tbuckley/cabot-search huggingface dataset:
Abstract 1291: Notch2 inhibition as a therapeutic intervention in osteosarcoma
Authors: Sankaranarayanan Kannan, John A. Livingston, Michael Roth, Jonathan Benjamin, Yifei Wang, Zhongting Zhang, Wendong Zhang, Chia-Chin Wu, Hannah Beird, Andrew Futreal, Richard Gorlick
Journal: Cancer Research (2019)

Abstract Notch signaling pathway is a mediator of cell differentiation and is critical for normal bone development. Four functional Notch ligands DLL1 and DLL4, and JAG1 and JAG2 showed various levels of affinity for Notch1-4 receptors. Dose dependent Notch signaling activation or blocking is attributed to anchored or soluble form of Notch ligands binding. Interestingly, Notch pathway is shown to play a dual role, either oncogenic or tumor suppressive, depending on signal dose and tissue-context. To understand Notch signaling activities in osteosarcoma (OS), we first studied the cell surface levels of Notch receptor expression in OS cell lines and patient derived xenograft (pdx) models. Cytometry based screening of NOTCH1-4 receptors showed NOTCH2 as a predominant surface expressed protein in most of the samples. Interestingly, the canonical Notch target genes HES1 and DTX1 were higher (~5-fold) in OS cells compared to mesenchymal cells (MSC). Subsequently, we evaluated selected Notch pathway gene expression in 48 patients with recurrent/metastatic OS by RNAseq analysis. High expression of Notch pathway-related genes was seen in a subset of patients. NOTCH2 expression was comparable between primary and metastatic OS specimens, highest as compared to other Notch receptors and was significantly higher than normal tissue. Thus we aimed to elucidate soluble Notch ligands mediated blocking of Notch signaling using immunoglobulin-G bound DLL-1, -3, and -4 and JAG-1, and -2 in in vitro studies using OS cells. Soluble DLL1-Fc treatment increased OS cell death as compared to the other Notch ligands as well as control-Fc cells. Addition of soluble DLL1 resulted in the decreased expression of Notch downstream genes such as HES1, DTX1 and HEY1. Taken together, these findings identify soluble DLL1 as a potent Notch pathway inhibitor in OS in vitro and support further exploration of NOTCH2 as a potential therapeutic target in OS. Citation Format: Sankaranarayanan Kannan, John A. Livingston, Michael Roth, Jonathan Benjamin, Yifei Wang, Zhongting Zhang, Wendong Zhang, Chia-Chin Wu, Hannah Beird, Andrew Futreal, Richard Gorlick. Notch2 inhibition as a therapeutic intervention in osteosarcoma [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 1291.
Impact on survival of surveillance imaging after first remission in follicular lymphoma.
Authors: Jimmy Mao, Christopher Sun Strouse, Max Goldman, Wanqi Chen, Zhengjia Chen, Matthew John Maurer, Oscar Calzada, Michael Churnetski, Christopher Flowers, James Robert Cerhan, Brian K. Link, Carrie A. Thompson, Jonathon Brett Cohen
Journal: Journal of Clinical Oncology (2019)

