tbuckley/cabot-search huggingface dataset:
Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil
Authors: R. J. Barst, N. Galie, R. Naeije, G. Simonneau, R. Jeffs, C. Arneson, L. J. Rubin
Journal: European Respiratory Journal (2006)

Pulmonary arterial hypertension (PAH) is fatal if untreated. Intravenous epoprostenol improves exercise capacity and haemodynamics in PAH, and increases survival in idiopathic PAH (IPAH). To evaluate the effects of subcutaneous (SC) treprostinil, a longer-acting prostacyclin analogue, followed by the addition of other PAH therapies if needed, 860 PAH patients treated with SC treprostinil for up to 4 yrs were followed. Survival is reported as Kaplan–Meier estimates. For 332 IPAH patients with baseline haemodynamics, observed survival is also compared with predicted survival using the National Institute of Health formula. Out of the 860 patients, 199 (23%) discontinued due to adverse events, 136 (16%) died, 117 (14%) discontinued due to deterioration, 29 (3%) withdrew consent and 11 (1%) underwent transplantation. In total, 97 patients (11%) switched from SC treprostinil to an alternative prostacyclin analogue; bosentan was added in 105 patients (12%) and sildenafil in 25 (3%). In conclusion, survival was 87–68% over 1–4 yrs for all 860 patients and 88–70% over 1–4 yrs with subcutaneous treprostinil monotherapy. For the idiopathic pulmonary arterial hypertension subset with baseline haemodynamics (n = 332), survival was 91–72% over 1–4 yrs. In contrast, predicted survival was 69–38% over 1–4 yrs. The safety profile for long-term subcutaneous treprostinil was consistent with previous short-term trials with no unexpected adverse events.
Coordination of DNA Mismatch Repair and Base Excision Repair Processing of Chemotherapy and Radiation Damage for Targeting Resistant Cancers
Authors: Timothy J. Kinsella
Journal: Clinical Cancer Research (2009)

Abstract DNA damage processing by mismatch repair (MMR) and/or base excision repair (BER) can determine the therapeutic index following treatment of human cancers using radiation therapy and several classes of chemotherapy drugs. Over the last decade, basic and translational cancer research in DNA repair has led to an increased understanding of how these two DNA repair pathways can modify cytotoxicity to chemotherapy and/or ionizing radiation treatments in both normal and malignant tissues. This Molecular Pathways article provides an overview of the current understanding of mechanisms involved in MMR and BER damage processing, including insights into possible coordination of these two DNA repair pathways after chemotherapy and/or ionizing radiation damage. It also introduces principles of systems biology that have been applied to better understand the complexities and coordination of MMR and BER in processing these DNA damages. Finally, it highlights novel therapeutic approaches to target resistant (or DNA damage tolerant) human cancers using chemical and molecular modifiers of chemotherapy and/or ionizing radiation including poly (ADP-ribose) polymerase inhibitors, methoxyamine and iododeoxyuridine (and the prodrug, 5-iodo-2-pyrimidinone-2'-deoxyribose).
Molecular Genetics of Acute Lymphoblastic Leukemia
Authors: Scott A. Armstrong, A. Thomas Look
Journal: Journal of Clinical Oncology (2005)

From its beginnings two decades ago with the analysis of chromosomal translocation breakpoints, research into the molecular pathogenesis of acute lymphoblastic leukemia (ALL) has now progressed to the large-scale resequencing of candidate oncogenes and tumor suppressor genes in the genomes of ALL cases blocked at various developmental stages within the B- and T-cell lineages. In this review, we summarize the findings of these investigations and highlight how this information is being integrated into multistep mutagenesis cascades that impact specific signal transduction pathways and synergistically lead to leukemic transformation. Because of these advances, fueled by improved technology for mutational analysis and the development of small-molecule drugs and monoclonal antibodies, the future is bright for a new generation of targeted therapies. Best illustrated by the successful introduction of imatinib mesylate, these new treatments will interfere with disordered molecular pathways specific for the leukemic cells, and thus should exhibit much less toxicity and fewer long-term adverse effects than currently available therapeutic modalities.
P04.07 * EXPRESSION PROFILE OF ANGIOGENIC FACTORS IN PAIRED INITIAL AND RECURRENT GLIOBLASTOMA
Authors: E. Tabouret, A. Tchoghandjian, E. Denicolai, C. Delfino, P. Metellus, M. Barrie, C. Boucard, L. Ouafik, D. Figarella-Branger, O. Chinot
Journal: Neuro-Oncology (2014)

