tbuckley/cabot-search huggingface dataset:
Simultaneous Antidepressant and Benzodiazepine New Use and Subsequent Long-term Benzodiazepine Use in Adults With Depression, United States, 2001-2014
Authors: Greta A. Bushnell, Til Stürmer, Bradley N. Gaynes, Virginia Pate, Matthew Miller
Journal: JAMA Psychiatry (2017)

Benzodiazepines have been prescribed for short periods to patients with depression who are beginning antidepressant therapy to improve depressive symptoms more quickly, mitigate concomitant anxiety, and improve antidepressant treatment continuation. However, benzodiazepine therapy is associated with risks, including dependency, which may take only a few weeks to develop.To examine trends in simultaneous benzodiazepine and antidepressant new use among adults with depression initiating an antidepressant, assess antidepressant treatment length by simultaneous new use status, estimate subsequent long-term benzodiazepine use in those with simultaneous antidepressant and benzodiazepine new use, and identify determinants of simultaneous new use and long-term benzodiazepine use.This cohort study using a US commercial claims database included commercially insured adults (aged 18-64 years) from January 1, 2001, through December 31, 2014, with a recent depression diagnosis who began antidepressant therapy but had not used antidepressants or benzodiazepines in the prior year.Simultaneous new use, defined as a new benzodiazepine prescription dispensed on the same day as a new antidepressant prescription.The proportion of antidepressant initiators with simultaneous new use and continuing antidepressant treatment for 6 months and the proportion of simultaneous new users receiving long-term (6-months) benzodiazepine therapy.Of the 765 130 adults (median age, 39 years; interquartile range, 29-49 years; 507 451 women [66.3%]) who initiated antidepressant treatment, 81 020 (10.6%) also initiated benzodiazepine treatment. The mean annual increase in the proportion simultaneously starting use of both agents from 2001 to 2014 was 0.49% (95% CI, 0.47%-0.51%), increasing from 6.1% (95% CI, 5.5%-6.6%) in 2001 to 12.5% (95% CI, 12.3%-12.7%) in 2012 and stabilizing through 2014 (11.3%; 95% CI, 11.1%-11.5%). Similar findings were apparent by age group and physician type. Antidepressant treatment length was similar in simultaneous new users and non-simultaneous new users. Among simultaneous new users, 12.3% (95% CI, 12.0%-12.5%) exhibited long-term benzodiazepine use (64.0% discontinued taking benzodiazepines after the initial fill). Determinants of long-term benzodiazepine use after simultaneous new use were longer initial benzodiazepine days' supply, first prescription for a long-acting benzodiazepine, and recent prescription opioid fills.One-tenth of antidepressant initiators with depression simultaneously initiated benzodiazepine therapy. No meaningful difference in antidepressant treatment at 6 months was observed by simultaneous new use status. Because of the risks associated with benzodiazepines, simultaneous new use at antidepressant initiation and the benzodiazepine regimen itself require careful consideration.
Omalizumab effectively protects against early and late allergic responses in asthma after 4 weeks
Authors: J. Trischler, A. Lieb, M. Arnold, J. Schulze, M. Rosewich, R. Schubert, I. Bottoli, S. Zielen
Journal: Allergy (2017)

Omalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. As new applications for omalizumab demand precise knowledge of the onset of effects, the objective of this study was to determine the time course of the early (EAR) and late allergic reaction (LAR).Ten patients (IgE>300 IU/mL and <700 IU/mL) with a significant response to allergen challenge were treated with omalizumab according to the approved dosing table. Bronchial allergen provocations (BAP) were repeated at weeks 1, 2, 4, and 8.EAR was significantly reduced after 4 weeks (ΔFEV1 28% vs 11%; P<.001), eNO (86 vs 53 ppb; P<.05) and basophil activation after 2 weeks (CD63 expression 79% vs 32%, P<.05) and LAR already after 1 week (ΔFEV1 26% vs 13%, P<.05).These results demonstrate the onset of protective effects earlier than previously determined, potentially improving seasonal utilization and combination with immunotherapy.
Screening mammography: a missed clinical opportunity? Results of the NCI Breast Cancer Screening Consortium and National Health Interview Survey Studies
Journal: JAMA (1990)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Anti-mdm2 siRNA induces cell cycle arrest and apoptosis in human breast cancer MCF-7 cells, and inhibits tumor growth in nude mouse models
Authors: Tie-Gang Liu, James Q. Yin, Bo-Yang Shang, Yong-Su Zhen, Rong-Guang Shao
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4600 