7536 Background: While most patients (pts) with follicular lymphoma (FL) achieve an initial response to treatment, the majority relapse. Recently, Goldman et al. reported that surveillance imaging (SI) in FL is not associated with improved post-relapse outcomes and is frequently associated with false positive scans (ASH 2017). The goal of this study was to validate these findings. Methods: Pts were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death, with events verified by medical records. Pts eligible for this study had biopsy proven FL grade 1, 2, or 3a who had achieved a response after induction therapy and later relapsed. Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse in relationship to planned follow-up visits and SI. Relapse detection was categorized either by clinical suspicion (CS) via history, exam, and/or labs; or by SI in an asymptomatic pt. Univariate survival analysis was conducted for each variable. The hazard ratio with 95% confidence interval based on Cox Proportional Hazard models was presented along with the log rank test p-value. Kaplan-Meier plots were produced to evaluate the difference in overall survival (OS) between groups. Results: 1121 FL pts were enrolled in MER from 2002-2015, of which 117 were eligible. Median age at diagnosis was 60 years (range 35-83), and 61% were men. Median time to relapse of the 117 pts was 26 months (range 9-125). At a median follow-up from relapse of 69 months (range 0.23-179), 26 pts died. Pts completed a median of 3 imaging studies (range 0-15) during post-induction surveillance. 63 relapses (56%) were detected based on CS; 50 (44%) were detected by SI; and 4 were unknown. There was no difference in OS from relapse for those with relapse detected via CS vs. SI (HR = 0.98 [0.45,2.12], p = 0.96). Conclusions: Routine SI does not appear to improve survival outcomes in FL after achieving first remission, and its common practice should be questioned. Further investigation of prognostic markers to identify high-risk FL pts who may benefit from SI is needed.
Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization
Authors: Alissa Cait, Erick Cardenas, Pedro A. Dimitriu, Nelly Amenyogbe, Darlene Dai, Jessica Cait, Hind Sbihi, Leah Stiemsma, Padmaja Subbarao, Piush J. Mandhane, Allen B. Becker, Theo J. Moraes, Malcolm R. Sears, Diana L. Lefebvre, Meghan B. Azad, Tobias Kollmann, Stuart E. Turvey, William W. Mohn
Journal: Journal of Allergy and Clinical Immunology (2019)
Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives (THPBs) as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators for the treatment of hyperlipidemia
Authors: Chenglin Wu, Cong Xi, Junhua Tong, Jing Zhao, Hualiang Jiang, Jiang Wang, Yiping Wang, Hong Liu
Journal: Acta Pharmaceutica Sinica B (2019)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds 15, 18, 22, (R)-22, and (S)-22 showed better performance in the low-density lipoprotein, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound 22, selected for in vivo evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human ether-à-go-go related gene (hERG) inhibition assay indicated the potential druggability for compound 22, which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.
Prognosis of urinary tract infection caused by KPC-producing Klebsiella pneumoniae: The impact of inappropriate empirical treatment
Authors: Jorge Rodriguez-Gómez, Elena Pérez-Nadales, Belen Gutiérrez-Gutiérrez, Isabel Machuca, Luis Martinez-Martinez, Francisco Rivera, Angela Cano, Juan Jose Castón, Juan Carlos Robles, Carmen de la Fuente, Fernando Rodríguez-López, Jesus Rodriguez-Baño, Julian Torre-Cisneros
Journal: Journal of Infection (2019)
Assisted dying: new legal challenge could test evidence for first time
Authors: Adrian O’Dowd
Journal: BMJ (2019)

A terminally ill man is launching a legal challenge to existing laws on assisted dying by using a new approach that could see expert witnesses explain their opinions in court to flesh out their evidence.

Phil Newby, a 48 year old man with motor neurone disease, is launching a legal challenge to the law criminalising assisted dying. Newby, who is a member of the pressure group Dignity in Dying, said that although he wanted to live well with his family for as long as possible, without a change …
Plectin Mutations in Progressive Familial Intrahepatic Cholestasis
Authors: Shang‐Hsin Wu, Jacob Shujui Hsu, Hui‐Ling Chen, Mu‐Ming Chien, Jia‐Feng Wu, Yen‐Hsuan Ni, Bang‐Yu Liou, Ming‐Chih Ho, Yung‐Ming Jeng, Mei‐Hwei Chang, Pei‐Lung Chen, Huey‐Ling Chen
Journal: Hepatology (2019)

Wu, Shang‐Hsin; Hsu, Jacob Shujui; Chen, Hui‐Ling; Chien, Mu‐Ming; Wu, Jia‐Feng; Ni, Yen‐Hsuan; Liou, Bang‐Yu; Ho, Ming‐Chih; Jeng, Yung‐Ming; Chang, Mei‐Hwei; Chen, Pei‐Lung; Chen, Huey‐Ling Author Information
Імуноморфологічні особливості змін локального імунного гомеостазу слизової оболонки шлунка при хронічних НР-асоційованих гастритах у дітей після ерадикаційної терапії
Authors: O.Ye. Abaturov, N.Yu. Zavgorodnya
Journal: GASTROENTEROLOGY (2013)

