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Sample records for arsenic-based antineoplastic drugs

  1. 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…

  2. 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).

  3. 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.

  4. Quantifying the carcinogenicity of antineoplastic drugs.

    PubMed

    Kaldor, J M; Day, N E; Hemminki, K

    1988-04-01

    It has been well established that many of the drugs used in cancer therapy are themselves potentially carcinogenic. It is therefore important to quantify the carcinogenic risk associated with specific agents, and to investigate ways of predicting their risk from animal and in vitro studies. In this paper, an index of carcinogenic potency is defined, and applied to published data on acute non-lymphocytic leukemia following therapy with cytotoxic drugs used as single agents. Carcinogenic potency estimates for rats and mice are also obtained for 15 antineoplastic drugs, and the potency correlation between humans and rodents is examined for the five agents for which there are data in common. The broader implications for quantitative cancer risk prediction are discussed.

  5. 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

    ... Hazardous Drugs in Healthcare Settings 2010 AGENCY: National Institute for Occupational Safety and Health... following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings... Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health...

  6. [Genotoxic risk assessment of nurses handling antineoplastic drugs].

    PubMed

    Boughattas, Aïcha Brahem; Bouraoui, Sana; Debbabi, Faten; El Ghazel, Hatem; Saad, Ali; Mrizak, Néjib

    2010-01-01

    The aim of this study is to assess the genotoxic effect of occupational exposure to antineoplastic drugs on oncology nurses in order to propose a strategy for adequate safety. The study included 20 oncology nurses from the Farhat Hached university hospital-Sousse (Tunisia) exposed to antineoplastic drugs compared to 20 controls. The two groups were paired according to sex, age, and smoking habits. The genotoxic risk assessment was carried out by the micronucleus test and chromosomal abnormalities. The search for the clinical effects of cytostatic drugs was based on a questionnaire. Determination of the level of the exposure to cytostatic was performed by calculation of the index of the exposure to these drugs. The median age of nurses was 36 years. A female prevalence (80%) was noted. The exposed period to cytostatic was 6.1 years. The middle index of cytostatic contact calculated for the whole of the nurses, was of 1.5. However this index becomes higher (>3) in nurses working at day care. A significant increase in frequencies rates for both micronucleus (9.40‰ vs 4.35‰) and chromosome abnormalities (1.85% vs 0.30%) were noted in exposed group more than controls. In conclusion, application of genotoxic tests may be useful to detect cytogenetic damage related to occupational exposure to a potentially cancerogenic environment. Results of the present biomonitoring study emphasize the need for developing safety programs.

  7. The handling of antineoplastic drugs in a major cancer center.

    PubMed

    Hoffman, D M

    1980-06-01

    It has long been known that many commonly used antineoplastic agents are carcinogenic. Yet most health care professionals take few precautions, if any, when handling these drugs. Recent findings suggest a possible hazard to personnel as evidenced by increased mutagenicity of urine of nurses exposed to anticancer drugs during preparation and administration of doses. Although more study is needed to determine the significance of these data, it would seem prudent to take measures to prevent any unnecessary exposure to these drugs by those preparing and administering them. The policies and procedures at the Memorial Sloan-Kettering Cancer Center require that chemotherapeutic drugs be prepared in a vertical laminar flow containment hood by personnel wearing sterile disposable gloves. Chemotherapeutic agents are specially labeled to ensure segregated disposal of waste, which is subsequently incinerated.

  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

    ... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 AGENCY: National Institute for Occupational... and Other Hazardous Drugs in Healthcare Settings 2012.'' NIOSH is making available a copy of Appendix... Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings...

  9. 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.

  10. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    PubMed

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  11. 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

  12. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute...

