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Sample records for antineoplastic drugs

  1. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  2. Antineoplastic drugs: Occupational exposure and health risks

    NARCIS (Netherlands)

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used.

  3. Antineoplastic drugs: Occupational exposure and health risks

    OpenAIRE

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with cyclophosphamide excrete the unmetabolized drug. The introduction of new guidelines and...

  4. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  5. Glycaemic adverse drug reactions from anti-neoplastics used in ...

    African Journals Online (AJOL)

    235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

  6. Exposure to antineoplastic drugs outside the hospital environment.

    Science.gov (United States)

    Meijster, T; Fransman, W; Veldhof, R; Kromhout, H

    2006-10-01

    The objectives were (i) to identify occupational populations outside hospitals working with antineoplastic drugs, (ii) to determine the size of the populations 'at risk', (iii) to identify major determinants and routes of exposure outside hospitals and (iv) to estimate exposure levels and frequencies relative to levels found in hospitals. The survey consisted of two phases; (i) identification of activities with potential exposure to antineoplastic drugs by literature review, interviews, questionnaires and workplace visits, (ii) exploratory measurements of exposure and surface contamination in selected sectors. Eight sectors were identified with potential exposure to antineoplastic drugs: pharmaceutical industry, pharmacies, universities, veterinary medicine, nursing homes, home care, laundry facilities, and waste treatment. Four sectors were of primary concern: veterinary medicine, home care, nursing homes and industrial laundries. The populations potentially exposed in these sectors vary considerably (from several tens to thousands of workers), as do their levels of exposure. Exposure measurements collected in the veterinary medicine sector showed that workers are indeed exposed to antineoplastic drugs and, in some cases (on gloves after administration), levels were 15 times higher than levels measured during administration in hospitals. Workers sorting contaminated hospital laundry in industrial laundry facilities were exposed to antineoplastic drugs through inhalation. For the home care and nursing homes sectors the highest exposure levels were found when cleaning toilets and washing treated patients. These two sectors are expected to have the largest exposed population (5,000-10,000 individuals). This study has resulted in a comprehensive overview of populations with potential exposure to antineoplastic drugs. Exposure levels can potentially be high compared with the hospital environment, because exposure routes are complex and awareness of the hazard (and

  7. Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

    Science.gov (United States)

    Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

    2017-11-23

    Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

  8. 75 FR 57044 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010

    Science.gov (United States)

    2010-09-17

    ... identified 24 drugs that fit the NIOSH definition of hazardous drugs. The second draft list also proposed... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010 AGENCY: National Institute for Occupational... publication of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  9. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-06-27

    ... removed 15 drugs from the 2012 list because they did not meet the NIOSH definition, were no longer... NIOSH-033-A] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in... of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  10. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Cornetta, Tommaso [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); ' Don Carlo Gnocchi' Foundation, Rome (Italy); Padua, Luca [' Don Carlo Gnocchi' Foundation, Rome (Italy); Department of Neuroscience, Neurology Institute, Catholic University, Rome (Italy); Testa, Antonella; Ievoli, Elena [Toxicology and Biomedical Sciences Section, ENEA Research Center, Casaccia (Rome) (Italy); Festa, Fabiola [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); Tranfo, Giovanna [Department of Occupational Hygiene, Italian Institute for Occupational Prevention and Safety, Monteporzio Catone (Rome) (Italy); Baccelliere, Luigi [S. Martino Hospital, Genova (Italy); Cozzi, Renata [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy)], E-mail: cozzi@bio.uniroma3.it

    2008-02-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.

  11. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    International Nuclear Information System (INIS)

    Cornetta, Tommaso; Padua, Luca; Testa, Antonella; Ievoli, Elena; Festa, Fabiola; Tranfo, Giovanna; Baccelliere, Luigi; Cozzi, Renata

    2008-01-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances

  12. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    Science.gov (United States)

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

    2015-05-01

    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  13. Injectable-antineoplastic-drug practices in Michigan hospitals.

    Science.gov (United States)

    Cohen, I A; Newland, S J; Kirking, D M

    1987-05-01

    Practices related to parenteral (injectable) antineoplastic drugs (PADs) in Michigan hospitals were surveyed. All hospitals in Michigan were surveyed to assess compliance with American Society of Hospital Pharmacists (ASHP) and Occupational Safety and Health Administration (OSHA) recommendations related to PADs. Other PAD-related practice issues not covered within those guidelines were also studied. Surveys were mailed to the pharmacy directors of the state's 192 acute-care hospitals. Included were questions concerning policies and procedures for ordering, storing, preparing, handling, labeling, transporting, administering, and disposing of PADs. Questions concerning staff education, spill cleanup, and personnel issues were also included. A total of 169 questionnaires were returned, yielding a response rate of 88%. Of those respondents, 132 indicated that they prepare PAD doses for inpatients. Adherence rates were high for several of the PAD-preparation recommendations, including handwashing (97%) and gloving (98.5%). Rates for gowning (71.2%), labeling of PAD doses as biohazards (chemical hazards) (73.5%), and use of Class II biological-safety cabinets (71.2%) were less favorable. Practice areas with relatively poor adherence rates included use of plastic-backed absorbent pads under PAD preparation areas (53.8%), storing PADs separately from other drugs (48.5%), informing prospective employees of potential risks of handling PADs (36.4%), availability of spill kits (36.4%), and attaching and priming i.v. tubing before adding PADs to i.v. containers (5.4%). Many pharmacy departments in Michigan hospitals can substantially improve their adherence to ASHP and OSHA recommendations related to PADs.

  14. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan.

    Science.gov (United States)

    Yoshida, Jin; Koda, Shigeki; Nishida, Shozo; Yoshida, Toshiaki; Miyajima, Keiko; Kumagai, Shinji

    2011-03-01

    The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A-E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.

  15. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-190] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute for Occupational Safety and Health (NIOSH) of the...

  16. Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-05-01

    Occupational exposure to antineoplastic drugs is associated with genotoxic effects, although comet assay analyzed parameters were higher in exposed comparing with controls, were not significant. Also the study of the susceptibility biomarkers did not show statistical significant differences, the small size of our sample hampered the finding of a possible association, let alone a causality relationship.

  17. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2013-10-01

    Full Text Available Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine. An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05. This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

  18. Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

    International Nuclear Information System (INIS)

    Hernandez-Esquivel, Luz; Marin-Hernandez, Alvaro; Pavon, Natalia; Carvajal, Karla; Moreno-Sanchez, Rafael

    2006-01-01

    Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O 2 consumption with half-maximal inhibitory concentrations (IC 5 ) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC 5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

  19. [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

    Science.gov (United States)

    Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

    2015-07-01

    The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  20. Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Huertas

    2015-07-01

    Full Text Available The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs.

  1. Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

    Science.gov (United States)

    Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

    2015-01-01

    Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

  2. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde

    Czech Academy of Sciences Publication Activity Database

    Mušák, L.; Šmerhovský, Z.; Halásová, E.; Osina, O.; Letková, L.; Vodičková, Ludmila; Poláková, Veronika; Buchancová, J.; Hemminki, K.; Vodička, Pavel

    2013-01-01

    Roč. 39, č. 6 (2013), s. 618-630 ISSN 0355-3140 Grant - others:MŠVV(SK) 26220220111; UK(SK) 1/0576/10 VEGA; MZd(SK) 2007/48-UK-13; GA MŠMT(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : anesthesiologist * antineoplastic drug * chromosomal aberration Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.095, year: 2013

  3. New approaches to wipe sampling methods for antineoplastic and other hazardous drugs in healthcare settings.

    Science.gov (United States)

    Connor, Thomas H; Smith, Jerome P

    2016-09-01

    At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with a variety of analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. Published studies on the use of wipe sampling to measure hazardous drugs on surfaces in healthcare settings drugs were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic. Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. Current recommendations are that all healthc a re settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use.

  4. [Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service].

    Science.gov (United States)

    Pacheco Ramos, María de la Paz; Arenaza Peña, Ainhoa Elisa; Santiago Pérez, Alejandro; Bilbao Gómez-Martino, Cristina; Zamora Barrios, María Dolores; Arias Fernández, María Lourdes

    2015-05-01

    To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months). 2- Usage period (22 months). On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation's errors. 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133) of the errors were identified by the robot and therefore didn't reach the patient (negative desviation - 4%). These errors were corrected manually. The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service

    Directory of Open Access Journals (Sweden)

    María de la Paz Pacheco Ramos

    2015-01-01

    Full Text Available Objective: To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. Methods: The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months. 2- Usage period (22 months. On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation´s errors. Results: 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133 of the errors were identified by the robot and therefore didn´t reach the patient (negative desviation - 4%. These errors were corrected manually. Conclusion: The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator

  6. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  7. Antineoplastic drugs and radiation: comparison of the phenomena determining the effectiveness of fractionated treatments

    International Nuclear Information System (INIS)

    Mauro, F.; Briganti, G.; Nervi, C.

    1983-01-01

    In the last ten years the criteria for effective radiotherapy regimens have been rediscussed by analyzing the dependence of radiation response upon the radiobiological phenomena affecting the results of fractionated treatments. In the original definition of H.R. Withers, these phenomena have been referred to as the four R's of radiotherapy, and today we suspect that their number may be higher than that. By analogy, and in spite of the fact that chemical cytotoxic agents are seldom radiomimetic in the strict sense of the word, a similar general analysis could be used to discuss the effectiveness of fractionated administrations of anti-neoplastic drugs. However, information is only available for the cell-cycle age-dependence of lethal and kinetic effects and the repair from potentially lethal damage induced by these agents. In the present work, an attempt is made to discuss some of the neglected R's of chemotherapy, with the aim of establishing (not exclusively empirical) criteria for drug scheduling and of clarifying some of the observations on interaction between agents. In particular, with regard to antineoplastic drugs, published and unpublished information is available not only for the well-known phenomenon of reassortment, but also for the shape of the survival curve, recovery (or potentiation) between dose fraction, and recruitment. Some advantages (and pitfalls) can be evidenced when applying this kind of radiobiological approach to chemotherapy

  8. Prophylaxis and management of antineoplastic drug induced nausea and vomiting in children with cancer

    Directory of Open Access Journals (Sweden)

    Sidharth Totadri

    2016-10-01

    Full Text Available Antineoplastic drug induced nausea and vomiting (AINV is a major adverse event which deeply impacts the quality of life of children with cancer. It additionally causes distress to parents and negatively impacts compliance to therapy. A robust AINV prophylaxis regimen is essential to achieve complete control; and prevent anticipatory, breakthrough and refractory AINV. With a wide array of available anti-emetics, standard guidelines for their use are crucial to ensure uniform and optimum prophylaxis. Chemotherapeutic agents are classified as having high, moderate, low or minimal emetic risk based on their potential to cause emesis in the absence of prophylaxis. Three drug regimen with aprepitant, ondansetron/granisetron and dexamethasone is recommended for protocols with high emetic risk. Although approved in children ≥12 years, there is mounting evidence for the use of aprepitant in younger children too. In protocols with moderate and low emetic risk, combination of ondansetron/granisetron and dexamethasone; and single agent ondansetron/granisetron are recommended, respectively. Metoclopramide is an alternative when steroids are contraindicated. Olanzapine and lorazepam are useful drugs for breakthrough AINV and anticipatory AINV. Knowledge of pediatric dosage, salient adverse events, drug interactions as well as cost of drugs is essential to prescribe anti-emetics accurately and safely in resource constrained settings. Non pharmacological interventions such as hypnosis, acupressure and psychological interventions can benefit a sub-group of patients without significant risk of adverse events.

  9. French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends.

    Science.gov (United States)

    Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher

    2016-08-01

    France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.

  10. To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects Labeling for Oral Antineoplastic Drugs.

    Science.gov (United States)

    Deng, Jiexin; Brar, Satjit S; Lesko, Lawrence J

    2017-12-02

    There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models. In 2000-2009, 80% (4 out of 5) of all approved oral antineoplastics with increased bioavailability in the fed state were labeled as "take on empty stomach." In contrast, we found that in 2010-2016 there is a greater diversity in food recommendations for drugs with increased bioavailability in the fed state. Currently, many oral oncology drugs are given with food to maximize their bioavailability; however, as seen from our case study of sonidegib, failure to fully adhere to label recommendations to either take with food or not could lead to adverse consequences in terms of safety and efficacy. © 2017, The American College of Clinical Pharmacology.

  11. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  12. Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

    Science.gov (United States)

    Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

    2011-01-01

    In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

  13. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  14. Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs.

    Science.gov (United States)

    Bartel, Sylvia B; Tyler, Timothy G; Power, Luci A

    2018-02-15

    Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  15. [Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process].

    Science.gov (United States)

    Gómez-Álvarez, Sandra; Porta-Oltra, Begoña; Hernandez-Griso, Marta; Pérez-Labaña, Francisca; Climente-Martí, Mónica

    2016-01-01

    to assess the impact of two closed-system drug transfer device on the local and environmental contamination and preparation times in the process of preparation of parenteral chemotherapy compared to the standard system. prospective observational study. Two different closed- systems providers, Care Fusion® and Icu Medical®, were compared to standard preparation. 15 nurses of Pharmacy Department prepared 5 preparations each one, one with the standard procedure and four using closed-systems. To evaluate the contamination, a fluorescein solution 0.5% was prepared. Two kind of contamination were evaluated, local (three points connection: closed-system connect vial, syringe and final infusion bags) and environmental (gloves and countertop). Percentage of contaminated preparations was obtained in each one. Time taken by each nurse in each preparation was recorded. 75 preparations were prepared. Local contamination was reduced 21% and 75% in closed-system Icu Medical® and Care Fusion® respectively. Care Fusion® closed system, local contamination was significantly lower than the standard system to the vial, syringe and final package, while Icu Medical® closed-systems only was significantly lower in the connection to the vial. Time of preparation was increased significantly with the use of closed-system between 23.4 and 30.5 seconds. both closed-systems drug transfer device have shown an improvement in contamination than the use of the standard system. However, preparation time has been significantly increased with the use of both systems. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  16. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  17. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  18. Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

    OpenAIRE

    Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

    2007-01-01

    The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymer...

  19. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    International Nuclear Information System (INIS)

    Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

    2011-01-01

    Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

  20. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  1. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    Directory of Open Access Journals (Sweden)

    Gelatti Umberto

    2011-03-01

    Full Text Available Abstract Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes and on the exposed nurses' clothes (pads. The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases will also be analysed. Using standardized questionnaires

  2. Drug: D01223 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01223 Drug Capecitabine (JAN/USAN/INN); Xeloda (TN) ... C15H22FN3O6 D01223.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic... ... DG01935 ... Fluoropyrimidine antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01935 ... Fluoropyrimidine antineoplasti...ic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic

  3. Oncogenic targets, magnitude of benefit, and market pricing of antineoplastic drugs.

    Science.gov (United States)

    Amir, Eitan; Seruga, Bostjan; Martinez-Lopez, Joaquin; Kwong, Ryan; Pandiella, Atanasio; Tannock, Ian F; Ocaña, Alberto

    2011-06-20

    The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

  4. Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites

    Czech Academy of Sciences Publication Activity Database

    Zounková, R.; Kovalová, L.; Bláha, Luděk; Dott, W.

    2010-01-01

    Roč. 81, č. 2 (2010), s. 253-260 ISSN 0045-6535 Institutional research plan: CEZ:AV0Z60050516 Keywords : cytotoxic drugs * ecotoxicity * metabolite Subject RIV: EF - Botanics Impact factor: 3.155, year: 2010

  5. Brain tumor chemo-radiotherapy: a study of direct intratumoral perfusion with antineoplastic drugs

    International Nuclear Information System (INIS)

    Rousseau, J.

    2007-10-01

    High grade gliomas are aggressive tumors for which current treatments remain palliative. Radiotherapy efficacy is restricted by the surrounding brain tissue tolerance. One method based on the concomitant use of chemotherapeutic drugs and external photon irradiation has been proposed to improve the treatment outcome. The systemic administration of drugs is not effective in achieving the therapeutic level of drug needed for brain tumor treatment. This is due to the blood brain barrier (BBB) that prevents molecules passing through the vascular endothelium. Recent methods have been developed to circumvent the BBB. Among them, convection-enhanced delivery (CED) relies on the continuous infusion of a fluid containing a therapeutic agent, under a pressure gradient. It permits a homogeneous and controlled drug distribution. The aims of this study were to characterise the CED method, and then to utilize it for glioma treatment in preclinical studies. Several drugs were tested: cisplatin, carbo-platin, oxaliplatin, and iodo-deoxyuridine. Two radiation modalities were evaluated: synchrotron stereotactic radiotherapy (monochromatic beam < 100 keV) and high energy irradiation (6 MV) obtained with a conventional medical linear accelerator. The results obtained reveal that the effectiveness of the combined treatment (platinated drug plus photon irradiation) is highly related to that of the chemotherapy. The data, obtained with the platinated chemotherapy, also show that high-energy X-ray irradiation (6 MV) is as effective as synchrotron X-ray irradiation. The results broaden the applicability of this chemotherapeutic approach to clinical trials. (author)

  6. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  7. Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells

    International Nuclear Information System (INIS)

    Wenzel, D.G.; Morgan, D.L.

    1983-01-01

    Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with 51 Cr were exposed to the following antitumor drugs alone or with O 3 : carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K 3 (Vit K). Release of 51 Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O 3 -induced loss of 51 Cr. Co-exposure of F-cells to drugs and O 3 resulted in a marked potentiation of O 3 -induced injury with Vit K, and an inhibition with Dox

  8. Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System

    Directory of Open Access Journals (Sweden)

    Chun-Yip Hon

    2011-09-01

    Conclusion: We found drug contamination on select surfaces at every stage of the medication system, which indicates the existence of an exposure potential throughout the facility. Our results suggest that a broader range of workers are potentially exposed than has been previously examined. These results will allow us to develop a more inclusive exposure assessment encompassing all healthcare workers that are at risk throughout the hospital medication system.

  9. Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation.

    Science.gov (United States)

    Sessink, Paul J M; Leclercq, Gisèle M; Wouters, Dominique-Marie; Halbardier, Loïc; Hammad, Chaïma; Kassoul, Nassima

    2015-04-01

    Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

    Science.gov (United States)

    Rubino, F M; Floridia, L; Pietropaolo, A M; Tavazzani, M; Colombi, A

    1999-01-01

    Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

  11. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.

    Science.gov (United States)

    Pal, Shipra; Sadhu, Arpita Sengupta; Patra, Swarup; Mukherjea, Kalyan K

    2008-11-12

    Cisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth. A Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets--Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with

  12. Drug: D01633 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01633 Drug Enocitabine (JAN/INN); Sunrabin (TN) ... C31H55N3O6 D01633.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... D...G01439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Therap

  13. Drug: D05134 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 5 D05134.gif ... Antineoplastic ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... ...DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic... D05134 Drug Nelarabine (JAN/USAN/INN); Nelzarabine (USAN); Arranon (TN) ... C11H15N5O

  14. Drug: D04134 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04134 Drug Fazarabine (USAN/INN) ... C8H12N4O5 D04134.gif ... Antineoplastic ... DG01958... ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplas...tic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... arabinofuranosyl de

  15. Drug: D01309 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01309 Drug Doxifluridine (JP17/INN); Furtulon (TN) ... C9H11FN2O5 D01309.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic ... DG0...1935 ... Fluoropyrimidine antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01935 ... Fluoropyrimidine antineoplastic Same as: C12739 Th

  16. Drug: D06221 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06221 Drug Triciribine phosphate (USAN) ... C13H17N6O7P D06221.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... CAS: 6

  17. Drug: D02368 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02368 Drug Gemcitabine (USAN/INN) ... C9H11F2N3O4 D02368.gif ... Antineoplastic ... DG01...958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arabi...nofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Same as: C07650 ATC

  18. Drug: D09712 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09712 Drug Elacytarabine (USAN/INN) ... C27H45N3O6 D09712.gif ... Antineoplastic ... DG0...1958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arab...inofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... Elacytarabine i

  19. Drug: D06100 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06100 Drug Tezacitabine (USAN); Tezacitabine monohydrate ... C10H12FN3O4. H2O D06100.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic

  20. Drug: D04197 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04197 Drug Floxuridine (USP/INN); FUDR (TN) ... C9H11FN2O5 D04197.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic ... DG01935 ... F...luoropyrimidine antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01935 ... Fluoropyrimidine antineoplastic Same as: C11736 ... TYMS [

  1. Drug: D10222 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10222 Drug Gemcitabine elaidate (USAN/INN) ... C27H43F2N3O5 D10222.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01...439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ATC code:

  2. Drug: D01651 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01651 Drug Ancitabine hydrochloride (JAN) ... C9H11N3O4. HCl D01651.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG0...1439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Same as:

  3. Drug: D07974 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07974 Drug Fluorouracil sodium salt; Fluorouracil (TN) ... C4H3FN2O2. xNa D07974.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic... ... DG01935 ... Fluoropyrimidine antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplasti...c ... DG01935 ... Fluoropyrimidine antineoplastic ATC code:

  4. Drug: D09722 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09722 Drug Sapacitabine (USAN/INN) ... C26H42N4O5 D09722.gif ... Antineoplastic ... DG01...958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arabi...nofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... nucleoside analo

  5. Drug: D04233 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04233 Drug Flurocitabine (USAN/INN) ... C9H10FN3O4 D04233.gif ... Antineoplastic ... DG0...1958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arab...inofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... CAS: 37717-

  6. Drug: D03637 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03637 Drug Cytarabine hydrochloride (USAN) ... C9H13N3O5. HCl D03637.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG...01439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ATC cod

  7. Drug: D07966 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07966 Drug Fludarabine (INN); Fluradosa (TN) ... C10H12FN5O4 D07966.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG0...1439 ... Arabinofuranosyl type antineoplastic Unclassified ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic Same as:

  8. Antineoplastic treatment of patients with renal insufficiency

    International Nuclear Information System (INIS)

    Rajec, J.; Mego, M.; Rajec, J.

    2011-01-01

    Kidneys are the main route of elimination for many antineoplastic drugs and their metabolites. The kidney dysfunction may lead to the drug cumulation in organism with the resulting increased systemic toxicity. A lot of used cytostatics requires a dose modification at different levels of renal insufficiency. Due to the lack of data from clinical trials, the limiting of systemic toxicity is difficult especially in patients with severe renal impairment or patients undergoing chronic hemodialysis. The following article is focused on the preventive strategies dealing with recommended dosing modification of various antineoplastic agents in patients with renal insufficiency. (author)

  9. Applicability of the comet assay in evaluation of DNA damage in healthcare providers' working with antineoplastic drugs: a systematic review and meta-analysis.

