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Sample records for arsenic-based antineoplastic drugs

  1. Arsenic-Based Antineoplastic Drugs and Their Mechanisms of Action

    PubMed Central

    Ralph, Stephen John

    2008-01-01

    Arsenic-based compounds have become accepted agents for cancer therapy providing high rates of remission of some cancers such as acute promyelocytic leukemia (APL). The mechanisms by which arsenic-containing compounds kill cells and reasons for selective killing of only certain types of cancer cells such as APLs have recently been delineated. This knowledge was gained in parallel with increasing understanding and awareness of the importance of intracellular redox systems and regulation of the production of reactive oxygen species (ROS) by controlling mitochondrial function. Many of the targets for the arsenic-containing compounds are mitochondrial proteins involved in regulating the production of ROS. Inhibition of these proteins by disulfide linkage of vicinal thiol groups often leads to increased production of ROS and induction of apoptotic signalling pathways. Sensitivity or resistance to the actions of arsenic-containing compounds on cancer cells and normal cells depends on the levels of transport systems for their uptake or efflux from the cells as well as their redox defence mechanisms. The exact mechanisms of arsenic toxicity as well as its anticancer properties are likely to be related and these aspects of arsenic metabolism are covered in this review. Greater understanding of the mechanisms of action of arsenic will help determine the risks of human exposure to this chemical. Novel organic arsenic-containing compounds and the lessons learned from studying their selective sensitivity in targeting dividing endothelial cells to inhibit angiogenesis raise the future possibility for designing better targeted antineoplastic arsenic-containing compounds with less toxicity to normal cells. PMID:18431449

  2. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  3. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    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).

  4. Tumor targeting using liposomal antineoplastic drugs

    PubMed Central

    Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan

    2008-01-01

    During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, 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. PMID:18488413

  5. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  6. PCNA Damage Caused by Anti-Neoplastic Drugs

    PubMed Central

    Bae, Soo In; Zhao, Ran; Snapka, Robert M.

    2008-01-01

    Structurally diverse chemotherapeutic and chemopreventive drugs, including camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian cells exposed to fluorescent light. This PCNA damage was caused by both nuclear and cytoplasmically localizing drugs. For some drugs, the PCNA crosslinking was evident even with very brief exposures to laboratory room lighting. In the absence of drugs, there was no detectable covalent crosslinking of PCNA trimers. Other proteins were photo-crosslinked to PCNA at much lower levels, including crosslinking of additional PCNA to the PCNA trimer. The proteins photo-crosslinked to PCNA did not vary with cell type or drug. PCNA was not crosslinked to itself or to other proteins by superoxide, hydrogen peroxide or hydroxyl radicals, but hydrogen peroxide caused mono-ubiquitination of PCNA. Quenching of PCNA photo-crosslinking by histidine, and enhancement by deuterium oxide, suggest a role for singlet oxygen in the crosslinking. SV40 large T antigen hexamers were also efficiently covalently photo-crosslinked by drugs and light. Photodynamic crosslinking of nuclear proteins by cytoplasmically localizing drugs, together with other evidence, argues that these drugs may reach the nucleoplasm in amounts sufficient to photodamage important chromosomal enzymes. The covalent crosslinking of PCNA trimers provides an extremely sensitive biomarker for photodynamic damage. The damage to PCNA and large T antigen raises the possibility that DNA damage signaling and repair mechanisms may be compromised when cells treated with antineoplastic drugs are exposed to visible light. PMID:18823950

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2015-12-01

    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. PMID:26058504

  9. Unexploited Antineoplastic Effects of Commercially Available Anti-Diabetic Drugs

    PubMed Central

    Papanagnou, Panagiota; Stivarou, Theodora; Tsironi, Maria

    2016-01-01

    The development of efficacious antitumor compounds with minimal toxicity is a hot research topic. Numerous cancer cell targeted agents are evaluated daily in laboratories for their antitumorigenicity at the pre-clinical level, but the process of their introduction into the market is costly and time-consuming. More importantly, even if these new antitumor agents manage to gain approval, clinicians have no former experience with them. Accruing evidence supports the idea that several medications already used to treat pathologies other than cancer display pleiotropic effects, exhibiting multi-level anti-cancer activity and chemosensitizing properties. This review aims to present the anticancer properties of marketed drugs (i.e., metformin and pioglitazone) used for the management of diabetes mellitus (DM) type II. Mode of action, pre-clinical in vitro and in vivo or clinical data as well as clinical applicability are discussed here. Given the precious multi-year clinical experience with these non-antineoplastic drugs their repurposing in oncology is a challenging alternative that would aid towards the development of therapeutic schemes with less toxicity than those of conventional chemotherapeutic agents. More importantly, harnessing the antitumor function of these agents would save precious time from bench to bedside to aid the fight in the arena of cancer. PMID:27164115

  10. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-12

    ... in the Federal Register June 27, 2012, (77 FR 38297). This notice is corrected as follows: On page... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute...

  11. 75 FR 57044 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care... Appendix A of the Alert. This guidance document does not have the force and effect of law. FOR...

  12. 76 FR 46299 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012: Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    ... Hazardous Drugs in Healthcare Settings 2012: Proposed Additions and Deletions to the NIOSH Hazardous Drug... Drugs in Healthcare Settings 2012: Proposed Additions and Deletions to the NIOSH Hazardous Drug List...: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings...

  13. Inhibitions of several antineoplastic drugs on serum sialic Acid levels in mice bearing tumors.

    PubMed

    Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

    2013-03-01

    Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement. PMID:23641340

  14. 78 FR 33097 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014: Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ...The National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC) announces the availability of the following draft document for public comment entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014: Proposed Additions and Deletions to the NIOSH Hazardous Drug List.'' The document and instructions......

  15. Adherence to safe handling guidelines by health care workers who administer antineoplastic drugs.

    PubMed

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2014-01-01

    The toxicity of antineoplastic drugs is well documented. Many are known or suspected human carcinogens where no safe exposure level exists. Authoritative guidelines developed by professional practice organizations and federal agencies for the safe handling of these hazardous drugs have been available for nearly three decades. As a means of evaluating the extent of use of primary prevention practices such as engineering, administrative and work practice controls, personal protective equipment (PPE), and barriers to using PPE, the National Institute for Safety and Health (NIOSH) conducted a web survey of health care workers in 2011. The study population primarily included members of professional practice organizations representing health care occupations which routinely use or come in contact with selected chemical agents. All respondents who indicated that they administered antineoplastic drugs in the past week were eligible to complete a hazard module addressing self-reported health and safety practices on this topic. Most (98%) of the 2069 respondents of this module were nurses. Working primarily in hospitals, outpatient care centers, and physician offices, respondents reported that they had collectively administered over 90 specific antineoplastic drugs in the past week, with carboplatin, cyclophosphamide, and paclitaxel the most common. Examples of activities which increase exposure risk, expressed as percent of respondents, included: failure to wear nonabsorbent gown with closed front and tight cuffs (42%); intravenous (I.V.) tubing primed with antineoplastic drug by respondent (6%) or by pharmacy (12%); potentially contaminated clothing taken home (12%); spill or leak of antineoplastic drug during administration (12%); failure to wear chemotherapy gloves (12%); and lack of hazard awareness training (4%). The most common reason for not wearing gloves or gowns was "skin exposure was minimal"; 4% of respondents, however, reported skin contact during handling and

  16. Adherence to Precautionary Guidelines for Compounding Antineoplastic Drugs: A Survey of Nurses and Pharmacy Practitioners.

    PubMed

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2015-01-01

    Precautionary guidelines detailing standards of practice and equipment to eliminate or minimize exposure to antineoplastic drugs during handling activities have been available for nearly three decades. To evaluate practices for compounding antineoplastic drugs, the NIOSH Health and Safety Practices Survey of Healthcare Workers was conducted among members of professional practice organizations representing primarily oncology nurses, pharmacists, and pharmacy technicians. This national survey is the first in over 20 years to examine self-reported use of engineering, administrative, and work practice controls and PPE by pharmacy practitioners for minimizing exposure to antineoplastic drugs. The survey was completed by 241 nurses and 183 pharmacy practitioners who compounded antineoplastic drugs in the seven days prior to the survey. They reported: not always wearing two pairs of chemotherapy gloves (85%, 47%, respectively) or even a single pair (8%, 10%); not always using closed system drug-transfer devices (75%, 53%); not always wearing recommended gown (38%, 20%); I.V. lines sometimes/always primed with antineoplastic drug (19%, 30%); and not always using either a biological safety cabinet or isolator (9%, 15%). They also reported lack of: hazard awareness training (9%, 13%); safe handling procedures (20%, 11%); and medical surveillance programs (61%, 45%). Both employers and healthcare workers share responsibility for adhering to precautionary guidelines and other best practices. Employers can ensure that: workers are trained regularly; facility safe-handling procedures reflecting national guidelines are in place and support for their implementation is understood; engineering controls and PPE are available and workers know how to use them; and medical surveillance, exposure monitoring, and other administrative controls are in place. Workers can seek out training, understand and follow facility procedures, be role models for junior staff, ask questions, and report

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

    SciTech Connect

    Hernandez-Esquivel, Luz; Marin-Hernandez, Alvaro; Pavon, Natalia; Carvajal, Karla; Moreno-Sanchez, Rafael . E-mail: rafael.moreno@cardiologia.org.mx

    2006-04-01

    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{sub 2} consumption with half-maximal inhibitory concentrations (IC{sub 5}) of 4 (CSII) and 4.6 (CSIII) {mu}M, 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{sub 5} = 2.6 {mu}M), 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 {mu}M 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.

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

    PubMed Central

    Heger, Zbynek; Cernei, Natalia; Kudr, Jiri; Gumulec, Jaromir; Blazkova, Iva; Zitka, Ondrej; Eckschlager, Tomas; Stiborova, Marie; Adam, Vojtech; Kizek, Rene

    2013-01-01

    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. PMID:24185911

  19. Comparison of three assays for genetic effects of antineoplastic drugs on cancer patients and their nurses

    SciTech Connect

    Krepinsky, A. ); Bryant, D.W.; Davison, L.; McCalla, D.R. ); Young, B. ); Heddle, J. ); Douglas, G. ); Michalko, K. )

    1990-01-01

    Three assays have been compared for their ability to detect genetic damage caused by antineoplastic drugs in cancer patients and possible damage in the nurses who administered these drugs. The assays were sister chromatid exchanges (SCE) and chromosomal aberrations in peripheral blood lymphocytes, and the Salmonella/mammalian microsome assay on urine. Three comparisons were made: (1) patients before versus after treatment; (2) the administering nurses immediately after their work period versus after a few days off that followed (work and off-work); (3) the exposed nurses versus other nurses who did not administer antineoplastic drugs (controls). The SCE assay did not distinguish between the work and off-work samples in either the exposed or control nurses. Chromosomal aberration was the only assay which showed significant difference between the two samples of the exposed nurses and, consequently, between the exposed and control nurses. There is no evidence that the increase was connected to occupational exposure.

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

    PubMed

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

    2015-01-01

    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. PMID:26276739

  1. Antineoplastic drug contamination on the hands of employees working throughout the hospital medication system.

    PubMed

    Hon, Chun-Yip; Teschke, Kay; Demers, Paul A; Venners, Scott

    2014-07-01

    We previously reported that antineoplastic drug contamination is found on various work surfaces situated throughout the hospital medication system (process flow of drug within a facility from initial delivery to waste disposal). The presence of drug residual on surfaces suggests that healthcare workers involved in some capacity with the system may be exposed through dermal contact. The purpose of this paper was to determine the dermal contamination levels of healthcare employees working throughout a hospital and to identify factors that may influence dermal contamination. We selected participants from six hospitals and wiped the front and back of workers' hands. Wipe samples were analyzed for cyclophosphamide (CP), a commonly used antineoplastic drug, using high-performance liquid chromatography-tandem mass spectrometry. Participants were asked about their frequency of handling antineoplastic drugs, known contact with CP on their work shift, gender, job title, and safe drug handling training. In addition, participants were surveyed regarding their glove usage and hand washing practices prior to wipe sample collection. We collected a total of 225 wipe samples. Only 20% (N = 44) were above the limit of detection (LOD) of 0.36ng per wipe. The average concentration was 0.36ng per wipe, the geometric mean < LOD, the geometric standard deviation 1.98, and the range < LOD to 22.8ng per wipe. Hospital employees were classified into eight different job categories and all categories had some dermal contamination levels in excess of the LOD. The job category with the highest proportion of samples greater than the LOD were those workers in the drug administration unit who were not responsible for drug administration (volunteer, oncologist, ward aide, dietician). Of note, the highest recorded concentration was from a worker who had no known contact with CP on their work shift. Our results suggest that a broader range of healthcare workers than previously believed, including

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

    PubMed Central

    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

  3. Pilot Evaluation of Dermal Contamination by Antineoplastic Drugs among Hospital Pharmacy Personnel

    PubMed Central

    Hon, Chun-Yip; Astrakianakis, George; Danyluk, Quinn; Chu, Winnie

    2011-01-01

    Background: It is believed that health care workers are exposed to antineoplastic drugs primarily via dermal contact. However, levels of occupational dermal contamination in Canada have not been formally investigated. Objective: To determine the potential dermal exposure to antineoplastic drugs among hospital pharmacy personnel in a metropolitan area in British Columbia. Methods: Six hospital pharmacies in the Vancouver area participated in this pilot study. Three pharmacy workers (a technician responsible for preparing drugs, a pharmacist responsible for checking drugs before administration, and a technician not responsible for preparing drugs but working in the pharmacy department) were selected from each site, for a total of 18 participants. Each worker’s hands were wiped with a premoistened tissue (one wipe per person), and the wipes were subsequently analyzed by high-performance liquid chromatography tandem mass spectrometry to determine levels of both cyclophosphamide and methotrexate (total of 36 analyses). Results: At 3 of the 6 sites, at least one hand-wipe sample was above the analytical detection limit. Of the 18 analyses from the 3 “positive” sites, 5 (28%) had measurable levels of cyclophosphamide and methotrexate. Cyclophosphamide was detected in 3 samples (geometric mean 0.98 ng, geometric standard deviation 2.72 ng, range from below limit of detection to 3.96 ng) and methotrexate in 2 samples (geometric mean 0.27 ng, geometric standard deviation 2.57 ng, range from below limit of detection to 0.27 ng). Conclusions: The results of this pilot study suggest that hospital pharmacy workers in Metro Vancouver are probably exposed to antineoplastic drugs, given that detectable levels of drug were found on the hands of some personnel. Further studies are recommended to confirm these findings. PMID:22479084

  4. Permeability of latex and polyvinyl chloride gloves to 20 antineoplastic drugs.

    PubMed

    Laidlaw, J L; Connor, T H; Theiss, J C; Anderson, R W; Matney, T S

    1984-12-01

    Permeability of latex and polyvinyl chloride (PVC) gloves to 20 injectable antineoplastic drugs was studied. Four types of gloves were evaluated: latex surgical gloves, latex examination gloves, and PVC gloves in two thicknesses. Each glove material was exposed to each drug for 90 minutes, and permeation was tested using a mutagenicity assay. Individual fingertips of thin PVC gloves and latex surgical gloves were tested for permeability at five time points (2-30 minutes) using a doxorubicin coloration assay. All drugs permeated the thin PVC gloves. Latex surgical gloves were definitely permeable to two drugs (carmustine and thiotepa) and exhibited borderline permeability to mechlorethamine hydrochloride. The thick PVC gloves were definitely permeable to four drugs (carmustine, thiotepa, mechlorethamine hydrochloride, and daunorubicin hydrochloride) and exhibited borderline permeability to two drugs (doxorubicin and mercaptopurine). The latex examination gloves were permeable to carmustine, thiotepa, mechlorethamine hydrochloride, and cyclophosphamide. Doxorubicin permeation of individual fingertips of thin PVC gloves varied in time and amount. Doxorubicin did not permeate the latex surgical glove material, but testing with thiotepa showed that individual fingertips of this material also varied in permeability. Glove thickness was a major determinant of permeability; latex surgical gloves were the least permeable and thin PVC gloves the most permeable to the antineoplastic drugs tested. Within individual gloves and glove types, time and amount of permeation were not uniform. PMID:6440436

  5. Detection and measurement of surface contamination by multiple antineoplastic drugs using multiplex bead assay

    PubMed Central

    Smith, Jerome P; Sammons, Deborah L; Robertson, Shirley A; Pretty, Jack; Debord, D Gayle; Connor, Thomas H; Snawder, John

    2015-01-01

    Objectives Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive. Since immunochemical methods may be cheaper and faster than instrumental methods, we wanted to explore their use for routine drug residue detection for preventing worker exposure. Methods In this study we examined the feasibility of using fluorescence covalent microbead immunosorbent assay (FCMIA) for simultaneous detection and semi-quantitative measurement of three antineoplastic drugs (5-fluorouracil, paclitaxel, and doxorubicin). The concentration ranges for the assay were 0–1000 ng/ml for 5-fluorouracil, 0–100 ng/ml for paclitaxel, and 0–2 ng/ml for doxorubicin. The surface sampling technique involved wiping a loaded surface with a swab wetted with wash buffer, extracting the swab in storage/blocking buffer, and measuring drugs in the extract using FCMIA. Results There was no significant cross reactivity between these drugs at the ranges studied indicated by a lack of response in the assay to cross analytes. The limit of detection (LOD) for 5-fluorouracil on the surface studied was 0.93 ng/cm2 with a limit of quantitation (LOQ) of 2.8 ng/cm2, the LOD for paclitaxel was 0.57 ng/cm2 with an LOQ of 2.06 ng/cm2, and the LOD for doxorubicin was 0.0036 ng/cm2 with an LOQ of 0.013 ng/cm2. Conclusion The use of FCMIA with a simple sampling technique has potential for low cost simultaneous detection and semi-quantitative measurement of surface contamination from multiple antineoplastic drugs. PMID:25293722

  6. Antineoplastic drug, carboplatin, protects mice against visceral leishmaniasis.

    PubMed

    Kaur, Tejinder; Makkar, Prerna; Randhawa, Kulbir; Kaur, Sukhbir

    2013-01-01

    In the present study, the leishmanicidal effect of two doses (5 and 10 mg/kg body weight) of the carboplatin was studied in Leishmania donovani-infected BALB/c mice. Mice were infected intracardially with promastigotes of L. donovani, and a month after infection, they were treated intraperitoneally with the two doses of the drug (5 and 10 mg/kg body weight) for five continuous days. Animals were sacrificed on 1 and 15 posttreatment days. Hepatic parasite load was assessed on Geimsa-stained imprints. Immune responses were studied by measuring delayed-type hypersensitivity (DTH) responses, serum IgG isotype levels (IgG1 and IgG2a) and cytokine levels [γ-interferon (IFN-γ), interleukin (IL)-10 and IL-2] in spleen cell cultures by ELISA. To study the drug-induced side effects, various haematological (haemoglobin and total leukocyte count), biochemical (liver and kidney function tests) and histological investigations (kidney, liver and spleen) were carried out. The antileishmanial potential of the drug was revealed by significant reduction in the parasite burden. The infected and treated animals were also found to exhibit increased DTH responses, higher IgG2a levels, lower IgG1 levels and greater cytokine (IFN-γ, IL-10 and IL-2) concentrations pointing towards the generation of mixed Th1/Th2 response. Liver and kidney function tests and histological studies of kidney, liver and spleen of treated mice revealed no side effects. Carboplatin cures mice of visceral leishmaniasis without causing any serious side effects, and the drug was found be more effective at a dose of 10 mg/kg body weight as compared to 5 mg/kg body weight. PMID:22961311

  7. Exposure of pharmacy personnel to mutagenic antineoplastic drugs

    SciTech Connect

    Nguyen, T.V.; Theiss, J.C.; Matney, T.S.

    1981-01-01

    The Salmonella reversion test was used to measure the mutagenic activities of urine concentrates from individuals preparing cancer chemotherapy agents for intravenous administration. Longitudinal studies were performed in which the total urine produced in 24 hour periods was collected, starting on a Sunday at 7:00 p.m. after a duty-free weekend and extending over an eight day period. There was no detectable increase in mutagenic activity in the urine concentrates of three pharmacy administrators who had no contact with these drugs. All six individuals admixing drugs in open-faced, horizontal laminar flow hoods displayed a two-fold increase in mutagenesis by the fourth day with peak values of 2.7 to 24-fold occurring on days five and six, reduced values by day seven with a return to the spontaneous level by day eight. When four of the six positive individuals in the preceding experiment admixed comparable amounts of chemotherapeutic drugs in a closed-faced, vertical laminar flow hood, no increase in mutagenic activity was detected in their urine concentrates over the eight day period.

  8. Permeability of four disposable protective-clothing materials to seven antineoplastic drugs.

    PubMed

    Laidlaw, J L; Connor, T H; Theiss, J C; Anderson, R W; Matney, T S

    1985-11-01

    The permeability of four types of protective-clothing material to seven injectable antineoplastic drugs was studied. The protective materials tested were Saranex-laminated Tyvek, polyethylene-coated Tyvek, nonporous Tyvek, and Kaycel. Circles 6 cm in diameter were cut from a single garment of each material and exposed to each drug. Permeation of cisplatin, etoposide, mitomycin, cyclophosphamide, carmustine, and thiotepa was assessed by the Salmonella mutagenicity test after four hours of exposure. Doxorubicin permeation was assessed qualitatively over an eight-hour exposure period using a coloration assay. Saranex-laminated Tyvek was not permeable under the test conditions. Polyethylene-coated Tyvek was slightly permeable to thiotepa and carmustine. Nonporous Tyvek was permeable to all seven drugs, and the Kaycel garment was permeable to all of the drugs except etoposide. In no instance did permeation exceed 3.3% of the applied drug dose. Saranex-laminated Tyvek was the most protective of the barrier garments, followed closely in effectiveness by the polyethylene-coated Tyvek. Clothing made from these two Tyvek composites would allow less air flow and, therefore, would be less comfortable to wear for extended periods. Garments made of nonporous Tyvek or Kaycel would be more comfortable, but their use should be accompanied by an awareness of their potential permeability to certain antineoplastic drugs. PMID:4073061

  9. Occupational exposure to antineoplastic drugs in four Italian health care settings.

    PubMed

    Sottani, Cristina; Porro, Benedetta; Imbriani, Marcello; Minoia, Claudio

    2012-08-13

    Exposure assessment of health care workers to antineoplastic drugs (ADs) is still an open issue since new, critical, and emerging factors may put pharmacists who prepare hazardous drugs or nurses who administer anti cancer agents to an increased risk of developing adverse health effects. Overall, eight pharmacies and nine patient areas have been surveyed in this study. Wipe and pad samples were experienced during the surveillance program in four Italian health care settings. Urine samples were collected from workers handling ADs. Cyclophosphamide (CP), ifosfamide (IF), and gemcitabine (GEM) were detected in all the work environments by using a LC-MS/MS method-based capable of analysing all the three drugs simultaneously. In total, 54% of wipe samples were positive for at least one drug and 19% of pad samples were shown to be contaminated by cyclophosphamide. Pharmacies were generally more contaminated than patient areas with the exception of one site where a nurse had an acute exposure during the cleaning-up of an hazardous drug solution spill. In total, 22 urine samples collected from pharmacists and 78 urine samples from nurses had no detectable concentrations of any antineoplastic drugs. Despite the adherence to the recommended safety practices residue contamination on surfaces and floors has continued to be assessed in all the investigated sites. PMID:21477641

  10. Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Gibaud, Stéphane; Jaouen, Gérard

    Although arsenic is a poison and has a predominantly unfavorable reputation, it has been used as pharmaceutical agent since the first century BC. In 1786, Thomas Fowler reported the effects of arsenic in the cure of agues, remittent fevers, and periodic headaches. From this time on and despite abusive use, some interesting indications began to appear for trypanosomiasis, syphilis, and blood diseases. The first significant organoarsenical drug (atoxyl) was synthesized by Pierre Antoine Béchamp in 1859 by chemically reacting arsenic acid with aniline but additional experimentations on the properties of arsenic led Paul Ehrlich, the founder of chemotherapy, to the discovery of salvarsan in 1910. From the Second World War, Ernst A.H. Friedheim greatly improved the treatment of trypanosomiasis by melaminophenyl arsenicals. Until the 1990s some organoarsenicals were used for intestinal parasite infections but carcinogenic effects were displayed and all the drugs have been withdrawn in USA, in Europe, and elsewhere. In 2003, arsenic trioxide (Trisenox®) was re-introduced for the treatment of very specific hematological malignancies.

  11. Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations.

    PubMed

    Connor, Thomas H; Zock, Matthew D; Snow, Amy H

    2016-09-01

    Surface wipe sampling for various hazardous agents has been employed in many occupational settings over the years for various reasons such as evaluation of potential dermal exposure and health risk, source determination, quality or cleanliness, compliance, and others. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine surface contamination of the workplace with these drugs. The purpose of this article is to review published studies of wipe sampling for antineoplastic and other hazardous drugs, to summarize the methods in use by various organizations and researchers, and to provide some basic guidance for conducting surface wipe sampling for these drugs in healthcare settings.  Recommendations on wipe sampling methodology from several government agencies and organizations were reviewed. Published reports on wipe sampling for hazardous drugs in numerous studies were also examined. The critical elements of a wipe sampling program and related limitations were reviewed and summarized.  Recommendations and guidance are presented concerning the purposes of wipe sampling for antineoplastic and other hazardous drugs in the healthcare setting, technical factors and variables, sampling strategy, materials required, and limitations. The reporting and interpretation of wipe sample results is also discussed.  It is recommended that all healthcare settings where antineoplastic and other hazardous drugs are handled consider wipe sampling as part of a comprehensive hazardous drug "safe handling" program. Although no standards exist for acceptable or allowable surface concentrations for these drugs in the healthcare setting, 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. A comprehensive safe-handling program for antineoplastic drugs may

  12. Toxicity of the mixture of selected antineoplastic drugs against aquatic primary producers.

    PubMed

    Elersek, Tina; Milavec, Sara; Korošec, Maša; Brezovsek, Polona; Negreira, Noelia; Zonja, Bozo; de Alda, Miren López; Barceló, Damià; Heath, Ester; Ščančar, Janez; Filipič, Metka

    2016-08-01

    The residues of antineoplastic drugs are considered as new and emerging pollutants in aquatic environments. Recent experiments showed relatively high toxicity of 5-fluorouracil (5-FU), imatinib mesylate (IM), etoposide (ET) and cisplatin (CP) that are currently among most widely used antineoplastic drugs, against phytoplankton species. In this study, we investigated the toxic potential of the mixture of 5-FU + IM + ET against green alga Pseudokirchneriella subcapitata and cyanobacterium Synechococcus leopoliensis, and the stability and sorption of these drugs to algal cells. Toxic potential of the mixture was predicted by the concepts of 'concentration addition' and 'independent action' and compared to the experimentally determined toxicity. In both test species, the measured toxicity of the mixture was at effects concentrations EC10-EC50 higher than the predicted, whereas at higher effect concentration (EC90), it was lower. In general, P. subcapitata was more sensitive than S. leopoliensis. The stability studies of the tested drugs during the experiment showed that 5-FU, IM and CP are relatively stable, whereas in the cultures exposed to ET, two transformation products with the same mass as ET but different retention time were detected. The measurements of the cell-linked concentrations of the tested compounds after 72 h exposure indicated that except for CP (1.9 % of the initial concentration), these drugs are not adsorbed or absorbed by algal cells. The results of this study showed that in alga and cyanobacteria exposure to the mixture of 5-FU + ET + IM, in particular at low effect concentration range, caused additive or synergistic effect on growth inhibition, and they suggest that single compound toxicity data are not sufficient for the proper toxicity prediction for aquatic primary producers. PMID:26755176

  13. Robotic system for i.v. antineoplastic drug preparation: description and preliminary evaluation under simulated conditions.

    PubMed

    Cote, D D; Torchia, M G

    1989-11-01

    A robotic system for preparing doses of i.v. antineoplastic drugs is described, and measurements made with the system are compared for accuracy and reproducibility with those made by pharmacists and technicians. System hardware consists of a robotic arm, a 16-bit microcomputer, a bar-code reader, a voice synthesizer, and an electronic balance. The software includes a menu-driven main program, executable files for each robotic activity, and an interface to allow control to pass between the program and the files. The program has routines for matching the software to the hardware; for entering information about the patient, the name of the drug ordered, and the dose; for checking the dose; for selecting the number and size of the vials to be used; for specifying the manipulations of the robotic arm; for printing labels; and for maintaining records. The robot fills an order by getting and placing a vial, inserting a needle into it and withdrawing the drug, weighing the vial, agitating the container to dissolve its contents, reading a bar code, placing a syringe in a syringe manipulator, and getting an i.v. container and injecting the drug into it. Detection of any errors by a series of self-checks arrests execution of an order. No significant differences in accuracy and precision were found between the robotic system and humans performing the same tasks under simulated conditions. The robotic system required less time than humans and eliminated the possibility of direct human contact with the i.v. admixture. Under simulated conditions, a robotic system developed to assist in the preparation of i.v. antineoplastic drugs was as accurate as a manual system and was more time efficient. PMID:2589345

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

    PubMed

    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. PMID:23929731

  15. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    PubMed Central

    Molinaro, Marilisa; Ameri, Pietro; Marone, Giancarlo; Petretta, Mario; Abete, Pasquale; Di Lisa, Fabio; De Placido, Sabino; Bonaduce, Domenico; Tocchetti, Carlo G.

    2015-01-01

    Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV) dysfunction, and heart failure (HF). The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF) is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure. PMID:26583088

  16. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    PubMed Central

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug. PMID:26622892

  17. Review of Experience of a Statewide Poison Control Center With Pediatric Exposures to Oral Antineoplastic Drugs in the Nonmedical Setting.

    PubMed

    Thornton, Stephen L; Liu, Jehnan; Soleymani, Kamyar; Romasco, Rebecca L; Farid, Hanieh; Clark, Richard F; Cantrell, F Lee

    2016-01-01

    The use of oral antineoplastic agents in nonmedical settings continues to increase. There are limited data available on pediatric exposures to these agents. We sought to identify characteristics of such exposures. We performed a retrospective review of database of a statewide poison system from 2000 to 2009 for all cases of pediatric exposures to oral antineoplastic agents, which took place in a nonmedical setting. Data collected include gender, age, agent of exposure, dose, drug concentration, reason for exposure, symptoms, outcomes, interventions, and length of hospital stay. There were a total of 328 patients. The mean average age was 4.1 years. Eighty-nine percentage (n = 293) was unintentional. Exposures to 21 different antineoplastic agents were identified. Methotrexate (n = 91) and 6-mercaptopurine (n = 47) were the most common agents encountered. Two hundred ninety-nine (91%) cases had no symptoms reported. When reported, gastrointestinal symptoms (n = 17) and central nervous system sedation (n = 6) were most common. One case of pancytopenia was reported. No deaths were reported in this series. Sixty-seven percent (n = 220) were managed at home, whereas 19 (6%) were admitted to a health care facility. Cases were followed by the poison control center for 0.34 days (SD = 1.40). In this study, exposures to oral antineoplastics were primarily unintentional, asymptomatic, and managed at home. Study limitations include possible reporting bias, inability to objectively confirm exposures, and limited duration of monitoring by the poison control center. In this retrospective review, no significant morbidity or mortality was reported from pediatric exposures to oral antineoplastic drugs in the nonmedical setting. PMID:23884076

  18. Investigations on nanoconfinement of low-molecular antineoplastic agents into biocompatible magnetic matrices for drug targeting.

    PubMed

    Tomoiaga, Alina Maria; Cioroiu, Bogdan Ionel; Nica, Valentin; Vasile, Aurelia

    2013-11-01

    Magnetic mesoporous silica nanoparticles are employed as biocompatible matrices to host low-molecular antineoplastic drugs. 5-Fluorouracil is a well-known antimetabolite drug used to treat many malignancies: colon, rectal, breast, head and neck, pancreatic, gastric, esophageal, liver and G-U (bladder, penile, vulva, prostate), skin cancers (basal cell and keratosis). Unfortunately severe gastrointestinal, hematological, neural, cardiac and dermatological toxic effects are often registered due to its cytotoxicity. Thus, this work focuses on development of a magnetic silica nanosystem, capable of hosting high amounts of 5-fluorouracil and delivers it in a targeted manner, under the influence of external magnetic field. There are few reports on nanoconfinement of this particular small molecule antimetabolite on mesoporous silica hosts. Therefore we have investigated different ways to confine high amounts of 5-FU within amino-modified and non-modified mesopores of the silica shell, from water and ethanol, under magnetic stirring and ultrasound irradiation. Also, we have studied the adsorption process from water as a function of pH in order to rationalize drug-support interactions. It is shown that nature of the solvent has great influence on diffusion of small molecules into mesopores, which is slower from alcoholic solutions. More importantly, sonication is proven as an excellent alternative to long adsorption tests, since the time necessary to reach equilibrium is drastically reduced to 1h and higher amounts of drug may be immobilized within the mesopores of amino-modified magnetic silica nanoparticles. These results are highly important for optimization of drug immobilization process in order to attain desired release profile. PMID:23777792

  19. Effects of some anti-neoplastic drugs on sheep liver sorbitol dehydrogenase.

    PubMed

    Alim, Zuhal; Beydemir, Şükrü

    2012-12-01

    Stress is an important factor for many diseases in living metabolisms. The mini pathway named as polyol is a critical junction for stress factors. This pathway has two enzymes: aldose reductase (AR) and sorbitol dehydrogenase (SDH). It is linked with some diseases such as diabetes mellitus and some cancer types. In particular, SDH is very sensitive and unstable in in vitro conditions. In this study, SDH was purified by using simple and rapid chromatographic methods such as DEAE-Sephadex and CM-Sephadex C-50 columns. Subunit and active form molecular weights were found as 39.8 kDa and 150 kDa, respectively. The in vitro effects of some antineoplastic drugs were investigated. IC(50) values were 0.025, 0.081, 0.291, 1.62, 4.86, 6.54 mM for dacarbazine, methotrexate, epirubicin hydrochloride, calcium folinate, gemcitabine hydrochloride, oxaliplatin, respectively. From these results, dacarbazine was lowest IC(50) value and it is the strongest inhibitor for liver SDH enzyme activity compared to the other drugs. PMID:22639851

  20. Predictors of adherence to safe handling practices for antineoplastic drugs: A survey of hospital nurses.

    PubMed

    Silver, Sharon R; Steege, Andrea L; Boiano, James M

    2016-01-01

    Despite growing awareness of the hazards of exposure to antineoplastic drugs (ADs), surveys continue to find incomplete adherence to recommended safe handling guidelines. A 2011 survey of healthcare workers presents an opportunity to examine factors associated with adherence among 1094 hospital nurses who administered ADs. Data for these hypothesis-generating analyses were taken from an anonymous, web-based survey of healthcare workers. Regression modeling was used to examine associations between a number of predictors (engineering controls, work practices, nurse perceptions, and nurse and hospital characteristics) and three outcomes reported by nurses: use of personal protective equipment (PPE); activities performed with gloves previously worn to administer ADs; and spills of ADs. Adherence to safe handling guidelines was not universal, and AD spills were reported by 9.5% of nurses during the week prior to the survey. Familiarity with safe handling guidelines and training in safe handling were associated with more reported PPE use. Nurse-perceived availability of PPE was associated with more reported PPE use and lower odds of reported spills. Use of closed system drug-transfer devices and luer-lock fittings also decreased the odds of self-reported AD spills, while more frequent AD administration increased the risk. AD administration frequency was also associated with performing more activities with gloves previously worn to administer ADs, and nurse perception of having adequate time for taking safety precautions with fewer such activities. The results suggest that training and familiarity with guidelines for safe handling of ADs, adequate time to adhere to guidelines, and availability of PPE and certain engineering controls are key to ensuring adherence to safe handling practices. Further assessment of training components and engineering controls would be useful for tailoring interventions targeting these areas. PMID:26556549

  1. Antineoplastic drugs determination by HPLC-HRMS(n) to monitor occupational exposure.

    PubMed

    Dal Bello, Federica; Santoro, Valentina; Scarpino, Valentina; Martano, Chiara; Aigotti, Riccardo; Chiappa, Alberta; Davoli, Enrico; Medana, Claudio

    2016-07-01

    The purpose of this study was to develop a simple, direct, multiresidue highly specific procedure to evaluate the possible surface contamination of selected antineoplastic drugs in several hospital environment sites by using wipe test sampling. 5-fluorouracil (5-FU), carboplatin (C-Pt), cyclophosphamide (CYC), cytarabine (CYT), doxorubicin (DOX), gemcitabine (GEM), ifosfamide (IFO), methotrexate (MET), and mitomycin C (MIT) belong to very different chemical classes but show good ionization properties under electrospray ionization (ESI) conditions (negative ion mode for 5-FU and positive ion mode in all other cases). HPLC (high performance liquid chromatography) coupled with HRMS (high resolution mass spectrometry) appears to be the best technique for direct analysis of these analytes, because neither derivatization nor complex extraction procedure for polar compounds in samples is requested prior the analysis. Sample preparation was limited to washing wipes with appropriate solvents. Chromatographic separation was achieved on C18 reversed phase columns. The HPLC-HRMS/MS method was validated in order to obtain robustness, sensitivity and selectivity. LLOQ (lower limit of quantitation) values provided a sensitivity good enough to evidence the presence of the drugs in a very low concentration range (<1 pg/cm(2) ). The method was applied for a study of real wipe tests coming from many areas from a hospital showing some positive samples. The low quantitation limits and the high specificity due to the high resolution approach of the developed method allowed an accurate description of the working environment that can be used to define procedural rules to limit working place contamination to a minimum. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26041114

  2. Interaction of human organic anion transporter 2 (OAT2) and sodium taurocholate cotransporting polypeptide (NTCP) with antineoplastic drugs.

    PubMed

    Marada, Venkata V V R; Flörl, Saskia; Kühne, Annett; Müller, Judith; Burckhardt, Gerhard; Hagos, Yohannes

    2015-01-01

    The ability of an antineoplastic drug to exert its cytostatic effect depends largely on the balance between its uptake into and extrusion from the cancer cells. ATP driven efflux transporter proteins drive the export of antineoplastic drugs and play a pivotal role in the development of chemoresistance. As regards uptake transporters, comparably less is known on their impact in drug action. In the current study, we characterized the interactions of two uptake transporter proteins, expressed mainly in the liver; the organic anion transporter 2 (OAT2, encoded by the SLC22A7 gene) and the sodium taurocholate cotransporting polypeptide (NTCP, encoded by the SLC10A1 gene), stably transfected in human embryonic kidney cells, with some antineoplastic agents that are routinely being used in cancer chemotherapy. Whereas NTCP did not show any strong interactions with the cytostatics tested, we observed a very strong inhibition of OAT2 mediated [(3)H] cGMP uptake in the presence of bendamustine, irinotecan and paclitaxel. The Ki values of OAT2 for bendamustine, irinotecan and paclitaxel were determined to be 43.3±4.33μM, 26.4±2.34μM and 10.4±0.45μM, respectively. Incubation of bendamustine with OAT2 expressing cells increased the caspase-3 activity, and this increase was inhibited by simultaneous incubation with bendamustine and probenecid, a well-known inhibitor of OATs, suggesting that bendamustine is a substrate of OAT2. A higher accumulation of irinotecan was observed in OAT2 expressing cells compared to control pcDNA cells by HPLC analysis of cell lysates. The accumulation was diminished in the presence of cGMP, the substrate we used to functionally characterize OAT2, suggesting specificity of this uptake and the fact that OAT2 mediates uptake of irinotecan. PMID:25481222

  3. Removal of antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil and a vasodilator drug pentoxifylline from wastewaters by ozonation.

