tbuckley/cabot-search huggingface dataset:
Abstract 1166: TDO2 overexpression is associated with cancer stem cells and poor prognosis in esophageal squamous cell carcinoma
Authors: Thang Quoc Pham, Naohide Oue, Yohei Sekino, Yuji Yamamoto, Naoya Sakamoto, Ririno Honma, Kazuhiro Sentani, Wataru Yasui
Journal: Cancer Research (2019)

Abstract Objective: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. We previously analyzed the gene expression profile of spheroid colonies and parental cells derived from gastric cancer (GC) cell lines by microarray analysis. Among the genes upregulated in spheroid colonies, tryptophan 2,3-dioxygenase (TDO2) is dramatically upregulated in MKN-1 cells (derived from adenosquamous cell carcinoma) compared with other GC cell lines. Expression of TDO2, an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. Methods: To explore the expression of TDO2 in cancer and normal samples, we used an online analytical tool, the Broad Institute TCGA Genome Data Analysis Center, http://firebrowse.org/. For quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we used 10 ESCC samples (tumor tissues and the corresponding non-neoplastic tissue). TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation was evaluated by RNA interference (RNAi). Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Modified Boyden chamber assays were performed to examine cell invasiveness. Results: TDO2 expression was upregulated in most cancers except for liver cancer and pancreas cancer. The fold change expression of TDO2 between normal and cancer tissue was the highest in esophageal cancer. TDO2 overexpression was associated with tumor stage, recurrence status and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation and invasive activity. Knockdown of TDO2 expression also induced inactivation of the EGFR signaling pathway. Conclusion: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC. Citation Format: Thang Quoc Pham, Naohide Oue, Yohei Sekino, Yuji Yamamoto, Naoya Sakamoto, Ririno Honma, Kazuhiro Sentani, Wataru Yasui. TDO2 overexpression is associated with cancer stem cells and poor prognosis in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1166.
2018 Update of the EULAR recommendations for the management of large vessel vasculitis
Authors: Bernhard Hellmich, Ana Agueda, Sara Monti, Frank Buttgereit, Hubert de Boysson, Elisabeth Brouwer, Rebecca Cassie, Maria C Cid, Bhaskar Dasgupta, Christian Dejaco, Gulen Hatemi, Nicole Hollinger, Alfred Mahr, Susan P Mollan, Chetan Mukhtyar, Cristina Ponte, Carlo Salvarani, Rajappa Sivakumar, Xinping Tian, Gunnar Tomasson, Carl Turesson, Wolfgang Schmidt, Peter M Villiger, Richard Watts, Chris Young, Raashid Ahmed Luqmani
Journal: Annals of the Rheumatic Diseases (2019)

Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Abstract 836: From tobacco smoking to mutation signature: The role of epigenetic changes in human cancers
Authors: Zhishan Chen, Wanqing Wen, Qiuyin Cai, Jirong Long, Xiao-ou Shu, Wei Zheng, Xingyi Guo
Journal: Cancer Research (2019)

Abstract Tobacco smoking is associated with a unique mutation signature in the human cancer genome. It is unclear whether tobacco smoking alters DNA methylations and gene expressions affect smoking-related mutation signature. In this study, we evaluated the smoking-related DNA methylation sites reported from five previous studies using peripheral blood cells to identify possible target genes. Using the mediation analysis approach, we evaluated whether the association of tobacco smoking with mutation signature was mediated through altered DNA methylation and expression of these target genes. Based on data obtained from 21,108 blood samples, we identified 374 smoking-related DNA methylation sites, annotated to 248 target genes. Using data from DNA methylations, gene expressions and smoking-related mutation signature generated from ~7,700 tumor tissue samples across 26 cancer types from The Cancer Genome Atlas (TCGA), we found 11 of the 248 target genes whose expressions were associated with smoking-related mutation signature at a Bonferroni-correction P &amp;lt; 0.001. This included four for head and neck cancer, and seven for lung adenocarcinoma. In lung adenocarcinoma, our results further showed that smoking increased the expression of three genes, AHRR, GPR15, and HDGF, and decreased the expression of two genes, CAPN8, and RPS6KA1, which were consequently associated with increased smoking-related mutation signature. Additional evidence showed that the elevated expression of AHRR (cg14817490) and GPR15 (cg19859270), were associated with smoking-altered hypomethylations. Our findings provide novel insight into the contributions of tobacco smoking to carcinogenesis through complex molecular mechanisms of the evaluated mutation signature by altered DNA methylation and gene expression. Citation Format: Zhishan Chen, Wanqing Wen, Qiuyin Cai, Jirong Long, Xiao-ou Shu, Wei Zheng, Xingyi Guo. From tobacco smoking to mutation signature: The role of epigenetic changes in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 836.
Evidence-Based Clinical Practice Guidelines for Management of Microcystic Adnexal Carcinoma
Authors: John A. Carucci, Theresa N. Canavan
Journal: JAMA Dermatology (2019)