    Science.gov (United States)

    Zare Sakhvidi, Mohammad Javad; Hajaghazadeh, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amir Houshang; Zare Sakhvidi, Fariba; Naghshineh, Elham

    2016-01-01

    Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers. To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers. We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis. Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15-2.71, p comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = -0.14; p comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results.

  10. Applicability of the comet assay in evaluation of DNA damage in healthcare providers’ working with antineoplastic drugs: a systematic review and meta-analysis

    Science.gov (United States)

    Zare Sakhvidi, Mohammad Javad; Hajaghazadeh, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amir houshang; Zare Sakhvidi, Fariba; Naghshineh, Elham

    2016-01-01

    Background Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers. Objective To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers. Methods We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis. Results Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15–2.71, p comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = −0.14; p comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results. PMID:27110842

  11. Photo-Fenton and Fenton-like processes for the treatment of the antineoplastic drug 5-fluorouracil under simulated solar radiation.

    Science.gov (United States)

    Koltsakidou, Α; Antonopoulou, M; Sykiotou, M; Εvgenidou, Ε; Konstantinou, I; Lambropoulou, D A

    2017-02-01

    In the present study, photo-Fenton and Fenton-like processes were investigated for the degradation and mineralization of the antineoplastic drug 5-fluorouracil (5-FU). For the optimization of photo-Fenton treatment under simulated solar light (SSL) radiation, the effects of several operating parameters (i.e., 5-FU concentration, Fe 3+ , and oxidant concentration) on the treatment efficiency were studied. According to the results, SSL/[Fe(C 2 Ο 4 ) 3 ] 3- /Η 2 Ο 2 process was the most efficient, since faster degradation of 5-FU and higher mineralization percentages were achieved. All the applied processes followed quite similar transformation routes which include defluorination-hydroxylation as well as pyrimidine ring opening, as demonstrated by the transformation products identified by high resolution mass spectrometry analysis. The toxicity of the treated solutions was evaluated using the Microtox assay. In general, low toxicity was recorded for the initial solution and the solution at the end of the photocatalytic treatment, while an increase in the overall toxicity was observed only at the first stages of SSL/Fe 3+ /Η 2 Ο 2 and SSL/Fe 3+ /S 2 O 8 2- processes.

  12. Antineoplastic drugs in veterinary oncology: excretion in dogs, contamination of the environment and exposure assessment of people at risk

    NARCIS (Netherlands)

    Janssens, T.

    2012-01-01

    Anticancer drugs themselves can cause adverse health effects when administered to human patients. In addition, it has become apparent that personnel in human medicine, occupationally exposed to these anticancer drugs, may also be at risk. The past decades, the use of chemotherapy in veterinary

  13. Introduction of antineoplastic drug NSC631570 in an inpatient and outpatient setting: Comparative evaluation of biological effects

    Directory of Open Access Journals (Sweden)

    Mariia Rudyk

    2016-04-01

    Full Text Available The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism's response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.

  14. Investigation of antineoplastic activity of chewing tablets based on dry oat extract and quercetin

    Directory of Open Access Journals (Sweden)

    Ярослав Ростиславович Андрійчук

    2015-07-01

    Full Text Available One of the main goals of domestic pharmaceutical science is development of new medicines. Thus, new tablet drug was created based on dry oat extract and quercetin. Investigation of antineoplastic activity was performed. Antineoplastic activity of investigational drug based on dry oat extract and quercetin was experimentally proved.

  15. Drug: D01244 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01244 Drug Tegafur (JP17/USAN/INN); Atillon (TN) ... C8H9FN2O3 D01244.gif ... Antineoplastic... ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic ... DG0193...5 ... Fluoropyrimidine antineoplastic Cyp substrate ... DG01638 ... CYP2A6 substrate Unclassified ... DG02018 ... Antimetab...olite ... DG01958 ... Nucleic acid derivative, antineoplastic ... DG01935 ... Fluoropyrimidine antineoplastic

  16. Analysis of anti-neoplastic drug in bacterial ghost matrix, w/o/w double nanoemulsion and w/o nanoemulsion by a validated 'green' liquid chromatographic method.

    Science.gov (United States)

    Youssof, Abdullah M E; Salem-Bekhit, Mounir M; Shakeel, Faiyaz; Alanazi, Fars K; Haq, Nazrul

    2016-07-01

    The objective of the present investigation was to develop and validate a 'green' reversed phase high-performance liquid chromatography (RP-HPLC) method for rapid analysis of a cytotoxic drug 5-fluorouracil (5-FU) in bulk drug, marketed injection, water-in-oil (w/o) nanoemulsion, double water-in-oil-in-water (w/o/w) nanoemulsion and bacterial ghost (BG) matrix. The chromatography study was carried out at room temperature (25±1°C) using an HPLC system with the help of ultraviolet (UV)-visible detector. The chromatographic performance was achieved with a Nucleodur 150mm×4.6mm RP C8 column filled with 5µm filler as a static phase. The mobile phase consisted of ethyl acetate: methanol (7:3% v/v) which was delivered at a flow rate of 1.0mLmin(-1) and the drug was detected in UV mode at 254nm. The developed method was validated in terms of linearity (r(2)=0.998), accuracy (98.19-102.09%), precision (% RSD=0.58-1.17), robustness (% RSD=0.12-0.53) and sensitivity with satisfactory results. The efficiency of the method was demonstrated by the assay of the drug in marketed injection, w/o nanoemulsion, w/o/w nanoemulsion and BG with satisfactory results. The successful resolution of the drug along with its degradation products clearly established the stability-indicating nature of the proposed method. Overall, these results suggested that the proposed analytical method could be effectively applied to the routine analysis of 5-FU in bulk drug, various pharmaceutical dosage forms and BG. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Impact of Robotic Antineoplastic Preparation on Safety, Workflow, and Costs

    Science.gov (United States)

    Seger, Andrew C.; Churchill, William W.; Keohane, Carol A.; Belisle, Caryn D.; Wong, Stephanie T.; Sylvester, Katelyn W.; Chesnick, Megan A.; Burdick, Elisabeth; Wien, Matt F.; Cotugno, Michael C.; Bates, David W.; Rothschild, Jeffrey M.

    2012-01-01

    Purpose: Antineoplastic preparation presents unique safety concerns and consumes significant pharmacy staff time and costs. Robotic antineoplastic and adjuvant medication compounding may provide incremental safety and efficiency advantages compared with standard pharmacy practices. Methods: We conducted a direct observation trial in an academic medical center pharmacy to compare the effects of usual/manual antineoplastic and adjuvant drug preparation (baseline period) with robotic preparation (intervention period). The primary outcomes were serious medication errors and staff safety events with the potential for harm of patients and staff, respectively. Secondary outcomes included medication accuracy determined by gravimetric techniques, medication preparation time, and the costs of both ancillary materials used during drug preparation and personnel time. Results: Among 1,421 and 972 observed medication preparations, we found nine (0.7%) and seven (0.7%) serious medication errors (P = .8) and 73 (5.1%) and 28 (2.9%) staff safety events (P = .007) in the baseline and intervention periods, respectively. Drugs failed accuracy measurements in 12.5% (23 of 184) and 0.9% (one of 110) of preparations in the baseline and intervention periods, respectively (P < .001). Mean drug preparation time increased by 47% when using the robot (P = .009). Labor costs were similar in both study periods, although the ancillary material costs decreased by 56% in the intervention period (P < .001). Conclusion: Although robotically prepared antineoplastic and adjuvant medications did not reduce serious medication errors, both staff safety and accuracy of medication preparation were improved significantly. Future studies are necessary to address the overall cost effectiveness of these robotic implementations. PMID:23598843

  18. Drug: D05522 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05522 Drug Pixantrone (USAN/INN); Pixuvri (TN) ... C17H19N5O2 D05522.gif ... Antineoplastic ... DG01727 ... Anthraqu...inone antineoplastic Other ... DG01529 ... Topoisomerase inhibitor ... DG01527 ... Topoisomera

  19. Drug: D08224 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08224 Drug Mitoxantrone (INN); Misostol (TN) ... C22H28N4O6 D08224.gif ... Antineoplastic ... DG01727 ... Anthraquin...one antineoplastic Other ... DG01529 ... Topoisomerase inhibitor ... DG01527 ... Topoisomerase

  20. A uniform procedure for reimbursing the off-label use of antineoplastic drugs according to the value-for-money approach.

    Science.gov (United States)

    Messori, A; Fadda, V; Trippoli, S

    2011-04-01

    National healthcare systems as well as local institutions generally reimburse numerous off-label uses of anticancer drugs, but an explicit framework for managing these payments is still lacking. As in the case of on-label uses, an optimal management of off-label uses should be aimed at a direct proportionality between cost and clinical benefit. Within this framework, assessing the incremental cost/effectiveness ratio becomes mandatory, and measuring the magnitude of the clinical benefit (e.g. gain in overall survival or progression-free survival) is essential.This paper discusses how the standard principles of cost-effectiveness and value-for-money can be applied to manage the reimbursement of off-label treatments in oncology. It also describes a detailed operational scheme to appropriately implement this aim. Two separate approaches are considered: a) a trial-based approach, which is designed for situations where enough information is available from clinical studies about the expected effectiveness of the off-label treatment; b) an individualized payment-by-results approach, which is designed for situations in which adequate information on effectiveness is lacking; this latter approach requires that each patient receiving off-label treatment is followed-up to determine individual outcomes and tailor the extent of payment to individual results.Some examples of application of both approaches are presented in detail, which have been extracted from a list of 184 off-label indications approved in 2010 by the Region of tuscany in italy. these examples support the feasibility of the two methods proposed.In conclusion, the scheme described in this paper represents an operational solution to an unsettled problem in the area of oncology drugs. © E.S.I.F.T. srl - Firenze

  1. Occupational rhinosinusitis due to etoposide, an antineoplastic agent

    DEFF Research Database (Denmark)

    Meyer, Harald W; Skov, Per Stahl

    2010-01-01

    This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent.......This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent....

  2. Brain tumor chemo-radiotherapy: a study of direct intratumoral perfusion with antineoplastic drugs; Chimio-radiotherapie des tumeurs cerebrales: interet de l'injection intratumorale de drogues antineoplasiques

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, J

    2007-10-15

    High grade gliomas are aggressive tumors for which current treatments remain palliative. Radiotherapy efficacy is restricted by the surrounding brain tissue tolerance. One method based on the concomitant use of chemotherapeutic drugs and external photon irradiation has been proposed to improve the treatment outcome. The systemic administration of drugs is not effective in achieving the therapeutic level of drug needed for brain tumor treatment. This is due to the blood brain barrier (BBB) that prevents molecules passing through the vascular endothelium. Recent methods have been developed to circumvent the BBB. Among them, convection-enhanced delivery (CED) relies on the continuous infusion of a fluid containing a therapeutic agent, under a pressure gradient. It permits a homogeneous and controlled drug distribution. The aims of this study were to characterise the CED method, and then to utilize it for glioma treatment in preclinical studies. Several drugs were tested: cisplatin, carbo-platin, oxaliplatin, and iodo-deoxyuridine. Two radiation modalities were evaluated: synchrotron stereotactic radiotherapy (monochromatic beam < 100 keV) and high energy irradiation (6 MV) obtained with a conventional medical linear accelerator. The results obtained reveal that the effectiveness of the combined treatment (platinated drug plus photon irradiation) is highly related to that of the chemotherapy. The data, obtained with the platinated chemotherapy, also show that high-energy X-ray irradiation (6 MV) is as effective as synchrotron X-ray irradiation. The results broaden the applicability of this chemotherapeutic approach to clinical trials. (author)

  3. Brain tumor chemo-radiotherapy: a study of direct intratumoral perfusion with antineoplastic drugs; Chimio-radiotherapie des tumeurs cerebrales: interet de l'injection intratumorale de drogues antineoplasiques

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, J

    2007-10-15

    High grade gliomas are aggressive tumors for which current treatments remain palliative. Radiotherapy efficacy is restricted by the surrounding brain tissue tolerance. One method based on the concomitant use of chemotherapeutic drugs and external photon irradiation has been proposed to improve the treatment outcome. The systemic administration of drugs is not effective in achieving the therapeutic level of drug needed for brain tumor treatment. This is due to the blood brain barrier (BBB) that prevents molecules passing through the vascular endothelium. Recent methods have been developed to circumvent the BBB. Among them, convection-enhanced delivery (CED) relies on the continuous infusion of a fluid containing a therapeutic agent, under a pressure gradient. It permits a homogeneous and controlled drug distribution. The aims of this study were to characterise the CED method, and then to utilize it for glioma treatment in preclinical studies. Several drugs were tested: cisplatin, carbo-platin, oxaliplatin, and iodo-deoxyuridine. Two radiation modalities were evaluated: synchrotron stereotactic radiotherapy (monochromatic beam < 100 keV) and high energy irradiation (6 MV) obtained with a conventional medical linear accelerator. The results obtained reveal that the effectiveness of the combined treatment (platinated drug plus photon irradiation) is highly related to that of the chemotherapy. The data, obtained with the platinated chemotherapy, also show that high-energy X-ray irradiation (6 MV) is as effective as synchrotron X-ray irradiation. The results broaden the applicability of this chemotherapeutic approach to clinical trials. (author)

  4. Toxicity classification and evaluation of four pharmaceuticals classes: antibiotics, antineoplastics, cardiovascular, and sex hormones

    International Nuclear Information System (INIS)

    Sanderson, Hans; Brain, Richard A.; Johnson, David J.; Wilson, Christian J.; Solomon, Keith R.

    2004-01-01

    Four different classes of environmental concern are quantitatively and qualitatively assessed for environmental hazards; antibiotics (n = 226), antineoplastics (n = 81), cardiovascular (n = 272), and sex hormones (n 92). These along with an ECOSAR scan of all pharmaceuticals (n = 2848) were then classified according to the OECD aquatic toxicity classification system. The predicted species susceptibility is: daphnid > fish > algae, and the predicted rank order of relative toxicity: sex hormones > cardiovascular antibiotics > antineoplastics (Table 1). Generally, a relatively large proportion (1/3) of all pharmaceuticals are potentially very toxic to aquatic organisms (Table 2). The qualitative risk assessment ranking relative to probability and potential severity for human and environmental health effects is: antibiotics > sex hormones > cardiovascular > antineoplastics. (Q)SARs and pharmacodynamic information should be used to prioritize and steer experimental risk assessments of pharmaceuticals, and potentially, also be used in new drug discovery optimizing efficacy and in minimising environmental hazards of new products. Nuclear receptors are relatively well conserved in evolution. Currently, antibacterial resistance represents the most significant human health hazard, and potentially the largest non-target organism hazard is sex hormones acting as endocrine modulators in wildlife. Data for the individual compounds are accessible via http://www.uoguelph.ca/~hsander/

  5. Drug: D03414 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03414 Drug Carubicin hydrochloride (USAN) ... C26H27NO10. HCl D03414.gif ... Antineoplastic... ... DG01682 ... Anthracycline antineoplastic ... CAS: 52794-97-5 PubChem: 17397554 ChEMBL: CHEMBL537408 LigandBox: D03414 ...

  6. Drug: D05510 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05510 Drug Piroxantrone hydrochloride (USAN) ... C21H25N5O4. 2HCl D05510.gif ... Antineoplastic... ... DG01727 ... Anthraquinone antineoplastic ... anthraquinone derivative ... CAS: 105118-12-5 PubChem: 47207179 LigandBox: D05510 ...

  7. Drug: D02894 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02894 Drug Ametantrone acetate (USAN) ... C22H28N4O4. (C2H4O2)2 D02894.gif ... Antineoplastic ... DG01727 ... Anthra...quinone antineoplastic ... anthraquinone derivative ... CAS: 70711-40-9 PubChem: 17397051 ChEMBL: CHEMBL2104059 LigandBox: D02894 NIKKAJI: J395.653I ...

  8. Mecanismos de cardiotoxicidad: antineoplásicos, anti-inflamatorios no esteroideos, antipsicóticos, cocaetileno y simpaticomiméticos Mechanisms of cardiotoxicity: antineoplastics, nonsteroidal anti-inflammatory drugs, antipsychotics, cocaethylene and sympathomimetics

    Directory of Open Access Journals (Sweden)

    Lukas Salazar

    2011-04-01

    Full Text Available La interacción constante del organismo humano con diferentes sustancias, que incluso en muchas ocasiones se consideran inofensivas, tiene un alto impacto sobre todos los sistemas, siendo el cardiovascular uno de los más afectados. Por lo tanto, es vital reconocer los mecanismos por los cuales estas sustancias ejercen su efecto tóxico sobre este sistema, bien sea afectando la estabilidad de membrana y la función contráctil o generando disfunción de organelos intracelulares y estrés oxidativo. Numerosos estudios han descubierto efectos lesivos de sustancias, como la clozapina y las catecolaminas, que han tenido amplio uso durante largos años. En la actualidad aún se realizan investigaciones que buscan esclarecer los mecanismos cardiotóxicos de medicamentos de formulación común, entre ellos antineoplásicos y anti-inflamatorios no esteroideos (AINE, así como de sustancias de uso habitual que causan adicción, tales como alcohol, cocaína y cocaetileno, su metabolito activo.The constant interaction of the human body with different substances that are even in many cases considered harmless has a high impact on all systems, being the cardiovascular system one of the most affected. Therefore, it is vital to recognize the mechanisms by which these substances exert their toxic effect on this system, either affecting the membrane stability and the contractile function, or generating intracellular organelles dysfunction and oxidative stress. Numerous studies have found that drugs which have been widely used for many years such as clozapine and catecholamines, have harmful effects. Research is still being done seeking to clarify the cardiotoxic mechanisms of drugs commonly formulated, including anticancer and non steroidal anti-inflammatory drugs (NSAIDs, as well as commonly used substances that cause addiction, such as alcohol, cocaine and cocaethylene, its active metabolite.

  9. Drug: D02758 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02758 Drug Acolbifene hydrochloride (USAN) ... C29H31NO4. HCl D02758.gif ... Other ... DG01619 ... Clomifene and tam...oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... Selective estrogen r

  10. Drug: D06551 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06551 Drug Afimoxifene (USAN/INN); Tamogel (TN) ... C26H29NO2 D06551.gif ... Other ... DG01619 ... Clomifene and tam...oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... Selective estrogen r

  11. Glycaemic Adverse Drug Reactions from Anti-Neoplastics Used in ...

    African Journals Online (AJOL)

    2017-06-01

    Jun 1, 2017 ... Diabetes mellitus (DM) or hyperglycemia is common in pancreatic ... Fasting hyperglycemia is a dose‑dependent risk factor for .... is primary therapy for solitary pancreatic endocrine tumors. ... well‑known risk factor associated with decreased OS for ... induce peripheral insulin resistance, and thereby,.

  12. Evaluation of real-time data obtained from gravimetric preparation of antineoplastic agents shows medication errors with possible critical therapeutic impact: Results of a large-scale, multicentre, multinational, retrospective study.

    Science.gov (United States)

    Terkola, R; Czejka, M; Bérubé, J

    2017-08-01

    Medication errors are a significant cause of morbidity and mortality especially with antineoplastic drugs, owing to their narrow therapeutic index. Gravimetric workflow software systems have the potential to reduce volumetric errors during intravenous antineoplastic drug preparation which may occur when verification is reliant on visual inspection. Our aim was to detect medication errors with possible critical therapeutic impact as determined by the rate of prevented medication errors in chemotherapy compounding after implementation of gravimetric measurement. A large-scale, retrospective analysis of data was carried out, related to medication errors identified during preparation of antineoplastic drugs in 10 pharmacy services ("centres") in five European countries following the introduction of an intravenous workflow software gravimetric system. Errors were defined as errors in dose volumes outside tolerance levels, identified during weighing stages of preparation of chemotherapy solutions which would not otherwise have been detected by conventional visual inspection. The gravimetric system detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at participating centres between July 2011 and October 2015 had error levels outside the accepted tolerance range set by individual centres, and prevented these doses from reaching patients. The proportion of antineoplastic preparations with deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%. The proportion of preparations with deviations >20% ranged from 0.21% to 1.27% across sites, with a mean of 0.71%. There was considerable variation in error levels for different antineoplastic agents. Introduction of a gravimetric preparation system for antineoplastic agents detected and prevented dosing errors which would not have been recognized with traditional methods and could have resulted in toxicity or suboptimal therapeutic outcomes for patients undergoing anticancer treatment.

  13. New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

    Science.gov (United States)

    Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

    2017-12-01

    The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.

  14. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  15. Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

    Science.gov (United States)

    Madrigal-Burgaleta, R; Berges-Gimeno, M P; Angel-Pereira, D; Ferreiro-Monteagudo, R; Guillen-Ponce, C; Pueyo, C; Gomez de Salazar, E; Alvarez-Cuesta, E

    2013-07-01

    Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    Price, Paul S.; Keenan, Russell E.; Swartout, Jeffrey C.

    2008-01-01

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  17. Integrated system for error prevention in process of drugs used in oncology

    International Nuclear Information System (INIS)

    Soriano Garcia, Jorge L; Lima Perez, Mayte; Gonzalez Gonzalez, Joaquin; Batista Albuerne, Noyde; Rodriguez Lopez, Roberto; Garcia Dieguez, Robin; Gonzalez Duennas, Marta; Ugando, Elizabeth

    2007-01-01

    Medication mistakes in case of chemotherapy or adjuvant treatment used in any stage of drug application process: prescription, transcription, preparation, dispense or administration, are a frequent cause of side effects of antineoplastic drugs. (Author)

  18. Sesquiterpene lactones: Mechanism of antineoplastic activity; relationship of cellular glutathione to cytotoxicity; and disposition

    International Nuclear Information System (INIS)

    Grippo, A.A.