BACKGROUND: Angiogenesis is one of the key features of Glioblastoma (GB). Our objective was to identify the changes in the expression of angiogenic factors in GB after radio-chemotherapy. METHODS: Analysis of all patients with available frozen tumor material from initial and recurrent surgery for GB treated with chemo-radiotherapy (CTRT) in first line setting in our institution between 2003 and 2009. Molecular screening was realized using two types of RT2Profiler PCR arrays (Qiagen®). The RNA expression profile of selected genes was validated using quantitative RT PCR. Protein expression was analyzed by immunohistochemistry (IHC). Explants of newly GB were treated with temozolomide, radiotherapy and anti-CXCR4 (AMD3100). RESULTS: Twenty nine patients were included with median age of 57.1 years (37.2-74.1). The RT2Profiler PCR arrays results allowed a selection of seven genes: VEGFA, VEGFR2, VEGFR1, Adrenomedullin, SDF1, CXCR4, and HIF1α. The steady state levels of CXCR4 RNA at recurrence was significantly increased (p = 0.029) while HIF1α RNA was significantly decreased (p = 0.009). A trend for a decrease of VEGFR2 RNA (p = 0.081) and an increase of SDF1 RNA (p = 0.107) was observed. Changes of SDF1 RNA tended to be correlated to changes of CXCR4 RNA (p = 0.077) and inversely correlated to changes of HIF1 α RNA (p = 0.064). By IHC, VEGFR2 staining was significantly decreased at recurrence (p = 0.004) while SDF1 expression tended to increased (p = .096). Medians initial and at recurrence overall survival (OSI and OSR) of this selected population were 25.5 (95% confidence interval (CI) 17-34) and 11.4 (95%CI 9-13.9) months respectively. By multivariate analysis, VEGFR2 RNA initial and at recurrence levels were significantly correlated to OSI (p = 0.019, Hazard ratio (HR) =3.650) and OSR (p = 0.024, HR = 2.536) while HIF1 α RNA level at baseline was correlated to OSI (p = 0.012, HR = 0.300). In newly GB explants, a higher anti-tumoral effect was observed with the combination of AMD3100 and CTRT versus CTRT alone. CONCLUSION: Acquired resistance of GB to chemo-radiation could be associated with a switch of angiogenic pattern from VEGFR2-HIF1α to SDF1-CXCR4 pathway, leading to new perspectives in angiogenic modulation and GB treatment.
IMPAIRED PLATELET PROSTACYCLIN BINDING IN ACUTE MYOCARDIAL INFARCTION
Authors: K. Jaschonek, H. Weisenberger, K.R. Karsch, W. Renn, W. Daiss, D. Schenzle, P. Ostendorf, S. Dalby Kristensen, E. Berg Schmidt, H. Rud Andersen, J. Dyerberg
Journal: The Lancet (1984)
Papillary and Follicular Thyroid Carcinomas Show Distinctly Different Microarray Expression Profiles and Can Be Distinguished by a Minimum of Five Genes
Authors: Micheala A. Aldred, Ying Huang, Sandya Liyanarachchi, Natalia S. Pellegata, Oliver Gimm, Sissy Jhiang, Ramana V. Davuluri, Albert de La Chapelle, Charis Eng
Journal: Journal of Clinical Oncology (2004)

