale phenotypic cell biology, tumourigenicity, drug screening, and multi-platform ‘omic studies (genomics, bulk and single cell transcriptomics, epigenomics, metabolomics, proteomics, ATACseq) on a large number of adult GBM patient-derived BTSC cultures. Using both in vitro and in vivo approaches and the above multi-platform approaches, we are investigating the unique growth and stem cell characteristics of the BTSCs. In addition, we are using BTSC cultures to investigate drug response and genetic targeting approaches to identify new therapeutic strategies for clinical translation and understand mechanisms of resistance and recurrence. The wealth of information derived from this project is being integrated using systems biology approaches and will be shared in the public domain via data visualization and big data sharing platforms. Contemporaneously, we are depositing a number of well-characterized BTSC cultures in the American Type Culture Collection repository for unrestricted access to the scientific community. Our cross-Canada multi-disciplinary Cancer Stem Cell Dream Team, comprised of scientists, clinicians and patient advocates supports the ideal of data and resource sharing to help improve patient outcome for this devastating disease. Our goal is to provide the broader community of scientists, clinicians and patient groups an enduring resource and data sharing model to advance our understanding of glioblastoma.
Citation Format: Hema A. Luchman, Fiona Coutinho, Samuel Weiss, Stand Up to Cancer Stem Cell Dream Team Consortium, Peter Dirks. Data and resource sharing: Advancing our understanding of glioblastoma [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 3058.
Abstract 3060: EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres through regulating HER3/ERBB3 expression as a therapeutic target against EGFR-positive non-small cell lung cancer
Authors: Cheng Chun-Chia , Chou Kuei-Fang , Wu Cheng-Wen , Su Nai-Wen , Peng Cheng-Liang , Su Ying-Wen , Chang Jungshan , Ho Ai-Sheng , Lin Huan-Chau , Chen Caleb Gon-Shen , Chang Yu-Cheng , Lim Ken-Hong , Chang Yi-Fang 
Published: August 2018

Abstract
Objectives: YM155, an inhibitor of interleukin enhancer-binding factor 3 (ILF3), significantly suppresses cancer stemness property, implying that ILF3 contributes to cell survival of cancer stem cells. However, the molecular function of ILF3 inhibiting cancer stemness remain unclear. This study aimed to uncover the potential function of ILF3 involving in cell survival of epidermal growth factor receptor (EGFR)-positive lung stem-like cancer, and investigate the potential role to improve the efficacy of anti-EGFR therapeutics.
Materials and Methods: The regulated association of EGFR and ILF3 was investigated at first. ILF3 was knockdowned and RNAseq was utilized to search for the putative genes regulated by ILF3. Meanwhile, HCC827- and A549-derived cancer stem-like cells were used to investigate the role of ILF3 in the formation of cancer stem-like tumorspheres.
Results: We found that EGFR induced ILF3 expression, and YM155 reduced EGFR expression. The knockdown of ILF3 reduced not only EGFR expression in mRNA and protein levels, but also cell proliferation in vitro and in vivo, demonstrating that ILF3 was an oncoprotein contributing to cancer cell survival. Moreover, the knockdown and inhibition of ILF3 by shRNA and YM155, respectively, reduced the formation and survival of HCC827- and A549-derived tumorspheres through inhibiting HER3/ERBB3 expression, and synergized the therapeutic efficacy of afatinib, a tyrosine kinase inhibitor, against EGFR-positive A549 lung cells.
Conclusion: This study demonstrated that ILF3 played an oncogenic role maintaining the EGFR-mediated cellular pathway as a therapeutic target to improve the therapeutic efficacy of afatinib. Therefore, we suggested that YM155, an ILF3 inhibitor, was potential for utilization in cancer therapy against the EGFR-positive cancers.
Citation Format: Chun-Chia Cheng, Kuei-Fang Chou, Cheng-Wen Wu, Nai-Wen Su, Cheng-Liang Peng, Ying-Wen Su, Jungshan Chang, Ai-Sheng Ho, Huan-Chau Lin, Caleb Gon-Shen Chen, Yu-Cheng Chang, Ken-Hong Lim, Yi-Fang Chang. EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres through regulating HER3/ERBB3 expression as a therapeutic target against EGFR-positive non-small cell lung 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 3060.
Abstract 3068: Chronic alcohol exposure induces malignant transformation of pancreatic ductal epithelial cells and generates stem cell characteristics
Authors: Yu We , Ma Yiming , Shankar Sharmila , Srivastava Rakesh K. 
Published: August 2018