    PubMed

    Lin, Angela Yu-Chen; Hsueh, Julia Han-Fang; Hong, P K Andy

    2015-01-01

    We investigated the ozonation of the antineoplastic drugs cyclophosphamide (CP), ifosfamide (IF), and 5-fluorouracil (5-FU) and of the vasodilator pentoxifylline (PEN) in distilled water, in pharmaceutical wastewater, and in hospital effluent at pH 5-11. Under an alkaline pH of 11, all of the target compounds rapidly degraded through the attack of hydroxyl radicals, which resulted in their complete removal within 5 min at an ozone supply rate of 3 g O3/h. Under acidic pH conditions, such as pH 5.6, CP and IF exhibited slower removal rates; however, compounds with unsaturated C-C bonds, such as 5-FU and PEN, were still removed at rapid rates under acidic conditions. Although the parent compounds were removed within minutes, the resulting ozonation byproducts were resistant to further ozonation and possessed increased Microtox acute toxicity. In distilled water, the resulting ozonation products exhibited minimal mineralization but high acute toxicity, whereas in naturally buffered pharmaceutical and hospital effluents, the byproducts were more amenable to removal and detoxification. PMID:25087496

  4. A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins

    PubMed Central

    Nusrat, Saima; Siddiqi, Mohammad Khursheed; Zaman, Masihuz; Zaidi, Nida; Ajmal, Mohammad Rehan; Alam, Parvez; Qadeer, Atiyatul; Abdelhameed, Ali Saber

    2016-01-01

    Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (Kb) ~105 M-1 and free energy (ΔG) ~ -7.5 kcal.mol-1. It also binds at site II of BSA but with lesser binding affinity (Kb) ~105 M-1 and ΔG ~ -6.5 kcal.mol-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra. PMID:27391941

  5. A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins.

    PubMed

    Nusrat, Saima; Siddiqi, Mohammad Khursheed; Zaman, Masihuz; Zaidi, Nida; Ajmal, Mohammad Rehan; Alam, Parvez; Qadeer, Atiyatul; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2016-01-01

    Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (Kb) ~105 M-1 and free energy (ΔG) ~ -7.5 kcal.mol-1. It also binds at site II of BSA but with lesser binding affinity (Kb) ~105 M-1 and ΔG ~ -6.5 kcal.mol-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra. PMID:27391941

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

    PubMed Central

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

    2008-01-01

    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 copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N′,N′-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble. PMID:18288243

  7. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    PubMed

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. PMID:26875816

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

    PubMed Central

    2011-01-01

    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, occupational exposure will

  9. Application and assessment of a regular environmental monitoring of the antineoplastic drug contamination level in pharmacies - the MEWIP project.

    PubMed

    Kiffmeyer, Thekla K; Tuerk, Jochen; Hahn, Moritz; Stuetzer, Hartmut; Hadtstein, Claudia; Heinemann, André; Eickmann, Udo

    2013-05-01

    A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived. PMID:23125441

  10. A multicenter study of biological effects assessment of pharmacy workers occupationally exposed to antineoplastic drugs in Pharmacy Intravenous Admixture Services.

    PubMed

    Zhang, Jingjing; Bao, Jianan; Wang, Renying; Geng, Zhou; Chen, Yao; Liu, Xinchun; Xie, Yongzhong; Jiang, Ling; Deng, Yufei; Liu, Gaolin; Xu, Rong; Miao, Liyan

    2016-09-01

    This multi-centered study was designed to evaluate the biological effects of exposure to antineoplastic drugs (ADs) at PIVAS (Pharmacy Intravenous Admixture Service) across ten Chinese hospitals. 8-hydroxy-2-deoxyguanosine (8-OHdG) was used as a biomarker of DNA oxidative damage and lymphocyte apoptosis assays using peripheral lymphocyte cells were used to detect primary DNA damage. The mutagenicity activity was estimated with the Ames fluctuation test. 158 exposed and 143 unexposed workers participated in this study. The urinary 8-OHdG/Cr concentrations of the exposed group was 22.05±17.89ng/mg Cr, which was significantly higher than controls of 17.36±13.50ng/mg Cr (P<0.05). The rate of early lymphocyte apoptosis was slightly increased in exposed group than that of the control group (P=0.087). The mutagenic activity was significantly higher in the exposed group relative to the control group (P<0.05). Moreover, while no statistically significant difference was observed, higher concentrations of 8-OHdG/Cr in urine and an early lymphocyte apoptosis rate were found in exposed group II as compared to exposed group I. In addition, a significant correlation between early lymphocyte apoptosis and exposure time to ADs was also observed (P<0.05). In conclusion, our study identified elevated biomarkers in PIVAS workers exposed to ADs. However whether these findings could lead to increased incidence of genotoxic responses remains to be further investigated. PMID:27179702

  11. Removal of polycyclic synthetic musks and antineoplastic drugs in ozonated wastewater: Quantitation based on the data of differential spectroscopy.

    PubMed

    Li, Wei; Nanaboina, Venkateswarlu; Chen, Fang; Korshin, Gregory V

    2016-03-01

    This study examined the degradation behavior of polycyclic musks (PMs) and antineoplastic drugs (ADs) and the absorbance spectra of effluent organic matter (EfOM) in municipal wastewater by ozone. Specific ozone doses used in the experiments ranged from 0 to 1mg O3/mg dissolved organic matter (DOC). The examined PMs included galaxolide, tonalide, celestolide, traseolide and phantolide. ADs included busulfan, chlorambucil, cyclophosphamide, dacarbazine, flutamide, ifosfamide, tamoxifen and methotrexate. Strong monotonic albeit nonlinear correlations were found to exist between relative changes of EfOM absorbance at 254 nm (i.e. ΔA254/A(0)254) and the degradation of the selected PMs and ADs. This result was interpreted based on the concept of the simultaneous oxidation of EfOM and, on the other hand, PMs and ADs. This interpretation showed that PMs were degraded primarily via OH radical attack, with tonalide and phantolide being less reactive compared with the other PMs. ADs such as cyclophosphamide, ifosfamide and busulfan were also determined to undergo oxidation by OH radicals. Comparison of the behavior of the radical probe para-chlorobenzoic acid and the examined ADs and PMs allowed evaluating corresponding reaction rate constants for reactions between these species and OH radicals. PMID:26555374

  12. Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

    PubMed Central

    Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

    2014-01-01

    The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses. PMID:24719678

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

    MedlinePlus

    ... drugs (for example, pharmacy and nursing personnel, physicians, operating room personnel, environmental services workers, workers in research ... personnel, pharmacists and pharmacy technicians, nursing personnel, physicians, operating room personnel, environmental services personnel, and workers in ...

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

    PubMed Central

    Tsunaka, Misae; Arai, Reina; Ohashi, Ayaka; Koyama, Takatoshi

    2016-01-01

    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. PMID:27504186

  15. The reversal of antineoplastic drug resistance in cancer cells by β-elemene.

    PubMed

    Zhang, Guan-Nan; Ashby, Charles R; Zhang, Yun-Kai; Chen, Zhe-Sheng; Guo, Huiqin

    2015-11-01

    Multidrug resistance (MDR), defined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, significantly limits the efficacy of antitumor drugs. A major mechanism that mediates MDR in cancer is the overexpression of adenosine triphosphate (ATP)-binding cassette transporters. These transporters bind to their respective substrates and catalyze their efflux from cancer cells, thereby lowering the intracellular concentrations of the substrates and thus attenuating or even abolishing their efficacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen-activated protein kinase pathway. In this review, we discuss the mechanisms by which β-elemene, a compound extracted from Rhizoma zedoariae that has clinical antitumor efficacy, overcomes drug resistance in cancer. PMID:26370907

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

    SciTech Connect

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

    1983-05-01

    Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with /sup 51/Cr were exposed to the following antitumor drugs alone or with O/sub 3/: carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K/sub 3/ (Vit K). Release of /sup 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/sub 3/-induced loss of /sup 51/Cr. Co-exposure of F-cells to drugs and O/sub 3/ resulted in a marked potentiation of O/sub 3/-induced injury with Vit K, and an inhibition with Dox.

  17. [A SOS induction test screening study for vegetables inhibiting mutagenicity caused by antineoplastic drugs].

    PubMed

    Zhao, Z Z; Huang, M T

    1992-03-01

    Using mutational and anti-mutational synchronous in SOS inductest (+/- S9), We found that 7 out of 11 kinds of commonly eaten vegetables had the ability to inhibit mutagenicity caused by chemical drugs such as Mitomycin C, Bleomycinia, Fluorouracil, Cis-Diaminodichloroplatinum, Arabinosylcytosin and mustargen, They were garlic, green Chinese onion, onion, garlic bulb, tomato, cucumber and water radish. The other 4 lacking this ability were rape, chinese toon, ginger and asparagus lettuce stalk. We believe that our results can be helpful in the preparation. of cancer patients' diet, who are receiving chemotherapy and in the prevention of cancer. PMID:1451586

  18. Prediction and assessment of ecogenotoxicity of antineoplastic drugs in binary mixtures.

    PubMed

    Kundi, Michael; Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Isidori, Marina

    2016-08-01

    The combined genotoxic effects of four anticancer drugs (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET], and imatinib mesylate [IM]) were studied testing their binary mixtures in two crustaceans that are part of the freshwater food chain, namely Daphnia magna and Ceriodaphnia dubia. Genotoxicity was assessed using the in vivo comet assay. Assessment was based on two distinct effect sizes determined from dose-response experiments. Doses for single and combined exposures expected to result in these effect sizes were computed based on Bliss independence as reference model. Statistical comparison by analysis of variance of single and combined toxicities allowed accepting or rejecting the independency hypothesis. The results obtained for D. magna showed independent action for all mixtures except for IM+5-FU that showed an antagonistic interaction. In C. dubia, most mixtures had antagonist interactions except IM+5-FU and IM+CDDP that showed Bliss independence. Despite the antagonistic interactions, our results demonstrated that combinations of anticancer drugs could be of environmental concern because effects occur at very low concentrations that are in the range of concentrations encountered in aquatic systems. PMID:26139396

  19. Peptidyl anthraquinones as potential antineoplastic drugs: synthesis, DNA binding, redox cycling, and biological activity.

    PubMed

    Gatto, B; Zagotto, G; Sissi, C; Cera, C; Uriarte, E; Palù, G; Capranico, G; Palumbo, M

    1996-08-01

    A series of new compounds containing a 9,10-anthracenedione moiety and one or two peptide chains at position 1 and/or 4 have been synthesized. The amino acid residues introduced are glycine (Gly), lysine (Lys), and tryptophan (Trp), the latter two in both the L- and D-configurations. The peptidyl anthraquinones maintain the ability of intercalating efficiently into DNA, even though the orientation within the base-pair pocket may change somewhat with reference to the parent drugs mitoxantrone (MX) and ametantrone (AM). The interaction constants of the mono-, di-, and triglycyl derivatives are well comparable to those found for AM but 5-10 times lower than the value reported for MX. On the other hand, the glycyl-lysyl compounds bind DNA to the same extent as (L-isomer) or even better than (D-isomer) MX. As for the parent drugs without peptidyl chains, the new compounds prefer alternating CG binding sites, although to different extents. The bis-Gly-Lys derivatives are the least sensitive to base composition, which may be due to extensive aspecific charged interactions with the polynucleotide backbone. As far as redox properties are concerned, all peptidyl anthraquinones show a reduction potential very close to that of AM and 60-80 mV less negative than that of MX; hence, they can produce free-radical-damaging species to an extent similar to the parent drugs. The biological activity has been tested in human tumor and murine leukemia cell lines. Most of the test anthraquinones exhibit cytotoxic properties close to those of AM and considerably lower than those of MX. Stimulation of topoisomerase-mediated DNA cleavage is moderately present in representatives of the glycylanthraquinone family, whereas inhibition of the background cleavage occurs when Lys is present in the peptide chain. For most of the test anthraquinones, the toxicity data are in line with the DNA affinity scale and the topoisomerase II stimulation activity. However, in the lysyl derivatives, for which

  20. Nuclear Targeting with an Auger Electron Emitter Potentiates the Action of a Widely Used Antineoplastic Drug.

    PubMed

    Imstepf, Sebastian; Pierroz, Vanessa; Raposinho, Paula; Bauwens, Matthias; Felber, Michael; Fox, Thomas; Shapiro, Adam B; Freudenberg, Robert; Fernandes, Célia; Gama, Sofia; Gasser, Gilles; Motthagy, Felix; Santos, Isabel R; Alberto, Roger

    2015-12-16

    We present the combination of the clinically well-proven chemotherapeutic agent, Doxorubicin, and (99m)Tc, an Auger and internal conversion electron emitter, into a dual-action agent for therapy. Chemical conjugation of Doxorubicin to (99m)Tc afforded a construct which autonomously ferries a radioactive payload into the cell nucleus. At this site, damage is exerted by dose deposition from Auger radiation. The (99m)Tc-conjugate exhibited a dose-dependent inhibition of survival in a selected panel of cancer cells and an in vivo study in healthy mice evidenced a biodistribution which is comparable to that of the parent drug. The homologous Rhenium conjugate was found to effectively bind to DNA, inhibited human Topoisomerase II, and exhibited cytotoxicity in vitro. The collective in vitro and in vivo data demonstrate that the presented metallo-conjugates closely mimic native Doxorubicin. PMID:26473388

  1. Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens.

    PubMed

    Kirstein, Mark N; Brundage, Richard C; Elmquist, William F; Remmel, Rory P; Marker, Paul H; Guire, Dan E; Yee, Douglas

    2006-04-01

    A dynamic 3-dimensional tissue culture system has been developed that will allow for control of gemcitabine exposure to mimic concentration-time profiles measured from biologic samples. Gemcitabine was infused into a central reservoir. Media is mixed and delivered through hollow fiber capillaries, where it diffuses into the extracapillary space containing anchorage-dependent MDA-231 cells. To test for control of gemcitabine concentration-time profiles, drug was first infused through bioreactors without cells, and gemcitabine concentrations were measured with HPLC. Concentrations could be controlled to simulate 30-min and 2.5 h infusions, and were similar in both the lumen and extracapillary space. MDA-231 cells were then seeded into control (n = 4) and gemcitabine treatment (n = 4) groups, and maintained in culture for 2 weeks. Gemcitabine (5.3 mg) was infused over 30 min to the treatment group, and blank media to the control group. Accuracy of measured gemcitabine maximum concentration (Cmax) was 83.4%, and area under the curve (AUC), 106.2%, relative to pre-experimental theoretical values. With cells present, gemcitabine AUC in the extracapillary space was 32% of the value in the lumen. For the control group, 21.2 million cells (94.3% viable) were recovered, and for the gemcitabine-treated group, 16.8 million cells (87.1 % viable). Flow cytometry showed that 13.3 % of cells in the control group were in S-phase and 34.3 % in the gemcitabine-treated group were in S-phase (p = 0.003). In conclusion, gemcitabine concentration-time profiles could be accurately controlled through dosage, infusion rate, and pump flow rate, and cells could be recovered afterward to evaluate drug treatment. PMID:16502018

  2. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    PubMed Central

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

  3. Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines.

    PubMed

    Arechavaleta-Velasco, Fabian; Zeferino-Toquero, Moises; Estrada-Moscoso, Isaias; Imani-Razavi, Fazlollah Shahram; Olivares, Aleida; Perez-Juarez, Carlos Eduardo; Diaz-Cueto, Laura

    2016-02-01

    Survival rate in ovarian cancer depends on the stage of the disease. RSK4, which has been considered as a tumor suppressor factor, controls cells invasion due to its antiinvasive and antimetastatic properties. Modulation of RSK4 expression could be an important event to increase the survival rate in ovarian cancer patients. Thus, the goal of the present study was to establish the differences in RSK4 expression among normal, benign and malignant ovarian tissues and to determine whether antineoplastic drugs regulate its expression in SKOV3 and TOV-112D cells. RSK4 levels in 30 malignant ovarian tumors, 64 benign tumors and 36 normal ovary tissues were determined by reverse transcription polymerase chain reaction and Western blot. Modulation of RSK4 expression by two antineoplastic drugs (cisplatin and vorinostat) was also studied in the SKOV3 and TOV-112D ovarian cancer cell lines using the same techniques. RSK4 mRNA and protein levels were decreased in malignant ovarian tumors as compared to benign tumors and normal tissue. These low-RSK4 levels were significantly associated with advanced stages of ovarian cancer. RSK4 expression was increased after incubation of SKOV3 and TOV-112D cell lines with cisplatin and vorinostat for 24 h. The combination of these antineoplastic drugs did not produce a synergistic or additive effect. These results suggest that RSK4 is expressed at low levels in malignant ovarian tumors, which correlates with advanced stages of the disease. Additionally, RSK4 expression is regulated by cisplatin and vorinostat in two ovarian cancer cell lines. PMID:26732474

  4. Quantitative analysis of the anti-proliferative activity of combinations of selected iron-chelating agents and clinically used anti-neoplastic drugs.

    PubMed

    Potuckova, Eliska; Jansova, Hana; Machacek, Miloslav; Vavrova, Anna; Haskova, Pavlina; Tichotova, Lucie; Richardson, Vera; Kalinowski, Danuta S; Richardson, Des R; Simunek, Tomas

    2014-01-01

    Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, we explored the combined anti-proliferative potential of four iron chelators, namely: desferrioxamine (DFO), salicylaldehyde isonicotinoyl hydrazone (SIH), (E)-N'-[1-(2-hydroxy-5-nitrophenyl)ethyliden] isonicotinoyl hydrazone (NHAPI), and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), plus six selected anti-neoplastic drugs. These six agents are used for breast cancer treatment and include: paclitaxel, 5-fluorouracil, doxorubicin, methotrexate, tamoxifen and 4-hydroperoxycyclophosphamide (an active metabolite of cyclophosphamide). Our quantitative chelator-drug analyses were designed according to the Chou-Talalay method for drug combination assessment. All combinations of these agents yielded concentration-dependent, anti-proliferative effects. The hydrophilic siderophore, DFO, imposed antagonism when used in combination with all six anti-tumor agents and this antagonistic effect increased with increasing dose. Conversely, synergistic interactions were observed with combinations of the lipophilic chelators, NHAPI or Dp44mT, with doxorubicin and also the combinations of SIH, NHAPI or Dp44mT with tamoxifen. The combination of Dp44mT with anti-neoplastic agents was further enhanced following formation of its redox-active iron and especially copper complexes. The most potent combinations of Dp44mT and NHAPI with tamoxifen were confirmed as synergistic using another estrogen receptor-expressing breast cancer cell line, T47D, but not estrogen receptor-negative MDA

  5. Minimizing Occupational Exposure to Antineoplastic Agents.

    PubMed

    Polovich, Martha

    2016-01-01

    The inherent toxicity of antineoplastic drugs used for the treatment of cancer makes them harmful to healthy cells as well as to cancer cells. Nurses who prepare and/or administer the agents potentially are exposed to the drugs and their negative effects. Knowledge about these drugs and the precautions aimed at reducing exposure are essential aspects of infusion nursing practice. This article briefly reviews the mechanisms of action of common antineoplastic drugs, the adverse outcomes associated with exposure, the potential for occupational exposure from preparation and administration, and recommended strategies for minimizing occupational exposure. PMID:27598070

  6. Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study

    PubMed Central

    Pinturaud, Marine; Soichot, Marion; Richeval, Camille; Humbert, Luc; Lebecque, Michèle; Sidikou, Ousseini; Barthelemy, Christine; Bonnabry, Pascal; Allorge, Delphine; Décaudin, Bertrand; Odou, Pascal

    2016-01-01

    Background The objective of this randomized, prospective and controlled study was to investigate the ability of a closed-system transfer device (CSTD; BD-Phaseal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices. Methods and Findings The 6-month study started with the opening of a new compounding unit. Two isolators were set up with 2 workstations each, one to compound with standard devices (needles and spikes) and the other using the Phaseal system. Drugs were alternatively compounded in each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxorubicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Significance was defined for p<0.05. Overall contamination was lower in the “Phaseal” isolator than in the “Standard” isolator (12.24% vs. 26.39%; p < 0.0001) although it differed according to drug. Indeed, the contamination rates of gemcitabine were 49.3 and 43.4% (NS) for the Standard and Phaseal isolators, respectively, whereas for ganciclovir, they were 54.2 and 2.8% (p<0.0001). Gemcitabine amounts were 220.6 and 283.6 ng for the Standard and Phaseal isolators (NS), and ganciclovir amounts were 179.9 and 2.4 ng (p<0.0001). Conclusion This study confirms that using a CSTD may significantly decrease the chemical contamination of barrier isolators compared to standard devices for some drugs, although it does not eliminate contamination totally. PMID:27391697

  7. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  8. Hydrogels for combination delivery of antineoplastic agents.

    PubMed

    Bouhadir, K H; Alsberg, E; Mooney, D J

    2001-10-01

    The systemic delivery of anticancer agents has been widely investigated during the past decade but localized delivery may offer a safer and more effective delivery approach. We have designed and synthesized a novel hydrogel to locally deliver antineoplastic agents, and demonstrate the different types of release that can be achieved from these hydrogels using three model drugs: methotrexate, doxorubicin, and mitoxantrone. Alginate was chemically modified into low molecular weight oligomers and cross-linked with a biodegradable spacer (adipic dihydrazide) to form biodegradable hydrogels. The model antineoplastic agents were loaded into the hydrogel via three different mechanisms. Methotrexate was incorporated within the pores of the hydrogel and was released by diffusion into the surrounding medium. Doxorubicin was covalently attached to the polymer backbone via a hydrolytically labile linker and was released following the chemical hydrolysis of the linker. Mitoxantrone was ionically complexed to the polymer and was released after the dissociation of this complex. These three release mechanisms could potentially be used to deliver a wide selection of antineoplastic agents, based on their chemical structure. This novel delivery system allows for the release of single or combinations of antineoplastic agents, and may find utility in localized antineoplastic agent delivery. PMID:11519782

  9. Potentiation of cytotoxicity by 3-aminobenzamide in DNA repair-deficient human tumor cell lines following exposure to methylating agents or anti-neoplastic drugs.

    PubMed

    Babich, M A; Day, R S

    1988-04-01

    We studied the potentiation by 3-aminobenzamide (3AB) of killing of nine human cell lines exposed to alkylating agents. Cell lines included normal, transformed and DNA repair-proficient and -deficient phenotypes. 3AB potentiated cell killing by the methylating agents methylmethanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in all lines tested. The degree of potentiation ranged from 1.7- to 3.8-fold, based on the LD99. The average potentiation observed with MMS (2.7-fold) was greater than with MNNG (2.2-fold). On average the potentiation of MMS and MNNG killing of repair-deficient Mer- lines (2.4-fold) was similar to that of repair-proficient Mer+ lines. The degree of 3AB potentiation of MNNG killing (2.0-fold) was similar in Mer+ Rem- lines and in Mer+ Rem+ lines. Mer+ Rem+, Mer+ Rem-, Mer- Rem+, and Mer- Rem- strains all appeared proficient in a 3AB-sensitive DNA repair pathway. Within experimental error, 20 mM 3AB did not inhibit the removal of the MNNG-induced methylpurines 7-methylguanine, O6-methylguanine and 3-methyladenine from the DNA of repair-proficient Mer+ Rem+ HT29 cells, consistent with evidence that 3AB inhibits the ligation step of excision repair. 3AB potentiated cell killing by the bifunctional alkylating agents 1-(2-chlorethyl)-1-nitrosourea or busulfan, two anti-neoplastic drugs, by only 0.9- to 1.5-fold. These drugs therefore produce DNA damage which is not efficiently repaired by the pathways that repair methylated bases. PMID:3356063

  10. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

    PubMed

    Roco, Angela; Quiñones, Luis; Agúndez, José A G; García-Martín, Elena; Squicciarini, Valentina; Miranda, Carla; Garay, Joselyn; Farfán, Nancy; Saavedra, Iván; Cáceres, Dante; Ibarra, Carol; Varela, Nelson

    2012-01-01

    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be

  11. Frequencies of 23 Functionally Significant Variant Alleles Related with Metabolism of Antineoplastic Drugs in the Chilean Population: Comparison with Caucasian and Asian Populations

    PubMed Central

    Roco, Ángela; Quiñones, Luis; Agúndez, José A. G.; García-Martín, Elena; Squicciarini, Valentina; Miranda, Carla; Garay, Joselyn; Farfán, Nancy; Saavedra, Iván; Cáceres, Dante; Ibarra, Carol; Varela, Nelson

    2012-01-01

    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be

  12. Antineoplastic activity of monocrotaline against hepatocellular carcinoma.

    PubMed

    Kusuma, Sandeep Solmon; Tanneeru, Karunakar; Didla, Swroopa; Devendra, Bellary Nagaraju; Kiranmayi, Patnala

    2014-01-01

    Plants are fantastic sources for present day life saving drugs. Monocrotaline a natural ligand exhibits dose-dependent cytotoxicity with potent antineoplastic activity. This study was intended to disclose the therapeutic potential of monocrotaline against hepatocellular carcinoma. The in silico predictions have highlighted the antineoplastic potential, druglikeness and biodegradability of monocrotaline. The in silico docking study has provided an insight and evidence for the antineoplastic activity of monocrotaline against p53, HGF and TREM1 proteins which play a threatening role in causing hepatocellular carcinoma. The mode of action of monocrotaline was determined experimentally by in vitro techniques such as XTT assay, NRU assay and whole cell brine shrimp assay have further supported our in silico studies. The in vitro cytotoxicity of monocrotaline was proved at IC50 24.966 µg/mL and genotoxicity at 2 X IC50 against HepG2 cells. Further, the credible druglike properties with non-mutagenicity, non-toxic on mammalian fibroblast and the potential antineoplastic activity through in vitro experimental validations established monocrotaline as a novel scaffold for liver cancer with superior efficacy and lesser side effects. PMID:25028149

  13. Antineoplastic compounds in the environment-substances of special concern.

    PubMed

    Kümmerer, Klaus; Haiß, Annette; Schuster, Armin; Hein, Arne; Ebert, Ina

    2016-08-01

    Antineoplastic drugs are important in the treatment of cancer. Some interact directly with the deoxyribonucleic acid (DNA) and are of utmost importance in terms of risk. As highly active compounds, antineoplastics and their metabolites are largely excreted into wastewater and are found in the aquatic environment up to the lower μg/L range. Their predicted environmental concentrations are often below the action limit set in the European Medicines Agency (EMA) guideline. An in-depth risk assessment regarding their presence and effects in the aquatic environment is often not performed, and there is a lack of knowledge. This study considered whether there is an underestimation of possible risks associated with the presence of antineoplastic drugs with regard to trigger value stated in the EMA and FDA guidelines. In a balance, we identified a total of 102 active pharmaceutical ingredients of the ATC-group L01 (antineoplastic agents), which are environmentally relevant. In Germany, 20.7 t of antineoplastic agents was consumed in 2012. The share of drugs with DNA-damaging properties increased within the last 6 years from 24 up to 67 %. Solely, capecitabine and 5-fluorouracil amount together 8 t-which corresponds to 39 % of the total antineoplastic consumption. Around 80 % of the total mass consumed could be attributed to prescriptions issued by office-based practitioners and is mostly excreted at home. Based on the different mode of actions, a case-by-case evaluation of the risk connected to their presence in the environment is recommended. DNA-damaging drugs should be assessed independently as no action limit can be assumed. PMID:25475615

  14. Analytical approaches for traditional chinese medicines exhibiting antineoplastic activity.

    PubMed

    Tsai, T H

    2001-11-25

    Traditional Chinese medicines have attracted great interest in recent researchers as alternative antineoplastic therapies. This review focuses on analytical approaches to various aspects of the antineoplastic ingredients of traditional Chinese medicines. Emphasis will be put on the processes of biological sample extraction, separation, clean-up steps and the detection. The problems of the extraction solvent selection and different types of column chromatography are also discussed. The instruments considered are gas chromatography, capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) connected with various detectors (ultraviolet, fluorescence, electrochemistry, mass, etc.). In addition, determinations of antineoplastic herbal ingredients, including camptothecin, taxol (paclitaxel), vinblastine. vincristine, podophyllotoxin, colchicine, and their related compounds, such as irinotecan, SN-38, topotecan, 9-aminocamptothecin, docetaxel (taxotere) and etoposide, are briefly summarized. These drugs are structurally based on the herbal ingredients, and some of them are in trials for clinical use. Evaluation of potential antineoplastic herbal ingredients, such as harringtonine, berberine, emodin, genistein, berbamine, daphnoretin, and irisquinone, are currently investigated in laboratories. Other folk medicines are excluded from this paper because their antineoplastic ingredients are unknown. PMID:11817032

  15. MPT0G066, a novel anti-mitotic drug, induces JNK-independent mitotic arrest, JNK-mediated apoptosis, and potentiates antineoplastic effect of cisplatin in ovarian cancer

    PubMed Central

    Huang, Han-Li; Chao, Min-Wu; Li, Ya-Chi; Chang, Li-Hsun; Chen, Chun-Han; Chen, Mei-Chuan; Cheng, Chun-Chun; Liou, Jing-Ping; Teng, Che-Ming; Pan, Shiow-Lin

    2016-01-01

    Developing new anticancer agents against ovarian cancer is an urgent medical need. MPT0G066, a novel synthetic arylsulfonamide compound, was shown to inhibit cell growth and decrease viability in human ovarian cancer cells. MPT0G066 induced arrest of the cell cycle at the multipolyploidy (MP) phase in SKOV3 and at the G2/M phase in A2780 cells, while increasing the proportion of cells in the subG1. Additionally, MPT0G066 induced c-Jun-NH2 terminal kinase (JNK) activation, influenced cell cycle regulatory and Bcl-2 family proteins, which triggered intrinsic apoptotic pathways through cleavage of caspase-3, -7, -9, and poly-(ADP-ribose) polymerase (PARP). Flow cytometry analysis of p-glycoprotein (p-gp) function showed that MPT0G066 was not a substrate of p-gp. Additionally, it was shown that MPT0G066 could decrease cell viability in multiple-drug-resistant human ovarian cancer cells. Furthermore, the combination of MPT0G066 and cisplatin presented a synergistic cytotoxic effect against ovarian cancer cell lines in vitro. MPT0G066 also significantly suppressed the growth of ovarian carcinoma and potentiated the antineoplastic effects of cisplatin in vivo. In conclusion, these findings indicate that MPT0G066 can be a potential anticancer agent against ovarian cancer that worthy of further development. PMID:27526962

  16. MPT0G066, a novel anti-mitotic drug, induces JNK-independent mitotic arrest, JNK-mediated apoptosis, and potentiates antineoplastic effect of cisplatin in ovarian cancer.

    PubMed

    Huang, Han-Li; Chao, Min-Wu; Li, Ya-Chi; Chang, Li-Hsun; Chen, Chun-Han; Chen, Mei-Chuan; Cheng, Chun-Chun; Liou, Jing-Ping; Teng, Che-Ming; Pan, Shiow-Lin

    2016-01-01

    Developing new anticancer agents against ovarian cancer is an urgent medical need. MPT0G066, a novel synthetic arylsulfonamide compound, was shown to inhibit cell growth and decrease viability in human ovarian cancer cells. MPT0G066 induced arrest of the cell cycle at the multipolyploidy (MP) phase in SKOV3 and at the G2/M phase in A2780 cells, while increasing the proportion of cells in the subG1. Additionally, MPT0G066 induced c-Jun-NH2 terminal kinase (JNK) activation, influenced cell cycle regulatory and Bcl-2 family proteins, which triggered intrinsic apoptotic pathways through cleavage of caspase-3, -7, -9, and poly-(ADP-ribose) polymerase (PARP). Flow cytometry analysis of p-glycoprotein (p-gp) function showed that MPT0G066 was not a substrate of p-gp. Additionally, it was shown that MPT0G066 could decrease cell viability in multiple-drug-resistant human ovarian cancer cells. Furthermore, the combination of MPT0G066 and cisplatin presented a synergistic cytotoxic effect against ovarian cancer cell lines in vitro. MPT0G066 also significantly suppressed the growth of ovarian carcinoma and potentiated the antineoplastic effects of cisplatin in vivo. In conclusion, these findings indicate that MPT0G066 can be a potential anticancer agent against ovarian cancer that worthy of further development. PMID:27526962

  17. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  18. 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.

    PubMed

    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. PMID:27154677

  19. Transport of physiological nucleosides and anti-viral and anti-neoplastic nucleoside drugs by recombinant Escherichia coli nucleoside-H(+) cotransporter (NupC) produced in Xenopus laevis oocytes.

    PubMed

    Loewen, Shaun K; Yao, Sylvia Y M; Slugoski, Melissa D; Mohabir, Nadira N; Turner, Raymond J; Mackey, John R; Weiner, Joel H; Gallagher, Maurice P; Henderson, Peter J F; Baldwin, Stephen A; Cass, Carol E; Young, James D

    2004-01-01

    The recently identified human and rodent plasma membrane proteins CNT1, CNT2 and CNT3 belong to a gene family (CNT) that also includes the bacterial nucleoside transport protein NupC. Heterologous expression in Xenopus oocytes has established that CNT1-3 correspond functionally to the three major concentrative nucleoside transport processes found in human and other mammalian cells (systems cit, cif and cib, respectively) and mediate Na(+) - linked uptake of both physiological nucleosides and anti-viral and anti-neoplastic nucleoside drugs. Here, one describes a complementary Xenopus oocyte transport study of Escherichia coli NupC using the plasmid vector pGEM-HE in which the coding region of NupC was flanked by 5'- and 3'-untranslated sequences from a Xenopus beta-globin gene. Recombinant NupC resembled human (h) and rat (r) CNT1 in nucleoside selectivity, including an ability to transport adenosine and the chemotherapeutic drugs 3'-azido-3'-deoxythymidine (AZT), 2',3'- dideoxycytidine (ddC) and 2'-deoxy-2',2'-difluorocytidine (gemcitabine), but also interacted with inosine and 2',3'- dideoxyinosine (ddl). Apparent affinities were higher than for hCNT1, with apparent K(m) values of 1.5-6.3 microM for adenosine, uridine and gemcitabine, and 112 and 130 microM, respectively, for AZT and ddC. Unlike the relatively low translocation capacity of hCNT1 and rCNT1 for adenosine, NupC exhibited broadly similar apparent V(max) values for adenosine, uridine and nucleoside drugs. NupC did not require Na(+) for activity and was H(+) - dependent. The kinetics of uridine transport measured as a function of external pH were consistent with an ordered transport model in which H(+) binds to the transporter first followed by the nucleoside. These experiments establish the NupC-pGEM-HE/oocyte system as a useful tool for characterization of NupC-mediated transport of physiological nucleosides and clinically relevant nucleoside therapeutic drugs. PMID:14668133

  20. Coping with arsenic-based pesticides on Dine (Navajo) textiles

    NASA Astrophysics Data System (ADS)

    Anderson, Jae R.

    Arsenic-based pesticide residues have been detected on Arizona State Museum's (ASM) Dine (Navajo) textile collection using a handheld portable X-ray (pXRF) spectrometer. The removal of this toxic pesticide from historic textiles in museums collections is necessary to reduce potential health risks to Native American communities, museum professionals, and visitors. The research objective was divided into three interconnected stages: (1) empirically calibrate the pXRF instrument for arsenic contaminated cotton and wool textiles; (2) engineer an aqueous washing treatment exploring the effects of time, temperature, agitation, and pH conditions to efficiently remove arsenic from wool textiles while minimizing damage to the structure and properties of the textile; (3) demonstrate the devised aqueous washing treatment method on three historic Navajo textiles known to have arsenic-based pesticide residues. The preliminary results removed 96% of arsenic from a high arsenic concentration (~1000 ppm) textile opposed to minimal change for low arsenic concentration textiles (<100 ppm).

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

    PubMed Central

    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

  2. Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs.

    PubMed

    Gagic, Zarko; Ivkovic, Branka; Srdic-Rajic, Tatjana; Vucicevic, Jelica; Nikolic, Katarina; Agbaba, Danica

    2016-06-10

    Tocopherols and tocotrienols belong to the family of vitamin E (VE) with the well-known antioxidant properties. For certain α-tocopherol and γ-tocotrienol derivatives used as the lead compounds in this study, antitumor activities against various cancer cell types have been reported. In the course of the last decade, structural analogs of VE (esters, ethers and amides) with an enhanced antiproliferative and proapoptotic activity against various cancer cells were synthesized. Within the framework of this study, seven amino acid esters of α-tocopherol (4a-d) and γ-tocotrienol (6a-c) were prepared using the EDC/DMAP reaction conditions and their ability to inhibit proliferation of the MCF-7 and MDA-MB-231 breast cancer cells and the A549 lung cancer cells was evaluated. Compound 6a showed an activity against all three cell lines (IC50: 20.6μM, 28.6μM and 19μM for the MCF-7, MDA-MB-231 and A549 cells, respectively), while compound 4a inhibited proliferation of the MCF-7 (IC50=8.6μM) and A549 cells (IC50=8.6μM). Ester 4d exerted strong antiproliferative activity against the estrogen-unresponsive, multi-drug resistant MDA-MB-231 breast cancer cell line, with IC50 value of 9.2μM. Compared with the strong activity of compounds 4a, 4d and 6a, commercial α-tocopheryl succinate and γ-tocotrienol showed only a limited activity against all three cell lines, with IC50 values >50μM. Investigation of the cell cycle phase distribution and the cell death induction confirmed an apoptosis of the MDA-MB-231 cells treated with 4d, as well as a synergistic effect of 4d with the known anticancer drug doxorubicin. This result suggests a possibility of a combined therapy of breast cancer in order to improve the therapeutic response and to lower the toxicity associated with a high dose of doxorubicin. The stability study of 4d in human plasma showed that ca. 83% initial concentration of this compound remains in plasma in the course of six hours incubation. The ligand based

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

    PubMed

    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. PMID:21571620

  4. Antineoplastic agents, 99. Amaryllis belladonna.

    PubMed

    Pettit, G R; Gaddamidi, V; Goswami, A; Cragg, G M

    1984-01-01

    Amaryllis belladonna bulbs were examined for constituents inhibitory against the murine P-388 lymphocytic leukemia (PS system). Two in vitro active alkaloids, acetylcaranine (2; 9PS ED50 0.23 microgram/ml) and ambelline (3; 9PS ED50 1.6 micrograms/ml), were isolated accompanied by undulatine. However, the non-chiral anhydrolycorinium chloride (5) was found to be the principal antineoplastic (3 PS, 64-69% life extension at dose levels 10 to 20 mg/kg in vivo, ED50 1.4 micrograms/ml in vitro) component. Quaternary chloride 5 has not been located previously among plant or animal biosynthetic products. PMID:6512532

  5. Microbial growth tests in anti-neoplastic injectable solutions.

    PubMed

    Paris, Isabelle; Paci, Angelo; Rey, Jean-Baptiste; Bourget, Philippe

    2005-03-01

    The Institut Gustave-Roussy (IGR) Department of Clinical Pharmacy (DCP) ensures the annual preparation of about 30 000 therapeutic batches of anti-neoplastic agents. High performance thin-layer chromatography (HPTLC) allows postproduction quality control of these batches. Although the centralized chemotherapy manufacturing unit has been recently ISO 9001:2000 certified, it was considered to improve the quality level of manufactured batches even further. The viability of micro-organisms (bacteria and fungi) in appropriate sterile media containing various anti-neoplastic agents at therapeutic concentration was assessed to demonstrate the lack of contamination during our manufacturing process in the isolator. After 14 days of incubation in these media, the results show the absence of contamination of the manufactured batches. This leads us to conclude that using sterile drugs and sterile medical devices in a sterile isolator allows the manufacture of sterile therapeutic batches with excellent confidence. PMID:16460598

  6. Exposure of hospital workers to airborne antineoplastic agents

    SciTech Connect

    deWerk Neal, A.; Wadden, R.A.; Chiou, W.L.

