tbuckley/cabot-search huggingface dataset:
Herceptin-refractory ovarian carcinoma cells differentially express genes involved in angiogenesis, invasion, and metastasis
Authors: Leopoldo L. Luistro, James A. Rosinski, Hongjin Bian, Nicholas M. Ponzio, Steve R. Ritland
Journal: Cancer Research (2005)

5085  We have previously reported the generation of a preclinical model of ovarian carcinoma with diminished response to Herceptin (Trastuzumab). SKOV-3 HR (Herceptin-refractory) subcutaneous xenograft tumors, unlike parental SKOV-3 xenografts, were not growth inhibited by Herceptin over a 4-week treatment period when implanted in athymic nu/nu mice. Herceptin has a 3-fold lower binding affinity on HER2 (erbB2) cell surface receptors of SKOV-3 HR cells, and was unable to inhibit the proliferation of these cells. To understand the cause of the experimentally-induced lack of response to Herceptin, microarray expression profiling (MEP) was performed on both the parental/Herceptin-susceptible and Herceptin-refractory cell lines. SKOV-3 and SKOV-3 HR cells were incubated with or without Herceptin up to 72 hours, cells harvested, RNA extracted, and cDNA scanned onto Affymetrix (U133A, U133B) gene chips. MEP results revealed an increased expression of angiogenic, metastatic, and invasive genes such as Angiopoietin 2, ICAM2, nestin, fibulin, MMP7, ceruloplasmin, CD24, FGFR3, and Vav3 oncogene in SKOV-3 HR cells. Alternatively, keratin 19, integrin alpha 3 and beta 4, uPAR and thrombomodulin were downregulated potentiating an epithelial to mesenchymal phenotypic transition. Interestingly, Mucin1 (MUC1) gene expression was also upregulated (4-5 fold) in basal and Herceptin-treated SKOV-3 HR cells. Glycosylated MUC1 is aberrantly overexpressed in breast and ovarian carcinomas. HER2 has been shown to regulate MUC1 expression in transformed mammary epithelial cells. MUC1 transmembrane overexpression on SKOV-3 HR cells could possibly affect Herceptin binding by direct steric hindrance onto HER2 receptors. Additionally, the MUC1 cytoplasmic tail has been reported to bind all four members of the HER/erbB family of tyrosine kinase receptors. Increased phosphorylation of MUC1 in SKOV-3 HR cells could potentiate downstream signaling pathways such as Ras/Raf/Erk (MAPK) leading to increased proliferation. Through the use of MEP, we hypothesize that increased expression of MUC1 and genes involved in angiogenesis, invasion, and metastasis may play a role in lack of Herceptin-response which drives an aggressive HER2-positive primary tumor with greater metastatic potential, thus leading to poor prognosis and shortened survival. It remains to be determined if similar changes occur in Herceptin-treated patients whose tumors progress.
Continuous exposure to the carcinogenic antiretroviral drug Zidovudine (AZT) alters metabolism of human cells in vitro
Authors: Ofelia A. Olivero, Irma L. Vazquez, Catherine Cooch, Rao L. Divi, Ainsley Weston, Miriam C. Poirier
Journal: Cancer Research (2005)

3304  Zidovudine (AZT), a thymidine analogue and a carcinogen, was the first drug found effective against the human immunodeficiency virus (HIV-1). The antiretroviral efficacy of AZT depends on phosphorylation for incorporation into DNA, and requires continuous therapy. The intracellular mono-, di- and tri-phosphorylation steps are catalyzed by thymidine kinase 1 (TK1), thymidylate kinase, and pyrimidine nucleoside diphosphate kinase, respectively. These studies were designed to investigate AZT metabolism in 2 types of human cells, MOLT-3 transformed lymphoblastoid cells and normal mammary epithelial cells under conditions of continuous AZT exposure. MOLT-3 cells were exposed to AZT (800 μM) for 14 passages. During that time levels of TK1 protein expression were determined by western blotting. The data showed that the enzymatically active form of TK1, the 24kDa monomer, was depleted by passage 5 and was not subsequently restored by passage 14. Concomitantly, the enzymatically-inactive TK1 48kDa dimer increased with duration of exposure. Depletion of the TK1 monomer correlated with a transient (5-fold) increase in doubling time (passages 2-4) and a final 2-fold increase in doubling time that was maintained from passage 5 to passage 14. Gene expression analysis of TK1, determined by real time PCR, showed a 5.7-fold down regulation at passage 1 and an 8.3-fold down-regulation at passage 5; these data correlated well with a loss in TK1 enzyme specific activity, by 30%-75%, determined by a radiochemically based enzyme assay. Incorporation of AZT into DNA was measured by radioimmunoassay, and mean values were 59.3, 72.4 and 54.6 molecules of AZT/106 nucleotides at passages 1, 5, and 14, respectively, suggesting that MOLT-3 cells may use an alternate pathway to phosphorylate AZT. In order to examine this phenomenon in normal human cells, we used NHMEC strains having naturally differing levels of TK1 expression. NHMEC strains expressing low levels of TK1 (n=2), determined by western blotting, showed no detectable incorporation of AZT into DNA when exposed to 200 μM AZT for 24 hr, while strains with high levels of TK1 expression(n=2) showed > 200 molecules of AZT/106 nucleotides. In summary, chronic AZT exposure in transformed MOLT-3 cells resulted in loss of TK1 expression and enzyme activity, but not loss of capacity to incorporate AZT into DNA. These data suggest that down-regulation of TK1 may be circumvented through employment of other pathways. In contrast, in the normal breast epithelial cells the capacity to incorporate AZT into DNA appears to be linked to the capacity of individual cell strains to express TK1.
Bioactive glass based scaffolds coated with gelatin for the sustained release of icariin
Authors: Theresa Reiter, Tanja Panick, Katharina Schuhladen, Judith A. Roether, Jasmin Hum, Aldo R. Boccaccini
Journal: Bioactive Materials (2018)