Abstract
Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol toxicity-related disease pathogeneses. Epidemiologic data indicate that heavy drinking is associated with high risk of pancreatic cancer. However the molecular mechanisms by which chronic ethanol exposure changes pathophysiology of human pancreatic ductal epithelial (HPNE) cells is not well understood. Cancer stem cells (CSCs) play significant role in cellular transformation, and their emergence is responsible for cancer initiation, progression and metastasis. SATB2 is required for normal mammalian development; however, it is not expressed in normal adult cells. Inappropriate activation of SATB2 gene may cause malignant cellular transformation. SATB2 regulates transcription of pluripotency maintaining factors which are required for sustaining the stem cells capacity for self-renewal. The main goal of the paper is to examine the molecular mechanisms by which chronic alcohol consumption induces cellular transformation of HPNE cells. To investigate the role of SATB2 at an early step of cell transformation, we utilized HPNE cells to generate progenitor cells either by chronic ethanol exposure or overexpression with SATB2. Our data demonstrate that chronic exposure of HPNE cells to ethanol induces cellular transformation by upregulating SATB2. Furthermore, during ethanol-induced cell transformation, cells gain the phenotype of progenitor cells / CSCs and express pluripotency maintaining factors and epithelial-mesenchymal transition (EMT) markers. Suppression of SATB2 expression in ethanol-transformed HPNE cells inhibits stemness and EMT. SATB2 is highly expressed in pancreatic cancer tissues derived from human and KrasG12D mice. In conclusion, chronic ethanol exposure may contribute in pancreatic carcinogenesis by inducing the expression of SATB2 gene.
Citation Format: We Yu, Yiming Ma, Sharmila Shankar, Rakesh K. Srivastava. Chronic alcohol exposure induces malignant transformation of pancreatic ductal epithelial cells and generates stem cell characteristics [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 3068.
Abstract 3075: Type IIB DNA topoisomerase is downregulated by trastuzumab and doxorubicin to synergize cardiotoxicity
Authors: Jiang Jiangsong , Mohan Nishant , Endo Yukinori , Shen Yi , Wu Wen Jin 
Published: August 2018

Abstract
Despite heightened risk of cardiotoxicity associated with combination therapy of anthracyclines and trastuzumab in HER2-positive breast cancer patients, little research effort has been invested in exploring the molecular mechanisms of cardiotoxicity induced by this combination therapy. Using human primary cardiomyocytes as a model, we demonstrate that trastuzumab downregulates both gene and protein expressions of type IIB DNA topoisomerase/DNA topoisomerase IIB (TOP2B), a major intracellular target mediating doxorubicin-induced cardiotoxicity. This downregulation of TOP2B in turn induces DNA damage activity and DNA double strand breaks. However, unlike doxorubicin, trastuzumab alone does not induce apoptosis. Further investigation discovers that concurrent or sequential treatment of doxorubicin and trastuzumab significantly reduces protein levels of TOP2B, enhances apoptosis induced by doxorubicin, and inhibits cell growth. Furthermore, treatment of cardiomyocytes with doxorubicin and trastuzumab in either concurrent or sequential setting also enhances production of reactive oxidative and nitrative species as compared to either trastuzumab or doxorubicin treatment in cardiomyocytes. Our data reveal that doxorubicin treatment increases the cellular level of ErbB2/HER2 protein and enhances downstream signaling activity of this pathway. Consequently, this may render cardiomyocytes more sensitive to trastuzumab treatment after doxorubicin exposure. This study provides molecular basis for significantly increased cardiotoxicity in cancer patients treated with anthracyclines and trastuzumab-based combination regimens.
Citation Format: Jiangsong Jiang, Nishant Mohan, Yukinori Endo, Yi Shen, Wen Jin Wu. Type IIB DNA topoisomerase is downregulated by trastuzumab and doxorubicin to synergize cardiotoxicity [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 3075.
Abstract 3076: Smoking behavior weakens the protective effect of mosaic loss of chromosome Y on lung cancer
Authors: Qin Na , Wang Cheng , Ma Zijian , Chen Jiaping , Shen Hongbing 
Published: August 2018

