bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-087: Stage specific re-calibration of E2F1 function after RB loss
Authors: Mandigo Amy C. , McNair Christopher , Xu Kexin , Li Fugen , Schiewer Matthew J. , Brown Myles , Knudsen Karen E. 
Published: July 2017

Abstract
Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy, and the third leading cause of cancer death in males in the United States. The development of the disease is reliant on the activity of the androgen receptor (AR), which promotes proliferation and is required for cell growth and survival. Deregulation of AR leads to the progression of PCa to the incurable form of disease termed castration-resistant prostate cancer (CRPC). One of the underlying mechanisms of AR deregulation is the loss of function of the retinoblastoma (RB) tumor suppressor protein. RB loss is almost exclusively seen in CRPC and is sufficient to induce a CRPC phenotype in primary PCa models. However, RB function is only lost in roughly 30% of tumors. The remaining 70% of tumors that progress to CRPC do so via other mechanisms and retain RB function. A subset of RB positive CRPC tumors progress to lose RB function even in this post-CRPC transition stage of disease. Biological assessment performed in isogenic RB knockdown, both hormone-sensitive and CRPC models, identified distinct functional consequences of RB loss depending on disease state. Transcriptome analysis identified opposing regulated gene signatures between disease stages. Further investigation of the E2F1 cistrome revealed differential E2F1 binding with RB loss in hormone sensitive and CRPC models, identifying distinct roles of E2F1, in the absence of RB, in different disease states. Data to be discussed reveal the stage-specific molecular pathways driven by E2F1 upon RB loss with the potential to promote disease progression.
Citation Format: Amy C. Mandigo, Christopher McNair, Kexin Xu, Fugen Li, Matthew J. Schiewer, Myles Brown, Karen E. Knudsen. Stage specific re-calibration of E2F1 function after RB loss [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 LB-087. doi:10.1158/1538-7445.AM2017-LB-087
Abstract LB-096: SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation
Authors: Wang Xiaofeng , Lee Ryan , Alver Burak , Haswell Jeffrey , Wang Su , Troisi Emma , Bernstein Bradley , Park Peter , Roberts Charles 
Published: July 2017

Abstract
The gene encoding SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is biallelically inactivated in nearly all rhabdoid tumors (RTs), highly aggressive and lethal cancers of early childhood. RTs are among the most genomically stable cancers, suggesting an epigenetic mechanism by which SMARCB1 loss drives cancer. Here, we show that despite having indistinguishable mutational landscapes, human RTs show distinct H3K27ac signatures at enhancers that reveal remnants of differentiation programs. In elucidating the mechanism underlying RTs, we find that SMARCB1 is not only essential for the integrity and abundance of SWI/SNF complexes, but also facilitates their targeting to appropriate enhancers. Loss of SMARCB1 alters enhancer targeting—markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers (SEs). We show that these retained SEs are essential for RT survival, including some that are shared across all RT types, such as SPRY1, and other lineage-specific SEs like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1.
Citation Format: Xiaofeng Wang, Ryan Lee, Burak Alver, Jeffrey Haswell, Su Wang, Emma Troisi, Bradley Bernstein, Peter Park, Charles Roberts. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation [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 LB-096. doi:10.1158/1538-7445.AM2017-LB-096
Abstract LB-138: Runx1 enhancer element marks stem cells in multiple organs
Authors: Yamamura Akihiro , Matsuo Junichi , Lim Yi Hui Melissa , Mon Naing Naing , Heng Dede Liana , Unno Michiaki , Yeoh Khay Guan , Osato Motomi , Ito Yoshiaki 
Published: July 2017