    1987-01-01

    Helenalin, a sesquiterpene lactone, inhibited the growth of P388 lymphocytic and L1210 lymphoid leukemia, and Ehrlich ascites and KB carcinoma cells. The L1210 leukemia cells were most sensitive to the cytotoxic effects of helenalin. Helenalin's antineoplastic effects were due to inhibition of DNA synthesis by suppressing the activities of enzymes involved in this biosynthetic pathway; i.e., IMP dehydrogenase, ribonucleoside diphosphate reductase, thioredoxin complex, GSH disulfide oxidoreductase and DNA polymerase α activities. The relationship of reduced glutathione (GSH) to the cytotoxic effects of helanalin was evaluated. L1210 cells, which were more sensitive to helenalin's toxicity, contained lower basal concentrations of GSH. Helenalin decreased the concentration of reduced glutathione in both L1210 and P388 leukemia cells. Concurrent administration of helanalin with agents reported to raise GSH concentrations did not substantially effect GSH levels, nor were survival times of tumor-bearing mice enhanced. Following intraperitoneal administration of 3 H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF 1 mice. Approximately 50% of 3 H-plenolin and/or its metabolites were eliminated via urine while lesser amounts of radioactive drug and/or metabolites were eliminated in the feces

  19. Spatially explicit prioritization of human antibiotics and antineoplastics in Europe.

    Science.gov (United States)

    Oldenkamp, Rik; Huijbregts, Mark A J; Hollander, Anne; Versporten, Ann; Goossens, Herman; Ragas, Ad M J

    2013-01-01

    This paper presents a screening tool for the location-specific prioritization of human pharmaceutical emissions in Europe, based on risk quotients for the aquatic environment and human health. The tool provides direction towards either monitoring activities or additional research. Its application is illustrated for a set of 11 human antibiotics and 7 antineoplastics. Risk quotients for the aquatic environment were highest for levofloxacin, doxycycline and ciprofloxacin, located in Northern Italy (Milan region; particularly levofloxacin) and other densely populated areas in Europe (e.g. London, Krakow and the Ruhr area). Risk quotients for human health not only depend on pharmaceutical and location, but also on behavioral characteristics, such as consumption patterns. Infants in eastern Spain that consume locally produced food and conventionally treated drinking water were predicted to run the highest risks. A limited comparison with measured concentrations in surface water showed that predicted and measured concentrations are approximately within one order of magnitude. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  1. Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.

    Science.gov (United States)

    Alvarez-Cuesta, E; Madrigal-Burgaleta, R; Angel-Pereira, D; Ureña-Tavera, A; Zamora-Verduga, M; Lopez-Gonzalez, P; Berges-Gimeno, M P

    2015-07-01

    Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans. © 2015 John Wiley & Sons A/S. Published by

  2. Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

    Science.gov (United States)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-10-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  3. Accelerator mass spectrometry analysis of "1"4C-oxaliplatin concentrations in biological samples and "1"4C contents in biological samples and antineoplastic agents

    International Nuclear Information System (INIS)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-01-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the "1"4C concentration in "1"4C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of "1"4C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a "1"4C content of water in three vacuum blood collection tubes and a syringe were measured. "1"4C was not detected from water in these devices. The mean "1"4C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of "1"4C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, "1"4C contents of the antineoplastic agents were quantitated. "1"4C contents were different among 10 antineoplastic agents; "1"4C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  4. Accelerator mass spectrometry analysis of {sup 14}C-oxaliplatin concentrations in biological samples and {sup 14}C contents in biological samples and antineoplastic agents

    Energy Technology Data Exchange (ETDEWEB)

    Toyoguchi, Teiko, E-mail: tteiko@med.id.yamagata-u.ac.jp [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kato, Kazuhiro; Tokanai, Fuyuki [Department of Physics, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata-shi, Yamagata 990-8560 (Japan)

    2015-10-15

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the {sup 14}C concentration in {sup 14}C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of {sup 14}C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a {sup 14}C content of water in three vacuum blood collection tubes and a syringe were measured. {sup 14}C was not detected from water in these devices. The mean {sup 14}C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of {sup 14}C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, {sup 14}C contents of the antineoplastic agents were quantitated. {sup 14}C contents were different among 10 antineoplastic agents; {sup 14}C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  5. The emerging role of antineoplastic agents in the treatment of keloids and hypertrophic scars: a review.

    Science.gov (United States)

    Shridharani, Sachin M; Magarakis, Michael; Manson, Paul N; Singh, Navin K; Basdag, Basak; Rosson, Gedge D

    2010-03-01

    The management of keloids and hypertrophic scars continues to challenge health-care providers. Though both forms of pathologic scarring are distinct entities at the macro and microscopic level, their etiologies and treatment are often similar. Potential treatment approaches are progressing, and combinations of treatment options have been proposed in the literature with promising outcomes. The treatment evolution has reached a level where molecular therapeutic modalities are being investigated. Currently, no gold standard treatment exists. Overall success rates and patient satisfaction seem to be slowly climbing, but additional investigational studies must continue to be performed. Several studies have investigated antineoplastic agents, and there seems to be a marked improvement in rates of recurrence, patient satisfaction, and overall quality of scar when these agents are used. Intralesional injection and/or wound irrigation with interferon-a2b, interferon-g, mitomycin-C, bleomycin, or 5-fluorouracil seems to have a positive effect on the reduction of pathologic scars. There is mounting evidence that these drugs used alone or in combination therapy, have the potential to be an integral part of the treatment paradigm for hypertrophic scars and keloids.

  6. Use of oral antineoplastic in special situations in a third level hospital: real life results

    Directory of Open Access Journals (Sweden)

    José Miguel Ferrari-Piquero

    2018-01-01

    Full Text Available Objective: To analyse the effectiveness and safety of oral antineoplastic drugs (ANEOs that are authorized in special situations in a third-level hospital and to compare the results obtained with the clinical evidence used for this authorization. Method: Descriptive observational and retrospective study. We included all adult patients who started treatment with ANEO in special situations during the year 2016. We collected demographic, treatment-related and clinical variables (overall survival (OS, progression-free survival (PFS. Adverse reactions and detected interactions were collected. An unadjusted comparison was made between the results of the available evidence and those of the study patients. Results: 34 patients were treated, 50% were men, the median age was 58 years (38-80 and they presented ECOG 1 in 64.7%. Most of the treated patients were diagnosed with advanced colorectal cancer, treated with trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8- 4.8 and the 8-month SG (95% CI 3.4-12.5 for all patients. 26% of patients required dose reduction because of treatment toxicity. We found 13 interactions, which affected 15 patients, only two of category X. Conclusions: The effectiveness of ANEO in special situations in our center is similar to that of available evidence. The impact on survival is low and adverse effects are common.

  7. Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

    Science.gov (United States)

    Alehashem, Maryam; Baniasadi, Shadi

    2018-01-01

    A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

  8. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    International Nuclear Information System (INIS)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua; Pollak, Michael; Gotlieb, Walter H.

    2011-01-01

    Highlights: ► siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. ► Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. ► Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. ► Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  9. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    Energy Technology Data Exchange (ETDEWEB)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Pollak, Michael [Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada); Gotlieb, Walter H., E-mail: walter.gotlieb@mcgill.ca [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. Black-Right-Pointing-Pointer Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. Black-Right-Pointing-Pointer Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. Black-Right-Pointing-Pointer Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  10. Evidence for tankyrases as antineoplastic targets in lung cancer

    International Nuclear Information System (INIS)

    Busch, Alexander M; Johnson, Kevin C; Stan, Radu V; Sanglikar, Aarti; Ahmed, Yashi; Dmitrovsky, Ethan; Freemantle, Sarah J

    2013-01-01

    New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β-catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β-catenin phosphorylation complex. This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and pharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo in mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative to controls. Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine transgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and TNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human lung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors XAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These inhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in conferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or shRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and syngeneic lung cancer models. Findings reported here uncovered deregulation of specific components of the Wnt pathway in both

  11. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  12. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  13. Dental anomalies in children submitted to antineoplastic therapy.

    Science.gov (United States)

    Carrillo, Camila Merida; Corrêa, Fernanda Nahás Pires; Lopes, Nilza Nelly Fontana; Fava, Marcelo; Odone Filho, Vicente

    2014-06-01

    Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  14. Dental anomalies in children submitted to antineoplastic therapy

    Directory of Open Access Journals (Sweden)

    Camila Merida Carrillo

    2014-06-01

    Full Text Available Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  15. [Blending powdered antineoplastic medicine in disposable ointment container].

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

    On dispensing powdered antineoplastic medicines, it is important to prevent cross-contamination and environmental exposure. Recently, we developed a method for blending powdered medicine in a disposable ointment container using a planetary centrifugal mixer. The disposable container prevents cross-contamination. In addition, environmental exposure associated with washing the apparatus does not arise because no blending blade is used. In this study, we aimed to confirm the uniformity of the mixture and weight loss of medicine in the blending procedure. We blended colored lactose powder with Leukerin(®) or Mablin(®) powders using the new method and the ordinary pestle and mortar method. Then, the blending state was monitored using image analysis. Blending variables, such as the blending ratio (1:9-9:1), container size (35-125 mL), and charging rate (20-50%) in the container were also investigated under the operational conditions of 500 rpm and 50 s. At a 20% charging rate in a 35 mL container, the blending precision of the mixtures was not influenced by the blending ratio, and was less than 6.08%, indicating homogeneity. With an increase in the charging rate, however, the blending precision decreased. The possible amount of both mixtures rose to about 17 g with a 20% charging rate in a 125 mL container. Furthermore, weight loss of medicines with this method was smaller than that with the pestle and mortar method, suggesting that this method is safer for pharmacists. In conclusion, we have established a precise and safe method for blending powdered medicines in pharmacies.

  16. Drug: D00966 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available if ... Antineoplastic ... DG01585 ... Estrogen receptor antagonist Other ... DG01619 ... Clomifene and tamoxifen derivative ... DG01620 ... Tam... D00966 Drug Tamoxifen citrate (JP17/USP); Nolvadex (TN) ... C26H29NO. C6H8O7 D00966.g

  17. Drug: D05192 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05192 Drug Nitromifene citrate (USAN) ... C27H28N2O4. C6H8O7 D05192.gif ... Other ... DG01619 ... Clomifene and tam...oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... DG01584 ... Estrogen recep

  18. Drug: D03912 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03912 Drug Droloxifene citrate (USAN) ... C26H29NO2. C6H8O7 D03912.gif ... Other ... DG01619 ... Clomifene and tam...oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic Chemical group: DG01265 ...

  19. Drug: D08559 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Antineoplastic ... DG01585 ... Estrogen receptor antagonist Other ... DG01619 ... Clomifene and tamoxifen derivative ... DG01620 ... Tam... D08559 Drug Tamoxifen (INN); Tamoxifen (TN); Tamoplex (TN) ... C26H29NO D08559.gif ... ...en [CPD:C16547] Indication: Metastatic breast cancer Use Tamoxifen to Patients who have factor V leiden muta

  20. Drug: D01853 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01853 Drug Miproxifene phosphate (JAN); Tat 59 ... C29H36NO5P D01853.gif ... Other ... DG01619 ... Clomifene and tam...oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... prodrug NR3A1 (ESR1)

  1. Drug: D04496 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... DG01621 ... Cloimifene-type osteoporosis agent ... Clomifene, tam... D04496 Drug Idoxifene (USAN/INN) ... C28H30INO D04496.gif ... Other ... DG01619 ... Clomifene and tam

  2. Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Takumi Tsuda

    Full Text Available Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG-loaded lactosome for near-infrared fluorescence (NIF imaging and photodynamic therapy (PDT for HCC.The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency. For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency.PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome.Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.

  3. Comparison of new nitrosoureas esters with modified steroidal nucleus for cytogenetic and antineoplastic activity.

    Science.gov (United States)

    Hussein, A; Mioglou-Kalouptsi, E; Papageorgiou, A; Karapidaki, I; Iakovidou-Kritsi, Z; Lialiaris, T; Xrysogelou, E; Camoutsis, C; Mourelatos, D

    2007-01-01

    Nitrosourea is decomposed under physiological conditions to react with biological macromolecules by two mechanisms: alkylation (with proteins and nucleic acids) and carbamoylation (with proteins but not nucleic acids). It has been suggested that the alkylating action is responsible for the therapeutic effects of nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In order to reduce systemic toxicity and improve specificity and distribution for cancer therapy, 2-haloethyl nitrosourea has been esterified with modified steroids, which are used as biological platforms for transporting the alkylating agent to the tumor site in a specific manner. The cytogenetic and antineoplastic effect were studied of seven newly synthesized esters of N,N-bis(2-chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic activity the cell Proliferation Rate Index (PRI) in cultures of normal human lymphocytes was used. The order of magnitude of the cytogenetic activity on a molar basis (15, 30, 120 microM) of the compounds was 7>6>3>5>2>4>1. The most active compound 7 has an enlarged (seven carbon atoms) A ring modified with a lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In the group of seven substances a correlation was observed between the magnitude of SCE response and the depression in PRI (r=-O, 65, p6>2>5>4>3>1 and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are in agreement with previous suggestions that the effectiveness in cytogenetic activity may well be correlated with antitumor effects [T/C: 248% for the compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug-treated animals (T) (excluding long term survivals) vs. corn-oil-treated controls (C)].

  4. The husk fiber of Cocos nucifera L. (Palmae) is a source of anti-neoplastic activity.

    Science.gov (United States)

    Koschek, P R; Alviano, D S; Alviano, C S; Gattass, C R

    2007-10-01

    In the present study, we investigated the in vitro anti-tumoral activities of fractions from aqueous extracts of the husk fiber of the typical A and common varieties of Cocos nucifera (Palmae). Cytotoxicity against leukemia cells was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (2 x 10(4)/well) were incubated with 0, 5, 50 or 500 microg/mL high- or low-molecular weight fractions for 48 h, treated with MTT and absorbance was measured with an ELISA reader. The results showed that both varieties have almost similar antitumoral activity against the leukemia cell line K562 (60.1 +/- 8.5 and 47.5 +/- 11.9% for the typical A and common varieties, respectively). Separation of the crude extracts with Amicon membranes yielded fractions with molecular weights ranging in size from 1-3 kDa (fraction A) to 3-10 kDa (fraction B) and to more than 10 kDa (fraction C). Cells were treated with 500 microg/mL of these fractions and cytotoxicity was evaluated by MTT. Fractions ranging in molecular weight from 1-10 kDa had higher cytotoxicity. Interestingly, C. nucifera extracts were also active against Lucena 1, a multidrug-resistant leukemia cell line. Their cytotoxicity against this cell line was about 50% (51.9 +/- 3.2 and 56.3 +/- 2.9 for varieties typical A and common, respectively). Since the common C. nucifera variety is extensively cultured in Brazil and the husk fiber is its industrial by-product, the results obtained in the present study suggest that it might be a very inexpensive source of new antineoplastic and anti-multidrug resistant drugs that warrants further investigation.

  5. Use of oral antineoplastic in special situations in a third level hospital: real life results.

    Science.gov (United States)

    Garcia-Muñoz, Carmen; Rodriguez-Quesada, Pedro Pablo; Ferrari-Piquero, José Miguel

    2018-01-01

    To analyse the effectiveness and safety of oral antineoplastic drugs  (ANEOs) that are authorized in special situations in a third-level hospital and to  compare the results obtained with the clinical evidence used for this  authorization. Descriptive observational and retrospective study. We included all  adult patients who started treatment with ANEO in special situations during the  year 2016. We collected demographic, treatment-related and clinical variables  (overall survival (OS), progression-free survival (PFS)). Adverse reactions and  detected interactions were collected. An unadjusted comparison was made  between the results of the available evidence and those of the study patients. 34 patients were treated, 50% were men, the median age was 58  years (38-80) and they presented ECOG 1 in 64.7%. Most of the treated  patients were diagnosed with advanced colorectal cancer, treated with  trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results  similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8- 4.8) and the 8-month SG (95% CI 3.4-12.5) for all patients. 26% of patients  required dose reduction because of treatment toxicity. We found 13 interactions,  which affected 15 patients, only two of category X. The effectiveness of ANEO in special situations in our center is  similar to that of available evidence. The impact on survival is low and adverse  effects are common. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  6. Oral antineoplastic agent interactions with medicinal plants and food: an issue to take into account.

    Science.gov (United States)

    Collado-Borrell, Roberto; Escudero-Vilaplana, Vicente; Romero-Jiménez, Rosa; Iglesias-Peinado, Irene; Herranz-Alonso, Ana; Sanjurjo-Sáez, María

    2016-11-01

    To review interactions between oral antineoplastic agents (OAAs) for the treatment of solid and hematological tumors and common food and medicinal plants. All potential interactions between OAAs, medicinal plants and food were reviewed. OAAs were considered to be drugs for oral administration that have direct antitumor activity and were approved by the European Medicines Agency in April 2015. We performed the literature search in Pubmed(®) considering only medicinal plants and food. In addition, available data were analyzed from each OAA in secondary data sources taken from Thomson Micromedex(®) and Lexi-comp(®), as well as in the summary of product characteristics. Fifty-eight OAAs were analyzed. We found interactions in 60.3 % of OAAs. Those with most interactions described were: imatinib and procarbazine (4 interactions) and erlotinib, vemurafenib, pomalidomide, medroxyprogesterone and methotrexate (3 interactions). We found 39 interactions (74.4 % important). St. John's wort was the medicinal plant with most interactions (92.6 % were considered important). The rest were: important (ginseng-imatinib, methotrexate-cola and tobacco-erlotinib and tobacco-pomalidomide) and moderate (caffeine-vemurafenib/medroxyprogesterone, medroxyprogesterone-ruxolitinib/St. John's wort, garlic-anagrelide and ginseng-procarbazine). Twenty-six interactions (61.5 % important). Grapefruit had most interactions (82.4 % were considered important). The rest were: important (alcohol-procarbazine) and moderate (dairy-estramustine, methotrexate-ethanol, procarbazine-tyramine, vitamin A-tretinoin/bexarotene and grapefruit-bexarotene/etoposide/sunitinib). A review of interactions of medicinal plants and food should be taken into account in the management of OAAs, since more than half have interactions with MPs and food, of which 70.3 % are considered important. The most relevant are HSJ, grapefruit, ginseng and tobacco. This review is intended to serve as a support to all healthcare

  7. Flavonoids from Heliotropium subulatum exudate and their evaluation for antioxidant, antineoplastic and cytotoxic activities II.

    Science.gov (United States)

    Singh, Bharat; Sahu, Pooran M; Sharma, Ram A

    2017-02-01

    The flavonoids are the largest group of phenolic compounds isolated from a wide range of higher plants. These compounds work as antimicrobials, anti-insect agents and protect plants from other types of biotic and abiotic stresses. Various researchers have suggested that flavonoids possessed antioxidant, antineoplastic and cytotoxic activities. The main objective of this study was to test dichloromethane fraction of resinous exudate of Heliotropium subulatum for their antioxidant, antineoplastic and cytotoxic activities, as well as to search new antioxidant and antineoplastic agents for pharmaceutical formulations. Five flavonoids were isolated from resinous exudate of this plant species and screened for their in vitro and in vivo antioxidant models (DPPH radical scavenging, reducing power, superoxide anion scavenging, metal chelating scavenging systems, catalase and lipid peroxidation), antineoplastic (Sarcoma 180), and cytotoxic (Chinese hamster V79 cells) activities. Tricetin demonstrated maximum antioxidant activity against both in vitro and in vivo experimental systems while galangin exhibited maximum inhibition (78.35%) at a dose of 10 µg/kg/day against Sarcoma 180. Similarly, it was found that galangin also showed highest activity (21.1 ± 0.15%) at a concentration of 70 µg/ml to Chinese hamster V79 cells. The observed results suggest that tricetin has a potential to scavenge free radicals in both in vitro and in vivo models while the galangin could be considered as antitumor and cytotoxic agent.

  8. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

  9. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

    Science.gov (United States)

    Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-01-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

  10. The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.

    Science.gov (United States)

    Craveiro, Rogerio B; Ehrhardt, Michael; Velz, Julia; Olschewski, Martin; Goetz, Barbara; Pietsch, Torsten; Dilloo, Dagmar

    2017-07-18

    Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

  11. Does applying technology throughout the medication use process improve patient safety with antineoplastics?

    Science.gov (United States)

    Bubalo, Joseph; Warden, Bruce A; Wiegel, Joshua J; Nishida, Tess; Handel, Evelyn; Svoboda, Leanne M; Nguyen, Lam; Edillo, P Neil

    2014-12-01

    Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the

  12. Perigos potenciais a que est��o expostos os trabalhadores de enfermagem na manipulação de quimioterápicos antineoplásicos: conhecê-los para prevení-los Riesgos potenciales a que están expuestos los trabajadores de enfermería en la manipulación de quimioterápicos antineoplásicos: conocerlos para prevenirlos Potential risks nursing workers are exposed to in handling antineoplastic drugs: know ledge for prevention

    Directory of Open Access Journals (Sweden)

    Fernanda Ludmilla Rossi Rocha

    2004-06-01

    data collection. Results disclosed that most of the workers consider that the manipulation of antineoplastic drugs offers risks to their health, but without the ability to identify these risks clearly.

  13. Dental root agenesis following radiation and antineoplastic therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdul Hafiz

    2016-01-01

    Full Text Available The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl.

  14. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  15. Clinical effect of Cystenosine on leukocytopenia at the time of therapy with radiation and antineoplastic agents

    International Nuclear Information System (INIS)

    Sato, Kazuhide; Usui, Ryu; Inoue, Hiroshi; Mihashi, Norio; Niibe, Hideo.

    1977-01-01

    Out of 62 cases, 25 cases received only radiotherapy, 11 cases received both radiotherapy and antineoplastic agents, and 26 cases received only antineoplastic agents. Total dose of x-ray ranges from 3000 to 6200 rad in 18 of 36 cases of the former two groups, and 2600 to 6260 rad of 60 Co dose were irradiated to 18 cases of the rest. This agent was administered 9 tablets per a day (one tablet contains 200 mg of inosine and 20 mg of cystine) for 19 to 142 days. Its effects on leukocytopenia showed marked effectiveness in 9 out of 25 cases treated with only radiation, effectiveness in 8 cases, and ineffectiveness in 3 cases. Its effective rate was 72.8%. The effective rate was 65.4% in the cases treated with only antineoplastic agents, and was 67.7% in all cases. A certain relationship between dose and the effective rate was not recognized. Radiation sickness, such as loss of appetite general fatigue and mausea, decreased gradually by using this agent. Side effect was not recognized particularly. (Kanao. N.)