The inactivation of apoptotic and tumor suppressor pathways and the overexpression of oncogenes are genomic features of human cancers. The suppression of mdm2 gene may be a new method for cancer therapy. RNAi technology has been identified to be a powerful tool for silencing endogenous or exogenous genes in mammalian cell lines. In the present study, we investigated the anticancer efficacy and molecular mechanisms of anti-mdm2 siRNA. Our results showed that the anti-mdm2 siRNA inhibited specially and effectively the expression of targeting mdm2 gene in human breast cancer MCF-7 cells. 36 h after transfection, 100 nM of anti-mdm2 siRNA reduced expression of mdm2 gene to background level with Western blotting analysis, and downregulation of expression of targeting mdm2 gene showed dose and time-dependent efficacy. MTT assay showed that the IC50 of anti-mdm2 siRNA was about 130 nM to MCF-7 cells. The transfection with anti-mdm2 siRNA induced apoptotic cell death accompanied with the condensation and fragmentation of cell nuclei, the release of cytochrome c from mitochondria to cytosol, decrease of Bcl-2 and NF-κB levels and increase of Bax and p53 levels. Anti-mdm2 siRNA also caused cell cycle arrest at G1 phase with changes of Cyclin and Cdk protein expressions. Furthermore, we demonstrated in vivo for the first time that anti-mdm2 siRNA possessed significant anticancer activity in human breast MCF-7 cancer model, and combination therapy of anti-mdm2 siRNA with mitomycin significantly improved the antitumor efficacy compared with the agents used alone. Following treatment of mitomycin and anti-mdm2 siRNA, tumor growth was inhibited by approximately 88.8% on day 23. The mock siRNA and transfection reagent of Lipofectamine 2000™ had minimal effect on tumor growth. These findings indicate that anti-mdm2 siRNA may eventually become a promising gene-specific drug used for the treatment of breast cancer and other tumors.
Global gene expression profiling clearly differentiates mouse plasma cell tumors from B-cell lymphomas but shows similarities with human multiple myelomas
Authors: Eun Sung Park, John D. Shaughnessy, Hongyang Wang, Ju-Seog Lee, Fenghuang Zhan, James D. Owens, Michael Potter, Siegfried Janz, J. Frederic Mushinski
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

255 

To gain insight into the molecular mechanisms of neoplastic transformation of B cells and plasma cells, global gene expression profiles were compared across ten subtypes of mouse plasma cell tumors (PCTs) and B-cell lymphomas (BCLs) using Affymetrix U74Av2 microarrays. Unsupervised hierarchical cluster analysis generated two main sub-clusters: one containing the PCTs and the other the BCLs. Two-sample t-test revealed 1654 genes that were significantly (p<0.001) differentially expressed between the two groups. Within the PCT group 98 genes discriminated tumors with accelerated onset brought about by v-Abl oncogene activity in the context of uniform Myc-activation. PCTs containing Myc-activating T(12;15) chromosomal translocations did not display gene expression patterns distinct from those with variant T(6;15) translocations, in which the breakpoint is in the Pvt-1 locus, 230 kb 3′ of Myc, suggesting that Myc activation was the initiating factor in both. When integrated with previously published Affymetrix array data from human multiple myelomas (MM) and tonsillar B cells, the mouse BCLs and human tonsillar B cells co-clustered, while PCTs clustered together with myelomas. Intriguingly, the IL-6-transgenic subset of mouse PCTs clustered more closely with MGUS and the MM1 subset of human myelomas, while the other PCT subsets clustered with the more aggressive MM2-MM4 myeloma subsets. What is more, the more aggressive types of PCTs, those accelerated by v-Abl expression, clustered with the most aggressive MM3 and MM4 subsets of human myelomas. Thus, despite dissimilarities in site of origin, mode of induction and chromosomal abnormalities, murine intraperitoneal PCTs and human bone marrow-localized MMs appear to share many similarities in gene expression and gene-activating signal transduction pathways. As such, mouse PCTs represent powerful model systems for the study of human myeloma and may present an opportunity to investigate the molecular mechanisms involved in increasing aggressiveness as myeloma progresses in malignancy.
Abstract 210: Thioredoxin-2 Inhibits Mitochondrial Ros Generation And Ask1 Activity To Maintain Cardiac Function
Authors: Wang Min, Qunhua Huang
Journal: Circulation Research (2013)

