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81. Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma? Full Text available with Trip Pro

Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma? Glioblastoma multiforme (GBM) represents one of the most frequent malignant brain tumors. Current therapies do not provide real solutions to this pathology. Their failure can be ascribed to a cell subpopulation with stem-like properties called glioma stem cells (GSCs). Therefore, new therapeutic strategies GSC-targeted are needed. PPARγ, a nuclear receptor involved in lipid metabolism, has already (...) been indicated as a promising target for antineoplastic therapies. Recent studies have reported that synthetic PPARγ agonists, already in clinical use for the treatment of type II diabetes, exhibit antineoplastic effects in a wide range of malignant tumor cells, including glioma cells. We investigated the effect of the synthetic PPARγ agonist Pioglitazone on viability, proliferation, morphology, and differentiation in six GSC lines isolated from GBM patients. We also analyzed Pioglitazone-induced

2016 PPAR Research

82. A mechanism for overcoming P-glycoprotein-mediated drug resistance: novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC Full Text available with Trip Pro

A mechanism for overcoming P-glycoprotein-mediated drug resistance: novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4 (...) -methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers. Thus, the combination of these agents should be considered as an effective rationalized therapy for potently treating advanced and resistant tumors that are often heterogeneous in terms of Pgp-expression. These studies demonstrate that both

2016 Cell death & disease

83. Myelofibrosis: an update on drug therapy in 2016 Full Text available with Trip Pro

for managing anemia of MF include danazol, immunomodulatory drugs and erythroid stimulating agents, either alone or in combination with ruxolitinib. Expert opinion: A number of other agents, representing diverse drug classes, are in various stages of development for MF. These include newer JAK inhibitors, other signaling inhibitors, epigenetic modifiers, anti-fibrotic agents, telomerase inhibitors, and activin receptor ligand traps (for anemia). Hopefully, these novel therapies will further extend (...) Myelofibrosis: an update on drug therapy in 2016 Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. Areas covered: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2

2016 Expert opinion on pharmacotherapy

84. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer Full Text available with Trip Pro

IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R (...) and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

2016 Proceedings of SPIE--the International Society for Optical Engineering

85. Safety assessment in rats and dogs of Acoustic Cluster Therapy, a novel concept for ultrasound mediated, targeted drug delivery Full Text available with Trip Pro

Safety assessment in rats and dogs of Acoustic Cluster Therapy, a novel concept for ultrasound mediated, targeted drug delivery Acoustic Cluster Therapy (ACT) represents a novel concept for targeted drug delivery. Ultrasound is applied to activate intravenously administered free-flowing clusters of microbubbles and microdroplets within the target pathology, depositing 20-30 μm large bubbles in the microvasculature for 5-10 min. Further application of ultrasound induces biomechanical effects (...) which increase vascular permeability and enhance localized extravasation of coadministered drugs. Herein we report investigations done to assess the preclinical safety of ACT, using doses up to 1 mL/kg (3 μL perfluoromethyl-cyclopentane/kg). In dogs, half the animals were exposed to ultrasound activation in the heart for 1 min, no ultrasound was applied in the other half. Posttreatment observation time was 24 h. Clinical signs, ophthalmoscopy, clinical pathology, macro-, and microscopy were used

2016 Pharmacology research & perspectives

86. Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report Full Text available with Trip Pro

Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report BACKGROUND Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment (...) . This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. CASE REPORT The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed

2016 The American journal of case reports

87. Repurposing FDA-approved drugs for anti-aging therapies Full Text available with Trip Pro

drugs for disease therapy, there has been little testing of these drugs for their effects on aging. The pool of FDA approved drugs therefore represents a large reservoir of drug candidates with substantial potential for anti-aging therapy. In this paper we employ FINDSITEcomb, a powerful ligand homology modeling program, to identify binding partners for proteins produced by temperature sensing genes that have been implicated in aging. This list of drugs with potential to modulate aging rates (...) Repurposing FDA-approved drugs for anti-aging therapies There is great interest in drugs that are capable of modulating multiple aging pathways, thereby delaying the onset and progression of aging. Effective strategies for drug development include the repurposing of existing drugs already approved by the FDA for human therapy. FDA approved drugs have known mechanisms of action and have been thoroughly screened for safety. Although there has been extensive scientific activity in repurposing

