Search results for "pyrimidine"

showing 10 items of 589 documents

Perspectives for the Treatment of Brucellosis in the 21st Century: The Ioannina Recommendations

2007

Policy Forum. Competing interests: ER has received research grants from Daiichi, Bayer, and Theravance and has served as a consultant to Pfizer, Theravance, Bayer, Wyeth, Rosetta, and BiondVax. Summary Points Brucellosis remains the commonest anthropozoonosis worldwide, and its treatment remains complex, requiring protracted administration of more than one antibiotic. In November 2006, a consensus meeting aimed at reaching a common specialist statement on the treatment of brucellosis was held in Ioannina, Greece under the auspices of the International Society of Chemotherapy and the Institute of Continuing Medical Education of Ioannina. The author panel suggests that the optimal treatment o…

:Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings]Veterinary medicine:Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides::Streptomycin [Medical Subject Headings]:Phenomena and Processes::Microbiological Phenomena::Drug Resistance Microbial [Medical Subject Headings]DiseaseGlobal Health:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]:Health Care::Population Characteristics::Health::World Health [Medical Subject Headings]Terminología como AsuntoBrucellosi:Organisms::Eukaryota::Animals [Medical Subject Headings]:Health Care::Health Care Economics and Organizations::Organizations::International Agencies::United Nations::World Health Organization [Medical Subject Headings]Policy ForumMedicine in Developing CountriesGentamicinasDrug Resistance MicrobialBrucelosisAdhesión a DirectrizGeneral MedicineHumanosDrug CombinationsAntibacterianosDoxycyclineStreptomycinEstreptomicinaMedicine:Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds with 4 or More Rings::Rifamycins::Rifampin [Medical Subject Headings]Drug Therapy CombinationGuideline AdherenceRifampinFluoroquinolonesSalud Mundialmedicine.medical_specialtyEfficacyResultado del TratamientoInvestigación BiomédicaRecurrenciaTherapeuticsWorld Health OrganizationMicrobiologyAntibiotic resistanceTerminology as Topic:Disciplines and Occupations::Social Sciences::Internationality::International Cooperation::Developing Countries [Medical Subject Headings]HumansMedical journalIntensive care medicineDeveloping Countries:Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Pyrimidines::Trimethoprim::Trimethoprim-Sulfamethoxazole Combination [Medical Subject Headings]medicine.diseaseCotrimoxazoleAnimalesQuimioterapia:Humanities::Humanities::History::History Modern 1601-::History 21st Century [Medical Subject Headings]GentamicinsBrucel·losiBiomedical ResearchCommunicable diseases:Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 2-Ring::Quinolines::Quinolones::Fluoroquinolones [Medical Subject Headings]Human diseaseRecurrence:Chemicals and Drugs::Pharmaceutical Preparations::Drug Combinations [Medical Subject Headings]:Information Science::Information Science::Communication::Language::Linguistics::Terminology as Topic [Medical Subject Headings]biologyIraqi patientsRMetaanalysis:Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Brucellosis [Medical Subject Headings]Historia del Siglo XXIAnti-Bacterial AgentsCombinación Trimetoprim-SulfametoxazolTreatment OutcomeInfectious Diseases:Disciplines and Occupations::Natural Science Disciplines::Science::Research::Biomedical Research [Medical Subject Headings]:Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons Cyclic::Hydrocarbons Aromatic::Polycyclic Hydrocarbons Aromatic::Naphthacenes::Tetracyclines::Doxycycline [Medical Subject Headings]Fluoroquinolonas:Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings]:Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides::Gentamicins [Medical Subject Headings]Países en Desarrollo:Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Therapy Combination [Medical Subject Headings]BrucellaHistory 21st CenturyBrucellosisWorld healthTrimethoprim Sulfamethoxazole Drug CombinationmedicineAnimals:Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings]Resistencia a Medicamentosbusiness.industryOrganización Mundial de la SaludBrucellosisMalalties infecciosesTerapèuticabiology.organism_classificationCombinación de MedicamentosDoxiciclinaTherapybusinessBrucella melitensisPLoS Medicine
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A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid …

2016

Abstract Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies co…

AdultMale0301 basic medicineProto-Oncogene Proteins c-aktAdministration OralPharmacologyIpatasertibDrug Administration SchedulePiperazines03 medical and health sciences0302 clinical medicineCell Line TumorNeoplasmsHumansPTENMedicineProtein Kinase InhibitorsProtein kinase BPI3K/AKT/mTOR pathwayAgedbiologybusiness.industryMiddle AgedXenograft Model Antitumor AssaysSmall moleculePyrimidines030104 developmental biologyOncologyCell culture030220 oncology & carcinogenesisPharmacodynamicsbiology.proteinFemalebusinessProto-Oncogene Proteins c-akt
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Phase I Pharmacokinetic/Pharmacodynamic Study of MLN8237, an Investigational, Oral, Selective Aurora A Kinase Inhibitor, in Patients with Advanced So…