Purpose We have previously conducted independent microarray expression analyses of the two most common types of nonmedullary thyroid carcinoma, namely papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In this study, we sought to combine our data sets to shed light on the similarities and differences between these tumor types. Materials and Methods Microarray data from six PTCs, nine FTCs, and 13 normal thyroid samples were normalized to remove interlaboratory variability and then analyzed by unsupervised clustering, t test, and by comparison of absolute and change calls. Expression changes in four genes not previously implicated in thyroid carcinogenesis were verified by reverse transcriptase polymerase chain reaction on these same samples, together with eight additional FTC tumors. Results PTCs showed two distinct groups of genes that were either over- or underexpressed compared with normal thyroid, whereas the predominant changes in FTCs were of decreased expression. Five genes could collectively distinguish the two tumor types. PTCs showed overexpression of CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6) but showed no change in expression of caveolin-1 (CAV1) or -2 (CAV2); conversely, FTCs did not express CLDN10 and had decreased expression of IGFBP6 and/or CAV1 and CAV2. Conclusion PTC and FTC show distinctive microarray expression profiles, suggesting that either they have different molecular origins or they diverge distinctly from a common origin. Furthermore, if verified in a larger series of tumors, these genes could, in combination with known tumor-specific chromosome translocations, form the basis of a valuable diagnostic tool.
Localization of H-2 antigens on mouse trophoblast cells.
Authors: S Chatterjee-Hasrouni, P K Lala
Journal: The Journal of Experimental Medicine (1979)

The presence of H-2 antigens of the paternal and maternal haplotypes on mouse trophoblast cells was examined at several stages of pregnancy by using a sensitive immunolabeling technique followed by quantitative radioautography. Results revealed the presence of H-2 antigens (determined by the K or D loci) of both parental haplotypes on the F1 trophoblast cells. At 14-16 d of gestation, the antigen density was equivalent to that on adult thymocytes and there was a further 50% increase on day 18. H-2 antigens of both parental haplotypes are also found to be expressed on 11-13 d trophoblast cells.
Breast Cancer Adjuvant Chemotherapy Decisions in Older Women: The Role of Patient Preference and Interactions With Physicians
Authors: Jeanne S. Mandelblatt, Vanessa B. Sheppard, Arti Hurria, Gretchen Kimmick, Claudine Isaacs, Kathryn L. Taylor, Alice B. Kornblith, Anne-Michelle Noone, Gheorghe Luta, Michelle Tallarico, William T. Barry, Lisa Hunegs, Robin Zon, Michael Naughton, Eric Winer, Clifford Hudis, Stephen B. Edge, Harvey Jay Cohen, Hyman Muss
Journal: Journal of Clinical Oncology (2010)

Breast cancer chemotherapy decisions in patients > or = 65 years old (older) are complex because of comorbidity, toxicity, and limited data on patient preference. We examined relationships between preferences and chemotherapy use.
A cell surface marker gene transferred with a retroviral vector into CD34+ cord blood cells is expressed by their T-cell progeny in the SCID- hu thymus
Authors: C Champseix, V Marechal, I Khazaal, O Schwartz, S Fournier, N Schlegel, G Dranoff, O Danos, P Blot, E Vilmer, JM Heard, B Peault, P Lehn
Journal: Blood (1996)
Procainamide delivery to ischemic canine myocardium following rapid intravenous administration.
Authors: T L Wenger, D J Browning, C E Masterton, M B Abou-Donia, F E Harrell, R J Bache, H C Strauss
Journal: Circulation Research (1980)