  16. Changes in the chemical composition of mineralised teeth in children after antineoplastic treatment.

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Dembowska-Bagińska, Bożenna; Brożyna, Agnieszka; Olczak-Kowalczyk, Dorota; Czarnowska, Elżbieta; Sowińska, Agnieszka

    2018-01-01

    Chemotherapy, neoplasms, and their complications linked to malabsorption, malnutrition, and metabolic disorders may lead to improper tooth development and frequent severe caries in patients during/after antineoplastic treatment and to a more frequent improper tooth development in patients undergoing chemotherapy during odontogenesis. However, the causes of these abnormalities remain unknown; there are no studies on the impact of antineoplastic treatment and its complications on the chemical composition of mineralised teeth. To compare the chemical composition of mineralised teeth extracted due to complicated caries in children after chemotherapy, and of teeth extracted due to orthodontic treatment in generally healthy children. The treatment group included five teeth extracted due to complicated caries in children after antineoplastic treatment. The control group included five teeth extracted due to orthodontic treatment in generally healthy children. The chemical composition of enamel, dentine, cementum, interior of the canal, and enamel abnormalities in teeth extracted from patients after chemotherapy and in generally healthy patients were assessed with energy-dispersive X-ray spectroscopy. Results were analysed statistically. The magnesium (Mg) and zinc (Zn) mass contents in the enamel of patients after chemotherapy increased and so did the calcium (Ca) to phosphorus (P) ratio when compared to controls. Areas with abnormal enamel in patients after chemotherapy had lower concentrations of Ca and P, and higher concentrations of trace elements (Mg, Cl, and Na). The levels of the assessed elements in dentine, cementum, and inside the canal were similar in both groups of teeth.

  17. Stability of allopurinol and of five antineoplastics in suspension.

    Science.gov (United States)

    Dressman, J B; Poust, R I

    1983-04-01

    The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

  18. List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012

    Science.gov (United States)

    ... supple- mental publication to the PDA Journal of Pharmaceutical Science and Technol- ogy. Provides definitions, design, and op- ... healthy workers. PDA: An international trade association serving pharmaceutical science and tech- nology. Formerly known as the Parenteral ...

  19. Drug: D03046 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available arasid (TN) ... C27H49N3O8P. Na. H2O D03046.gif ... Antineoplastic ... DG01958 ... Nucleic acid derivative, antineoplastic... ... DG01439 ... Arabinofuranosyl type antineoplastic ... DG01439 ... Arabinofuranosyl type antineoplastic Unclassi...fied ... DG02018 ... Antimetabolite ... DG01958 ... Nucleic acid derivative, antineoplastic ... ... DG01439 ... Arabinofuranosyl type antineoplastic Therapeutic category: 4224 ATC code: L01BC01 Chemical group

  20. On/off-switchable anti-neoplastic nanoarchitecture

    Science.gov (United States)

    Patra, Hirak K.; Imani, Roghayeh; Jangamreddy, Jaganmohan R.; Pazoki, Meysam; Iglič, Aleš; Turner, Anthony P. F.; Tiwari, Ashutosh

    2015-09-01

    Throughout the world, there are increasing demands for alternate approaches to advanced cancer therapeutics. Numerous potentially chemotherapeutic compounds are developed every year for clinical trial and some of them are considered as potential drug candidates. Nanotechnology-based approaches have accelerated the discovery process, but the key challenge still remains to develop therapeutically viable and physiologically safe materials suitable for cancer therapy. Here, we report a high turnover, on/off-switchable functionally popping reactive oxygen species (ROS) generator using a smart mesoporous titanium dioxide popcorn (TiO2 Pops) nanoarchitecture. The resulting TiO2 Pops, unlike TiO2 nanoparticles (TiO2 NPs), are exceptionally biocompatible with normal cells. Under identical conditions, TiO2 Pops show very high photocatalytic activity compared to TiO2 NPs. Upon on/off-switchable photo activation, the TiO2 Pops can trigger the generation of high-turnover flash ROS and can deliver their potential anticancer effect by enhancing the intracellular ROS level until it crosses the threshold to open the ‘death gate’, thus reducing the survival of cancer cells by at least six times in comparison with TiO2 NPs without affecting the normal cells.

  1. The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

    Science.gov (United States)

    Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

    2011-10-01

    Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

  2. Observational study of drug-drug interactions in oncological inpatients

    Directory of Open Access Journals (Sweden)

    María Sacramento Díaz-Carrasco

    2018-01-01

    Full Text Available Objective: To determine the prevalence of potential clinically relevant drug- drug interactions in adult oncological inpatients, as well as to describe the most frequent interactions. A standard database was used. Method: An observational, transversal, and descriptive study including patients admitted to the Oncology Service of a reference hospital. All prescriptions were collected twice a week during a month. They were analysed using Lexicomp® database, recording all interactions classified with a level of risk: C, D or X. Results: A total of 1 850 drug-drug interactions were detected in 218 treatments. The prevalence of treatments with at least one clinically relevant interaction was 95%, being 94.5% for those at level C and 26.1% for levels D and X. The drugs most commonly involved in the interactions detected were opioid analgesics, antipsychotics (butyrophenones, benzodiazepines, pyrazolones, glucocorticoids and heparins, whereas interactions with antineoplastics were minimal, highlighting those related to paclitaxel and between metamizole and various antineoplastics. Conclusions: The prevalence of clinically relevant drug-drug interactions rate was very high, highlighting the high risk percentage of them related to level of risk X. Due to the frequency of onset and potential severity, highlighted the concomitant use of central nervous system depressants drugs with risk of respiratory depression, the risk of onset of anticholinergic symptoms when combining morphine or haloperidol with butylscopolamine, ipratropium bromide or dexchlorpheniramine and the multiple interactions involving metamizole.

  3. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  4. QSPR modeling of octanol/water partition coefficient of antineoplastic agents by balance of correlations.

    Science.gov (United States)

    Toropov, Andrey A; Toropova, Alla P; Raska, Ivan; Benfenati, Emilio

    2010-04-01

    Three different splits into the subtraining set (n = 22), the set of calibration (n = 21), and the test set (n = 12) of 55 antineoplastic agents have been examined. By the correlation balance of SMILES-based optimal descriptors quite satisfactory models for the octanol/water partition coefficient have been obtained on all three splits. The correlation balance is the optimization of a one-variable model with a target function that provides both the maximal values of the correlation coefficient for the subtraining and calibration set and the minimum of the difference between the above-mentioned correlation coefficients. Thus, the calibration set is a preliminary test set. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  5. Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

    Science.gov (United States)

    Gérard, S; Bréchemier, D; Lefort, A; Lozano, S; Abellan Van Kan, G; Filleron, T; Mourey, L; Bernard-Marty, C; Rougé-Bugat, M E; Soler, V; Vellas, B; Cesari, M; Rolland, Y; Balardy, L

    2016-01-01

    The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

  6. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ye J

    2016-08-01

    Full Text Available Jun Ye,1,2 Xuejun Xia,1,2 Wujun Dong,1,2 Huazhen Hao,1,2 Luhua Meng,1,2 Yanfang Yang,1,2 Renyun Wang,1,2 Yuanfeng Lyu,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: There is no effective clinical therapy for triple-negative breast cancers (TNBCs, which have high low-density lipoprotein (LDL requirements and express relatively high levels of LDL receptors (LDLRs on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231 and non-TNBC (MCF7 cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native

  7. Adherence of paclitaxel drug in magnetite chitosan nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Escobar Zapata, Edna V.; Martinez Perez, Carlos A.; Rodriguez Gonzalez, Claudia A.; Castro Carmona, Javier S. [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico); Quevedo Lopez, Manuel A. [Departamento de Polimeros y Materiales, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora (Mexico); Garcia-Casillas, Perla E., E-mail: pegarcia@uacj.mx [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico)

    2012-09-25

    Highlights: Black-Right-Pointing-Pointer Chitosan silica magnetite adsorbs antineoplastic drug. Black-Right-Pointing-Pointer Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV-Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.

  8. Adherence of paclitaxel drug in magnetite chitosan nanoparticles

    International Nuclear Information System (INIS)

    Escobar Zapata, Edna V.; Martínez Pérez, Carlos A.; Rodríguez González, Claudia A.; Castro Carmona, Javier S.; Quevedo Lopez, Manuel A.; García-Casillas, Perla E.

    2012-01-01

    Highlights: ► Chitosan silica magnetite adsorbs antineoplastic drug. ► Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV–Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.

  9. Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

    Science.gov (United States)

    Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

    2009-08-06

    Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing

  10. Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

    Science.gov (United States)

    Dranitsaris, G; Altmayer, C; Quirt, I

    1997-06-01

    Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

  11. Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo.

    Science.gov (United States)

    Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia

    2014-01-30

    This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

    Directory of Open Access Journals (Sweden)

    М. R. Fil

    2014-12-01

    Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

  13. BEL β-trefoil: a novel lectin with antineoplastic properties in king bolete (Boletus edulis) mushrooms.

    Science.gov (United States)

    Bovi, Michele; Cenci, Lucia; Perduca, Massimiliano; Capaldi, Stefano; Carrizo, Maria E; Civiero, Laura; Chiarelli, Laurent R; Galliano, Monica; Monaco, Hugo L

    2013-05-01

    A novel lectin was purified from the fruiting bodies of king bolete mushrooms (Boletus edulis, also called porcino, cep or penny bun). The lectin was structurally characterized i.e its amino acid sequence and three-dimensional structure were determined. The new protein is a homodimer and each protomer folds as β-trefoil domain and therefore we propose the name Boletus edulis lectin (BEL) β-trefoil to distinguish it from the other lectin that has been described in these mushrooms. The lectin has potent anti-proliferative effects on human cancer cells, which confers to it an interesting therapeutic potential as an antineoplastic agent. Several crystal forms of the apoprotein and of complexes with different carbohydrates were studied by X-ray diffraction. The structure of the apoprotein was solved at 1.12 Å resolution. The interaction of the lectin with lactose, galactose, N-acetylgalactosamine and T-antigen disaccharide, Galβ1-3GalNAc, was examined in detail. All the three potential binding sites present in the β-trefoil fold are occupied in at least one crystal form and are described in detail in this paper. No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein.

  14. The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.

    Science.gov (United States)

    Ehrhardt, Michael; Craveiro, Rogerio B; Velz, Julia; Olschewski, Martin; Casati, Anna; Schönberger, Stefan; Pietsch, Torsten; Dilloo, Dagmar

    2018-04-01

    Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53-mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c-kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi-modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Polypharmacology of Approved Anticancer Drugs.

    Science.gov (United States)

    Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

    2017-01-01

    The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients

    International Nuclear Information System (INIS)

    Monroy-Cisneros, Karina; Esparza-Romero, Julián; Valencia, Mauro E.; Guevara-Torres, Alfonso G.; Méndez-Estrada, Rosa O.; Anduro-Corona, Iván; Astiazarán-García, Humberto

    2016-01-01

    Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm 2 in femoral neck and 0.063 g/cm 2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm 2 in femoral neck and 0.035 g/cm 2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm 2 (p = 0.003). The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status

  17. Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

    Science.gov (United States)

    Bontempo, P; Doto, A; Miceli, M; Mita, L; Benedetti, R; Nebbioso, A; Veglione, M; Rigano, D; Cioffi, M; Sica, V; Molinari, A M; Altucci, L

    2012-02-01

    Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. © 2011 Blackwell Publishing Ltd.

  18. Drug: D04783 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ... Antineoplastic ... DG01727 ... Anthraquinone antineoplastic ... anthraquinone derivative TOP2 [HSA:7153 7155] [KO:K03164] ... CAS: 132937-89-4 PubChem: 47206593 LigandBox: D04783 ...

  19. Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2017-03-01

    One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine-reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5'-phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10 -9  M and 10 -7  M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  20. Guidelines for safe handling of hazardous drugs: A systematic review.

    Science.gov (United States)

    Bernabeu-Martínez, Mari A; Ramos Merino, Mateo; Santos Gago, Juan M; Álvarez Sabucedo, Luis M; Wanden-Berghe, Carmina; Sanz-Valero, Javier

    2018-01-01

    To review the scientific literature related to the safe handling of hazardous drugs (HDs). Critical analysis of works retrieved from MEDLINE, the Cochrane Library, Scopus, CINHAL, Web of Science and LILACS using the terms "Hazardous Substances", "Antineoplastic Agents" and "Cytostatic Agents", applying "Humans" and "Guidelines" as filters. Date of search: January 2017. In total, 1100 references were retrieved, and from those, 61 documents were selected based on the inclusion and exclusion criteria: 24 (39.3%) documents related to recommendations about HDs; 27 (44.3%) about antineoplastic agents, and 10 (33.3%) about other types of substances (monoclonal antibodies, gene medicine and other chemical and biological agents). In 14 (23.3%) guides, all the stages in the manipulation process involving a risk due to exposure were considered. Only one guide addressed all stages of the handling process of HDs (including stages with and without the risk of exposure). The most described stages were drug preparation (41 guides, 67.2%), staff training and/or patient education (38 guides, 62.3%), and administration (37 guides, 60.7%). No standardized informatics system was found that ensured quality management, traceability and minimization of the risks associated with these drugs. Most of the analysed guidelines limit their recommendations to the manipulation of antineoplastics. The most frequently described activities were preparation, training, and administration. It would be convenient to apply ICTs (Information and Communications Technologies) to manage processes involving HDs in a more complete and simpler fashion.

  1. Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

    Science.gov (United States)

    Opoku, A R; Geheeb-Keller, M; Lin, J; Terblanche, S E; Hutchings, A; Chuturgoon, A; Pillay, D

    2000-11-01

    Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage. Copyright 2000 John Wiley & Sons, Ltd.

  2. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy.

    Science.gov (United States)

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; Almeida, Ana Maria de; Gozzo, Thais de Oliveira

    2016-10-10

    to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. identificar os fatores relacionados ao diagnóstico de enfermagem náusea entre pacientes oncológicos durante o tratamento quimioterápico. revisão integrativa de quatro bases eletrônicas de dados (PUBMED, EMBASE, CINAHL e LILACS) com as palavras-chaves neoplasia, agentes antineoplásicos e náusea. dos 1258 artigos identificados, somente 30 atenderam aos critérios de inclusão. Os fatores relacionados mais frequentes foram: idade abaixo de 50 anos, doença do movimento, sexo feminino, potencial emético do quimioterápico, ansiedade, estímulo condicionado e expectativa de náuseas depois do tratamento. diante dos resultados encontrados e da incidência de náusea entre os pacientes oncológicos em tratamento quimioterápico, observa-se diferença importante entre as evidências encontradas e as utilizadas pela NANDA International, Inc. Apesar da definição estar adequada entre os fatores relacionados, não há menção à quimioterapia mesmo com inúmeros estudos, com diferentes delineamentos

  3. Bringing Radiotracing to Titanium-Based Antineoplastics: Solid Phase Radiosynthesis, PET and ex Vivo Evaluation of Antitumor Agent [45Ti](salan)Ti(dipic)

    DEFF Research Database (Denmark)

    Severin, Gregory; Nielsen, Carsten H.; Jensen, Andreas Tue Ingemann

    2015-01-01

    We present a novel solid-phase based 45Ti radiolabeling methodology and the implementation of 45Ti-PET in titanium-based antineoplastics using the showcase compound [45Ti](salan)Ti(dipic). This development is intended to allow elucidation of the biodistribution and pharmacokinetics of promising new...

  4. Optimal Anti-cancer Drug Profiles for Effective Penetration of the Anti-cancer Drug Market by Generic Drugs in Japan.

    Science.gov (United States)

    Shibata, Shoyo; Matsushita, Maiko; Saito, Yoshimasa; Suzuki, Takeshi

    2017-01-01

    The increased use of generic drugs is a good indicator of the need to reduce the increasing costs of prescription drugs. Since there are more expensive drugs compared with other therapeutic areas, "oncology" is an important one for generic drugs. The primary objective of this article was to quantify the extent to which generic drugs in Japan occupy each level of the Anatomical Therapeutic Chemical (ATC) classification system. The dataset used in this study was created from publicly available information obtained from the IMS Japan Pharmaceutical Market database. Data on the total amount of sales and number of prescriptions for anti-cancer drugs between 2010 and 2016 in Japan were selected. The data were categorized according to the third level of the ATC classification system. All categories of the ATC classification system had increased market shares in Japan between 2010 and 2016. The barriers to market entry were relatively low in L01F (platinum anti-neoplastics), L01C (plant-based neoplastics), L02B (cytostatic hormone antagonists), and L01D (anti-neoplastic antibiotics) but were high in L02A (cytostatic hormones), L01H (protein kinase inhibitors), and L01B (anti-metabolites). Generic cancer drugs could bring savings to Japanese health care systems. Therefore, their development should be directed toward niche markets, such as L02A, L01H, and L01B, and not competitive markets.

  5. Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

    Science.gov (United States)

    Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander

    2017-01-01

    Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted. PMID:27009803

  6. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  7. New Antimicrobial Approaches: Reuse of Old Drugs.

    Science.gov (United States)

    Savoia, Dianella

    2016-01-01

    The global situation of antibiotic resistance and the reduction of investments in antibiotics research by the pharmaceutical industry suggest the need for specific cost-effective approaches in order to identify drugs for the therapy of many microbial infections. Among the viable alternative anti-infective compounds, drug repurposing, i.e. to find new uses for previously approved medicines, revealed some encouraging in vitro and in vivo results. In this article the reader has a panoramic view of the updated references on the strategies encountered during the repositioning process. New findings are reported about the anti-microbial efficacy of antipsychotic, cardiovascular, anti-inflammatory and anti-neoplastic drugs. This approach may enhance the portfolio of pharmaceutical companies reducing the need for pharmacokinetic and toxicity studies; the development of new uses of old drugs for different infectious diseases, leading to better health for patients, also in poor, tropical countries, appears to be having better results.

  8. Drug cocktail optimization in chemotherapy of cancer.

    Directory of Open Access Journals (Sweden)

    Saskia Preissner

    Full Text Available BACKGROUND: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP. Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. OBJECTIVE: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. DATA SOURCES AND METHODS: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. RESULTS: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

  9. PTTG1 attenuates drug-induced cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yunguang Tong

    Full Text Available As PTTG1 (pituitary tumor transforming gene abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1(-/- exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1(-/- senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001. p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1(-/- cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1(-/- cells after treatment, suggesting transcriptional regulation of p21. p21 knock down abrogated the observed senescent effects of these drugs, indicating that PTTG1 likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated SW620 colon cancer cells response to doxorubicin and TSA mediated by p21. Subcutaneously xenografted PTTG1(-/- HCT116 cells developed smaller tumors and exhibited enhanced responses to doxorubicin. PTTG1(-/- tumor tissue derived from excised tumors exhibited increased doxorubicin-induced senescence. As senescence is a determinant of cell responses to anti-neoplastic treatments, these findings suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment outcomes.

  10. Acute respiratory failure caused by organizing pneumonia secondary to antineoplastic therapy for non-Hodgkin's lymphoma

    Science.gov (United States)

    Santana, Adriell Ramalho; Amorim, Fábio Ferreira; Soares, Paulo Henrique Alves; de Moura, Edmilson Bastos; Maia, Marcelo de Oliveira

    2012-01-01

    Interstitial lung diseases belong to a group of diseases that typically exhibit a subacute or chronic progression but that may cause acute respiratory failure. The male patient, who was 37 years of age and undergoing therapy for non-Hodgkin's lymphoma, was admitted with cough, fever, dyspnea and acute hypoxemic respiratory failure. Mechanical ventilation and antibiotic therapy were initiated but were associated with unfavorable progression. Thoracic computed tomography showed bilateral pulmonary "ground glass" opacities. Methylprednisolone pulse therapy was initiated with satisfactory response because the patient had used three drugs related to organizing pneumonia (cyclophosphamide, doxorubicin and rituximab), and the clinical and radiological symptoms were suggestive. Organizing pneumonia may be idiopathic or linked to collagen diseases, drugs and cancer and usually responds to corticosteroid therapy. The diagnosis was anatomopathological, but the patient's clinical condition precluded performing a lung biopsy. Organizing pneumonia should be a differential diagnosis in patients with apparent pneumonia and a progression that is unfavorable to antimicrobial treatment. PMID:23917942

  11. Effects of antineoplastic agents and ionizing irradiation on a human testicular cancer xenograft

    International Nuclear Information System (INIS)

    Osieka, R.; Pfeiffer, R.; Glatte, P.; Schmidt, C.G.; Bamberg, M.; Scherer, E.

    1985-01-01

    Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease. (orig.) [de

  12. Factors associated with prescribing restriction on oncology formulary drugs in Malaysia.

    Science.gov (United States)

    Fatokun, Omotayo; Olawepo, Michael N

    2016-10-01

    Background Drugs listed on formularies are often subjected to a variety of utilization restriction measures. However, the degree of restriction is influenced by multiple factors, including the characteristics and attributes of the listed drugs. Objective To identify the factors that are associated with the levels of prescribing restriction on oncology formulary drugs in Malaysia. Setting Oncology formulary in Malaysia. Method The Malaysia Drug Code assigned to each of the drug products on the Malaysia Ministry of Health (MOH) drug formulary was used to identify oncology drugs belonging to WHO ATC class L (antineoplastic and immunomodulating agents). Main outcome measures Categories of prescribing restrictions, therapeutic class, drug type, administration mode, number of sources and the post-approval use period. Results Oncology drugs having a shorter post-approval use period (p Malaysia MOH drug formulary.

  13. A rationale for the use of proton pump inhibitors as antineoplastic agents.

    Science.gov (United States)

    De Milito, Angelo; Marino, Maria Lucia; Fais, Stefano

    2012-01-01

    It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic acid and protons, otherwise detrimental to cell survival is crucial for malignant cells to maintain cellular pH homeostasis. As a consequence of the upregulated expression and/or function of several pH-regulating systems, cancer cells display an alkaline intracellular pH (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins, proton pumps play an important role in both drug-resistance and metastatic spread, thus representing a suitable therapeutic target. Proton pump inhibitors (PPI) have been reported as cytotoxic drugs active against several human tumor cells and preclinical data have prompted the investigation of PPI as anticancer agents in humans. This review will update the current knowledge on the antitumor activities of PPI and their potential applications.

  14. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy.

    Science.gov (United States)

    Leite Cavalcanti, Alessandro; José de Macêdo, Dário; Suely Barros Dantas, Fernanda; Dos Santos Menezes, Karla; Filipe Bezerra Silva, Diego; Alves de Melo Junior, William; Fabia Cabral Cavalcanti, Alidianne

    2018-04-24

    Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%). Acute lymphoid leukemia was the most frequent neoplasm (37.3%). Regarding the maximum oral mucositis, grade 2 (41.2%) was predominant, with jugal mucosa (29.9%) and tongue (17.7%) being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%). Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  15. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Alessandro Leite Cavalcanti

    2018-04-01

    Full Text Available Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%. Acute lymphoid leukemia was the most frequent neoplasm (37.3%. Regarding the maximum oral mucositis, grade 2 (41.2% was predominant, with jugal mucosa (29.9% and tongue (17.7% being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%. Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  16. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  17. Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

    Directory of Open Access Journals (Sweden)

    Irma Edith Carranza-Torres

    2015-01-01

    Full Text Available Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of ​​intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control decreased significantly (P<0.05; however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

  18. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  19. Synthesis of novel amides based on acridone scaffold with interesting antineoplastic activity.