Gelatin-coated, 3D sponge-like scaffolds based on 45S5 bioactive glass were produced using the foam replication technique. Compressive strength tests of gelatin-coated samples compared to uncoated scaffolds showed significant strengthening and toughening effects of the gelatin coating with compressive strength values in the range of cortical bone. Additionally, the crosslinked gelatin network (using either caffeic acid or N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-hxdroxysuccinimide (NHS) as crosslinking agent) was shown to be a suitable candidate for the sustained release of the bioactive molecule icariin. Concerning bioactivity of the produced scaffolds, characterization by FTIR and SEM indicated the formation of hydroxyapatite (HA) in all samples after immersion in simulated body fluid (SBF) for 14 days, highlighting the favorable combination of mechanical robustness, bioactivity and drug delivery capability of this new type of scaffolds.
Comprehensive mRNA-based screen for tyrosine kinase fusions and a de novo alternative transcription initiation site in soft tissue sarcomas
Authors: Y. Suehara, S. Kohsaka, A. Kurisaki, K. Akaike, T. Hayashi, K. Mogushi, T. Okubo, Y. Kim, S. Sato, E. Kobayashi, K. Kaneko, H. Mano, T. Saito
Journal: Annals of Oncology (2018)
Abstract 16746: Cardiovascular Disease Outcomes After Breast Cancer in Postmenopausal Women: Results From the Women’s Health Initiative
Authors: Na-Jin Park, Yuefang Chang, Catherine Bender, Yvette Conley, Nancy E Davidson, G J Van Londen, Randi Foraker, Sylvia Wassertheil-Smoller, Marcia L Stefanick, Rowan Chlebowski, Lewis Kuller
Journal: Circulation (2015)

Introduction: A growing population of older breast cancer (BC) survivors may be at risk of cardiovascular disease (CVD). Pre-existing CVD risk factors may impact on subsequent development of CVD after BC among postmenopausal women. Objectives: (1) To describe baseline CVD risk factors among postmenopausal women with and without BC prior to diagnosis of BC; and (2) To examine independent associations of BC with individual and composite CVD events (i.e., the first occurrence of coronary heart disease [CHD], angina, coronary revascularization, congestive heart failure, peripheral arterial disease, and stroke) and mortality outcomes (i.e., all-cause, CVD, and CHD death) after BC adjusting for baseline characteristics and CVD risk factors. Methods: This prospective cohort study included 101,916 women in the Women’s Health Initiative (WHI) (including 4,340 women with invasive BC) aged 50-79 years without CVD at baseline (1993-1998) through December 2010. Over a period of 10 years after BC, CVD morbidity and mortality outcomes were identified and age-adjusted rates per 1,000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox models were determined for women who did and did not develop BC. Results: Regardless of BC status, baseline CVD risk factors prior to BC, such as smoking, hypertension, diabetes and hypercholesterolemia, were strong predictors of CVD outcomes in postmenopausal women. Multivariable Cox models revealed that women who developed BC (n = 4,340) had a similar risk of composite CVD (HR = 0.91, 95% CI, 0.82-1.02), but a higher risk of CHD (HR=1.33, 95% CI, 1.12-1.58), compared with women without BC (n = 97,576). Women aged 70-79 and on hormonal therapy at the WHI entry with localized BC during follow-up period had the highest CHD death rate. The results were similar after excluding women with baseline cancer at the WHI study entry. Conclusions: These results emphasize the great need for identification and timely management of pre-existing CVD risk factors for postmenopausal women with BC. CVD accounts for almost as many deaths as BC among women with localized disease, indicating that improved effort to prevent and treat CVD risk factors could improve survival of postmenopausal BC survivors.
Firearm Storage and Adult Alcohol Misuse Among Washington State Households With Children
Authors: Erin R. Morgan, Anthony Gomez, Frederick P. Rivara, Ali Rowhani-Rahbar
Journal: JAMA Pediatrics (2018)