2012

Abstract Purpose: Aurora A kinase (AAK) is a key regulator of mitosis and a target for anticancer drug development. This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors. Experimental Design: Patients received MLN8237 once daily or twice daily for 7, 14, or 21 consecutive days, followed by 14 days recovery, in 21-, 28-, or 35-day cycles. Dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) for the 7- and 21-day schedules were determined. Pharmacokinetic parameters were derived from plasma concentration–time profiles. AAK inhibition in…

AdultMaleCancer ResearchNeutropeniaMaximum Tolerated DoseBiopsyAurora A kinaseAntineoplastic AgentsProtein Serine-Threonine KinasesPharmacologyNeutropeniachemistry.chemical_compoundPharmacokineticsAurora KinasesNeoplasmsBiopsyHumansMedicineStomatitisAgedNeoplasm StagingStomatitismedicine.diagnostic_testbusiness.industryCancerAzepinesMiddle Agedmedicine.diseasePyrimidinesOncologychemistryPharmacodynamicsAlisertibFemalebusinessClinical Cancer Research
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[18F]5-fluoro-2-deoxyuridine-PET for imaging of malignant tumors and for measuring tissue proliferation

2003

The nucleoside 5-fluoro-2-deoxyuridine is a pyrimidine analogue accumulating in proliferative cells. We prospectively evaluated biodistribution of the PET tracer [(18)F]5-fluoro-2-deoxyuridine (FdUrd), its value for imaging malignant tumors, and its correlation to both [(18)F]2-fluoro-2-deoxyglucose (FDG)-PET findings and histological proliferation indices. In 11 previously untreated patients (5 lung carcinoma; 3 soft tissue sarcoma; 2 gastrointestinal carcinoma; 1 non-Hodgkin lymphoma [NHL]), mean doses of 290 MBq FdUrd and 390 MBq FDG were administered intravenously on subsequent days. Static PET scans were initiated 50-70 min after administration and the mean standardized uptake values (…

AdultMaleCancer ResearchPathologymedicine.medical_specialtyLung NeoplasmsProliferation indexUrinary BladderKidneyBone and BonesPyrimidine analogueFluorodeoxyglucose F18NeoplasmsmedicineCarcinomaHumansTissue DistributionRadiology Nuclear Medicine and imagingProspective StudiesAgedGastrointestinal NeoplasmsNeoplasm StagingPharmacologymedicine.diagnostic_testbusiness.industryLymphoma Non-HodgkinSoft tissue sarcomaKidney metabolismSarcomaGeneral MedicineMiddle Agedmedicine.diseaseLymphomaKi-67 AntigenLiverOncologyPositron emission tomographyFemaleSarcomaRadiopharmaceuticalsbusinessNuclear medicineCell DivisionTomography Emission-Computed
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Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.

2003

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 c…

AdultMaleCancer Researchmedicine.medical_specialtyAntimetabolites AntineoplasticFusion Proteins bcr-ablAlpha interferonAntineoplastic AgentsBiologyGastroenterologyPiperazinesCytogeneticsRecurrenceRisk Factorshemic and lymphatic diseasesInternal medicineLeukemia Myelogenous Chronic BCR-ABL PositivemedicineHumansProspective StudiesRNA MessengerneoplasmsInterferon alfaAgedHematologyABLCross-Over Studiesbreakpoint cluster regionCytarabineInterferon-alphaImatinibHematologyMiddle Agedmedicine.diseasePrognosisPyrimidinesTreatment OutcomeOncologyImmunologyBenzamidesCytarabineImatinib MesylateFemaleChronic myelogenous leukemiamedicine.drugLeukemia
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Rosuvastatin Prevents Conduit Artery Endothelial Dysfunction Induced by Ischemia and Reperfusion by a Cyclooxygenase-2–Dependent Mechanism

2010

ObjectivesThe purpose of this study was to determine whether single-dose rosuvastatin (40 mg) protects against ischemia and reperfusion (IR)–induced endothelial dysfunction in humans and whether this effect is cyclooxygenase (COX)-2 dependent.BackgroundAnimal studies have demonstrated that rosuvastatin can limit damage and improve recovery after IR.MethodsIn a double-blind, parallel design, 20 volunteers were randomized to a single dose of oral rosuvastatin (40 mg) or placebo. Twenty-four hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protoc…

AdultMaleEndotheliumendotheliumAdolescentPremedicationIschemiaMyocardial Reperfusion InjuryPharmacologyPlaceboYoung AdultDouble-Blind Methodmedicineischemia reperfusionHumansRosuvastatinEndothelial dysfunctionRosuvastatin CalciumSulfonamidesCyclooxygenase 2 Inhibitorsbusiness.industryModels Cardiovascularnutritional and metabolic diseases3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitormedicine.diseaseFluorobenzenesVasodilationRosuvastatin Calciummedicine.anatomical_structurePyrimidinesCelecoxibCyclooxygenase 2AnesthesiaIschemic Preconditioning MyocardialRadial ArteryCelecoxibIschemic preconditioningPyrazolesFemaleEndothelium VascularHydroxymethylglutaryl-CoA Reductase InhibitorsbusinessCardiology and Cardiovascular Medicinerosuvastatinmedicine.drugJournal of the American College of Cardiology
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Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma : results From the Open-Label, Multicenter, Phase II DAWN Study