    Science.gov (United States)

    Mahajan, Anand A; Rane, Rajesh A; Amritkar, Anish A; Naphade, Shital S; Miniyar, Pankaj B; Bangalore, Pavan Kumar; Karpoormath, Rajshekhar

    2015-01-01

    In search of novel cytotoxic agents based on acridone scaffold, twenty five derivatives of acridone-2- carboxamide were synthesized and evaluated against a panel of eleven cancer cell lines by using MTT assay. Amides, A5 and A8 (IC50 = 0.3 µM) exhibited good cytotoxicity against MCF7. Compound A22 (IC50 = 4.3 µM) was found to be selectively cytotoxic against cancer cell line MCF7 and KB403. Particularly, promising cytotoxic activities were shown by amides A6 (IC50 = 0.7 µM), A16 (IC50 = 6.3 µM), A8 (IC50 = 0.9 µM ), A21 (IC50 = 1.3 µM), A5 (IC50 = 2.9 µM), A8 (IC50 = 2.8 µM), A14 (IC50 = 0.8 µM), A9 (IC50 = 0.8 µM) and A8 (IC50 = 0.4 µM) against cell lines; PA1, WRL68, CaCO2, TK-10, K-562, PC-3, HOP-92, ECV-304 and UACC-257, respectively. The favorable cytotoxic profile and non-toxicity towards normal human cells displayed by the derivative revealed their potential for further anticancer drug developments.

  20. Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

    Science.gov (United States)

    Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

    2016-01-01

    Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

  1. Inhibition of RecBCD enzyme by antineoplastic DNA alkylating agents.

    Science.gov (United States)

    Dziegielewska, Barbara; Beerman, Terry A; Bianco, Piero R

    2006-09-01

    To understand how bulky adducts might perturb DNA helicase function, three distinct DNA-binding agents were used to determine the effects of DNA alkylation on a DNA helicase. Adozelesin, ecteinascidin 743 (Et743) and hedamycin each possess unique structures and sequence selectivity. They bind to double-stranded DNA and alkylate one strand of the duplex in cis, adding adducts that alter the structure of DNA significantly. The results show that Et743 was the most potent inhibitor of DNA unwinding, followed by adozelesin and hedamycin. Et743 significantly inhibited unwinding, enhanced degradation of DNA, and completely eliminated the ability of the translocating RecBCD enzyme to recognize and respond to the recombination hotspot chi. Unwinding of adozelesin-modified DNA was accompanied by the appearance of unwinding intermediates, consistent with enzyme entrapment or stalling. Further, adozelesin also induced "apparent" chi fragment formation. The combination of enzyme sequestering and pseudo-chi modification of RecBCD, results in biphasic time-courses of DNA unwinding. Hedamycin also reduced RecBCD activity, albeit at increased concentrations of drug relative to either adozelesin or Et743. Remarkably, the hedamycin modification resulted in constitutive activation of the bottom-strand nuclease activity of the enzyme, while leaving the ability of the translocating enzyme to recognize and respond to chi largely intact. Finally, the results show that DNA alkylation does not significantly perturb the allosteric interaction that activates the enzyme for ATP hydrolysis, as the efficiency of ATP utilization for DNA unwinding is affected only marginally. These results taken together present a unique response of RecBCD enzyme to bulky DNA adducts. We correlate these effects with the recently determined crystal structure of the RecBCD holoenzyme bound to DNA.

  2. [Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

    Science.gov (United States)

    Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

    2012-01-01

    Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

  3. ET-09DECOY OLIGONUCLEOTIDE DERIVED FROM MGMT ENHANCER HAS AN ANTINEOPLASTIC ACTIVITY IN-VITRO AND IN-VIVO

    Science.gov (United States)

    Canello, Tamar; Ovadia, Haim; Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    INTRODUCTION: Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, correlates with a better therapeutic response and with increased survival. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through binding of p65/NF-kappaB homodimers to the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer. METHODS AND RESULTS: In an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to MGMT enhancer, the potential of the MGMT-kB1-LODN to enhance cell killing was studied in vitro in two glioma cell lines (T98G and U87) and a melanoma cell line (A375P). All three cell lines manifested a significant enhanced cell killing effect following exposure to temozolomide (TMZ) when first transfected with MGMT-kb1-LODN, and also induced a significant cell killing when administered as monotherapy. These results were confirmed also in-vivo on A375P Melanoma xenografts. Intratumoral (Intralesional - IL) injection of MGMT-kB1-LODN with or without IP injection of TMZ induced significant tumor growth inhibition either as a monotherapy or in combination with TMZ. The long-term effect of MGMT-kB1-LODN monotherapy was evaluated using a repetitive IL injection every 4 to 5 days for 55 days with either MGMT-κB1 LODN or control ODN or vehicle. A significant difference (p < 0.01) in tumor volume was obtained by MGMT-κB1-LODN compared to both control groups. Moreover, two out of the seven mice treated with MGMT-κB1-LODN demonstrated tumor regression by day 55 and no tumor recurrence was observed five months later. CONCLUSION: The results of these experiments show that the MGMT-kB1-LODN has a substantial antineoplastic effect when used either in combination with

  4. Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

    Directory of Open Access Journals (Sweden)

    Coppola C

    2016-11-01

    Full Text Available Carmela Coppola,1 Gennaro Riccio,1 Antonio Barbieri,2 Maria Gaia Monti,3 Giovanna Piscopo,1 Domenica Rea,2 Claudio Arra,2 Carlo Maurea,1 Claudia De Lorenzo,4,5 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 2Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 3Department of Translational Medical Sciences, University Federico II, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy; 5CEINGE Biotecnologie Avanzate, Naples, Italy Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage.Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response.Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01. Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional

  5. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  9. Equitable Prices of Single-Source Drugs in Thailand.

    Science.gov (United States)

    Ngorsuraches, Surachat; Chaiyakan, Kanokkan

    2015-08-01

    In Thailand, total drug expenditure has grown rapidly. Recently, the Thai government has addressed the issue of drug pricing, but the prices of single-source drugs remain a major challenge. To examine equitable prices of single-source drugs in Thailand. A total of 98 single-source and high-expenditure drugs were examined. Unit prices from the Drug and Medical Supplies Information Center (DMSIC) and National Average Drug Acquisition Cost (NADAC) were used to represent drug prices at the provider level in Thailand and the U.S., respectively. Data for measuring drug affordability, e.g., dose and poverty line, were obtained from Micromedex online and the National Statistical Office (NSO). The U.S. drug prices were adjusted by the Human Development Index (HDI) to be equitable prices for Thailand. Purchasing Power Parity (PPP) was used to convert US currency into Thai baht. All prices in this study were based on the year 2012. Catastrophic, Impoverishment, and WHO/Health Action International (HAI) approaches were used to determine Thai citizens' ability to afford the study drugs. Finally, uncertainty analyses were conducted. From all study drugs, 55 single-source drugs were priced higher than their equitable prices, ranging from 0.38 to 422.36% higher. Among these, 28 items were antineoplastic drugs. The prices of drugs outside the National List of Essential Medicines (NLEM), as well as the country's newer drugs, tended to be higher than their calculated equitable prices. The majority of drugs in Thailand priced higher than equitable prices were unaffordable for most Thai citizens. The uncertainty analyses revealed that almost all results were relatively robust. Most single-source drug prices in Thailand were higher than their equitable prices, and were likely to be unaffordable to Thai citizens.

  10. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lahm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, A.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neuzil, J.

    2002-01-01

    Roč. 8, - (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA ČR GA312/99/0348 Institutional research plan: CEZ:AV0Z5052915 Keywords : Vitamin E, Antineoplastic Agent, Tumor Necrosis Factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  11. Biological activity of some novel synthesized 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives: In vitro and in vivo antineoplastic activity

    Directory of Open Access Journals (Sweden)

    Satyajit Dutta

    2014-12-01

    Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives and the basic compound 2-(4-methylphenylsulfonamidopentanedioic acid have been synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ovarian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female swiss albino mice against Ehrlich ascites carcinoma (EAC. Among the synthesized compounds, ureide, anilide, p-nitoanilide and o-bromoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid bis amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

  12. Ontology-based systematic representation and analysis of traditional Chinese drugs against rheumatism.

    Science.gov (United States)

    Liu, Qingping; Wang, Jiahao; Zhu, Yan; He, Yongqun

    2017-12-21

    Rheumatism represents any disease condition marked with inflammation and pain in the joints, muscles, or connective tissues. Many traditional Chinese drugs have been used for a long time to treat rheumatism. However, a comprehensive information source for these drugs is still missing, and their anti-rheumatism mechanisms remain unclear. An ontology for anti-rheumatism traditional Chinese drugs would strongly support the representation, analysis, and understanding of these drugs. In this study, we first systematically collected reported information about 26 traditional Chinese decoction pieces drugs, including their chemical ingredients and adverse events (AEs). By mostly reusing terms from existing ontologies (e.g., TCMDPO for traditional Chinese medicines, NCBITaxon for taxonomy, ChEBI for chemical elements, and OAE for adverse events) and making semantic axioms linking different entities, we developed the Ontology of Chinese Medicine for Rheumatism (OCMR) that includes over 3000 class terms. Our OCMR analysis found that these 26 traditional Chinese decoction pieces are made from anatomic entities (e.g., root and stem) from 3 Bilateria animals and 23 Mesangiospermae plants. Anti-inflammatory and antineoplastic roles are important for anti-rheumatism drugs. Using the total of 555 unique ChEBI chemical entities identified from these drugs, our ChEBI-based classification analysis identified 18 anti-inflammatory, 33 antineoplastic chemicals, and 9 chemicals (including 3 diterpenoids and 3 triterpenoids) having both anti-inflammatory and antineoplastic roles. Furthermore, our study detected 22 diterpenoids and 23 triterpenoids, including 16 pentacyclic triterpenoids that are likely bioactive against rheumatism. Six drugs were found to be associated with 184 unique AEs, including three AEs (i.e., dizziness, nausea and vomiting, and anorexia) each associated with 5 drugs. Several chemical entities are classified as neurotoxins (e.g., diethyl phthalate) and allergens (e

  13. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  14. Drug: D04672 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available r ... DG01619 ... Clomifene and tamoxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... DG01621 ... Cloimife...ne-type osteoporosis agent ATC code: G03XC03 ... Clomifene, tamoxifen derivative Treatment and prevention of o

  15. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

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    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  17. Drug Allergy

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    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  18. Drug Monographs: Olaratumab and Rucaparib.

    Science.gov (United States)

    Solimando, Dominic A; Waddell, J Aubrey

    2017-04-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information presented in this review is based on published data and clinical expertise and includes information not included in the product labeling. Incorporation of such published data provides a more robust assessment of the drugs and assists pharmacists in evaluation of orders for off-label use of these agents.

  19. Drug Monographs: Atezolizumab and Everolimus.

    Science.gov (United States)

    Green, Matthew A; Waddell, J Aubrey; Solimando, Dominic A

    2016-11-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The authors are not employees of, under contract to, recipients of funding to review products from, or in any other way affiliated with either Genentech, Inc. or Novartis Pharmaceuticals Corporation. The information presented in this review is based on published data and clinical expertise and includes information not included in the product labeling. Incorporation of such published data provides a more robust assessment of the drugs and assists pharmacists in evaluation of orders for off-label use of these agents.

  20. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

    Science.gov (United States)

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-02-24

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug-drug interactions.

  1. Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

    Science.gov (United States)

    Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    2015-01-01

    Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

  2. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  3. Drug Safety

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    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  4. Drug Abuse

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    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  5. Drug Facts

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  7. Club Drugs

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    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  8. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    Science.gov (United States)

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  9. Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

  10. The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

    Directory of Open Access Journals (Sweden)

    Danilo Ciccone Miguel

    2010-11-01

    Full Text Available The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

  11. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    Science.gov (United States)

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  12. Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case

    Directory of Open Access Journals (Sweden)

    Menenakos Charalambos

    2006-06-01

    Full Text Available Abstract Background Taurolidine (TRD is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2, N0, V0. 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

  13. Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Stipp, Maria Carolina; Bezerra, Iglesias de Lacerda; Corso, Claudia Rita; Dos Reis Livero, Francislaine A; Lomba, Luiz Alexandre; Caillot, Adriana Rute Cordeiro; Zampronio, Aleksander Roberto; Queiroz-Telles, José Ederaldo; Klassen, Giseli; Ramos, Edneia A S; Sassaki, Guilherme Lanzi; Acco, Alexandra

    2017-03-15

    Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of alpha-interferon alone and combined with other antineoplastic agents on renal cell carcinoma determined by the tetrazolium microculture assay.

    Science.gov (United States)

    Homma, Y; Aso, Y

    1994-01-01

    The antiproliferative effect of various alpha-interferons (alpha-IFNs), alone or combined with other agents, on a renal cell carcinoma cell line was evaluated by the tetrazolium microculture assay to examine the rationale for combination therapies. Cells incubated in 96-week microculture plates at 5 x 10(3)/well were exposed to various agents for 3 days. There were no obvious differences in the growth inhibition caused by the 5 kinds of alpha-IFN examined as single agents. The combination of alpha-IFN with the following agents was also assessed: 5-fluorouracil (5FU), methotrexate (MTX), mitomycin C, bleomycin, cis-diaminedichloroplatinum (CDDP), vinblastine, etoposide (ETOP), alpha-IFN, tumor necrosis factor-alpha (TNF), and alpha-difluoromethylornithine. Synergism was observed for the combination of alpha-IFN+TNF, while the other combinations had additive or subadditive effects. No interference or antagonism was found. Trimodal combinations of alpha-IFN+MTX with either 5FU, ETOP, or CDDP all showed subadditive effects. These results indicated that an increased antiproliferative effect, although not necessarily synergistic, was obtained by the combination of alpha-IFN with a variety of antineoplastic agents, providing a rationale to seek for combination therapies including alpha-IFN for treating renal cell carcinoma.

  15. New drugs in Brazil: do they meet Brazilian public health needs?

    Directory of Open Access Journals (Sweden)

    Carlos Cezar Flores Vidotti

    2008-07-01

    Full Text Available OBJECTIVES: To describe the new drugs marketed in Brazil during the period 2000-2004, compare the description to the country's burden of disease, and suggest initiatives capable of addressing the situation from the perspective of a developing country. METHODS: Records of new drugs were surveyed in an official drug registration database. The new drugs were categorized by Anatomical Therapeutic Chemical classification, indication, and innovation, and compared with the needs of the country's burden of disease. Data on the morbidity and mortality rates of selected diseases (diabetes, Hansen's disease, hypertension, tuberculosis were retrieved from official documents and the literature. RESULTS: During the period investigated, 109 new drugs were launched. Most were general anti-infectives for systemic use (19, followed by antineoplastic and immunomodulating agents (16. The number of new drugs launched in 2004 was roughly one-third that of 2000. Of 65 new drugs, only one-third can be classified as innovative. Most new drugs were intended to treat noninfectious diseases that typically affect developed countries, diseases that constitute only a fraction of the country's challenges. CONCLUSIONS: A mismatch occurs between public health needs and the new drugs launched on the Brazilian market. Not only did the number of new drugs decrease in the study period, but only a few were actually new in therapeutic terms. Developing countries must acquire expertise in research and development to strengthen their capacity to innovate and produce the drugs they need.

  16. Pharmacovigilance in oncology: pattern of spontaneous notifications, incidence of adverse drug reactions and under-reporting

    Directory of Open Access Journals (Sweden)

    Marília Berlofa Visacri

    2014-04-01

    Full Text Available The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.

  17. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza

    2010-05-01

    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  18. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  19. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  1. Drug Facts

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    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  2. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  3. Drug Facts

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    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  4. Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

    International Nuclear Information System (INIS)

    Moulder, J.E.; Hopwood, L.E.; Volk, D.M.; Davies, B.M.

    1991-01-01

    The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors

  5. CELLULAR DISTRIBUTION STUDIES OF THE NITRIC OXIDE-GENERATING ANTINEOPLASTIC PRODRUG JS-K, FORMULATED IN PLURONIC P123 MICELLES

    Science.gov (United States)

    Kaur, Imit; Terrazas, Moises; Kosak, Ken M.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

    2014-01-01

    Objective Nitric oxide (NO) possesses anti-tumor activity. It induces differentiation and apoptosis in acute myeloid leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small cell lung cancer, glioma and liver cancer. Using the Pluronic® P123 polymer, we have developed a micelle formulation for JS-K in order to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells. Methods We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions. Key findings Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed. Conclusions We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K’s anti-leukemic properties. PMID:23927471

  6. Dexamethasone-(C21-phosphoramide-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549

    Directory of Open Access Journals (Sweden)

    Coyne CP

    2016-08-01

    did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10-9 M and 10-5 M. Rapid increases in antineoplastic cytotoxicity were observed at and between the dexamethasone equivalent concentrations of 10-9 M and 10-7 M where cancer cell death increased from 7.7% to a maximum of 64.9% (92.3%–35.1% residual survival, respectively, which closely paralleled values for “free” noncovalently bound dexamethasone. Discussion: Organic chemistry reaction regimens were optimized to develop a multiphase synthesis regimen for dexamethasone-(C21-phosphoramide-[anti-EGFR]. Attributes of dexamethasone-(C21-phosphoramide-[anti-EGFR] include a high dexamethasone molar incorporation-index, lack of extraneous chemical group introduction, retained EGFR-binding avidity (“targeted” delivery properties, and potential to enhance long-term pharmaceutical moiety effectiveness. Keywords: dexamethasone, anti-EGFR, organic chemistry reactions, synthesis, selective “targeted” delivery, covalent immunopharmaceuticals, EGFR 

  7. Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

    Science.gov (United States)

    Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

    2013-08-01

    Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

  8. Drug Facts

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    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  10. [Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

    Science.gov (United States)

    Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

    2014-03-04

    Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  11. Radiation induction of drug resistance in RIF-1 tumors and tumor cells

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Moulder, J.E.

    1989-01-01

    The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

  12. Drug delivery systems based on biocompatible imino-chitosan hydrogels for local anticancer therapy.

    Science.gov (United States)

    Ailincai, Daniela; Tartau Mititelu, Liliana; Marin, Luminita

    2018-11-01

    A series of drug delivery systems were prepared by chitosan hydrogelation with citral in the presence of an antineoplastic drug: 5-fluorouracil. The dynamic covalent chemistry of the imine linkage allowed the obtaining of supramolecular tridimensional architectures in which the drug has been homogenously dispersed. Fourier-transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WXRD) and polarized light microscopy (POM) measurements were used in order to follow the hydrogelation and drug encapsulation processes. The ability of the prepared systems to release the drug has been investigated by UV-Vis spectroscopy using a calibration curve and by fitting the results with different mathematic models. To mimic the behavior of the hydrogel matrix in bio-environmental conditions in view of applications, their enzymatic degradability was monitored in the presence of lysozyme. The in vivo side effects of the systems, in terms of their influence on the blood elements, biochemical and immune parameters were monitored on white Swiss mice by intraperitoneal administration of the injectable obtained hydrogels. All the characteristics of the obtained systems, such as micro-porous morphology, uniform drug encapsulation, enzymatic degradability, lack of side effects, other than the one of the drug itself, along with their ability to release the drug in a sustained manner proved that these material meet the requirements for the development of drug delivery systems, making them suitable for being applied in intraperitoneal chemotherapy.

  13. The impact of religiosity and individual prayer activities on advanced cancer patients' health: is there any difference in function of whether or not receiving palliative anti-neoplastic therapy?

    Science.gov (United States)

    Paiva, Carlos Eduardo; Paiva, Bianca Sakamoto Ribeiro; Yennurajalingam, Sriram; Hui, David

    2014-12-01

    Consecutive patients (n = 221) presenting for initial consultation at a palliative care outpatient clinic were prospectively interviewed and then followed until death. Individual prayer activity (IPA) and global religion scores were associated with quality of life, symptoms, inflammatory markers, and survival. Analyses were adjusted for whether patients were still receiving anti-neoplastic therapies (ANTs) or not. Higher religion scores were associated with lower levels of inflammation in advanced cancer patients still undergoing ANTs. Additionally, higher IPA was an independent good prognostic factor in patients on active ANTs. Further studies are necessary to confirm these findings and to investigate possible biological mechanisms involved.

  14. The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity.

    Science.gov (United States)

    Morén, Constanza; Juárez-Flores, Diana Luz; Cardellach, Francesc; Garrabou, Glòria

    2016-01-01

    Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. One hundred and forty-five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage.

  15. Secretory phospholipase A2 responsive liposomes exhibit a potent anti-neoplastic effect in vitro, but induce unforeseen severe toxicity in vivo

    DEFF Research Database (Denmark)

    Østrem, Ragnhild Garborg; Parhamifar, Ladan; Pourhassan, Houman

    2017-01-01

    The clinical use of liposomal drug delivery vehicles is often hindered by insufficient drug release. Here we present the rational design of liposomes optimized for secretory phospholipase A2 (sPLA2) triggered drug release, and test their utility in vitro and in vivo. We hypothesized...

  16. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  17. Molecular fundamentals of drug interactions in the therapy of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2014-03-01

    Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  18. A new in vitro screening system for anticancer drugs for the treatment of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Hanauske, U.; Hanauske, A.R.; Clark, G.M.; Tsen, D.; Buchok, J.; Hoff, D.D. von

    1989-01-01

    We have evaluated a semiautomated radiometric assay (BACTEC 460 system) for screening of activity of anticancer drugs against human non-small cell lung cancer cell lines. Cells from seven cell lines were exposed to standard antineoplastic agents at four different concentrations using a 1-h incubation. Alpha 2-interferon was tested using a continuous incubation. In vitro drug activity was analyzed as a function of the clinically achievable serum concentration. Our results indicate that two cell lines (CALU-3, SK-MES-1) exhibit in vitro drug sensitivity patterns closest to those observed in clinical studies. These two cell lines might therefore be most useful for screening new anticancer compounds for activity against non-small cell lung cancer. The radiometric assay is a semiautomated system which has advantages over other, more time-consuming screening systems

  19. Drug Facts

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    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  20. Prescription Drugs

    Science.gov (United States)

    ... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... Future survey highlights drug use trends among the Nation’s youth for marijuana, alcohol, cigarettes, e-cigarettes (e- ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  2. Drug Facts

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    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  3. Drug Facts

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    Full Text Available ... Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of ... Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1- ...

