tbuckley/cabot-search huggingface dataset:
Abstract 4274: RNA methylation regulates osteosarcoma growth and progression via autophagy
Authors: Panneerdoss Subbarayalu, Pooja Yadav, Manjeet Rao
Journal: Cancer Research (2019)

Abstract Osteosarcoma (OS) is the most common primary bone tumor and third most common cancer in children/teens, after lymphomas and brain tumors. OS is treated by surgery and multi-modal chemotherapy. Even though this treatment regimen has improved the 5-year survival rate to 60-70%, once osteosarcoma metastasize to lung and other bones, the survival is significantly reduced. Moreover, the quality of life for patients who do survive is often substantially reduced due to the toxicity associated with the chemotherapy. Since several decades, there hasn’t been any improvement in the osteosarcoma treatment outcome. Therefore, it is important to understand the molecular mechanism of osteosarcoma growth and metastasis and an urgent need to develop effective drug, which can be safe and effective for treating OS patients. We discovered that RNA methylation may regulate OS growth and progression by affecting autophagy. Our studies revealed that RNA demethylase AlkB homolog 5 (ALKBH5) supports OS viability, migration and invasion as well as tumor growth. We discovered several autophagy related genes were significantly altered in ALKBH5-silenced OS cells compared to scrambled control. Importantly, levels of LC3, which is a universal marker for monitoring autophagy, was significantly increased in ALKBH5 depleted OS cells. Furthermore, we found that autophagy initiation complex protein ULK1 level was drastically increased in ALKBH5-silenced cells when compared to scrambled control. To further establish the role of autophagy in osteosarcomogenesis, we treated OS cells with chloroquine, which is a well-known autophagy inhibitor and is currently being investigated for treating adult cancers in clinical trials. Interestingly, silencing of ALKBH5 significantly improved the efficacy of chloroquine as revealed by drastically reduced viability and invasive ability of OS cells. In conclusion, our study is first to shows that RNA methylation plays a critical role osteosarcoma growth and progression by regulating autophagy. Citation Format: Panneerdoss Subbarayalu, Pooja Yadav, Manjeet Rao. RNA methylation regulates osteosarcoma growth and progression via autophagy [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 4274.
A systematic review and meta-analysis of patient data from the West Africa (2013–16) Ebola virus disease epidemic
Authors: A.M. Rojek, A. Salam, R.J. Ragotte, E. Liddiard, A. Elhussain, A. Carlqvist, M. Butler, N. Kayem, L. Castle, L.'O. Odondi, K. Stepniewska, P.W. Horby
Journal: Clinical Microbiology and Infection (2019)

Over 28 000 individuals were infected with Ebola virus during the West Africa (2013-2016) epidemic, yet there has been criticism of the lack of robust clinical descriptions of Ebola virus disease (EVD) illness from that outbreak.To perform a meta-analysis of published data from the epidemic to describe the clinical presentation, evolution of disease, and predictors of mortality in individuals with EVD. To assess the quality and utility of published data for clinical and public health decision-making.Primary articles available in PubMed and published between January 2014 and May 2017.Studies that sequentially enrolled individuals hospitalized for EVD and that reported acute clinical outcomes.We performed meta-analyses using random-effect models and assessed heterogeneity using the I2 method. We assessed data representativeness by comparing meta-analysis estimates with WHO aggregate data. We examined data utility by examining the availability and compatibility of data sets.In all, 3653 articles were screened and 34 articles were included, representing 16 independent cohorts of patients (18 overlapping cohorts) and at least 6168 individuals. The pooled estimate for case fatality rate was 51% (95% CI 46%-56%). However, pooling of estimates for clinical presentation, progression, and predictors of mortality in individuals with EVD were hampered by significant heterogeneity, and inadequate data on clinical progression. Our assessment of data quality found that heterogeneity was largely unexplained, and data availability and compatibility were poor.We have quantified a missed opportunity to generate reliable estimates of the clinical manifestations of EVD during the West Africa epidemic. Clinical data standards and data capture platforms are urgently needed.
Correcting Meta-analyses and Reviews Affected by Retracted Research
Authors: Andrew Grey, Alison Avenell, Mark Bolland
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract P356: Prevalence of Left Ventricular Hypertrophy versus Atrial Fibrillation on Electrocardiogram in Stroke Patients
Authors: Hassan Tahir, Mazen Omar, Bassam A Omar, G. Mustafa Awan, Christopher Malozzi
Journal: Circulation (2018)