2018

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee–assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle …

AdultMaleOncologyCancer Researchmedicine.medical_specialtymedicine.drug_classFollicular lymphomaPhases of clinical researchTyrosine-kinase inhibitor03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePiperidinesRecurrenceT-Lymphocyte SubsetsChemoimmunotherapyInternal medicineBiomarkers TumormedicineHumansLymphoma FollicularProtein Kinase InhibitorsAgedAged 80 and overManchester Cancer Research Centrebusiness.industryResearchInstitutes_Networks_Beacons/mcrcAdenineMiddle Agedmedicine.diseaseLymphomaPyrimidinesTreatment OutcomeOncologychemistry030220 oncology & carcinogenesisIbrutinibPyrazolesFemaleRefractory Follicular LymphomabusinessProgressive disease030215 immunology
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Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral b…

2001

We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT. At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP). Patients were evaluated for hematologic, cytogenetic and molecular response, survival and toxicity. In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses. Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response. Two of five patients had transient reductions in WBC and…

AdultMaleOncologyCancer Researchmedicine.medical_specialtymedicine.medical_treatmentFusion Proteins bcr-ablAntineoplastic AgentsPhiladelphia chromosomeTransplantation AutologousPiperazinesLeukemia Myelogenous Chronic BCR-ABL Positivehemic and lymphatic diseasesInternal medicinemedicineHumansEnzyme InhibitorsChemotherapyABLbusiness.industryHematopoietic Stem Cell Transplantationbreakpoint cluster regionHematologyMiddle AgedProtein-Tyrosine Kinasesmedicine.diseaseCombined Modality TherapyHematologic ResponseBlood Cell CountPyrimidinesTreatment OutcomeImatinib mesylateOncologyBenzamidesToxicityImmunologyImatinib MesylateFemaleComplicationbusinessLeukemia
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Efficacy and safety of imatinib in adult patients with c-kit–positive acute myeloid leukemia

2004

Abstract This phase 2 pilot study was conducted to determine the efficacy and safety of imatinib mesylate in patients with c-kit–positive acute myeloid leukemia (AML) refractory to or not eligible for chemotherapy. Twenty-one patients were enrolled and received imatinib 600 mg orally once daily. Five responses were seen primarily in patients, starting with relatively low blast counts in bone marrow (BM) and peripheral blood (PB): 2 patients who were considered refractory on chemotherapy on the basis of persistence of blasts in PB and BM met the criteria for complete hematologic remission, 1 patient had no evidence of leukemia, and 2 patients achieved a minor response. Treatment with imatini…

AdultMaleOncologymedicine.medical_specialtyAdolescentmedicine.medical_treatmentDNA Mutational AnalysisImmunologyAntineoplastic AgentsCell CountPilot ProjectsBiochemistryPiperazineshemic and lymphatic diseasesInternal medicineHumansMedicinePhosphorylationneoplasmsAgedSalvage TherapyChemotherapybusiness.industryRemission InductionMyeloid leukemiaImatinibCell BiologyHematologyMiddle Agedmedicine.diseaseImmunohistochemistryClinical trialProto-Oncogene Proteins c-kitLeukemiaPyrimidinesTreatment OutcomeImatinib mesylatemedicine.anatomical_structureLeukemia MyeloidAcute DiseaseBenzamidesImmunologyImatinib MesylateImmunohistochemistryFemaleBone marrowBlast Crisisbusinessmedicine.drugBlood
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Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB ) study with therapeutic implications.

2009

Aims:  To analyse the presence of collagen type I alpha 1–platelet-derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables. Methods and results:  Multiplex reverse transcriptase-polymerase chain reaction was carried out using frozen tissue. Our series contained 14 men and six women. Histologically, most cases were of conventional type (n = 9), followed by fibrosarcoma (n = 4), Bednar tumour (n = 2), sclerosing (n = 2), myoid (n = 1) and atrophic (n = 1) DFSP, and giant cell fibroblastoma (n = 1). Immunohistochemistry revealed CD34 express…

AdultMalePathologymedicine.medical_specialtyHistologySkin NeoplasmsAdolescentCD34Antineoplastic AgentsBiologyCollagen Type IPiperazinesPathology and Forensic MedicineYoung AdultDermatofibrosarcoma protuberansmedicineHumansAgedDNA PrimersAged 80 and overPDGFBBase SequenceDermatofibrosarcomaGeneral MedicineGiant-cell fibroblastomaMiddle Agedmedicine.diseaseMohs SurgeryCollagen Type I alpha 1 ChainImatinib mesylatePyrimidinesFusion transcriptCOL1A1/PDGFB Fusion GeneBenzamidesImatinib MesylateFemaleGene FusionDermatofibrosarcomaGenes sisHistopathology
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