Abstract
Enhancer element (270bp) in the non-coding region between P1 and P2 promoters of Runx1 gene, termed eR1, drives the expression of Runx1 in hematopoietic stem cells (1). This element also targets the expression in stem cells in multiple tissues, including stomach (fundus and corpus) (2), intestine, colon, pancreas, liver, mammary gland and lung. Location of the cells identified by eR1 in each tissue was different from that previously shown by other stem cell markers, such as Lgr5. Nevertheless, in vivo lineage tracing results showed that eR1+ cells are differentiated into all the cell types in the tissue until one year post tamoxifen injection. To demonstrate the stem/progenitor activity in eR1+ cells, we isolated functional units of each organ from eR1-CreERT2; Rosa-tdTomato mice 1 day after tamoxifen injection, dissociated them into single cells and incubated in vitro. Mature organoids were generated from eR1+ cells, suggesting that eR1+ cells have potential to function as stem cells. When we examined the organoids generated from the stomach fundus, all the cells within the organoid showed Tomato color, suggesting they were originated from eR1+ cells. On the contrary, the antral organoids were mixture of Tomato positive and Tomato negative cells. Possible explanation for the mixture of color would be that there are more than one type of stem cells in the antrum and eR1+ and eR1- cells jointly made organoids. Since Lgr5+ stem cells have been described at the base (3) and CCK2R stem cells at +4 position (4) of antrum, whereas eR1+ stem cells are at isthmus of antrum (2), we must examine whether eR1- cells are Lgr5+ cells or CCK2R cells. Interestingly, mixture of eR1+ and eR1- organoids were observed in other GI tract organs. We found that contribution of eR1+ is 100% in proximal stomach and gradually decreased towards rectum (18%). Growth factor requirement of eR1+ stem cells were analyzed by withdrawing each factor. We found that eR1+ stem cells do not require Wnt and jagged1 but eR1- cells require Wnt in antrum. We are studying step-wise carcinogenesis using these organoids.
Reference
1. Ng et al. Stem Cells 2010, 28:1869-81.
2. Matsuo J, Yamamura A et al, Gastroenterology 2016, PMID 27670082.
3. Barker et al, Cell Stem Cells 2010, 6:25-36.
4. Hayakawa et al, Gut 2015, 64:544-553.
Citation Format: Akihiro Yamamura, Junichi Matsuo, Yi Hui Melissa Lim, Naing Naing Mon, Dede Liana Heng, Michiaki Unno, Khay Guan Yeoh, Motomi Osato, Yoshiaki Ito. Runx1 enhancer element marks stem cells in multiple organs [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 LB-138. doi:10.1158/1538-7445.AM2017-LB-138
Abstract LB-192: Phenotyping human myeloid derived suppressor cells (MDSC) subsets
Authors: Talmadge James E. , Britton Holly , Dafferner Alicia , Warkentin Phyllis , Cole Kathryn 
Published: July 2017

Abstract
MDSCs are heterogeneous occurring at varying stages of commitment and differentiation. They increase in cancer and other patients with inflammatory diseases and may best be defined based on their ability to suppress T and B cell responses. In recent years these cells have demonstrated clinical relevance, including a negative correlation with prognosis and overall survival in cancer patients increasing with tumor progression and stage. MDSCs were originally described in mice based on a lack of phenotypic markers, i.e. null cells, or predicated on their function, as natural suppressor (NS) cells. Subsequently they were found in humans, based on CD34 expression supporting a hematopoietic progenitor phenotype. The identification of human phenotype(s) is complicated by the association of suppressor cell function with multiple phenotypes. This includes two main subsets defined based on the expression or lack of myeloid and lymphoid markers, with specific phenotypes extent investigator dependent. There is a consensus that MDSCs constitute a continuum of immature to differentiated myeloid cells ranging from multi-potential hematopoietic progenitors to morphologically differentiated granulocytic and monocytic leukocytes. One trending hypothesis is that MDSC phenotypes form three subsets include macrophage (M-) MDSCs with a monocytic morphology, expressing CD14 and no CD15 or CD66b and granulocytic (G)-MDSCs phenotypically characterized by CD15 and/or CD66B expression and no CD14; and an immature (i-) MDSC defined as linage negative, CD33+ cells. Unfortunately, there is no consensus on markers extent to CD14 and CD15 although linage negative and DR- provide a common theme; although not commonly utilized between laboratories and MDSC subset. We provide herein a Flow cytometric strategy utilizing single staining tube and a linear phenotypic characterization that is supported by density and T-cell suppression confirmation. We suggest that staining with Lin, HLA-DR, CD14, CD15, CD11b, CD33 antibodies provides sufficient markers to subset into the three MDSC phenotypes that can be further subset with CD16. PDL1 and CD34 expression. Interestingly the majority of iMDSC express CD34 on the CD33+ cells together with CD14 or CD15 supporting a plastic phenotype with myeloid commitment. All subset can be further, delineated based on CD16 expression further suggesting immaturity. We will note, that some cancer patients express these cell phenotypes at very high levels in the circulation; although the preponderance of G-MDSC vs M-MDSC varies between patients.
Citation Format: James E. Talmadge, Holly Britton, Alicia Dafferner, Phyllis Warkentin, Kathryn Cole. Phenotyping human myeloid derived suppressor cells (MDSC) subsets [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 LB-192. doi:10.1158/1538-7445.AM2017-LB-192
Abstract LB-229: Mutation spectra of aflatoxin B1 in vivo establish biomarkers of exposure for human hepatocellualr carcinoma
Authors: Chawanthayatham Supawadee , Valentine Charles C. , Fedeles Bogdan I. , Slocum Stephen L. , Wogan Gerald N. , Croy Robert G. , Essigmann John M. 
Published: July 2017