Background: While atrial fibrillation is a well established cause of stroke, a strong association has been previously postulated between left ventricular hypertrophy (LVH) and stroke. The prevalence and significance of LVH by electrocardiogram in stroke patients, however, is not clear. Objectives: To examine the prevalence of left ventricular hypertrophy by electrocardiographic (EKG) criteria, versus atrial fibrillation or flutter, in patients receiving an EKG for a diagnosis of stroke. Methods: An EKG database from a university cardiology noninvasive lab was examined for the diagnosis of stroke or CVA over a one year period. The EKGs were evaluated for the presence of LVH or atrial fibrillation/flutter. The results were analyzed using a categorical Chi square test. Results: There was a total of 14,798 EKGs performed over one year, 1,439 of which reported LVH (9.7%). There were 272 EKGs with a diagnosis of acute stroke or CVA (1.7% of total EKGs). Out of these, there were 174 EKGs in sinus rhythm without LVH (64%), 78 EKGs in sinus rhythm with LVH (29%, P &lt; 0.05), and 20 EKGs in atrial fibrillation or atrial flutter (7.4%). Discussion: Stroke is major health problem associated with increased mortality and morbidity. Hypertension is a well established risk factor for stroke in addition to cardiovascular events, and when long-standing and uncontrolled, causes left ventricular hypertrophy on EKG. In our cohort nearly one third of patients with stroke were in sinus rhythm, but had left ventricular hypertrophy by EKG, a prevalence that was four time that of atrial fibrillation or atrial flutter, and three time the prevalence of LVH in the overall database. Therefore, LVH by EKG appears to predict an increased risk of stroke, and thereby need for aggressive work-up and risk factor modification. Further studies to examine blood pressure and other cardiovascular risk factors as correlates of LVH on EKG will help shed further light on this important observation.
Abstract 4779: Coxsackievirus A11 as a novel oncolytic viral therapy for human colorectal cancer
Authors: Hisanobu Ogata, Beibei Wang, Shoei Miyamoto, Yuto Takishima, Miyako Sagara, Mutsunori Murahashi, Hideya Onishi, Kenzaburo Tani
Journal: Cancer Research (2019)

Abstract Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world. It is the third most common cancer worldwide and the fourth most common cause of death. FOLFOX is known as the effective chemotherapy for stage III and stage IV CRC. Oxaliplatin (L-OHP) is a third-generation platinum agent used among FOLFOX in CRC treatment. Patients with L-OHP-resistant CRC has a worse prognosis. Coxsackievirus is a virus that belongs to a family of nonenveloped, linear, positive-sense ssRNA viruses, Picornaviridae and the genus Enterovirus. Enteroviruses are among the most common and important human pathogens, and ordinarily its members are transmitted by the fecal-oral route. Coxsackieviruses share many characteristics with poliovirus. Coxsackieviruses are among the leading causes of aseptic meningitis. Recently, coxsackievirus A21, which is also called Cavatak, has already been reported to have the oncolytic activity. In this study, we tested whether coxsackievirus A11 (CVA11) has an oncolytic activity or not in CRC. Through our first screening assay, we found that CVA11 displayed the potent oncolytic activities in 4 of 5 various human CRC cell lines including two L-OHP-resistant CRC cells. Mechanistically, the CVA11-mediated cytotoxicity was significantly impaired when PI3K or Wnt inhibitor was added to the CVA11 infection. CVA11 had little effect on the L-OHP-resistant CRC. The pretreatment with L-OHP in L-OHP-resistant CRC cells displayed enhanced oncolytic activity of CVA11 in L-OHP-resistant CRC cells, whereas either L-OHP or CVA11 treatment alone caused slight oncolytic activity. These results suggest that L-OHP pretreatment could sensitize the susceptibility of CRC cells to CVA11 infection. Furthermore, our results of in vivo mouse study showed that intratumoral CVA11 administrations with pretreatment of L-OHP significantly suppressed the outgrowth of L-OHP-resistant xenografts. This combination therapy was more effective than the treatment with only CVA11. Altogether, our findings showed that the combination therapy with L-OHP and CVA11 displayed a remarkable oncolytic activity against L-OHP-resistant human CRC both in vitro and in vivo. Our study also provides the therapeutic potential for L-OHP-resistant CRC by Coxsackieviruse. Note: This abstract was not presented at the meeting. Citation Format: Hisanobu Ogata, Beibei Wang, Shoei Miyamoto, Yuto Takishima, Miyako Sagara, Mutsunori Murahashi, Hideya Onishi, Kenzaburo Tani. Coxsackievirus A11 as a novel oncolytic viral therapy for human colorectal cancer [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 4779.
Quantitative proteome analysis of oral tongue squamous cell carcinoma by laser capture microdissection, stable isotope labeling and liquid chromatography-mass spectrometry.
Authors: Shen Hu, Xiaofeng Zhou, Bao-Lin Huang, Joseph Loo, David Wong
Journal: Cancer Research (2005)