    1983-04-01

    Practices for handling antineoplastic drugs were surveyed, and ambient-air sampling for four antineoplastic agents was conducted in outpatient oncology clinics. A questionnaire was administered in 1981 to the nurse or pharmacist in charge of drug preparation at 10 hospital oncology clinics. At three sites, air samples were collected during working hours in medication-preparation rooms and nearby offices. The air-sampling pumps contained filters at breathing-zone height; room air was drawn through each filter for 40 hours. Extracts from the filters were assayed by high-performance liquid chromatography (HPLC) for fluorouracil and cyclophosphamide in seven sets of samples and methotrexate and doxorubicin in five sets of samples. Mass spectrometry (MS) was used to confirm detection of fluorouracil. Total use of each monitored drug was recorded at each site. Nine clinics had no ventilation hood, and drugs were prepared by nurses in eight clinics. Routine use of gloves (three clinics) and masks (one clinic) was uncommon, and wastes were disposed of in uncovered receptacles in four of the clinics. Eating and drinking occurred in seven of the preparation rooms. At the main air-sampling site, fluorouracil (0.12-82.26 ng/cu m) was detected in air during 200 of the 320 hours monitored. Cyclophosphamide (370 ng/cu m) was present during 80 hours. In the two other sites, fluorouracil was detected by HPLC but not confirmed by MS, and no cyclophosphamide was detected. No detectable amounts of methotrexate and doxorubicin were present. Fluorouracil was the most frequently used drug, and cyclophosphamide was second. Results suggest that personnel handling antineoplastic drugs are subject to potential systemic absorption of these agents by inhalation.

  7. Intestinal and Liver Toxicity of Antineoplastic Drugs

    PubMed Central

    McDonald, George B.; Tirumali, Nigendra

    1984-01-01

    This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington, Seattle. Taken from a transcription, it has been edited by Drs Paul G. Ramsey, Assistant Professor of Medicine, and Philip J. Fialkow, Professor and Chairman of the Department of Medicine. PMID:6375139

  8. Potential antineoplastic effects of Aloe-emodin: a comprehensive review.

    PubMed

    Chen, Ruie; Zhang, Jinming; Hu, Yangyang; Wang, Shengpeng; Chen, Meiwan; Wang, Yitao

    2014-01-01

    Aloe-emodin (AE), a bioactive anthraquinone derived from both Aloe vera and Rheum officinale, has recently been demonstrated to have various pharmacological activities. With the widespread popularity of natural products, such as antineoplastic drugs, AE has attracted much attention due to its remarkable antineoplastic activity on multiple tumor cells involving multi-channel mechanisms, including the disruption of cell cycle, induction of apoptosis, anti-metastasis, antiangiogenic, and strengthening of immune function. Experimental data have revealed AE as a potentially potent anti-cancer candidate. Despite this, the pharmaceutical application of AE is still in a fledging period as most research has concentrated on the elucidation of the molecular mechanism of action of existing treatments, rather than the development of novel formulations. Therefore, the present review summarizes the potential toxicity, molecular mechanism, pharmacokinetic characteristics, and pharmaceutical development of AE as an antineoplastic agent. This is based on its physicochemical properties, in an attempt to encourage further research on AE as a potential anti-cancer agent. PMID:24707862

  9. Monitoring method for surface contamination caused by selected antineoplastic agents.

    PubMed

    Larson, R R; Khazaeli, M B; Dillon, H Kenneth

    2002-02-01

    A method of evaluating surface contamination caused by selected antineoplastic agents was studied. The antineoplastic agents tested were cyclophosphamide, ifosfamide, doxorubicin hydrochloride, fluorouracil, and paclitaxel. Each agent was reconstituted and prepared as a stock solution. A 0.1-mL portion of each solution was spread evenly over a 600-cm2 area of a stainless steel surface, a resin countertop surface, and a vinyl flooring surface. After drying, the surfaces were wiped with each of two types of commercially available wiping materials (What-man no. 42 filters and Kimberly-Clark Kimwipes). A blend of methanol, acetonitrile, and buffered water was used both as the wetting agent for wiping the surfaces and as a desorbing solution. The desorbate was analyzed for drug concentration by reverse-phase high-performance liquid chromatography (HPLC). Mean +/- S.D. percent total recovery ranged from 72.4% +/- 17.6% to 95.3% +/- 2.9% for the vinyl surface wiped with filters, 91.5% +/- 5.4% to 104.7% +/- 0.8% for the resin surface wiped with filters, 73.9% +/- 2.3% to 95.3% +/- 1.7% for the stainless steel surface wiped with filters, and 18.2% +/- 1.4% to 372.8% +/- 8.0% for the stainless steel surface wiped with Kimwipes. Results were best for ifosfamide and cyclophosphamide. Kimwipes were deemed ineffective for this monitoring method because an ingredient interfered with the quantitative analytical tests. A wipe-sampling, desorption, and HPLC method for monitoring surface contamination by selected antineoplastic agents was sufficiently accurate and sensitive to evaluate surfaces typically found in both the pharmacy and drug administration areas of oncology treatment facilities. PMID:11862639

  10. Design and synthesis of novel antineoplastic agents inspired from marine bromopyrrole alkaloids.

    PubMed

    Rane, Rajesh A; Bangalore, Pavan Kumar; Naphade, Shital S; Patel, Harun M; Palkar, Mahesh B; Karpoormath, Rajshekhar

    2015-01-01

    Azetidin-2-one, a β -lactam four-membered heterocyclic ring is widely identified for its diverse medicinal properties. Ezetimibe a cholesterol absorption inhibitor and Aztreonam a potent cephalosporinase inhibitor proved the medicinal value of azetidin-2-ones. On the other hand marine bromopyrrole alkaloids are well known for their diverse biological significance. Hence twenty novel conjugates of azetidin-2-ones integrated with 4,5-dibromopyrrole motif were synthesized and screened for antineoplastic activity using MTT assay. Synthesized hybrids displayed good antineoplastic profile particularly towards breast cancer cell line MCF7, where hybrid 5e displayed maximum cytotoxicity (IC50 = 0.5 µM). The selective cytotoxicity displayed by these conjugates towards tested cancer cells with non-toxicity against normal human VERO cells indicated their potential for further antineoplastic drug development. PMID:25495466

  11. Membrane transport of antineoplastic agents

    SciTech Connect

    Goldman, I.D. )

    1986-01-01

    This book contains 13 chapters. Some of the chapter titles are: Methods for Quantifying the Transport of Drugs Across Brain Barrier Systems; Liposomes as Drug Carriers in Cancer Chemotherapy; Genetic and Bioochemical Characterization of Multidrug Resistance; Membrane Transport of Anthracyclines; and The Cellular Pharmacology of Methotrexate.

  12. Serine deprivation enhances antineoplastic activity of biguanides.

    PubMed

    Gravel, Simon-Pierre; Hulea, Laura; Toban, Nader; Birman, Elena; Blouin, Marie-José; Zakikhani, Mahvash; Zhao, Yunhua; Topisirovic, Ivan; St-Pierre, Julie; Pollak, Michael

    2014-12-15

    Metformin, a biguanide widely used in the treatment of type II diabetes, clearly exhibits antineoplastic activity in experimental models and has been reported to reduce cancer incidence in diabetics. There are ongoing clinical trials to evaluate its antitumor properties, which may relate to its fundamental activity as an inhibitor of oxidative phosphorylation. Here, we show that serine withdrawal increases the antineoplastic effects of phenformin (a potent biguanide structurally related to metformin). Serine synthesis was not inhibited by biguanides. Instead, metabolic studies indicated a requirement for serine to allow cells to compensate for biguanide-induced decrease in oxidative phosphorylation by upregulating glycolysis. Furthermore, serine deprivation modified the impact of metformin on the relative abundance of metabolites within the citric acid cycle. In mice, a serine-deficient diet reduced serine levels in tumors and significantly enhanced the tumor growth-inhibitory actions of biguanide treatment. Our results define a dietary manipulation that can enhance the efficacy of biguanides as antineoplastic agents that target cancer cell energy metabolism. PMID:25377470

  13. Hypersensitivity reactions to oxaliplatin and other antineoplastic agents.

    PubMed

    Syrigou, Ekaterini; Syrigos, Kostas; Saif, M Wasif

    2008-03-01

    Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States. PMID:18377776

  14. Gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy in the years 2000

    PubMed Central

    Castagnola, Elio; Ruberto, Eliana; Guarino, Alfredo

    2016-01-01

    AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children. METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: “gastrointestinal infection AND antineoplastic chemotherapy AND children”, “gastrointestinal infection AND oncology AND children”, “liver infection AND antineoplastic chemotherapy AND children”, “liver abscess AND chemotherapy AND child”, “neutropenic enterocolitis AND chemotherapy AND children”, “thyphlitis AND chemotherapy AND children”, “infectious diarrhea AND children AND oncology”, “abdominal pain AND infection AND children AND oncology”, “perianal sepsis AND children AND oncology”, “colonic pseudo-obstruction AND oncology AND child AND chemotherapy”, “microflora AND children AND malignancy”, “microbiota AND children AND malignancy”, “fungal flora AND children AND malignancy”. We also analysed evidence from several articles and book references. RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the

  15. Application of electrolysis for detoxification of an antineoplastic in urine.

    PubMed

    Kobayashi, Toyohide; Hirose, Jun; Sano, Kouichi; Kato, Ryuji; Ijiri, Yoshio; Takiuchi, Hiroya; Tanaka, Kazuhiko; Goto, Emi; Tamai, Hiroshi; Nakano, Takashi

    2012-04-01

    Antineoplastics in excreta from patients have been considered to be one of the origins of cytotoxic, carcinogenic, teratogenic, and mutagenic contaminants in surface water. Recent studies have demonstrated that antineoplastics in clinical wastewater can be detoxified by electrolysis. In this study, to develop a method for the detoxification of antineoplastics in excreta, methotrexate solution in the presence of human urine was electrolyzed and evaluated. We found that urine inhibits detoxification by electrolysis; however, this inhibition decreased by diluting urine. In urine samples, the concentrations of active chlorine generated by anodic oxidation from 0.9% NaCl solution for inactivation of antineoplastics increased in dilution-dependent and time-dependent manner. These results indicate that electrolysis with platinum-based iridium oxide composite electrode is a possible method for the detoxification of a certain antineoplastic in urine. PMID:22154144

  16. Calcium channel antagonist properties of the antineoplastic antiestrogen tamoxifen in the PC12 neurosecretory cell line

    SciTech Connect

    Greenberg, D.A.; Carpenter, C.L.; Messing, R.O.

    1987-01-01

    In view of existing evidence that Ca2+ may be important for tumor cell growth and metastasis, we investigated the effects of three antineoplastic drugs on K+-stimulated /sup 45/Ca2+ uptake through voltage-dependent Ca2+ channels of the PC12 neurosecretory cell line. The agents chosen for study (vinblastine, doxorubicin, and tamoxifen) were those previously shown to inhibit Ca2+/calmodulin- or Ca2+/phospholipid-activated protein kinases. Neither vinblastine nor doxorubicin altered /sup 45/Ca2+ uptake at concentrations that inhibit these Ca2+-dependent enzymes. However, tamoxifen reduced uptake (50% inhibitory dose, 8.6 +/- 0.9 (SE) microM) and competed for Ca2+ channel antagonist binding sites labeled by (/sup 3/H)-(+)PN200-110 (ki = 2.2 +/- 0.3 microM). Ca2+ channel antagonist properties may contribute to the effects of antineoplastic agents such as tamoxifen.

  17. Antineoplastic effects of mammalian target of rapamycine inhibitors.

    PubMed

    Salvadori, Maurizio

    2012-10-24

    Cancer after transplantation is the third cause of death and one of the more relevant comorbidities. Aim of this review is to verify the role of different pathogenetic mechanisms in cancer development in transplant patients and in general population as well. In particular has been outlined the different role exerted by two different families of drug as calcineurin inhibitor and mammalian target of rapamycin (mTOR) inhibitor. The role of mTOR pathways in cell homeostasis is complex but enough clear. As a consequence the mTOR pathway deregulation is involved in the genesis of several cancers. Hence the relevant role of mTOR inhibitors. The authors review the complex mechanism of action of mTOR inhibitors, not only for what concerns the immune system but also other cells as endothelial, smooth muscle and epithelial cells. The mechanism of action is still now not completely defined and understood. It implies the inhibition of mTOR pathway at different levels, but mainly at level of the phosphorylation of several intracellular kinases that contribute to activate mTOR complex. Many prospective and retrospective studies in transplant patients document the antineoplastic role of mTOR inhibition. More recently mTOR inhibitors proven to be effective in the treatment of some cancers also in general population. Kidney cancers, neuroendocrine tumors and liver cancers seem to be the most sensitive to these drugs. Best results are obtained with a combination treatment, targeting the mTOR pathway at different levels. PMID:24175199

  18. Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (review).

    PubMed

    Möhler, Hanns; Pfirrmann, Rolf W; Frei, Karl

    2014-10-01

    Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti‑oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications. PMID:25175943

  19. Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

    PubMed Central

    MÖHLER, HANS; PFIRMAN, ROLF W.; FREI, KARL

    2014-01-01

    Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti-oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications. PMID:25175943

  20. The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ

    PubMed Central

    Rousseaux, Christel; El-Jamal, Noura; Dubuquoy, Laurent

    2013-01-01

    Epidemiological evidences suggested that 5-aminosalicylic acid (5-ASA) therapy may prevent the development of colorectal cancer in inflammatory bowel disease patients. Our aim is to investigate whether peroxisome proliferator-activated receptor-γ (PPARγ) mediates the antineoplastic effects of 5-ASA. HT-29 and Caco-2 cells were treated by 5-ASA, rosiglitazone (PPARγ ligand) or etoposide (anticarcinogenic drug). Epithelial cell growth, proliferation and apoptosis were assessed by cell count, Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. The antineoplastic effect of 5-ASA was evaluated in a xenograft tumor model in SCID mice and in azoxymethane (AOM)-induced colon carcinogenesis in A/JOlaHsd mice. The role of PPARγ was examined by administration of PPARγ antagonist, GW9662 and in PPAR knockdown cells. Compared with untreated cells, treatment of HT-29 cells by 5-ASA inhibited significantly cell growth and cell proliferation (respectively, 60% and 63%) and induced apoptosis in 75% of cells. These effects were abolished by co-treatment with GW9662 and blunted in PPAR knockdown cells. Contrarily to etoposide, similar inhibitory effects of GW9662 were obtained in HT-29 cells treated with rosiglitazone. In the xenograft model, GW9662 abolished the therapeutic effect of 5-ASA, which decreased tumor weight and volume by 80% in SCID mice compared with untreated mice. In A/JOlaHsd mice, 5-ASA suppressed colon carcinogenesis by decreasing the number of aberrant crypt foci (75%) and aberrant crypts (22%) induced by AOM treatment with an absence of 5-ASA response after GW9662 administration. In conclusion, 5-ASA exerts potent antineoplastic effects that are mediated through PPARγ. These data provide new rational for designing more effective and safe antineoplastic PPARγ ligands with topical effects. PMID:23843037

  1. Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent.

    PubMed

    Sur, P; Das, M; Gomes, A; Vedasiromoni, J R; Sahu, N P; Banerjee, S; Sharma, R M; Ganguly, D K

    2001-05-01

    The antineoplastic effect of Trigonella foenum graecum seed extract has been evaluated in the Ehrlich ascites carcinoma (EAC) model in Balb-C mice. Intra-peritoneal administration of the alcohol extract of the seed both before and after inoculation of EAC cell in mice produced more than 70% inhibition of tumour cell growth with respect to the control. Treatment with the extract was found to enhance both the peritoneal exudate cell and macrophage cell counts. The extract also produced a significant antiinflammatory effect. We report here the antiinflammatory and antineoplastic effects, of Trigonella foenum graecum seed extract. PMID:11351364

  2. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata.

    PubMed

    Sima, Peter; Vetvicka, Vaclav

    2011-11-10

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID:22087433

  3. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata

    PubMed Central

    Sima, Peter; Vetvicka, Vaclav

    2011-01-01

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID:22087433

  4. Antineoplastic and Apoptotic Potential of Traditional Medicines Thymoquinone and Diosgenin in Squamous Cell Carcinoma

    PubMed Central

    Das, Subhasis; Dey, Kaushik Kumar; Dey, Goutam; Pal, Ipsita; Majumder, Abhijit; MaitiChoudhury, Sujata; kundu, Subhas C.; Mandal, Mahitosh

    2012-01-01

    Thymoquinone (TQ) and diosgenin (DG), the active ingredients obtained from black cumin (Nigella sativa) and fenugreek (Trigonella foenum graecum), respectively, exert potent bioactivity, including anticancer effects. This study investigated the antineoplastic activity of these agents against squamous cell carcinoma in vitro and sarcoma 180–induced tumors in vivo. TQ and DG inhibited cell proliferation and induced cytotoxicity in A431 and Hep2 cells. These agents induced apoptosis by increasing the sub-G1 population, LIVE/DEAD cytotoxicity, chromatin condensation, DNA laddering and TUNEL-positive cells significantly (P<0.05). Increased Bax/Bcl-2 ratio, activation of caspases and cleavage of poly ADP ribose polymerase were observed in treated cells. These drugs inhibited Akt and JNK phosphorylations, thus inhibiting cell proliferation while inducing apoptosis. In combination, TQ and DG had synergistic effects, resulting in cell viability as low as 10%. In a mouse xenograft model, a combination of TQ and DG significantly (P<0.05) reduced tumor volume, mass and increased apoptosis. TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer. PMID:23077516

  5. Immune-dependent antineoplastic effects of cisplatin plus pyridoxine in non-small-cell lung cancer.

    PubMed

    Aranda, F; Bloy, N; Pesquet, J; Petit, B; Chaba, K; Sauvat, A; Kepp, O; Khadra, N; Enot, D; Pfirschke, C; Pittet, M; Zitvogel, L; Kroemer, G; Senovilla, L

    2015-06-01

    cis-Diamminedichloroplatinum(II) (CDDP), which is mostly referred to as cisplatin, is a widely used antineoplastic. The efficacy of cisplatin can be improved by combining it with the vitamin B6 precursor pyridoxine. Here, we evaluated the putative synergistic interaction of CDDP with pyridoxine in the treatment of an orthotopic mouse model of non-small-cell lung cancer (NSCLC). CDDP and pyridoxine exhibited hyperadditive therapeutic effects. However, this synergy was only observed in the context of an intact immune system and disappeared when the otherwise successful drug combination was applied to the same NSCLC cancer implanted in the lungs of athymic mice (which lack T lymphocytes). Immunocompetent mice that had been cured from NSCLC by the combined regimen of CDDP plus pyridoxine became resistant against subcutaneous rechallenge with the same (but not with an unrelated) cancer cell line. In vitro, CDDP and pyridoxine did not only cause synergistic killing of NSCLC cells but also elicited signs of immunogenic cell death including an endoplasmic reticulum stress response and exposure of calreticulin at the surface of the NSCLC cells. NSCLC cells treated with CDDP plus pyridoxine in vitro elicited a protective anticancer immune response upon their injection into immunocompetent mice. Altogether, these results suggest that the combined regimen of cisplatin plus pyridoxine mediates immune-dependent antineoplastic effects against NSCLC. PMID:25065595

  6. Antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and depsipeptide on Raji lymphoma cells.

    PubMed

    Shaker, Sepideh; Bernstein, Mark; Momparler, Richard L

    2004-06-01

    Epigenetic alterations, such as aberrant DNA methylation and histone deacetylation, can silence genes that suppress leukemogenesis. The objective of our study was to investigate the in vitro antineoplastic and gene re-activation activity of 5-aza-2'-deoxycytidine (5AZA), a potent inhibitor of DNA methylation, and depsipeptide (depsi), an inhibitor of histone deacetylase, on Raji lymphoma cells. The combination of 5AZA with depsi produced a significantly greater inhibition of growth and colony formation than either agent alone. Using RT-PCR, we observed that combination also produced a synergistic activation of E-cadherin, a gene that is silenced by aberrant DNA methylation in Raji cells. This latter interaction indicates that there is cross-talk between DNA methylation and histone modifications in chromatin for E-cadherin in this cell line. 5AZA and depsi may be an interesting drug combination to investigate in patients with lymphoma. PMID:15138563

  7. Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase.

    PubMed Central

    Ponti, M; Forrow, S M; Souhami, R L; D'Incalci, M; Hartley, J A

    1991-01-01

    A polymerase stop assay has been developed to determine the DNA nucleotide sequence specificity of covalent modification by antineoplastic agents using the thermostable DNA polymerase from Thermus aquaticus and synthetic labelled primers. The products of linear amplification are run on sequencing gels to reveal the sites of covalent drug binding. The method has been studied in detail for a number of agents including nitrogen mustards, platinum analogues and mitomycin C, and the sequence specificities obtained accord with those obtained by other procedures. The assay is advantageous in that it is not limited to a single type of DNA lesion (as in the piperidine cleavage assay for guanine-N7 alkylation), does not require a strand breakage step, and is more sensitive than other primer extension procedures which have only one cycle of polymerization. In particular the method has considerable potential for examining the sequence selectivity of damage and repair in single copy gene sequences in genomic DNA from cells. Images PMID:2057351

  8. Viral-associated trichodysplasia secondary to antineoplastic treatment in a patient with lymphoblastic leukemia.

    PubMed

    Celeiro-Muñoz, Catuxa; González-Vilas, Daniel; Sánchez-Aguilar, Dolores; Suárez-Peñaranda, José Manuel

    2014-06-01

    Viral-associated trichodysplasia spinulosa is an unusual condition with distinctive clinical and histopathological features. Initially described in patients immunosupressed as a result of solid organ transplantation, it has also been reported in patients treated with immunosuppressive drugs other than cyclosporine or being treated for hematological malignancies. Patients presented with disseminated follicular, hyperkeratotic papules, and variable degrees of alopecia. Histopathological examination revealed shaftless bulbous and dilated hair follicles with keratotic plugging of the infundibulum. The authors reported a case of viral-associated trichodysplasia in a 5-year-old boy treated for a lymphoblastic leukemia. Eruption persisted, although treated with emollients and keratolytics, but resolved spontaneously after completing the antineoplastic medication. PMID:24887966

  9. Chronic Arsenic Poisoning Probably Caused by Arsenic-Based Pesticides: Findings from an Investigation Study of a Household

    PubMed Central

    Li, Yongfang; Ye, Feng; Wang, Anwei; Wang, Da; Yang, Boyi; Zheng, Quanmei; Sun, Guifan; Gao, Xinghua

    2016-01-01

    In addition to naturally occurring arsenic, man-made arsenic-based compounds are other sources of arsenic exposure. In 2013, our group identified 12 suspected arsenicosis patients in a household (32 living members). Of them, eight members were diagnosed with skin cancer. Interestingly, all of these patients had lived in the household prior to 1989. An investigation revealed that approximately 2 tons of arsenic-based pesticides had been previously placed near a well that had supplied drinking water to the family from 1973 to 1989. The current arsenic level in the well water was 620 μg/L. No other high arsenic wells were found near the family’s residence. Based on these findings, it is possible to infer that the skin lesions exhibited by these family members were caused by long-term exposure to well water contaminated with arsenic-based pesticides. Additionally, biochemical analysis showed that the individuals exposed to arsenic had higher levels of aspartate aminotransferase and γ-glutamyl transpeptidase than those who were not exposed. These findings might indicate the presence of liver dysfunction in the arsenic-exposed individuals. This report elucidates the effects of arsenical compounds on the occurrence of high levels of arsenic in the environment and emphasizes the severe human health impact of arsenic exposure. PMID:26784217

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

    SciTech Connect

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

    2008-11-15

    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.

  11. Amido analogs of mitoxantrone: physico-chemical properties, molecular modeling, cellular effects and antineoplastic potential.

    PubMed

    Zagotto, G; Moro, S; Uriarte, E; Ferrazzi, E; Palù, G; Palumbo, M

    1997-03-01

    To assess the effects of amido substitution in the side-chains of the anticancer drug mitoxantrone (MX) two analogs were synthesized, having hydroxyethylaminoacetyl- and hydroxyethylaminopropionyl- substituents at the nitrogens located at positions 1, 4 of the anthracenedione ring system. The novel derivatives exhibit DNA-affinity and redox properties similar to the parent drug. However, unlike MX, they are not able to stimulate DNA cleavage, as shown by alkaline elution experiments. Molecular modeling studies using ab initio quantum mechanical methods show that, while the stereochemistry of the drug molecule is not appreciably affected when an amide group replaces the aromatic amino function, the reverse is true for the electrostatic properties. Indeed, overlapping of electron density of MX with its analogs is very poor. Moreover, a reversal in the direction of MX dipole moment occurs in the amido congeners. This may explain the lack of recognition of the cleavable topoisomerase II-DNA complex and loss of cleavage stimulation. However, the new derivatives exhibit pharmacological activity comparable to that found for MX, as they are remarkably cytotoxic and are active in vivo against P388 murine leukemia. Hence, amido substitution may lead to a different mechanism of cytotoxicity, not related to classical protein or free radical-mediated DNA damage, which points to a novel type of antineoplastic pharmacophore. PMID:9113065

  12. Gold(III)–pyrrolidinedithiocarbamato Derivatives as Antineoplastic Agents**

    PubMed Central

    Nardon, Chiara; Chiara, Federica; Brustolin, Leonardo; Gambalunga, Alberto; Ciscato, Francesco; Rasola, Andrea; Trevisan, Andrea; Fregona, Dolores

    2015-01-01

    Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [AuIIIBr2(PDT)] and [AuIIICl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [AuIIIBr2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [AuIIIBr2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells. PMID:25969817

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

    SciTech Connect

    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 {alpha} 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 {sup 3}H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF{sub 1} mice. Approximately 50% of {sup 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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

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

    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.

  16. Spectrofluorimetric determination of the antineoplastic agent lomustine based on the sensitizing effect of β-cyclodextrin.

    PubMed

    Fisli, Hassina; Bensouilah, Nadjia; Abdaoui, Mohamed

    2016-05-01

    The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding on the photophysical properties of the antineoplastic drug lomustine were analysed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The LSER method enabled the overall solvent effects to be quantitatively estimated and separated into specific and non-specific contributions. The molecular encapsulation of lomustine by β-cyclodextrin (β-CD) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameter and the effect of the solvent used. It was concluded that β-CD forms a 1:1 inclusional complex with lomustine in acetonitrile solution and its association constant was calculated to be 500 M(-1) . In addition, and for the first time, a simple, rapid and high sensitive fluorimetric method for the determination of lomustine was developed based upon the enhancement effect produced through complex formation with β-CD. The new approach for the quantification of lomustine in the presence of β-CD was described in aqueous and organic solutions. Better limits of detection (0.31 µg ml(-1) ) and quantification (1.05 µg ml(-1) ) were obtained in aqueous solution with respect to those obtained in organic solvent. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26510489

  17. In vivo kinetics of micronuclei induction by bifunctional alkylating antineoplastics.

    PubMed

    Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia L; López-Iturbe, Rosario; Alvaro-Delgadillo, Horacio

    2004-05-01

    The aim of the present study was to determine in vivo the kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in mice, as an approach for studying the mechanism of micronuclei induction by mitomycin C, cis-diamine dichloroplatinum, busulfan and bis-chloroethylnitrosourea, bifuctional alkylating antineoplastic agents having different patterns of crosslink induction. The kinetics of MN-PCE induction was established by scoring the frequency of MN-PCE in 2000 PCE in peripheral blood, for periods of 8 or 10 h after acute treatment and up to 80 h, with different doses of the agent. The kinetics of MN-PCE induction and particularly the times of maximal induction by different bifunctional alkylating agents were compared with the kinetics previously obtained for ethylnitrosourea, methylnitrosourea and 6-mercaptopurine, agents that cause MN-PCE mainly in the first, second and third divisions after exposure, respectively. The results obtained in the present study allow us to conclude that: (i) bifunctional alkylating agents have very different efficiencies of genotoxic and cytotoxic action; (ii) all assayed bifunctional alkylating agents induced micronuclei during the first cell division, owing to the mistaken repair of primary lesions, e.g. excision; (iii) busulfan and bis-chloroethylnitrosourea showed an additional late mechanism of micronuclei induction, which is expressed at the third division and seems to be related to the mismatch repair process. PMID:15123786

  18. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma

    PubMed Central

    Kwak, Tae Won; Shin, Hee Jae; Jeong, Young-Il; Han, Myoung-Eun; Oh, Sae-Ock; Kim, Hyun-Jung; Kim, Do Hyung; Kang, Dae Hwan

    2015-01-01

    Background The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight when compared with the control. Conclusion These results reveal that streptochlorin is a promising chemotherapeutic agent to the treatment of cholangiocarcinoma. PMID:25931814

  19. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    PubMed Central

    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

  20. Chondroitin sulfate derived theranostic nanoparticles for targeted drug delivery.

    PubMed

    Varghese, Oommen P; Liu, Jianping; Sundaram, Karthi; Hilborn, Jöns; Oommen, Oommen P

    2016-08-16

    Glycosaminoglycan derived nanoparticles are a promising delivery system owing to their unique tumour targeting ability. Exploiting fluorescein for inducing amphiphilicity in these biopolymers provides inherent imaging and drug stabilization capabilities by π-π stacking interactions with aromatic antineoplastic agents. This offers a versatile and highly customizable nanocarrier with narrow size distribution and high drug loading efficiency (80%) with sustained drug release. PMID:27431007

  1. Taurolidine: cytotoxic and mechanistic evaluation of a novel antineoplastic agent.

    PubMed

    Calabresi, P; Goulette, F A; Darnowski, J W

    2001-09-15

    Bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)methane (taurolidine) is a synthetic broad-spectrum antibiotic that reacts with bacterial cell membrane components to prevent adhesion to epithelial cell surfaces. Reflecting the key role of adhesion in the growth and development of human solid tumors, studies were initiated to assess the antiproliferative activity of this agent in selected human and murine tumor cell lines. A 3-day exposure to Taurolidine inhibited the growth of all of the cell lines evaluated with IC(50)s ranging from 9.6-34.2 microM. Studies to identify the mechanism responsible for this effect were conducted in NIH-3T3 murine fibroblasts and the PA-1 and SKOV-3 human ovarian tumor cells. These studies revealed that a 48-h exposure to taurolidine had little effect on cell cycle distribution in PA-1 and SKOV-3 cells but significantly increased the appearance of DNA debris in the sub-G(0)/G(1) region, an effect consistent with an induction of apoptosis. In contrast, in NIH-3T3 cells, taurolidine exposure did not increase DNA debris in the sub-G(0)/G(1) region. Additional studies assessed phosphotidylserine externalization after a 24-h exposure to taurolidine using annexin-V binding as a cell surface marker. These studies revealed that taurolidine increased the percentage of annexin-V-positive cells by 4-fold and 3-fold in PA-1 and SKOV-3 cells, respectively. In NIH-3T3 cells, taurolidine exposure slightly increased ( approximately 5%) annexin-V binding. Parallel studies revealed that exposure to taurolidine also resulted in poly(ADP-ribose) polymerase cleavage in both ovarian tumor cell lines but not in NIH-3T3 cells. Finally, murine-based studies were conducted to assess the antineoplastic activity of three consecutive daily i.p. bolus injections of taurolidine at doses ranging from 5-mg injection/mouse to 30-mg injection/mouse. The 20-mg injection dose produced approximately 10% mortality and was identified as the maximally tolerated dose in this model

  2. Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy.

    PubMed

    El Hammoumi, Massine; El Marjany, Mohamed; Moussaoui, Driss; Doudouh, Aberahim; Mansouri, Hamid; Kabiri, El Hassane

    2015-07-01

    The aim of our work is to promote the awareness about the development of sarcoidosis after antineoplastic therapy in order to avoid diagnostic errors with FDG-PET/CT findings. We report the observation of three women with breast, cervix and stomach treated cancers who developed a sarcoidosis after the end of anti-neoplastic therapy. The utility of FDG-PET/CT is in pinpointing the organs candidates for diagnostic biopsy and not distinguishing between the malignancy and granulomatous or inflammatory diseases. PMID:25294405

  3. Improved genetically modified Escherichia coli strain for prescreening antineoplastic agents.

    PubMed Central

    Bartus, H R; Mirabelli, C K; Auerbach, J I; Shatzman, A R; Taylor, D P; Johnson, R K; Rosenberg, M; Crooke, S T

    1984-01-01

    Clinical experience suggests that drugs that interact with and damage DNA are useful in cancer chemotherapy (H. Umezawa , p. 43-72, in V. T. DeVita , Jr., and H. Busch [ed.], Methods in Cancer Research; Cancer Drug Development, vol. XVI, 1979). Prescreening systems for antitumor agents in natural products require assays that are exquisitely sensitive, since the active components are often produced in quantities of micrograms per milliliter or less. One assay used to identify agents that interact with DNA is the biochemical induction assay, utilizing Escherichia coli BR 513 (R. K. Elespuru and R. J. White, Cancer Res. 43:2819-2830, 1983). In this paper we describe a genetic modification of strain BR 513 that displays an expanded spectrum of activity. This strain may provide an improved prescreen for detecting natural products that interact with DNA. PMID:6203484

  4. Antineoplastic Agents 552. Oxidation of Combretastatin A-1

    PubMed Central

    Pettit, George R.; Thornhill, Andrew J.; Moser, Bryan R.; Hogan, Fiona

    2009-01-01

    The very unstable (< 10 min at rt) o-quinone (5) derived from the vicinal diphenol anticancer drug combretastatin A-1 (1) has been obtained by careful oxidation with NaIO4 and tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine (6) allowed o-quinone 5 to be trapped as the stable phenazine derivative (7). For further confirmation, 5 was also captured as a dimethoxyphenylenediamine-derived phenazine (11). Both phenazines 7 and 11 significantly inhibited (ED50 ~ 0.2 μg/mL) growth of the murine P388 lymphocytic leukemia cell line and provided a new SAR insight in the combretastatin series of naturally occurring anticancer drugs. PMID:18729517

  5. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization.

    PubMed

    Castells, Mariana; Sancho-Serra, Maria del Carmen; Simarro, Maria

    2012-09-01

    Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies. PMID:22576054

  6. The isolation and structure of 13,18-dehydroglaucarubinone, a new antineoplastic quassinoid from Simarouba amara.

    PubMed

    Polonsky, J; Varon, Z; Jacquemin, H; Pettit, G R

    1978-09-15

    An investigation of the Guyana plant Simarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2'-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2'-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid 2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388. PMID:720499

  7. The association between the antineoplastic drug daunomycin and iron. evidence for polynuclear aggregates

    NASA Astrophysics Data System (ADS)

    Matzanke, B. F.; Bill, E.; Winkler, H.; Trautwein, A. X.

    1992-04-01

    In contrast to literature data, at millimolar iron and daunomycin (DN) concentrations no solitary Fe(DN)3 complexes are formed in appreciable amounts. The Mössbauer spectroscopic analysis revealed severe dependencies on temperature and on the metal ligand ratio. Two species can be discerned: exchange-coupled polynuclear aggregates, which are magnetically highly anisotropic and another superparamagnetic system, exhibiting much less magnetic anisotropy. The cooperative phenomena observed are attributed to stacking effects of daunomycin.

  8. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... A at http://www.cdc.gov/niosh/docs/2012-150 . Background: The NIOSH Alert: NIOSH published... September 2004 ( http://www.cdc.gov/niosh/docs/2004-165/ ). Appendix A of this Alert defined hazardous...

  9. Antineoplastic Agents 553. The Texas Grasshopper Brachystola magna1

    PubMed Central

    Pettit, George R.; Meng, Yanhui; Herald, Delbert L.; Knight, John C.; Day, John F.

    2011-01-01

    Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines) -guided separation of an extract prepared from the previously chemically uninvestigated Texas grasshopper Brachystola magna led to isolation of the cancer cell growth inhibitory pancratistatin (1), narciclasine (2) and ungeremine (3). Pancratistatin (1) was first isolated from the bulbs of Hymenocallis littoralis (a.k.a. Pancratium littorale Jacq) and the original crystal structure was deduced by X-ray analysis of a monomethyl ether derivative. In the present study a crystal of pancratistatin (1) was isolated from an extract of B. magna, which led to the X-ray crystal structure of this anticancer drug. Since isoquinoline derivatives 1–3 are previously known only as constituents of amaryllidaceous plants, some of the interesting implications of their rediscovery in the grasshopper B. magna that does not appear to utilize amaryllis family plants were discussed. PMID:16124772

  10. Antineoplastic agents. 553. The Texas grasshopper Brachystola magna.

    PubMed

    Pettit, George R; Meng, Yanhui; Herald, Delbert L; Knight, John C; Day, John F

    2005-08-01

    Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines) guided separation of an extract prepared from the previously chemically uninvestigated Texas grasshopper Brachystola magna led to isolation of the cancer cell growth inhibitory pancratistatin (1), narciclasine (2), and ungeremine (3). Pancratistatin (1) was first isolated from the bulbs of Hymenocallis littoralis), and the original crystal structure was deduced by X-ray analysis of a monomethyl ether derivative. In the present study pancratistatin (1) was isolated from an extract of B. magna, which led to the X-ray crystal structure of this anticancer drug. Since isoquinoline derivatives 1-3 are previously known only as constituents of amaryllidaceous plants, some of the interesting implications of their rediscovery in the grasshopper B. magna that does not appear to utilize amaryllis family plants were discussed. PMID:16124772

  11. Early effects of the antineoplastic agent salinomycin on mitochondrial function.

    PubMed

    Managò, A; Leanza, L; Carraretto, L; Sassi, N; Grancara, S; Quintana-Cabrera, R; Trimarco, V; Toninello, A; Scorrano, L; Trentin, L; Semenzato, G; Gulbins, E; Zoratti, M; Szabò, I

    2015-01-01

    Salinomycin, isolated from Streptomyces albus, displays antimicrobial activity. Recently, a large-scale screening approach identified salinomycin and nigericin as selective apoptosis inducers of cancer stem cells. Growing evidence suggests that salinomycin is able to kill different types of non-stem tumor cells that usually display resistance to common therapeutic approaches, but the mechanism of action of this molecule is still poorly understood. Since salinomycin has been suggested to act as a K(+) ionophore, we explored its impact on mitochondrial bioenergetic performance at an early time point following drug application. In contrast to the K(+) ionophore valinomycin, salinomycin induced a rapid hyperpolarization. In addition, mitochondrial matrix acidification and a significant decrease of respiration were observed in intact mouse embryonic fibroblasts (MEFs) and in cancer stem cell-like HMLE cells within tens of minutes, while increased production of reactive oxygen species was not detected. By comparing the chemical structures and cellular effects of this drug with those of valinomycin (K(+) ionophore) and nigericin (K(+)/H(+) exchanger), we conclude that salinomycin mediates K(+)/H(+) exchange across the inner mitochondrial membrane. Compatible with its direct modulation of mitochondrial function, salinomycin was able to induce cell death also in Bax/Bak-less double-knockout MEF cells. Since at the concentration range used in most studies (around 10 μM) salinomycin exerts its effect at the level of mitochondria and alters bioenergetic performance, the specificity of its action on pathologic B cells isolated from patients with chronic lymphocytic leukemia (CLL) versus B cells from healthy subjects was investigated. Mesenchymal stromal cells (MSCs), proposed to mimic the tumor environment, attenuated the apoptotic effect of salinomycin on B-CLL cells. Apoptosis occurred to a significant extent in healthy B cells as well as in MSCs and human primary

  12. Disposition of antineoplastic agents in the very young child.

    PubMed Central

    McLeod, H. L.; Relling, M. V.; Crom, W. R.; Silverstein, K.; Groom, S.; Rodman, J. H.; Rivera, G. K.; Crist, W. M.; Evans, W. E.