Abstract
Responding to a need to identify the mutational processes that are responsible for malignant transformation, highly accurate duplex sequencing (DS) was employed to monitor acquisition of context-dependent high-resolution mutational spectra (MS) during the process of hepatocarcinogenesis. Aflatoxin B1 (AFB1) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB1-DNA adducts in hepatocytes seeds a population of mutations, mainly G:C&gt;T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Four-day old male mice were treated with AFB1 using a regimen that induced hepatocellular carcinoma within 72 weeks. The DS technology revealed a distinctive MS of AFB1 at 10 weeks after dosing, well before evidence of neoplasia. Importantly, 25% of all mutations were G&gt;T in one trinucleotide context (5’-CGC-3’), which is also a hotspot mutation in human liver tumors whose incidence correlates with AFB1 exposure. At 72 weeks, livers were separated into tumor tissue and normal surrounding cellular fractions (primarily hepatocytes). The MS in normal cells surrounding the tumors revealed clear evidence of previous AFB1 exposure with predominantly G:C&gt;T:A mutations and strong representation of the CGC&gt;CTC hotspot. Analysis of tumor tissue revealed a more complex pattern than that observed in surrounding hepatocyte fraction; tumor MS were a composite of the 10-week spectrum and a more heterogeneous set of mutations that emerged during tumor outgrowth. The 10-week AFB1-exposed mouse MS was then used as bait to computationally identify human HCC sequences that have similarity to it. This analysis revealed that the mouse spectrum has striking similarity to human HCCs from hepatitis B infected people who have the R249S mutation in P53. The data also provide insight into the molecular basis for the synergism between hepatitis B exposure and AFB1. The MS provided by DS technology provides a method to identify mutational processes in normal and tumor tissues enabling reconstruction of the molecular etiology of human hepatocarcinogenesis and other genetic diseases.
Citation Format: Supawadee Chawanthayatham, Charles C. Valentine III, Bogdan I. Fedeles, Stephen L. Slocum, Gerald N. Wogan, Robert G. Croy, John M. Essigmann. Mutation spectra of aflatoxin B1 in vivo establish biomarkers of exposure for human hepatocellualr 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 LB-229. doi:10.1158/1538-7445.AM2017-LB-229
Abstract LB-245: Immunohistochemical study of MAGI-2 expression in lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon
Authors: Liao Zhiming 
Published: July 2017

