tbuckley/cabot-search huggingface dataset:
Abstract LB-173: Epitope mapping of mTERT for vaccine development
Authors: Yurong Song, Jason Marshall, Sudipto Das, Thorkell Andresson, Amanda Corbel, Shizuko Sei, Robert H. Shoemaker, Ligia Pinto
Journal: Cancer Research (2018)

Abstract Telomerase reverse transcriptase (TERT) is one of two essential components of telomerase, an enzyme complex that generates and maintains telomeres. Telomerase is expressed mainly in embryonic and adult stem cells. Telomere biology has recently been implicated in the pathogenesis of a variety of diseases, and mutations in telomerase components result in a predisposition to solid malignancies. More recent findings show that TERT is not only expressed in late stage primary tumor cells and metastatic cells, but also expressed in incipient cancer stem cells and/or tumor-initiating cells, indicating that TERT has essential roles at every stage of tumorigenesis. However, the clinical benefit of a TERT (hTERT)-targeting vaccine, given as a single agent or in combination with chemotherapeutic agents, has been limited in patients with advanced cancer, possibly due to insufficient epitope coverage as well as tumor-induced immune suppression. Thus, targeting TERT in tumor-initiating cells in early stage lesions may be more effective in preventing cancer development and progression. To develop cancer preventive TERT vaccines, novel immunogenic epitopes must be first identified and evaluated in a relevant preclinical model of tumorigenesis. The goal of this project is to identify the epitopes of mouse TERT (mTERT) with high immunogenicity via epitope mapping using two approaches. The first one consists in washing off the MHC I-bound mTERT peptides (Mild Acid Elution; MAE) from the cell surface of mTERT-overexpressing cells (SPON-10-mTERT cells generated from spontaneous lung tumors developed in an A/J mouse), followed by mass spectrometry analysis. The initial mass spec analysis showed one 14-mer peptide from MAE with 22 PSMs, with a good XCorr score compared to peptide from PBS elution control with only 1 PSMs, with lower XCorr score. The second approach is to inject overlapping mTERT peptides covering the whole protein sequence in mice, and then splenocytes from these mice will be stimulated in vitro using mTERT peptide library to determine immunogenic peptides. Both approaches are in progress to identify potential mTERT epitopes. Funded by NCI Contract No. HHSN261200800001E Citation Format: Yurong Song, Jason Marshall, Sudipto Das, Thorkell Andresson, Amanda Corbel, Shizuko Sei, Robert H. Shoemaker, Ligia Pinto. Epitope mapping of mTERT for vaccine development [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 LB-173.
Abstract 13053: HAS-BLED Score and Atrial Fibrillation Type as Risk Factors for Bleeding Complications Associated With Catheter Ablation of Atrial Fibrillation among Patients Receiving Direct Oral Anticoagulants
Authors: Kohki Nakamura, Shigeto Naito, Kentaro Minami, Takehito Sasaki, Koji Kumagai, Nobusada Funabashi, Yoshio Kobayashi, Shigeru Oshima
Journal: Circulation (2016)

Purpose: This study aimed to identify predictors of thromboembolic and hemorrhagic events associated with catheter ablation of atrial fibrillation (AF) among patients receiving periprocedural direct oral anticoagulants (DOACs). Methods: We retrospectively studied 1034 consecutive AF patients (64±11 years; 777 males) receiving dabigatran (n=208), rivaroxaban (n=465), apixaban (n=292), or edoxaban (n=69) before AF ablation. The DOACs were continued in 61 (5.9%) patients and discontinued in 973 (94.1%) on the day of the procedure. No heparin bridging was performed before the ablation. During the procedure, heparin was given to maintain an activated clotting time (ACT) of 300-350 seconds. Major bleeding was defined as cardiac tamponade or pericardial effusions requiring drainage, intracranial and gastrointestinal hemorrhages, retroperitoneal bleeding, and bleeding requiring a blood transfusion, and vascular access site complications requiring intervention. Minor bleeding was defined as bleeding other than major bleeding. Results: No symptomatic thromboembolisms occurred. The incidence of major and minor bleeding was 0.6% and 8.8%, respectively, and did not significantly differ among the DOACs (P=0.351 and 0.177; Figure 1). In the multivariate logistic regression analysis, the HAS-BLED score and LSP-AF were significant positive predictors of bleeding complications (odds ratios, 1.358 and 1.956; 95% CIs, 1.108-1.665 and 1.196-3.198; P=0.003 and 0.007), but the DOAC type and dose (standard/reduced), periprocedural continuation of the DOACs, total heparin dosage, and intraprocedural ACT were not significant predictors. The periprocedural bleeding risk increased with higher HAS-BLED scores (Figure 2). Conclusions: Periprocedural DOAC treatment with adequate intraprocedural anticoagulation was effective in preventing symptomatic thromboembolisms. A higher HAS-BLED score and LSP-AF can be high risk factors for bleeding complications.
Abstract 5223: IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma
Authors: Ssu-Chuan Lai, Te-Sheng Chang, Yu-Ting Su, Yu-Chih Wu, Yung-Che Kuo, Pei-Chi Lan, Yen-Hua Huang
Journal: Cancer Research (2018)