    1992-01-01

    Maturation of physiologic process which govern the disposition of pharmacologic agents can yield significant changes in absorption, distribution, metabolism, and elimination of drugs in neonates, infants and children. However, there are very little data concerning the disposition of anticancer drugs in young children. Pharmacokinetic data for six anticancer agents were compared in infants less than 1 year of age and children greater than 1 year of age treated at St Jude Children's Research Hospital. No pharmacokinetic data were available for infants less than 2 months of age. Median methotrexate clearance tended to be lower in four infants (0.26-0.99 years) vs 108 children (1-19 years): 80 vs 103 ml min-1 m-2, respectively (P = 0.01). There was no difference in the median 42 h methotrexate concentration. Teniposide systemic clearance and terminal half-life and cytarabine systemic clearance were not different between the two groups. There was no significant difference in etoposide systemic clearance when normalised to body surface area (ml min-1 m-2), however a significantly lower systemic clearance relative to body weight (ml min-1 kg-1) was observed in two infants, 0.5 to 1 year of age, vs 23 children, 3-18 years of age. Doxorubicin systemic clearance was not significantly different between the two groups when systemic clearance was expressed in ml min-1 kg-1. However, there was a trend toward a lower rate of systemic clearance in ml min-1 m-2 in infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1503923

  13. Early effects of the antineoplastic agent salinomycin on mitochondrial function

    PubMed Central

    Managò, A; Leanza, L; Carraretto, L; Sassi, N; Grancara, S; Quintana-Cabrera, R; Trimarco, V; Toninello, A; Scorrano, L; Trentin, L; Semenzato, G; Gulbins, E; Zoratti, M; Szabò, I

    2015-01-01

    Salinomycin, isolated from Streptomyces albus, displays antimicrobial activity. Recently, a large-scale screening approach identified salinomycin and nigericin as selective apoptosis inducers of cancer stem cells. Growing evidence suggests that salinomycin is able to kill different types of non-stem tumor cells that usually display resistance to common therapeutic approaches, but the mechanism of action of this molecule is still poorly understood. Since salinomycin has been suggested to act as a K+ ionophore, we explored its impact on mitochondrial bioenergetic performance at an early time point following drug application. In contrast to the K+ ionophore valinomycin, salinomycin induced a rapid hyperpolarization. In addition, mitochondrial matrix acidification and a significant decrease of respiration were observed in intact mouse embryonic fibroblasts (MEFs) and in cancer stem cell-like HMLE cells within tens of minutes, while increased production of reactive oxygen species was not detected. By comparing the chemical structures and cellular effects of this drug with those of valinomycin (K+ ionophore) and nigericin (K+/H+ exchanger), we conclude that salinomycin mediates K+/H+ exchange across the inner mitochondrial membrane. Compatible with its direct modulation of mitochondrial function, salinomycin was able to induce cell death also in Bax/Bak-less double-knockout MEF cells. Since at the concentration range used in most studies (around 10 μM) salinomycin exerts its effect at the level of mitochondria and alters bioenergetic performance, the specificity of its action on pathologic B cells isolated from patients with chronic lymphocytic leukemia (CLL) versus B cells from healthy subjects was investigated. Mesenchymal stromal cells (MSCs), proposed to mimic the tumor environment, attenuated the apoptotic effect of salinomycin on B-CLL cells. Apoptosis occurred to a significant extent in healthy B cells as well as in MSCs and human primary fibroblasts. The

  14. Which drugs are contraindicated during breastfeeding? Practice guidelines.

    PubMed Central

    Moretti, M. E.; Lee, A.; Ito, S.

    2000-01-01

    QUESTION: Many breastfeeding mothers are concerned about taking medications that might affect their babies. Are there any guidelines on which drugs are safe? ANSWER: Only a few drugs pose a clinically significant risk to breastfed babies. In general, antineoplastics, drugs of abuse, some anticonvulsants, ergot alkaloids, and radiopharmaceuticals should not be taken, and levels of amiodarone, cyclosporine, and lithium should be monitored. Images p1757-a PMID:11013791

  15. On/off-switchable anti-neoplastic nanoarchitecture

    NASA Astrophysics Data System (ADS)

    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.

  16. On/off-switchable anti-neoplastic nanoarchitecture

    PubMed Central

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

    2015-01-01

    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. PMID:26415561

  17. On/off-switchable anti-neoplastic nanoarchitecture.

    PubMed

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

    2015-01-01

    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. PMID:26415561

  18. Antineoplastic copper coordinated complexes (Casiopeinas) uncouple oxidative phosphorylation and induce mitochondrial permeability transition in cardiac mitochondria and cardiomyocytes.

    PubMed

    Silva-Platas, Christian; Guerrero-Beltrán, Carlos Enrique; Carrancá, Mariana; Castillo, Elena Cristina; Bernal-Ramírez, Judith; Oropeza-Almazán, Yuriana; González, Lorena N; Rojo, Rocío; Martínez, Luis Enrique; Valiente-Banuet, Juan; Ruiz-Azuara, Lena; Bravo-Gómez, María Elena; García, Noemí; Carvajal, Karla; García-Rivas, Gerardo

    2016-02-01

    Copper-based drugs, Casiopeinas (Cas), exhibit antiproliferative and antineoplastic activities in vitro and in vivo, respectively. Unfortunately, the clinical use of these novel chemotherapeutics could be limited by the development of dose-dependent cardiotoxicity. In addition, the molecular mechanisms underlying Cas cardiotoxicity and anticancer activity are not completely understood. Here, we explore the potential impact of Cas on the cardiac mitochondria energetics as the molecular mechanisms underlying Cas-induced cardiotoxicity. To explore the properties on mitochondrial metabolism, we determined Cas effects on respiration, membrane potential, membrane permeability, and redox state in isolated cardiac mitochondria. The effect of Cas on the mitochondrial membrane potential (Δψm) was also evaluated in isolated cardiomyocytes by confocal microscopy and flow cytometry. Cas IIIEa, IIgly, and IIIia predominately inhibited maximal NADH- and succinate-linked mitochondrial respiration, increased the state-4 respiration rate and reduced membrane potential, suggesting that Cas also act as mitochondrial uncouplers. Interestingly, cyclosporine A inhibited Cas-induced mitochondrial depolarization, suggesting the involvement of mitochondrial permeability transition pore (mPTP). Similarly to isolated mitochondria, in isolated cardiomyocytes, Cas treatment decreased the Δψm and cyclosporine A treatment prevented mitochondrial depolarization. The production of H2O2 increased in Cas-treated mitochondria, which might also increase the oxidation of mitochondrial proteins such as adenine nucleotide translocase. In accordance, an antioxidant scavenger (Tiron) significantly diminished Cas IIIia mitochondrial depolarization. Cas induces a prominent loss of membrane potential, associated with alterations in redox state, which increases mPTP opening, potentially due to thiol-dependent modifications of the pore, suggesting that direct or indirect inhibition of mPTP opening might

  19. Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines.

    PubMed

    Walters, Denise K; Muff, Roman; Langsam, Bettina; Gruber, Philipp; Born, Walter; Fuchs, Bruno

    2007-08-01

    Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent. PMID:17458504

  20. Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection

    PubMed Central

    2013-01-01

    Background Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. Methods Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. Results At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased

  1. Hypolipidemic, anti-obesity, anti-inflammatory, anti-osteoporotic, and anti-neoplastic properties of amine carboxyboranes.

    PubMed Central

    Hall, I H; Chen, S Y; Rajendran, K G; Sood, A; Spielvogel, B F; Shih, J

    1994-01-01

    The amine-carboxyborane derivatives were shown to be effective antineoplastic/cytotoxic agents with selective activity against single-cell and solid tumors derived from murine and human leukemias, lymphomas, sarcomas, and carcinomas. The agents inhibited DNA and RNA synthesis in preference to protein synthesis in L1210 lymphoid leukemia cells. Inosine-monophosphate dehydrogenase apparently is a target site of the compounds; similar effects on phosphoribosyl-pyrophosphate amido transferase, orotidine-monophosphate decarboxylase, and both nucleoside and nucleotide kinases were observed. Deoxyribonucleotide pool levels were reduced in the cells; DNA strand scission was observed with the agents. In rodents, the amine carboxyboranes were potent hypolipidemic agents, lowering both serum cholesterol and triglyceride concentrations, in addition to lowering cholesterol content of very low-density lipoprotein and low-density lipoprotein (LDL) and elevating high-density lipoprotein (HDL) cholesterol concentrations. De novo regulatory enzymes involved in lipid synthesis were also inhibited (e.g., hypocholesterolemic 3-hydroxy-3-methyl-Coenzyme A reductase, acyl-Coenzyme A cholesterol acyltransferase, and sn-glycerol-3-phosphate acyltransferase). Concurrently, the agents modulated LDL and HDL receptor binding, internalization, and degradation, so that less cholesterol was delivered to the plaques and more broken down from esters and conducted to the liver for biliary excretion. Tissue lipids in the aorta wall of the rat were reduced and fewer atherosclerotic morphologic lesions were present in quail aortas after treatment with the agents. Cholesterol resorption from the rat intestine was reduced in the presence of drug. Genetic hyperlipidemic mice demonstrated the same types of reduction after treatment with the agents. The agents would effectively lower lipids in tissue based on the inhibition of regulatory enzymes in pigs. These findings should help improve domestic meat

  2. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  3. Correcting for bias in relative risk estimates due to exposure measurement error: a case study of occupational exposure to antineoplastics in pharmacists.

    PubMed Central

    Spiegelman, D; Valanis, B

    1998-01-01

    OBJECTIVES: This paper describes 2 statistical methods designed to correct for bias from exposure measurement error in point and interval estimates of relative risk. METHODS: The first method takes the usual point and interval estimates of the log relative risk obtained from logistic regression and corrects them for nondifferential measurement error using an exposure measurement error model estimated from validation data. The second, likelihood-based method fits an arbitrary measurement error model suitable for the data at hand and then derives the model for the outcome of interest. RESULTS: Data from Valanis and colleagues' study of the health effects of antineoplastics exposure among hospital pharmacists were used to estimate the prevalence ratio of fever in the previous 3 months from this exposure. For an interdecile increase in weekly number of drugs mixed, the prevalence ratio, adjusted for confounding, changed from 1.06 to 1.17 (95% confidence interval [CI] = 1.04, 1.26) after correction for exposure measurement error. CONCLUSIONS: Exposure measurement error is often an important source of bias in public health research. Methods are available to correct such biases. PMID:9518972

  4. Aptamers as targeting delivery devices or anti-cancer drugs for fighting tumors.

    PubMed

    Scaggiante, Bruna; Dapas, Barbara; Farra, Rossella; Grassi, Mario; Pozzato, Gabriele; Giansante, Carlo; Fiotti, Nicola; Tamai, Elisa; Tonon, Federica; Grassi, Gabriele

    2013-06-01

    Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials. In this review we update the findings about the use of aptamers as "escort" molecules able to drive drugs into the cells and as antineoplastic drugs. Current anti-neoplastic treatments suffer from the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemotherapies into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemotherapies. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use. PMID:23687927

  5. Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity.

    PubMed

    Chen, Chunying; Xing, Gengmei; Wang, Jiangxue; Zhao, Yuliang; Li, Bai; Tang, Jun; Jia, Guang; Wang, Tiancheng; Sun, Jin; Xing, Li; Yuan, Hui; Gao, Yuxi; Meng, Huan; Chen, Zhen; Zhao, Feng; Chai, Zhifang; Fang, Xiaohong

    2005-10-01

    [Gd@C82(OH)22]n particles (22 nm in a saline solution) of a dose level as low as 10(-7) mol/kg exhibit a very high antineoplastic efficiency ( approximately 60%) in mice. A dose increment of 1 x 10(-7) mol/kg increases the tumor inhibition rate 26%. [Gd@C82(OH)22]n particles have a strong capacity to improve immunity and interfere with tumor invasion in normal muscle cells, nearly without toxicity in vivo and in vitro. Unlike conventional antineoplastic chemicals, the high antitumor efficiency of nanoparticles is not due to toxic effects to cells because they do not kill the tumor cells directly and only about 0.05% of the used dose is found in the tumor tissues. Results suggest that fullerene derivatives with proper surface modifications and sizes may help realize the dream of tumor chemotherapeutics of high-efficacy and low-toxicity. PMID:16218736

  6. MAGE-A expression clusters and antineoplastic treatment in head and neck cancer.

    PubMed

    Hartmann, Stefan; Meyer, Till J; Brands, Roman C; Haubitz, Imme R; Linz, Christian; Seher, Axel; Kübler, Alexander C; Müller-Richter, Urs D A

    2015-06-01

    The nonsurgical treatment of head and neck squamous cell carcinoma (HNSCC) usually consists of radiation and chemotherapy. In general, the treatment efficacy of chemotherapy in head and neck cancer is limited. Apart from the placenta, testis and fetal keratinocytes, melanoma-associated antigens-A (MAGE-A) are only found in malignancies. Even though their molecular role remains unclear, several subgroups have been found to contribute to resistance to different chemotherapeutic agents. In the present study, established human squamous cell carcinoma cell lines were incubated with various concentrations of cisplatin, 5-fluorouracil, paclitaxel, docetaxel, cetuximab and panitumumab for 5, 10, 20 and 40 h. The treatment efficacy was measured dynamically by real-time cell analysis (RTCA). In addition, we determined the expression of all known MAGE-A subgroups (MAGE-A1 to MAGE-A12, excluding pseudogene MAGE-A7) by reverse transcription quantitative polymerase chain reaction. Of note, one cell line showed only a marginal expression of MAGE-A antigens, whereas another cell line showed a distinct expression of almost all the MAGE-A subgroups. The expression pattern varied in the other cell lines. MAGE-A4 was the most highly expressed of all the subgroups, and MAGE-A8 could not be detected. With the exception of MAGE-A6, -A8, -A9 and -A10, the expression levels differed significantly between the cell lines. Factor analysis suggested simplifying the MAGE-A expression level into two groups. Spearman's rank correlation revealed a significant association between MAGE-A expression and treatment efficacy for 20.8% (25/120) of the experiments. In 100% of these cases (25/25), Spearman's Rho revealed a positive correlation between clustered MAGE-A expression and poor treatment efficacy. Our data highlight the fact that higher a MAGE-A expression correlates with a poorer outcome of antineoplastic treatment. Clustered MAGE-A expression analysis may help to identify patients who are at a

  7. Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 expression in human breast carcinoma cells.

    PubMed

    Gagnon, Jacynthe; Shaker, Sepideh; Primeau, Mélanie; Hurtubise, Annie; Momparler, Richard L

    2003-03-01

    Genes that suppress tumorigenesis can be silenced by epigenetic events, such as aberrant DNA methylation and modification of chromatin structure. Inhibitors of DNA methylase and histone deacetylase (HDAC) can potentially reverse these events. The aim of this study was to determine the in vitro antineoplastic activity of 5-aza-2'-deoxycytidine (5-AZA-CdR), a potent inhibitor of DNA methylase, in combination with depsipeptide (depsi), an inhibitor of HDAC, on human breast carcinoma cells. We observed a synergistic antineoplastic interaction between 5-AZA-CdR and depsi in their capacity to inhibit colony formation of Hs578T and MCF-7 breast carcinoma cells. In order to understand the molecular mechanism of this interaction, we investigated the effect of these drugs on the activation of the 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 (TIMP3) cancer-related genes, which were reported to be silenced by aberrant methylation in many breast tumor cell lines. 14-3-3sigma was reported to produce G cell cycle arrest following DNA damage. E-cadherin and TIMP3 function as suppressors of tumor metastasis. Semi-quantitative RT-PCR was used to determine the effect of the co-administration of 5-AZA-CdR and depsi on four breast carcinoma cell lines for the reactivation of these genes. We observed a synergistic activation of E-cadherin by the combination in Hs578T, MDA-MB-231 and MDA-MB-435 tumor cells. For 14-3-3sigma, we demonstrated an additive to synergistic activation by the combination for Hs578T and MDA-MB-435 tumor cells, respectively. In the MCF-7 tumor cells, the drug combination produced a synergistic activation of TIMP3. The association between the synergistic antineoplastic activity and the synergistic activation of the target genes in this study suggests that the mechanism of anticancer activity of 5-AZA-CdR, in combination with depsi, is probably related to their enhanced activation of different types of tumor suppressor genes that have been

  8. Synthesis of N-methylarylnitrones derived from alkyloxybenzaldehydes and antineoplastic effect on human cancer cell lines.

    PubMed

    Costa, Débora S S; Martino, Thiago; Magalhães, Fernanda C; Justo, Graça; Coelho, Marsen G P; Barcellos, Julio C F; Moura, Victor B; Costa, Paulo R R; Sabino, Kátia C C; Dias, Ayres G

    2015-05-01

    New O-isoprenylated-N-methylarylnitrones derived from isomeric o, m and p-hydroxybenzaldehydes have been prepared and the antineoplastic effects on human cancer cell lines were evaluated. The O-geranylated nitrone LQB-278 (1b) and its isomers 2b and 3b inhibited the NO production, but the anti-leukemic activity was drastically dependent on nitrone isomer, with the 1b being the most effective one (IC₅₀ of 6.7 μM) on Jurkat leukemia cell, by MTT assay. In addition, 1b up-regulated p21CIP1/WAF1/Sdi1 protein expression (flow cytometry), a cell cycle inhibitor, reduced cell growth, and induced DNA fragmentation (increased sub-G1 phase cells) and phosphatidylserine externalization in plasmatic membrane (increased annexin V positive cells). Finally, the 1b up-regulation of p21 expression and apoptosis induction seem to be the mechanisms by which it promotes its anti-leukemic effects, making this new molecular architecture a promising prototype for leukemia intervention. PMID:25813896

  9. Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

    PubMed

    Dudek, Maxine C; Wong, Kaitlyn E; Bassa, Lotfi M; Mora, Maria Carmen; Ser-Dolansky, Jennifer; Henneberry, Jean M; Crisi, Giovanna M; Arenas, Richard B; Schneider, Sallie S

    2015-12-01

    Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin β1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma. PMID:26159852

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

    PubMed

    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. PMID:24269717

  11. New Trends on Antineoplastic Therapy Research: Bullfrog (Rana catesbeiana Shaw) Oil Nanostructured Systems.

    PubMed

    Amaral-Machado, Lucas; Xavier-Júnior, Francisco H; Rutckeviski, Renata; Morais, Andreza R V; Alencar, Éverton N; Dantas, Teresa R F; Cruz, Ana K M; Genre, Julieta; da Silva-Junior, Arnóbio A; Pedrosa, Matheus F F; Rocha, Hugo A O; Egito, Eryvaldo S T

    2016-01-01

    Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS). The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD) were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for normal fibroblast (3T3) and melanoma (B16F10) cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%). The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about -25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy. PMID:27144557

  12. Bryostatin 1, a novel antineoplastic agent and protein kinase C activator, induces human myalgia and muscle metabolic defects: a 31P magnetic resonance spectroscopic study.

    PubMed Central

    Hickman, P. F.; Kemp, G. J.; Thompson, C. H.; Salisbury, A. J.; Wade, K.; Harris, A. L.; Radda, G. K.

    1995-01-01

    Bryostatin 1, a novel antineoplastic agent and protein kinase C (PKC) activator, has been found to induce myalgia (muscle pain) 48 h after administration in clinical trials. This is the dose-limiting toxicity and has restricted the duration of therapy in phase I trials. To investigate the mechanisms and try to increase toleration of the drug, we studied calf muscle metabolism of 14 patients at rest and during exercise and subsequent recovery using 31P magnetic resonance spectroscopy (MRS) before and 4 h, 48-72 h and 1-2 weeks following bryostatin therapy. In resting muscle there was a significant (P < 0.001) increase in the phosphodiester/adenosine 5'-triphosphate (PDE/ATP) ratio 48 h post bryostatin and in patients with myalgia compared with pre-bryostatin control studies. Following exercise, patients with myalgia showed significantly slower phosphocreatine (PCr) and ADP recovery half-time (P < or = 0.05) suggesting impaired mitochondrial (oxidative) energy production, possibly due to a direct effect on the mitochondria or secondary to reduced blood flow. The apparent proton efflux rate following exercise was significantly reduced 4 h after bryostatin (P < or = 0.05), suggesting reduced blood flow. The rate of post-exercise reoxygenation was studied in four patients by near-infrared spectroscopy 4 h post bryostatin. In three of these the rate was reduced, consistent with reduced muscle blood flow. Bryostatin 1 appeared to cause a long-lasting impairment of oxidative metabolism and proton washout from muscle, consistent with a vasoconstrictive action. Thus these studies provide evidence for two mechanisms of the dose-limiting toxicity for bryostatin. Prospective studies on the use of vasodilators to improve the tolerance of the drug should be carried out. PMID:7547256

  13. Non-steroidal drug-induced glaucoma

    PubMed Central

    Razeghinejad, M R; Pro, M J; Katz, L J

    2011-01-01

    Numerous systemically used drugs are involved in drug-induced glaucoma. Most reported cases of non-steroidal drug-induced glaucoma are closed-angle glaucoma (CAG). Indeed, many routinely used drugs that have sympathomimetic or parasympatholytic properties can cause pupillary block CAG in individuals with narrow iridocorneal angle. The resulting acute glaucoma occurs much more commonly unilaterally and only rarely bilaterally. CAG secondary to sulfa drugs is a bilateral non-pupillary block type and is due to forward movement of iris–lens diaphragm, which occurs in individuals with narrow or open iridocorneal angle. A few agents, including antineoplastics, may induce open-angle glaucoma. In conclusion, the majority of cases with glaucoma secondary to non-steroidal medications are of the pupillary block closed-angle type and preventable if the at-risk patients are recognized and treated prophylactically. PMID:21637303

  14. Designer peptide antagonist of the leptin receptor with peripheral antineoplastic activity.

    PubMed

    Beccari, Serena; Kovalszky, Ilona; Wade, John D; Otvos, Laszlo; Surmacz, Eva

    2013-06-01

    The obesity hormone leptin has been implicated in the development and progression of different cancer types, and preclinical studies suggest that targeting leptin signaling could be a new therapeutic option for the treatment of cancer, especially in obese patients. To inhibit pro-neoplastic leptin activity, we developed leptin receptor (ObR) peptide antagonists capable of blocking leptin effects in vitro and in vivo. Our lead compound (Allo-aca), however, crosses the blood-brain-barrier (BBB), inducing undesirable orexigenic effects and consequent weight gain. Thus, redesigning Allo-aca to uncouple its central and peripheral activities should produce a superior compound for cancer treatment. The aim of this study was to generate novel Allo-aca analogs and test their biodistribution in vivo and anti-neoplastic activity in vitro in breast and colorectal cancer cells. Examination of several Allo-aca analogs resulted in the identification of the peptidomimetic, d-Ser, that distributed only in the periphery of experimental animals. d-Ser inhibited leptin-dependent-proliferation of ObR-positive breast and colorectal cancer cells in vitro at 1nM concentration without exhibiting any partial agonistic activity. d-Ser efficacy was demonstrated in monolayer and three-dimensional cultures, and its antiproliferative action was associated with the inhibition of several leptin-induced pathways, including JAK/STAT3, MAPK/ERK1/2 and PI3K/AKT, cyclin D1, and E-cadherin. In conclusion, d-Ser is the first leptin-based peptidomimetic featuring peripheral ObR antagonistic activity. The novel peptide may serve as a prototype to develop new therapeutics, particularly for the management of obesity-related cancers. PMID:23567149

  15. Synthesis and in vitro antineoplastic evaluation of silver nanoparticles mediated by Agrimoniae herba extract

    PubMed Central

    Qu, Ding; Sun, Wenjie; Chen, Yan; Zhou, Jing; Liu, Congyan

    2014-01-01

    A rapid synthesis of silver nanoparticles (AgNPs) using Agrimoniae herba extract as reducing agent and stabilizer (A. herba-conjugated AgNPs [AH-AgNPs]) were designed, characterized, and evaluated for antitumor therapy feasibility. In this study, critical factors in the preparation of silver nanoparticles, including extraction time, reaction temperature, the concentration of AgNO3, and A. herba extract amount, were investigated using ultraviolet-visible spectroscopy. AH-AgNPs with well-defined spherical shape, homogeneous distributional small size (30.34 nm), narrow polydispersity index (0.142), and high negative zeta potential (−36.8 mV) were observed by transmission electron microscopy and dynamic light scattering. Furthermore, the results of X-ray diffraction and Fourier-transform infrared spectroscopy further indicated successful preparation of AH-AgNPs. Acceptable long-term storage stability of AH-AgNPs was also confirmed. More importantly, AH-AgNPs displayed significantly higher antiproliferative effect against a human lung carcinoma cell line (A549 cells) compared with A. herba extract and bare AgNPs prepared by sodium citrate. The half-maximal inhibitory concentrations of AH-AgNPs, bare AgNPs, and A. herba extract were 38.13 μg · mL−1, 184.87 μg · mL−1, and 1.147 × 104 μg · mL−1, respectively. It is suggested that AH-AgNPs exhibit a strong antineoplastic effect on A549 cells, pointing to feasibility of antitumor treatment in the future. PMID:24790429

  16. One-Step Way to Form Prodrug Micelles with High Amount Drug Loading.

    PubMed

    Zhang, Jing; Wu, Dan; Feng, Jie

    2016-06-01

    Prodrug micelles with high amount drug loading were obtained via one-step way. Antineoplastic drug doxorubicin (DOX), used as hydrophobic tail, was conjugated to hydrophilic head mPEG via hydrazone bonds, allowing drug release under intracellular condition. Free DOX was loaded into the hydrophobic core of micelles during the conjugation step simultaneously. Total drug content of the prodrug micelles was up to 61.2%. Endocytosis experiments confirmed that the prodrug micelles achieved good cellular-uptake ability. In vitro experiments indicated that the prodrug micelles showed better therapy efficacy than free drug in cancerous cells. PMID:27427600

  17. [Latin-American plants as a source of new antineoplastic drugs, current situation and new opportunities against cancer].

    PubMed

    Orrego Escobar, Eduardo Freddy

    2015-01-01

    Cancer is one of the most relevant pandemics in modern world. There is a clear predominance of this pathology with distinct epidemiological characteristics in developing and developed countries. Effective, low-cost treatment and prophylaxis strategies that also have minimal side effects are needed. The present work is a brief revision of research that show the great therapeutic potential of plants, highlighting those carried out in Latin America with local plants considering that this is a yet incipient field of study. The great pool of organic compounds and other substances such as proteins indicate that they might provide a reliable alternative in the search for new actors in the battle against cancer. PMID:25918942

  18. Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation.

    PubMed

    Tabolacci, Claudio; Rossi, Stefania; Lentini, Alessandro; Provenzano, Bruno; Turcano, Lorenzo; Facchiano, Francesco; Beninati, Simone

    2013-01-01

    Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity. To improve the growth-inhibiting effect of anticancer agents, we found that the combined treatment of cells with aloin and low doses of cisplatin increases the antiproliferative activity of aloin. The results suggest that aloin possesses antineoplastic and antimetastatic properties, exerted likely through the induction of melanoma cell differentiation. PMID:22139409

  19. Effects on bone metabolism of new therapeutic strategies with standard chemotherapy and biologic drugs

    PubMed Central

    Ciolli, Stefania

    2013-01-01

    Summary Recent biological advances have provided the framework for novel therapeutic strategies in oncology. Many new treatments are now based on standard cytotoxic drugs plus biologic agents. In Multiple Myeloma, a plasma cell neoplasm characterized by a severe bone disease, biologic drugs such as proteasome inhibitors and immunomodulatory agents, above their antineoplastic efficacy have a beneficial effects on bone disease. Bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells into osteoblasts, resulting in new bone formation. Immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These data reflect the utility of targeting endogenous mesenchymal stem/progenitor cells for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:24554928

  20. Conformational analysis of antineoplastic antifolates: the crystal structure of trimetrexate and the aminopterine derivative 4-[N-[(2,4-diamino-6-pteridinyl)methyl]amino]benzoic acid.

    PubMed

    Sutton, P A; Cody, V

    1987-10-01

    The crystal structures of trimetrexate (TMQ) (2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoli ne) and 4-[N-[(2,4-diamino-6-pteridinyl)methyl]amino]benzoic acid (PMAB) were determined to examine their conformational features with respect to the enzyme-bound form of methotrexate (MTX). TMQ and MTX are antineoplastic drugs that act by inhibiting the enzyme dihydrofolate reductase. The molecular conformation of TMQ is extended with the trimethoxyanilino ring twisted 89 degrees from the quinazoline plane, and the molecular conformation of PMAB is completely planar. The geometry of the 2,4-diaminopteridine and 2,4-diaminoquinazoline rings are sensitive to protonation, and both TMQ and PMAB have geometries characteristic to a free base. TMQ crystallizes as a dimethyl sulfoxide hydrate. The quinazoline ring forms an antiparallel stacking arrangement in the lattice and forms a network of N...O hydrogen bonds with the solvent molecules. In PMAB there are both pteridine-benzoic acid (N...O) hydrogen bonds and pteridine-pteridine (N...N) hydrogen bonds. Although the molecular conformation of TMQ and PMAB differ from enzyme-bound MTX, rotational energy barriers calculated using CAMSEQ indicate that they can adopt a similar conformation to that seen for MTX complexed with dihydrofolate reductase. These energy calculations show that PMAB is quite flexible and further suggest that the 5-methyl in TMQ reduces its conformational flexibility in a different manner than the N(10)-methyl in MTX. These structural data also show that full geometry optimization and proper parameterization of electronic effects at N(10) are required to accurately represent antifolate conformational preferences for enzyme binding. PMID:2958629

  1. New Antimicrobial Approaches: Reuse of Old Drugs.

    PubMed

    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 antiinfective 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. PMID:26245476

  2. Drug Cocktail Optimization in Chemotherapy of Cancer

    PubMed Central

    Preissner, Saskia; Dunkel, Mathias; Hoffmann, Michael F.; Preissner, Sarah C.; Genov, Nikolai; Rong, Wen Wei; Preissner, Robert; Seeger, Karlheinz

    2012-01-01

    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. PMID:23236419

  3. Rapid, in vivo, evaluation of antiangiogenic and antineoplastic gene products by nonviral transfection of tumor cells.

    PubMed

    Weiss, Jonathan M; Shivakumar, Rama; Feller, Stephanie; Li, Lin-Hong; Hanson, Art; Fogler, William E; Fratantoni, Joseph C; Liu, Linda N

    2004-05-01

    Using a nonviral, electroporation-based gene transfection approach, we demonstrate the efficient and consistent transfection of two poorly immunogenic tumor cell lines: B16F10 melanoma and renal carcinoma (RENCA). Three genes, IL-12, angiostatin (AS), and an endostatin:angiostatin fusion protein (ES:AS) were subcloned into a DNA plasmid containing EBNA1-OriP, which was then transfected into B16F10 and RENCA cells. Significant levels of protein were secreted into the culture supernatants of transfected cells in vitro. Transfected tumor cells were injected subcutaneously into mice. All the three transgenes were capable of significantly delaying and reducing the formation of primary B16F10 and RENCA tumors, as well as B16F10 lung metastases. By day 11 post-injection, all control mice that received either mock-transfected or empty vector DNA-transfected B16F10 tumor cells had developed large primary tumors. In contrast, mice that received IL-12-transfected B16F10 cells did not develop appreciable tumors until day 17, and these were significantly smaller than controls. Similar results were observed for the RENCA model, in which only one of the IL-12 mice had developed tumors out to day 31. Expression of AS or ES:AS also significantly delayed and reduced primary tumors. Overall, ES:AS was more effective than AS alone. Furthermore, 25% of the AS mice and 33% of the ES:AS mice remained tumor-free at day 17, by which point all control mice had significant tumors. Mouse survival rates also correlated with the extent of tumor burden. Importantly, no lung metastases were detected in the lungs of mice that had received either AS or ES:AS-transfected B16F10 tumor cells and significantly fewer metastases were found in the IL-12 group. The consistency of our transfection results highlight the feasibility of directly electroporating tumor cells as a means to screen, identify, and validate in vivo potentially novel antiangiogenic and/or antineoplastic genes. PMID:15031722

  4. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.

    PubMed

    Zaccara, Gaetano; Perucca, Emilio

    2014-12-01

    Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P-glycoprotein) and can reduce the efficacy of co-administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of

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

    PubMed

    Severin, Gregory W; Nielsen, Carsten H; Jensen, Andreas I; Fonslet, Jesper; Kjær, Andreas; Zhuravlev, Fedor

    2015-09-24

    We present a novel solid-phase based (45)Ti radiolabeling methodology and the implementation of (45)Ti-PET in titanium-based antineoplastics using the showcase compound [(45)Ti](salan)Ti(dipic). This development is intended to allow elucidation of the biodistribution and pharmacokinetics of promising new Ti-based therapeutics. PMID:26312993

  6. Antineoplastic Agents 454. Synthesis of the Strong Cancer Cell Growth Inhibitors trans-Dihydronarciclasine and 7-Deoxy-trans-dihydronarciclasine1a

    PubMed Central

    Pettit, George R.; Ducki, Sylvie; Eastham, Stephen A.; Melody, Noeleen

    2009-01-01

    To further pursue the antineoplastic leads offered by our isolation of trans-dihydronarciclasine (1a) and 7-deoxy-trans-dihydronarciclasine (1c) from two medicinal plant species of the Amaryllidaceae family, a practical palladium-catalyzed hydrogenation procedure was developed for synthesis of these isocarbostyrils from narciclasine (2a) and 7-deoxynarciclasine (2c). PMID:19522518

  7. Antineoplastic agents LXIV: 1,4-Bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1]heptane dihydrogen dimaleate.

    PubMed

    Pettit, G R; Gieschen, D P; Pettit, W E

    1979-12-01

    The 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1]heptane dication (II) exhibits remarkable antineoplastic activity. Detailed evaluation of several dianion derivatives showed a curative response level against the murine P-388 lymphocytic leukemia, colon 26, CD8F1 mammary, and the Walker 256 carcinosarcoma (rat) tumor systems. In addition, significant cancer chemotherapeutic activity was found against the murine L-1210 lymphoid leukemia, colon 38, and B16 melanocarcinoma tumor systems. The bicyclo dication (II) first was isolated, evaluated, and stored as the diperchlorate derivative (IIa). Because of the promising anticancer activity of IIa, procedures were developed for obtaining other anion derivatives for comparative biological purposes. Several naturally occurring substances were evaluated, and the dihydrogen dimaleate derivative (IIi) obtained by an ion-exchange technique was the most suitable. PMID:529047

  8. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines

    PubMed Central

    Ishiguro, Kimiko; Zhu, Yong-Lian; Lin, Z. Ping; Penketh, Philip G.; Shyam, Krishnamurthy; Zhu, Rui; Baumann, Raymond P.; Sartorelli, Alan C.; Rutherford, Thomas J.; Ratner, Elena S.

    2016-01-01

    Although epithelial ovarian cancers (EOCs) are initially treated with platinum-based chemotherapy, EOCs vary in platinum responsiveness. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive EOC cell lines is valuable for development of therapeutic strategies to avoid platinum inefficacy and to exploit platinum sensitivity. TOV-21G devoid of FANCF expression, OV-90 and SKOV-3 were employed as examples of platinum-sensitive, platinum-intermediate and platinum-resistant cell lines, respectively. Antineoplastic agents examined included mitomycin C, doxorubicin, etoposide, gemcitabine, chlorambucil, paclitaxel, triapine and X-rays. Their effectiveness against cell lines was analyzed by clonogenic assays. Cytotoxic profiles of mitomycin C and carboplatin were similar, with mitomycin C exhibiting greater potency and selectivity against TOV-21G than carboplatin. Cytotoxic profiles of doxorubicin, etoposide and X-rays overlapped with that of carboplatin, while OV-90 overexpressing Rad51 was more resistant to chlorambucil than SKOV-3. The efficacy of paclitaxel and triapine was independent of platinum sensitivity or resistance. Consistent with these cytotoxic profiles, cisplatin/mitomycin C, triapine, and paclitaxel differed in the capacity to induce phosphorylation of H2AX, and produced unique inhibitory patterns of DNA/RNA syntheses in HL-60 human leukemia cells. Paclitaxel and triapine in combination produced additive antitumor effects in M109 murine lung carcinoma. In conclusion, mitomycin C is potentially more effective against Fanconi anemia pathway-deficient EOCs than carboplatin. Doxorubicin and etoposide, because of their overlapping cytotoxic properties with carboplatin, are unlikely to be efficacious against platinum-refractory EOCs. Paclitaxel and triapine are effective regardless of platinum sensitivity status, and promising in combination for both platinum-sensitive and platinum-refractory EOCs

  9. New antineoplastic agent, MK615, from UME (a Variety of) Japanese apricot inhibits growth of breast cancer cells in vitro.