Background: Increasing evidence indicates that mitochondrial-derived reactive oxygen species (ROS) and cellular apoptosis contribute to the pathogenesis of cardiac dysfunction. Mitochondrial thioredoxin (Trx2) is a key protein regulating cellular redox and survival, However, but its role in normal cardiac growth has not been determined. Methods and Results: We have generated cardiac-specific Trx2 knockout mice (Trx2-cKO) to determine the physiological importance of the Trx2 system in the heart. Trx2-cKO mice developed a spontaneous dilated cardiomyopathy at 1 month of age with increased heart size, fibrosis, reduced ventricular wall thickness, and progressive contractile dysfunction, resulting in death due to heart failure by 4 months of age. Cardiac changes in Trx2-cKO mice were accompanied by disruption of mitochondrial integrity and function, as evident by alterations in mitochondrial number, ultrastructure, membrane potential and ATP production. Increases in ASK1 signaling and ROS production preceded mitochondrial damage, cellular apoptosis and contractile dysfunction in both Trx2-cKO hearts and isolated cardiomyocytes. Moreover, deletion of ASK1 attenuates ROS production, mitochondrial dysfunction and cellular apoptosis in Trx2-deficient cardiomyocytes. These data indicate that ASK1 is a major target of Trx2 and that activation of ASK1 is causally associated with mitochondrial dysfunction, ROS production and cellular apoptosis. We also detected reduced Trx2 expression and increased ASK1 activity in human hearts from patients with cardiomyopathy, suggesting that this mechanism is clinically important. Conclusion: Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial ROS production and ASK1-dependent apoptosis. These results suggest that pharmacological inhibition of ASK1 may provide a therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure.
Rearrangements of Tyrosine Kinase (TK) Genes in Chronic Myeloproliferative Disorders (CMPD): A FISH Study
Authors: Paolo Bernasconi, Irene Dambruoso, Marina Boni, Paola Maria Cavigliano, Ilaria Giardini, Barbara Rocca, Rita Zappatore, Marilena Caresana, Antonella Orlando, Ilaria Casetti, Chiara Elena, Elisa Rumi, Mario Cazzola
Journal: Blood (2016)
Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: Surgical results from an international randomized trial (BrighTNess).
Authors: Mehra Golshan, Sibylle Loibl, Jens Bodo Huober, Joyce O'Shaughnessy, Hope S. Rugo, Norman Wolmark, Mark D. McKee, David Maag, Danielle Marie Sullivan, Vincent L. Giranda, Xuan Liu, Gunter Von Minckwitz, Charles E. Geyer, William M. Sikov, Michael Untch
Journal: Journal of Clinical Oncology (2017)

514 Background: Neoadjuvant systemic therapy (NST) increases the frequency of breast-conserving therapy (BCT) in stage II-III breast cancer, but there is little data on how often it converts patients (pts) from BCT-ineligible (BCT-I) to BCT-eligible (BCT-E) and on the impact of other factors on surgical choices. We collected surgical assessment and management data from an international randomized trial of NST in triple-negative breast cancer (TNBC). Methods: Women with operable TNBC were randomized to veliparib (V) with carboplatin (C) and paclitaxel (P), placebo with C and P or placebo with P followed by doxorubicin and cyclophosphamide. The surgeons assessed BCT candidacy by clinico-radiographic criteria before and after NST; surgical management was at surgeon and patient discretion. We assessed interactions between BCT eligibility pre- and post-NST, germline BRCA mutation ( gBRCA) status, continent of treatment and achievement of pathologic complete response(pCR) and percentage of pts who underwent BCT versus mastectomy. Results: Pre- and post-NST surgical assessments were available for 604 pts who underwent surgery. BCT rates are listed in the Table. The BCT rate was 68% among pts deemed BCT-E after NST. pCR rates were identical between BCT-E pts who chose BCT (55%) vs. mastectomy (53%). Of 141 pts deemed BCT-I at baseline, 75 (53%) converted to BCT-E but only 42 (56%) of these opted for BCT. pCR rates were 49% in BCT-E converts vs. 36% in those remained BCT-I. gBRCA pts (n = 84) were less likely to choose BCT even if they were BCT-E. Pts treated in North America (NA) were less likely to choose BCT (55% vs. 80% for Europe and Asia P&lt;0.0001) even among non- gBRCA considered BCT-E post-NST (61% vs. 85% P&lt;0.0001). Conclusions: This largest prospective analysis of the impact of NST in TNBC demonstrates a conversion rate from BCT-I to BCT-E of 53%. BCT rates were lower in pts with gBRCA; the much higher mastectomy rate among BCT-E pts in NA merits investigation. Clinical trial information: NCT02032277. [Table: see text]
The interplay between adipose tissue and the cardiovascular system: is fat always bad?
Authors: Ioannis Akoumianakis, Charalambos Antoniades
Journal: Cardiovascular Research (2017)