Abstract
Introduction
MAGI-2 (Membrane Associated Guanylate Kinases Inverted 2) is a scaffolding protein that interacts with PTEN in shutting off the Pi3K/AKT pathway. MAGI-2 suppresses AKT by enhancing PTEN function and its protein stability. In this study, we examined the protein expression of MAGI-2 in normal tissues and various solid tumors by immunohistochemistry (IHC).
Methodology
An IHC study of MAGI-2 was performed on normal tissue and tumor tissues from prostate (34 cases), ovary (95 cases), urinary bladder (92 cases), pancreas (88 cases), liver (2 cases), colon (2 cases), and lymphoma (185 cases). MAGI-2 staining intensity was semi-quantitatively scored using a 0-3 scale. Percent positive rate of MAGI-2 was calculated for carcinomas from prostate, urinary bladder, ovary, pancreas, liver, colon, and lymphoma.
Results
In normal tissues, MAGI-2 was detectable by IHC mostly in follicle area of the tonsil or lymph node and in the cuboidal or columnar epithelium of several organs (skin, urinary bladder, breast, fallopian tube, small intestine, colon, prostate, adrenal gland, and thyroid). The protein expression of MAGI-2 was higher in tumor cells than in their adjacent normal tissues from prostate, urinary bladder, ovary, pancreas, lymph node, liver, and colon. The positive rate of MAGI-2 was 100% for invasive prostate adenocarcinoma (34/34 cases), 82% for ovarian adenocarcinoma (78/95 cases), 76 % for urinary bladder carcinoma (70/92 cases), 62 % of pancreatic adenocarcinoma (55/88 cases), 83 % for diffuse large B-cell lymphoma ( 135/163 cases), 80 % for follicular B-cell lymphoma (8/10 cases), 67% for non-Hodgkin B-cell lymphoma (6/9 cases), 0% for small lymphocytic B-cell lymphoma (0/3 cases), 100% for colon adenocarcinoma (2/2 cases), and 100% for hepatocellular carcinoma (2/2 cases).
Conclusions
MAGI-2 is overexpressed in most lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon, but it is not detectable in small lymphocytic B-cell lymphoma by IHC for this study.
Citation Format: Zhiming Liao. Immunohistochemical study of MAGI-2 expression in lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon [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 LB-245. doi:10.1158/1538-7445.AM2017-LB-245
Abstract LB-288: An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED
Authors: Qi Wei , Zhao Kehao , Gu Justin , Huang Ying , Wang Youzhen , Zhang Hailong , Zhang Man , Zhang Jeff , Yu Zhengtian , Li Ling , Teng Lin , Chuai Shannon , Zhang Chao , Zhao Mengxi , Chan HoMan , Chen Zijun , Fang Douglas , Qi Fei , Feng Leying , Feng Lijian , Gao Yuan , Ge Hui , Ge Xinjian , Lingel Andreas , Li Guobin , Lin Ying , Liu Yueqin , Luo Fangjun , Shi Minlong , Wang Long , Wang Zhaofu , Yu Yanyan , Zeng Jue , Zeng Chenhui , Zhang Lijun , Zhang Qiong , Zhou Shaolian , Oyang Counde , Atadja Peter , Li En 
Published: July 2017

Abstract
Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12 and plays pivotal roles in transcriptional regulation through its histone H3K27 methyltransferase activity. Dysregulation of PRC2 is observed in multiple human cancers, for example, the catalytic subunit EZH2 is overexpressed in a wide range of human cancers and gain-of-function mutations of EZH2 within its catalytic site have been reported in human B-cell lymphoma, parathyroid carcinoma and melanoma. Small molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported and showed anti-lymphoma efficacy in pre-clinical studies. EED within the PRC2 complex allosterically activate the enzymatic activity by binding to tri-methylated H3K27 (H3K27me3). Here we report the discovery of EED226, a potent and selective PRC2 inhibitor directly binding to the H3K27me3 binding pocket of EED. EED226 induces conformational change upon binding EED leading to loss of PRC2 activity. EED226 shows similar activity as SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show EED226 inhibits PRC2 activity via an allosteric mechanism and offers opportunity for treatment of PRC2-dependent cancers.
Citation Format: Wei Qi, Kehao Zhao, Justin Gu, Ying Huang, Youzhen Wang, Hailong Zhang, Man Zhang, Jeff Zhang, Zhengtian Yu, Ling Li, Lin Teng, Shannon Chuai, Chao Zhang, Mengxi Zhao, HoMan Chan, Zijun Chen, Douglas Fang, Fei Qi, Leying Feng, Lijian Feng, Yuan Gao, Hui Ge, Xinjian Ge, Andreas Lingel, Guobin Li, Ying Lin, Yueqin Liu, Fangjun Luo, Minlong Shi, Long Wang, Zhaofu Wang, Yanyan Yu, Jue Zeng, Chenhui Zeng, Lijun Zhang, Qiong Zhang, Shaolian Zhou, Counde Oyang, Peter Atadja, En Li. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED [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 LB-288. doi:10.1158/1538-7445.AM2017-LB-288
A new genus and species of Pseudococcidae (Hemiptera: Sternorrhyncha: Coccomorpha) from China
Authors: DONG QIN-GANG , ZHANG JIANG-TAO , WU SAN-AN 
Published: July 2017