    PubMed

    Nakagawa, Aya; Sawada, Tokihiko; Okada, Toshie; Ohsawa, Tatsushi; Adachi, Masakazu; Kubota, Keiichi

    2007-01-01

    MK615 is an extract mixture containing hydrophobic substances from Japanese apricot. In this study, the antineoplastic effects of MK615 against breast cancer cells were investigated. Two breast cancer cell lines, MDA-MB-468 (MDA) and MCF7, were cultured with (600, 300, and 150 mug/mL) or without MK615. After 72 hours of incubation, growth inhibition was evaluated by MTT assay. The cells were then cultured with MK615 (300 mug/mL) and morphological changes were studied by light and electron microscopy. Finally, the mechanism of the antineoplastic effect of MK615 was evaluated by cell cycle and apoptosis assay. MK615 inhibited the growth of MDA and MCF7 in a dose-dependent manner. The percentage growth inhibition of MDA at dosages of 600, 300, and 150 mug/mL was 59.2%, 52.4%, and 23.3%, respectively, and that for MCF7 was 83.5%, 52.7%, and 16.6%, respectively. Morphological changes after MK615 treatment included massive vacuolization in the cytoplasm and apoptotic changes in the nucleus. These changes began to be apparent after at least 6 hours of incubation. Cell cycle analysis showed that MK615 increased the proportion of cells in the G2-M phase in both MDA (7.8-11.7%) and MCF7 (8.1-18.7%), and finally both cell lines became apoptotic. The proportion of apoptotic cells increased with incubation time. MK615 effectively inhibits the growth of breast cancer cells in vitro, possibly by cell cycle modification and apotosis induction. MK615 should be further investigated as a promising anti-breast cancer agent. PMID:17214792

  10. Metformin, an Adjunct Antineoplastic Therapy, Divergently Modulates Tumor Metabolism and Proliferation, Interfering with Early Response Prediction Using 18F-FDG PET Imaging

    PubMed Central

    Habibollahi, Peiman; van den Berg, Nynke S.; Kuruppu, Darshini; Loda, Massimo; Mahmood, Umar

    2013-01-01

    Over the last several years epidemiological data has emerged which suggests that the anti-diabetic drug metformin (MET), an AMP-activated protein kinase (AMPK) activator, improves progression free survival in multiple cancers; more than 30 clinical trials are underway to confirm this finding. We postulated that the role of AMPK as a central cellular energy sensor would result in opposite effects on glucose uptake and proliferation, suggesting different roles for 18F-FDG and 18F-FLT in assessing its effectiveness as an anti-neoplastic agent. Methods Colon cancer cell lines HT29 (human) and MC26 (murine) were treated for 24 or 72hrs with a range of MET (0–10mM). Western blotting was used to study the activation of AMPK after MET treatment. Glucose uptake and cell proliferation were measured by cell retention studies with either 18F-FDG or 18F-FLT. EdU (a thymidine analogue) and Annexin-Propidium Iodine flow cytometry were performed to determine cell cycle S-phase and apoptotic changes. In vivo 18F-FDG and 18F-FLT PET images were acquired before and 24hrs after MET treatment on HT29 tumor bearing mice. Results After 24hrs of MET incubation, phosphorylated AMPK increased several fold in both cell lines while total AMPK was unchanged. In cell retention studies, 18F-FDG uptake increased whereas 18F-FLT retention decreased significantly in both cell lines. Cells in S-phase decreased 36% in HT29 and 33% in MC26 cells following MET therapy. Apoptosis increased 10.5× and 5.8×, in HT29 and MC26 cells, respectively after 72hrs of incubation with MET. PET imaging showed increased 18F-FDG uptake (mean SUV: 0.71±0.03 and 1.29±0.11 pre and post MET therapy, p<0.05) and decreased 18F-FLT uptake (mean SUV: 1.18±0.05 and 0.89±0.01 pre and post MET therapy, p<0.05) in HT29 tumor bearing mice. Conclusion MET, through activation of the AMPK pathway, exerts a dose dependent increase in tumor glucose uptake while decreasing cell proliferation in human and murine colon cancer cells

  11. Antiplatelet drugs induce apoptosis in cultured cancer cells.

    PubMed

    Chen, W H; Yin, H L; Chang, Y Y; Lan, M Y; Hsu, H Y; Liu, J S

    1997-10-01

    In order to understand if antiplatelet drugs possess direct antineoplastic property, we tested the apoptotic effect of 5 popularly marketed antiplatelet drugs in Taiwan in 6 cultured cancer cell lines (Hep 3B hepatocarcinoma, U87-MG malignant glioma, PC-3 prostate adenocarcinoma, HeLa cervical adenocarcinoma, HL-60 preleukemia and K-562 chronic myelogenous leukemia). While acetylsalicylate and flunarizine exerted no effect on these cancer cells, pentoxifyline (PTX), dipyridamole (DYA) and ticlopidine hydrochloride (T. HCl) displayed a time and dose-dependent apoptotic effect on them except for HL-60 and K-562 cells. PTX induced apoptosis in U87-MG, Hep 3B and HeLa cells, DYA in HeLa cells, while T. HCl in U87-MG, Hep 3B, PC-3 and HeLa cells. Adriamycin also provoked apoptotic effect in all 6 cell lines but neither PTX, DYA nor T. HCl acted synergy with adriamycin to HeLa cells, implicating that they may share a similar pathway for inducing apoptosis. Therefore, our results show that the antiplatelet drugs do possess antineoplastic property in vitro. A co-administration of antiplatelet drugs is noteworthy for an alternative adjunctive therapy in cancer patients. PMID:9385774

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

    PubMed Central

    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

  13. Preclinical evaluation of antineoplastic activity of inhibitors of DNA methylation (5-aza-2'-deoxycytidine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemic cells.

    PubMed

    Shaker, Sepideh; Bernstein, Mark; Momparler, Louise F; Momparler, Richard L

    2003-05-01

    During the development of leukemia, genes that suppress growth and induce differentiation can be silenced by aberrant DNA methylation and by changes in chromatin structure that involve histone deacetylation. It has been reported that a positive interaction between DNA methylation and histone deacetylation takes place to inhibit transcription. Based on this observation, our working hypothesis was that a combination of inhibitors of these processes should produce an enhancement of their antineoplastic activity on leukemic cells. The cytosine nucleoside analog, 5-aza-2'-deoxycytidine (5AZA), is a potent inhibitor of DNA methylation, which can activate tumor suppressor genes in leukemic cells that have been silenced by aberrant methylation. In clinical trials, 5AZA was demonstrated to be an active antileukemic agent. Histone deacetylase inhibitors (HDI) can also activate gene expression in leukemic cell lines by producing changes in chromatin configuration, and show antineoplastic activity in preclinical studies. In this report, we investigated the in vitro antineoplastic activity of 5AZA, alone and in combination with the HDI, trichostatin A (TSA) and depsipeptide (FR901228, depsi), on the human myeloid leukemic cell lines, HL-60 and KG1a. The results showed that the combination of 5AZA with TSA or depsi produced a greater inhibition of growth and DNA synthesis and a greater loss of clonogenicity than either agent alone. These results suggest that 5AZA used in combination with HDI may be an interesting chemotherapeutic regimen to investigate in patients with acute myeloid leukemia that is resistant to conventional chemotherapy. PMID:12620295

  14. 5-Azacytidine and 5-aza-2'-deoxycytidine behave as different antineoplastic agents in B16 melanoma.

    PubMed Central

    Cortvrindt, R.; Bernheim, J.; Buyssens, N.; Roobol, K.

    1987-01-01

    The antiproliferative effects of 5-azacytidine (acaCyd) and 5-aza-2'-deoxycytidine (azadCyd) were studied in murine B16 melanoma and a series of B16 melanoma derived mutant strains with selective resistances to the respective drugs. The in vitro cytotoxicities of azaCyd and azadCyd on B16 wild type, expressed in terms of IC50 values, were found to be 5 microM and 0.2 microM, respectively. The in vitro cytotoxicity of both drugs was dependent on the duration of exposure. Uridine and cytidine were able to reverse the in vitro cytotoxicity of azaCyd, but not of azadCyd. Conversely, 2'-deoxycytidine was able to reverse the cytotoxic effect of azadCyd but not of azaCyd. Thymidine and 2'-deoxyuridine had no detectable effects on the in vitro cytotoxicity of either azaCyd or azadCyd. B16 melanoma mutant strains that were selected for resistance to azaCyd showed no cross-resistance to azadCyd, cytosine arabinoside or the fluorinated pyrimidine analogues FUrd, FCyd, FdUrd and FdCyd. Mutant strains that were selected for resistance to azadCyd showed no cross-resistance to azaCyd or fluorinated pyrimidine analogs, but only to cytosine arabinoside. The combined data suggest that azaCyd and azadCyd follow different routes of intracellular metabolic activation and exert their cytotoxic activity via different intracellular targets. PMID:2444244

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

    SciTech Connect

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

    2011-10-22

    Highlights: {yields} ConA induces cancer cell death targeting apoptosis and autophagy. {yields} ConA inhibits cancer cell angiogenesis. {yields} ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca{sup 2+}/Mn{sup 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-{kappa}B-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.

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

    PubMed Central

    Carranza-Torres, Irma Edith; Guzmán-Delgado, Nancy Elena; Coronado-Martínez, Consuelo; Bañuelos-García, José Inocente; Viveros-Valdez, Ezequiel; Morán-Martínez, Javier; Carranza-Rosales, Pilar

    2015-01-01

    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. PMID:26075250

  17. Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo.

    PubMed

    Algire, C; Amrein, L; Bazile, M; David, S; Zakikhani, M; Pollak, M

    2011-03-10

    Hypothesis-generating epidemiological research has suggested that cancer burden is reduced in diabetics treated with metformin and experimental work has raised questions regarding the role of direct adenosine monophosphate-activated protein kinase (AMPK)-mediated anti-neoplastic effects of metformin as compared with indirect effects attributable to reductions in circulating insulin levels in the host. We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor. Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin. These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1. PMID:21102522

  18. Drug-induced immune hemolytic anemia associated with albumin-bound paclitaxel.

    PubMed

    Thomas, Roby; Shillingburg, Alexandra

    2015-08-01

    Drug-induced immune hemolytic anemia (DIIHA) is rare, with only 1 patient in 1 million affected by the condition.1 Garratty identified 125 drugs indicated in DIIHA of which 11% were antineoplastic agents, and neither paclitaxel nor albumin-bound paclitaxel were included.2 In addition, we did not find any reports in our own search of the literature. Taxanes are known to cause anemia as a result of their myelosuppressive effects, but an immune hemolysis is rare. To our knowledge, we present here the first case of DIIHA with nab-paclitaxel. PMID:26859672

  19. [Contribution of antineoplastic biotherapy in the treatment of leukemia in children].

    PubMed

    Rousseau, R; Bollard, C; Heslop, H

    2002-03-01

    Improvements in the chemotherapeutic and transplant regimens have had a significant impact in improving survival rates for pediatric leukemia. However, there are still major problems to address including what options are available for patients with chemoresistant disease and what strategies are available to avoid toxicity associated with highly cytotoxic treatment regimens. Gene and immunotherapy protocols hold great promise. Using gene transfer of a marker gene, a number of biologic issues in the therapy of leukemia have been addressed. For example, by gene marking autologous bone marrow grafts it has been possible to demonstrate that infused marrow contributes to relapse in acute and chronic myeloid leukemias. In the allogeneic transplant setting, genetically modified T-cells have proven valuable for the prophylaxis and treatment of viral diseases and may have an important role in preventing or treating disease relapse. Gene transfer is also being used to modify tumor function, enhance immunogenicity, and confer drug-resistance to normal hematopoietic stem cells. With the continued scientific advancements in this field, gene therapy will almost certainly have a major impact on the treatment of pediatric leukemia in the future. PMID:11938542

  20. An insight into purine, tyrosine and tryptophan derived marine antineoplastic alkaloids.

    PubMed

    Palkar, Mahesh B; Rane, Rajesh A; Thapliyal, Neeta; Shaikh, Mahamadhanif S; Alwan, Wesam S; Jain, Kavita S; Karunanidhi, Sivanandhan; Patel, Harun M; Hampannavar, Girish A; Karpoormath, Rajshekhar

    2015-01-01

    There is an ever-increasing need for the development of new drugs with safe and improved profile for the treatment of cancer. From time immemorial, nature has been considered as an abundant source of medicinal compounds having therapeutic properties. An enormous chemical diversity is present in thousands and millions of species of microorganisms, marine organisms, plants and animals that can act as potential therapeutic agents against various types of human cancer. Literature survey revealed that many alkaloids isolated from marine cyanobacteria, fungi, algae, sponges and tunicates displayed a wide range of anticancer properties like antiproliferative, antiangiogenic, induction of apoptosis, promoting cytotoxicity by inhibition of topoisomerase activities and tubulin polymerization. In this context, bastadins derived from tyrosine-based alkaloids have been reported as one the important class of anticancer agents. In particular bastadin 6 (24), seems to be a promising natural lead compound for the development of marine natural product-based anticancer therapeutic agents. This review mainly highlights the pharmacologically active scaffolds like purine, tyrosine and tryptophan containing marine alkaloids that exhibit biological activity, including anti-angiogenesis, cytotoxicity and anticancer activity. PMID:25553433

  1. Antineoplastic activity of ouabain and pyrithione zinc in acute myeloid leukemia.

    PubMed

    Tailler, M; Senovilla, L; Lainey, E; Thépot, S; Métivier, D; Sébert, M; Baud, V; Billot, K; Fenaux, P; Galluzzi, L; Boehrer, S; Kroemer, G; Kepp, O

    2012-07-26

    Despite recent progress in the treatment of acute myeloid leukemia (AML), the prognosis of this rather heterogeneous disease remains poor and novel chemotherapeutics that specifically target leukemic cells must be developed. To address this need at the preclinical level, we implemented a high content imaging-based screen for the identification of small agents that induce AML cell death in vitro. Among a panel of 1040 Food and Drug Administration-approved agents, we identified pyrithione zinc (PZ) and ouabain (OUA) as potential antileukemic compounds. Both PZ and OUA efficiently induced cell death associated with apoptotic chromatin condensation and inhibition of nuclear factor-κB survival signaling, leading to reduced expression of antiapoptotic proteins, in several AML cell lines. PZ- and OUA-induced cell death was associated with the permeabilization of the outer mitochondrial membrane and led to the release of cytochrome c followed by caspase activation. Both PZ and OUA exerted significant anticancer effects in vivo, on human AML cells xenografts as well as ex vivo, on CD34(+) (but not CD34(-)) malignant myeloblasts from AML patients. Altogether, our results suggest that PZ and OUA may exhibit antileukemic effects by inducing the apoptotic demise of AML cells. PMID:22105358

  2. Antineoplastic Treatment and Renal Injury: An Update on Renal Pathology Due to Cytotoxic and Targeted Therapies.

    PubMed

    Troxell, Megan L; Higgins, John P; Kambham, Neeraja

    2016-09-01

    Cancer patients experience kidney injury from multiple sources, including the tumor itself, diagnostic procedures, hypovolemia, infection, and drug exposure, superimposed upon baseline chronic damage. This review will focus on cytotoxic or targeted chemotherapy-associated renal injury. In this setting, tubulointerstitial injury and thrombotic microangiopathy (vascular injury) are more common than other forms of kidney injury including glomerular. Cisplatin, pemetrexed, and ifosfamide are well-known causes of acute tubular injury/necrosis. Acute interstitial nephritis seems underrecognized in this clinical setting. Interstitial nephritis is emerging as an "immune-related adverse effect" (irAE's) with immune checkpoint inhibitors in small numbers of patients. Acute kidney injury is rarely reported with targeted therapies such as BRAF inhibitors (vemurafinib, dabrafenib), ALK inhibitors (crizotinib), and mTOR inhibitors (everolimus, temsirolimus), but additional biopsy data are needed. Tyrosine kinase inhibitors and monoclonal antibodies that block the vascular endothelial growth factor pathway are most commonly associated with thrombotic microangiopathy. Other causes of thrombotic microangiopathy in the cancer patients include cytotoxic chemotherapies such as gemcitabine and mitomycin C, hematopoietic stem cell transplant, and cancer itself (usually high-stage adenocarcinoma with marrow and vascular invasion). Cancer patients are historically underbiopsied, but biopsy can reveal type, acuity, and chronicity of renal injury, and facilitate decisions concerning continuation of chemotherapy and/or initiation of renoprotective therapy. Biopsy may also reveal unrelated and unanticipated findings in need of treatment. PMID:27403615

  3. An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents.

    PubMed

    Lazarus, H M; Imperia, P S; Botti, R E; Mack, R J; Lass, J H

    1989-01-01

    We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation. Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment. 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated. Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M). A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M. We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside. Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes. Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic. Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%). Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic. Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system. These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies. Our model may be useful in the toxicologic study of future topical

  4. NVX-412, a New Oncology Drug Candidate, Induces S-Phase Arrest and DNA Damage in Cancer Cells in a p53-Independent Manner

    PubMed Central

    Hebar, Alexandra; Rütgen, Barbara C.; Selzer, Edgar

    2012-01-01

    The new molecular entity quinoxalinhydrazide derivative NVX-412 was identified as a promising drug candidate for the treatment of various cancer types due to its strong cytotoxic activity and relative specificity. Here, we provide first data about the mechanisms of action of NVX-412. We show that NVX-412 exerts its anti-neoplastic activity in a p53-independent manner and induces S-phase arrest and DNA damage as assessed by γH2AX staining. We suggest a bi-modal (dose-dependent) mode of action of NVX-412, being primarily cytostatic at lower and predominantly cytotoxic at higher concentrations. Based on the broad and consistent anti-neoplastic activity observed, NVX-412 holds promise as an effective drug candidate for the treatment of various cancer types, especially for hematological malignancies with highly unmet medical need. PMID:23028738

  5. HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK

    PubMed Central

    Gschwantler-Kaulich, Daphne; Grunt, Thomas W.; Muhr, Daniela; Wagner, Renate; Kölbl, Heinz; Singer, Christian F.

    2016-01-01

    Background HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. Methods Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively. Results All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. Conclusion We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines. PMID:26735495

  6. Antiepileptic Drug Interactions - Principles and Clinical Implications

    PubMed Central

    Johannessen, Svein I; Landmark, Cecilie Johannessen

    2010-01-01

    Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict

  7. Pharmacodynamics of drug-induced weight gain.

    PubMed

    Kulkarni, S. K.; Kaur, Gurpreet

    2001-08-01

    Body weight gain during treatment with drugs for any kind of disease may represent improvement of the disease itself. However, sometimes these drug-induced alterations of the body's appetite-regulating mechanisms result in excessive weight gain, thus jeopardizing compliance with prescribed medication. A number of drugs are capable of changing body weight as an adverse consequence of their therapeutic effect. Included in this category are the psychotropic drugs such as antipsychotics, antidepressants and mood stabilizers. Antipsychotics are well-known culprits of weight gain. The low-potency (e.g., chlorpromazine and thioridazine) and atypical agents (e.g., clozapine, olanzapine, quetiapine and risperidone) are most often associated with weight gain. Antidepressants such as tricyclic antidepressants and monoamine oxidase (MAO) inhibitors are most often associated with significant weight gain. The tertiary tricyclic antidepressant amitriptyline is thought to induce the most weight gain. Mood stabilizers such as lithium carbonate, valproic acid and carbamazepine also induce weight gain in a considerable number of patients. Treatment with corticosteroids is associated with dose-dependent body weight gain in many patients and corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases body weight. Finally, sulfonylurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause body weight gain as well. (c) 2001 Prous Science. All rights reserved. PMID:12743638

  8. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  9. MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

    PubMed

    Mao, Jenny T; Xue, Bingye; Smoake, Jane; Lu, Qing-Yi; Park, Heesung; Henning, Susanne M; Burns, Windie; Bernabei, Alvise; Elashoff, David; Serio, Kenneth J; Massie, Larry

    2016-08-01

    Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer. PMID:27289489

  10. Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics.

    PubMed

    Winkler, Gian C; Barle, Ester Lovsin; Galati, Giuseppe; Kluwe, William M

    2014-10-01

    There is no nationally or internationally binding definition of the term "cytotoxic drug" although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term "cytotoxic drug" is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly - including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term "cytotoxic drugs" in current regulations, it is expected that its use will continue for the near future. PMID:24956585

  11. Environmental and biological monitoring of platinum-containing drugs in two hospital pharmacies using positive air pressure isolators.

    PubMed

    Kopp, Bettina; Crauste-Manciet, Sylvie; Guibert, Agnès; Mourier, Wilhelmine; Guerrault-Moro, Marie-Noelle; Ferrari, Sylvie; Jomier, Jean-Yves; Brossard, Denis; Schierl, Rudolf

    2013-04-01

    Environmental and biological monitoring of platinum containing drugs was implemented in two French hospital pharmacies using positive air pressure isolators and having similar working procedures when preparing antineoplastic drugs. Wipe sampling of surfaces, gloves, and vials was performed in the preparation room and in storage areas. All employees involved in the preparation of antineoplastic drugs were tested for urinary platinum on Monday before work and Friday after shift. Only traces of platinum were detected on surfaces in the preparation room outside the isolators (less than 1.61 pg cm(-2)). However, in one center, significant contamination was found in the storage area of the drug vials, which can most likely be linked to the rupture of a platinum vial and due to inefficient cleaning procedures. Surfaces inside the isolators were found to be contaminated (maximum: 198.4 pg cm(-2)). A higher level of contamination was detected in one pharmacy and could be explained by the lack of overgloving with regular changes during the preparation process. Nitrile gloves used during drug handling outside the isolator showed the highest platinum concentration (maximum: 5.86 ng per pair). With regards to platinum urine concentration, no significant difference was found between exposed and unexposed pharmacy personnel. Isolator technology combined with individual protective measures seems to be efficient to protect workers from occupational exposure to antineoplastic drugs, whereas specific individual protective procedures implemented were focussing on the risk of handling vials outside the isolator (e.g. high frequency of glove changing). Moreover, overgloving inside the isolator would contribute to substantially decrease inner surface contamination and should be recommended in order to limit the transfer of chemical contamination to the end products. PMID:23091112

  12. Drug allergies

    MedlinePlus

    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 ...

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

    PubMed Central

    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

  14. Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells

    PubMed Central

    Hurtubise, Annie; Bernstein, Mark L; Momparler, Richard L

    2008-01-01

    Background Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetylation, silence the expression of tumor suppressor genes (TSGs) and play an important role in tumorigenesis. These epigenetic changes can be reversed by using 5-aza-2'-deoxycytidine (5AZA-CdR), a potent inhibitor of DNA methylation, in combination with an inhibitor of histone deacetylase (HDAC). Results Here, we used a clonogenic assay to evaluate the in vitro antineoplastic activity of 5AZA-CdR in combination with different HDAC inhibitors on EWS cells. We observed that the HDAC inhibitors, MS-275, trichostatin-A, phenylbutyrate, LAQ824 and depsipeptide, enhanced the antineoplastic action of 5AZA-CdR on EWS cells. The combination of 5AZA-CdR and MS-275 showed marked synergy, and was correlated with significant reactivation of the expression of two TSGs, E-cadherin and tumor suppressor lung cancer-1 (TSLC1), in a EWS cell line. Conclusion These results suggest the value of future clinical studies investigating the combination of 5AZA-CdR and MS-275 in patients with advanced EWS. PMID:19014694

  15. Pharmacokinetics and Drug Dosing in Obese Children

    PubMed Central

    Kendrick, Jennifer G.; Carr, Roxane R.; Ensom, Mary H.H.

    2010-01-01

    OBJECTIVES To review pharmacokinetics in obese children and to provide medication dosing recommendations. METHODS EMBASE, MEDLINE, and International Pharmaceutical Abstracts databases were searched using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney function test, creatinine, pediatric, and child. RESULTS We identified 10 studies in which the authors examined drug dosing or pharmacokinetics for obese children. No information was found for drug absorption or metabolism. Obese children have a higher percent fat mass and a lower percent lean mass compared with normal-weight children. Therefore, in obese children, the volume of distribution of lipophilic drugs is most likely higher, and that of hydrophilic drugs is most likely lower, than in normal-weight children. Serum creatinine concentrations are higher in obese than normal-weight children. Total body weight is an appropriate size descriptor for calculating doses of antineoplastics, cefazolin, and succinylcholine in obese children. Initial tobramycin doses may be determined using an adjusted body weight, although using total body weight in the context of monitoring serum tobramycin concentrations would also be an appropriate strategy. We found no information for any of the opioids; antibiotics such as penicillins, carbapenems, vancomycin, and linezolid; antifungals; cardiac drugs such as digoxin and amiodarone; corticosteroids; benzodiazepines; and anticonvulsants. In particular, we found no information about medications that are widely distributed to adipose tissue or that can accumulate there. CONCLUSIONS The available data are limited because of the small numbers of participating children, study design, or both. The number and type of drugs that have been studied limit our understanding of the pharmacokinetics in obese children. In the absence of dosing information for obese children, it is important to consider the nature and severity of a child's illness

  16. Pharmacogenomic information in drug labels: European Medicines Agency perspective.

    PubMed

    Ehmann, F; Caneva, L; Prasad, K; Paulmichl, M; Maliepaard, M; Llerena, A; Ingelman-Sundberg, M; Papaluca-Amati, M

    2015-06-01

    Pharmacogenomics (PGx) has a growing impact on healthcare and constitutes one of the major pillars of personalised medicine. For the purpose of improved individualised drug treatment, there is an increasing effort to develop drugs suitable for specific subpopulations and to incorporate pharmacogenomic drug labels in existing and novel medicines. Here, we review the pharmacogenomic drug labels of all 517 medicinal products centrally approved in the European Union (EU) since the establishment of the European Medicines Agency in 1995. We identified all pharmacogenomic-related information mentioned in the product labels and classified it according to its main effect and function on drug treatment, that is, metabolism, transport and pharmacodynamics, and according to the place of the respective section of the Summary of Product Characteristics (SmPC). The labels are preferentially present in drugs having antineoplastic properties. We find that the number of drugs with pharmacogenomic labels in EU increases now steadily and that it will be an important task for the future to refine the legislation on how this information should be utilised for improvement of drug therapy. PMID:25707393

  17. Drug-Induced Ocular Hypertension and Angle-Closure Glaucoma.

    PubMed

    Badhu, Badri P; Bhattarai, Balkrishna; Sangraula, Himal P

    2013-01-01

    The objective of this study was to review the available literature on the drugs causing ocular hypertension and glaucoma. Electronic literature search was carried out using the Web sites www.pubmed.gov and www.google.com published through the year 2011. The search words were "drug induced ocular hypertension" and "drug induced glaucoma" used in combination. The articles published or translated into English were studied. Quite a significant number of drugs commonly prescribed by various physicians of different specialties can induce ocular hypertension or glaucoma. A brief account of various drugs that can induce ocular hypertension has been given in this article. Those drugs are parasympatholytics; steroids; anticholinergics, adrenergics, and antidepressants; cholinomimetics; antineoplastic agents; antipsychotic and antiparkinsonism agents; H1 and H2 receptor blockers; botulinum toxin, cardiac agents, and anticoagulants; silicone oil; sulfa drugs; and anesthetic agents. Rational use of these drugs and knowledge of their potential adverse effects can help prevent the devastating complications resulting in loss of vision and compromised quality of life. PMID:26108110

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

    PubMed

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

    2016-01-01

    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. PMID:27229857

  19. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... Adverse reactions to drugs are common. (adverse means unwanted or unexpected.) Almost any drug can cause an adverse reaction. Reactions range from irritating ...

  20. Drug Safety

    MedlinePlus

    ... 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 ...

  1. Club Drugs

    MedlinePlus

    ... 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 ...

  2. New strategies to deliver anticancer drugs to brain tumors

    PubMed Central

    Laquintana, Valentino; Trapani, Adriana; Denora, Nunzio; Wang, Fan; Gallo, James M.; Trapani, Giuseppe

    2009-01-01

    BACKGROUND Malignant brain tumors are among the most challenging to treat and at present there are no uniformly successful treatment strategies. Standard treatment regimens consist of maximal surgical resection followed by radiotherapy and chemotherapy. The limited survival advantage attributed to chemotherapy is partially due to low CNS penetration of antineoplastic agents across the blood-brain barrier (BBB). OBJECTIVE The objective of this paper is to review recent approaches to deliver anticancer drugs into primary brain tumors. METHODS Both preclinical and clinical strategies to circumvent the BBB are considered that includes chemical modification and colloidal carriers. CONCLUSION Analysis of the available data indicates that novel approaches may be useful for CNS delivery, yet an appreciation of pharmacokinetic issues, and improved knowledge of tumor biology will be needed to significantly impact drug delivery to the target site. PMID:19732031

  3. Drugs, drugs--who has the drugs?

    PubMed

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims. PMID:22423518

  4. Plasmodium Drug Targets Outside the Genetic Control of the Parasite

    PubMed Central

    Sullivan, David J.

    2014-01-01

    Drug development often seeks to find “magic bullets” which target microbiologic proteins while not affecting host proteins. Paul Ehrlich tested methylene blue as an antimalarial but this dye was not superior to quinine. Many successful antimalarial therapies are “magic shotguns” which target many Plasmodium pathways with little interference in host metabolism. Two malaria drug classes, the 8-aminoquinolines and the artemisinins interact with cytochrome P450s and host iron protoporphyrin IX or iron, respectively, to generate toxic metabolites and/or radicals, which kill the parasite by interference with many proteins. The non 8-amino antimalarial quinolines like quinine or piperaquine bind heme to inhibit the process of heme crystallization, which results in multiple enzyme inhibition and membrane dysfunction. The quinolines and artemisinins are rapidly parasiticidal in contrast to metal chelators, which have a slower parasite clearance rate with higher drug concentrations. Iron chelators interfere with the artemisinins but otherwise represent a strategy of targeting multiple enzymes containing iron. Interest has been revived in antineoplastic drugs that target DNA metabolism as antimalarials. Specific drug targeting or investigation of the innate immunity directed to the more permeable trophozoite or schizont infected erythrocyte membrane has been under explored. Novel drug classes in the antimalarial development pipeline which either target multiple proteins or unchangeable cellular targets will slow the pace of drug resistance acquisition. PMID:22973888

  5. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

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

    PubMed Central

    Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon

    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. PMID:26078967

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

    PubMed

    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. PMID:26078967

  8. Drug interactions with the newer antiepileptic drugs (AEDs)--Part 2: pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders.

    PubMed

    Patsalos, Philip N

    2013-12-01

    Since antiepileptic drugs (AEDs) are prescribed to treat various non-epilepsy-related disorders in addition to the fact that patients with epilepsy may develop concurrent disorders that will need treatment, the propensity for AEDs to interact with non-AEDs is considerable and indeed can present a difficult clinical problem. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs (eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide) and drugs used to treat non-epilepsy disorders. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. Pharmacokinetic interactions relate to hepatic enzyme induction or inhibition and involved a variety of drugs including psychoactive drugs, cardioactive drugs, oral contraceptives, antituberculous agents, analgesics and antineoplastic drugs. A total of 68 pharmacokinetic interactions have been described, with lamotrigine (n = 22), topiramate (n = 18) and oxcarbazepine (n = 7) being associated with most, whilst lacosamide, pregabalin, stiripentol and vigabatrin are associated with none. Overall, only three pharmacodynamic interactions have been described and occur with oxcarbazepine, perampanel and pregabalin. PMID:23794036

  9. Use of a chemically modified antisense oligonucleotide library to identify and validate Eg5 (kinesin-like 1) as a target for antineoplastic drug development.

    PubMed

    Koller, Erich; Propp, Stephanie; Zhang, Hong; Zhao, Chenguang; Xiao, Xiaokun; Chang, MingYi; Hirsch, Scott A; Shepard, Peter J; Koo, Seongjoon; Murphy, Cain; Glazer, Robert I; Dean, Nicholas M

    2006-02-15

    A library of 2'-methoxyethyl-modified antisense oligonucleotides (2'MOE ASO) targeting 1,510 different genes has been developed, validated, and used to identify cell cycle regulatory genes. The most effective molecular target identified was Eg5 (kinesin-like-1), which when inhibited gave the largest increase in 4N DNA in various tumor cells. The Eg5 ASO reduced Eg5 levels, inhibited proliferation, increased apoptosis, and altered the expression of other cell cycle proteins, including survivin and Aurora-A. To examine the therapeutic utility of the Eg5 ASO, the compound was also evaluated in xenograft models. Treatment with Eg5 ASO produced a statistically significant reduction of tumor growth, reduction in Eg5 expression in the tumors, and changes in histone phosphorylation, consistent with a loss of Eg5 protein expression. These data show, for the first time, the utility of a 2'MOE ASO library for high-throughput cell culture-based functional assays and suggest that an Eg5 ASO also has potential in a therapeutic strategy. PMID:16489005

  10. A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs

    PubMed Central

    Gidwani, Bina; Vyas, Amber

    2015-01-01

    Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents. PMID:26582104

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

    PubMed

    Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Fabossi, Isabella Aviles; Lívero, Francislaine Aparecida Dos Reis; Stolf, Aline Maria; Alves de Souza, Carlos Eduardo; Gomes, Liana de Oliveira; Constantin, Rodrigo Polimeni; Furman, Aline Emmer Ferreira; Strapasson, Regiane Lauriano Batista; Teixeira, Simone; Zampronio, Aleksander Roberto; Muscará, Marcelo Nicolás; Stefanello, Maria Elida Alves; Acco, Alexandra

    2013-01-01

    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. PMID:23408945

  12. 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.

    PubMed

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    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 LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  13. Uncaria tomentosa Exerts Extensive Anti-Neoplastic Effects against the Walker-256 Tumour by Modulating Oxidative Stress and Not by Alkaloid Activity

    PubMed Central

    Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Fabossi, Isabella Aviles; Lívero, Francislaine Aparecida dos Reis; Stolf, Aline Maria; Alves de Souza, Carlos Eduardo; Gomes, Liana de Oliveira; Constantin, Rodrigo Polimeni; Furman, Aline Emmer Ferreira; Strapasson, Regiane Lauriano Batista; Teixeira, Simone; Zampronio, Aleksander Roberto; Muscará, Marcelo Nicolás; Stefanello, Maria Elida Alves; Acco, Alexandra

    2013-01-01

    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. PMID:23408945

  14. 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

    PubMed Central

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    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 LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  15. Drug Facts

    MedlinePlus Videos and Cool Tools

    ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  16. Drug Reactions

    MedlinePlus

    ... 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 gingko and blood thinners ...

  17. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  18. Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer.

    PubMed

    Matlapudi, Megha Shyam; Moin, Afrasim; Medishetti, Raghavender; Rajendra, K; Raichur, Ashok M; Kumar, B R Prashantha

    2015-01-01

    Two antineoplastic agents, Imatinib (IM) and 5-Fluorouracil (FU) were conjugated by hydrolysable linkers through an amide bond and entrapped in polymeric Human Serum Albumin (HSA) nanoparticles. The presence of dual drugs in a common carrier has the advantage of reaching the site of action simultaneously and acting at different phases of the cell cycle to arrest the growth of cancer cells before they develop chemoresistance. The study has demonstrated an enhanced anticancer activity of the conjugate, and conjugate loaded stealth HSA nanoparticles (NPs) in comparison to the free drug in A-549 human lung carcinoma cell line and Zebra fish embryos (Danio rerio). Hydrolysability of the conjugate has also been demonstrated with complete hydrolysis being observed after 12 h. In vivo pharmacodynamics study in terms of tumor volume and pharmacokinetics in mice for conjugate (IM-SC-FU) and conjugate loaded nanoparticles showed significant anti-cancer activity. The other parameters evaluated were particle size (86nm), Poly Dispersive Index (PDI) (0.209), zeta potential (-49mV), drug entrapment efficiency (96.73%) and drug loading efficiency (89%). Being in stealth mode gives the potential for the NPs to evade Reticulo-Endothelial system (RES), achieve passive targeting by Enhanced Permeation Retention (EPR) effect with controlled release of the therapeutic agent. As the conjugate cleaves into individual drugs in the tumor environment, this promises better suppression of cancer chemoresistance by delivering dual drugs with different modes of action at the same site, thereby synergistically inhibiting the growth of cancerous tissue. PMID:25961796

  19. Sequence-specific interactions of drugs interfering with the topoisomerase-DNA cleavage complex.

    PubMed

    Palumbo, Manlio; Gatto, Barbara; Moro, Stefano; Sissi, Claudia; Zagotto, Giuseppe

    2002-07-18

    DNA-processing enzymes, such as the topoisomerases (tops), represent major targets for potent anticancer (and antibacterial) agents. The drugs kill cells by poisoning the enzymes' catalytic cycle. Understanding the molecular details of top poisoning is a fundamental requisite for the rational development of novel, more effective antineoplastic drugs. In this connection, sequence-specific recognition of the top-DNA complex is a key step to preferentially direct the action of the drugs onto selected genomic sequences. In fact, the (reversible) interference of drugs with the top-DNA complex exhibits well-defined preferences for DNA bases in the proximity of the cleavage site, each drug showing peculiarities connected to its structural features. A second level of selectivity can be observed when chemically reactive groups are present in the structure of the top-directed drug. In this case, the enzyme recognizes or generates a unique site for covalent drug-DNA binding. This will further subtly modulate the drug's efficiency in stimulating DNA damage at selected sites. Finally, drugs can discriminate not only among different types of tops, but also among different isoenzymes, providing an additional level of specific selection. Once the molecular basis for DNA sequence-dependent recognition has been established, the above-mentioned modes to generate selectivity in drug poisoning can be rationally exploited, alone or in combination, to develop tailor-made drugs targeted at defined loci in cancer cells. PMID:12084456

  20. Controlled delivery of bPEI-niclosamide complexes by PEO nanofibers and evaluation of its anti-neoplastic potentials.

    PubMed

    Kumar, S Uday; Gopinath, P

    2015-07-01

    Since the turn of the 21st century, nanofiber based drug delivery systems have evolved drastically to attain controlled and sustained delivery of various bioactive molecules. In spite of such efforts, the tangible interface existing between the target cells and the drug molecules could not be narrowed down. This drawback has been overcome in this work by realizing nanofiber based scaffold for delivery of polymer-drug complexes rather than just the drug. In course with this, in the present study a differentially cross-linkable bPEI-PEO (branched-polyethylenimine-poly(ethylene oxide)) based nanofiber is fabricated for tunable delivery of bPEI-niclosamide complexes. Hydrophilic bPEI-niclosamide complexes are pre-synthesized and stabilized by crosslinking agent, which were then incorporated into bPEI-PEO nanofibers by electrospinning. The niclosamide loaded nanofibers by virtue of bPEI moieties presence were then cross-linked to different degrees which in turn altered bPEI-niclosamide release profile. The release kinetics of bPEI-niclosamide complexes from nanofibers was elucidated further by Korsmeyer-Peppas model. Apart from this, the versatile nature of bPEI-PEO nanofibers was also validated for different drug loading concentration and extent of crosslinking. The fibers antitumor efficacy was then assessed against A549 (Non-small cell lung cancer cells) and U-87 MG (glioblastoma cells) at two different time points (at 48h and 96h) in order to realize the importance of release profile in manifestation of different therapeutic outcomes. Thus, this work endows niclosamide a new life for anticancer application which has remained elusive till date due to its hydrophobic nature. PMID:25988281

  1. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  2. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  3. Drug diversion

    PubMed Central

    Wood, Danielle

    2015-01-01

    SUMMARY Prescription drug diversion has significant health, legal and social implications. Deaths from misuse of prescription drugs account for a significant proportion of overdose deaths. The drugs most commonly involved are analgesics, particularly opioids, and psychoactive drugs, particularly benzodiazepines. Diverted drugs are most often sourced from a family member or friend, but are also sourced from overseas pharmacies or laboratories, or bought from drug dealers. Drug diversion can be mitigated by good prescribing practices. Systems for monitoring the prescribing and dispensing of medicines are being instituted across Australia. PMID:26648654

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

    SciTech Connect

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

    1991-02-01

    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. Drug use in children: cohort study in three European countries

    PubMed Central

    Verhamme, Katia M C; Nicolosi, Alfredo; Murray, Macey L; Neubert, Antje; Caudri, Daan; Picelli, Gino; Sen, Elif Fatma; Giaquinto, Carlo; Cantarutti, Luigi; Baiardi, Paola; Felisi, Maria-Grazia; Ceci, Adriana; Wong, Ian C K

    2008-01-01

    Objective To provide an overview of drug use in children in three European countries. Design Retrospective cohort study, 2000-5. Setting Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). Participants 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). Main outcome measure Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. Results Three levels of drug use could be distinguished in the study population: high (>10/100 children per year), moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. Conclusion This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs. PMID:19029175

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

    PubMed

    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

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

    PubMed Central

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    Purpose 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. Materials and methods 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. Results 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

  8. A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors.

    PubMed

    Shah, Rashmi R; Roberts, Samantha A; Shah, Devron R

    2013-09-01

    We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison. The FDA had granted priority review to 12 TKIs but the EMA/CHMP did not grant the equivalent accelerated assessment to any. The FDA granted accelerated approvals to six (38%) and CHMP granted (the equivalent) conditional approvals to four (29%) of these agents. On average, the review and approval times were 205.3 days in the US compared with 409.6 days in the European Union (EU). The active review times, however, were comparable (225.4 days in the EU and 205.3 days in the US). Since oncology drug development lasts about 7 years, the 20 days difference in review times between the two agencies is inconsequential. Clock stops during review and the time required to issue an approval had added the extra 184.2 days to review time in the EU. We suggest possible solutions to expedite the EU review and approval processes. However, post-marketing emergence of adverse efficacy and safety data on gefitinib and lapatinib, respectively, indicate potential risks of expedited approvals. We challenge the widely prevalent myth that early approval translates into early access or beneficial impact on public health. Both the agencies collaborate closely but conduct independent assessments and make decisions based on distinct legislation, procedures, precedents and societal expectations. PMID:23362829

  9. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  10. Drug Control

    ERIC Educational Resources Information Center

    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)

  11. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  12. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  13. [Microvascular architecture of human tumors transplanted in nude mice--its relationship to sensitivity to antineoplastic agents].