Obesity is a risk factor for cardiovascular disease (CVD). However, clinical research has revealed a paradoxically protective role for obesity in patients with chronic diseases including CVD, suggesting that the biological 'quality' of adipose tissue (AT) may be more important than overall AT mass or body weight. Importantly, AT is recognised as a dynamic organ secreting a wide range of biologically active adipokines, microRNAs, gaseous messengers, and other metabolites that affect the cardiovascular system in both endocrine and paracrine ways. Despite being able to mediate normal cardiovascular function under physiological conditions, AT undergoes a phenotypic shift characterised by acquisition of pro-oxidant and pro-inflammatory properties in cases of CVD. Crucially, recent evidence suggests that AT depots such as perivascular AT and epicardial AT are able to modify their phenotype in response to local signals of vascular and myocardial origin, respectively. Utilisation of this unique property of certain AT depots to dynamically track cardiovascular biology may reveal novel diagnostic and prognostic tools against CVD. Better understanding of the mechanisms controlling the 'quality' of AT secretome, as well as the communication links between AT and the cardiovascular system, is required for the efficient management of CVD.
Evidence on public health interventions in humanitarian crises
Authors: Karl Blanchet, Anita Ramesh, Severine Frison, Emily Warren, Mazeda Hossain, James Smith, Abigail Knight, Nathan Post, Christopher Lewis, Aniek Woodward, Maysoon Dahab, Alexander Ruby, Vera Sistenich, Sara Pantuliano, Bayard Roberts
Journal: The Lancet (2017)
Abstract P277: Cardioprotection Enabled by Proteomic Remodeling of the Mitochondrial Respiratory Chain
Authors: Christopher Lotz, Ning Deng, Jun Zhang, Yueju Wang, Chenggong Zong, David Liem, Ji-Youn Youn, Hua Cai, Christine Wu, John Yates, James Weiss, Peipei Ping
Journal: Circulation Research (2011)

The mitochondrial respiratory chain is a collection of five multi-protein complexes, whose unobstructed functionality represents a pivotal element at the crossroads of cell death or survival. However, its molecular composition and stochiometric information remains elusive and the adaptive abilities of the chain remain largely unknown. We employed a quantitative proteomic approach to investigate the hypothesis that cardioprotection against ischemic injury is afforded by a salutary proteomic remodeling of the mitochondrial respiratory chain. The respiratory chain of cardiac mitochondria isolated from wild type (WT) mice and from mice expressing a constitutively active protein kinase Cε (AE-PKCε) were characterized using 15N-stable isotope labeled murine models (SILAM), as well as a label-free method in conjunction with high resolution LC-MS/MS, respectively. Enzymatic function of electron transport chain and the ATP synthase were evaluated (n=7/group); and mitochondrial superoxide production was examined by ESR-spectroscopy (n=3/group). Three novel and important observations are made: (i) five individual respiratory complexes exhibited a molar ratio of 1:1:1.4:1.2:4.5 in the WT-heart; (ii) subunits within the five complexes encoded by the mitochondrial genome were expressed at much lower abundance (p&lt;0.05) than those encoded by the nuclear genome; and (iii) Genetic cardioprotection by AE-PKCε elicited a proteomic remodeling of complex I and III, mitochondria from AE-PKCε exhibited an increased expression of multiple subunits, including the catalytic complex III subunit Cyc1. This finding was accompanied by a preserved complex III activity (p&lt;0.05), as well as tempered superoxide production (p&lt;0.01) subsequent to Ca2+-induced damage. This is the first study documenting a salutary proteomic remodeling of the mitochondrial respiratory machinery in cardioprotection. Quantitative proteomics technology enabled novel information and new insights into mitochondrial biology.
Phospholipase A2 and acute pancreatitis in rats Reply
Authors: T BERTSCH, E G FISCHER, Y HORI, S FURUE, K KUWABARA, J IKEUCHI, K TANAKA, H ONOYAMA, M YAMAMOTO
Journal: Gut (1999)