We were pleased to read the clinical practice guidelines for management of microcystic adnexal carcinoma (MAC) proposed by Worley et al.1 We would like to comment on several highly informative points made by these authors.
OCT Angiography Metrics Predict Progression of Diabetic Retinopathy and Development of Diabetic Macular Edema
Authors: Zihan Sun, Fangyao Tang, Raymond Wong, Jerry Lok, Simon K.H. Szeto, Jason C.K. Chan, Carmen K.M. Chan, Clement C. Tham, Danny S. Ng, Carol Y. Cheung
Journal: Ophthalmology (2019)
Возрастные и гендерные особенности циркулирующих иммунных комплексов и липидного метаболизма при воспалительных заболеваниях кишечника
Authors: M.V. Stoikevych, I.A. Klenina, O.M. Tatarchuk, V.A. Karachinova, N.S. Fedorova
Journal: GASTROENTEROLOGY (2019)

Цель: определить уровень циркулирующих иммунных комплексов (ЦИК) и состояние липидного обмена у пациентов с возрастными и гендерными особенностями протекания воспалительных заболеваний кишечника (ВЗК). Материалы и методы. Проведено обследование 80 пациентов с ВЗК: 53 с неспецифическим язвенным колитом (НЯК) и 27 с болезнью Крона (БК). Они были разделены на две группы в зависимости от пола: 40 мужчин и 40 женщин. Кроме того, все больные были разделены на группы в зависимости от возраста: молодые (45 человек — 28 с НЯК и 17 с БК); среднего возраста (15 пациентов — 10 с НЯК и 5 с БК); пожилые (20 человек — 15 с НЯК и 5 с БК). Контрольную группу составили 20 практически здоровых людей. В сыворотке крови определяли уровень ЦИК, общего холестерина, триглицеридов, холестерина липопротеинов высокой, низкой и очень низкой плотности (ЛПОНП), коэффициент атерогенности. Результаты. Уровень ЦИК в сыворотке крови достоверно превышал норму у женщин с ВЗК — в 1,57 раза (р &lt; 0,05), что можно рассматривать как показатель интенсивности воспаления, вовлечения иммунной системы в патологический процесс. У женщин с НЯК уровень ЦИК достоверно повышен — в 1,62 раза (р &lt; 0,05) по сравнению с контрольной группой. При ВЗК содержание ЦИК зависело от возраста больных, оно было достоверно повышено — в 1,5 раза (р &lt; 0,05) и 1,4 раза (р &lt; 0,05) у пациентов среднего и пожилого возраста соответственно в сравнении с молодыми больными. Установлена корреляция между уровнем ЦИК и возрастом (r = +0,552; р = 0,025). Выявлено нарушение липидного обмена у женщин с НЯК, что выражалось в снижении уровня триглицеридов в сыворотке крови в 1,7 раза (р &lt; 0,001), а у мужчин с БК происходило уменьшение данного показателя в 1,5 раза (р &lt; 0,05) по сравнению с контрольной группой. У женщин с НЯК достоверно снижался уровень ЛПОНП в сыворотке крови — в 2 раза (р &lt; 0,05), а у мужчин с БК — в 1,8 раза (р &lt; 0,05) по сравнению с контрольной группой. Установлено достоверное уменьшение уровня триглицеридов — в 1,5 раза (р &lt; 0,05) и в 1,6 раза (р &lt; 0,05) у молодых пациентов с НЯК и БК соответственно и в 1,6 раза (р &lt; 0,05) у пациентов среднего возраста с БК. Параллельно наблюдалась выраженная тенденция к снижению уровня холестерина у всех молодых пациентов с ВЗК. Установлено достоверное уменьшение коэффициента атерогенности у молодых больных. Выводы. Проведенные исследования позволили установить и подтвердить наличие биохимических изменений со стороны липидного обмена и уровня ЦИК у пациентов с воспалительными заболеваниями кишечника.
The influence of parvovirus B19 (B19V) on the results of chemotherapy in adult patients with lymphoma.
Authors: Tatiana A. Zykova, Oleg I. Kit, Irina B. Lysenko, Nailya K. Guskova, Elena A. Shevyakova, Nadezhda V. Nikolaeva, Olga N. Shatokhina, Elena A. Kapuza, Tatiana F. Pushkareva, Lilia A. Velikorodnaya
Journal: Journal of Clinical Oncology (2019)

