tbuckley/cabot-search huggingface dataset:
Anti-apoptotic effects of Notch-1 in cervical cancer cells are mediated by NF-κB and AKT
Authors: Lynda L. Song, Jian-Zhong Qin, Brian J. Nickoloff, Lucio Milele
Journal: Cancer Research (2004)

5008  Activation of Notch receptors mediates survival signals in cells from various solid tumors. We have previously shown that pharmacological or genetic silencing of Notch-1 signaling effectively induced apoptosis and significantly enhanced the cytotoxic effects of various anti-neoplastic agents acting in S, G2 or M phases of the cell cycle. We have also demonstrated that inhibition of Notch-1 expression or activity has dramatic anti-neoplastic effects in vitro and in vivo. However, the mechanism(s) of Notch-induced survival signals remain unclear. Activation of NF-κB and AKT and inhibition of JNK by constitutively active Notch-1 have been described in some models. We studied the mechanism of survival signals induced by Notch-1 in cervical cancer CaSki cells, which are unable to grow in vitro or form tumors in vivo when transduced with antisense Notch-1. We found that blocking Notch activation with a gamma-secretase inhibitor (GSI) caused dose-dependent cell death in CaSki cells. Expression of intracellular (constitutively active) Notch-1 (ICN) protected cells from this effect. GSI also caused dose-dependent inhibition of NF-κB reporter activity, which was diminished when the cells were transfected with ICN. NF-κB inhibition was also observed after specific silencing of Notch-1 expression by siRNA. AKT has been reported to be downstream of Notch-1 and can induce NF-κB activation by phosphorylating IKK (I-κB kinase). Consistent with this, our data show that NF-κB activity was strongly activated in CaSki cells transfected with constitutively active AKT. Notch-1 upregulated the phosphorylation but not the total level of AKT in CaSki cells. Silencing Notch-1 signaling led to down-regulation of pAKT and inhibition of NF-κB. JNK phosphorylation was increased in CaSki nuclear extracts after GSI treatment. However, JNK inhibitory drugs did not prevent GSI-induced apoptosis, suggesting that JNK does not play a central role in cell death induced by GSI. Taken together, our data support a model in which Notch-1 exerts its anti-apoptotic functions in cervical cancer cells by activating NF-κB transcription factors via the PKB-AKT pathway. Our data support the investigational use of combinations of GSIs or other Notch inhibitors with AKT inhibitors and/or NF-κB inhibitors for the treatment of advanced cervical cancer. (Supported by NIH grant CA84065)
Abstract LB-176: Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese
Authors: Jing Han, Jing Ni, Meng Zhu, Jin Guang Fu, Zhi Bin Hu
Journal: Cancer Research (2019)

Abstract The etiology of persistent hepatitis B virus (HBV) infection is complex and multifactorial, polygenic event with viral, environmental and genetic components being considered as the risk factors. Genome-wide association study (GWAS) has been applied into the exploration of genetic etiology of persistent hepatitis B virus infection among Chinese. However, the mechanisms beyond the genetic variants identified by GWAS located in noncoding regions are largely unknown. To further explore the causal gene of persistent hepatitis B virus (HBV) infection, we used a new approach developed by Gusev and Ko, leveraging expression imputation from large-scale GWAS data by using a small set of individuals with both genotype and gene expression data as a reference panel, to perform a transcriptome-wide association study (TWAS).Based on Genotype-Tissue Expression (GTEx) database, we included 97 individuals with both gene expression data in liver and SNP array data in blood as a reference panel. We first estimated the cis SNP heritability (cis-hg2) for each gene in 97 liver tissues using genome-wide complex trait analysis (GCTA) software, and kept cis-heritable genes for subsequent analysis. Then, we estimated the effect sizes of cis-SNPs on gene expression using genome-wide efficient mixed-model association (GEMMA) algorithm. Using the effect sizes trained from the reference panel, we imputed the gene expression levels for our existing NJMU HEP GWAS cohort (951 persistent hepatitis B virus (HBV) infection patients and 937 controls) and correlated the imputed gene expression values with persistent hepatitis B virus (HBV) infection trait. The cis-hg2 estimate was significantly nonzero for 2588 genes (P&amp;lt;0.05). The average cis-hg2value was 0.438. Using GTEx database as a reference panel. In the training set, After FDR correction, we identified three potentially persistent hepatitis B virus (HBV) infection -associated genes, those genes were located in 6p21.3(HLA-DPA1,PTWAS=2.02×10-7), 3q21.1(PARP9, PTWAS=2.2×10-4) and 22q11.21 (TMEM191A, PTWAS= 3.8×10-4)respectively. 6p21.3 and 22q11.21 as our previous reported. 3q21.1 was a novel region. Citation Format: Jing Han, Jing Ni, Meng Zhu, Jin Guang Fu, Zhi Bin Hu. Transcriptome-wide association study revealed a novel gene associated with persistent hepatitis B virus infection among Chinese [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 LB-176.
Abstract 5227: Chromatin folding disruptions in human cancers
Authors: Kadir C. Akdemir
Journal: Cancer Research (2019)