  13. Permeability of nitrile rubber, latex, polyurethane, and neoprene gloves to 18 antineoplastic drugs.

    PubMed

    Connor, T H

    1999-12-01

    The permeability of four glove materials to various antineoplastic drugs was studied. Eighteen antineoplastic drugs posing potential health hazards to handlers were prepared at the highest concentrations normally encountered by hospital personnel. Four glove materials-nitrile rubber, latex, polyurethane, and neoprene-were exposed to the drugs for 30, 60, 90, and 120 minutes. Glove thickness was measured with an electronic digital caliper. Random samples of material were selected from the glove fingertips, and triplicate samples were tested for each drug at each interval. For a majority of the drugs, a bacterial mutagenicity assay was used to measure the amount of drug (if any) that permeated the material. High-performance liquid chromatography was used for drugs not tested with the bacterial assay. The nitrile gloves were the thinnest (0.12 mm), and the latex gloves were the thickest (0.18 mm). The four materials were generally impermeable to each drug. One sample of the nitrile gloves appeared to have a defect, allowing >5% of the drug solution to pass through at 30 minutes. One sample each of the latex, polyurethane, and neoprene gloves demonstrated minimal permeability (< or =1%): One latex glove sample was permeated by carmustine, and paclitaxel permeated one sample each of the polyurethane and neoprene materials. Nitrile rubber, latex, polyurethane, and neoprene gloves were impermeable to 18 antineoplastic drugs in most, but not all, cases.

  14. Causes of Health Care Workers’ Exposure to Antineoplastic Drugs: An Exploratory Study

    PubMed Central

    Hon, Chun-Yip; Abusitta, Dina

    2016-01-01

    Background: The exposure of health care workers to antineoplastic drugs is associated with several adverse health effects, including reproductive toxicities and mutagenic effects. Recent studies have confirmed that Canadian health care workers are at risk of exposure to these agents. However, the causes leading to occupational exposure to antineoplastic drugs are unknown. Objective: To perform an exploratory study to ascertain the immediate and contributing causes of health care workers’ exposure to antineoplastic drugs. Methods: Participants were recruited from 6 acute care facilities in Vancouver, British Columbia. Those agreeing to participate were asked to complete a questionnaire about previous exposure to antineoplastic drugs while at work and to describe the circumstances of each exposure incident. Responses were qualitatively analyzed, and the causes of each incident were classified as immediate (unsafe work acts and/or unsafe working conditions) or contributing (related to the management of the organization, the environment, and/or the physical and mental status of the worker). Results: Completed questionnaires were received from 120 participants, 18 (15.0%) of whom reported having had previous occupational exposure to antineoplastic drugs. Qualitative analysis of the responses showed 4 categories of immediate causes (needlestick injury, spill, direct contact, and other unintended exposure) and 3 categories of contributing causes (poor communication, inadequate controls, and lack of training). Some incidents had multiple immediate and/or contributing causes. Conclusions: According to a review of the immediate and contributing causes identified in this study, many of the exposure incidents were deemed preventable. A “hierarchy of controls” should be implemented, including (in the following order) engineering controls, administrative controls, and personal protective equipment. The findings of this study can be used to develop job safety analyses

  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. Adherence to Safe Handling Guidelines by Health Care Workers Who Administer Antineoplastic Drugs

    PubMed Central

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

    2015-01-01

    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

  18. 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.

  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

    2015-07-01

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

  1. 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

  2. Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India

    PubMed Central

    Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha

    2016-01-01

    Objectives: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Materials and Methods: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. Results: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. Conclusions: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society. PMID:27721535

  3. 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.

  4. Exposure of pharmacy personnel to mutagenic antineoplastic drugs.

    PubMed

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

    1982-11-01

    The Salmonella reversion test was used to measure the mutagenic activities of urine concentrates from individuals preparing cancer chemotherapy agents for i.v. administration. Longitudinal studies were performed in which the total urine produced in 24-hr periods was collected, starting on a Sunday at 7 p.m. after a duty-free weekend and extending over an 8-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 2-fold increase in mutagenesis by the fourth day with peak values of 2.7- to 24-fold occurring on Days 5 and 6, reduced values by Day 7, and a return to the spontaneous level by Day 8. When four of the six positive individuals in the preceding experiment admixed comparable amounts of chemotherapeutic drugs in a closed-face, vertical laminar flow hood, no increase in mutagenic activity was detected in their urine concentrates over the 8-day period.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Examination of the kinetics of degradation of the antineoplastic drug 5-fluorouracil by chlorine and bromine.