e19022 Background: The purpose of the study was to reveal the prevalence of B19V in adult patients with lymphomas and the influence of B19V on the on the results of chemotherapy (CT). Methods: The study included 41 patients aged 48.9±2.3 years: 12 with Hodgkin’s lymphoma (HL), 29 with Non-Hodgkin’s lymphoma (NHL) (21 aggressive, 8 indolent). Patients received CT according to the tumor immunophenotype. B19V DNA was determined in plasma and in bone marrow (BM) by qPCR, B19V IgМ and IgG in the serum by ELISA. Results: 78.0% of patients had B19V IgG, mean concentration was 158.1±12.9 U/mL. B19V DNA in plasma was detected in 7.3%, in BM in 48.8%. Viral load in plasma was 68.7±35.8 IU/mL, in BM – 438240.0±281316.8 IU/mL. Seroprevalence and the mean concentration of B19V IgG was higher in NHL than in HL (79.3% vs 75.0% and 161.4±16.3 vs 153.6±20.5, p &gt; 0.05). In NHL, the number of seropositive patients and the mean level of B19V IgG were higher in aggressive than in indolent tumors (81% vs 75% and 177.9±19.3 U/mL vs 114.4±22.8 U/mL, p = 0.052). B19V IgМ were not found. B19V DNA in plasma was found only in NHL patients (10.3%). The frequency of B19V DNA detection in plasma was higher in indolent (12.5%) than in aggressive lymphomas (9.5%), while DNA concentration was higher in aggressive lymphomas (102.5±20.5 IU/mL vs 1.0±0.0 IU/mL, p &gt; 0.05). B19V DNA detection frequency in BM was similar in HL (50.0%) and NHL (48.3%, p &gt; 0.05), but the mean B19V DNA concentration was higher in NHL than in HL: 624496.9±395398.3 IU/mL vs 3640.5±1649.2 IU/mL, p &gt; 0.05. In NHL, B19V DNA in BM was more frequent in indolent than in aggressive lymphomas (50.0% vs 47.6%), and the average concentration was higher in aggressive lymphomas (865689.2±541738.6 IU/mL vs 21516.3±19352.8 IU/mL, p &gt; 0.05). Complete remission was observed in 68.3% of patients, partial remission 17.0%, stabilization 4.8%, progression 9.9%. CT results depended neither on serostatus and B19V IgG concentration nor on B19V DNA presence in BM or plasma (p &gt; 0.05). Conclusions: All parameters of the viral infection (B19V IgG, DNA) were higher in NHL than in HL (p &gt; 0.05). The mean concentration of B19V IgG was higher in aggressive NHLs than in indolent ones (p = 0.052). B19V infection did not influence results of antitumor CT (p &gt; 0.05) in adult patients with lymphoma.
Laparoscopic sleeve gastrectomy reverses non-alcoholic fatty liver disease modulating oxidative stress and inflammation
Authors: Noemí Cabré, Fedra Luciano-Mateo, Salvador Fernández-Arroyo, Gerard Baiges-Gayà, Anna Hernández-Aguilera, Montserrat Fibla, Raul Fernández-Julià, Marta París, Fàtima Sabench, Daniel Del Castillo, Javier A. Menéndez, Jordi Camps, Jorge Joven
Journal: Metabolism (2019)
Biologic Activity of Cold-Reacting Autoantibodies
Authors: Waldemar Pruzanski, Kenneth H. Shumak
Journal: New England Journal of Medicine (1977)