400  Quantitative proteome analysis of tongue squamous cell carcinoma was performed by using laser capture microdissection (LCM) and mass spectrometry. LCM allowed for the one-step procurement of homogeneous populations of normal/tumor epithelial cells from tissue sections. The protein expression profiles of dissected normal/cancer cells were examined using a quantitative proteomics approach based on stable isotope labeling and liquid chromatography-mass spectrometry (LC-MS). Both protein extracts were reduced, alkylated and digested with trypsin. The resulting peptides were labeled with iTRAQ 114 and 117 reagents, respectively. Both labeled peptides were then combined and analyzed simultaneously by nanoflow LC-QTOF MS for protein identification and quantitation. A total of 115 proteins were found to be differentially expressed, including 37 up-regulated (1.2-3 fold change) and 78 down-regulated (1.2-4 fold change) proteins in human tongue cancer tissue. A number of proteins altered at their expression levels were found to be tumor- or cell cycle-associated. Additional normal/cancer subjects are currently being examined to search for proteins that are significantly differentially expressed. These tumor-related proteins hold the potential to be diagnostic biomarkers and/or therapeutic targets of this specific cancer. Supported by PHS grants RO1-DE15970 and UO1- DE016275.
Two lipids based on lipidomics as novel biomarkers for early detection of squamous cell lung cancer.
Authors: Youping Deng, Junmei Ai, Jeffrey Allen Borgia, Hankui Chen, Brett Mahon, Michael J. Liptay, Philip Bonomi, James L. Mulshine
Journal: Journal of Clinical Oncology (2013)

11114 Background: Lipids play roles in membrane structure, energy storage, and signal transduction as well as lung cancer. Lipidomics, a new technology aims to measure all the lipids in a cell, has not been applied to diagnostic test development for a variety of cancer types. Here, we adopt lipidomics as a means to identify plasma lipid markers for the early detection of lung cancer and complement CT-based methods for lung cancer screening. Methods: Using mass spectrometry, we profiled 390 individual lipids in a training discovery cohort comprised of cohorts that were either at “high-risk” for lung cancer (n=22) and squamous cell carcinoma at early stages (n=22). Cases had a minimum of two years clinical follow-up and were matched in terms of race, sex, age and smoking status. Gain ratio feature selection and local weighted classification model were employed to find the best training classifier, which was further validated against an additional cohort, including high-risk individuals (n= 20) and squamous cell carcinoma patients (n=17). Results: In the training discovery stage, we found 20 distinct lipids that were significantly distributed between high-risk and cases of squamous cell carcinoma. We further defined a two lipid marker panel had a training accuracy at 95.5% sensitivity, 90.9% specificity and 95.2% AUC (Area under ROC curve). The validation accuracy against the additional cohort is 100.0% sensitivity, 90.0% specificity and 99.0% AUC (Table). The power for sample size we used in both discovery training and validation stages were over 90%. Conclusions: Using lipidomics we identified two lipid markers capable of discerning cases of squamous cell carcinoma from individuals at high risk for lung cancer, with a high sensitivity, specificity and accuracy. The markers maybe further developed as a quick, safe blood test for early diagnosis of squamous cell lung cancer and reduce unnecessary follow-up imaging or invasive procedures. [Table: see text]
Erectile Dysfunction after Allogeneic Hematopoietic Stem Cell Transplant: Results from a Single Center Experience
Authors: Angelo Andreini, Nicola Zampieri, Claudio Costantini, Giovanni Malerba, Costanza Bruno, Gianluca Salvagno, Giuseppe Francia, Michele Gottardi, Michela Rimondini, Giuseppe Lippi, Isacco Ferrarini, Fabio Benedetti, Giovanni Pizzolo, Cristina Tecchio
Journal: Blood (2017)
Abstract 19891: The Aging-regulated Protein PNUTS is Essential for Maintenance of Endothelial Cell-cell Interaction
Authors: Noelia Lozano-Vidal, Christoph Dieterich, Stefanie Dimmeler, Reinier A Boon
Journal: Circulation (2017)