Abstract Purpose: Chronic hepatic inflammatory cytokine interleukin 6 (IL-6) appears important role in pluripotent transcription factor OCT4 expression particularly in HBV-related hepatocellular carcinomas (HBV-HCC). However, the underlying mechanism still remains largely unknown. Experimental Design: Serum levels of IL-6 were detected using ELISA assays (n = 120). The effects of IL-6 on DNMT/OCT4 expression in HCC were examined using real-time QPCR analysis, RNA interference, and xenograft animal models. The DMNT/OCT4 protein and phospho-STAT (p-STAT) were detected by western blotting. OCT4, and DNMT expression levels in tissues (n = 144) were analyzed by real-time Q-PCR and was correlated with early tumor recurrence using Kaplan-Meier survival analysis. Results: A high positive correlation between the expression levels of OCT4 and epigenetic DNMT family in human HCC tissues was observed. High serum levels of IL-6 were significantly correlated with high OCT4 and DNMT expression. IL-6 stimulated the DNMT expression STAT3-dependently, which stimulated the OCT4 expression in both the cell lines and the xenografted mouse tumors. The inhibition STAT phosphorylation/DNMT expression by dominant negative STAT-Y705F plasmid transfection or DNMT RNA interference significantly suppressed the IL-6-induced OCT4 expression in vitro. Conclusions: The expression of pluripotency-related OCT4 is associated with early tumor recurrence and is regulated by IL-6-induced epigenetic DNMTs in HCC. Citation Format: Ssu-Chuan Lai, Te-Sheng Chang, Yu-Ting Su, Yu-Chih Wu, Yung-Che Kuo, Pei-Chi Lan, Yen-Hua Huang. IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma [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 5223.
The Electrocardiogram in Population Studies
Authors: Henryblackburn, Ancelkeys, Ernstsimonson, Penttirautaharju, Svenpunsar
Journal: Circulation (1960)

Information now available about the prevalence and incidence of coronary heart disease is seriously deficient because of the lack of standardized and objective methods of collection, tabulation, interpretation, and reporting of survey data. Chief reliance in the objective diagnosis of coronary heart disease rests on the electrocardiogram, a crucial tool in population studies. A classification system for the electrocardiogram in epidemiologic studies has been developed, tested, and herein presented. It is adapted to the usual clinical reading technics of the electrocardiographer. It embodies criteria widely employed and of diagnostic and prognostic import, but no stipulations about interpretation are made. The system permits more valid comparisons of data on heart disease between populations. It is susceptible to modern methods of data processing.
School District Crisis Preparedness, Response, and Recovery Plans — United States, 2006, 2012, and 2016
Authors: Judy Kruger, Nancy Brener, Rebecca Leeb, Amy Wolkin, Rachel Nonkin Avchen, Eric Dziuban
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Children spend the majority of their time at school and are particularly vulnerable to the negative emotional and behavioral impacts of disasters, including anxiety, depressive symptoms, impaired social relationships, and poor school performance (1). Because of concerns about inadequate school-based emergency planning to address the unique needs of children and the adults who support them, Healthy People 2020 includes objectives to improve school preparedness, response, and recovery plans (Preparedness [PREP]-5) (2). To examine improvements over time and gaps in school preparedness plans, data from the 2006, 2012, and 2016 School Health Policies and Practices Study (SHPPS) were analyzed to assess changes in the percentage of districts meeting PREP-5 objectives. Findings from these analyses indicate that districts met the PREP-5 objective for requiring schools to include post-disaster mental health services in their crisis preparedness plans for the first time in 2016. However, trend analyses did not reveal statistically significant increases from 2006 to 2016 in the percentage of districts meeting any of the PREP-5 objectives. Differences in preparedness were detected in analyses stratified by urbanicity and census region, highlighting strengths and challenges in emergency planning for schools. To promote the health and safety of faculty, staff members, children, and families, school districts are encouraged to adopt and implement policies to improve school crisis preparedness, response, and recovery plans.
Abstract 2339: Targeting ICMT in pancreatic cancer
Authors: Kanjoormana A. Manu, Tin F. Chai, Jing T. Teh, Wan Zhu, Patrick J. Casey, Mei Wang
Journal: Cancer Research (2018)