    PubMed

    Li, Wei; Tanumihardja, Jessica; Masuyama, Takaaki; Korshin, Gregory

    2015-01-23

    This study examined the degradation of the widely used antineoplastic drug 5-fluorouracil (5FU) by chlorine and bromine. 5FU was determined to interact readily with free chlorine and bromine but was stable in the presence of chloramine. The removal of 5FU followed a second-order kinetic pattern. Apparent rates (kapp) of 5FU removal by chlorine and bromine were strongly pH dependent and had maximum 14.8M(-1)s(-1) and 1.9×10(3)M(-1)s(-1)kapp values, respectively at pH 7. Modeling of the dependence of the kapp values vs. pH indicated the presence of a relatively acidic (pK 6.4 vs. 8.5 of 5FU per se) 5FU intermediate generated in the presence of halogen species. Spectrophotometric measurements confirmed the increased acidity of 5FU chlorination products and allowed proposing a degradation pathway of 5FU by chlorine. This pathway suggests that 5FU chlorination proceeds via chlorine incorporation at the 6th carbon in the heterocyclic ring of 5FU.

  11. A review of surface wipe sampling compared to biologic monitoring for occupational exposure to antineoplastic drugs.

    PubMed

    Kibby, Thomas

    2017-03-01

    The potential for adverse health effects from occupational exposure to antineoplastic drugs (AD) is well known. Control measures recommended by the NIOSH Alert ([3]) include medical and biologic monitoring, and environmental monitoring where available. At present no guidelines or published best practices exist to guide EHS managers on how to carry out this biologic or environmental monitoring. Studies investigating surface wipe sampling for AD have been numerous in the past decade, but very limited research exists to correlate surface contamination with actual absorption by pharmacists and nurses. This article reviews the studies with concurrent surface wipe sampling and urine monitoring for the same AD, and tests their correlation. Methodologic limitations are reviewed. Twenty-one studies were identified that concurrently measured surface contamination by AD by wipe sampling and AD absorption by urine monitoring. Two studies directly evaluated the AD by wipe sampling and urine levels and neither found a statistically significant correlation. Six studies reported a decrease in both surface and urine levels following interventions to reduce contamination or exposure. Only one study directly evaluated the personal protective equipment and handling techniques employed by the studied workers, which can be viewed as a major confounder of absorption. While no statistically significant correlation was found between wipe sampling and urine monitoring for AD, decreases in urine and wipe levels following interventions to reduce exposure were noted. Limitations in the data and recommendations for future research are reviewed.

  12. 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.

  13. 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.

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

    PubMed

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

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

  15. Highly sensitive LC-MS/MS methods for urinary biological monitoring of occupational exposure to cyclophosphamide, ifosfamide, and methotrexate antineoplastic drugs and routine application.

    PubMed

    Canal-Raffin, Mireille; Khennoufa, Karim; Martinez, Béatrice; Goujon, Yves; Folch, Celia; Ducint, Dominique; Titier, Karine; Brochard, Patrick; Verdun-Esquer, Catherine; Molimard, Mathieu