У статті наведені результати стандартного морфологічного, імуногістохімічного дослідження біоптатів слизової оболонки шлунка та визначення бета-дефензину-2 у дітей, хворих на хронічний НР-асоційований гастрит, з урахуванням CagA-статусу, до та після антихелікобактерної терапії, модифікованої холекальциферолом. Продемонстровано підвищення ефективності комплексного лікування завдяки протизапальному, імуномодулюючому, антипроліферативному ефектам холекальциферолу.
Abstract 3550: microRNA-211 promotes aggressive melanoma growth <i>in vivo</i> by epigenetic modification, and contributes to BRAFV600E inhibitor resistance via ERK5 signaling
Authors: Bongyong Lee, Anupama Sahoo, Junko Sawada, Dimitrios G. Zisoulis, John Marchica, Sanjay Sahoo, Fabiana I Alves De Lima Layng, Darren Finlay, Joseph Mazar, Piyush Joshi, Masanobu Komatsu, Kristiina Vuori, Garth Powis, Petrus R. de Jong, Animesh Ray, Ranjan J. Perera
Journal: Cancer Research (2019)

Abstract The microRNA miR-211 is an established participant in melanomagenesis, but controversy exists as to whether it acts as a bone fide tumor suppressor or oncogene. Here we ectopically expressed miR-211 in the BRAF v600E-mutant A375 melanoma cell line and examined its effect in xenografts in vivo. The miR-211 ectopic expression promoted aggressive tumor xenograft growth with extensive cell proliferation, and angiogenesis. ChIP-seq and single cell sequencing analysis of xenograft tissues demonstrated that aggressive tumor formation is partly associated with H3K27me3 and H3K4me3, and migration of cells from mouse tissues to tumor locus. Interrogation of xenograft transcriptomics data revealed activation of the ERK5 pathway, itself negatively regulated by miR-211 target genes, BIRC2 and DUSP6, further confirmed as direct miR-211 target genes by RNA immunopurification with RNA-seq (RIP-seq) and site-directed mutagenesis. miR-211 conferred resistance to the BRAF inhibitor vemurafenib, and MEK inhibitor cobimetinib with corresponding increases in ERK5 phosphorylation. The miR-211-ERK5 axis may represent a novel therapeutic target, but however, miR-211 is exquisitely pleiotropic in the complex in vivo tumor environment and its context must be considered carefully in diagnostic and therapeutic development. Citation Format: Bongyong Lee, Anupama Sahoo, Junko Sawada, Dimitrios G. Zisoulis, John Marchica, Sanjay Sahoo, Fabiana I Alves De Lima Layng, Darren Finlay, Joseph Mazar, Piyush Joshi, Masanobu Komatsu, Kristiina Vuori, Garth Powis, Petrus R. de Jong, Animesh Ray, Ranjan J. Perera. microRNA-211 promotes aggressive melanoma growth in vivo by epigenetic modification, and contributes to BRAFV600E inhibitor resistance via ERK5 signaling [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 3550.
Does specialized psychological treatment for offending reduce recidivism? A meta-analysis examining staff and program variables as predictors of treatment effectiveness
Authors: Theresa A. Gannon, Mark E. Olver, Jaimee S. Mallion, Mark James
Journal: Clinical Psychology Review (2019)

A meta-analysis was conducted to examine whether specialized psychological offense treatments were associated with reductions in offense specific and non-offense specific recidivism. Staff and treatment program moderators were also explored. The review examined 70 studies and 55,604 individuals who had offended. Three specialized treatments were examined: sexual offense, domestic violence, and general violence programs. Across all programs, offense specific recidivism was 13.4% for treated individuals and 19.4% for untreated comparisons over an average follow up of 66.1 months. Relative reductions in offense specific recidivism were 32.6% for sexual offense programs, 36.0% for domestic violence programs, and 24.3% for general violence programs. All programs were also associated with significant reductions in non-offense specific recidivism. Overall, treatment effectiveness appeared improved when programs received consistent hands-on input from a qualified registered psychologist and facilitating staff were provided with clinical supervision. Numerous program variables appeared important for optimizing the effectiveness of specialized psychological offense programs (e.g., arousal reconditioning for sexual offense programs, treatment approach for domestic violence programs). The findings show that such treatments are associated with robust reductions in offense specific and non-offense specific recidivism. We urge treatment providers to pay particular attention to staffing and program implementation variables for optimal recidivism reductions.
Abstract 4463: Tumor-derived cell-free DNA from bronchoalveolar lavage fluid (BALF): A potential liquid biopsy analysis in lung cancer patients
Authors: Yuhua Gong, Xinyu Zhang, Chun Li, Weiran Wang, Maosong Ye, Yancheng Zhao, Xin Yi, Yaping Xu, Qin Hu, Yanfang Guan, Ling Yang, Xuefeng Xia, Min Zhou, Jian'an Huang, Hua Zhang, Tao Ren, Qian Shen, Kai Wang, Yingyong Hou, Xin Zhang
Journal: Cancer Research (2019)