Abstract Introduction: Pancreatic Cancer remains one of the most difficult to treat human cancers with the 5-year survival as low as 5%. No targeted therapy yet developed against Pancreatic cancer. Here we want to target Isoprenylcysteine carboxylmethyltransferase (ICMT), an enzyme that post translationally modifies a group of proteins including several small GTPases against Pancreatic Cancer. Method: ICMT inhibition was achieved using lentivirus expressing ICMT shRNA and a pharmacological inhibitor named Cysmethynil. We evaluated a panel of human pancreatic cancer cell lines and identified those that are sensitive to ICMT inhibition by cell viability assay. This responsiveness to ICMT inhibition was confirmed in in vivo xenograft tumor mouse models using both Cysmethynil and shRNA-targeting ICMT. Flow cytometry analysis after DAPI or PI staining is used to detect cell cycle arrest and apoptosis. We used western blot analysis to study autophagy, apoptosis and cell cycle markers. ShRNA for P21 is used for p21 knock down studies. SiRNA for p53 is used to study whether p21 induction is p53 dependent. BNIP3, ULK1 and ATG5 knock down was done using specific shRNAs to study their role in ICMT inhibition induced autophagy and apoptosis. BCL-xL is over expressed in the cells using retroviral vectors to study the role of apoptosis in ICMT inhibition induced cell death. Cell and mitochondrial respiration was determined by oxygen consumption rate analysis using Seahorse XF24 analyzer. Summary: In sensitive pancreatic cancer cells, ICMT inhibition induces mitochondrial respiratory deficiency and cellular energy depletion, leading to significant upregulation of p21 and p21 dependent induction of BNIP3 leading to autophagy and apoptosis. But unlike in prostate and liver cancer, ICMT inhibition induced apoptosis not the autophagy responsible for inhibition of cell viability in pancreatic cancer. Conclusion: These findings suggest ICMT is a potential therapeutic target against pancreatic cancers and atleast in pancreatic cancer, ICMT inhibition induced apoptosis but not autophagy responsible for its therapeutic efficacy. Citation Format: Kanjoormana A. Manu, Tin F. Chai, Jing T. Teh, Wan Zhu, Patrick J. Casey, Mei Wang. Targeting ICMT in pancreatic 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 2339.
Abstract B39: The origins of endometriosis-associated cancers
Authors: Dawn Cochrane, Basile Tessier-Cloutier, Katherine Lawrence, Tayyebeh Nazeran, Anthony Karnezis, Clara Salamanca, Timothy Lee, Angela Cheng, Jessica McAlpine, Lien Hoang, Blake Gilks, David Huntsman
Journal: Clinical Cancer Research (2018)