This study delineates the time course of procainamide accumulation in myocardium after bolus administration and its relationship to regional myocardial blood flow.The left circumflex coronary artery was ligated in 28 open-chest dogs.This was followed 40 minutes later by injection into the left atrium of labeled microspheres. 14C-labeled procainamide, 1.5 mg/kg, was then administered as a single 1-minute infusion in 24 dogs, and four dogs were killed at each of six different times (1.5-15 minutes) after onset of drug infusion.In four additional dogs, the same dose of labeled drug was administered as a 1-minute infusion repeated every 5 minutes; after the fifth dose, the animals were killed.Myocardial sections were analyzed for regional blood flow and regional procainamide concentration.In the ischemic region, procainamide accumulated more slowly, and peak concentrations were lower than in the nonischemic region, being lowest in the most severely ischemic sections.The drug was thus distributed heterogenously through the myocardium early after bolus administration.Over time, however, this distribution became more homogenous with concentrations in nonischemic sections falling off more rapidly than in ischemic sections.Predicted steady state concentrations were achieved after 15 minutes in mildly ischemic sections (0.31-0.90 ml/min per g) but had not been reached by 25 minutes in severely ischemic sections.We conclude that ischemic myocardium, a potential site of antiarrhythmic drug action, represents a progression of pharmacokinetic compartments increasingly distal from the central compartment, depending on the severity of ischemia.CircRes 46: [789][790][791][792][793][794][795] 1980 THE HEART is generally considered to be in rapid distribution equilibrium with the central pharmacokinetic compartment because it is highly perfused (Gibaldi and Perrier, 1975;Koch-Weser, 1977).However, if the rate of drug equilibration between plasma and myocardium is related to perfusion, then ischemic areas of myocardium should behave as peripheral pharmacokinetic compartments.Depending on their blood flow, such areas might therefore be classifiable as more proximal or more distal, that is, requiring less or more time to equilibrate with the central compartment.Because ventricular premature depolarizations in patients with coronary artery disease probably originate from areas of ischemic myocardium (Waldo and Kaiser, 1973;Boineau and Cox, 1973), the sites of action of antiarrhythmic drugs may be in periph-
Antithrombotic effects of recombinant human soluble thrombomodulin (rhs‐TM) on arteriovenous shunt thrombosis in rats
Authors: Yoshikazu Aoki, Ryoichi Takei, Mitsunobu Mohri, Yasunori Gonda, Komakazu Gomi, Taisuke Sugihara, Takao Kiyota, Shuji Yamamoto, Torao Ishida, Ikuro Maruyama
Journal: American Journal of Hematology (1994)

Abstract We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs‐TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs‐TM (0.5–4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose‐dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25–200 U/kg) and in those treated with rhs‐TM (0.5–4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs‐TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs‐TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs‐TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis. © 1994 Wiley‐Liss, Inc.
Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial
Authors: Bradley J Monk, Andrés Poveda, Ignace Vergote, Francesco Raspagliesi, Keiichi Fujiwara, Duk-Soo Bae, Ana Oaknin, Isabelle Ray-Coquard, Diane M Provencher, Beth Y Karlan, Catherine Lhommé, Gary Richardson, Dolores Gallardo Rincón, Robert L Coleman, Thomas J Herzog, Christian Marth, Arija Brize, Michel Fabbro, Andrés Redondo, Aristotelis Bamias, Marjan Tassoudji, Lynn Navale, Douglas J Warner, Amit M Oza
Journal: The Lancet Oncology (2014)
Targeting <i>miR-21</i> to Treat Psoriasis
Authors: Juan Guinea-Viniegra, María Jiménez, Helia B. Schonthaler, Raquel Navarro, Yolanda Delgado, María José Concha-Garzón, Erwin Tschachler, Susanna Obad, Esteban Daudén, Erwin F. Wagner
Journal: Science Translational Medicine (2014)

Targeting miR-21 may be a new way to treat psoriasis.
Measuring and Monitoring Success in Compressing Morbidity
Authors: James F. Fries
Journal: Annals of Internal Medicine (2003)

The Compression of Morbidity paradigm, introduced in 1980, maintains that if the average age at first infirmity, disability, or other morbidity is postponed and if this postponement is greater than increases in life expectancy, then cumulative lifetime morbidity will decreasecompressed between a later onset and the time of death. The National Long-Term Care Survey, the National Health Interview Survey, and other data now document declining disability trends beginning in 1982 and accelerating more recently. The decline is about 2% per year, contrasted with a decline in mortality rates of about 1% per year, thereby documenting compression of morbidity in the United States at the population level. Longitudinal studies now link good health risk status with long-term reductions in cumulative lifetime disability; persons with few behavioral health risks have only one-fourth the disability of those who have more risk factors, and the onset of disability is postponed from 7 to 12 years, far more than any increases in longevity in the groups. Randomized, controlled trials of health enhancement programs in elderly populations show reduction in health risks, improved health status, and decreased medical care utilization. Health policy initiatives now being undertaken have promise of increasing and consolidating health gains for the elderly.
Increased bronchoalveolar granulocytes and granulocyte/macrophage colony-stimulating factor during exacerbations of chronic bronchitis
Authors: B Balbi, C Bason, E Balleari, F Fiasella, A Pesci, R Ghio, F Fabiano
Journal: European Respiratory Journal (1997)