Firearm injuries and fatalities among children are an important public health problem. Children living with an adult misusing alcohol may be at a heightened risk for self-harm or unintentional injury, highlighting the need to investigate the association between household firearm storage and adult alcohol misuse.To characterize household firearm presence among children by various sociodemographic characteristics, and to assess the association between children living in a home with an unsafely stored firearm and an adult reporting alcohol misuse.This cross-sectional investigation uses data from the 2013 and 2016 Behavioral Risk Factor Surveillance System in the state of Washington, a program that administers a telephone survey statewide to randomly selected noninstitutionalized adults at least 18 years of age about their health-related risk behaviors, chronic health conditions, and use of preventive services. The 2013 and 2016 data included 5241 responses to the firearm ownership and storage module and the Random Child Selection module (intended for a randomly selected child younger than age 18 years and reported by an adult living in the same household). Data for this study were collected from January 1 through December 31, 2013, and January 1 through December 31, 2016. Data were analyzed from March through May 2018.The primary outcomes were a child's residence in a firearm-owning home, the manner in which household firearms were stored, and the adult respondent's alcohol consumption.Among the 3443 children living in a non-firearm-owning household, 50.7% were male (all values given as a percentage only are weighted); among those reporting specific age, the weighted mean age was 9.3 years (unweighted mean [SD], 10.1 [5.2] years). In the 1756 children living in a firearm-owning household, 52.5% were male; among those reporting specific age, the weighted mean age was 9.1 years (unweighted mean [SD], 9.8 [5.4] years). An estimated 470 000 children (29.4%; 95% CI, 27.3%-31.7%) in the state resided in a firearm-owning household. Among them, 258 000 children (54.6%; 95% CI, 51.5%-57.6%) lived with at least 1 firearm that was not stored safely (ie, not locked and unloaded). Firearms were more likely to be stored unsafely in homes in which an adult reported alcohol misuse (prevalence ratio: 1.20; 95% CI, 1.07-1.35).Children living in a household with an adult who misuses alcohol may be more likely to live with an unsafely stored firearm, which is concerning given the association between adult alcohol misuse and children's risk for sustaining injury.
The Cumulative Sex Wage Gap in Cardiology
Authors: Norman C. Wang
Journal: JAMA Cardiology (2018)

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 Cardiology 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 Cardiology journal
Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial
Authors: Pekka Jakkula, Matti Reinikainen, Johanna Hästbacka, Pekka Loisa, Marjaana Tiainen, Ville Pettilä, Jussi Toppila, Marika Lähde, Minna Bäcklund, Marjatta Okkonen, Stepani Bendel, Thomas Birkelund, Anni Pulkkinen, Jonna Heinonen, Tuukka Tikka, Markus B. Skrifvars
Journal: Intensive Care Medicine (2018)

We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury.Using a 23 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15 kPa) or moderate hyperoxia (PaO2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months.In total 120 patients were included in the analyses. There was a clear separation in PaCO2 (p < 0.001) and PaO2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO2 group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO2 group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes.Both high-normal PaCO2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected.ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.
Негативні ефекти зловживання послаблюючими засобами у лікарській практиці
Authors: Yu.M. Stepanov, O.N. Vlasova, M.V. Stoikevych
Journal: GASTROENTEROLOGY (2018)

Зловживання проносними засобами — це розлад, що характеризується незрозумілою і мінливою низкою шлунково-кишкових, електролітних і кислотно-лужних відхилень, що можуть призвести як до виникнення хронічних захворювань, так і до смертельних наслідків. Зловживання самоіндукуєтся, завуальоване і пов’язане з психологічними відхиленнями, що ускладнює постановку діагнозу. Як безпечний проносний засіб пацієнтам, які потребують тривалого лікування запорів, може бути рекомендований препарат ИзіДу.
Abstract 16599: Low Diastolic Blood Pressures Are Associated With an Increased Risk of Myocardial Infarction, Peripheral Arterial Disease, and All-Cause Mortality, but Not Cerebrovascular Accident - A Reanalysis of ALLHAT
Authors: Nathan K Itoga, Daniel S Tawfik, Charles K Lee, Satoshi Maruyama, Nicholas J Leeper, Tara I Chang
Journal: Circulation (2017)