Introduction: Phosphatase 1 Nuclear Targeting Subunit (PNUTS, official gene name PPP1R10) is a nuclear protein described to act as a binding platform for the PP1 phosphatase complex. PNUTS has rece...
Abstract 17040: Obstructive Sleep Apnea and Ventricular Tachycardia, Results From National Inpatient Sample
Authors: Abdullah S Abdullah, Amr Salama, Abdul Wahab, Nathan Ritter
Journal: Circulation (2017)

Introduction: Obstructive sleep apnea (OSA) has been reported as an independent risk factor for the development of atrial fibrillation and conduction disorders among other detrimental cardiac outco...
Abstract 1106: TNF-α Blockade Prevents Mitochondrial Dysfunction in the Heart and Attenuates Hypertensive Response in Salt Sensitive Hypertensive Rats
Authors: Nithya Mariappan, Srinivas Sriramula, Masudul Haque, Francis Joseph
Journal: Circulation (2006)

Recent studies suggest that the hypertension induced end organ damage is due to an imbalance in the reactive oxygen species production and antioxidant defense. In this study, we demonstrate that tu...
Abstract 3028: STAT3 represses miR-145-5p to exacerbate HER3 expression for surviving EGFR-TKIs in lung cancers
Authors: Chun-Chia Cheng, Ya-Wen Chiang, Ken-Hong Lim, Jungshan Chang, Ai-Sheng Ho, Yi-Fang Chang
Journal: Cancer Research (2019)

Abstract HER3 exerts resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), resulting in tumor relapse in lung cancers. Previously, we have demonstrated that EGFR induces HER3 overexpression and that contributes to the formation of cancer stem-like tumorspheres. However, the cellular mechanism of EGFR in regulating HER3 expression was obscure. We hypothesized that EGFR-downstream STAT3 participates in HER3 expression since STAT3 contributes to cancer stemness and surviving EGFR-TKIs. First, RNAseq was used to uncover the potential genes involving in formation of lung cancer HCC827-derived stem-like tumorspheres. EGFR-positive lung cancer cell lines (HCC827, A549, H1975) were individually treated with a panel containing 172 compounds which targeting to stem cell-associated genes in order to searching potential agents against EGFR-positive lung cancers. In addition, gene knockdown and RNAseq were used for investigating the molecular mechanism of STAT3 on regulating tumor progression and survival of lung cancers. We found that BBI608, a STAT3 inhibitor, was a potential therapeutic agent specifically reducing the cell viability of EGFR-positive lung cancers. Interestingly, the inhibitory effects caused by BBI608 were similar with that derived from YM155, an ILF3 inhibitor, both compounds reduced G9a-mediated HER3 expression. We, furthermore, demonstrated that STAT3 upregulated G9a to silence miR-145-5p for exacerbating HER3 expression in this study. In conclusion, this study figured out the potential cellular function of STAT3 in EGFR-positive lung cancers. We also evaluated that BBI608 was potential to eradicate EGFR-positive lung cancers and demonstrated that STAT3 regulated expression of HER3, indicating that STAT3 was a reliable therapeutic target against EGFR-TKI-resistant lung cancers. Note: This abstract was not presented at the meeting. Citation Format: Chun-Chia Cheng, Ya-Wen Chiang, Ken-Hong Lim, Jungshan Chang, Ai-Sheng Ho, Yi-Fang Chang. STAT3 represses miR-145-5p to exacerbate HER3 expression for surviving EGFR-TKIs in lung 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 3028.
Stents for the gastrointestinal tract
Authors: Todd H. Baron, Peter D. Siersema
Journal: Endoscopy (2019)