Abstract
Mosaic loss of chromosome Y (mLOY) is the most commonly detectable mosaic chromosomal event in cancers, however, the underlying relationship with tumorigenesis is still unclear. We conducted a Mendelian randomization study to systematically investigate the effect of mLOY on lung cancer based on published GWASs study. We identified that genetically defined mLOY was a protective factor for lung cancer in non-smokers but not in smokers (lifelong non-smokers: OR=0.80, CI=0.69-0.93, P=4.03×10-3; ever-smokers: OR=0.96, CI=0.89-1.04, P=2.90×10-1; PHeterogeneity=3.83×10-2). A U-shaped curve between the copy-number level of chromosome Y and lung cancer risk was further fitted (P for Linearity Wald=8.81×10-10) to support that heavy mLOY caused by acquired damaging environmental factors may have different effects on lung cancer from the genetically defined mLOY, while genetically predicted mLOY was linearly associated with decreased lung cancer risk (P for Linearity Wald=0.15). Taken together, we proposed a two “sides” model: the “natural” mLOY reduced the lung cancer risk, while the effect can be abolished by aberrant loss of chromosome Y caused by environmental risk factors. Our results revealed a complex relationship between mLOY and lung cancer, and emphasized the importance of heterogeneity in the mLOY studies.
Citation Format: Na Qin, Cheng Wang, Zijian Ma, Jiaping Chen, Hongbing Shen. Smoking behavior weakens the protective effect of mosaic loss of chromosome Y on lung 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 3076.
Abstract 308: Yeast Bax Inhibitor, BXI1, is involved in calcium homeostasis of the ER in Saccharomyces cerevisiae
Authors: Andrews Nicholas , Mello Nicholas , McDonough Liam , Alisch Joseph , Eagan David , Mullin James , Gonzalez Alfredo , Austriaco Nicanor 
Published: August 2018

Abstract
Yeast Bax inhibitor-1 (BXI1/YBH3) encodes a protein that belongs to the Bax Inhibitor (TMBIM) family of proteins that all contain a transmembrane BAX inhibitor motif. The crystal structure of a prokaryotic member of the family, BsYetJ, has revealed that the Bax inhibitor proteins are pH sensitive calcium leaks. In mammals, the Bax inhibitor family of proteins has cytoprotective properties that are most evident in paradigms of endoplasmic reticulum (ER) stress. Our published studies have shown that yeast Bxi1p is localized to the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by ER stress. BXI1 is thought to act via a mechanism involving altered calcium dynamics. We now show that cells lacking BXI1 accumulate higher levels of calcium in their ER as compared to their wildtype counterparts. We have also over expressed Bxi1p in E.coli and have used a fura-2 based calcium assay to show that the protein facilitates the influx of extracellular calcium into the cell. Our preliminary data with Δbxi1 Δpmr1 double mutants suggest that Bxi1p and Pmr1p, the Golgi-ER calcium pump, function in an antagonistic manner. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.]
Citation Format: Nicholas Andrews, Nicholas Mello, Liam McDonough, Joseph Alisch, David Eagan, James Mullin, Alfredo Gonzalez, Nicanor Austriaco. Yeast Bax Inhibitor, BXI1, is involved in calcium homeostasis of the ER in Saccharomyces cerevisiae [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 308.
Abstract 3082: Epidermal-specific overexpression of T-cell protein tyrosine phosphatase in mouse attenuates chemically-induced skin carcinogenesis
Authors: Kim Mihwa , Morales Liza D. , Jang Iksoon , Tsin Andrew , Kim Dae Joon 
Published: August 2018