    PubMed

    Okazaki, M; Kubota, T; Hanatani, Y; Maruyama, K; Tsuyuki, K; Nakada, M; Asanuma, F; Ishibiki, K; Abe, O

    1982-08-01

    Microangiographic study was performed with ten human tumors serially transplanted into nude mice to clarify the role of tumor vessels on the chemosensitivity of the human tumors. Five gastric carcinomas, two colon carcinomas, one breast carcinoma, one cholangiocarcinoma, and one hemangiopericytoma were used for the experiments. Seven tumors revealed hypervascular network of vessels, whereas hypovascular patterns of tumor vessels were observed in the other three tumors. It was found that the histologically differentiated tumors were hypervascular and undifferentiated tumors were hypovascular, with statistically significant differences (p less than 0.05). Each tumor possessed the vascular network similar to human tumors originated from the same organs. No discernible changes of microangiographic features were noticed by serial transfers. As the chemosensitivities of these tumors depended mainly on their original tissues, these chemosensitivities could not be explained only by tumor vascularities or drug transferences. However, in the tumors with similar chemosensitive spectra, less susceptible tumors were observed to possess the irregular vascular networks in comparison with sensitive strains. From these considerations, tumor vessels were thought to have some role on vascular flow and drug transference which affected chemosensitivity of human tumors. PMID:7184456

  14. Drug Survey.

    ERIC Educational Resources Information Center

    Gill, Wanda E.; And Others

    Results of a survey of student perceptions of drugs and drug use that was conducted at Bowie State College are presented. Studies that have been conducted on college students' use of alcohol, marijuana, and cocaine in the last five years are reviewed, along with additional studies relating to the general population and the following drugs:…

  15. Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment.

    PubMed

    Rong, Zi-Jie; Yang, Lian-Jun; Cai, Bao-Ta; Zhu, Li-Xin; Cao, Yan-Lin; Wu, Guo-Feng; Zhang, Zan-Jie

    2016-05-01

    To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic

  16. Extracellular L-asparaginase from a protease-deficient Bacillus aryabhattai ITBHU02: purification, biochemical characterization, and evaluation of antineoplastic activity in vitro.

    PubMed

    Singh, Yogendra; Gundampati, Ravi Kumar; Jagannadham, Medicherla V; Srivastava, S K

    2013-12-01

    An extracellular L-asparaginase produced by a protease-deficient isolate, Bacillus aryabhattai ITBHU02, was purified to homogeneity using ammonium sulfate fractionation and subsequent column chromatography on diethylaminoethyl-Sepharose fast flow and Seralose CL-6B. The enzyme was purified 68.9-fold with specific activity of 680.47 U mg(-1). The molecular weight of the purified enzyme was approximately 38.8 kDa on SDS-PAGE and 155 kDa on native PAGE gel as well as gel filtration column revealing that the enzyme was a homotetramer. The optimum activity of purified L-asparaginase was achieved at pH 8.5 and temperature 40 °C. Kinetic studies depicted that the K m, V max, and k cat values of the enzyme were 0.257 mM, 1.537 U μg(-1), and 993.93 s(-1), respectively. Circular dichroism spectroscopy has showed that the enzyme belonged to α + β class of proteins with approximately 74 % α-helices and 12 % β-sheets. BLASTP analysis of N-terminal sequence K-T-I-I-E-A-V-P-E-L-K-K-I-A of purified L-asparaginase had shown maximum similarity with Bacillus megaterium DSM 319. In vitro cytotoxicity assays with HL60 and MOLT-4 cell lines indicated that the L-asparaginase has significant antineoplastic properties. PMID:23996139

  17. Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization.

    PubMed

    Stefani, Christian; Al-Eisawi, Zaynab; Jansson, Patric J; Kalinowski, Danuta S; Richardson, Des R

    2015-11-01

    Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) Cu(II/I) redox potentials; (2) ability to induce cellular (64)Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-l-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones). PMID:26335599

  18. Synthesis, characterization, and in vitro anti-neoplastic activity of novel vic-dioximes bearing thiosemicarbazone side groups and their mononuclear complexes.

    PubMed

    Babahan, İlknur; Özmen, Ali; Orhan, Nil; Kazar, Didem; Değirmenci, Esin Hafize

    2014-04-01

    Two novel vicinal dioxime ligands containing thiosemicarbazone units, (2E)-2-[4-(diethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazine carbothioamide (L(1)H2) and (2E)-2-[4-(dimethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazinecarbothioamide (L(2)H2), were synthesized. Using the HL-60 human leukemia cell line, the in vitro anti-neoplastic activity of these thiosemicarbazone-oxime derivatives was evaluated. Mononuclear nickel(II), copper(II), and cobalt(II) complexes with a metal:ligand ratio of 1:2 for both the L(1)H2 and L(2)H2 ligands were also synthesized. To characterize these compounds, Fourier transform-infrared spectroscopy (FT-IR), mass spectrometry (MS), magnetic susceptibility measurements, (1)H and (13)C nuclear magnetic resonance (NMR), ultraviolet-visible (UV-Vis) absorption spectroscopy, heteronuclear multiple-bond correlation (HMQC), and elemental analysis were performed. For L(1)H2, L(2)H2, and each of their derivatives, antiproliferative effects against HL-60 cells were exhibited and the associated IpC50 values ranged from 5μM to 20μM. Furthermore, L(1)H2 and its derivatives inhibited the proliferation of HL-60 cells more effectively than L(2)H2, and 5μM [Cu(L(1)H)2] exhibited the strongest antiproliferative activity. PMID:24651042

  19. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  20. Attempts at the production of more selective antitumourals. Part II. The antineoplastic activity of cyclophosphazenes linked to spermine

    NASA Astrophysics Data System (ADS)

    Sournies, François; Labarre, Jean-François; Spreafico, Federico; Filippeschi, Stefania; Quan Jin, Xing

    1986-09-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to spermine. Synthesis, NMR and mass spectra of the vectorized drug (in which two N 3P 3Az 4 active principles are linked to spermine in a DISPIROBINO configuration) are described. Results obtained with this compound in 6 murine tumour systems (L1210 and P388 leukaemias, 3LL carcinoma, M5076 reticulum cell sarcoma, B16 melanoma and line 16 mammary carcinoma), are also described and compared with results previously obtained about the targeting of gem-N 3P 3Az 4Cl 2 through 1,3-diaminopropane and 1,4-diaminobutane (putrescine).

  1. Berbamine enhances the antineoplastic activity of gemcitabine in pancreatic cancer cells by activating transforming growth factor-β/Smad signaling.

    PubMed

    Jin, Xiaoli; Wu, Yulian

    2014-05-01

    Drug-resistance to gemcitabine chemotherapy in pancreatic cancer is still an unsolved problem. Combinations of other chemotherapy drugs with gemcitabine have been shown to increase the efficacy of gemcitabine-based treatment. In this study, the effect of berbamine on the antitumor activity of gemcitabine was evaluated in human pancreatic cancer cell lines Bxpc-3 and Panc-1, and the underlying mechanisms were explored. Our results demonstrated that berbamine exhibited a time- and dose-dependent inhibitory effect in the pancreatic cancer cell lines. Berbamine enhanced gemcitabine-induced cell growth inhibition and apoptosis in these cells. Combined treatment of berbamine and gemcitabine resulted in down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL) and up-regulation of pro-apoptotic proteins (Bax, Bid). More importantly, berbamine treatment in combination with gemcitabine activated the transforming growth factor-β/Smad (TGF-β/Smad) signaling pathway, as a result of a decrease in Smad7 and an increase in transforming growth factor-β receptor II (TβRII) expression. Changes in downstream targets of Smad7, such as up-regulation of p21 and down-regulation of c-Myc and Cyclin D1 were also observed. Therefore, berbamine could enhance the antitumor activity of gemcitabine by inhibiting cell growth and inducing apoptosis, possibly through the regulation of the expression of apoptosis-related proteins and the activation of TGF-β/Smad signaling pathway. Our study indicates that berbamine may be a promising candidate to be used in combination with gemcitabine for pancreatic cancer treatment. PMID:24619961

  2. COPD - control drugs

    MedlinePlus

    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. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  4. Drug dependence

    MedlinePlus

    ... men References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Kowalchuk A, Reed BC. Drug abuse. In: ...

  5. Drug abuse

    MedlinePlus

    ... abuse References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman ...

  6. Anti-neoplastic activities of sepia officinalis ink and coelatura aegyptiaca extracts against Ehrlich ascites carcinoma in Swiss albino mice

    PubMed Central

    Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A

    2015-01-01

    Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537

  7. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  8. Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral agents.

    PubMed

    Verri, A; Focher, F; Priori, G; Gosselin, G; Imbach, J L; Capobianco, M; Garbesi, A; Spadari, S

    1997-01-01

    We demonstrate that human 2'-deoxycytidine kinase (dCK) is a nonenantioselective enzyme because it phosphorylates beta-D-2'-deoxycytidine (D-dCyd), the natural substrate, and beta-L-2'-deoxycytidine (L-dCyd), its enantiomer, with the same efficiency. Kinetic studies showed that L-dCyd is a competitive inhibitor of the phosphorylation of D-dCyd with a Kl value of 0.12 microM, which is lower than the K(m) value for D-dCyd (1,2 microM). Chemical modifications of either the base or the pentose ring strongly decrease the inhibitory potency of L-dCyd, L-dCyd is resistant to cytidine deaminase and competes in cell cultures with the natural D-dCyd as substrate for dCK, thus reducing the incorporation of exogenous [3H]dCyd into DNA. L-dCyd had no effect on the pool of dTTP deriving from the salvage or from the de novo synthesis, does not inhibit short term RNA and protein syntheses, and shows little or no cytotoxicity. Our results indicate a catalytic similarity between human dCK and herpetic thymidine kinases, enzymes that also lack stereospecificity. This functional analogy underlines the potential role of dCK as activator of L-deoxycytidine analogs as antiviral and antineoplastic agents and lends support to the hypothesis that herpesvirus thymidine kinase might have evolved from a captured cellular dCK gene, developing the ability to phosphorylate thymidine and retaining that to phosphorylate deoxycytidine. PMID:9016355

  9. Drug Reactions

    MedlinePlus

    ... using any of these products. Some types of food may also cause adverse drug reactions. For example, grapefruit and grapefruit juice, as well as alcohol and caffeine, may affect how drugs work. Every time your doctor ... interactions with any foods or beverages. What about medicines I've used ...

  10. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  11. [Club drugs].

    PubMed

    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. PMID:22525626

  12. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  13. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  14. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  15. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  16. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  17. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

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

    PubMed Central

    2010-01-01

    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 of adoption of new

  19. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  20. Drug misuse.

    PubMed

    Waller, T

    1992-12-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  1. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Drugs@FDA: FDA Approved Drug Products FDA Home Drug Databases Drugs@FDA - FAQ | Instructions | ... 6332) Contact FDA For Government For Press Combination Products Advisory Committees Science & Research Regulatory Information Safety Emergency ...

  2. Toxic effects of cisplatin cytostatic drug in mussel Mytilus galloprovincialis.

    PubMed

    Trombini, Chiara; Garcia da Fonseca, Taina; Morais, Matilde; Rocha, Thiago Lopes; Blasco, Julián; Bebianno, Maria João

    2016-08-01

    Antineoplastic drugs used in chemotherapy were detected in aquatic environment: despite the very low concentrations (ng L(-1) to ug L(-1)), due to their potent mechanism of action they could have adverse effects on non-target aquatic organisms particularly under chronic exposure. Cisplatin (CDDP) is one of the most effective anticancer drug currently in use but information on its ecotoxicological effects is very limited. In this study, Mytilus galloprovincialis was used to investigate the toxic effects related to CDDP exposure. Mussels were exposed to cisplatin (100 ng L(-1)) for 14 days: antioxidant (superoxide dismutase, catalase, total and selenium-dependent glutathione peroxidase) and phase II (glutathione-S-transferase) enzymes activities, oxidative damage (lipid peroxidation), genotoxicity (DNA damage) and neurotoxicity (acetylcholinesterase) was evaluated. Results indicate that CDDP at tested concentration induce changes in the antioxidant capacity, oxidative stress in target organs (digestive gland and gills) as well as DNA damage in mussel hemocytes and neurotoxicity representing a risk for non-target organisms. PMID:27183200

  3. Roles of sildenafil in enhancing drug sensitivity in cancer.

    PubMed

    Shi, Zhi; Tiwari, Amit K; Patel, Atish S; Fu, Li-Wu; Chen, Zhe-Sheng

    2011-06-01

    The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter-mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter-mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs. PMID:21610107

  4. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  5. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated. PMID:18472067

  6. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided. PMID:11366758

  7. CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A.

    PubMed

    Chu, Jennifer; Galicia-Vázquez, Gabriela; Cencic, Regina; Mills, John R; Katigbak, Alexandra; Porco, John A; Pelletier, Jerry

    2016-06-14

    Targeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation that controls ribosome recruitment flux is eukaryotic initiation factor (eIF) 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition. PMID:27239032

  8. Synthesis, characterization, and magnetically guided antiproliferative activity studies of drug-loaded superparamagnetic nanovectors

    NASA Astrophysics Data System (ADS)

    Luna, Carlos; Vázquez Ortega, Salvador; Barriga-Castro, Enrique Díaz; Mendoza-Reséndez, Raquel; Gómez-Treviño, Alberto

    2015-05-01

    Commonly, the key players in anticancer therapies and, more specifically, antineoplastic drugs display poor water solubility and slow dissolution rates. As a consequence, they present low bioavailability, poor tissue distribution, and unfavorable pharmacokinetic profiles, limiting their use. To overcome these barriers and improve efficacy, various drug formulations and delivery strategies have been developed. For example, nanoparticles can be used as drug delivery vehicles and current research is encouraging. However, the intra-tumoral diffusion of functionalized nanovehicles remains to be achieved. In the present study, the anticancer drug paclitaxel was loaded into superparamagnetic nanoparticles and characterized. Novel in vitro experiments based on one or two layers of cells revealed important information about the conditions required to achieve efficient drug intra-tumoral diffusion, using these superparamagnetic nanovectors, once they have been localized by external magnetic fields. These studies indicated that ultralow concentrations of paclitaxel (i.e., tenths of ng/μl) significantly reduce the viability of neoplastic cells when they are delivered with control using these nanovectors. Moreover, we showed that a discontinuous application of a magnetic field promotes the localization of the nanoparticles in a targeted region and favors the subsequent dissemination of the nanoparticles between cellular layers.

  9. Drug Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug resistance refers to both intrinsic and acquired abilities of cells or organisms to become insensitive or refractory to chemotherapeutic intervention. The advent of antibiotics is considered one of the most important medicinal developments in human history, which has led to significantly reduce...

  10. Club Drugs

    MedlinePlus

    ... Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known as Roofies Methamphetamine, also known as Speed, Ice, Chalk, Meth, Crystal, Crank, and Glass Lysergic Acid Diethylamide (LSD), also ...

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

    PubMed

    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. PMID:3882257

  12. Doxorubicin induces drug efflux pumps in Candida albicans.

    PubMed

    Kofla, Grzegorz; Turner, Vincent; Schulz, Bettina; Storch, Ulrike; Froelich, Daniela; Rognon, Bénédicte; Coste, Alix T; Sanglard, Dominique; Ruhnke, Markus

    2011-02-01

    Candida albicans is one of the most important opportunistic fungal pathogens. It can cause serious fungal diseases in immunocompromised patients, including those with cancer. Treatment failures due to the emergence of drug-resistant C. albicans strains have become a serious clinical problem. Resistance incidents were often mediated by fungal efflux pumps which are closely related to the human ABC transporter P-glycoprotein (P-gp). P-gp is often overexpressed in cancer cells and confers resistance to many cytotoxic drugs. We examined whether cytotoxic drugs commonly used for cancer treatment (doxorubicin and cyclophosphamide) could alter the expression of genes responsible for the development of fluconazole resistance in Candida cells in the way they can influence homologous genes in cancer cell lines. ABC transporters (CDR1 and CDR2) and other resistance genes (MDR1 and ERG11) were tested by real-time PCR for their expression in C. albicans cells at the mRNA level after induction by antineoplastic drugs. The results were confirmed by a lacZ gene reporter system and verified at the protein level using GFP and immunoblotting. We showed that doxorubicin is a potent inducer of CDR1/CDR2 expression in C. albicans at both the mRNA and protein level and thus causes an increase in fluconazole MIC values. However, cyclophosphamide, which is not a substrate of human P-gp, did not induce ABC transporter expression in C. albicans. Neither doxorubicin nor cyclophosphamide could influence the expression of the other resistance genes (MDR1 and ERG11). The induction of CDR1/CDR2 by doxorubicin in C. albicans and the resulting alteration of antifungal susceptibility might be of clinical relevance for the antifungal treatment of Candida infections occurring after anticancer chemotherapy with doxorubicin. PMID:20818920

  13. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  14. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  15. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  16. Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

    NASA Astrophysics Data System (ADS)

    Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

    1997-05-01

    The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

  17. Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems.

    PubMed

    Jelezova, Ivelina; Drakalska, Elena; Momekova, Denitsa; Shalimova, Natalia; Momekov, Georgi; Konstantinov, Spiro; Rangelov, Stanislav; Pispas, Stergios

    2015-10-12

    Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells. PMID:26159739

  18. Down-regulation of telomerase activity by anticancer drugs in human ovarian cancer cells.

    PubMed

    Kunifuji, Yasumasa; Gotoh, Sadao; Abe, Tetsuya; Miura, Masayoshi; Karasaki, Yuji

    2002-07-01

    Maintenance of telomere length is crucial for survival of cells. Telomerase, an enzyme that is responsible for elongation of shortened telomeres, is active in human germ cells as well as most tumor tissues and experimentally immortalized cells. In contrast, most mature somatic cells in human tissues express undetectable or low telomerase activity, implying the existence of a stringent and negative regulatory mechanism. In this study we report the effects of anticancer drugs on telomerase activity in human cancer cells. In assaying for telomerase activity, we basically followed the original TRAP assay system, but with some modifications. A down-regulation of telomerase activity was found when cells of a human ovarian cancer cell line, A2780, were treated with;cis-diamminedichloroplatinum(II) (CDDP; cisplatin). However, down-regulation of telomerase activity was not found in cells of a cisplatin-resistant cell line, A2780CP, treated with cisplatin. On the other hand, telomerase activity in both the cell lines A2780 and A2780CP was reduced when A2780 or A2780CP was treated with adriamycin, an anthracycline antibiotic having a broad spectrum of antineoplastic activity. The different effects on the telomerase activity of the two types of anticancer drugs may be due the distinct chemical functions of these drugs. The present results may indicate a positive relationship between anticancer effects and down-regulation of telomerase activity by anticancer drugs. PMID:12172504

  19. Antineoplastic Activity of New Transition Metal Complexes of 6-Methylpyridine-2-carbaldehyde-N(4)-ethylthiosemicarbazone: X-Ray Crystal Structures of [VO2(mpETSC)] and [Pt(mpETSC)Cl

    PubMed Central

    Elsayed, Shadia A.; El-Hendawy, Ahmed M.; Mostafa, Sahar I.; Jean-Claude, Bertrand J.; Todorova, Margarita; Butler, Ian S.

    2010-01-01

    New complexes of dioxovanadium(V), zinc(II), ruthenium(II), palladium(II), and platinum(II) with 6-methylpyridine-2-carbaldehyde-N(4)-ethylthiosemicarbazone (HmpETSC) have been synthesized. The composition of these complexes is discussed on the basis of elemental analyses, IR, Raman, NMR (1H, 13C, and 31P), and electronic spectral data. The X-ray crystal structures of [VO2(mpETSC)] and [Pt(mpETSC)Cl] are also reported. The HmpETSC and its [Zn(HmpETSC)Cl2] and [Pd(mpETSC)Cl] complexes exhibit antineoplastic activity against colon cancer human cell lines (HCT 116). PMID:20671978

  20. Attempts at the production of more selective antitumourals. Part I. The antineoplastic activity of cyclophosphazenes linked to the polyamines 1,3-diaminopropane and 1,4-diaminobutane (putrescine)

    NASA Astrophysics Data System (ADS)

    Labarre, Jean-François; Guerch, Guy; Sournies, François; Spreafico, Federico; Filippeschi, Stefania

    1984-06-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to 1,3-diaminopropane and 1,4-diaminobutane (putrescine). Synthesis, mass spectrum and NMR as well as X-ray crystal structures of the two spirocyclic N 3P 3Az 4 [HN(CH 2) 3,4NH] derivatives (in which the N 3P 3Az 4 active principle is linked to the diamine in a spiro configuration) are described. Results obtained with these compounds in 3 murine tumour systems (L1210 and P388 leukaemias and P815 mastocytoma), showing their potent antineoplastic activity in vivo obtainable at well-tolerated doses, are also described.

  1. [Emergent drugs (I): smart drugs].

    PubMed

    Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

    2011-01-01

    In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects. PMID:21904408

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

    PubMed Central

    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

  3. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  4. Urine drug screen

    MedlinePlus

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

  5. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  6. Drugs Approved for Leukemia

    Cancer.gov

    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

    Cancer.gov

    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. Drugs Approved for Neuroblastoma

    Cancer.gov

    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.

  9. Drug abuse first aid

    MedlinePlus

    Drug abuse is the misuse or overuse of any medication or drug, including alcohol. This article discusses first ... use of these drugs is a form of drug abuse. Legitimate medications can be abused by people who ...

  10. Chirality-mediated polypeptide micelles for regulated drug delivery.

    PubMed

    Ding, Jianxun; Li, Chen; Zhang, Ying; Xu, Weiguo; Wang, Jincheng; Chen, Xuesi

    2015-01-01

    Two kinds of triblock poly(ethylene glycol)-polyleucine (PEG-PLeu) copolymers were synthesized through the ring-opening polymerization of L-Leu N-carboxyanhydride (NCA), or equivalent D-Leu NCA and L-Leu NCA with amino-terminated PEG as a macroinitiator. The amphiphilic copolymers spontaneously self-assembled into spherical micellar aggregations in an aqueous environment. The micelle with a racemic polypeptide core exhibited smaller critical micelle concentration and diameter compared to those with a levorotatory polypeptide core. A model anthracycline antineoplastic agent, i.e., doxorubicin (DOX), was loaded into micelles through nanoprecipitation, and the PEG-P(D,L-Leu) micelle exhibited higher drug-loading efficacy than that with a P(L-Leu) core-this difference was attributed to the flexible and compact P(L-Leu) core. Sustained in vitro DOX release from micelles with both levorotatory and racemic polypeptide cores was observed, and the DOX-loaded PEG-P(D,L-Leu) micelle exhibited a slower release rate. More interestingly, DOX-loaded micelles exhibited chirality-mediated antitumor efficacy in vitro and in vivo, which are all better than that of free DOX. Furthermore, both enhanced tumor inhibition and excellent security in vivo were confirmed by histopathological or in situ cell apoptosis analyses. Therefore, DOX-loaded PEG-PLeu micelles appear to be an interesting nanoscale polymeric formulation for promising malignancy chemotherapy. PMID:25278445

  11. Nuclear export of proteins and drug resistance in cancer

    PubMed Central

    Turner, Joel G.; Dawson, Jana; Sullivan, Daniel M.

    2015-01-01

    The intracellular location of a protein is crucial to its normal functioning in a cell. Cancer cells utilize the normal processes of nuclear-cytoplasmic transport through the nuclear pore complex of a cell to effectively evade anti-neoplastic mechanisms. CRM1-mediated export is increased in various cancers. Proteins that are exported in cancer include tumor-suppressive proteins such as retinoblastoma, APC, p53, BRAC1, FOXO proteins, INI1/hSNF5, galectin-3, Bok, nucleophosmin, RASSF2, Merlin, p21CIP, p27KIP1, N-WASP/FAK, estradiol receptor and Tob, drug targets topoisomerase I and IIα and BCR-ABL, and the molecular chaperone protein Hsp90. Here, we review in detail the current processes and known structures involved in the export of a protein through the nuclear pore complex. We also discuss the export receptor molecule CRM1 and its binding to the leucine-rich nuclear export signal of the cargo protein and the formation of a nuclear export trimer with RanGTP. The therapeutic potential of various CRM1 inhibitors will be addressed, including leptomycin B, ratjadone, KOS-2464, and specific small molecule inhibitors of CRM1, N-azolylacrylate analogs, FOXO export inhibitors, valtrate, acetoxychavicol acetate, CBS9106, and SINE inhibitors. We will also discuss examples of how drug resistance may be reversed by targeting the exported proteins topoisomerase IIα, BCR-ABL, and galectin-3. As effective and less toxic CRM1 export inhibitors become available, they may be used as both single agents and in combination with current chemotherapeutic drugs. We believe that the future development of low-toxicity, small-molecule CRM1 inhibitors may provide a new approach to treating cancer. PMID:22209898

  12. Some considerations in the experimental approach to distinguishing between membrane transport and intracellular disposition of antineoplastic agents, with specific reference to fluorodeoxyuridine, actinomycin D, and methotrexate

    SciTech Connect

    Goldman, D.; Bowen, D.; Gewirtz, D.A.

    1981-01-01

    Analysis of the interaction between an anticancer agent and the intact cell can provide important clues to cytotoxic determinants and mechanisms of drug selectivity and resistance. This can be very useful in optimally evaluating single and multidrug regimens in test systems, designing new agents, and evaluating drug metabolism and binding to cellular target sites. This cellular pharmacokinetic approach requires very meticulous attention to experimental design, especially the time dimension chosen for study, and an appropriate framework for data analysis. This paper reviews cellular pharmacokinetic principles and experimental approaches that can be applied in uptake studies with cytotoxic agents, focusing, as examples, on studies from this laboratory with fluorodeoxyuridine, actinomycin D, and methotrexate.

  13. Drugs and the Brain.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  14. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

    PubMed

    De Santis, S; Pace, A; Bove, L; Cognetti, F; Properzi, F; Fiore, M; Triaca, V; Savarese, A; Simone, M D; Jandolo, B; Manzione, L; Aloe, L

    2000-01-01

    The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds. PMID:10656436

  15. Anti-Neoplastic Cytotoxicity of SN-38-Loaded PCL/Gelatin Electrospun Composite Nanofiber Scaffolds against Human Glioblastoma Cells In Vitro.

    PubMed

    Zhu, Xiaodong; Ni, Shilei; Xia, Tongliang; Yao, Qingyu; Li, Haoyuan; Wang, Benlin; Wang, Jiangang; Li, Xingang; Su, Wandong

    2015-12-01

    Electrospun poly(ε-caprolactone) (PCL)/gelatin (GT) scaffolds were developed to provide controlled release of 7-ethyl-10-hydroxy camptothecin (SN-38). Acetic acid was introduced to improve the miscibility of PCL and GT to produce a homogeneous nanofiber membrane mixture. The effect of SN-38 content in binary mixtures on processability, fiber morphology, water sorption, swelling, and drug release was investigated. Electrospun PCL/GT blend nonwoven fibers showed fiber surface roughness, decreased PCL crystallinity, and increased swelling with increasing drug content of 1, 2, and 4 wt %. Additionally, increasing the SN-38 concentration reduced the degradation rate of the GT. Furthermore, we hypothesize the existence of a drug content saturation point in the monoaxial fiber to explain the different drug release patterns of PG2 compared with those of PG1 and PG4. The matrix also showed good biodegradation and anti-tumor function. Our results demonstrate that SN-38-loaded PCL/GT fibers can be obtained by electrospinning. The SN-38-loaded fibers merit further evaluation as a means to potentially prevent locoregional recurrence following surgical tumor resection. PMID:26505475

  16. Antineoplastic agents 552. Oxidation of combretastatin A-1: Trapping the o-Quinone intermediate considered metabolic product of the corresponding phosphate prodrug

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The very unstable (< 10 min at rt) o-quinone derived from the vicinol diphenol anticancer drug combretastatin A-1 has been obtained by careful oxidation with NaIO4 employing tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine allowed o-quinone 5 to be trapp...

  17. Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.

    PubMed

    Madonna, Rosalinda; Cadeddu, Christian; Deidda, Martino; Mele, Donato; Monte, Ines; Novo, Giuseppina; Pagliaro, Pasquale; Pepe, Alessia; Spallarossa, Paolo; Tocchetti, Carlo Gabriele; Zito, Concetta; Mercuro, Giuseppe

    2015-09-01

    Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies. PMID:26168714

  18. ‘One-pot’ synthesis of multifunctional GSH-CdTe quantum dots for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Chen, Xiaoqin; Tang, Yajun; Cai, Bing; Fan, Hongsong

    2014-06-01

    A novel quantum dots-based multifunctional nanovehicle (DOX-QD-PEG-FA) was designed for targeted drug delivery, fluorescent imaging, tracking, and cancer therapy, in which the GSH-CdTe quantum dots play a key role in imaging and drug delivery. To exert curative effects, the antineoplastic drug doxorubicin hydrochloride (DOX) was loaded on the GSH-CdTe quantum dots through a condensation reaction. Meanwhile, a polyethylene glycol (PEG) shell was introduced to wrap the DOX-QD, thus stabilizing the structure and preventing clearance and drug release during systemic circulation. To actively target cancer cells and prevent the nanovehicles from being absorbed by normal cells, the nanoparticles were further decorated with folic acid (FA), allowing them to target HeLa cells that express the FA receptor. The multifunctional DOX-QD-PEG-FA conjugates were simply prepared using the ‘one pot’ method. In vitro study demonstrated that this simple, multifunctional nanovehicle can deliver DOX to the targeted cancer cells and localize the nanoparticles. After reaching the tumor cells, the FA on the DOX-QD-PEG surface allowed folate receptor recognition and increased the drug concentration to realize a higher curative effect. This novel, multifunctional DOX-QD-PEG-FA system shows great potential for tumor imaging, targeting, and therapy.

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

    ERIC Educational Resources Information Center

    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)…

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

    NASA Astrophysics Data System (ADS)

    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.

  1. NAD(P) biosynthesis enzymes as potential targets for selective drug design.

    PubMed

    Magni, G; Di Stefano, M; Orsomando, G; Raffaelli, N; Ruggieri, S

    2009-01-01

    NAD(P) biosynthetic pathways can be considered a generous source of enzymatic targets for drug development. Key reactions for NAD(P) biosynthesis in all organisms, common to both de novo and salvage routes, are catalyzed by NMN/NaMN adenylyltransferase (NMNAT), NAD synthetase (NADS), and NAD kinase (NADK). These reactions represent a three-step pathway, present in the vast majority of living organisms, which is responsible for the generation of both NAD and NADP cellular pools. The validation of these enzymes as drug targets is based on their essentiality and conservation among a large variety of pathogenic microorganisms, as well as on their differential structural features or their differential metabolic contribution to NAD(P) homeostasis between microbial and human cell types. This review describes the structural and functional properties of eubacterial and human enzymes endowed with NMNAT, NADS, and NADK activities, as well as with nicotinamide phosphoribosyltransferase (NamPRT) and nicotinamide riboside kinase (NRK) activities, highlighting the species-related differences, with emphasis on their relevance for drug design. In addition, since the overall NMNAT activity in humans is accounted by multiple isozymes differentially involved in the metabolic activation of antineoplastic compounds, their individual diagnostic value for early therapy optimization is outlined. The involvement of human NMNAT in neurodegenerative disorders and its role in neuroprotection is also discussed. PMID:19355893

  2. Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

    PubMed

    Franqui-Machin, Reinaldo; Wendlandt, Erik B; Janz, Siegfried; Zhan, Fenghuang; Tricot, Guido

    2015-12-01

    Multiple myeloma (MM) remains a largely incurable, genetically heterogeneous plasma-cell malignancy that contains - just like many other cancers - a small fraction of clonogenic stem cell-like cells that exhibit pronounced self-renewal and differentiation capacities, but also pronounced drug resistance. These MM stem cells (MMSCs) are a controversial but highly significant issue in myeloma research because, in our opinion, they are at the root of the failure of anti-neoplastic chemotherapies to transform myeloma to a manageable chronic disease. Several markers including CD138-, ALDH1+ and SP have been used to identify MMSCs; however, no single marker is reliable for the isolation of MMSC. Nonetheless, it is now known that MMSCs depend on self-renewal and pro-survival pathways, such as AKT, Wnt/β-catenin, Notch and Hedgehog, which can be targeted with novel drugs that have shown promise in pre-clinical and clinical trials. Here, we review the pathways of myeloma "stemness", the interactions with the bone marrow microenvironment that promote drug resistance, and the obstacles that must be overcome to eradicate MMSCs and make myeloma a curable disease. PMID:26415231

  3. Design, synthesis, and pharmacokinetic evaluation of a chemical delivery system for drug targeting to lung tissue.

    PubMed

    Saah, M; Wu, W M; Eberst, K; Marvanyos, E; Bodor, N

    1996-05-01

    We espouse the application of a novel chemical delivery system (CDS) approach to a delivery mechanism for drug targeting to lung tissue using the 1,2-dithiolane-3-pentyl moiety of lipoic acid as the "targetor moiety". The synthesis and the physicochemical and pharmacokinetic evaluation of a CDS modeling the lipoyl and other ester derivatives of chlorambucil (an antineoplastic agent) and cromolyn (a bischromone used in antiasthma prophylaxis) as compared with their respective parent drugs are described. The chlorambucil CDS was synthesized by esterifying the alcohol derivative of lipoic acid with chlorambucil using dicyclohexylcarbodiimide as the coupling agent. The cromolyn CDS was prepared by a multistep synthetic procedure culminating in the reaction of the alkyl bromide derivative of lipoic acid with the disodium salt of the bischromone compound. All the esters were highly lipophilic unlike the parent compounds. The in-vitro kinetic and in-vivo pharmacokinetic studies showed that the respective CDSs were sufficiently stable in buffer and biological media, hydrolyzed rapidly into the respective active parent drugs, and significantly enhanced delivery and retention of the active compound to lung tissue in comparison with the underivatized parent compounds used in conventional therapy. PMID:8742941

  4. Synergistic Nanomedicine: Passive, Active, and Ultrasound-Triggered Drug Delivery in Cancer Treatment.

    PubMed

    Elkhodiry, Mohamed A; Momah, Christian C; Suwaidi, Shaima R; Gadalla, Dina; Martins, Ana M; Vitor, Rute F; Husseini, Ghaleb A

    2016-01-01

    Nanocarriers are heavily researched as drug delivery vehicles capable of sequestering antineoplastic agents and then releasing their contents at the desired location. The feasibility of using such carriers stems from their ability to produce a multimodel delivery system whereby passive, ligand and triggered targeting can be applied in the fight against cancer. Passive targeting capitalizes on the leaky nature of tumor tissue which allows for the extravasation of particles with a size smaller than 0.5 µm into the tumors. Ligand targeting utilizes the concept of receptor-mediated endocytosis and involves the conjugation of ligands onto the surface of nanoparticles, while triggered targeting involves the use of external and internal stimuli to release the carriers contents upon reaching the diseased location. In this review, micelles and liposomes have been considered due to the promising results they have shown in vivo and in vitro and their potential for advancements into clinical trials. Thus, this review focuses on the most recent advancements in the field of micellar and liposomal drug delivery and considers the synergistic effect of passive- and ligand-targeting strategies, and the use of ultrasound in triggering drug release at the tumor site. PMID:27398430

  5. Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

    PubMed Central

    Janz, Siegfried; Zhan, Fenghuang; Tricot, Guido

    2015-01-01

    Multiple myeloma (MM) remains a largely incurable, genetically heterogeneous plasma-cell malignancy that contains – just like many other cancers – a small fraction of clonogenic stem cell-like cells that exhibit pronounced self-renewal and differentiation capacities, but also pronounced drug resistance. These MM stem cells (MMSCs) are a controversial but highly significant issue in myeloma research because, in our opinion, they are at the root of the failure of anti-neoplastic chemotherapies to transform myeloma to a manageable chronic disease. Several markers including CD138−, ALDH1+ and SP have been used to identify MMSCs; however, no single marker is reliable for the isolation of MMSC. Nonetheless, it is now known that MMSCs depend on self-renewal and pro-survival pathways, such as AKT, Wnt/β-catenin, Notch and Hedgehog, which can be targeted with novel drugs that have shown promise in pre-clinical and clinical trials. Here, we review the pathways of myeloma “stemness”, the interactions with the bone marrow microenvironment that promote drug resistance, and the obstacles that must be overcome to eradicate MMSCs and make myeloma a curable disease. PMID:26415231

  6. Indices of drug misuse for prescription drugs.

    PubMed

    Davis, H; Baum, C; Graham, D J

    1991-07-01

    Few studies of prescription-drug misuse have taken into account the numbers of prescriptions dispensed for specific drugs. Using data from the Drug Abuse Warning Network (DAWN) and the National Prescription Audit, we calculated indices of drug misuse for specific prescription drugs that are used mainly in outpatient settings and are either benzodiazepines, barbiturates, other sedative-hypnotics, analgesics, or CNS stimulants. In 1983-1985 the drugs associated with the highest numbers of DAWN medical examiner-reported drug-misuse deaths were codeine, diazepam, propoxyphene, phenobarbital, and secobarbital. However, the drugs with the highest indices of DAWN medical examiner-reported drug-misuse deaths/100,000 dispensed prescriptions were methamphetamine, methaqualone, amobarbital, secobarbital, and glutethimide. An index of fatality risk, calculated as 100 x DAWN medical examiner-reported drug-misuse deaths/DAWN emergency room-reported drug-misuse episodes, suggested that the risk of death from a glutethimide-associated drug-misuse episode had increased 92% from 1975-1979 to 1983-1983 and in 1983-1985 was the highest for the drugs studied. These indices might assist public health authorities attempting to design effective strategies to efficiently address the problem of prescription-drug misuse. PMID:1960000

  7. Anti-Neoplastic and Calcium Modulatory Action of Caffeic Acid Phenethyl Ester and Dasatinib in C6 Glial Cells: A Therapeutic Perspective.