    2016-10-21

    Highly sensitive ESI-LC-MS/MS methods were developed for urinary biological monitoring of occupational exposure to cyclophosphamide (CP), ifosfamide (IF), and methotrexate (MTX), which are hazardous antineoplastic drugs frequently handled by healthcare professionals. Extraction methods consisted of liquid/liquid extraction for simultaneous urinary CP and IF assays, and of solid phase extraction for the urinary MTX assay. A good linearity (r2>0.997), precision (CV<14.6%), and accuracy (bias<9.9%) were achieved for all compounds. The limit of detection (LOD) was 10pg/ml and the lower limit of quantification (LOQ) was 20pg/ml for all three drugs. Applying these methods in routine, more than 116 healthcare professionals occupationally exposed to antineoplastic drugs were monitored and 635 urines were analysed. Eleven healthcare professionals (9.5%) were found to be contaminated to at least one of the three antineoplastic drugs. Among analysed urines, 22 samples were found positives. The measured concentrations ranged from 20.1 to 1850pg/ml and, for six samples, concentrations were at CP trace level, between the LOD and LOQ values (10-20pg/ml). Such efficient analytical tools combining high specificity with high sensitivity are essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to these widely used antineoplastic drugs. These methods allow to monitor the healthcare professionals exposure to antineoplastic drugs in the aim to assess the effectiveness of collective and individual protective measures.

  16. 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.

  17. 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

  18. 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

  19. 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

    ... 276 drugs received special warnings (usually black box warnings) based on reported adverse effects in... Hazardous Drugs in Healthcare Settings 2014: Proposed Additions and Deletions to the NIOSH Hazardous Drug... Drugs in Healthcare Settings 2014: Proposed Additions and Deletions to the NIOSH Hazardous Drug...

  20. 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

    ... on reported adverse effects in patients. The complete list of these drugs can be found at: http://www... 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...

  1. 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.

  2. Toxicity of exposure to binary mixtures of four anti-neoplastic drugs in Daphnia magna and Ceriodaphnia dubia.

    PubMed

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

    2014-12-01

    Anticancer drugs, interfering with DNA in every living organism, may pose a threat to aquatic environment, even more when they occur as complex mixtures. We investigated the combined long term toxic potential of four anti-neoplastic drugs (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET] and imatinib mesylate [IM]) testing their binary mixtures on two primary consumers of the freshwater aquatic chain with close phylogenetic relationship: Daphnia magna and Ceriodaphnia dubia. The combined toxicities were assessed using two distinct effect sizes that should be observed if Bliss independence holds. Direct statistical comparison by analysis of variance of single and combined toxicities under the assumption of Bliss independence allowed to accept or reject the independency hypothesis. Independency was confirmed for all mixtures both in D. magna and in C. dubia, except for IM+ ET and IM+CDDP in D. magna and for ET+CDDP and ET+5-FU in C. dubia which at the highest concentrations showed an antagonistic interaction. A synergic tendency was found testing IM+CDDP on C. dubia at the lowest concentration selected. Thus, the chronic ecotoxicological data evaluated in this study show not only a potential environmental risk of anticancer drugs, especially considering their potential synergistic effects, but also the necessity to integrate statistical models with experimental data to establish the real environmental impact of such compounds.

  3. 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

  4. Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican hospitals: a multicentric study.

    PubMed

    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.

  5. 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

  6. Characterization of latex-antineoplastic drug complexes by differential scanning calorimetry and microphotography.

    PubMed

    Gallardo, V; Ruiz, M A; Morales, E; Zouaki, J; Campos, J; Conejo-García, A; Gallo, M A; Espinosa, A

    2006-12-01

    Choline kinase inhibitors have recently been identified as potentially useful antitumoral agents. Here we determine the best conditions for obtaining drug-polymer complexes with 5-fluorouracil (5-FU), and JCR791B, a new drug representing a significant advance in the development of new molecules to inhibit tumour proliferation. As polymers we used the cellulose derivatives Aquacoat and Aquateric. The variables in the adsorption process measured were time to adsorbent-adsorbate equilibrium, pH and concentration. The drug-polymer complexes were characterized by differential scanning calorimetry and microphotography. Our results show that adsorption of 5-FU and JCR was similar with both polymers although slightly greater with Aquacoat. The chemical structure of the drug and its solubility in water and oil are fundamental characteristics that determine the performance of polymers as drug carriers able to provide controlled release.