Abstract Background: Bronchoalveolar lavage (BAL) is the most common technique for sampling the components of the alveolar space. Here, we evaluated the potential use of BAL fluid (BALF) in liquid biopsy in lung cancer. Methods: This study enrolled 56 lung cancer patients. And 57 BALF (separated supernatant and precipitate) samples and 56 peripheral blood lymphocytes samples were collected. 57 formalin-fixed Paraffin-embedded (FFPE) tissues were also obtain. We utilized a 1021-gene NGS panel in matched tissue DNA, BALF supernatant cfDNA and BALF precipitate DNA to identify somatic mutations with white blood cell DNA as a germline control. Results: Mutations were identified in 52 (~91.22%) BALF precipitate samples and 55 (~96.49%) BALF supernatant samples, comparing to 53 (92.98%) in tumor samples. EGFR mutations were observed in 22 BALF precipitate samples and 24 supernatant samples. Among these, 23 were also identified in matched tumor samples. One BALF precipitate samples specific and two BALF supernatant samples specific EGFR mutations were confirmed by Cobas assay. In addition, gene fusions including ALK, ROS1 and RET were found in 6 tumors, 4 BALF precipitate samples and 5 supernatant samples, respectively. In total, there were 195 mutations identified in the tumor samples, of which 147 (~75.4%) mutations were detected in the matched BALF precipitate samples, 168 (~86.1%) mutations were detected in the matched BALF supernatant samples and 145 (~74.4%) mutations were shared in three types of samples. Tumor mutation burden (TMB) were calculated, and the consistency between tissue and BALF precipitate was 90% and the consistency between tissue and BALF supernatant was 94%. Conclusions: Liquid biopsy using BALF shown high potential to profiling genetic alterations of patients with lung cancer, which might be implemented and standardized into clinical use. Citation Format: Yuhua Gong, Xinyu Zhang, Chun Li, Weiran Wang, Maosong Ye, Yancheng Zhao, Xin Yi, Yaping Xu, Qin Hu, Yanfang Guan, Ling Yang, Xuefeng Xia, Min Zhou, Jian'an Huang, Hua Zhang, Tao Ren, Qian Shen, Kai Wang, Yingyong Hou, Xin Zhang. Tumor-derived cell-free DNA from bronchoalveolar lavage fluid (BALF): A potential liquid biopsy analysis in lung cancer patients [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 4463.
Abstract 16423: Association of Demographic and Geospatial Factors With the Provision of Bystander CPR Following Out-of-Hospital Cardiac Arrest
Authors: David G Buckler, Anne V Grossestreuer, David N Karp, Steve Balian, Brendan G Carr, Douglas J Wiebe, Benjamin S Abella
Journal: Circulation (2017)