    PubMed

    Balkhi, Henah M; Gul, Taseen; Haq, Ehtishamul

    2016-01-01

    Gliomas are often recognized as highly heterogeneous cancerous phenotype. They are perpetually recurrent, obstinately resistant to treatment and hence almost incurable. Drug development studies to date have revealed only modest effect in attenuating growth of these tumors. The present study was aimed at elucidating the potential of targeting glioma through a novel combination of drugs in comparison to single agent. Here, we show that the combined administration of Caffeic acid phenethyl ester [CAPE] and Dasatinib exerts a strong antitumor action on C6 glioma cells. Combinational treatment inhibits proliferation, induces apoptosis, modulates astrocytic phenotype and decreases cell density. Results suggest that combinational therapy inhibits migration and invasiveness, decreases cell survival fraction and hence clonogenic property of C6 cells. The Nitric oxide [NO] levels were significantly reduced by combination treatment at all time points and effect was persistent over the time in comparison to single drug treatment. Atomic Absorption Spectroscopy [AAS] analysis of intracellular and extracellular calcium revealed that the treatment with CAPE and Dasatinib strongly modulates the calcium [Ca(2+)] levels. Herein, we demonstrate that treatment of C6 glioma cells with CAPE and Dasatinib significantly decrease the activity of catalase [CAT]. The results in totality suggest that the combinational therapy remarkably reduces the proliferation of glioma cells possibly through different mechanisms, targeting multiple pathways involved in tumor growth, proliferation and development implicating the relevance of using these drugs in combination therapy for effective treatment of glioma. In vitro results suggest that CAPE and Dasatinib cotreatment could be therapeutically exploited for the management of gliomas. PMID:26553160

  8. Drug combination therapy increases successful drug repositioning.

    PubMed

    Sun, Wei; Sanderson, Philip E; Zheng, Wei

    2016-07-01

    Repositioning of approved drugs has recently gained new momentum for rapid identification and development of new therapeutics for diseases that lack effective drug treatment. Reported repurposing screens have increased dramatically in number in the past five years. However, many newly identified compounds have low potency; this limits their immediate clinical applications because the known, tolerated plasma drug concentrations are lower than the required therapeutic drug concentrations. Drug combinations of two or more compounds with different mechanisms of action are an alternative approach to increase the success rate of drug repositioning. PMID:27240777

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

    PubMed

    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. PMID:24741306

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

    PubMed Central

    Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila MM; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy CR; 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. PMID:24741306

  11. [Drug-related psoriasis].

    PubMed

    Piérard-Franchimont, C; Piérard, G E

    2012-03-01

    Psoriasis is a common genetic disorder that may be initiated (drug-induced psoriasis) or exacerbated (drug-triggered psoriasis) by some drug intakes. Beta-blockers, lithium, some antimelarial drugs, non steroidal anti-inflammatory agents and tetracyclines are recognized to influence the clinical course of psoriasis. Other drugs are likely or possibly involved in this process. PMID:22611830

  12. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  13. [Drug-drug interactions in antirheumatic treatment].

    PubMed

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  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

    PubMed Central

    Dokla, Eman M.; Mahmoud, Amr H.; Elsayed, Mohamed S. A.; El-Khatib, Ahmed H.; Linscheid, Michael W.; Abouzid, Khaled A.

    2012-01-01

    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 GI50 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, which is

  15. Medicare Prescription Drug Coverage

    MedlinePlus

    ... D is the name of Medicare's prescription drug coverage. It's insurance that helps people pay for prescription ... monthly cost. Private companies provide Medicare prescription drug coverage. You choose the drug plan you like best. ...

  16. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  17. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  18. Drug Retention Times

    SciTech Connect

    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

  19. Drug Retention Times

    SciTech Connect

    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.

  20. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  1. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  2. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  3. Attitudes towards drug legalization among drug users.

    PubMed

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin. PMID:11853137

  4. Sustained Accumulation of Microtubule-Binding Chemotherapy Drugs in the Peripheral Nervous System: Correlations with Time Course and Neurotoxic Severity.

    PubMed

    Wozniak, Krystyna M; Vornov, James J; Wu, Ying; Nomoto, Kenichi; Littlefield, Bruce A; DesJardins, Christopher; Yu, Yanke; Lai, George; Reyderman, Larisa; Wong, Nancy; Slusher, Barbara S

    2016-06-01

    Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying the toxicities are unclear. At their MTDs, the microtubule-binding drugs paclitaxel and ixabepilone induce more severe neuropathy in mice relative to eribulin mesylate, paralleling their toxicity profiles in clinic. We hypothesized that the severity of their neurotoxic effects might be explained by the levels at which they accumulate in the peripheral nervous system. To test this hypothesis, we compared their pharmacokinetics and distribution in peripheral nerve tissue. After administration of a single intravenous dose, each drug was rapidly cleared from plasma but all persisted in the dorsal root ganglia (DRG) and sciatic nerve (SN) for up to 72 hours. Focusing on paclitaxel and eribulin, we performed a 2-week MTD-dosing regimen, followed by a determination of drug pharmacokinetics, tissue distribution, and multiple functional measures of peripheral nerve toxicity for 4 weeks. Consistent with the acute dosing study, both drugs persisted in peripheral nervous tissues for weeks, in contrast to their rapid clearance from plasma. Notably, although eribulin exhibited greater DRG and SN penetration than paclitaxel, the neurotoxicity observed functionally was consistently more severe with paclitaxel. Overall, our results argue that sustained exposure of microtubule-binding chemotherapeutic agents in peripheral nerve tissues cannot by itself account for their associated neurotoxicity. Cancer Res; 76(11); 3332-9. ©2016 AACR. PMID:27197173

  5. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  6. A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice.

    PubMed

    Liechtenstein, Therese; Perez-Janices, Noemi; Gato, Maria; Caliendo, Fabio; Kochan, Grazyna; Blanco-Luquin, Idoia; Van der Jeught, Kevin; Arce, Frederick; Guerrero-Setas, David; Fernandez-Irigoyen, Joaquin; Santamaria, Enrique; Breckpot, Karine; Escors, David

    2014-09-15

    Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to produce very large numbers of melanoma-infiltrating MDSCs ex vivo without inducing tumors in mice. These MDSCs were used to study their differentiation, immunosuppressive activities and were compared to non-neoplastic counterparts and conventional dendritic cells using unbiased systems biology approaches. Differentially activated/deactivated pathways caused by cell type differences and by the melanoma tumor environment were identified. MDSCs increased the expression of trafficking receptors to sites of inflammation, endocytosis, changed lipid metabolism, and up-regulated detoxification pathways such as the expression of P450 reductase. These studies uncovered more than 60 potential novel therapeutic targets. As a proof of principle, we demonstrate that P450 reductase is the target of pro-drugs such as Paclitaxel, which depletes MDSCs following chemotherapy in animal models of melanoma and in human patients. Conversely, P450 reductase protects MDSCs against the cytotoxic actions of other chemotherapy drugs such as Irinotecan, which is ineffective for the treatment of melanoma. PMID:25151659

  7. A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice

    PubMed Central

    Liechtenstein, Therese; Perez-Janices, Noemi; Gato, Maria; Caliendo, Fabio; Kochan, Grazyna; Blanco-Luquin, Idoia; Van der Jeught, Kevin; Arce, Frederick; Guerrero-Setas, David; Fernandez-Irigoyen, Joaquin; Santamaria, Enrique; Breckpot, Karine; Escors, David

    2014-01-01

    Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to produce very large numbers of melanoma-infiltrating MDSCs ex vivo without inducing tumors in mice. These MDSCs were used to study their differentiation, immunosuppressive activities and were compared to non-neoplastic counterparts and conventional dendritic cells using unbiased systems biology approaches. Differentially activated/deactivated pathways caused by cell type differences and by the melanoma tumor environment were identified. MDSCs increased the expression of trafficking receptors to sites of inflammation, endocytosis, changed lipid metabolism, and up-regulated detoxification pathways such as the expression of P450 reductase. These studies uncovered more than 60 potential novel therapeutic targets. As a proof of principle, we demonstrate that P450 reductase is the target of pro-drugs such as Paclitaxel, which depletes MDSCs following chemotherapy in animal models of melanoma and in human patients. Conversely, P450 reductase protects MDSCs against the cytotoxic actions of other chemotherapy drugs such as Irinotecan, which is ineffective for the treatment of melanoma. PMID:25151659

  8. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  9. Young drug addicts and the drug scene.

    PubMed

    Lucchini, R

    1985-01-01

    The drug scene generally comprises the following four distinct categories of young people: neophytes, addicts who enjoy a high status vis-à-vis other addicts, multiple drug addicts, and non-addicted drug dealers. It has its own evolution, hierarchy, structure and criteria of success and failure. The members are required to conform to the established criteria. The integration of the young addict into the drug scene is not voluntary in the real sense of the word, for he is caught between the culture that he rejects and the pseudo-culture of the drug scene. To be accepted into the drug scene, the neophyte must furnish proof of his reliability, which often includes certain forms of criminal activities. The addict who has achieved a position of importance in the drug world serves as a role model for behaviour to the neophyte. In a more advanced phase of addiction, the personality of the addict and the social functions of the drug scene are overwhelmed by the psychoactive effects of the drug, and this process results in the social withdrawal of the addict. The life-style of addicts and the subculture they develop are largely influenced by the type of drug consumed. For example, it is possible to speak of a heroin subculture and a cocaine subculture. In time, every drug scene deteriorates so that it becomes fragmented into small groups, which is often caused by legal interventions or a massive influx of new addicts. The fragmentation of the drug scene is followed by an increase in multiple drug abuse, which often aggravates the medical and social problems of drug addicts. PMID:4075000

  10. Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1.

    PubMed

    Sala-Rabanal, Monica; Loo, Donald D F; Hirayama, Bruce A; Turk, Eric; Wright, Ernest M

    2006-07-01

    The human intestinal proton-coupled oligopeptide transporter hPEPT1 has been implicated in the absorption of pharmacologically active compounds. We have investigated the interactions between a comprehensive selection of drugs, and wild-type and variant hPEPT1s expressed in Xenopus oocytes, using radiotracer uptake and electrophysiological methods. The beta-lactam antibiotics ampicillin, amoxicillin, cephalexin and cefadroxil, the antineoplastics delta-aminolevulinic acid (delta-ALA) and bestatin, and the neuropeptide N-acetyl-Asp-Glu (NAAG), were transported, as judged by their ability to evoke inward currents. When the drugs were added in the presence of the typical substrate glycylsarcosine (Gly-Sar), the inward currents were equal or less than that induced by Gly-Sar alone. This suggests that the drugs are transported at a lower turnover rate than Gly-Sar, but may also point towards complex interactions between dipeptides, drugs and the transporter. Gly-Sar and the drugs also modified the kinetics of hPEPT1 presteady-state charge movement, by causing a reduction in maximum charge (Qmax) and a shift of the midpoint voltage (V0.5) to more negative potentials. Our results indicate that the substrate selectivity of hPEPT1 is: Gly-Sar > NAAG, delta-ALA, bestatin > cefadroxil, cephalexin > ampicillin, amoxicillin. Based on steady-state and presteady-state analysis of Gly-Sar and cefadroxil transport, we proposed an extension of the 6-state kinetic model for hPEPT1 function that globally accounts for the observed presteady-state and steady-state kinetics of neutral dipeptide and drug transport. Our model suggests that, under saturating conditions, the rate-limiting step of the hPEPT1 transport cycle is the reorientation of the empty carrier within the membrane. Variations in rates of drug cotransport are predicted to be due to differences in affinity and turnover rate. Oral availability of drugs may be reduced in the presence of physiological concentrations of dietary

  11. Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells.

    PubMed

    Tsaur, Igor; Hudak, Lukasz; Makarević, Jasmina; Juengel, Eva; Mani, Jens; Borgmann, Hendrik; Gust, Kilian M; Schilling, David; Bartsch, Georg; Nelson, Karen; Haferkamp, Axel; Blaheta, Roman A

    2015-08-01

    A significant proportion of men diagnosed with prostate cancer (PCa) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid (VPA), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (IFNα) on PCa cell growth and dissemination capacity were investigated. For that purpose, the human PCa cell lines, PC-3, DU-145 and LNCaP were treated with the combined regimen or separate single agents. Cell growth was investigated by the MTT dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin α and β subtypes were investigated by flow cytometry, western blotting and RT-PCR. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal-regulated kinases (ERK)1/2 activation were also assessed. The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients. PMID:25808196

  12. Drugs and Young People

    MedlinePlus

    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 ...

  13. Utah Drug Use Questionnaire.

    ERIC Educational Resources Information Center

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  14. Skeletal muscle in cancer cachexia: the ideal target of drug therapy.

    PubMed

    Bossola, Maurizio; Pacelli, Fabio; Tortorelli, Antonio; Rosa, Fausto; Doglietto, Giovan Battista

    2008-06-01

    Cancer cachexia is a debilitating and life-threatening syndrome that accounts for at least 20% of deaths in neoplastic patients. Cancer cachexia significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. The loss of lean body mass is the main characteristic of cancer cachexia and the principal cause of function impairment, fatigue and respiratory complications. It is the result of an imbalance between protein synthesis and protein degradation, the mechanisms underlying such alteration being multiple and partially known. Current therapy of cancer cachexia continues to be extremely poor. However, in the last decade, the attention has focused just on the skeletal muscle, as a potential target of therapy, with the aim to discover drugs capable to inhibit the catabolic processes and to stimulate the anabolic pathways. The skeletal muscle has been faced at different levels such as the mediators (cytokines and tumor-derived factors), the receptors (TNF-alpha and androgen receptors), the proteolytic pathways (calpains and ubiquitin-proteasome), the intracellullar signalling pathways (NF-kB, AP-1, FOXO, PKR), and the negative modulators of muscle growth/hypertrophy (myostatin, GSK3-beta). Most of the drugs that have been tested have shown to be effective, at least in experimental models of cancer cachexia. It remains to define their safety, tolerance and efficacy in humans through large, adequate, clinical trials. However, the impression is that there is a light at the back of the tunnel. PMID:18537552

  15. Identification of drugs that restore primary cilium expression in cancer cells

    PubMed Central

    Khan, Niamat Ali; Willemarck, Nicolas; Talebi, Ali; Marchand, Arnaud; Binda, Maria Mercedes; Dehairs, Jonas; Rueda-Rincon, Natalia; Daniels, Veerle W.; Bagadi, Muralidhararao; Raj, Deepak Balaji Thimiri Govinda; Vanderhoydonc, Frank; Munck, Sebastian; Chaltin, Patrick; Swinnen, Johannes V.

    2016-01-01

    The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties. PMID:26862738

  16. Regulation of Multi-drug Resistance in hepatocellular carcinoma cells is TRPC6/Calcium Dependent

    PubMed Central

    Wen, Liang; Liang, Chao; Chen, Enjiang; Chen, Wei; Liang, Feng; Zhi, Xiao; Wei, Tao; Xue, Fei; Li, Guogang; Yang, Qi; Gong, Weihua; Feng, Xinhua; Bai, Xueli; Liang, Tingbo

    2016-01-01

    Hepatocellular carcinoma (HCC) is notoriously refractory to chemotherapy because of its tendency to develop multi-drug resistance (MDR), whose various underlying mechanisms make it difficult to target. The calcium signalling pathway is associated with many cellular biological activities, and is also a critical player in cancer. However, its role in modulating tumour MDR remains unclear. In this study, stimulation by doxorubicin, hypoxia and ionizing radiation was used to induce MDR in HCC cells. A sustained aggregation of intracellular calcium was observed upon these stimuli, while inhibition of calcium signalling enhanced the cells’ sensitivity to various drugs by attenuating epithelial-mesenchymal transition (EMT), Hif1-α signalling and DNA damage repair. The effect of calcium signalling is mediated via transient receptor potential canonical 6 (TRPC6), a subtype of calcium-permeable channel. An in vivo xenograft model of HCC further confirmed that inhibiting TRPC6 enhanced the efficacy of doxorubicin. In addition, we deduced that STAT3 activation is a downstream signalling pathway in MDR. Collectively, this study demonstrated that the various mechanisms regulating MDR in HCC cells are calcium dependent through the TRPC6/calcium/STAT3 pathway. We propose that targeting TRPC6 in HCC may be a novel antineoplastic strategy, especially combined with chemotherapy. PMID:27011063

  17. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  18. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter. PMID:26773302

  19. Practice Gaps: Drug Reactions.

    PubMed

    Wolverton, Stephen E

    2016-07-01

    The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions. PMID:27363888

  20. Monitoring of drug-drug and drug-food interactions.

    PubMed

    Garabedian-Ruffalo, S M; Syrja-Farber, M; Lanius, P M; Plucinski, A

    1988-07-01

    A program for detecting and preventing potentially serious drug-drug and drug-food interactions is described. Two clinical pharmacists developed drug interaction alert (DIA) cards for each potential interaction to be monitored. The cards contain information about the proposed mechanism and potential result of the interaction, as well as information about how to monitor or circumvent the interaction. Staff pharmacists check for the occurrence of potential interactions daily as they verify the filling of the patient-medication cassettes; a poster of all the interactions that are included in the program is posted in each satellite pharmacy to serve as a quick reference for the pharmacists. When a pharmacist detects a potential interaction, he or she completes a DIA card and places it in the medication cassette drawer (if the notice is directed to the nurse) or on the front of the patient's chart (if the notice is directed to the physician). The program was introduced to hospital personnel through inservice education programs and departmental newsletters. The results of a quality assurance review indicated that 95 of 279 (34%) cards dispensed to nurses and 40 of 49 (82%) cards dispensed to physicians resulted in some form of action. The program to detect and prevent potentially serious drug-drug and drug-food interactions has been successful. PMID:3414718

  1. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    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 food-drug 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. PMID:22043389

  2. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  3. The complex metabolic network gearing the G1/S transition in leukemic stem cells: Hints to a rational use of antineoplastic agents

    PubMed Central

    D'Amico, Massimo; Mannini, Antonella; Mini, Enrico; Rovida, Elisabetta; Dello Sbarba, Persio; Olivotto, Massimo; Marzi, Ilaria

    2015-01-01

    We defined the stem cell profile of K562 line, demonstrating the expression of the Embryonic Transcription Factors Oct3/4, Sox2, Klf4 and Nanog. This profile was associated with a high vulnerability to the physiological oxidizable substrate pyruvate. remarkably, this substrate was shown to be innocuous, even at the highest doses, to normal differentiated cells. This vulnerability is based on a complex metabolic trim centered on the cellular redox state expressed by the NADP/NADPH ratio geared by the mitochondrial respiratory chain. Flow cytometry revealed that the inhibition of this chain by antimycin A produced cell accumulation in the S phase of cell cycle and apoptosis. This block negatively interferes with the aerobic synthesis of purines, without affecting the anaerobic synthesis of pyrimidines. This imbalance was reproduced by using two antifolate agents, LY309887 and raltitrexed (TDX), inhibitors of purine or pyrimidine synthesis, respectively. All this revealed the apparent paradox that low doses of TDX stimulated, instead of inhibiting, leukemia cell growth. This paradox might have significant impact on therapy with regard to the effects of TDX during the intervals of administration, when the drug concentrations become so low as to promote maintenance of dormant cancer cells in hypoxic tissue niches. PMID:26396171

  4. Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells

    NASA Astrophysics Data System (ADS)

    Guduru, Rakesh; Liang, Ping; Runowicz, Carolyn; Nair, Madhavan; Atluri, Venkata; Khizroev, Sakhrat

    2013-10-01

    The nanotechnology capable of high-specificity targeted delivery of anti-neoplastic drugs would be a significant breakthrough in Cancer in general and Ovarian Cancer in particular. We addressed this challenge through a new physical concept that exploited (i) the difference in the membrane electric properties between the tumor and healthy cells and (ii) the capability of magneto-electric nanoparticles (MENs) to serve as nanosized converters of remote magnetic field energy into the MENs' intrinsic electric field energy. This capability allows to remotely control the membrane electric fields and consequently trigger high-specificity drug uptake through creation of localized nano-electroporation sites. In in-vitro studies on human ovarian carcinoma cell (SKOV-3) and healthy cell (HOMEC) lines, we applied a 30-Oe d.c. field to trigger high-specificity uptake of paclitaxel loaded on 30-nm CoFe2O4@BaTiO3 MENs. The drug penetrated through the membrane and completely eradicated the tumor within 24 hours without affecting the normal cells.

  5. Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells

    PubMed Central

    Guduru, Rakesh; Liang, Ping; Runowicz, Carolyn; Nair, Madhavan; Atluri, Venkata; Khizroev, Sakhrat

    2013-01-01

    The nanotechnology capable of high-specificity targeted delivery of anti-neoplastic drugs would be a significant breakthrough in Cancer in general and Ovarian Cancer in particular. We addressed this challenge through a new physical concept that exploited (i) the difference in the membrane electric properties between the tumor and healthy cells and (ii) the capability of magneto-electric nanoparticles (MENs) to serve as nanosized converters of remote magnetic field energy into the MENs' intrinsic electric field energy. This capability allows to remotely control the membrane electric fields and consequently trigger high-specificity drug uptake through creation of localized nano-electroporation sites. In in-vitro studies on human ovarian carcinoma cell (SKOV-3) and healthy cell (HOMEC) lines, we applied a 30-Oe d.c. field to trigger high-specificity uptake of paclitaxel loaded on 30-nm CoFe2O4@BaTiO3 MENs. The drug penetrated through the membrane and completely eradicated the tumor within 24 hours without affecting the normal cells. PMID:24129652

  6. [Drug Interactions and Pharmacokinetics of Psychotropic Drugs].

    PubMed

    Suzuki, Eiji

    2015-01-01

    Pharmacokinetics is the field dedicated to investigating the absorption, distribution, metabolism and excretion of drugs. Absorption of drugs is affected when they are taken together with a meal. Depending on the drug, the area under the concentration curve is affected by whether a medication is taken before or after a meal. Combined use of drugs with a high plasma protein binding fraction may be dangerous, since drug efficacy is impacted by efficiency, which in turn is affected by the degree to which it binds to proteins. Even more significant is the issue of "drug/drug" interactions that arise due to inhibition of the cytochrome P450 (CYP) hepatic microsomal enzyme system. Some antidepressants, such as paroxetine and fluvoxamine, are strong inhibitors of the CYP system. In the case of a medication that depends on renal clearance for elimination, caution is required when taking such a drug if it influences renal function. When a medicinal effect changes, pharmacodynamic changes must also be considered. PMID:26514046

  7. Granulomatous Drug Eruptions.

    PubMed

    Dodiuk-Gad, Roni P; Shear, Neil H

    2015-07-01

    Granuloma formation is usually regarded as a means of defending the host from persistent irritants of either exogenous or endogenous origin. Noninfectious granulomatous disorders of the skin encompass a challenging group of diseases owing to their clinical and histologic overlap. Drug reactions characterized by a granulomatous reaction pattern are rare, and defined by a predominance of histiocytes in the inflammatory infiltrate. This review summarizes current knowledge on the various types of granulomatous drug eruptions, focusing on the 4 major types: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, and drug-induced sarcoidosis. PMID:26143430

  8. Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006)

    PubMed Central

    2010-01-01

    Background Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost. Methods Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated. Results During the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. PMID:20942906

  9. Case series in drug safety: a review to determine characteristics and quality.

    PubMed

    Abou Chakra, Claire Nour; Pariente, Antoine; Pinet, Marion; Nkeng, Lenhangmbong; Moore, Nicholas; Moride, Yola

    2010-12-01

    Case series and case reports are a cornerstone of drug safety research; however, the characteristics of case series published in the literature remain poorly examined. A narrative review of case series addressing drug safety, published in the literature between 1 January 2003 and 15 July 2009, and identified through a PubMed search, was conducted in order to determine their characteristics and quality according to the criteria found in the US FDA Pharmacovigilance Guidance 2005. Of 130 publications that met the search criteria, 11.5% included an analytical component and 88.5% were descriptive. The median number of cases included in a given case series was 7 (range 2-2195) and the median time period for recruitment of the cases was 23 months (range 0.5-96). Overall, 43.1% of case series consisted of individual case reports, while 24.6% originated from cohorts and 21% from pharmacovigilance databases. Of the case series, 65.1% concerned adults (age ≥18 years), 11.6% elderly (age ≥65 years) and 8.5% youth (<18 years). Adverse effects involved mainly the skin (18.5%) and the circulatory system (13.8%). The main suspected drug classes (Anatomical Therapeutic Chemical classification) were nervous system drugs (23.1%) and antineoplastic and immunomodulating agents (20.0%). On average, six out of the possible nine US FDA Pharmacovigilance Guidance Criteria were fulfilled, with 27% of publications fulfilling at least seven criteria. Only 10% reported data on co-morbidity. In conclusion, this review highlights the reporting gaps and heterogeneity in published case series with respect to size, recruitment period and quality. PMID:21077699

  10. 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.

    PubMed

    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. PMID:14715664

  11. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  12. Treatment of unresectable stage IV metastatic melanoma with aviscumine after anti-neoplastic treatment failure: a phase II, multi-centre study

    PubMed Central

    2014-01-01

    Background Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV. Methods A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population. Results One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57–85) and median overall survival (mOS) was 335 days (95% CI 210–604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3–4 treatment-emergent drug-related adverse events occurred in 9% of patients. Conclusion These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents. Trial registration ClinicalTrials.gov: NCT00658437 PMID:25324973

  13. Prescription Drug Abuse

    MedlinePlus

    ... 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 narcotic painkillers, ...

  14. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  15. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  16. [Drugs and crime].

    PubMed

    Nishizawa, Munehide

    2010-08-01

    In law-related problems on drugs and crime, there are two types: (1) possession/use of drugs, (2) crimes caused by mental distress after the use of drugs. In this paper, I will focus on the former type called 'drug crimes'. Since drugs cause medically negative effects on the human body, the management/use of drugs is limited by the law which prescribes penalties. At the present, the management/use of narcotics, other mentally stimulating drugs, opium and its raw material, an opium poppy, cannabis, and antihypnotics are limited by six laws, including criminal laws. In this paper, I will introduce the contents of these laws, and the current situation of 'drug crimes'. PMID:20715491

  17. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  18. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  19. Drug-induced hypoglycemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000310.htm Drug-induced hypoglycemia To use the sharing features on this page, please enable JavaScript. Drug-induced hypoglycemia is low blood sugar that results from medication. ...

  20. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  1. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  2. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  3. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that was ... prescription drugs can lead to addiction. These include narcotic painkillers, sedatives, tranquilizers, and stimulants. Every medicine has ...

  4. Drug-induced nightmares.

    PubMed

    2000-12-01

    (1) A wide variety of drugs have been implicated in nightmares, often on inadequate evidence. (2) Recurrent nightmares can be induced by many drugs, and not only agents with psychotropic or neurological effects. PMID:11475499

  5. Neuropathy secondary to drugs

    MedlinePlus

    Neuropathy secondary to drugs is a loss of sensation or movement in a part of the body ... weakness. Many medicines may affect the development of neuropathy, including: Heart or blood pressure drugs: Amiodarone Hydralazine ...

  6. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  7. Treating Prescription Drug Addiction

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  8. Neuropathy secondary to drugs

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000700.htm Neuropathy secondary to drugs To use the sharing features on this page, please enable JavaScript. Neuropathy secondary to drugs is a loss of sensation ...

  9. Drug abuse first aid

    MedlinePlus

    ... or extremely dry, hot skin Tremors Unconsciousness ( coma ) Violent or aggressive behavior Drug withdrawal symptoms also vary ... jeopardize your own safety. Some drugs can cause violent and unpredictable behavior. Call for professional assistance. Do ...

  10. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  11. Other Drugs of Abuse

    MedlinePlus

    ... can make you pass out. It's called a "date rape" drug because someone can secretly put it in your ... you without your permission. Rohypnol (roofies) is a date rape pill and can ... about these drugs . Bath Salts are drugs made with chemicals like ...

  12. Drug Education Guidelines.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing.

    In order to supply drug education guidelines for its schools, the Michigan State Board of Education created an advisory council of professionals from the fields of drugs and education, parents, and high school and college students. The council developed the present set of guidelines designed to define the role of the school in drug education and…

  13. The Drug Problem.

    ERIC Educational Resources Information Center

    Gose, Ben

    1995-01-01

    Drug law violations have risen sharply on college campuses, but officials disagree on the reason. Some students feel administrators are invading their privacy. The trend is attributed to several factors, including changes in how violations are counted, reduced tolerance of increased drug use by non-drug-using students, and more vigorous…

  14. Keeping Youth Drug Free.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This guide is designed to help caregivers prevent children from getting involved in drugs. It details six key prevention principles, including actions caregivers can take that can help their child make healthy choices. Each section includes language to use with children, activities to do, information about drugs, statistics about youth drug use,…

  15. Drugs of Abuse.

    ERIC Educational Resources Information Center

    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…

  16. Strategies against Drugs.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1996-01-01

    The main private organization in Germany dedicated to combatting drug addition--the DHS and the Federal Health Information Agency (BzGA) jointly estimate the number of persons addicted to "illegal" drugs in Germany at around 200,000. Yet, people may grow up immune to drug addiction if they acquire a stable basis for self-confidence and…

  17. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  18. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    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…

  19. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  20. Drug Education Handbook.

    ERIC Educational Resources Information Center

    Gilmore, Robert

    This handbook on drug education is divided into nine sections. Section 1, An Approach to Drug Education, proffers information and advice on such subjects as student ploys, confidentiality, and student questions about marijuana vs. alcohol. Two major ideas in this chapter are that drug education should be integrated into the total curriculum and…

  1. Immediate Drug Hypersensitivity.

    PubMed

    Wickner, Paige G; Hong, David

    2016-07-01

    Drug allergy affects a large percentage of the general population. A listed drug allergy can also have broad implications for many aspects of patient care. Here, we will review recent advances in the arena of drug allergies with a focus on antibiotics, monoclonals, NSAIDs, and chemotherapeutics. PMID:27333778

  2. National Drug Control Strategy.

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, Washington, DC.

    This report presents a comprehensive blueprint for new direction and effort in the national fight against illegal drug use. It is the result of an intensive review of federal anti-drug efforts to date and incorporates advice and recommendations from hundreds of interested and involved anti-drug leaders outside the federal government. The…

  3. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

  4. Drug Monographs: Ixazomib and Necitumumab.

    PubMed

    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. PMID:27303088

  5. Drug Monographs: Ibrutinib and Ramucirumab

    PubMed Central

    Solimando, Dominic A.; Waddell, J. Aubrey

    2014-01-01

    Abstract 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. PMID:25477594

  6. Reduction in Surface Contamination With Cyclophosphamide in 30 US Hospital Pharmacies Following Implementation of a Closed-System Drug Transfer Device

    PubMed Central

    Sessink, Paul J.M.; Trahan, Jason; Coyne, Joseph W.

    2013-01-01

    Purpose: In a follow-up to a previous study, surface contamination with the antineoplastic drug cyclophosphamide was compared in 30 US hospital pharmacies from 2004 to 2010 following preparation with standard drug preparation techniques or the PhaSeal closed system drug transfer device (CSTD). Methods: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils (the front leading edge of the BSC), floors in front of BSCs, and countertops in the pharmacy, and they were analyzed for contamination with cyclophosphamide. Contamination was reassessed after a minimum of 6 months following the implementation of the CSTD. Surface contamination (ng/cm2) was compared between the 2 techniques and between the previous and current test periods and evaluated with the Kruskal-Wallis test. Results: With the use of CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination with cyclophosphamide was observed (P < .0001). Median values for surface contamination with cyclophosphamide were reduced by 86% compared to 95% in the previous study. Conclusions: The CSTD significantly reduced, but did not totally eliminate, surface contamination with cyclophosphamide. In addition to other protective measures, increased usage of CSTDs should be employed to help protect health care workers from exposure to hazardous drugs. PMID:24421463

  7. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePlus

    ... microscope by a specially trained physician (dermatopathologist). In addition, your doctor may want to perform blood work to look for signs of an allergic reaction. The best treatment for a drug rash is ...

  8. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death. PMID:11364863

  9. European drug information centers.

    PubMed

    Markind, J E; Stachnik, J M

    1996-09-01

    Drug information is a clinical specialty throughout the United States and Europe. This professional support service not only addresses drug information requests, but also provides pharmacy (drug) and therapeutics support, newsletter publication, fee-for-service consultation, education, drug policy development, and research. Although the primary services of drug information centers (DICs) in Europe are similar to those in the United States, substantial differences have been reported. Recent surveys have compared the locations, resources, staff, and services of the DICs throughout Europe. DICs in the United States and Europe play a pivotal role in the provision of pharmaceutical care to patients as well as providing support to hospital functions. PMID:9025433

  10. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  11. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

  12. Guideline on controlled drugs.

    PubMed

    2016-06-01

    The National Institute for Health and Care Excellence has published a guideline for using and managing controlled drugs safely in all NHS settings except care homes. The institute's aims are to improve working practices, make sure they comply with legislation, and ensure robust governance arrangements are in place and reduce the safety risks associated with controlled drugs. The guideline includes recommendations on record keeping, risk assessment, reporting drug-related incidents, prescribing and administering, monitoring drug use, and developing systems for the destruction and disposal of controlled drugs. It is available at www.nice.org.uk/guidance/ng46. PMID:27246424

  13. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePlus

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  14. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  15. Drugs Approved for Wilms Tumor

    Cancer.gov

    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.

  16. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  17. Drugs Approved for Liver Cancer

    Cancer.gov

    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.

  18. Drugs Approved for Esophageal Cancer

    Cancer.gov

    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.

  19. Drugs Approved for Vulvar Cancer

    Cancer.gov

    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.

  20. Drugs Approved for Endometrial Cancer

    Cancer.gov

    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.

  1. Drugs Approved for Bone Cancer

    Cancer.gov

    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.

  2. COPD - quick-relief drugs

    MedlinePlus

    COPD - quick-relief drugs; Chronic obstructive pulmonary disease - control drugs; Chronic obstructive airways disease - quick-relief drugs; Chronic obstructive lung disease - quick-relief drugs; Chronic bronchitis - quick-relief ...

  3. Drugs Approved for Penile Cancer

    Cancer.gov

    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.

  4. DEA Multimedia Drug Library: Marijuana

    MedlinePlus

    ... OPERATIONS Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip DRUG INFO Drug Fact Sheets ... Operations Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip Drug Info Drug Fact Sheets ...

  5. Drugs Approved for Skin Cancer

    Cancer.gov

    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.

  6. Drugs Approved for Vaginal Cancer

    Cancer.gov

    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.

  7. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    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.

  8. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

    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.

  9. Serious drug interactions.

    PubMed

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  10. Incidence of potential drug-drug interactions with antidiabetic drugs.

    PubMed

    Samardzic, I; Bacic-Vrca, V

    2015-06-01

    In an effort to achieve normoglycemia more than one antidiabetic agent is usually needed. Diabetes is associated with several comorbidities and patients with diabetes are often treated with multiple medications. Therefore, patients with diabetes are especially exposed to drug-drug interactions (DDIs). The aim of this study was to analyse the incidence and type of potential DDIs of antidiabetic drugs in patients with diabetes. This retrospective study analyzed pharmacy record data of 225 patients with diabetes mellitus. Both type 1 and type 2 diabetic patients who were taking at least one antidiabetic agent during the period of six months were included. We investigated associated therapy in that period in order to identify potential DDIs with antidiabetic therapy. Potential interactions were identified by Lexicomp Lexi-Interat Online (Lexi-Comp, Inc., Hudson, USA) software which categorizes potential DDIs according to clinical significance in five types (A, B, C, D and X). Categories C, D and X are of clinical concern and always require medical attention (therapy monitoring, therapy modification or avoiding combination). We found that 80.9% of patients had at least one potential category C interaction while there were no D and X interactions. Most frequently encountered potential DDI (n = 176) included antidiabetic drugs and thiazide or thiazide like diuretics. Patients with diabetes are exposed to a large number of potential clinically significant DDIs that may require appropriate monitoring. Using databases of DDIs could be helpful in reducing the risk of potential clinically significant DDIs. PMID:26189304

  11. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  12. Commonly used gastrointestinal drugs.

    PubMed

    Aggarwal, Annu; Bhatt, Mohit

    2014-01-01

    This chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threatening extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod have been grave enough to lead to their withdrawal from many world markets. Awareness and recognition of the neurotoxicity of gastrointestinal drugs is essential to help weigh the benefit of their use against possible adverse effects, even if uncommon. Furthermore, as far as possible, drugs such as metoclopramide and others that can lead to tardive dyskinesias should be used for as short time as possible, with close clinical monitoring and patient education. PMID:24365343

  13. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia. PMID:25047526

  14. Percutaneous absorption of drugs.

    PubMed

    Wester, R C; Maibach, H I

    1992-10-01

    The skin is an evolutionary masterpiece of living tissue which is the final control unit for determining the local and systemic availability of any drug which must pass into and through it. In vivo in humans, many factors will affect the absorption of drugs. These include individual biological variation and may be influenced by race. The skin site of the body will also influence percutaneous absorption. Generally, those body parts exposed to the open environment (and to cosmetics, drugs and hazardous toxic substances) are most affected. Treating patients may involve single daily drug treatment or multiple daily administration. Finally, the body will be washed (normal daily process or when there is concern about skin decontamination) and this will influence percutaneous absorption. The vehicle of a drug will affect release of drug to skin. On skin, the interrelationships of this form of administration involve drug concentration, surface area exposed, frequency and time of exposure. These interrelationships determine percutaneous absorption. Accounting for all the drug administered is desirable in controlled studies. The bioavailability of the drug then is assessed in relationship to its efficacy and toxicity in drug development. There are methods, both quantitative and qualitative, in vitro and in vivo, for studying percutaneous absorption of drugs. Animal models are substituted for humans to determine percutaneous absorption. Each of these methods thus becomes a factor in determining percutaneous absorption because they predict absorption in humans. The relevance of these predictions to humans in vivo is of intense research interest. The most relevant determination of percutaneous absorption of a drug in humans is when the drug in its approved formulation is applied in vivo to humans in the intended clinical situation. Deviation from this scenario involves the introduction of variables which may alter percutaneous absorption. PMID:1296607

  15. Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells.

    PubMed

    Donnenberg, Vera S; Meyer, E Michael; Donnenberg, Albert D

    2009-01-01

    Multiple drug resistance, mediated by the expression and activity of ABC-transporters, is a major obstacle to antineoplastic therapy. Normal tissue stem cells and their malignant counterparts share MDR transporter activity as a major mechanism of self-protection. Although MDR activity is upregulated in response to substrate chemotherapeutic agents, it is also constitutively expressed on both normal tissue stem cells and a subset of tumor cells prior to the initiation of therapy, representing a built-in obstacle to therapeutic ratio. Constitutive and induced MDR activity can be detected in cellular subsets of disaggregated tissues, using the fluorescent substrates Rhodamine 123 and Hoechst 33342 for ABCB1 (also known as P-gp and MDR1) and ABCG2 (BCRP1). In this chapter, we will describe the complete procedure for the detection of MDR activity, including: (1) Preparing single-cell suspensions from tumor and normal tissue specimens; (2) An efficient method to perform cell surface marker staining on large numbers of cells; (3) Flow cytometer setup and controls; (4) Simultaneous measurement of Hoechst 33342 and Rhodamine123 transport; and (5) Data acquisition and analysis. PMID:19582433

  16. Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs.