Introduction: Current blood pressure (BP) guidelines focus on lowering systolic BP (SBP) to reduce cardiovascular events; however, recent literature has associated low diastolic BP (DBP) with incre...
Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: A cohort study
Authors: Romain Neugebauer, Katherine A. Su, Zheng Zhu, Monica Sokil, Mary-Margaret Chren, Gary D. Friedman, Maryam M. Asgari
Journal: Journal of the American Academy of Dermatology (2018)
Minimum Specifications for a Lifebox Surgical Headlight for Resource-Constrained Settings
Authors: Jared A. Forrester, Kris Torgeson, Thomas G. Weiser
Journal: JAMA Surgery (2018)

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
Functional alterations of myeloid cells during the course of Alzheimer’s disease
Authors: Aaron D. Thome, Alireza Faridar, David R. Beers, Jason R. Thonhoff, Weihua Zhao, Shixiang Wen, Belen Pascual, Joseph C. Masdeu, Stanley H. Appel
Journal: Molecular Neurodegeneration (2018)

Neuroinflammation is a hallmark of neurodegenerative disease and a significant component of the pathology of Alzheimer’s disease (AD). Patients present with extensive microgliosis along with elevated pro-inflammatory signaling in the central nervous system and periphery. However, the role of peripheral myeloid cells in mediating and influencing AD pathogenesis remains unresolved. Peripheral myeloid cells were isolated from peripheral blood of patients with prodromal AD (n = 44), mild AD dementia (n = 25), moderate/severe AD dementia (n = 28), and age-matched controls (n = 54). Patients were evaluated in the clinic for AD severity and categorized using Clinical Dementia Rating (CDR) scale resulting in separation of patients into prodromal AD (CDR0.5) and advancing forms of AD dementia (mild-CDR1 and moderate/severe-CDR2/3). Separation of peripheral myeloid cells into mature monocytes or immature MDSCs permitted the delineation of population changes from flow cytometric analysis, RNA phenotype analysis, and functional studies using T cell suppression assays and monocyte suppression assays. During stages of AD dementia (CDR1 and 2/3) peripheral myeloid cells increase their pro-inflammatory gene expression while at early stages of disease (prodromal AD—CDR0.5) pro-inflammatory gene expression is decreased. MDSCs are increased in prodromal AD compared with controls (16.81% vs 9.53%) and have markedly increased suppressive functions: 42.4% suppression of activated monocyte-produced IL-6 and 78.16% suppression of T cell proliferation. In AD dementia, MDSC populations are reduced with decreased suppression of monocyte IL-6 (5.22%) and T cell proliferation (37.61%); the reduced suppression coincides with increased pro-inflammatory signaling in AD dementia monocytes. Peripheral monocyte gene expression is pro-inflammatory throughout the course of AD, except at the earliest, prodromal stages when pro-inflammatory gene expression is suppressed. This monocyte biphasic response is associated with increased numbers and suppressive functions of MDSCs during the early stages and decreased numbers and suppressive functions in later stages of disease. Prolonging the early protective suppression and reversing the later loss of suppressive activity may offer a novel therapeutic strategy.
Validation of Serum Test for Advanced Liver Fibrosis in Patients With Nonalcoholic Steatohepatitis
Authors: Rohit Loomba, Anjali Jain, Anna Mae Diehl, Cynthia D. Guy, Dana Portenier, Ranjan Sudan, Seema Singh, Claire Faulkner, Lisa Richards, Kelly D. Hester, Lauren Okada, Xiao-jun Li, Larry Mimms, Manal F. Abdelmalek
Journal: Clinical Gastroenterology and Hepatology (2018)
The US Food and Drug Administration’s Authorization of the First Cannabis-Derived Pharmaceutical
Authors: Y. Tony Yang, Jerzy P. Szaflarski
Journal: JAMA Neurology (2018)

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 Neurology 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 Neurology journal
Persistence of CRISPR/Cas9-Edited Hematopoietic Stem and Progenitor Cells and Reactivation of Fetal Hemoglobin in Nonhuman Primates
Authors: Olivier Humbert, Stefan Radtke, Ray R Carillo, Anai M Perez, Sowmya Somashekar Reddy, Lauren E Schefter, Christopher Lux, Sowmya Pattabhi, Olivier Negre, Ciaran M Lee, Jennifer Adair, Christopher Peterson, Gang Bao, David J. Rawlings, Andrew M. Scharenberg, Hans-Peter Kiem
Journal: Blood (2018)