Congratulations to Endoscopy for its 50th anniversary! In a landmark article, Eckart Frimberger described for the first time the use of an expandable metal stent for esophageal placement [1]. The spiral stent was wound onto a pediatric endoscope so that it was the same diameter as the shaft. After dilation of the stricture to 1 – 2 mm larger than the diameter of the stent (10 mm), the stent was passed across the stricture and released in the esophagus where it subsequently expanded to its maximal diameter of 13 – 15 mm. The stent was placed for palliation of malignant dysphagia in 10 patients with adenocarcinoma of the esophagus, and there were no insertion-related adverse events.
Abstract 2574: Werner syndrome helicase is required for the survival of cancer cells with microsatellite instability
Authors: Lorn Kategaya, Senthil K. Perumal, Jeffrey H. Hager, Lisa D. Belmont
Journal: Cancer Research (2019)

Abstract Werner Syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss of function mutations in WRN lead to premature aging and pre-disposition to cancer. We evaluated synthetic lethality (SL) between not only of WRN, but also of another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines. We found that WRN exhibited SL with a DNA mismatch repair protein MutL homolog 1 (MLH1), loss of which is associated with high microsatellite instability (MSI-H). We then demonstrated that MSI-H cells exhibited increased double-stranded DNA breaks, altered cell cycles and decreased viability in response to WRN knockdown. Although WRN is the only human RecQ enzyme with a distinct exonuclease domain, only loss of helicase activity drives the MSI SL interaction. This SL interaction in MSI cancer cells positions WRN as a relevant therapeutic target in patients with MSI-H tumors. Citation Format: Lorn Kategaya, Senthil K. Perumal, Jeffrey H. Hager, Lisa D. Belmont. Werner syndrome helicase is required for the survival of cancer cells with microsatellite instability [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 2574.
Abstract 337: Degradation of AXL overcome acquired cross-resistance to gefitinib and osimertinib in non-small cell lung cancer cells
Authors: Donghwa Kim, Duc-Hiep Bach, Yan-hua Fan, Thi-Thu-Trang Luu, Ji-Young Hong, Hyen-Joo Park, Sang Kook Lee
Journal: Cancer Research (2019)

Abstract Epidermal growth factor receptor (EGFR) mutation is one of the major driver oncogenes in non-small cell lung cancer (NSCLC) and most frequently found in Asian patients. Although the first generation of EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have led to improved prognoses for NSCLC patients, acquired resistance has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. Recently, AXL has been reported to play a role in drug resistance mechanisms for many anti-cancer drugs, including erlotinib and cetuximab, as well as in ionizing radiation therapy for multiple cancers. In the present study, we demonstrate the involvement of AXL in the acquired resistance to gefitinib and osimertinib of EGFR-mutant NSCLC cells, then show the combination effect of an AXL degrader and EGFR-TKIs to overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells. We found that AXL was overexpressed and its degradation was delayed in EGFR-TKI-resistant NSCLC cells. Yuanhuadine (YD), a natural antitumor agent, effectively suppressed the expression of AXL by accelerating protein degradation. YD combined with gefitinib or osimertinib synergistically inhibited the growth of resistant cells in vitro and suppressed tumor growth in a nude mouse xenograft model. Moreover, administration of YD with gefitinib effectively delayed gefitinib-driven acquired resistance in a long-term xenograft model. Our results suggest that the combination of YD with either gefitinib or osimertinib is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC by targeting AXL degradation. Citation Format: Donghwa Kim, Duc-Hiep Bach, Yan-hua Fan, Thi-Thu-Trang Luu, Ji-Young Hong, Hyen-Joo Park, Sang Kook Lee. Degradation of AXL overcome acquired cross-resistance to gefitinib and osimertinib in non-small cell lung cancer cells [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 337.