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showing 10 items of 5959 documents

Association of 5-FU Therapeutic Drug Monitoring to DPD Phenotype Assessment May Reduce 5-FU Under-Exposure

2020

In order to limit 5-fluorouracil (5-FU) toxicity, some health agencies recommend evaluating dihydropyrimidine dehydrogenase (DPD) deficiency before any 5-FU treatment introduction. In our study, we investigated relationships between 5-FU clearance and markers of DPD activity such as uracilemia (U), dihydrouracilemia (UH2)/U ratio, or genotype of the gene encoding DPD (DPYD). All patients with gastrointestinal cancers who received 5-FU-based regimens form March 2018 to June 2020 were included in our study. They routinely benefited of a pre-therapeutic DPYD genotyping and phenotyping. During 5-FU infusion, blood samples were collected to measure 5-FU steady-state concentration in order to ada…

0301 basic medicinemedicine.medical_specialtyUH2/U ratioFOLFIRINOXtherapeutic drug monitoringuracilemiaPharmaceutical Sciencelcsh:Medicinelcsh:RS1-441GastroenterologyArticlelcsh:Pharmacy and materia medica03 medical and health sciences0302 clinical medicinePharmacokineticsInternal medicineDrug DiscoveryDihydropyrimidine dehydrogenaseMedicine5-FUmedicine.diagnostic_testbusiness.industrylcsh:RDPDmedicine.diseasePrimary tumorGI cancer030104 developmental biologyDocetaxelTherapeutic drug monitoring030220 oncology & carcinogenesisToxicityUH<sub>2</sub>/U ratioMolecular MedicineDPYDbusinesspharmacokineticsmedicine.drugPharmaceuticals
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Beta-glucans and cancer: The influence of inflammation and gut peptide

2017

Dietary β-glucans are soluble fibers with potentially health-promoting effects. Gut peptides are important signals in the regulation of energy and glucose homeostasis. This article reviews the effects of different enriched β-glucan food consumption on immune responses, inflammation, gut hormone and cancer. Gut hormones are influenced by enriched β-glucan food consumption and levels of such peptide as YY, ghrelin, glucagon-like peptide 1 and 2 in humans influence serum glucose concentration as well as innate and adaptive immunity. Cancer cell development is also regulated by obesity and glucose dishomeostasy that are influenced by β-glucan food consumption that in turn regulated gut hormones.

0301 basic medicinemedicine.medical_specialtybeta-GlucansInflammationbeta-Glucan03 medical and health sciences0302 clinical medicineImmune systemGlucagon-Like Peptide 1Functional FoodNeoplasmsInternal medicineβ-GlucanDrug DiscoveryGlucagon-Like Peptide 2medicineAnimalsHumansInsulinGlucose homeostasisPeptide YYCancerInflammationPharmacologyPYYAnimalChemistryDrug Discovery3003 Pharmaceutical Sciencedigestive oral and skin physiologyOrganic ChemistryGeneral MedicineGlucagon-like peptide-2Glucagon-like peptide-1GhrelinGlucose030104 developmental biologyEndocrinology030220 oncology & carcinogenesisPeptide YYNeoplasmGhrelinmedicine.symptomGLP-1GLP-2HumanHormoneEuropean Journal of Medicinal Chemistry
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Clinical application of mutational analysis in breast cancer patients: The relevance of PIK3CA analysis for precision medicine

2019

Abstract Background The identification of biomarkers to drive treatment is one of the most important objectives of precision medicine. During last years, the role of PIK3CA mutations have been related to clinical benefit deriving from treatment with PI3K, and mTOR inhibitors. In breast cancer (BC), PIK3CA mutations are widely present and the use, in clinical trials, of selective inhibitors improved clinical outcomes. The aim of this study is to assess the value of a monocentric genomic screening program to select patients for trials with experimental targeted agents. Methods We examined PIK3CA mutation in a cohort of 312 metastatic BC patients diagnosed at Hospital Clinico Valencia-INCLIVA …