  4. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  5. Drug Facts

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    Full Text Available ... Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs ... Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call ...

  6. Drug Facts

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    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  7. Drug Facts

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    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  8. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the ...

  10. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  11. Drug Testing

    Science.gov (United States)

    ... testing, substance abuse testing, toxicology screen, tox screen, sports doping tests What is it used for? Drug screening is used to find out whether or not a person has taken a certain drug or drugs. It ... Sports organizations. Professional and collegiate athletes usually need to ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  13. Drug Facts

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    Full Text Available ... can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  17. Drug Facts

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    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  18. Drug: D02747 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available site: 31; 121; 131; 134) ... Antineoplastic ... DG01752 ... Interferone Therapeutic category: 6399 ATC code: L03AB11 Chronic hepatitis... B [DS:H00412] ... R: Interferon alfa-2a [DR:D00745] Treatment of hepatitis C IFNAR1 [HSA:34

  19. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... ABStrAct. Since drugs became both a public and social issue in Nigeria, fear about both the real and .... drugs as being morally reprehensible, and ..... tice system (see for instance, Shaw, 1995; ..... A cut throat business:.

  20. A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.

    Science.gov (United States)

    Falagas, Matthew E; Fragoulis, Konstantinos N; Karydis, Ioannis

    2006-12-20

    Drug treatment is becoming more expensive due to the increased cost for the introduction of new drugs, and there seems to be an uneven distribution of medication cost for different therapeutic categories. We hypothesized that the cost of new antimicrobial agents may differ from that of other therapeutic categories and this may play a role in the stagnation of development of new antibiotics. We performed a pharmaco-economical comparative analysis of the drug cost of treatment for new agents introduced in the United States drug market in various therapeutic categories. We calculated the drug cost (in US dollars) of a ten-day treatment of all new drugs approved by the FDA during the period between January 1997 and July 2003, according to the 2004 Red Book Pharmacy's Fundamental Reference. New anti-neoplastic agents were found to be the most expensive drugs in comparison to all other therapeutic categories, with a median ten-day drug-treatment cost of US$848 compared to the median ten-day drug-treatment costs of all other categories ranging from US$29 to US$301. On the other hand, new antimicrobial drugs were found to be much less expensive, with a median ten-day drug-treatment cost of US$137 and $US85 for all anti-microbial agents and for anti-microbial agents excluding anti-HIV medications, respectively. The drug-treatment cost of new medications varies considerably by different therapeutic categories. This fact may influence industry decisions regarding the development of new drugs and may play a role in the shortage of new antimicrobial agents in the fight against the serious problem of antimicrobial resistance.

  1. Does the use of melatonin overcome drug resistance in cancer chemotherapy?

    Science.gov (United States)

    Asghari, Mohammad Hossein; Ghobadi, Emad; Moloudizargari, Milad; Fallah, Marjan; Abdollahi, Mohammad

    2018-03-01

    Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound. Reduced sensitivity and also resistance of cancer cells to antineoplastic agents are common events which might arise as a result of genomic instability of the malignant cells. Genetic mutations provide numerous mechanisms for these cells to resist cytotoxic therapies. Melatonin, due to its pleitropic effects, is able to correct these alterations in favour of sensitization to antineoplastic agents as evident by increased response to treatment via modulating the expression and phosphorylation status of drug targets, the reduced clearance of drugs by affecting their metabolism and transport within the body, decreased survival of malignant cells via altering DNA repair and telomerase activity, and enhanced responsiveness to cell death-associated mechanisms such as apoptosis and autophagy. These effects are presumably governed by melatonin's interventions in the main signal transduction pathways such as Akt and MAPK, independent of its antioxidant properties. Possessing such a signaling altering nature, melatonin can considerably affect the drug-resistance mechanisms employed by the malignant cells in breast, lung, hepatic, and colon cancers as well as different types of leukemia which are the subject of the current review. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  3. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  4. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  5. Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays. General considerations, the nitrosoureas and alkylating agents.

    Science.gov (United States)

    Bosanquet, A G

    1985-01-01

    In vitro drug sensitivity of tumour biopsies is currently being determined using a variety of methods. For these chemosensitivity assays many drugs are required at short notice, and this in turn means that the drugs must generally be stored in solution. There are, however, a number of potential problems associated with dissolving and storing drugs for in vitro use, which include (a) drug adsorption; (b) effects of freezing; (c) drug stability under the normal conditions of dilution and setting up of an in vitro assay; and (d) insolubility of drugs in normal saline (NS) or phosphate-buffered saline (PBS). These problems are considered in general, and some recommendations for use of solutions of drugs in in vitro assays are suggested. The nitrosoureas and alkylating agents are also investigated in greater detail in this respect. The nitrosoureas are found to be very labile in PBS at pH 7, with 5% degradation (t0.95) occurring in 10-50 min at room temperature. These values are increased about 10-fold on refrigeration and about 5- to 10-fold on reduction of the pH of the medium to pH 4-5. At pH 7 and room temperature, t0.95 is observed in under 1 h with the alkylating agents nitrogen mustard, chlorambucil, melphalan, 2,5-diaziridinyl-3,6-bis(2-hydroxyethylamino)-1,4-benzoquinone (BZQ), dibromodulcitol, dibromomannitol, treosulphan, and procarbazine. Of the other alkylating agents, 4-hydroperoxycylophosphamide (sometimes used in vitro in place of cyclophosphamide), busulphan, dianhydrogalactitol, aziridinylbenzoquinone (AZQ), and dacarbazine have a t0.95 of between 2 and 24 h, while ifosfamide and pentamethylmelamine are both stable in aqueous solution for greater than 7 days. About half the drugs studied in detail have been stored frozen in solution for in vitro use, although very little is known about their stability under these conditions.

  6. In vitro anticancer drug test: A new method emerges from the model of glioma stem cells

    Directory of Open Access Journals (Sweden)

    Gabriele Riva

    2014-01-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV astrocytoma and the most common malignant brain tumor. Current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. The failure of current therapies may be due to the presence, within the tumor, of cells characterized by enhanced self-renewal capacity, multilineage differentiation potential and elevated invasive behavior, called glioma stem cells (GSCs. To evaluate the pharmacological efficacy of selected drugs on six GSC lines, we set up a multiple drug responsivity assay based on the combined evaluation of cytomorphological and functional parameters, including the analysis of polymorphic nuclei, mitotic index and cell viability. In order to understand the real pharmacological efficacy of the tested drugs, we assigned a specific drug responsivity score to each GSC line, integrating the data produced by multiple assays. In this work we explored the antineoplastic effects of paclitaxel (PTX, an inhibitor of microtubule depolymerization, utilized as standard treatment in several cancers, and of valproic acid (VPA, an inhibitor of histone deacetylases (HDACs with multiple anticancer properties. We classified the six GSC lines as responsive or resistant to these drugs, on the basis of their responsivity scores. This method can also be useful to identify the best way to combine two or more drugs. In particular, we utilized the pro-differentiating effect of VPA to improve the PTX effectiveness and we observed a significant reduction of cell viability compared to single treatments.

  7. Safe Handling of Cytotoxic Drugs and Risks of Occupational Exposure to Nursing Staffs

    Directory of Open Access Journals (Sweden)

    Somayeh Hanafi

    2016-05-01

    Full Text Available Background: Inherent toxicity of cytotoxic drugs is the basis for their potential adverse risks from occupational exposure to the nursing staff. In Iran, chemotherapy regimens are prescribed and administered according to the world updated protocols. But little is done regarding the protective standards in this field.Methods: An observational cross-sectional survey was conducted among nurses who work in three tertiary care teaching hospitals in Tehran, Iran in 2012. All participants worked in one of the hospital wards handling cytotoxic drugs (preparation and administration. A questionnaire was used for interviewing all subjects, and observing them preparing and administering the drugs. We examined all adverse effects associated with handling of antineoplastic drugs.Results: Totally 270 adverse reactions were reported. The most frequently reported adverse effects included headache and vertigo (40 cases, hair loss (36 cases, skin rashes and itching (31 cases, and burning sensation in eyes (31 cases. In all hospital wards, the standards were met in not more than 50% of the items.Conclusion: Monitoring the personnel who are directly involved in handling of cytotoxic drugs is of great importance. Furthermore, educating the personnel in the field of standards of cytotoxic drugs handling could increase the nursing staff’s knowledge regarding these drugs’ adverse reactions.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  9. Drug Facts

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  10. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  11. Chemotherapy drug handling in first opinion small animal veterinary practices in the United Kingdom: results of a questionnaire survey.

    Science.gov (United States)

    Edery, E G

    2017-05-27

    To investigate how first opinion small animal veterinary surgeons in the UK handled chemotherapeutic agents, a questionnaire was distributed at the 2014 British Small Animal Veterinary Association congress and by internet. Chemotherapy was regularly offered by 70.4 per cent of the respondents. Gold standards defined according to available guidelines for safe handling of antineoplastic drugs were poorly followed by general practitioners with only 2 per cent of respondents complying with all of them. Dedicated facilities for preparation and administration of cytotoxic drugs were variably available among participants. The level of training of staff indirectly involved in handling chemotherapy was appropriate in less than 50 per cent of practices. No association was found between demographic characteristics of the sampled population and the decision to perform chemotherapy. The results of this study raise concerns about the safety of the veterinary staff in first opinion practices involved in handling chemotherapy. British Veterinary Association.

  12. Forecasting drug utilization and expenditure in a metropolitan health region

    Directory of Open Access Journals (Sweden)

    Korkmaz Seher

    2010-05-01

    Full Text Available Abstract Background New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning, forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011. Methods Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee. Results The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs. Conclusions The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate

  13. Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation

    DEFF Research Database (Denmark)

    Jensen, P B; Roed, H; Skovsgaard, T

    1990-01-01

    doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg...... the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross......-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo....

  14. Applying ligands profiling using multiple extended electron distribution based field templates and feature trees similarity searching in the discovery of new generation of urea-based antineoplastic kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Eman M Dokla

    Full Text Available This study provides a comprehensive computational procedure for the discovery of novel urea-based antineoplastic kinase inhibitors while focusing on diversification of both chemotype and selectivity pattern. It presents a systematic structural analysis of the different binding motifs of urea-based kinase inhibitors and the corresponding configurations of the kinase enzymes. The computational model depends on simultaneous application of two protocols. The first protocol applies multiple consecutive validated virtual screening filters including SMARTS, support vector-machine model (ROC = 0.98, Bayesian model (ROC = 0.86 and structure-based pharmacophore filters based on urea-based kinase inhibitors complexes retrieved from literature. This is followed by hits profiling against different extended electron distribution (XED based field templates representing different kinase targets. The second protocol enables cancericidal activity verification by using the algorithm of feature trees (Ftrees similarity searching against NCI database. Being a proof-of-concept study, this combined procedure was experimentally validated by its utilization in developing a novel series of urea-based derivatives of strong anticancer activity. This new series is based on 3-benzylbenzo[d]thiazol-2(3H-one scaffold which has interesting chemical feasibility and wide diversification capability. Antineoplastic activity of this series was assayed in vitro against NCI 60 tumor-cell lines showing very strong inhibition of GI(50 as low as 0.9 uM. Additionally, its mechanism was unleashed using KINEX™ protein kinase microarray-based small molecule inhibitor profiling platform and cell cycle analysis showing a peculiar selectivity pattern against Zap70, c-src, Mink1, csk and MeKK2 kinases. Interestingly, it showed activity on syk kinase confirming the recent studies finding of the high activity of diphenyl urea containing compounds against this kinase. Allover, the new series

  15. Interferon-β lipofection I. Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids.

    Science.gov (United States)

    Villaverde, M S; Gil-Cardeza, M L; Glikin, G C; Finocchiaro, L M E

    2012-07-01

    We evaluated the effect of hIFNβ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNβ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNβ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy-sensitive EW7 monolayers, the combination of hIFNβ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNβ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy-resistant EW7 spheroids or M8 cells, the combination of hIFNβ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNβ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNβ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNβ-expressing cells killed more than 60 or 80% of cell population, respectively.

  16. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  17. [Club drugs].

    Science.gov (United States)

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  18. Drug Facts

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  19. Drug Facts

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  20. Drug Facts

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  1. Drug Facts

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    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  2. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  3. Drugged Driving

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  4. Club Drugs

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  5. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  6. Drug Facts

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    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  7. Drug Facts

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    Full Text Available ... 800-662-HELP (4357) at any time to find drug treatment centers near you. I want my ... is making positive changes in her life. She finds support from family and friends who don't ...

  8. Drug Facts

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  9. Drug Facts

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    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  10. Drug Reactions

    Science.gov (United States)

    ... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life Issues Insurance & Bills Self Care Working With Your Doctor Drugs, Procedures & Devices Over-the- ...

  11. Drug Facts

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    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  12. Drug Resistance

    Science.gov (United States)

    ... Drug-resistance testing is also recommended for all pregnant women with HIV before starting HIV medicines and also in some pregnant women already taking HIV medicines. Pregnant women will work with their health ...

  13. Drug Facts

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    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  14. Drug Addiction

    Science.gov (United States)

    ... as hearing colors Impulsive behavior Rapid shifts in emotions Permanent mental changes in perception Rapid heart rate ... Drug use can negatively affect academic performance and motivation to excel in school. Legal issues. Legal problems ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  16. Insights into CYP2B6-mediated drug–drug interactions

    Directory of Open Access Journals (Sweden)

    William D. Hedrich

    2016-09-01

    Full Text Available Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

  17. DGIdb 3.0: a redesign and expansion of the drug-gene interaction database.

    Science.gov (United States)

    Cotto, Kelsy C; Wagner, Alex H; Feng, Yang-Yang; Kiwala, Susanna; Coffman, Adam C; Spies, Gregory; Wollam, Alex; Spies, Nicholas C; Griffith, Obi L; Griffith, Malachi

    2018-01-04

    The drug-gene interaction database (DGIdb, www.dgidb.org) consolidates, organizes and presents drug-gene interactions and gene druggability information from papers, databases and web resources. DGIdb normalizes content from 30 disparate sources and allows for user-friendly advanced browsing, searching and filtering for ease of access through an intuitive web user interface, application programming interface (API) and public cloud-based server image. DGIdb v3.0 represents a major update of the database. Nine of the previously included 24 sources were updated. Six new resources were added, bringing the total number of sources to 30. These updates and additions of sources have cumulatively resulted in 56 309 interaction claims. This has also substantially expanded the comprehensive catalogue of druggable genes and anti-neoplastic drug-gene interactions included in the DGIdb. Along with these content updates, v3.0 has received a major overhaul of its codebase, including an updated user interface, preset interaction search filters, consolidation of interaction information into interaction groups, greatly improved search response times and upgrading the underlying web application framework. In addition, the expanded API features new endpoints which allow users to extract more detailed information about queried drugs, genes and drug-gene interactions, including listings of PubMed IDs, interaction type and other interaction metadata.

  18. Marketed drugs used for the management of hypercholesterolemia as anticancer armament

    Directory of Open Access Journals (Sweden)

    Papanagnou P

    2017-09-01

    Full Text Available Panagiota Papanagnou,1 Theodora Stivarou,2 Ioannis Papageorgiou,1 Georgios E Papadopoulos,3 Anastasios Pappas1 1Department of Urology, Agios Savvas Cancer Hospital, Athens, Greece; 2Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute, Athens, Greece; 3Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece Abstract: The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor–patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity. This review aims to present the anticancer properties of drugs used for the management of hypercholesterolemia. A global view of the antitumorigenicity of all marketed antihypercholesterolemic drugs is of major importance, given that atherosclerosis, which is etiologically linked to hypercholesterolemia, is a leading worldwide cause of morbidity and mortality, while hypercholesterolemia and tumorigenesis are known to be interrelated. In vitro, in vivo and clinical literature data accumulated so far outline the mechanistic basis of the antitumor function of these agents and how they could find application at the clinical setting. Keywords: antihypercholesterolemic agents, cancer, synergism, repurposing

  19. Healthcare professionals and pharmacovigilance of pediatric adverse drug reactions: a 5-year analysis of Adverse Events Reporting System database of the Food and Drug Administration.

    Science.gov (United States)

    Bigi, Caterina; Tuccori, Marco; Bocci, Guido

    2017-02-17

    To analyze the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (FDA), investigating the characteristics of pediatric adverse drug reactions (ADRs) and describing the effective participation of healthcare professionals in the reporting activity. Reports of ADRs were obtained from the FDA website. Only ADRs in pediatric subjects (divided by age, by country and by professional category) were included into the analysis. The drugs suspected as primary cause of the ADRs in pediatric subjects and their principal anatomic group according to the Anatomical Therapeutic Chemical classification system were considered. To classify the ADRs, the Medical Dictionary for Regularity Activities terminology was adopted. Between 2008 and 2012, FDA collected 113,077 ADRs in pediatric patients. Of the total pediatric ADR reports, those performed by medical doctors were 32%, followed by consumers (26%) and healthcare professionals (25%). Most of the ADR reports were related to the adolescent group (39%). Healthcare professionals resulted the category with the highest rate of ADR reports in neonates and infants. Drugs acting on nervous system and antineoplastic/immunomodulating agents were the most involved the pediatric ADR reports. Pyrexia, convulsion, vomiting and accidental overdose were the reactions more reported both from healthcare professionals and medical doctors. The present study describes the pediatric ADR reports of the FDA database through healthcare professional's perspective, describing the various aspects of pediatric pharmacovigilance.

  20. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  1. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  2. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  3. A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

    Science.gov (United States)

    Wu, Daocheng; Wan, Mingxi

    2008-01-01

    Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

  4. THE PROSPECTIVE OBSERVATIONAL STUDY ON CUTANEOUS ADVERSE DRUG REACTIONS TO CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Prakash Mani

    2016-07-01

    Full Text Available INTRODUCTION There are a wide spectrum of adverse cutaneous drug reactions (ACDRs varying from transient maculopapular rash to fatal toxic epidermal necrolysis (TEN. With the advent of newer and targeted therapy in the field of dermatology, the pattern of cutaneous adverse drug eruptions and the drugs responsible for them keep changing every year. Hence, this study was undertaken to ascertain the clinical spectrum of ACDRs and the causative drugs, in a tertiary care centre in South India. MATERIALS AND METHODS This study was a prospective, observational study conducted in Department of Medical Oncology, Government Rajaji Hospital, Madurai Medical College, Madurai during the period of March 2015 - August 2015 (6 months. Severity of the reaction was assessed using CTCAE (Common Terminology Criteria for Adverse Events scale version 4.1. Causality of the drug was assessed using Naranjo Causality Assessment Scale. The scale was calculated first for the regimen and then for individual drugs separately. The adverse events with score of 6 or more (probable and definite adverse events were taken for the study. RESULTS AND CONCLUSION The overall incidence of ACDRs found in this study was 85%. Alopecia was the commonest ACDR occurring in 51.6% of patients. Nail pigmentation and supravenous pigmentation were the next common ACDRs, recorded in 35% and 16% of patients respectively. Imatinib caused generalised hypopigmentation in 40% of patients. Bleomycin induced, flagellate erythema and pigmentation in 17% of patients and stomatitis was seen in 11% of patients. Acneiform eruptions were recorded with erlotinib and gefitinib therapy. Supravenous pigmentation was common with 5-fluorouracil and docetaxel, occurring in 53% & 48% respectively. Newer targeted therapies like EGFR (Epidermal growth factor receptor inhibitors recorded low incidence of ACDRs like alopecia as against conventional antineoplastic agents. The cancer chemotherapeutic drugs are associated

  5. Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

    Science.gov (United States)

    Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila M M; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy C R; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

    2014-01-01

    Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

  6. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  7. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    tests (LFTs) to monitor hepatotoxicity (liver [hepatic] damage) is uncommon in many resource-poor ... cholesterol ester storage disease. ... The problem with many patients is that they are taking several drugs often ... Urine, saliva and other body fluids may be coloured orange-red: this can be very alarming to patients.

  8. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  9. Capping Drugs

    Indian Academy of Sciences (India)

    preventing disease in human beings or in animals. In the process ... of requirement. In the process, they may cause toxic side effects. .... the liver to release the physiologically active drug. Similarly ... patients addicted to alcohol. However, it is a ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  11. The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

    Science.gov (United States)

    Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia

    2014-09-01

    To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

  12. The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients.

    Science.gov (United States)

    El-Najjar, Nahed; Jantsch, Jonathan; Gessner, André

    2017-08-28

    Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

  13. Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Yurgel VC

    2014-03-01

    Full Text Available Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Graduação em Biotecnologia (PPGB, Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil*These authors contributed equally to this workAbstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt2] and MTX(OEt2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt2 solution and MTX(OEt2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231

  14. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  15. Drug Safety: Managing Multiple Drugs

    Science.gov (United States)

    ... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

  16. Venetoclax (ABT-199 Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

    Directory of Open Access Journals (Sweden)

    Johanna Weiss

    2016-02-01

    Full Text Available Venetoclax (ABT-199 represents a specific B-cell lymphoma 2 (Bcl-2 inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1, breast cancer resistance protein (BCRP, and organic anion transporting polypeptides (OATPs was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions.

  17. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

    Science.gov (United States)

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-01-01

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions. PMID:26927160

  18. Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

    Directory of Open Access Journals (Sweden)

    Dina Indrati

    2011-07-01

    Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

  19. Interacción de los antineoplásicos orales con los alimentos: revisión sistemática Antineoplastic oral agents and drug-nutrient interactions: a sistematic review

    OpenAIRE

    N. V. Jiménez Torres; I. Romero Crespo; M. Ballester Solaz; A. Albert Marí; V. Jiménez Arenas

    2009-01-01

    Introducción: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los aliment...

  20. Effect of radiation and combined chemoradiation therapy on cardiac activity in patients with esophagus cancer. [Combined effects of /sup 60/Co. gamma. rays and methylglyoxal-bis(guanylhydrazone) an antineoplastic drug

    Energy Technology Data Exchange (ETDEWEB)

    Neklyudova, V I; Shkhvatsabaya, L V; Ivanova, E M

    1978-12-01

    The results of a comparative study of the effect of radiation and combined chemoradiation therapy with methyl-GAG in 51 patients with cancer of the chest region of the esophagus indicate an adverse effect of these methods of treatment on cardiac activity. Against the background of chemoradiation therapy, these changes were more marked due perhaps to some cardiotoxic effect of methyl-GAG. However, the changes induced did not lead to considerable disorders of hemodynamics during treatment.