Phospholipase A 2 and acute pancreatitis in rats EDITOR,-Phospholipase A 2 (PLA 2 ) is an enzyme that cleaves fatty acids from phospholipids, leading to the generation of inflammatory eicosanoids. 1 The group II isoenzyme of phospholipase A 2 (PLA 2 -II) is raised in peripheral blood during various inflammatory states. 2 PLA 2 is induced in vitro and in vivo by the classic acute phase cytokine interleukin 6. 3 4 Therefore PLA 2 -II can be regarded as an acute phase protein.With great interest we read the well designed study of Furue et al (Gut 1997;41:826-31) who could clearly show that most PLA 2 activity during sodium deoxycholate induced acute pancreatitis in rats is due to the group II isoenzyme.Furue and colleagues suggested that the liver is the main source of this enzyme in their experiments because Nevalainen and coworkers 5 and Crowl and coworkers 3 described PLA 2 -II activity in human hepatocytes.We agree with the suggestion of Furue et al that PLA 2 -II is produced in human hepatocytes like classic acute phase proteins.This was also demonstrated by our group, 6 but we think that the extrapolation of these findings from human tissue to animal experiments, as done by Furue et al, requires some clarification.Hatch et al were able to show that liver macrophages and not hepatocytes were the main source of PLA 2 -II in rats during endotoxin induced acute phase reaction. 7As a consequence, liver macrophages but not hepatocytes could also be the main source of PLA 2 -II in the animal experiments presented by Furue and collaborators.Therefore an alternative pathogenetic mechanism leading to liver damage in experimental induced acute pancreatitis should be taken into account.Our alternative pathogenetic sequence is that PLA 2 -II released by liver macrophages attacks adjacent already damaged liver tissue, thus leading to complete destruction of hepatocytes with subsequent release of aminotransferases into the circulation, as shown by Furue et al.In conclusion, we agree that PLA 2 -II could be an important mediator of liver failure in acute pancreatitis, but alternative pathomechanisms resulting from diVerent production sites should be discussed.
Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.
Authors: Si-Yu Wang, Zui Liu, Wei Ou, Ning Li, Hui-qi Wu, Xiao-Yong Mao, Cheng Yuan
Journal: Journal of Clinical Oncology (2017)

e20626 Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has been proved to be effective and safe in treating patients with advanced gastric cancer who failed to second-line chemotherapy. As the VEGFR-2 targeted therapy has made encouraging progress in the treatment of a broad range of malignancies, we aimed to explore the efficacy and safety of apatinib in treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Methods: In this open-label single-arm, phase II study, patients were treated with apatinib alone in daily dose of 250 mg, po, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Results: From January 28, 2016 to December 31, 2016, 33 patients were enrolled, including 9 patients with squamous carcinoma and 24 patients with adenocarcinoma. Fourteen patients were detected as EGFR mutations and all the cases have no anaplastic lymphoma kinase (ALK) fusion gene. The median progression free survival (mPFS) of the whole group was 4.0 (95% confidence interval [CI], 0-8.2) months, while the mPFS of adenocarcinoma was 4.0 (95% CI, 2.1-5.9) months and the mPFS of squamous carcinoma was 5.5 (95% CI, 0-13.9) months (P = 0.245). Among the 33 patients, partial response was noted in 3 patients (9.09 %) and stable disease in 14 (42.42%). The disease control rate (DCR) was 51.52%. The common side effects of apatinib were hypertension, hand-foot syndrome and proteinuria, which accounted for 33.33%, 24.24%, and 15.15%, and no grade 3/4 adverse reactions occurred. The toxicity of apatinib was controllable and tolerable. Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Prospective studies are needed for further investigation.