Although inflammatory changes are found throughout the airways of patients with chronic bronchitis, the mechanisms of the pathogenesis of chronic bronchitis are still unclear. The aim of this study was to investigate airways inflammation in patients with and without an exacerbation of bronchitis. Thirteen chronic bronchitic patients and nine normal subjects were studied. Eight of the patients were studied under baseline conditions (B), and five during an exacerbation of bronchitis (E). Bronchoscopy and bronchoalveolar lavage (BAL) with cytological analysis were performed, and the levels of granulocyte/macrophage colony-stimulating factor (GM-CSF) were determined in sera and in BAL supernatants by a solid phase enzyme immunoassay. Compared with patients under baseline conditions, chronic bronchitic patients with an exacerbation had increased numbers of BAL neutrophils (10+/-3 and 83+/-18x10(3) cells x mL(-1), respectively; p<0.0001) and of BAL eosinophils (1.9+/-0.5 and 6.7/-1.9x10(3) cells x mL(-1), respectively; p=0.014). Patients with chronic bronchitis, as a whole, had significantly increased levels of BAL GM-CSF compared to control subjects (36+/-5 and 19+/-4 pg x mL(-1), respectively; p=0.035), and similar levels of serum GM-CSF. Serum levels of GM-CSF were markedly increased in chronic bronchitic patients with an exacerbation, as compared with patients under baseline conditions (1.4+/-0.4 and 13+/-1 pg x mL(-1), respectively; p <0.0001). BAL levels of GM-CSF were also increased in chronic bronchitic patients with an exacerbation (25+/-5 and 54+/-8 pg x mL(-1), respectively; p=0.009). During exacerbations of chronic bronchitis there are changes in the cell populations in bronchoalveolar lavage of patients consistent with a recruitment of polymorphonuclear leucocytes in the airway lumen. The increased levels of granulocyte/macrophage colony-stimulating factor might suggest a role for this cytokine in the inflammatory processes of chronic bronchitis.
Laparoendoscopic Single-site Surgery in Urology: Worldwide Multi-institutional Analysis of 1076 Cases
Authors: Jihad H. Kaouk, Riccardo Autorino, Fernando J. Kim, Deok Hyun Han, Seung Wook Lee, Sun Yinghao, Jeffrey A. Cadeddu, Ithaar H. Derweesh, Lee Richstone, Luca Cindolo, Anibal Branco, Francesco Greco, Mohamad Allaf, René Sotelo, Evangelos Liatsikos, Jens-Uwe Stolzenburg, Abhay Rane, Wesley M. White, Woong Kyu Han, Georges-Pascal Haber, Michael A. White, Wilson R. Molina, Byong Chang Jeong, Joo Yong Lee, Wang Linhui, Sara Best, Sean P. Stroup, Soroush Rais-Bahrami, Luigi Schips, Paolo Fornara, Phillip Pierorazio, Camilo Giedelman, Jae Won Lee, Robert J. Stein, Koon Ho Rha
Journal: European Urology (2011)
Search for hepatitis B virus cell receptors reveals binding sites for interleukin 6 on the virus envelope protein.
Authors: A R Neurath, N Strick, P Sproul
Journal: The Journal of Experimental Medicine (1992)

The major target organ for hepatitis B virus (HBV) is the liver. However, cells other than hepatocytes, including peripheral blood lymphocytes and monocytes, may become infected with HBV. The cell receptor binding site was assigned to the preS(21-47) segment of the HBV envelope protein. HBV receptors were detected on human liver and hepatoma cells, on B lymphocytes, and, as shown here, on monocytes, and T cell lines, activated by Escherichia coli lipopolysaccharide and concanavalin A, respectively. The cell receptors for HBV have not been characterized until now. The detection of HBV receptors and their "activation antigen" characteristic on distinct cells suggested paths for identification of the receptors with already defined cell surface proteins. This search revealed that interleukin 6 contains recognition sites for the preS(21-47) sequence and mediates HBV-cell interactions. Thus, HBV belongs to a group of viruses utilizing cytokines or cytokine receptors for replication and interference with the host immune system.
Study Reveals Gaps in Advice to New Mothers on Infant Care
Authors: Julie A. Jacob
Journal: JAMA (2015)

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