0301 basic medicinemedicine.medical_specialtybusiness.industryHematologymedicine.diseaseDiscovery and development of mTOR inhibitorsPrecision medicineGenomic screeningClinical trialMutational analysis03 medical and health sciences030104 developmental biology0302 clinical medicineBreast cancerOncology030220 oncology & carcinogenesisInternal medicineCohortmedicinebusinessTriple negativeAnnals of Oncology
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2019

PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray ab…

0301 basic medicinemedicine.medical_specialtybusiness.industrySirolimus therapyLow doseDiscovery and development of mTOR inhibitorsGastroenterology03 medical and health sciences030104 developmental biology0302 clinical medicinePrimary outcome030220 oncology & carcinogenesisSirolimusInternal medicinemedicineAsymmetric overgrowthbusinessAdverse effectPathologicalGenetics (clinical)medicine.drugGenetics in Medicine
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Modulation of Heart Rate by Acute or Chronic Aerobic Exercise. Potential Effects on Blood Pressure Control.

2017

It was initially assumed that heart rate and arterial blood pressure were modulated by normal respiration and muscle contraction. The arterial baroreflex, an inverse relationship between blood pressure and heart rate, was later reported. Nonetheless, it was then assumed that those responses involved vagal modulation. We summarize available evidence on the modulation of heart rate by acute or chronic aerobic exercise as well as its potential implications on blood pressure (BP) control. Numerous studies have tried to clarify whether aerobic exercise modifies neurally-mediated vasoconstriction, but they report contradictory results. In view of these incongruities, the aim of this narrative rev…

0301 basic medicinemedicine.medical_specialtyhypertensionBlood Pressureexercise; arterial baroreflex; autonomous nervous system; blood pressure; heart rate; hypertension.Disease03 medical and health sciences0302 clinical medicineHeart Rateautonomous nervous systemInternal medicineDrug DiscoveryHeart rateRespirationHeart rate variabilityMedicineAerobic exerciseAnimalsHumansCardiovascular fitnessExercisePharmacologybusiness.industryarterial baroreflex030229 sport sciences030104 developmental biologyBlood pressureCardiologymedicine.symptombusinessVasoconstrictionCurrent pharmaceutical design
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Impact of Communicative and Informative Strategies on Influenza Vaccination Adherence and Absenteeism from Work of Health Care Professionals Working …

2019

Every year, about 20% of health care workers (HCWs) acquire influenza, continuing to work and encouraging virus spreading. Influenza vaccination coverage rates and absenteeism from work among HCWs of the University Hospital (UH) of Palermo were analyzed before and after the implementation of several initiatives in order to increase HCWs&rsquo

0301 basic medicinemedicine.medical_specialtyinformative strategieshealth care facilities manpower and serviceseducation030106 microbiologyImmunologylcsh:MedicineArticlehealth care workers03 medical and health sciences0302 clinical medicineDrug DiscoveryHealth caremedicineHealth care workerPharmacology (medical)030212 general & internal medicineWeb sitePharmacologyvaccination coveragebusiness.industrylcsh:Rvirus diseasesMean ageCommunication campaignUniversity hospitalinfluenza vaccinationVaccinationInfectious DiseasesWork (electrical)Vaccination coverageFamily medicineInformative strategieAbsenteeismcommunication campaignsbusinessVaccines
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Management of Ponatinib in Patients with Chronic Myeloid Leukemia with Cardiovascular Risk Factors

2019

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hype…

0301 basic medicinemedicine.medical_specialtymedicine.drug_class030106 microbiologyCardiovascular risk factorsType 2 diabetesDiseaseTyrosine-kinase inhibitorSettore MED/15 - Malattie Del Sangue03 medical and health scienceschemistry.chemical_compound0302 clinical medicineInternal medicineDrug DiscoverymedicinePharmacology (medical)In patientAdverse effectPharmacologybusiness.industryPonatinibChronic myeloid leukemiaMyeloid leukemiaGeneral Medicinemedicine.diseaseCardiovascular riskInfectious DiseasesOncologychemistry030220 oncology & carcinogenesisPonatinibbusiness
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Immunotherapeutic properties of chemotherapy