  1. Influence of Alternative Tubulin Inhibitors on the Potency of a Epirubicin-Immunochemotherapeutic Synthesized with an Ultra Violet Light-Activated Intermediate: Influence of incorporating an internal/integral disulfide bond structure and Alternative Tubulin/Microtubule Inhibitors on the Cytotoxic Anti-Neoplastic Potency of Epirubicin-(C3-amide)-Anti-HER2/neu Synthesized Utilizing a UV-Photoactivated Anthracycline Intermediate.

    Science.gov (United States)

    Coyne, C P; Jones, Toni; Bear, Ryan

    2012-11-01

    Immunochemotherapeutics, epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] with an internal disulfide bond, and epirubicin-(C 3 - amide )-[anti-HER2/ neu ] were synthesized utilizing succinimidyl 2-[(4,4'-azipentanamido) ethyl]-1,3'-dithioproprionate or succinimidyl 4,4-azipentanoate respectively. Western blot analysis was used to determine the presence of any immunoglobulin fragmentation or IgG-IgG polymerization. Retained HER2/ neu binding characteristics of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] were validated by cell-ELISA using a mammary adenocarcinoma (SKBr-3) population that highly over-expresses trophic HER2/ neu receptor complexes. Cytotoxic anti-neoplastic potency of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] between epirubicin-equivalent concentrations of 10 -10 M and 10 -6 M was determined by measuring the vitality/proliferation of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3 cell type). Cytotoxic anti-neoplastic potency of benzimidazoles (albendazole, flubendazole, membendazole) and griseofulvin were assessed between 0-to-2 μg/ml and 0-to-100 μg/ml respectively while mebendazole and griseofulvin were analyzed at fixed concentrations of 0.35 μg/ml and 35 g/ml respectively in dual combination with gradient concentrations of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ]. Cytotoxic anti-neoplastic potency for epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) was nearly identical at epirubicin-equivalent concentrations of 10 -10 M and 10 -6 M. The benzimadazoles also possessed cytotoxic anti-neoplastic activity with flubendazole and albendazole being the most and least potent respectively. Similarly, griseofulvin had cytotoxic anti-neoplastic activity and was more potent than

  2. Adverse Drug Reaction Reporting Pattern in Turkey: Analysis of the National Database in the Context of the First Pharmacovigilance Legislation.

    Science.gov (United States)

    Ozcan, Gulnihal; Aykac, Emel; Kasap, Yelda; Nemutlu, Nergiz T; Sen, Ebru; Aydinkarahaliloglu, N Demet

    2016-03-01

    In Turkey, pharmacovigilance began in 1985. A fully structured adverse drug reaction (ADR)-reporting system was established with the publication of the first pharmacovigilance regulation in 2005. Subsequent regulation published in 2014 brought further improvements to the system. In this study, we aimed to analyse the ADR-reporting pattern in the context of the first pharmacovigilance legislation in Turkey. We analysed ADR reports submitted to the Turkish Pharmacovigilance Center (TUFAM) from 2005 to 2014 with respect to reporting rate (RR), patient characteristics, type of the ADRs, suspected drugs, source of the report and the profession of the reporter. The annual RR increased gradually over the study period. RRs for females were greater than those for males. RRs were highly correlated with age. Most commonly reported ADRs were skin and subcutaneous tissue disorders. Most commonly suspected drugs were antineoplastic and immunomodulating agents. There was no remarkable change in reporting pattern of ADRs, patient characteristics or classes of suspected drugs over the years. The most common source of reports was spontaneous reporting. Contribution of the reports from studies increased gradually. Most of the reports were reported by physicians. RRs by pharmacists increased substantially over the years. This study showed that the annual RR increased gradually over the 9-year study period. This increase was neither due to an increased reporting of a specific group of ADRs or drugs, nor to an increased reporting in a specific group of patients. There was a general increase in RR in parallel to pharmacovigilance activities.

  3. Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

    Directory of Open Access Journals (Sweden)

    Funda Karbek Akarca

    2017-12-01

    Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis

  4. Controllable fabrication and characterization of biocompatible core-shell particles and hollow capsules as drug carrier

    Science.gov (United States)

    Hao, Lingyun; Gong, Xinglong; Xuan, Shouhu; Zhang, Hong; Gong, Xiuqing; Jiang, Wanquan; Chen, Zuyao

    2006-10-01

    SiO 2@CdSe core-shell particles were fabricated by controllable deposition CdSe nanoparticles on silica colloidal spheres. Step-wise coating process was tracked by the TEM and XRD measurements. In addition, SiO 2@CdSe/polypyrrole(PPy) multi-composite particles were synthesized based on the as-prepared SiO 2@CdSe particles by cationic polymerization. The direct electrochemistry of myoglobin (Mb) could be performed by immobilizing Mb on the surface of SiO 2@CdSe particles. Immobilized with Mb, SiO 2@CdSe/PPy-Mb also displayed good bioelectrochemical activity. It confirmed the good biocompatible property of the materials with protein. CdSe hollow capsules were further obtained as the removal of the cores of SiO 2@CdSe spheres. Hollow and porous character of CdSe sub-meter size capsules made them becoming hopeful candidates as drug carriers. Doxorubicin, a typical an antineoplastic drug, was introduced into the capsules. A good sustained drug release behavior of the loading capsules was discovered via performing a release test in the PBS buffer (pH 7.4) solution at 310 k. Furthermore, SiO 2@CdSe/PPy could be converted to various smart hollow capsules via selectively removal of their relevant components.

  5. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  6. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  8. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  9. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  10. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  11. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  12. Prescription Drug Abuse

    Science.gov (United States)

    ... drug abuse. And it's illegal, just like taking street drugs. Why Do People Abuse Prescription Drugs? Some people abuse prescription drugs ... common risk of prescription drug abuse is addiction . People who abuse ... as if they were taking street drugs. That's one reason most doctors won't ...

  13. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  14. Drug Monographs: Avelumab and Ribociclib.

    Science.gov (United States)

    Waddell, J Aubrey; Solimando, Dominic A

    2017-07-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  15. Gynecomastia and drugs: a critical evaluation of the literature.

    Science.gov (United States)

    Nuttall, Frank Q; Warrier, Rohit S; Gannon, Mary C

    2015-05-01

    A large number of medications have been implicated in the genesis of gynecomastia. However, gynecomastia is common in men, asymptomatic, increases with age, and is considered to be due to an increased estradiol/testosterone ratio. This complicates the interpretation of medication-related gynecomastia. Therefore, we have reviewed the literature in order to assess the data relating gynecomastia onset with utilization of specific medications. The literature was searched in PubMed and the Ovid/Medline databases from the 1946 to January 2015 with the search terminology of "gynecomastia, drugs/medications." A few other articles were found and included. One hundred ten publications were reviewed. Sixty-three were single case reports. There were 24 population-based studies of which 8 were HIV-infected patients treated with antiretroviral agents. Among the case reports, 49 were for individual medications, and 2 were reports of antineoplastic or antiretroviral drug regimens. In the great majority, mastodynia with or without breast enlargement was present and referred to as gynecomastia. Generally, hormonal profiles could not explain the breast enlargement. The pain/tenderness and breast enlargement resolved spontaneously over time. Many different medications have been associated with the presence of "gynecomastia." Generally, it presents as a syndrome characterized by a single painful/tender breast (mastodynia) associated with breast enlargement and is transient. We suggest that these cases be referred to as an acute gynecomastia syndrome. This syndrome also occurs independent of medication use. Thus, in an individual patient, whether it is medication induced often remains uncertain. The pathogenesis remains unknown.

  16. Natural products against cancer: A comprehensive bibliometric study of the research projects, publications, patents and drugs

    Directory of Open Access Journals (Sweden)

    Jian Du

    2014-01-01

    Full Text Available Objectives: To analyze multi-source data including awards, publications, patents and drugs, and try to draw the whole landscape of the research and development community in the area of natural products (NPs against cancer. Materials and Methods: Awards, publications, patents and drugs data from National Institute of Health/Natural Science Foundation of China (NIH/NSFC, PubMed, Derwent Innovation Index and Cortellis were collected. Bibliometric methodologies and technology are used to investigate publications/patents/drugs, their contents and relationships. Results: NIH and NSFC respectively demonstrated a stable and sustained expenditure growth in this area. The number of publications is continuously increasing. Yet the annual patent applications worldwide and FDA drug approvals were little changed or not obviously fluctuated in 2003-2013. USA and several Asia-pacific countries/territories are important contributing powers. We described the evolution of major research topics by those MeSH Major Topics indexed in PubMed with the largest growth range in three intervals, and analyzed hot research topics in the recent 10 years which include NPs or NPs derivatives, cell line/animal model, laboratory technologies and activation mechanisms. Conclusions: China published the most publications and received the most patent applications, but drug discovery performance is no better than USA and Japan. Research on anti-neoplastic structures and compounds originated from Chinese traditional medicine (TCM, medicinal plants, herbal medicine and marine NPs are major research topics in the recent 10 years. There still exits translational gap between basic research and drug discovery. Translational research should be undertaken to strengthen the applicability of NPs.

  17. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    Science.gov (United States)

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  18. Revisiting the structure of the anti-neoplastic glucans of Mycobacterium bovis Bacille Calmette-Guerin. Structural analysis of the extracellular and boiling water extract-derived glucans of the vaccine substrains.

    Science.gov (United States)

    Dinadayala, Premkumar; Lemassu, Anne; Granovski, Pierre; Cérantola, Stéphane; Winter, Nathalie; Daffé, Mamadou

    2004-03-26

    The attenuated strain of Mycobacterium bovis Bacille Calmette-Guérin (BCG), used worldwide to prevent tuberculosis and leprosy, is also clinically used as an immunotherapeutic agent against superficial bladder cancer. An anti-tumor polysaccharide has been isolated from the boiling water extract of the Tice substrain of BCG and tentatively characterized as consisting primarily of repeating units of 6-linked-glucosyl residues. Mycobacterium tuberculosis and other mycobacterial species produce a glycogen-like alpha-glucan composed of repeating units of 4-linked glucosyl residues substituted at some 6 positions by short oligoglucosyl units that also exhibits an anti-tumor activity. Therefore, the impression prevails that mycobacteria synthesize different types of anti-neoplastic glucans or, alternatively, the BCG substrains are singular in producing a unique type of glucan that may confer to them their immunotherapeutic property. The present study addresses this question through the comparative analysis of alpha-glucans purified from the extracellular materials and boiling water extracts of three vaccine substrains. The polysaccharides were purified, and their structural features were established by mono- and two-dimensional NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the enzymatic and chemical degradation products of the purified compounds. The glucans isolated by the two methods from the three substrains of BCG were shown to exhibit identical structural features shared with the glycogen-like alpha-glucan of M. tuberculosis and other mycobacteria. Incidentally, we observed an occasional release of dextrans from Sephadex columns that may explain the reported occurrence of 6-substituted alpha-glucans in mycobacteria.

  19. Investigation of the host-guest complexation between 4-sulfocalix[4]arene and nedaplatin for potential use in drug delivery

    Science.gov (United States)

    Fahmy, Sherif Ashraf; Ponte, Fortuna; Abd El-Rahman, Mohamed K.; Russo, Nino; Sicilia, Emilia; Shoeib, Tamer

    2018-03-01

    Macromolecules including macrocyclic species have been reported to have the potential to encapsulate biologically active compounds such as drugs through host-guest complexation to increase their solubility, stability and bioavailability. In this paper the first experimental and theoretical investigation of the complexation between nedaplatin, a second generation antineoplastic drug, and p-4-sulfocalix[4]arene, a macromolecule possessing a bipolar amphiphilic structure with good biocompatibility and relatively low haemolytic toxicity for potential use as a drug delivery system is presented. Data from 1H NMR, UV, Job's plot analysis, HPLC and DFT calculations are detailed and suggest the formation of a 1:1 complex. The stability constant of the complex was experimentally estimated to be 3.6 × 104 M- 1 and 2.1 × 104 M- 1 which correspond to values of - 6.2 and - 5.9 kcal mol- 1, respectively for the free energy of complexation while the interaction free energy is calculated to be - 4.9 kcal mol- 1. The formed species is shown to be stabilised in solution through hydrogen bonding between the host and the guest which may allow for this strategy to be effective for potential use in drug delivery.

  20. Surface-enhanced Raman spectroscopy of the anti-cancer drug irinotecan in presence of human serum albumin.

    Science.gov (United States)

    Vicario, A; Sergo, V; Toffoli, G; Bonifacio, A

    2015-03-01

    The development of nanotechnological devices and their clinical application in medicine has become increasingly important, especially in the context of targeted and personalized therapy. This is particularly important in cancer therapy, where antitumor drugs are highly cytotoxic and often exert their therapeutic effect at concentrations close to systemic toxicity. In the last years a growing number of studies has started to report the use of plasmonic nanoprobes in the field of theranostics, broadening the application of vibrational spectroscopies like Raman scattering and surface enhanced Raman scattering (SERS) in biomedicine. The present work aims to identify and characterize the vibrational profiles of a widely used anticancer drug, irinotecan (CPT-11). With a rational approach, SERS experiments have been performed on this analyte employing both Au and Ag colloids, starting from simple aqueous solutions up to albumin mixtures. A major step forward for drug detection in albumin solutions has been taken with the adoption of a simple deproteinization strategy, and a two-in-one-step separation and identification by coupling thin layer chromatography, TLC, with SERS (TLC-SERS). The latter has revealed to be a valid system for protein separation and simultaneous analyte detection, showing a potential to become an innovative, sensitive and low cost method for antineoplastic drug profiling in patients' body fluids. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  2. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  3. Information for Consumers (Drugs)

    Science.gov (United States)

    ... approved drugs Drugs@FDA Information on FDA-approved brand name and generic drugs including labeling and regulatory history Drugs with Approved Risk Evaluation and Mitigation Strategies (REMS) REMS is a risk management plan required by FDA for certain prescription drugs, ...

  4. Drugs and lactation

    International Nuclear Information System (INIS)

    Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

    1988-01-01

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

  5. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  6. Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

    Directory of Open Access Journals (Sweden)

    Sana Abbasi

    2012-01-01

    Full Text Available Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI- enhanced human serum albumin (HSA nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs.

  7. Predicting Anatomical Therapeutic Chemical (ATC) Classification of Drugs by Integrating Chemical-Chemical Interactions and Similarities

    Science.gov (United States)

    Chen, Lei; Zeng, Wei-Ming; Cai, Yu-Dong; Feng, Kai-Yan; Chou, Kuo-Chen

    2012-01-01

    The Anatomical Therapeutic Chemical (ATC) classification system, recommended by the World Health Organization, categories drugs into different classes according to their therapeutic and chemical characteristics. For a set of query compounds, how can we identify which ATC-class (or classes) they belong to? It is an important and challenging problem because the information thus obtained would be quite useful for drug development and utilization. By hybridizing the informations of chemical-chemical interactions and chemical-chemical similarities, a novel method was developed for such purpose. It was observed by the jackknife test on a benchmark dataset of 3,883 drug compounds that the overall success rate achieved by the prediction method was about 73% in identifying the drugs among the following 14 main ATC-classes: (1) alimentary tract and metabolism; (2) blood and blood forming organs; (3) cardiovascular system; (4) dermatologicals; (5) genitourinary system and sex hormones; (6) systemic hormonal preparations, excluding sex hormones and insulins; (7) anti-infectives for systemic use; (8) antineoplastic and immunomodulating agents; (9) musculoskeletal system; (10) nervous system; (11) antiparasitic products, insecticides and repellents; (12) respiratory system; (13) sensory organs; (14) various. Such a success rate is substantially higher than 7% by the random guess. It has not escaped our notice that the current method can be straightforwardly extended to identify the drugs for their 2nd-level, 3rd-level, 4th-level, and 5th-level ATC-classifications once the statistically significant benchmark data are available for these lower levels. PMID:22514724

  8. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  9. Drug Reactions - Multiple Languages

    Science.gov (United States)

    ... PDF Drug Interactions - HIV medicines, part 6 - English MP3 Drug Interactions - HIV medicines, part 6 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Drug Interactions - HIV medicines, part 6 - English MP4 ...

  10. Teenagers and drugs

    Science.gov (United States)

    Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. Do not hesitate, get help right away. The ...

  11. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  12. Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH2 -vitamina D3 Vitamin D and cancer: antineoplastic effects of 1α,25(OH2-vitamin D3

    Directory of Open Access Journals (Sweden)

    Verónica González Pardo

    2012-04-01

    Full Text Available La forma hormonalmente activa de la vitamina D, 1α,25(OH2-vitamina D3 (1α,25(OH2D3, además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.The hormonal form of vitamin D, 1α,25(OH2-vitamin D3 (1α,25(OH2D3, in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

  13. Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Manda, K.; Bhatia, A. L.

    2004-07-01

    Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs.

  14. Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

    International Nuclear Information System (INIS)

    Manda, K.; Bhatia, A. L.

    2004-01-01

    Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs

  15. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Kirsi Ketola

    Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

  16. Effects of Drugs

    Science.gov (United States)

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... who aren't yet born. Drug use can hurt the body and the brain, sometimes forever. Drug use can also lead to addiction, a long-lasting brain disease in which people ...

  17. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  18. DRUG POLICY AND DRUG ADDICTION IN TURKEY

    OpenAIRE

    İLHAN, Mustafa Necmi

    2018-01-01

    The NationalStrategy Document on Drugs and Emergency Action Plan started with thecontributions of all the relevant institutions within the year of 2014 wasprepared and after that in accordance with the Prime Ministry Notice entitledFight Against Drugs published within this scope, the committees for FightAgainst Drugs were established (under the presidency of Deputy Prime Ministerand with the help of Ministry of Health, Ministry of Justice, Ministry of Laborand Social Security, Ministry of Fam...

  19. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  20. International Drug Control Policy

    Science.gov (United States)

    2009-08-24

    Common illegal drugs include cannabis, cocaine, opiates, and synthetic drugs. International trade in these drugs represents a lucrative and what...into effect, decriminalizing “personal use” amounts of marijuana , heroin, cocaine, methamphetamine, and other internationally sanctioned drugs.15 While...President Calls for Legalizing Marijuana ,”CNN.com, May 13, 2009. 15 “Mexico Legalizes Drug Possession,” Associated Press, August 21, 2009. 16 In support

  1. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  2. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  3. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  4. New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management.

    Science.gov (United States)

    Kroschinsky, Frank; Stölzel, Friedrich; von Bonin, Simone; Beutel, Gernot; Kochanek, Matthias; Kiehl, Michael; Schellongowski, Peter

    2017-04-14

    Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity. Cytokine-release syndrome (CRS) describes a complex of symptoms including fever, hypotension, and skin reactions as well as lab abnormalities. CRS may occur after the infusion of monoclonal or bispecific antibodies (MABs, BABs) targeting immune effectors and tumor cells and is a major concern in recipients of chimeric antigen receptor (CAR) modified T lymphocytes as well. BAB and CAR T-cell treatment may also be compromised by central nervous system (CNS) toxicities such as encephalopathy, cerebellar alteration, disturbed consciousness, or seizures. While CRS is known to be induced by exceedingly high levels of inflammatory cytokines, the pathophysiology of CNS events is still unclear. Treatment with antibodies against inhibiting immune checkpoints can lead to immune-related adverse events (IRAEs); colitis, diarrhea, and endocrine disorders are often the cause for ICU admissions.Respiratory distress is the main reason for ICU treatment in cancer patients and is attributable to infectious agents in most cases. In addition, some of the new drugs are reported to cause non-infectious lung complications. While drug-induced interstitial pneumonitis was observed in a substantial number of patients treated with phosphoinositol-3-kinase inhibitors, IRAEs may also affect the lungs.Inhibitors of angiogenetic pathways have increased the antineoplastic portfolio. However, vessel formation

  5. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ...

  7. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  8. Drug Monographs: Ixazomib and Necitumumab.

    Science.gov (United States)

    Lawson, Fern E; Waddell, J Aubrey; Solimando, Dominic A

    2016-05-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  9. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against

  10. Food-Drug Interactions

    Directory of Open Access Journals (Sweden)

    Arshad Yar Khan

    2011-03-01

    Full Text Available The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction, food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction or another disease the person has (drug-disease interaction. A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least fooddrug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

  11. The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design.

    Science.gov (United States)

    Giacomini, Elisa; Rupiani, Sebastiano; Guidotti, Laura; Recanatini, Maurizio; Roberti, Marinella

    2016-01-01

    The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes.

  12. Workplace Activity in Health Professionals Exposed to Chemotherapy Drugs: An Otoneurological Perspective

    Directory of Open Access Journals (Sweden)

    Fernandes, Natália Martinez

    2016-02-01

    Full Text Available Introduction The manipulation of antineoplastic drugs presents high risk for accidents and occupational diseases. Objective To evaluate the auditory and vestibular systems of workers who are exposed to chemotherapeutic treatment in the University Hospital of Universidade Federal de Santa Maria, Brazil, and to identify the use of individual protection equipment, related to the obtained results. Methods This study is a cross-sectional study using a quantitative method. We evaluate 33 male and female workers, ranging from 21–60 years old, of the nursing and pharmacy sectors. The workers underwent conventional Audiologic Assessment; Transient Evoked Otoacoustic Emissions; and Computerized Vectoelectronystagmography. Results The majority of the sample was female (90.9%. Individual protection equipment was used by 90.9% of the workers. Complaints of dizziness were reported by 56.25% of nursing workers and 52.94% of pharmacy workers. Audiological and vestibular assessment results were within normal limits, 96.97% and 74.20%, respectively. However, audiometric configuration of notch type was identified in 75.75% of all workers. Audiometric notches (76% and altered caloric test (100% were often associated with decreased use of coal masks. Conclusion Among the workers evaluated, the vestibulocochlear system was within the normal limits. The presence of notch configuration indicates the need to use individual protection equipment.