IN 1832, Elliotson described a patient with heart disease and "cold fits" who passed bloody urine "whenever the east wind blew."1 Half a century later, Rosenbach described patients in whom hemoglobinuria occurred after their feet were immersed in ice water.2,3 In 1904, Donath and Landsteiner showed that in such patients an autolysin combined with red cells in the cold; lysis resulted from the action of labile serum factors (now known to be complement) when the temperature was subsequently raised.4In 1903, Landsteiner detected autoagglutination when blood from various mammalian species was chilled,5 but it was not until . . .
Abstract 3281: The association between body mass index (BMI) and risk of pancreatic cancer depends on age at BMI assessment
Authors: Eric J. Jacobs, Christina C. Newton, Alpa V. Patel, Victoria L. Stevens, Farhad Islami, W. Dana Flanders, Susan M. Gapstur
Journal: Cancer Research (2019)

Abstract Importance: Pancreatic cancer rates in the United States have steadily increased since the early 2000’s despite declines in smoking. This increase is not easily explained by population increases in body mass index (BMI) given the relatively weak association between BMI and pancreatic cancer risk typically observed in epidemiologic studies. Most of these studies, however, assessed BMI in older adulthood, which may be less strongly associated with pancreatic cancer than BMI earlier in adult life. Objective: To examine the association between BMI and pancreatic cancer mortality by age at BMI assessment. Design: Prospective cohort study. Setting: Cancer Prevention Study II (CPS-II), a nationwide study of cancer mortality enrolled in 1982 and followed through 2014. Participants: 963,317 US adults aged 30 to 89 years at enrollment. Exposure: BMI calculated from height and weight reported at enrollment. Main outcomes and measures: A total of 8,354 participants died of pancreatic cancer during follow-up. Hazard ratios (HRs) for BMI were calculated using multivariable proportional hazards regression models. Population attributable fractions by birth cohort were calculated using HRs from CPS-II and BMI distributions from nationally representative National Health and Examination Surveys (NHANES). Results: HRs declined with increasing age at BMI assessment. HRs per 5 BMI units among those aged 30-49, 50-59, 60-69, and 70-89 years at assessment were 1.25 (95% confidence interval (CI) 1.18-1.33), 1.19 (95% CI 1.14-1.23), 1.14 (95% CI 1.08-1.21) and 1.13 (95% CI 1.02-1.26), respectively (p-trend = 0.005). The prevalence of obesity in early middle age is substantially higher in more recent US birth cohorts than in earlier ones. Therefore, based on a HR of 1.25 per 5 BMI units at age 45 years, we estimate that 28% of pancreatic cancer deaths in the US among those born from 1970-74 will be attributable to BMI levels &amp;gt; 25 kg/m2, nearly twice the equivalent percentage in those born in the 1930s. Conclusions and Relevance: BMI before age 50 may be more strongly associated with pancreatic cancer risk than BMI at older ages. These results underscore the importance of preventing excess weight gain before middle age for reducing rates of this highly fatal cancer. Citation Format: Eric J. Jacobs, Christina C. Newton, Alpa V. Patel, Victoria L. Stevens, Farhad Islami, W. Dana Flanders, Susan M. Gapstur. The association between body mass index (BMI) and risk of pancreatic cancer depends on age at BMI assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3281.
Abstract 3846: Targeting epigenetic dysregulation in isocitrate dehydrogenase mutant glioblastoma
Authors: Thomas K. Sears, Sandipan Datta, Gino Cortopassi, James Angelastro, Kevin Woolard
Journal: Cancer Research (2019)