2017

IF 5.363; International audience; Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations. In this review, we will summarize which immunological processes are involved in the antica…

0301 basic medicinemedicine.medical_treatmentAntineoplastic Agents[SDV.CAN]Life Sciences [q-bio]/Cancer[ SDV.CAN ] Life Sciences [q-bio]/Cancer03 medical and health sciencesImmune systemNeoplasmsDrug DiscoveryAnimalsHumansMedicineCytotoxicityPharmacologyChemotherapybusiness.industryImmunogenicityImmunotherapyImmune checkpointGastrointestinal Microbiome3. Good healthBlockade030104 developmental biologyImmunologyCancer cellCancer researchImmunotherapybusinessCurrent Opinion in Pharmacology
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Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers

2016

A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the c…

0301 basic medicinemedicine.medical_treatmentPhotodynamic therapyChemistry Techniques SyntheticAntiproliferative activityPhotochemistry01 natural sciencesPhotodynamic therapychemistry.chemical_compound7]cyclohepta[1Drug DiscoveryTriplet stateAmineschemistry.chemical_classificationPhotosensitizing AgentsCell DeathSinglet OxygenChemistrySinglet oxygenGeneral MedicineAntiproliferative activity; Photodynamic therapy; Photosensitizing agents; Pyrrolo[3′; 2′:6; 7]cyclohepta[1; 2-d]pyrimidin-2-amines; Reactive oxygen species; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; PharmacologyPyrrolo[3′2′:67]cyclohepta[12-d]pyrimidin-2-amineSettore ING-IND/22 - Scienza E Tecnologia Dei Materiali2-d]pyrimidin-2-aminesFlash photolysisReactive oxygen specieKineticsAntineoplastic AgentsAbsorbance03 medical and health sciencesCell Line TumormedicineHumansPyrrolo[3′Cell ProliferationPharmacologyReactive oxygen speciesPhotosensitizing agentPhotolysis010405 organic chemistry2′:6Drug Discovery3003 Pharmaceutical SciencePhotodissociationOrganic ChemistryCombinatorial chemistrySettore CHIM/08 - Chimica Farmaceutica0104 chemical sciencesAntiproliferative activity; Photodynamic therapy; Photosensitizing agents; Pyrrolo[3′2′:67]cyclohepta[12-d]pyrimidin-2-amines; Reactive oxygen species; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; PharmacologyKinetics030104 developmental biologyDrug DesignReactive oxygen species
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Immunogenicity of a Fully Synthetic MUC1 Glycopeptide Antitumor Vaccine Enhanced by Poly(I:C) as a TLR3-Activating Adjuvant.

2017

Fully synthetic MUC1 glycopeptide antitumor vaccines have a precisely specified structure and induce a targeted immune response without suppression of the immune response when using an immunogenic carrier protein. However, tumor-associated aberrantly glycosylated MUC1 glycopeptides are endogenous structures, “self-antigens”, that exhibit only low immunogenicity. To overcome this obstacle, a fully synthetic MUC1 glycopeptide antitumor vaccine was combined with poly(inosinic acid:cytidylic acid), poly(I:C), as a structurally defined Toll-like receptor 3 (TLR3)-activating adjuvant. This vaccine preparation elicited extraordinary titers of IgG antibodies which strongly bound human breast cancer…

0301 basic medicinemedicine.medical_treatmentchemical and pharmacologic phenomenaBiochemistryCancer Vaccines03 medical and health sciencesMice0302 clinical medicineImmune systemCancer immunotherapyAdjuvants ImmunologicDrug DiscoverymedicineAnimalsHumansGeneral Pharmacology Toxicology and PharmaceuticsMUC1PharmacologyVaccines SyntheticbiologyChemistryImmunogenicityOrganic ChemistryMucin-1GlycopeptidesDendritic CellsVirologyGlycopeptideToll-Like Receptor 3030104 developmental biologyPoly I-C030220 oncology & carcinogenesisTLR3biology.proteinMolecular MedicineAntibodyAdjuvantChemMedChem
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