Abstract Genomic material within the nucleus is folded into successive layers in order to package and organize the long string of linear DNA. This hierarchical level of folding is closely associated with transcriptional regulation and DNA replication. Genes within the same folding domain demonstrate similar expression and histone-modification profiles. Therefore, boundaries separating different domains have important roles in reinforcing the stability of these domain-wide features. Indeed, domain boundary disruptions in human genetic disorders or human cancers lead to misregulation of certain genes, due to de novo enhancer exposure to promoters. However, the frequency of boundary disruptions in human cancers, and whether there are recurrently affected boundaries in specific cancer types, remains unclear. Here, to understand effects and distributions of somatic structural variations (SVs) across TADs, we utilized 288,457 high-confidence somatic structural variations from 2658 tumor-normal pair high-coverage whole genome sequencing datasets across various cancer types. We comprehensively profiled structural variations effects on the domain boundaries and the regulation of genes in human cancers. Our findings demonstrate that the impact of TAD disruptions are substantially varied across tumor types and these events are reflective of overall SV burden and type. Notably, most of the TAD disruptions could result in appreciable changes in nearby gene expression in cancer cells. In addition, we demonstrated that SVs can lead to fusion of discrete TADs. Notably, complex rearrangements drastically change chromatin folding maps in the cancer genomes. Note: This abstract was not presented at the meeting. Citation Format: Kadir C. Akdemir. Chromatin folding disruptions 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 5227.
Positive Predictive Values and Potential Success of Suicide Prediction Models
Authors: Ives Cavalcante Passos, Pedro Ballester
Journal: JAMA Psychiatry (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Abstract 19365: Serial Changes in ST2 are Superior to Other Biomarkers in the Prediction of Adverse Events in a Cohort of Ambulatory Chronic Heart Failure Patients
Authors: Amy K Saenger, Wayne L Miller, Alan J Lueke, Diane E Grill, Allan S Jaffe
Journal: Circulation (2012)

Background: Disease progression in heart failure (HF) reflects multiple neurohormonal derangements resulting in adverse prognosis in the absence of overt clinical events. ST2 is up-regulated in response to cardiac injury/hemodynamic stress while modulating cardiac remodeling via inflammatory and apoptotic pathways. Accordingly, we evaluated changes in ST2 over time in conjunction with troponin T (cTnT) and BNP in ambulatory patients with chronic HF. Methods: A cohort of 191 NYHA class III-IV HF patients was prospectively evaluated with serial specimens collected every 3 months over a 2-year period. Primary end points were death or cardiac transplantation; secondary end points were combined death/transplantation and HF-related hospitalization. Plasma ST2 (Critical Diagnostics) was evaluated against contemporary cTnT (Roche 4th generation) and BNP (Shinogi) assays. Gender specific cut-points (&gt;49.3 and &gt;33.5 ng/mL for males and females, respectively) and a clinically defined optimal cut-point for ST2 (&gt;35 ng/mL) were evaluated. Results: Time-dependent analyses (dichotomous and continuous variable) demonstrated ST2 gender specific cut-points were superior to a single ST2 cut-point and associated with an increased risk of death or transplantation (HR 4.8, 95% CI 2.8 to 8.3, p&lt;0.0001) and combined death/transplantation/HF-hospitalization (HR 2.1, 95% CI 1.7 to 2.5, p&lt;0.0001). Although cTnT remained the strongest predictor of death/transplantation (HR 3.2, 95% CI 1.6 to 5.4, p&lt;0.0001) in multivariate analyses adjusted for cTnT and BNP, ST2 (HR 3.0, 95% CI 1.6 to 5.4, p=0.0003) added significantly to predictive accuracy. Furthermore, elevated ST2 was the only independent predictor of HF-hospitalization (HR 1.7, 95% CI 1.4 to 2.1, p&lt;0.0001). In these models BNP was no longer significantly predictive (HR 1.2, 95% CI 0.7 to 2.2, p=0.58). Conclusions: Serial monitoring of changes in ST2 using gender specific cut-points adds to the diagnostic ability of cTnT in predicting mortality and/or transplantation in outpatients with chronic HF. ST2 uniquely predicts HF-hospitalization/death/transplantation, suggesting a serial monitoring strategy with cTnT and ST2 will optimize identification of HF patients at increased risk for events.
Cancer and Other Outcomes After Surgery With Fluoridated Anesthesia
Authors: Declan T. Waugh
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Multicenter, Open-Label, Phase II Study of Bendamustine and Rituximab Followed by 90-Yttrium (Y) Ibritumomab Tiuxetan for Untreated Follicular Lymphoma (Fol-BRITe)
Authors: Frederick Lansigan, Cristiana A. Costa, Bassem I. Zaki, Stephanie P. Yen, Eric S. Winer, Helen Ryan, Darcie Findley, Sara R. Metzler, Lynn Shaw, Bonnie Toaso, Todd A. MacKenzie, Youdinghuan Chen, Anne W. Beaven
Journal: Clinical Cancer Research (2019)

Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL.The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II-IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%.Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57-0.89).This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.
The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs
Authors: Chao-Jie Wang, Chun-Chao Zhu, Jia Xu, Ming Wang, Wen-Yi Zhao, Qiang Liu, Gang Zhao, Zi-Zhen Zhang
Journal: Molecular Cancer (2019)

UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear.We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells' migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo.UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, -26b, -193a and - 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model.UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment.
Abstract CT176: Phase III PANOVA study of tumor treating fields (150 kHz) in combination with nab-paclitaxel and gemcitabine for front-line treatment of locally-advanced pancreatic adenocarcinoma (LAPC)
Authors: Uri Weinberg, Ori Farber, Moshe Giladi, Zeev Bomzon, Eilon Kirson
Journal: Cancer Research (2019)

Abstract Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of patients with glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase II PANOVA study [NCT01971281] of TTFields in pancreatic cancer (metastatic and LAPC) combined with nab-paclitaxel and gemcitabine, demonstrated no TTFields-related serious adverse events; key TTFields-related AEs was manageable skin toxicity. TTFields plus gemcitabine and nab-paclitaxel showed median PFS was 12.7 months. The Phase III PANOVA-3 trial [NCT03377491] is designed to test the efficacy of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2 once weekly). TTFields (150kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. The PANOVA-3 study is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Citation Format: Uri Weinberg, Ori Farber, Moshe Giladi, Zeev Bomzon, Eilon Kirson. Phase III PANOVA study of tumor treating fields (150 kHz) in combination with nab-paclitaxel and gemcitabine for front-line treatment of locally-advanced pancreatic adenocarcinoma (LAPC) [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 CT176.
Role of brain imaging in disorders of brain–gut interaction: a Rome Working Team Report
Authors: Emeran A Mayer, Jennifer Labus, Qasim Aziz, Irene Tracey, Lisa Kilpatrick, Sigrid Elsenbruch, Petra Schweinhardt, Lukas Van Oudenhove, David Borsook
Journal: Gut (2019)

Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain–gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
Abstract 14690: Microrna-495 Mediates the Angiogenic Potential of iPSC-Derived Endothelial Cells in Infarcted Heart
Authors: Jialiang Liang, Wei Huang, Wenfeng Cai, Meifeng Xu, Christian Paul, Ronald Millard, Yigang Wang
Journal: Circulation (2015)

Background and Objective: miR-495 inhibition is known to enhance mesoderm differentiation, but its role in angiogenesis is not clear. The present study seeks to determine whether miR-495 mediates angiogenesis induced by human induced pluripotent stem cells (hiPSCs) in infarcted heart. Methods: The miR-495 in hiPSCs was knocked down via lentivirus. ECs were generated from hiPSCs (hiECs) and sorted by MACS using CD144 antibody (Fig. 1A). In vitro : the angiogenic potential of hiEC Anti-495 (hiEC Scr as control) was analyzed by tube formation and expression of angiogenic genes was detected by PCR array. In vivo : hiECs were transplanted into infarcted heart of immunodeficient mice (LAD ligation); after 4 weeks, hearts were harvested for immunostaining and genome PCR to identify implanted cells. Results: In vitro : The tube length of hiEC Anti-495 was increased (Fig. 1B) and multiple angiogenic genes (EFNB2, TIE2, IGF1, and JAG1) were upregulated in hiEC Anti-495 as compared to hiEC Scr (Fig. 1C). In vivo : Implantation of hiEC Anti-495 increased the isolectin-B4 + capillary density in the infarcted heart (Fig. 1D). hiEC Anti-495 integrated into mouse vascular networks, whereas the structural integration of hiEC Scr was seldom observed. Human DNA derived from hiEC Anti-495 in infarcted heart was higher as compared to hiEC Scr (Fig.1E). Conclusion: miR-495 represents a promising mediator for promoting angiogenic potential and functional integration of hiPSC-derived ECs for the treatment of infarcted heart.
Pulmonary surfactant in health and human lung diseases: state of the art
Authors: M Griese
Journal: European Respiratory Journal (1999)

Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease. The most applied intervention for these symptoms is the use of chest physiotherapy to increase bronchial mucus transport and reduce retention of mucus in the airways. Chest physiotherapy interventions can be evaluated using different outcome variables, such as bronchial mucus transport measurement, measurement of the amount of expectorated mucus, pulmonary function, medication use, frequency of exacerbation and quality of life. Measurement of the transport rate of mucus in the airways using a radioactive tracer appears to be an appropriate outcome variable for short-term studies. Evaluation of chest physiotherapy only with pulmonary function tests appears to be inadequate in short-term studies. The popularity of using pulmonary function tests is probably based more on the availability of the instruments than on a theoretical basis related to the question of chest physiotherapy improving mucus transport. Quality of life and progression of the disease are not often used as outcome variables, but it may be worthwhile to use these in the future.