Abstract Glioblastoma (GBM) is an incurable form of brain cancer with a median survival time (MdST) of ~15 months after treatment with chemoradiotherapy. Identification of a CpG Island Methylator Phenotype (CIMP) subtype of GBM (G-CIMP), represents a significant clinical discovery, as these patients have an enhanced survival, with a MdST of 3 years. G-CIMP is characterized by a mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2), which results in production of the oncometabolite 2-hydroxglutarate, an inhibitor of α-ketoglutarate-dependent demethylases. This results in aberrant DNA methylation, transcriptional repression, and may drive tumorigenesis. Here, we present data showing that G-CIMP is significantly more sensitive in vitro to inhibitors of the two arms of epigenetic regulation of transcription: the transcriptional activation arm and the transcriptional repression arm. Drug targets include the Bromodomain and Extraterminal (BET) and Histone Deacetylase (HDAC) proteins, involved in epigenetic transcriptional activation of oncogenes and repression of tumor suppressors, respectively. G-CIMP cells show a profound loss of cell viability at submicromolar concentrations using the small molecule inhibitors JQ1 and Panobinostat, which target BET and HDAC proteins, respectively. Western blot analysis indicates that BET inhibition elicits preferential loss of histone phosphorylation and acetylation in G-CIMP, notably serine 10 of Histone 3 and lysine 27 of Histone 3 (H3K27Ac), respectively. Both epigenetic marks are associated with positively regulating transcription. H3K27Ac is a superenhancer with known functions in activating oncogene transcription. These data ultimately suggest that G-CIMP tumor cells are reliant on established epigenetic transcriptional regulation to maintain cell viability. The global methylation status of these tumors may make them particularly sensitive to pharmacologic disruption of these epigenetic pathways. These studies provide a strong foundation for future preclinical work evaluating the prospective treatment of G-CIMP with combinatorial therapy using BET and/or HDAC inhibitors. Citation Format: Thomas K. Sears, Sandipan Datta, Gino Cortopassi, James Angelastro, Kevin Woolard. Targeting epigenetic dysregulation in isocitrate dehydrogenase mutant glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3846.
Conserved <i>NPPB</i> + Border Zone Switches From MEF2- to AP-1–Driven Gene Program
Authors: Karel van Duijvenboden, Dennis E.M. de Bakker, Joyce C.K. Man, Rob Janssen, Marie Günthel, Matthew C. Hill, Ingeborg B. Hooijkaas, Ingeborg van der Made, Petra H. van der Kraak, Aryan Vink, Esther E. Creemers, James F. Martin, Phil Barnett, Jeroen Bakkers, Vincent M. Christoffels
Journal: Circulation (2019)

Background: Surviving cells in the postinfarction border zone are subjected to intense fluctuations of their microenvironment. Recently, border zone cardiomyocytes have been specifically implicated in cardiac regeneration. Here, we defined their unique transcriptional and regulatory properties, and comprehensively validated new molecular markers, including Nppb , encoding B-type natriuretic peptide, after infarction. Methods: Transgenic reporter mice were used to identify the Nppb -positive border zone after myocardial infarction. Transcriptome analysis of remote, border, and infarct zones and of purified cardiomyocyte nuclei was performed using RNA-sequencing. Top candidate genes displaying border zone spatial specificity were histologically validated in ischemic human hearts. Mice in which Nppb was deleted by genome editing were subjected to myocardial infarction. Chromatin accessibility landscapes of border zone and control cardiomyocyte nuclei were assessed by using assay for transposase-accessible chromatin using sequencing. Results: We identified the border zone as a spatially confined region transcriptionally distinct from the remote myocardium. The transcriptional response of the border zone was much stronger than that of the remote ventricular wall, involving acute downregulation of mitochondrial oxidative phosphorylation, fatty acid metabolism, calcium handling, and sarcomere function, and the activation of a stress-response program. Analysis of infarcted human hearts revealed that the transcriptionally discrete border zone is conserved in humans, and led to the identification of novel conserved border zone markers including NPPB , ANKRD1 , DES , UCHL1, JUN , and FOXP1 . Homozygous Nppb mutant mice developed acute and lethal heart failure after myocardial infarction, indicating that B-type natriuretic peptide is required to preserve postinfarct heart function. Assay for transposase-accessible chromatin using sequencing revealed thousands of cardiomyocyte lineage-specific MEF2-occupied regulatory elements that lost accessibility in the border zone. Putative injury-responsive enhancers that gained accessibility were highly associated with AP-1 (activator protein 1) binding sites. Nuclear c-Jun, a component of AP-1, was observed specifically in border zone cardiomyocytes. Conclusions: Cardiomyocytes in a discrete zone bordering the infarct switch from a MEF2-driven homeostatic lineage-specific to an AP-1–driven injury-induced gene expression program. This program is conserved between mouse and human, and includes Nppb expression, which is required to prevent acute heart failure after infarction.