  13. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

  14. Influence of drugs on gap junctions in glioma cell lines and primary astrocytes in vitro

    Directory of Open Access Journals (Sweden)

    Zahra eMoinfar

    2014-05-01

    Full Text Available Gap junctions (GJs are hemichannels on cell membrane. Once they are intercellulary connected to the neighboring cells, they build a functional syncytium which allows rapid transfer of ions and molecules between cells. This characteristic makes GJs a potential modulator in proliferation, migration and development of the cells. So far, several types of GJs are recognized on different brain cells as well as in glioma. Astrocytes, as one of the major cells that maintain neuronal homeostasis, express different types of GJs that let them communicate with neurons, oligodendrocytes and endothelial cells of the blood brain barrier; however, the main GJ in astrocytes is connexin 43. There are different cerebral diseases in which astrocyte GJs might play a role. Several drugs have been reported to modulate gap junctional communication in the brain which can consequently have beneficial or detrimental effects on the course of treatment in certain diseases. However, the exact cellular mechanism behind those pharmaceutical efficacies on GJs is not well-understood. Accordingly, how specific drugs would affect GJs and what some consequent specific brain diseases would be are the interests of the authors of this chapter. We would focus on pharmaceutical effects on GJs on astrocytes in specific diseases where GJs could possibly play a role including: 1 migraine and a novel therapy for migraine with aura, 2 neuroautoimmune diseases and immunomodulatory drugs in the treatment of demyelinating diseases of the central nervous system such as multiple sclerosis, 3 glioma and antineoplastic and anti-inflammatory agents that are used in treating brain tumors and 4 epilepsy and anticonvulsants that are widely used for seizures therapy. All of the above-mentioned therapeutic categories can possibly affect GJs expression of astrocytes and the role is discussed in the upcoming chapter.

  15. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases.

    Science.gov (United States)

    Al-Bari, Md Abdul Alim

    2015-01-01

    Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  17. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  18. Inflammatory Drug (NSAID)

    African Journals Online (AJOL)

    Inflammatory Drug (NSAID)-Induced Seizures in a Patient with HIV Infection ... interaction not supported by existing literature, and it is possible that the background HIV infection may have a role to .... Foods and Drug Administration and Control.

  19. CMS Drug Spending

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released several information products that provide spending information for prescription drugs in the Medicare and Medicaid programs. The CMS Drug Spending...

  20. Drug Enforcement Administration

    Science.gov (United States)

    ... de informacin confidencial --> DEA NEWS The Drug Enforcement Administration and Discovery Education name grand winner of Operation ... JUN 15 (Washington) The United States Drug Enforcement Administration, DEA Educational Foundation and Discovery Education awarded Porter ...

  1. Antimicrobial (Drug) Resistance

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Antimicrobial (Drug) Resistance Go to Information for Researchers ► Credit: ... and infectious diseases. Why Is the Study of Antimicrobial (Drug) Resistance a Priority for NIAID? Over time, ...

  2. Drugs to be Discontinued

    Data.gov (United States)

    U.S. Department of Health & Human Services — Companies are required under Section 506C of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (as amended by the Food and Drug Administration Safety and...

  3. Prescription Drug Profiles PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Prescription Drug Profiles Public Use Files (PUFs) drawn from Medicare prescription drug claims for the year of the date on which the...

  4. Prescription Drug Abuse

    Science.gov (United States)

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

  5. National Drug IQ Challenge

    Science.gov (United States)

    ... National Drug IQ Challenge 2017 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge 2016 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 ...

  6. Medication/Drug Allergy

    Science.gov (United States)

    ... Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor Ask a ... risk for adverse reactions to medications. Facts about Allergies The tendency to develop allergies may be inherited. ...

  7. Drugs in sport

    OpenAIRE

    Robinson, D

    2007-01-01

    This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i) actions of drugs and hormones, ii) medication and nutritional supplements in sport, iii) the latest doping control regulations of the WADA, iv) the use of banned therapeutic drugs in sport, v) an...

  8. Sociology of Drug Consumption

    OpenAIRE

    2004-01-01

    In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption) are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual...

  9. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  10. Drug interactions with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Hesslewood, S.; Leung, E.

    1994-01-01

    Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged. (orig.)

  11. Drugs of Abuse.

    Science.gov (United States)

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  12. Drug Enforcement Administration.

    Science.gov (United States)

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  13. Collegiate Drug Management Guide.

    Science.gov (United States)

    Janosik, Steven M.; Anderson, David S.

    A checklist to help colleges and universities reevaluate their policies and procedures regarding drug use among college students is presented. It is designed to supplement the "Collegiate Alcohol Risk Assessment Guide." In this guide drugs other than alcohol are of concern, although alcohol is viewed by many as the "drug of choice" among college…

  14. Writing Drug Cultures

    DEFF Research Database (Denmark)

    Nissen, Morten

    2012-01-01

    The paper juxtaposes the cultural mediation of experience through drugs with that performed with text. As a sample of the currently radically changing relations between professional and lay knowledge in the field of drug interventions, the website of a Copenhagen institution for young drug users ...

  15. Dynamics of Drug Use

    Science.gov (United States)

    Rollins, Joan H.; Holden, Raymond H.

    1977-01-01

    This paper analyzes data from interviews with 167 drug users in the community, including age, sex, birth order, education, family constellation, and circumstances of first drug use. The majority of subjects had tried to stop using drugs, but most had been unsuccessful at the time of the interview. (Author)

  16. Drugs in breast milk.

    Science.gov (United States)

    Hervada, A R; Feit, E; Sagraves, R

    1978-09-01

    The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...

  18. Metabolism and disposition of a novel antineoplastic JS-38 (Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl)) in rats.

    Science.gov (United States)

    Zhang, Hong; Liu, Quanhai; Fan, Tingting; Fang, Yu; Li, Ying; Wang, Guoping

    2012-03-01

    The metabolism and catabolism of a novel antineoplastic (ID code JS-38),Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl), were investigated in Wistar rats (3 female, 3 male). LC/UV, LC/MS, LC/MS/MS, NMR and acid hydrolysis methods showed that the metabolic process of JS-38 consists of a series of acetylation and glucoronation that form a metabolic product with a unique pharmacologic property of accelerating bone-marrow cell formation, and also showed a novel metabolic pathway of being acetylated and glucuronated in series.

  19. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  20. Abuse of prescription drugs.

    Science.gov (United States)

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

  1. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user. Based on anecdotal evidence, most people “party” during extended time away from the work environment. Therefore, the following scenarios were envisioned: (1) a person uses an illicit drug at a party on Saturday night (infrequent user); (2) a person uses a drug one time on Friday night and once again on Saturday night (infrequent user); and (3) a person uses a drug on Friday night, uses a drug twice on Saturday night, and once again on Sunday (frequent user).

  2. Rings in drugs.

    Science.gov (United States)

    Taylor, Richard D; MacCoss, Malcolm; Lawson, Alastair D G

    2014-07-24

    We have analyzed the rings, ring systems, and frameworks in drugs listed in the FDA Orange Book to understand the frequency, timelines, molecular property space, and the application of these rings in different therapeutic areas and target classes. This analysis shows that there are only 351 ring systems and 1197 frameworks in drugs that came onto the market before 2013. Furthermore, on average six new ring systems enter drug space each year and approximately 28% of new drugs contain a new ring system. Moreover, it is very unusual for a drug to contain more than one new ring system and the majority of the most frequently used ring systems (83%) were first used in drugs developed prior to 1983. These observations give insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond.

  3. [Drugs in pregnancy].

    Science.gov (United States)

    Danchev, N; Astrug, A; Tsankova, V; Nikolova, I

    2006-01-01

    The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.

  4. Derrida and drugs

    OpenAIRE

    Gough, Tim

    2008-01-01

    Derrida, in the interview Rhetoric of Drugs (1993), following on from the explication of the notion of pharmakon (both poison and beneficial drug, at the same time), outlines a possible �theory� of drugs and addiction. It has several key features:\\ud � there are no drugs in nature: the definition of �drug� is an institutionalised one\\ud � the concept of drugs is non-scientific, non-positive\\ud � drugs are a parasitism �at once accidental and essential�; and are thus a topic ...

  5. [Evaporation of selected cytotoxic drugs and permeation of protective gloves--research into the occupational risks of health care personnel handling hazardous cytotoxic drugs (CYTO project)].

    Science.gov (United States)

    Dolezalová, L; Odráska, P; Gorná, L; Prudilová, M; Vejpustková, R; Bláha, L

    2009-01-01

    The CYTO project studies an important aspect of healthcare provision -long-term occupational exposure, both threshold and below-threshold, to chemical agents with carcinogenic and mutagenic properties, with the major focus on antineoplastic drugs.This contribution presents experimental results from the first stages of the project's experimental work, i.e. an evaluation of the physico-chemical characteristics of cytostatic agents (evaporation) and an investigation into protective glove permeation. In co-operation with IUTA (Institut für Energie- und Umwelttechnik e.V., Duisburg, Germany), the vapour pressure of paclitaxel, doxorubicin and dacarbazine was measured following OECD guideline No. 104: Vapour pressure curve--vapour pressure balance. Furthermore, the evaporation of cytostatic drugs was examined in actual laboratory conditions by monitoring the airborne concentration using the passive sampling technique. Besides the evaporation of selected drugs, the permeation of cisplatin, cyclophosphamide, doxorubicin, 5-fluorouracil and paclitaxel through different types of gloves (vinyl, latex, nitrile) was assessed. Although our experiments showed relatively slow evaporation of the evaluated cytostatic drugs (the highest pressure in paclitaxel was 0.024 Pa), equilibrium concentrations may go up to milligrams per cubic metre. Nevertheless, analytical measurements of airborne contamination did not confirm these concentration levels. The glove permeation experiments with cytostatics showed good resistance of nitrile gloves (which were impermeable to all five drugs). Other materials should be avoided while handling cytostatic agents (e.g. maximum permeation of cyclophosphamide through latex was 19 microg/sq cm/hr). Although the volatility of cytostatic agents is low, it cannot be neglected considering the chronic character of exposure. However, in order to estimate actual occupational exposure, future research should focus on the development of sensitive analytical

  6. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) ...

  8. Drugs Approved for Esophageal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. Drugs Approved for Liver Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  10. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  11. Drugs Approved for Vaginal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  12. Drugs Approved for Skin Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  13. Drugs Approved for Vulvar Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  14. Drugs Approved for Wilms Tumor

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  15. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Penile Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  18. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens ... Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and ... Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing ... please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis ( ... Party" "Text Message" NIDA Home Site Map Accessibility Privacy FOIA(NIH) Working at NIDA FAQs Contact Subscribe ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse are among the main ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  5. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

  6. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  7. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  8. Recreational drugs of abuse.

    Science.gov (United States)

    Albertson, Timothy E

    2014-02-01

    The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

  9. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  10. Discontinued drugs in 2012: cardiovascular drugs.

    Science.gov (United States)

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products.

  11. Abuse of prescription drugs.

    OpenAIRE

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disable...

  12. Radiopharmaceutical drug review process

    International Nuclear Information System (INIS)

    Frankel, R.

    1985-01-01

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  13. Drug procurement and management.

    Science.gov (United States)

    Salhotra, V S

    2003-03-01

    A strong drug procurement and management system under the RNTCP is critical to programme success. Significant improvements in manufacturing, inspection, supply, storage and quality control practices and procedures have been achieved due to an intensive RNTCP network. Drugs used in RNTCP are rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin. Patients of TB are categorised into I, II and III and each category has a different standarised treatment. Procurement, distribution system and quality assurance of drugs are narrated in brief in this article.

  14. Grapefruit and drug interactions.

    Science.gov (United States)

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  15. Drug Trafficking in Haiti

    National Research Council Canada - National Science Library

    Burns, DeEtta

    2002-01-01

    .... The thesis argues that Haiti's geographic location, political culture, illegal immigrants, entrepreneurial class and weak institutions have made it a major transshipment point for drugs to the United...

  16. Drugs in East Germany.

    Science.gov (United States)

    Dressler, J; Müller, E

    1997-09-01

    Germany was divided into two parts after World War II. The closed border and a nonconvertible currency in the Eastern part were the factors that did not allow a drug market to develop. Alcohol and medicaments were used as substitute drugs. Since Germany was reunified 5 years ago, there are now the same conditions prevailing for the procurement and sale of drugs in East Germany as there are in the Western German states. This report describes the current state of drug traffic, especially in Saxony, under the new social conditions.

  17. Population and Drugs

    OpenAIRE

    Feberová, Beata

    2008-01-01

    PEOPLE AND DRUGS II. Author: Križanová L. Tutor: Práznovcová L. Dept. of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic Background: It is necessary to rationalize the system of funding of health service. One of the ways how to achieve this aim is monitoring of drug prescription and patient's financial participation on the therapy. Aim of study: Observation and analysis of drug prescription aimed at the prescription of the drug...

  18. Drug induced lung disease

    International Nuclear Information System (INIS)

    Schaefer-Prokop, Cornelia; Eisenhuber, Edith

    2010-01-01

    There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

  19. Microwave Assisted Drug Delivery

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    In this work, the microwave radiation is adopted for remote activation of pharmaceutical drug capsules inside the human body in order to release drugs at a pre-determined time and location. An array of controllable transmitting sources is used to produce a constructive interference at a certain...... focus point inside the body, where the drugs are then released from the specially designed capsules. An experimental setup for microwave activation has been developed and tested on a body phantom that emulates the human torso. A design of sensitive receiving structures for integration with a drug...

  20. Projecting future drug expenditures--2009.

    Science.gov (United States)

    Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

    2009-02-01

    Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

  1. DRUGS IN SPORT

    Directory of Open Access Journals (Sweden)

    David R. Mottram

    2005-12-01

    Full Text Available This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i actions of drugs and hormones, ii medication and nutritional supplements in sport, iii the latest doping control regulations of the WADA, iv the use of banned therapeutic drugs in sport, v an assessment of the prevalence of drug taking in sport. FEATURES A common, uniform strategy and evidence-based approach to organizing and interpreting the literature is used in all chapters. This textbook is composed of twelve parts with sub-sections in all of them. The topics of the parts are: i An introduction to drugs and their use in sport, ii Drug use and abuse in sport, iii Central nervous system stimulants, iv WADA regulations in relation to drugs used in the treatment of respiratory tract disorders, v Androgenic anabolic steroids, vi Peptide and glycoprotein hormones and sport, vii Blood boosting and sport, viii Drug treatment of inflammation in sports injuries, ix Alcohol, anti-anxiety drugs and sport, x Creatine, xi Doping control and sport, xii Prevalence of drug misuse in sport. Each specific chapter has been systematically developed from the data available in prospective, retrospective, case-control, and cross-sectional studies. The tables and figures are numerous, helpful and very useful. AUDIENCE The book provides a very useful resource for students on sports related courses, coaches and trainers, researchers, nutritionists, exercise physiologists, pharmacologists, healthcare professionals in the fields of sports medicine and those involved in the management and administration side of sport. The readers are going to discover that this is an excellent reference book. Extensively revised new edition of this book is also a first-rate resource for

  2. Drugs and Alcohol

    Science.gov (United States)

    Scott, Victor F.

    1978-01-01

    Millions of people in this country take medications, and millions drink alcohol. Both are drugs and have effects on the organs and systems with which they or their metabolites come in contact. This short article discusses some of the combined effects of prescribed drugs and alcohol on some systems, with special emphasis on the liver. PMID:712865

  3. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  4. Alternative drugs of abuse.

    Science.gov (United States)

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  5. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  6. Student Drug Use.

    Science.gov (United States)

    Nowlis, Helen H.

    This paper discusses the nature and extent of student drug use, its meaning and significance, society's response to it, and some of the problems resulting from efforts to control it. Drugs are any substance which by its chemical nature affects the structure or function of the living organism. Abuse refers to any use of a non-medically approved…

  7. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  8. Vaginal drug distribution modeling.

    Science.gov (United States)

    Katz, David F; Yuan, Andrew; Gao, Yajing

    2015-09-15

    This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Drugs in sport.

    Science.gov (United States)

    McGrath, J C; Cowan, D A

    2008-06-01

    This themed issue of the British Journal of Pharmacology has been compiled and edited by Ian McGrath, Regius Professor of Physiology at University of Glasgow and David Cowan, Director of the Drug Control Centre at King's College London. It contains 11 articles covering the mechanisms of action of the major groups of drugs used illicitly in sport. The articles, written by experts in how drugs work, set out where drugs can or cannot affect sporting performance, how this relates to their legitimate medicinal use, their other detrimental effects and how they can be detected. Publication coincides with Olympic year, when sport is highlighted in the public mind and much speculation is made concerning the use of drugs. The articles provide a framework of expert, accurate knowledge to inform and facilitate these debates and to help to overcome the ill-informed and dangerous anecdotal information by which sports men and women are persuaded to misuse drugs in the mistaken belief that this will improve their performance without present or future ill effects. A unique article is included by the Spedding brothers, Mike with a long career in drug discovery and Charlie, the 1984 Los Angeles Olympic Marathon Bronze Medallist and still the English National Marathon record holder. From their unique experience, they describe the insidious and unfair way that drug-assisted performance undermines the ethos of sport and endangers the vital place of sport in maintaining the health of the population.

  10. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  11. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

  12. Current obesity drug treatment

    Directory of Open Access Journals (Sweden)

    Marcio C. Mancini

    2006-03-01

    Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.

  13. Drugs, Alcohol & Pregnancy.

    Science.gov (United States)

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  14. Drug Impact Index.

    Science.gov (United States)

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  15. [Drug-Drug Interactions with Consideration of Pharmacogenetics].

    Science.gov (United States)

    Ozawa, Shogo

    2018-01-01

     Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.

  16. Parents who use drugs

    DEFF Research Database (Denmark)

    Rhodes, Tim; Bernays, Sarah; Houmøller, Kathrin

    2010-01-01

    Parents who use drugs parent in a context of heightened concern regarding the damaging effects of parental drug use on child welfare and family life. Yet there is little research exploring how parents who use drugs account for such damage and its limitation. We draw here upon analyses of audio......-recorded depth qualitative interviews, conducted in south-east England between 2008 and 2009, with 29 parents who use drugs. Our approach to thematic analysis treated accounts as co-produced and socially situated. An over-arching theme of accounts was 'damage limitation'. Most damage limitation work centred...... on efforts to create a sense of normalcy of family life, involving keeping drug use secret from children, and investing heavily in strategies to maintain ambiguity regarding children's awareness. Our analysis highlights that damage limitation strategies double-up in accounts as resources of child protection...

  17. Metabonomics and drug development.

    Science.gov (United States)

    Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

    2015-01-01

    Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

  18. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  19. Drug therapy of leprosy

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2016-01-01

    Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

  20. Drug Pricing Reforms

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

    2015-01-01

    Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

  1. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  2. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Joseph A., E-mail: jaludwig@mdanderson.org; Lamhamedi-Cherradi, Salah-Eddine [Departments of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Lee, Ho-Young [Departments of Thoracic Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Naing, Aung [Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Benjamin, Robert [Departments of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2011-07-26

    The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas.

  3. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    International Nuclear Information System (INIS)

    Ludwig, Joseph A.; Lamhamedi-Cherradi, Salah-Eddine; Lee, Ho-Young; Naing, Aung; Benjamin, Robert

    2011-01-01

    The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas

  4. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

    Directory of Open Access Journals (Sweden)

    Aung Naing

    2011-07-01

    Full Text Available The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R, in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas.

  5. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  6. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Testicular Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  8. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  9. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  10. Herb-drug interactions.

    Science.gov (United States)

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  11. Drug abuse in athletes

    Directory of Open Access Journals (Sweden)

    Reardon CL

    2014-08-01

    Full Text Available Claudia L Reardon, Shane Creado Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. Keywords: doping, athletes, steroids, drug abuse, mental illness

  12. Anticancer drugs during pregnancy.

    Science.gov (United States)

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

    Science.gov (United States)

    Kuete, Victor; Donfack, Arno R Nanfack; Mbaveng, Armelle T; Zeino, Maen; Tane, Pierre; Efferth, Thomas

    2015-08-01

    Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry. Anthraquinones 1 and 2 displayed cytotoxic effects with IC50 values below 81 μM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC50 values for compounds 1 and 2 ranged from 3.12 μM and 12.18 μM (towards leukemia CCRF-CEM cells) and from 30.32 μM and 80.11 μM (towards gliobastoma U87MG.ΔEGFR cells) respectively, and from 0.20 μM (against CCRF-CEM cells) to 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers.

  14. Effects of combinations of chemotherapy and radiation on the emergence of drug resistant cells in 9L rat brain tumor spheroids

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Arundel, C.; Vines, C.M.

    1987-01-01

    Repeated administration of antineoplastic chemotherapeutic agents is generally considered to induce and/or select for drug resistant cells. The authors recently begun to investigate whether chemotherapy interdigitated with radiation can minimize or eliminate the emergence of drug resiistent cells in 9L rat brain tumor spheroids grown from defined mixtures of cells sensitive (9L) and resistant (R/sub 3/) to BCNU. In this experimental system, the sister chromatid exchange (SCE) assay is used to quantitate the proportions of sensitive and resistant cells within the spheroids. While 9L and R/sub 3/ cell have different sensitivities to BCNU, they are equally sensitive to radiation. Mixed-cell spheroids consisting of 1% R/sub 3/ cells were treated with three doses of BCNU (10 μM) every 72 hr resulting in a shift in the 9L to R/sub 3/ ratio to greater than 50% R/sub 3/ cells. The combined protocols to be investigated will involve γ rays administered either 36 hr before or after each BCNU treatment. By initiating these combined protocols on spheroids of different sizes, the effectiveness of each protocol is evaluated with respect to the number of resistant cells present

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Notes Podcasts E-Newsletters Public Education Projects National Drug & Alcohol Facts Week NIDA TV PEERx Drugs & Health Blog ... Award for Addiction Science USA Science & Engineering Festival Drug & Alcohol Chat Day HBO Addiction Project Learn the Link ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, GA: CDC, DHHS. Retrieved November 2017. How are Drug ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in providing ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe sexual practices, ... effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect ...

  20. State Drug Utilization Data 2003

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...

  2. State Drug Utilization Data 2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  3. State Drug Utilization Data 2009

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  4. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  5. State Drug Utilization Data 2016

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  6. Drugs Approved for Lung Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  9. Drugs + HIV, Learn the Link

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    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search ... Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/ ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in ...

  11. Drugs + HIV, Learn the Link

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    Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... groups of young people, guiding the use of technology, the discussion between friends, and the importance of ...

  12. State Drug Utilization Data 2017

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  13. State Drug Utilization Data 1996

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  14. Drugs Approved for Thyroid Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ...

  16. State Drug Utilization Data 2008

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  17. State Drug Utilization Data 1992

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  18. State Drug Utilization Data 1995

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  19. State Drug Utilization Data 1998

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  20. State Drug Utilization Data 2014

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...