Introduction: Bystander CPR (bCPR) is associated with increased short- and long-term survival following out-of-hospital cardiac arrest (OHCA). Provision of bCPR varies greatly and while some demogr...
Roundup from BMA’s annual representative meeting
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The BMA will co-host its first conference on gender bias with the Medical Women’s Federation this November, the association’s chair of council, Chaand Nagpaul, announced at the BMA’s annual representative this week. He said he was “deeply saddened” by the recent allegations of sexism in the BMA and affirmed his commitment to making it an inclusive organisation. All BMA elected members will undertake equality and diversity training, and all members will be able to access online modules on equality, he said. Sexism in …
Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial
Authors: Diego Cadavid, Michelle Mellion, Raymond Hupperts, Keith R Edwards, Peter A Calabresi, Jelena Drulović, Gavin Giovannoni, Hans-Peter Hartung, Douglas L Arnold, Elizabeth Fisher, Richard Rudick, Sha Mi, Yi Chai, Jie Li, Yiwei Zhang, Wenting Cheng, Lei Xu, Bing Zhu, Susan M Green, Ih Chang, Aaron Deykin, Sarah I Sheikh, Eduardo Agüera Morales, Abdullatif Al Khedr, Radek Ampapa, Rafael Arroyo, Martin Belkin, Robert Bonek, Alexey Boyko, Ruggero Capra, Diego Centonze, Pierre Clavelou, Marc Debouverie, Jelena Drulovic, Keith Edwards, Nikos Evangelou, Evgeniy Evdoshenko, Oscar Fernández, Victoria Fernández Sánchez, Mark Freedman, Steven Freedman, Waldemar Fryze, Antonio Garcia-Merino, Mira Gavric-Kezic, Angel Ghezzi, Olivier Gout, Luigi Grimaldi, Barry Hendin, Hanka Hertmanowska, Rogier Hintzen, Pavel Hradilek, Raymond Hupperts, Jan Ilkowski, Evelina Ivashinenkova, Guillermo Izquierdo, Francois Jacques, Gabor Jakab, Farit Khabirov, Gabriela Klodowska-Duda, Samuel Komoly, Smiljana Kostic, Ivana Kovarova, Marcelo Kremenchuzky, Christopher Laganke, Yves LaPierre, Maciej Maciejowski, Francois Grand Maison, Girolama Alessandra Marfia, Sergio Martínez Yélamos, Eva Meluzinova, Xavier Montalban, Ronald Murray, Robert Naismith, Scott Newsome, Viet Nguyen, Delia Oreja, Gabriel Pardo, Elena Pasechnik, Francesco Patti, Andrzej Potemkowski, Semen Prokopenko, Peiqing Qian, Alfredo Rodríguez-Antigüedad, Howard Rossman, Csilla Rozsa, Fernando Sánchez López, Krzysztof Selmaj, Eli Silber, Adam Stepien, Anna Stepniewska, Maciej Swiat, Gordana Toncev, Ayman Tourbah, Tatyana Trushnikova, Antonio Uccelli, Marta Vachova, Martin Valis, Laszlo Vecsei, Sandrine Wiertlewski, Mauro Zaffaroni, Tomasz Zielinski
Journal: The Lancet Neurology (2019)
Abstract 1979: Interaction of atorvastatin and CX3CR1-fractalkine in androgen-dependent prostate cancer cells: Effect on PI3K pathway
Authors: Belal Al-Husein
Journal: Cancer Research (2019)

Abstract Prostate cancer (PC) management lacks any targeted therapies. Statins have shown anticancer effects against PC in both in vitro and in vivo studies. CX3CR1 is a receptor expressed by many cancer cells, including PC. In this research, we studies the interaction between atorvastatin and CX3CR1/fractalkine on androgen-dependent PC cell line 22Rv1 vs. normal prostatic cells, RWPE1. Experimental settings were based on testing effect of atorvastatin in presence of fractalkine or by removing its effect using fractalkine neutralizing antibodies. MTT proliferation assay and adhesion assay, together with testing the expression of CX3CR1, p-AKT and p-GSK-3 were used. Results showed that fractalkine partially blunts the effect atorvastatin on proliferation and adhesion of PC cells. Similar effects were not noticed on normal prostatic cells. Western blotting showed a dose-dependent reduction in the expression of CX3CR1, p-akt and p-GSK-3 in presence of fractalkine, that was further enhanced when fractalkine was neutralized using specific antibodies. Results suggest the deprivation of fractalkine as a synergistic mechanism to enhance effects of atorvastatin and probably other anticancer agents. Citation Format: Belal Al-Husein. Interaction of atorvastatin and CX3CR1-fractalkine in androgen-dependent prostate cancer cells: Effect on PI3K pathway [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 1979.
CCL5 is associated with poor prognosis in locally advanced pancreatic cancer (LAPC): biomarker analysis from the randomised phase II SCALOP trial
Authors: F. Willenbrock, C. Cox, C. Wilhelm-benartzic, R. Owens, A. Sabbagh, A. Abraham, T. Maughan, C. Hurt, E. O’Neill, S. Mukherjee
Journal: Annals of Oncology (2019)