Abstract Both clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are associated with ovarian endometriotic cysts, which is believed to be the precursor lesion of these cancers. Women with endometriotic cysts have up to a 3-fold increased risk of developing CCOC and ENOC. It is perplexing that these two clinically distinct histotypes of ovarian cancer arise from the same precursor lesion. We have performed whole-genome sequencing of ovarian cancer histotypes and found that while some genomic features are more common to one histotype than the other, there is not a single feature that is unique to either histotype. Lacking genomic evidence that could explain the differences between these histotypes, we hypothesized that these cancers arise from distinct cells of origin within endometrial tissue, and the cellular context accounts for their differences. We performed global proteomic analysis of ovarian cancer histotypes and identified CTH as a marker for CCOC. Upon examination of normal Müllerian tissues, we found that CTH is highly expressed in the ciliated cells of endometrium (both ectopic endometrium and endometriosis) and of the fallopian tube, with very little expression in the secretory cells of these tissues. We also find that other ciliated cell markers are expressed in CCOC, whereas endometrial secretory cell markers are expressed in ENOC. We propose a new model of CCOC and ENOC histogenesis wherein ENOC is derived from cells of secretory cell lineage whereas CCOC is derived from, or shares similarities to, cells of ciliated cell lineage. There remain, however, many unanswered questions. For example, while CCOC and ENOC occur at roughly equal prevalence, ciliated cells of the endometrium are rare compared to secretory cells. Cells in the endometriotic cyst are exposed to factors such as inflammation and reactive oxygen species, which could influence differentiation of endometrial progenitor cells into the secretory or ciliated cell lineage. To test factors that promote ciliated cell differentiation in normal endometrium, we treated organoid cultures of normal endometrium with IL-6 and Notch pathway modulators. We propose that ovarian cancer histotypes arise from different cells of origin and that the biology of the normal cells will be partly responsible for determining the phenotype of the cancers. Citation Format: Dawn Cochrane, Basile Tessier-Cloutier, Katherine Lawrence, Tayyebeh Nazeran, Anthony Karnezis, Clara Salamanca, Timothy Lee, Angela Cheng, Jessica McAlpine, Lien Hoang, Blake Gilks, David Huntsman. The origins of endometriosis-associated cancers. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B39.
Coronary Sinus-Ventricular Accessory Connections Producing Posteroseptal and Left Posterior Accessory Pathways
Authors: YingxianSun, MauricioArruda, KenichiroOtomo, KarenBeckman, HiroshiNakagawa, JamesCalame, SunnyPo, PeterSpector, DanielLustgarten, LisaHerring, RalphLazzara, WarrenJackman
Journal: Circulation (2002)

Background— The coronary sinus (CS) has a myocardial coat (CSMC) with extensive connections to the left and right atria. We postulated that some posteroseptal and left posterior accessory pathways (CSAPs) result from connections between a cuff of CSMC extending along the middle cardiac vein (MCV) or posterior coronary vein (PCV) and the ventricle. The purpose of the present study was to use CS angiography and mapping to define and determine the incidence of CSAPs and determine the relationship to CS anatomy. Methods and Results— CSAP was defined by accessory pathway (AP) potential or earliest activation in the MCV or PCV and late activation at anular endocardial sites. A CSAP was identified in 171 of 480 patients undergoing ablation of a posteroseptal or left posterior AP. CS angiography revealed a CS diverticulum in 36 (21%) and fusiform or bulbous enlargement of the small cardiac vein, MCV, or CS in 15 (9%) patients. The remaining 120 (70%) patients had an angiographically normal CS. A CSMC extension po...
Angiotensin II Stimulation In Vitro Induces Hypertrophy of Normal and Postinfarcted Ventricular Myocytes
Authors: YuLiu, AnnarosaLeri, BaoshengLi, XiaoweiWang, WeiCheng, JanKajstura, PieroAnversa
Journal: Circulation Research (1998)

Abstract—To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II–mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volum...
Abstract 14464: Long-term Embolic Outcomes After Detection of Left Ventricular Thrombus by Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Imaging
Authors: ChristopherChoo, FelipeKazmirczak, AfshinFarzaneh-Far, Jeffrey RMisialek, Ko-Hsuan AChen, JeremyMarkowitz, Prabhjot SNijjar, MehmetAkcakaya, Jonathan WWeinsaft, ChetanShenoy
Journal: Circulation (2017)