A new mealybug genus, Dorsoceraricoccus Dong & Wu gen. nov. (Hemiptera: Sternorrhyncha: Coccomorpha: Pseudococcidae), is described to contain Dysmicoccus muajatae Williams as type species, and a new species, Dorsoceraricoccus ningboensis Dong & Wu sp. nov., collected from Zhejiang Province, China on Digitaria sp. (Poaceae). For the new species, the adult female is described and illustrated. In addition, a key to genera of the subfamily Pseudococcinae now known from China and a key to adult female now in Dorsoceraricoccus gen. nov. are provided.
Explanatory models and distress in primary caregivers of patients with acute psychotic presentations: A study from South India
Authors: Joy Deepa S , Manoranjitham SD , Samuel P , Jacob KS 
Published: July 2017

Background: Emotional distress among caregivers of people with mental illness is common, changes overtime and requires appropriate coping strategies to prevent long-term disability. Explanatory models, which underpin understanding of disease and illness, are crucial to coping. Aim: To study the association of explanatory models and distress among caregivers of people with acute psychotic illness. Method: A total of 60 consecutive patients and their primary caregivers who presented to the Department of Psychiatry, Christian Medical College, Vellore, were recruited for the study. Positive and Negative Syndrome Scale (PANSS), Short Explanatory Model Interview (SEMI) and the General Health Questionnaire-12 (GHQ-12) were used to assess severity of psychosis, explanatory models of illness and emotional distress. Standard bivariate and multivariable statistics were employed. Results: Majority of the caregivers simultaneously held multiple models of illness, which included medical and non-medical perspectives. The GHQ-12 score were significantly lower in people who held multiple explanatory models of illness when compared to the caregivers who believed single explanations. Conclusion: Explanatory models affect coping in caregivers of patients with acute psychotic presentations. There is a need to have a broad-based approach to recovery and care.
The effect of risk communication on the acceptance of policies for high-risk facilities in South Korea: with particular focus on the mediating effects of risk perception
Authors: Lee Dae-Woong , Kwon Gi-Heon 
Published: July 2017

Continuous technological development has resulted in a new type of risk to human lives: what is now regarded as “socially created risk.” Ideas on risk have increasingly focused on subjective, rather than objective, risk. This shift is clearly observable in the case of location policies for nuclear energy facilities. The South Korean public is often suspicious of new energy facilities; for example, in the case of nuclear power, they are suspicious of the risk of involuntary exposure to dangerous radiation, which cannot be effectively controlled. Therefore, the South Korean government is continuously discussing how to increase the acceptance of such high-risk facilities by managing the public’s risk perceptions. The research question was as follows: “Does the Korean government’s risk communication strategy have a positive impact on the public’s risk perceptions and acceptance of policies?” This study analyzed whether communicating risks helps boost public acceptance of high-risk facilities. A structural equation model and multiple group analyses were used for empirical analysis. The study explores government perspectives in terms of insecurity and conflict caused by scientific advancements, and uncertain public perceptions of high-risk facilities such as nuclear power plants. It provides empirical results regarding risk communication and implications for public policy that decrease risk perception and increase the acceptance of such policies. Points for practitioners This study analyzes whether risk communication can solve the problem of low public acceptance of high-risk facilities, based on their risk perception. As a result, this study contributes to policy implications regarding risk communication as a way to control risk perception and increase policy acceptance. In particular, it is critical to develop strategies for risk communication in which the public shares the decision-making process with governmental bodies and energy providers.