2016 Biogerontology

88. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease Full Text available with Trip Pro

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules (...) , gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy.This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches.It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide

2016 Current neuropharmacology

89. Small molecule inhibitors of the Dishevelled‐CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy Full Text available with Trip Pro

Small molecule inhibitors of the Dishevelled‐CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also (...) , the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs. We previously identified that CXXC5 is a negative feedback regulator of the Wnt/β-catenin pathway via its interaction with Dishevelled (Dvl) and suggested the Dvl-CXXC5 interaction as a potential target for anabolic therapy of osteoporosis. Here, we screened small-molecule inhibitors of the Dvl-CXXC5 interaction via a newly established in vitro assay

2016 EMBO molecular medicine

90. Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy

provided by the National Library of Medicine related topics: related topics: available for: Arms and Interventions Go to Arm Intervention/treatment Active Comparator: group 1- MTX+LEF+HCQ Active Comparator: Combination of Methotrexate (up to 25 mg per week), Leflunomide (20 mg once a day) and Hydroxychloroquine (200-400 mg once at night). All drugs are to be taken orally. Duration of therapy is for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose (...) Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved

2016 Clinical Trials

91. Oncofertility considerations in adolescents and young adults given a diagnosis of melanoma: Fertility risk of Food and Drug Administration-approved systemic therapies. Full Text available with Trip Pro

and Drug Administration (FDA)-approved melanoma therapies with a new risk category system.We conducted a retrospective review of FDA, European Union, and Health Canada regulatory filings, along with previously published reports to grade fertility risk of systemic melanoma therapies. The proposed fertility risk category system is analogous to the FDA's A/B/C/D/X/N pregnancy-risk categories.For female patients, 58% of treatments represent a fertility risk (Category C and D), 33% have unknown risk (...) Oncofertility considerations in adolescents and young adults given a diagnosis of melanoma: Fertility risk of Food and Drug Administration-approved systemic therapies. Melanoma is the most common cancer diagnosed for patients ages 25 to 29 years, the group with the highest birth rates in the United States. Oncofertility is a new field addressing the reproductive needs of patients with cancer facing fertility-threatening treatments.We sought to assess gender-specific fertility risk for Food

2016 Journal of American Academy of Dermatology

92. Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes. (Abstract)

Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes. Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research (...) ; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's

2016 Frontiers in Neuroendocrinology

93. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants. Full Text available with Trip Pro

In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants. Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic (...) , as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal responders with no treatment changes.DS enables a larger window of detection of emerging BCR-ABL1 KD mutations predicting for an impending relapse. A 'Warning' response may represent a rational trigger, besides 'Failure', for DS-based mutation screening in CML patients undergoing second-line TKI therapy.

2016 BMC Cancer

94. Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer. Full Text available with Trip Pro

Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer. The rapidly expanding arsenal of chemotherapeutic agents approved in the past 5 years represents significant progress in the field. However, this poses a challenge for oncologists to choose which drug or combination of drugs is best for any individual. Because only a fraction of patients respond to any drug, efforts have been made to devise strategies to personalize care. The majority of efforts have involved (...) , response biomarkers represent a less expensive and more convenient means of monitoring therapy, although an ideal response biomarker has not yet been described. A framework for future response biomarker discovery is described.

2016 BMC Cancer

95. Medical Representatives' Intention to Use Information Technology in Pharmaceutical Marketing Full Text available with Trip Pro

Medical Representatives' Intention to Use Information Technology in Pharmaceutical Marketing Electronic detailing (e-detailing), the use of electronic devices to facilitate sales presentations to physicians, has been adopted and expanded in the pharmaceutical industry. To maximize the potential outcome of e-detailing, it is important to understand medical representatives (MRs)' behavior and attitude to e-detailing. This study investigates how information technology devices such as laptop (...) computers and tablet PCs are utilized in pharmaceutical marketing, and it analyzes the factors influencing MRs' intention to use devices.This study has adopted and modified the theory of Roger's diffusion of innovation model and the technology acceptance model. To test the model empirically, a questionnaire survey was conducted with 221 MRs who were working in three multinational or eleven domestic pharmaceutical companies in Korea.Overall, 28% and 35% of MRs experienced using laptop computers

2016 Healthcare informatics research

96. Interaction and medical inducement between pharmaceutical representatives and physicians: a meta-synthesis Full Text available with Trip Pro