Introduction: Late gadolinium enhancement cardiovascular magnetic resonance imaging (LGE-CMR) enables detection of left ventricular (LV) thrombus with greater accuracy than echocardiography, particularly for small and mural thrombi. There are few data on long-term embolic outcomes after detection of LV thrombus by LGE-CMR. Objectives: This study aimed to assess the incidence and associations of long-term embolic outcomes in patients with LV thrombus detected by LGE-CMR. Methods: In a retrospective cohort study of 109 consecutive patients with LV thrombus detected by LGE-CMR, we investigated the long-term incidence of embolic events: stroke, transient ischemic attack (TIA) or extra-cranial systemic arterial embolization. We also investigated the association of embolic events with size and morphology of LV thrombus. Results: Despite the use of anticoagulation in 86% of patients, embolic events occurred in 16 patients including 8 strokes, 5 TIAs and 5 extra-cranial systemic arterial embolizations. The 5-year...
Abstract 3362: Mice with a “deletor” phenotype allow high resolution detection of lymphoid leukemia tumor suppressor genes
Authors: Mianmian Yin, Timour Baslan, Amy Freeland, Steven C. Pruitt, Peter D. Aplan
Journal: Cancer Research (2018)

Abstract Mice that are homozygous for a deficiency allele of the DNA replication factor minichromosome maintenance protein 2 (designated Mcm2def) are born viable and are healthy for the first 2 months of life. Beginning at three months, these mice develop precursor T-cell lymphoblastic leukemia/lymphoma (pre-T LBL). Copy number aberration (CNA) analysis showed that these pre-T LBL samples had 8-14 small (100-1000 kb) interstitial deletions per sample. Remarkably, all mice had two or more deletions that encompassed genes known to be relevant for human pre-T LBL, including Pten, Cdkn1a, Tcf3, and Tcf12. Mice that express a NUP98-HOXD13 (NHD13) transgene develop a wide array of leukemias, most commonly myeloid, less commonly T-cell, and, rarely, B-lineage. To identify myeloid tumor suppressor genes, we crossed the NHD13 transgene onto the Mcm2def background. All Mcm2def:NHD13+ mice developed pre-T LBL by 3 months of age, reflecting the highly penetrant nature of the Mcm2def phenotype. None of the Mcm2def:NHD13+ mice developed myeloid leukemia. Surprisingly, approximately 30% of the Mcm2def:NHD13+ mice developed concurrent B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and pre-T LBL. The thymus was typically infiltrated with pre-T LBL cells, whereas the bone marrow and spleen were infiltrated with BCP-ALL cells, characterized by clonal VDJ rearrangement and CD19 staining. Parenchymal organs (lung, kidney, liver) were variably infiltrated with pre-T LBL, BCP-ALL, or both. CNA analysis showed that the pre-T LBL were characterized by Pten, CDkn1a, Tcf3, and Tcf12 deletions, similar to the Mcm2def pre-T LBL, whereas the BCP-ALL were characterized by homozygous or heterozygous deletions of Pax5 and a 400 kb region encompassing Cebpb and Ptpn1. There were no shared deletions present in both BCP-ALL and pre-T LBL from the same mouse, indicating that the BCP-ALL and pre-T LBL arose independently, and not from a common precursor. The high frequency (5/7 samples) of acquired Pax5 deletions in the BCP-ALL samples serves to validate the model; whereas the finding of Cebpb/Ptpn1 deletions (5/7 samples) suggests an unanticipated role of either Cebpb or Ptpn1 in BCP-ALL. Citation Format: Mianmian Yin, Timour Baslan, Amy Freeland, Steven C. Pruitt, Peter D. Aplan. Mice with a “deletor” phenotype allow high resolution detection of lymphoid leukemia tumor suppressor genes [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 3362.
Metronomic oral doxorubicin in combination of Chk1 inhibitor MK-8776 for p53-deficient breast cancer treatment
Authors: Seung Woo Chung, Gui Chul Kim, Seho Kweon, Hanul Lee, Jeong Uk Choi, Foyez Mahmud, Hyo Won Chang, Ji Won Kim, Woo-Chan Son, Sang Yoon Kim, Youngro Byun
Journal: Biomaterials (2018)