Abstract
Tyrosine phosphorylation signaling, which is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is critical in maintaining cellular homeostasis. The aberrant increase of tyrosine phosphorylation by mutation and/or overexpression of PTKs can contribute to skin carcinogenesis. While PTKs have been extensively studied in skin carcinogenesis, PTPs have not been studied due to their inactivation by environmental toxicants. Our recent studies showed that T-cell protein tyrosine phosphatase (TC-PTP; encoded by Ptpn2) deficiency in mouse epidermis significantly increased skin tumor formation, demonstrating TC-PTP deficiency predisposes mice to skin carcinogenesis. To further examine the tumor suppressive role of TC-PTP in skin carcinogenesis, we generated epidermal-specific TCPTP-overexpressing (K5HA.Ptpn2) transgenic mice. TC-PTP overexpression led to sensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP overexpression in epidermis significantly reduced epidermal thickness and hyperproliferation compared to wild-type control following treatment with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, TC-PTP overexpression significantly induced epidermal differentiation following TPA treatment as evidenced by the increased expression of epidermal differentiation markers loricrin, involucrin, keratin 10, and transglutaminase 5 in comparison to control. Two-stage skin carcinogenesis analysis using a DMBA/TPA regimen clearly revealed that K5HA.Ptpn2 mice exhibited delayed tumor development and significantly reduced tumor numbers compared to control mice. Taken together, our results suggest that TC-PTP is a potential therapeutic target for the prevention of skin cancer given its ability to promote epidermal apoptosis and differentiation and inhibit epidermal proliferation.
Citation Format: Mihwa Kim, Liza D. Morales, Iksoon Jang, Andrew Tsin, Dae Joon Kim. Epidermal-specific overexpression of T-cell protein tyrosine phosphatase in mouse attenuates chemically-induced skin carcinogenesis [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 3082.
Abstract 3083: Ameliorative effect of ethanolic extract of Annona muricata against sodium arsenite-induced hepatotoxicty in Wistar rats
Authors: Adegboyega Adenike M. 
Published: August 2018

Abstract
Ingestion of arsenic in drinking water causes cancer at multiple tissues and there is no cure. Cancer has become a great monster to human race, as it places a significant emotional and economic burden on families and governments all over the world. Research is therefore directed at chemoprevention using medicinal herbs for the management of arsenicosis. In this study, we evaluated the in vitro antioxidant and protection offered by Annona muricata L. (AM) against sodium arsenite induced hepatotoxicity in rats. Antioxidant and radical scavenging activities of AM were compared to vitamin C and butylated hydroxytoluene (BHT). Proximate and phytochemical analyses were also carried out. Hepatoprotective study was investigated with six groups of rats that received distilled water (Control), 5.0 mg/kg bwt of NaAsO2, 250 mg/kg bwt AM, 500 mg/kg bwt AM, NaAsO2 plus 250 mg/kg AM, NaAsO2 and 500 mg/kg AM. The NaAsO2 was given once on days 7, 14 and 21, while AM was administered orally daily for 21 days. Serum transaminases and alkaline phosphatase activities were determined and liver histopathology carried out. AM contained 2.00% ash, 1.94% crude fat, 25.65% crude fibre, 2.88% protein and 58.62% carbohydrate. Phytochemical analysis indicated the presence of alkaloids, flavonoids and cardiac glycosides. The reducing power and metal chelating ability was in the order Vit C &gt; BHT &gt; AM, while for DPPH scavenging ability AM &gt; Vit C &gt; BHT. The NaAsO2 significantly (p &lt; 0.05) increased the liver function enzymes relative to control. However, AM treatment markedly reduced the marker enzymes and restores the severe vaculation of hepatocytes in the NaAsO2 group to near normal. Our findings suggest that AM may constitute a remedy against arsenic induced hepatic injuries.
Citation Format: Adenike M. Adegboyega. Ameliorative effect of ethanolic extract of Annona muricata against sodium arsenite-induced hepatotoxicty in Wistar rats [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 3083.