Interaction and medical inducement between pharmaceutical representatives and physicians: a meta-synthesis It has been proven that the interaction between pharmaceutical representatives and physicians can directly influence the latter's prescribing behaviour. This meta-synthesis aims to explore the available studies regarding the nature of the interaction that takes place between pharmaceutical representatives and physicians. It highlights the different aspects of that interaction (...) , the United Kingdom, Yemen, and Japan. Six main themes were derived from the included articles: 1-the frequency of pharmaceutical representatives' visits, 2-the perceived ethical acceptability of the interactions between pharmaceutical representatives and physicians, 3-the attitudes held by physicians towards visits by pharmaceutical representatives, 4-their perception of the effect of such visits on prescription patterns, 5-reasons to accept or reject pharmaceutical representatives, and lastly, 6

2016 Journal of pharmaceutical policy and practice

97. The Quality of Medicines Used in Children and Supplied by Private Pharmaceutical Wholesalers in Kinshasa, Democratic Republic of Congo: A Prospective Survey. Full Text available with Trip Pro

The Quality of Medicines Used in Children and Supplied by Private Pharmaceutical Wholesalers in Kinshasa, Democratic Republic of Congo: A Prospective Survey. Poor-quality medicines are a threat to public health in many low- and middle-income countries, and prospective surveys are needed to inform corrective actions. Therefore, we conducted a cross-sectional survey on a sample of products used for children and available in the private market in Kinshasa, Democratic Republic Congo: amoxicillin (...) (AX) and artemether/lumefantrine (AL), powders for suspension, and paracetamol (PC) tablets 500 mg. Overall, 417 products were covertly purchased from 61 wholesalers. To obtain a representative sample, the products were weighted on their market shares and a subset of 239 samples was randomly extracted to undergo in-depth visual inspection locally, and they were chemically assessed at two accredited laboratories in Belgium. Samples were defined of "poor-quality" if they failed to comply

2018 American Journal of Tropical Medicine & Hygiene

98. Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers. Full Text available with Trip Pro

Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers. Despite strong efficacy in randomized trials, the population effectiveness of pharmaceutical aids in long-term smoking cessation is lacking, possibly because of confounding (factors that are associated with both pharmaceutical aid use and difficulty quitting). Matching techniques in longitudinal studies can remove this confounding bias.Using the nationally representative Tobacco Use (...) Supplement to the Current Population Survey (TUS-CPS), we assessed the effectiveness of medications to aid quitting among baseline adult smokers who attempted to quit prior to one year of follow-up in two longitudinal studies: 2002-2003 and 2010-2011. Pharmaceutical aid users and nonusers with complete data (n = 2129) were matched using propensity score models with 12 potential confounders (age, sex, race-ethnicity, education, smoking intensity, nicotine dependence, previous quit history, self-efficacy

2017 Journal of the National Cancer Institute

99. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy Full Text available with Trip Pro

no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs' targeting abilities with hypericin's phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy (...) Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap

2015 International journal of nanomedicine

100. Impact of Anemia and Dual Antiplatelet Therapy on Mortality in Patients Undergoing Percutaneous Coronary Intervention with Drug-Eluting Stents Full Text available with Trip Pro

Impact of Anemia and Dual Antiplatelet Therapy on Mortality in Patients Undergoing Percutaneous Coronary Intervention with Drug-Eluting Stents The objective was to assess the impact of baseline anemia on all-cause mortality and whether 12-month dual antiplatelet therapy (DAPT) affects 1-year mortality linked to anemia in patients after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 4109 enrolled patients divided into three groups based on their pre-procedural (...) hemoglobin (Hb) level: Hb < 100 mg/L represented moderate-severe anemia; 100 mg/L ≤ Hb < 120 mg/L for women and 100 mg/L ≤ Hb < 130 mg/L for men represented mild anemia; Hb ≥ 20 mg/L for women and Hb ≥ 130 mg/L for men represented no anemia. DAPT medications were prescribed when patients were discharged. There were significant differences in 30-day and 1-year mortality between moderate-severe anemia and no anemia patients (HR 8.05, 95% CI 1.46 to 44.33, P = 0.017; HR 3.93, 95% CI 1.11 to 13.98, P = 0.034

2015 Scientific reports

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