    PubMed

    Mercurio, Valentina; Pirozzi, Flora; Lazzarini, Edoardo; Marone, Giancarlo; Rizzo, Paola; Agnetti, Giulio; Tocchetti, Carlo G; Ghigo, Alessandra; Ameri, Pietro

    2016-06-01

    Heart failure (HF) is a complication of oncological treatments that may have dramatic clinical impact. It may acutely worsen a patient's condition or it may present with delayed onset, even years after treatment, when cancer has been cured or is in stable remission. Several studies have addressed the mechanisms of cancer therapy-related HF and some have led to the definition of disease models that hold valid for other and more common types of HF. Here, we review these models of HF based on the cardiotoxicity of antineoplastic drugs and classify them in cardiomyocyte-intrinsic, paracrine, or potentially secondary to effects on cardiac progenitor cells. The first group includes HF resulting from the combination of oxidative stress, mitochondrial dysfunction, and activation of the DNA damage response, which is typically caused by anthracyclines, and HF resulting from deranged myocardial energetics, such as that triggered by anthracyclines and sunitinib. Blockade of the neuregulin-1/ErbB4/ErbB2, vascular endothelial growth factor/vascular endothelial growth factor receptor and platelet-derived growth factor /platelet-derived growth factor receptor pathways by trastuzumab, sorafenib and sunitinib is proposed as paradigm of cancer therapy-related HF associated with alterations of myocardial paracrine pathways. Finally, anthracyclines and trastuzumab are also presented as examples of antitumor agents that induce HF by affecting the cardiac progenitor cell population. PMID:27103426

  17. Physiologically-based pharmacokinetic modeling of target-mediated drug disposition of bortezomib in mice.

    PubMed

    Zhang, Li; Mager, Donald E

    2015-10-01

    Bortezomib is a reversible proteasome inhibitor with potent antineoplastic activity that exhibits dose- and time-dependent pharmacokinetics (PK). Proteasome-mediated bortezomib disposition is proposed as the primary source of its nonlinear and apparent nonstationary PK behavior. Single intravenous (IV) doses of bortezomib (0.25 and 1 mg/kg) were administrated to BALB/c mice, with blood and tissue samples obtained over 144 h, which were analyzed by LC/MS/MS. A physiologically based pharmacokinetic (PBPK) model incorporating tissue drug-target binding was developed to test the hypothesis of proteasome-mediated bortezomib disposition. The final model reasonably captured bortezomib plasma and tissue PK profiles, and parameters were estimated with good precision. The rank-order of model estimated tissue target density correlated well with experimentally measured proteasome concentrations reported in the literature, supporting the hypothesis that binding to proteasome influences bortezomib disposition. The PBPK model was further scaled-up to humans to assess the similarity of bortezomib disposition among species. Human plasma bortezomib PK profiles following multiple IV dosing (1.3 mg/m(2)) on days 1, 4, 8, and 11 were simulated by appropriately scaling estimated mouse parameters. Simulated and observed bortezomib concentrations after multiple dosing were in good agreement, suggesting target-mediated bortezomib disposition is likely for both mice and humans. Furthermore, the model predicts that renal impairment should exert minimal influence on bortezomib exposure in humans, confirming that bortezomib dose adjustment is not necessary for patients with renal impairment. PMID:26391023

  18. A marriage of two “Methusalem” drugs for the treatment of psoriasis?

    PubMed Central

    Glossmann, Hartmut; Reider, Norbert

    2013-01-01

    In this article we present arguments that the “antidiabetic” drug metformin could be useful as an add-on therapy to methotrexate for the treatment of psoriasis and, perhaps, for rheumatoid arthritis as well. Biochemical data suggest that both drugs may share a common cellular target, the AMP-activated protein kinase (AMPK). This enzyme is a master regulator of metabolism and controls a number of downstream targets, e.g., important for cellular growth or function in many tissues including T-lymphocytes. Clinical observations as well as experimental results argue for anti-inflammatory, antineoplastic and antiproliferative activities of metformin and a case-control study suggests that the drug reduces the risk for psoriasis. Patients with psoriasis have higher risk of metabolic syndrome, type 2 diabetes and cardiovascular mortality. Metformin has proven efficacy in the treatment of prediabetes and leads to a pronounced and sustained weight loss in overweight individuals. We expect that addition of metformin to methotrexate can lead to positive effects with respect to the PASI score, reduction of the weekly methotrexate dose and of elevated cardiovascular risk factors in patients with metabolic syndrome and psoriasis. For reasons explained later we suggest that only male, overweight patients are to be included in a pilot trial. On the other side of the coin are concerns that the gastrointestinal side effects of metformin are intolerable for patients under low dose, intermittent methotrexate therapy. Metformin has another side effect, namely interference with vitamin B12 and folate metabolism, leading to elevated homocysteine serum levels. As patients must receive folate supplementation and will be controlled with respect to their B12 status increased hematological toxicity is unlikely to result. PMID:24194965

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

    PubMed Central

    Moinfar, Zahra; Dambach, Hannes; Faustmann, Pedro M.

    2014-01-01

    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. PMID:24904426

  20. Drug addiction in China.

    PubMed

    Lu, Lin; Wang, Xi

    2008-10-01

    Drug addiction in China began with the importation of Indian opium by the British in the 16th century and brought severe social and health problems. While drug abuse abated following the establishment of People's Republic of China, modernization and Westernization in the 1980s led to the reemergence of this problem. Drug abuse in China became epidemic, facilitating the spread of HIV/AIDS. The Chinese government has made great efforts to address these problems, focusing both on treatments of drug addiction and on harm-reduction programs. Although the new trends of drug addiction in China pose great public health challenges, these government interventions are likely to successfully stem the problem of drug abuse in the future. PMID:18991965

  1. Grapefruit and drug interactions.

    PubMed

    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

  2. New Antithrombotic Drugs

    PubMed Central

    Eikelboom, John W.; Samama, Meyer Michel

    2012-01-01

    This article focuses on new antithrombotic drugs that are in or are entering phase 3 clinical testing. Development of these new agents was prompted by the limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this article (1) outlines the rationale for development of new antithrombotic agents; (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs; and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents. PMID:22315258

  3. How physicians choose drugs.

    PubMed

    Denig, P; Haaijer-Ruskamp, F M; Zijsling, D H

    1988-01-01

    A drug choice model which includes the physician's attitudes, norms and personal experiences with drugs, was tested. One hundred and sixty-nine physicians were asked to estimate the model's components for the treatment of irritable bowel syndrome (IBS) and of renal colic. Given three drugs for both indications, the physicians gave their expectancies about the treatment outcomes, professional acceptability, patient demand and their personal experiences with the drugs. They also stated the value they assign to each of these components when choosing a drug for IBS and for renal colic. The influence of patient demand on the choice of a specific drug appeared to be negligible. The combined effect of the other three elements of the model predicted the stated drug of first choice correctly in 74% (for IBS) and 78% (for renal colic) of the cases, but further analysis showed that only the drug choices for renal colic were as reasoned as the model assumed. Expectancies and values about treatment outcomes determined the drug choice only in part. For choosing a drug for renal colic, the professional environment was more important. Moreover it was found that drug preferences were more related to expectancies about efficacy than to expectancies about side effects for both disorders. The findings can be useful when trying to change prescribing behaviour. Only a limited effect can be expected from the provision of technical drug information. Especially information about costs is unlikely to change prescribing easily, unless values and norms are changed as well. The importance of the professional environment implies that educational programmes in groups might be more effective than individual approaches. PMID:3238456

  4. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  5. Drug-induced panniculitides.

    PubMed

    Borroni, G; Torti, S; D'Ospina, R M; Pezzini, C

    2014-04-01

    A substantial number of all panniculitides fails to recognize a specific etiology, and that is true also for a relatively frequent type of panniculitis, such as erythema nodosum (EN). Between the recognized causative factors of panniculitides, infectious, physical agents, autoimmune mechanisms and neoplastic disorders are well known. On the contrary, the role of drugs as inducers of panniculitides is marginally considered, and their report limited to anecdotal observations, often without due histopathological support. Since the clinical and histopathological features of drug-induced panniculitides are indistinguishable from those caused by other agents, the causative relationship may be demonstrated by the history of previous drug intake and by clinical improvement after drug discontinuation. We reviewed the currently reported descriptions of drug-induced panniculitis, including a few exemplificative original observations. EN results as the most frequently reported drug-induced panniculitis. Among the causative drugs of EN a variety of medications, with disparate, or even opposite, mechanisms of action are reported, thus limiting the understanding of the pathogenesis. Common causative drugs include oral contraceptives, nonsteroidal anti-inflammatory drugs, antiobiotics and leukotriene-modifying agents. Unfortunately, in several cases, the diagnosis of drug-induced EN is done on clinical findings alone. In those cases, the lack of histopathological support does not allow to define a precise clinicopathological correlation on etiologic grounds. Drug-induced lobular and mixed panniculitides, including eosinophilic panniculitis, are even more rarely described. Reported causative agents are glatiramer acetate, interferon beta and heparin (at sites of injections), and systemic steroids, tyrosine kinase inhibitors and BRAF with subcutaneous fat involvement at distance. In view of the recent introduction of new classes of drugs, attention should be paid to disclose their

  6. Discontinued drugs in 2012: cardiovascular drugs.

    PubMed

    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. PMID:23992034

  7. Adverse Drug Interactions

    PubMed Central

    Becker, Daniel E.

    2011-01-01

    The potential for interactions with current medications should always be considered when administering or prescribing any drug. Considering the staggering number of drugs patients may be taking, this task can be daunting. Fortunately, drug classes employed in dental practice are relatively few in number and therapy is generally brief in duration. While this reduces the volume of potential interactions, there are still a significant number to be considered. This article will review basic principles of drug interactions and highlight those of greatest concern in dental practice. PMID:21410363

  8. Street drugs: everyone's business.

    PubMed

    Su'a, F

    1989-11-01

    In the profession of law enforcement, we see drug abuse as our most serious crime problem. We also realize that simply making arrests, by itself, won't solve the problem. The drug business might be the filthiest business on earth, but it's not a business that forces customers to buy dope. Dope dealers may be ruthless and may even kill, but no one forces anyone to buy drugs at gunpoint. The truth is that drug dealers would go nowhere, were it not for the customers. PMID:2592190

  9. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  10. [The importance of therapeutic drug monitoring for psychotropic drugs].

    PubMed

    Messer, Thomas; Schmauss, Max

    2006-05-15

    The goal of therapeutic drug monitoring (TDM) is the optimization of the psychiatric pharmacotherapy. Above all, TDM is absolutely indicated for the prevention of adverse drug effects or poisoning. TDM is well-established for therapies with antidepressants, antipsychotic drugs and mood stabilizers. For anti-dementia drugs, anxiolytic drugs, hypnotic drugs and medications for treating addiction, monitoring is currently applied to the interpretation of side effects, drug interactions and to forensic questions. PMID:20104722

  11. Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements.

    PubMed

    Calandra, Eleonora; Posocco, Bianca; Crotti, Sara; Marangon, Elena; Giodini, Luciana; Nitti, Donato; Toffoli, Giuseppe; Traldi, Pietro; Agostini, Marco

    2016-07-01

    Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters. In order to determine the drug concentration during the administration protocol, we developed a quantitative MALDI-MS method using CHCA as MALDI matrix. Here, we demonstrate that MALDI-TOF can be applied in a routine setting for therapeutic drug monitoring in humans offering quick and accurate results. To reach this aim, we cross validated, according to FDA and EMA guidelines, the MALDI-TOF method in comparison with a standard LC-MS/MS method, applying it for the quantification of 108 patients' plasma samples from a clinical trial. Standard curves for irinotecan were linear (R (2) ≥ 0.9842) over the concentration ranges between 300 and 10,000 ng/mL and showed good back-calculated accuracy and precision. Intra- and inter-day precision and accuracy, determined on three quality control levels were always <12.8 % and between 90.1 and 106.9 %, respectively. The cross-validation procedure showed a good reproducibility between the two methods, the percentage differences within 20 % in more than 70 % of the total amount of clinical samples analysed. PMID:27235158

  12. Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.

    PubMed

    Juárez-Cedillo, Teresa; Martinez-Hernández, Cynthia; Hernández-Constantino, Angel; Garcia-Cruz, Juan Carlos; Avalos-Mejia, Annia M; Sánchez-Hurtado, Luis A; Islas Perez, Valentin; Hansten, Philip D

    2016-04-01

    Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug-drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross-sectional study between January and April 2014; all patients 70 years or older, hospitalized for >24 hr and prescribed at least one medication were included in the study. Drug-drug interactions were estimated by combining Stockley's, Hansten and Tatro drug interactions. Drug-drug interactions were weighted using a risk-analysis method based on failure modes, effects and criticality analysis. We calculated a criticality index for each drug involved in the drug-drug interactions based on the severity of the interaction mechanism, the frequency the drug was involved in drug-drug interactions and the risk of drug-drug interactions in patients with impaired renal function. The average number of drugs consumed in the hospital was 6 ± 2.69, involving 160 active ingredients. The most frequent were as follows: Furosemide, followed by Enalapril. Of drug-drug interactions, 2% were classified as contraindicated, 14% advised against and 83% advised caution during the hospital stay. Thirty-four drug-drug interactions were assessed, of which 23 were pharmacodynamic drug-drug interactions and 12 were pharmacokinetic drug-drug interactions (1 was both). The clinical risk calculated for each drug-drug interaction included heparins + non-steroidal anti-inflammatory drugs (NSAIDs) or Digoxin + Calcium Gluconate, cases which are pharmacodynamic drug-drug interactions with agonist effect and clinical risk of bleeding, one of the most common clinical risks in the hospital. An index of clinical risk for drug-drug interactions can be calculated based on severity by the interaction mechanism, the frequency that the drug is involved in drug-drug interactions and the risk of drug-drug interactions in an

  13. Aprepitant: drug-drug interactions in perspective.

    PubMed

    Aapro, M S; Walko, C M

    2010-12-01

    The implications of chemotherapeutic drug-drug interactions can be serious and thus need to be addressed. This review concerns the potential interactions of the antiemetic aprepitant, a neurokinin-1 receptor antagonist indicated for use (in Europe) in highly emetogenic chemotherapy and moderately emetogenic chemotherapy (MEC) in combination with a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and corticosteroids and (in the United States) in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin. When considering use of aprepitant for prevention of chemotherapy-induced nausea and vomiting, its potential drug-drug interaction profile as a moderate inhibitor of cytochrome P-450 isoenzyme 3A4 (CYP3A4) has been a source of concern for some physicians and other health care professionals. We explore in this paper how real those concerns are. Our conclusion is that either no interaction or no clinically relevant interaction exists with chemotherapeutic agents (intravenous cyclophosphamide, docetaxel, intravenous vinorelbine) or 5-HT3 antagonists (granisetron, ondansetron, palonosetron). For relevant interactions, appropriate measures, such as corticosteroid dose modifications and extended International Normalized Ratio monitoring of patients on warfarin therapy, can be taken to effectively manage them. Therefore, the concern of negative interactions remains largely theoretical but needs to be verified with new agents extensively metabolized through the 3A4 pathway. PMID:20488873

  14. Hyaluronic Acid-Based Hydrogels as 3D Matrices for in Vitro Evaluation of Chemotherapeutic Drugs Using Poorly Adherent Prostate Cancer Cells

    PubMed Central

    Gurski, Lisa A.; Jha, Amit K.; Zhang, Chu; Jia, Xinqiao; Farach-Carson, Mary C.

    2009-01-01

    The current investigation aimed to develop a biomimetic, three-dimensional (3D) culture system for poorly adherent bone metastatic prostate cancer cells (C4-2B) for use as an in vitro platform for anti-cancer drug screening. To this end, hyaluronic acid (HA) derivatives carrying complementary aldehyde (HAALD) and hydrazide (HAADH) groups were synthesized and characterized. In situ encapsulation of C4-2B cells was achieved by simple mixing of HAALD and HAADH in the presence of the cells. Unlike two-dimensional (2D) monolayer culture in which cells adopt an atypical spread morphology, cells residing in the HA matrix formed distinct clustered structures which grew and merged, reminiscent of real tumors. Anti-cancer drugs added to the media surrounding the cell/gel construct diffused into the gel and killed the embedded cells. The HA hydrogel system was used successfully to test the efficacy of anti-cancer drugs including camptothecin, docetaxel, and rapamycin, alone and in combination, including specificity, dose and time responses. Responses of cells to anti-neoplastics differed between the 3D HA hydrogel and 2D monolayer systems. We suggest that the data obtained from 3D HA systems is superior to that from conventional 2D monolayers as the 3D system better reflects the bone metastatic microenvironment of the cancer cells. PMID:19695694

  15. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2005-01-01

    The Vernonia School District v. Acton Supreme Court decision in 1995, forever changed the landscape of the legality of drug testing in schools. This decision stated that students who were involved in athletic programs could be drug tested as long as the student's privacy was not invaded. According to some in the medical profession, there are two…

  16. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  17. DRUG INDUCED CHOLESTASIS

    PubMed Central

    Padda, Manmeet S.; Sanchez, Mayra; Akhtar, Abbasi J.; Boyer, James L.

    2011-01-01

    Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug induced cholestasis. This review summarizes their variable clinical presentations, examines the, role of transport proteins in hepatic drug clearance and toxicity and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. PMID:21480339

  18. Vaginal drug distribution modeling.

    PubMed

    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. PMID:25933938

  19. Drug Education. PREP-36.

    ERIC Educational Resources Information Center

    Chow, Stanley; And Others

    What schools can do and are doing to prevent the abuse of drugs by their students is the focus of this report. The first section of the report "An Overview of Current Efforts" presents the findings of a one-year study of drug education in the United States, with a subjective analysis of the various approaches in the field. In the second section…

  20. Is Drug Education Useful?

    ERIC Educational Resources Information Center

    Hozinsky, Murray

    1971-01-01

    The author contends that the overall effect of drug education has not produced a discernible reduction in drug use. Schools can be of aid to students by proper selection of resource people, committed to self-preparation and growth. (Author/BY)

  1. "Precision" drug development?

    PubMed

    Woodcock, J

    2016-02-01

    The concept of precision medicine has entered broad public consciousness, spurred by a string of targeted drug approvals, highlighted by the availability of personal gene sequences, and accompanied by some remarkable claims about the future of medicine. It is likely that precision medicines will require precision drug development programs. What might such programs look like? PMID:26331240

  2. Automated drug identification system

    NASA Technical Reports Server (NTRS)

    Campen, C. F., Jr.

    1974-01-01

    System speeds up analysis of blood and urine and is capable of identifying 100 commonly abused drugs. System includes computer that controls entire analytical process by ordering various steps in specific sequences. Computer processes data output and has readout of identified drugs.

  3. Implantable Drug Dispenser

    NASA Technical Reports Server (NTRS)

    Collins, E. R. J.

    1983-01-01

    Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

  4. Dimensions of Drug Information

    ERIC Educational Resources Information Center

    Sharp, Mark E.

    2011-01-01

    The high number, heterogeneity, and inadequate integration of drug information resources constitute barriers to many drug information usage scenarios. In the biomedical domain there is a rich legacy of knowledge representation in ontology-like structures that allows us to connect this problem both to the very mature field of library and…

  5. Drugs, Alcohol & Pregnancy.

    ERIC Educational Resources Information Center

    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…

  6. Drug and Substance Abuse

    MedlinePlus

    ... Latest Research Getting More Help Related Topics Anxiety COPD Delirium Depression Pain Management Prevention Related News Older Adults Who Drink Alcohol at Risk for Drug Interactions Monday, November 23, 2015 Join our e-newsletter! Aging & Health A to Z Drug and Substance Abuse ...

  7. Enhancing Drug Court Success

    ERIC Educational Resources Information Center

    Deschenes, Elizabeth Piper; Ireland, Connie; Kleinpeter, Christine B.

    2009-01-01

    This study evaluates the impact of enhanced drug court services in a large county in Southern California. These enhanced services, including specialty counseling groups, educational/employment resources, and increased Residential Treatment (RT) beds, were designed to increase program retention and successful completion (graduation) of drug court.…

  8. Student Drug Use.

    ERIC Educational Resources Information Center

    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…

  9. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2007-01-01

    In 2002, the United States Supreme Court confirmed that in the school's role of in loco parentis, drug testing of students who were involved in athletics and extracurricular activities was constitutional. In a state of the union address, George W. Bush stated that drug testing in schools had been effective and was part of "our aggressive…

  10. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  11. APPLE against Drugs.

    ERIC Educational Resources Information Center

    Holt, Camille B.

    1987-01-01

    The author describes the formation of a citizens' group in Clarkesville, Tennessee, to educate the town's youth about the health risks of drug use. This group developed a curriculum entitled "I'm Special" designed to teach self-esteem and decision-making skills to fourth graders, to enable them to deal with peer pressure to try or use drugs. (CH)

  12. Canadian drug regulatory framework.

    PubMed

    Kelly, L; Lazzaro, M; Petersen, C

    2007-03-01

    The role of regulatory drug submission evaluators in Canada is to critically assess both the data submitted and the sponsor's interpretation of the data in order to reach an evidence-, and context-based recommendation as to the potential benefits and potential harms (i.e., risks) associated with taking the drug under the proposed conditions of use. The purpose of this document is to outline the regulatory framework in which this assessment occurs, including: defining what "authorization to market a drug in Canada" means, in terms of the role of the sponsor, the responsibility of Health Canada in applying the Food and Drugs Act prior to and after marketing authorization, and the distinction between regulatory authorization versus physician authorization; highlighting organizational, process and legal factors within Health Canada related to authorization of clinical trials and authorization to market a drug; considerations during the review process, such as regulatory and scientific issues related to the drug, patient populations and trial designs; application of international guidelines, and decisions from other jurisdictions; regulatory realities regarding drug authorization, including the requirement for wording in the Product Monograph to accurately reflect the information currently available on the safe and effective use of a drug, and that hypothesis-confirming studies are essential to regulatory endorsement; current issues related to the review of therapies for dementia, such as assessing preventative treatments, and therapies that have symptomatic versus disease-modifying effects, statistical issues regarding missing data, and trial design issues. PMID:17469674

  13. Tartrazine-containing drugs.

    PubMed Central

    Bartle, W. R.

    1976-01-01

    Pharmaceutical manufacturers producing or distributing drugs in Canada were surveyed between December 1974 and March 1975 to determine which of their products contained tartrazine, a pyrazole aniline dye. A list of some 580 drug products of the 156 manufacturers who responded is presented for aid in managing the tartrazine-sensitive patients. PMID:953903

  14. Drugs and Addictions.

    ERIC Educational Resources Information Center

    Smith, S. Mae; Miller, Eva

    The effects of drug abuse and dependence vary, depending on the type of drug, polydrug use, and characteristics of the user. The influence of genetic, neurochemical, neuropsyiological, sociocultural, and economic factors suggest that the etiology of substance abuse and dependence is multiply determined. Models explaining the causation of substance…

  15. Interoception and Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.

    2013-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

  16. Prescription Drug Abuse

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  17. Environment and drug trafficking.

    PubMed

    Bryson, L O

    1992-01-01

    Illicit drug trafficking is a very complex matter, not only because it causes serious and pernicious problems in the socio-economic sphere, but because drug-taking can lead to personal degradation. To this situation, lamentable enough in itself, must be added the immense ecological and environmental damage, which presents grave and serious dangers for the planet. PMID:1302599

  18. Flaws of drug instrumentalization.

    PubMed

    Swendsen, Joel; Le Moal, Michel

    2011-12-01

    The adaptive use of drugs, or "drug instrumentalization," is presented as a reality that the scientific literature has largely ignored. In this commentary, we demonstrate why this concept has limited value from the standpoint of nosology, why it should not be viewed as "adaptive," and why it has dangerous implications for policy and public health efforts. PMID:22074977

  19. Interoception and drug addiction.

    PubMed

    Paulus, Martin P; Stewart, Jennifer L

    2014-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an "embodied" experience of drug uses together with the individual's predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. PMID:23855999

  20. Probabilistic drug connectivity mapping

    PubMed Central

    2014-01-01

    Background The aim of connectivity mapping is to match drugs using drug-treatment gene expression profiles from multiple cell lines. This can be viewed as an information retrieval task, with the goal of finding the most relevant profiles for a given query drug. We infer the relevance for retrieval by data-driven probabilistic modeling of the drug responses, resulting in probabilistic connectivity mapping, and further consider the available cell lines as different data sources. We use a special type of probabilistic model to separate what is shared and specific between the sources, in contrast to earlier connectivity mapping methods that have intentionally aggregated all available data, neglecting information about the differences between the cell lines. Results We show that the probabilistic multi-source connectivity mapping method is superior to alternatives in finding functionally and chemically similar drugs from the Connectivity Map data set. We also demonstrate that an extension of the method is capable of retrieving combinations of drugs that match different relevant parts of the query drug response profile. Conclusions The probabilistic modeling-based connectivity mapping method provides a promising alternative to earlier methods. Principled integration of data from different cell lines helps to identify relevant responses for specific drug repositioning applications. PMID:24742351

  1. Impact and Roles of Drug Information in Drug Education

    ERIC Educational Resources Information Center

    Goodstadt, Michael S.

    1975-01-01

    Evidence is presented elucidating the role of knowledge about drugs in facilitating or impeding drug use. The issues considered include (1) the role of drug information in previous "education" programs, (2) the source and uses of drug information, (3) the impact of this information, and (4) the alternative roles for drug information. (Author)

  2. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  3. [Drugs and diarrhea].

    PubMed

    Haschke, Manuel

    2014-09-01

    Drug induced diarrhea is a frequent adverse event. The pathophysiological mechanisms include intraluminal accumulation of osmotically active substances, increased secretion or impaired resorption of gastrointestinal fluids, stimulation of gastrointestinal motility, or inflammation of gastrointestinal mucosa. For many drugs, however, the causative mechanism is unknown. A careful drug history, including non-prescription drugs and additives that frequently cause diarrhea, is essential for the identification of potential causative substances. The clinical course of drug-induced diarrhea in many cases is mild and self-limited. In severe cases fluid-and electrolyte substitution, symptomatic and in certain cases specific therapy can be necessary. Symptomatic treatment primarily includes opioids and intraluminal adsorbents. In special cases octreotide or scopolamine can be used. PMID:25154693

  4. Computational drug discovery

    PubMed Central

    Ou-Yang, Si-sheng; Lu, Jun-yan; Kong, Xiang-qian; Liang, Zhong-jie; Luo, Cheng; Jiang, Hualiang

    2012-01-01

    Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field. PMID:22922346

  5. Antineoplastic constituents of some Southern African plants.

    PubMed

    Charlson, A J

    1980-12-01

    Extracts of several Southern African plants which have been used in folk remedies have been prepared, and the extracts were tested in a variety of experimental tumour test-systems. Raphionacme hirsuta and Cheilanthes contracta have been used in African anticancer medicines. Extracts of these plants showed antitumor activity in some rodent test-systems, but the results were not confirmed. In the folk-lore, Haemanthus natalensis has been used in emetics and Urginea capitata preparations have been used to vaccinate African chiefs. Extracts of these plants showed significant cytotoxicity in the KB cell culture test-system. Infusions of Brunsvigia radulosa have been used as folk remedies for abdominal troubles. An extract of this Amaryllis plant increased the life span of P-388 leukaemic mice. Amaryllis bellandonna has also been investigated. Extracts of Amaryllis belladonna had to be fractionated in order to produce significant antitumour activity in the P-388 lymphocytic leukaemia test-system. PMID:7421280

  6. Cytotoxic drugs in drinking water: a prediction and risk assessment exercise for the thames catchment in the United kingdom.

    PubMed

    Rowney, Nicole C; Johnson, Andrew C; Williams, Richard J

    2009-12-01

    Cytotoxic, also known as antineoplastic, drugs remain an important weapon in the fight against cancer. This study considers the water quality implications for the Thames catchment (United Kingdom) arising from the routine discharge of these drugs after use, down the drain and into the river. The review focuses on 13 different cytotoxic drugs from the alkylating agent, antimetabolite, and anthracycline antibiotic families. A geographic-information-system-based water quality model was used in the present study. The model was informed by literature values on consumption, excretion, and fate data to predict raw drinking water concentrations at the River Thames abstraction points at Farmoor, near Oxford, and Walton, in West London. To discover the highest plausible values, upper boundary values for consumption and excretion together with lower removal values for sewage treatment were used. The raw drinking water cytotoxic drug maximum concentrations at Walton (the higher of the two) representative of mean and low flow conditions were predicted to be 11 and 20 ng/L for the five combined alkylating agents, 2 and 4 ng/L for the three combined antimetabolites, and 0.05 and 0.10 ng/L the for two combined anthracycline antibiotics, respectively. If they were to escape into tap water, then the highest predicted concentrations would still be a factor of between 25 and 40 below the current recommended daily doses of concern. Although the risks may be negligible for healthy adults, more concern may be associated with special subgroup populations, such as pregnant women, their fetuses, and breast-feeding infants, due to their developmental vulnerability. PMID:19691418

  7. Off-Label Drug Use

    MedlinePlus

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  8. PECTIN IN CONTROLLED DRUG DELIVERY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

  9. Drugs, Society, and Human Behavior.

    ERIC Educational Resources Information Center

    Ray, Oakley

    The varied aspects of drugs, their source, abuse, chemical composition, and physical, personal, and social effects are explored. Seven units cover the following areas: (1) an overview on drug use, a brief history of drugs and discussion of social implications; (2) the human nervous system and the actions of drugs; (3) "nondrug drugs" such as…

  10. Drugs Approved for Testicular Cancer

    Cancer.gov

    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.

  11. Drugs Approved for Cervical Cancer

    Cancer.gov

    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.

  12. Drugs Approved for Hodgkin Lymphoma

    Cancer.gov

    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.

  13. Drugs Approved for Myeloproliferative Neoplasms

    Cancer.gov

    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.

  14. Drugs Approved for Multiple Myeloma

    Cancer.gov

    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.

  15. Is the Drug Problem Soluble?

    ERIC Educational Resources Information Center

    Jonas, Steven

    1989-01-01

    Concludes that the principle drug problems in the United States arise from the use of cigarette tobacco and alcoholic beverages. Identifies a drug culture as the persistent force in society that promotes drug use. Points out that the influence of the primary drug industries inhibit attempts to deal effectively with drug problems. (KO)

  16. Drug discovery in academia.

    PubMed

    Verkman, A S

    2004-03-01

    Drug discovery and development is generally done in the commercial rather than the academic realm. Drug discovery involves target discovery and validation, lead identification by high-throughput screening, and lead optimization by medicinal chemistry. Follow-up preclinical evaluation includes analysis in animal models of compound efficacy and pharmacology (ADME: administration, distribution, metabolism, elimination) and studies of toxicology, specificity, and drug interactions. Notwithstanding the high-cost, labor-intensive, and non-hypothesis-driven aspects of drug discovery, the academic setting has a unique and expanding niche in this important area of investigation. For example, academic drug discovery can focus on targets of limited commercial value, such as third-world and rare diseases, and on the development of research reagents such as high-affinity inhibitors for pharmacological "gene knockout" in animal models ("chemical genetics"). This review describes the practical aspects of the preclinical drug discovery process for academic investigators. The discovery of small molecule inhibitors and activators of the cystic fibrosis transmembrane conductance regulator is presented as an example of an academic drug discovery program that has yielded new compounds for physiology research and clinical development. PMID:14761879

  17. Anti-Microtubule Drugs.

    PubMed

    Florian, Stefan; Mitchison, Timothy J

    2016-01-01

    Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug-disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment. PMID:27193863

  18. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  19. Benzylpiperazine: "A messy drug".

    PubMed

    Katz, D P; Deruiter, J; Bhattacharya, D; Ahuja, M; Bhattacharya, S; Clark, C R; Suppiramaniam, V; Dhanasekaran, M

    2016-07-01

    Designer drugs are synthetic structural analogues/congeners of controlled substances with slightly modified chemical structures intended to mimic the pharmacological effects of known drugs of abuse so as to evade drug classification. Benzylpiperazine (BZP), a piperazine derivative, elevates synaptic dopamine and serotonin levels producing stimulatory and hallucinogenic effects, respectively, similar to the well-known drug of abuse, methylenedioxymethamphetamine (MDMA). Furthermore, BZP augments the release of norepinephrine by inhibiting presynaptic autoreceptors, therefore, BZP is a "messy drug" due to its multifaceted regulation of synaptic monoamine neurotransmitters. Initially, pharmaceutical companies used BZP as a therapeutic drug for the treatment of various disease states, but due to its contraindications and abuse potential it was withdrawn from the market. BZP imparts predominately sympathomimetic effects accompanied by serious cardiovascular implications. Addictive properties of BZP include behavioral sensitization, cross sensitization, conditioned place preference and repeated self-administration. Additional testing of piperazine derived drugs is needed due to a scarcity of toxicological data and widely abuse worldwide. PMID:27207154

  20. Anticancer drugs during pregnancy.

    PubMed

    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. PMID:27284093

  1. Teratogenic drugs and their drug interactions with hormonal contraceptives.

    PubMed

    Ahn, M R; Li, L; Shon, J; Bashaw, E D; Kim, M-J

    2016-09-01

    The US Food and Drug Administration (FDA) Guidance for Industry-Drug Interaction Studies, recommends that a potential human teratogen needs to be studied in vivo for effects on contraceptive steroids.(1) This article highlights the need to evaluate the drug-drug interactions (DDIs) between drugs with teratogenic potential and hormonal contraceptives (HCs) during drug development. It also addresses the FDA's effort of communicating DDI findings in product labels to mitigate the risk of unintended pregnancy. PMID:27090193

  2. [Antidepressant drugs and breastfeeding].

    PubMed

    Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe

    2007-01-01

    The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect. PMID:17345878

  3. Antiviral Drug Allergy

    PubMed Central

    Milpied-Homsi, Brigitte; Moran, Ellen M.; Phillips, Elizabeth J.

    2014-01-01

    Antiviral drugs used to treat HIV and hepatitis C are common causes of delayed drug hypersensitivities for which many of the more severe reactions have been recently shown to be immunogenetically mediated such as abacavir hypersensitivity where HLA-B*57:01 is now used routinely as a screening test to exclude patients carrying this allele from abacavir prescription. Most antiviral drug allergies consist of mild to moderate delayed rash without other serious features (e.g. fever, mucosal involvement, blistering rash, organ impairment. In these cases treatment can be continued with careful observation and symptomatic management and the discontinuation rate is low. PMID:25017682

  4. [New anthelmintic drugs].

    PubMed

    Apt, W

    1990-09-01

    New anti-helminthic drugs have appeared lately: benzimidazoles (mebendazole, flubendazol, and abendazole), praziquantel and ivermectin. Mebendazol and flubendazol are poorly absorbed and are effective for ascaris, oxyuriasis and trycocephalus both in adults and children. Abendazole is well absorbed and may be considered the drug of choice for ascaris and oxyuriasis at a single 400 mg dose. This drug may also be used for hydatid cyst when surgery is not possible and for cysticercosis of the nervous system. Praziquantel is useful for treatment of tenia infections and ivermectin is useful for strongyloides and trichostrongyloides. Detailed dose schedules for different parasitic diseases are given in the text. PMID:2152732

  5. Drug-induced epistaxis?

    PubMed Central

    Watson, M G; Shenoi, P M

    1990-01-01

    To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of nonsteroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function. PMID:2325058

  6. Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma

    PubMed Central

    Santoro, Marco; Lamhamedi-Cherradi, Salah-Eddine; Menegaz, Brian A.; Ludwig, Joseph A.; Mikos, Antonios G.

    2015-01-01

    Three-dimensional tumor models accurately describe different aspects of the tumor microenvironment and are readily available for mechanistic studies of tumor biology and for drug screening. Nevertheless, these systems often overlook biomechanical stimulation, another fundamental driver of tumor progression. To address this issue, we cultured Ewing sarcoma (ES) cells on electrospun poly(ε-caprolactone) 3D scaffolds within a flow perfusion bioreactor. Flow-derived shear stress provided a physiologically relevant mechanical stimulation that significantly promoted insulin-like growth factor-1 (IGF1) production and elicited a superadditive release in the presence of exogenous IGF1. This finding is particularly relevant, given the central role of the IGF1/IGF-1 receptor (IGF-1R) pathway in ES tumorigenesis and as a promising clinical target. Additionally, flow perfusion enhanced in a rate-dependent manner the sensitivity of ES cells to IGF-1R inhibitor dalotuzumab (MK-0646) and showed shear stress-dependent resistance to the IGF-1R blockade. This study demonstrates shear stress-dependent ES cell sensitivity to dalotuzumab, highlighting the importance of biomechanical stimulation on ES-acquired drug resistance to IGF-1R inhibition. Furthermore, flow perfusion increased nutrient supply throughout the scaffold, enriching ES culture over static conditions. Our use of a tissue-engineered model, rather than human tumors or xenografts, enabled precise control of the forces experienced by ES cells, and therefore provided at least one explanation for the remarkable antineoplastic effects observed by some ES tumor patients from IGF-1R targeted therapies, in contrast to the lackluster effect observed in cells grown in conventional monolayer culture. PMID:26240353

  7. Prescription Drugs and Cold Medicines

    MedlinePlus

    ... Abuse » Prescription Drugs & Cold Medicines Prescription Drugs & Cold Medicines Email Facebook Twitter What is Prescription Drug Abuse: ... treatment of addiction. Read more Safe Disposal of Medicines Disposal of Unused Medicines: What You Should Know ( ...

  8. Drugs Approved for Thyroid Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) ...

  9. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  10. Drugs Approved for Brain Tumors

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Brain Tumors This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Brain Tumors Afinitor (Everolimus) Afinitor Disperz (Everolimus) Avastin (Bevacizumab) ...

  11. Drugs Approved for Breast Cancer

    MedlinePlus

    ... 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) Keoxifene (Raloxifene Hydrochloride) Nolvadex (Tamoxifen ...

  12. Drugs Approved for Pancreatic Cancer

    Cancer.gov

    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.

  13. Drugs Approved for Breast Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Drugs Approved for Lung Cancer

    Cancer.gov

    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.

  15. Drugs Approved for Bladder Cancer

    Cancer.gov

    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.

  16. Drugs Approved for Bone Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Bone Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Bone Cancer Abitrexate (Methotrexate) Cosmegen (Dactinomycin) Dactinomycin Denosumab Doxorubicin Hydrochloride ...

  17. Drugs Approved for Myeloproliferative Disorders

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Myeloproliferative Neoplasms This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Myeloproliferative Neoplasms Adriamycin PFS (Doxorubicin Hydrochloride) Adriamycin RDF (Doxorubicin Hydrochloride) ...

  18. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  19. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  20. [Lifestyle drugs in medicine].

    PubMed

    Harth, Wolfgang; Seikowski, Kurt; Hermes, Barbara; Gieler, Uwe

    2008-01-01

    Lifestyle drugs have become an important new group of medications, which are taken by healthy people to increase the individual well-being and quality of life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the main groups. The wish for eternal youth, beauty and potency is central, and lifestyle medications are also requested to influence cosmetic findings, which are usually simply a result of the natural aging process. Lifestyle drugs seem to be harmless, but the physician must pay attention to possible abuse, side effects, risks and complications. Additionally, however, lifestyle drugs are also frequently used by patients suffering from emotional disorders such as somatoform disorders. Medicalization of physiological life is then expected to solve psychosocial problems, but without success. The use of lifestyle medications in somatoform disorders is contraindicated and psychotherapy or psychopharmacological treatment come first. With this overview article, we would like to make an update of new lifestyle drugs. PMID:18330527