  7. 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

  8. 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.

  9. 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.

  10. The pharmacokinetics of JS-38, a novel antineoplastic drug, in rats.

    PubMed

    Ng, Hong Zha; Fang, Yu; Li, Ying; Fan, Ting-Ting; Qin, Yan; Liu, Quan-Hai

    2008-01-01

    To evaluate the pre-clinical pharmacokinetics of JS-38(C22H1404N2S2F6, MW: 548), a study was conducted in Wistar rats (3 female, 2 male: 200-250 g about 6 or 7 months). The concentration-time curve of JS-38 in rats demonstrated the pharmacokinetic (PK) characteristics of a two-compartmental model. The area under the concentration-time curve from zero to infinity (AUC(0-infinity)) for the low, middle and high dosage (i.e., 20, 50 and 125 mg x kg(-1)) amounted to 46.850 +/- 19.946, 161.101 +/- 58.877 and 312.565 +/- 187.273 mg/L x h respectively; a positive correlation was demonstrated between the AUC(0-infinity). and the dosages in question (r = 0.99). The average time to reach maximum concentration (Tmax) was 3.( RSD: 20.4% and the half-life (t(1/2)) was 11.4 h( RSD: 8.8% P > 0.05. For the low, middle and high dosage, the maximum concentration (Cmax) was 4.882, 11.248, and 13.431 microg x mL(-1) respectively. After the administration of JS-38, except for the brain and spinal marrow, the drug distribution in the different body tissues varied, in particular in the liver, intestine and thyroid gland. A significant distribution of JS-38 was detected in cancerous tissues, and its concentrations demonstrated a tendency increase over time. There was a certain degree of distribution in the bone marrow. The urine samples showed that JS-38 nearly was practically not eliminated in its original form. The amount eliminated after 72h via the bile was only 1.03 +/- 0.1% of the administered dose. In the rat model, most of the JS-38 in its original form (53.58 +/- 22.28%) was excreted via the feces. When the intragastric administration of doses of 20, 50 and 125 mg x kg(-1) was compared with i.v. administered JS-38 (1 mg x kg(-1)), the absolute bioavailability amounted to 22.2 +/- 9.5%, 30.4 +/- 14.5% and 23.6 +/- 11.3% respectively. It was found that this compound is well absorbed in to the system and that it shows favorable PK properties. The outcome of this early pre

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

    PubMed

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

    2015-04-01

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

  12. Pharmacology of antineoplastic agents in pregnancy.

    PubMed

    Wiebe, V J; Sipila, P E

    1994-04-01

    The use of antineoplastic agents in pregnant women poses obvious risks to both the patient and the developing fetus, particularly during organogenesis. While the use of antineoplastics during pregnancy is often unavoidable, the physician may limit the risks by having a clear knowledge of the pharmacology and teratogenic potential of individual agents. Specific physiologic changes in the pregnant patient, such as enhanced renal excretion of drugs, increased or decreased hepatic function, altered gastrointestinal absorption and enterohepatic circulation, altered plasma protein binding, an increase in plasma volume (50%), and creation of a fluid filled 3rd compartment (amniotic fluid) for water soluble drugs may all significantly influence the pharmacology of antineoplastic agents. These physiological changes may effect the pregnant patients ability to absorb orally administered drugs, metabolize drugs to either active or inactive metabolites, and eliminate cytotoxically active drugs. A resulting reduction in concentration x time (C x T) for drug exposure to the maternal system may reduce the efficacy of the antineoplastic agents, while an increase in C x T may expose the patient and her fetus to undue toxicity. The timing of drug administration to gestational age is also a critical factor for some drugs. While many drugs result in adverse effects on the fetus regardless of gestational age, others appear to pose less of a threat if administered beyond the first trimester. This review addresses the pharmacology, pharmacokinetics and the teratogenic potential of individual antineoplastic agents that are commonly used in pregnant patients. The aim of this review is to help the physician select, on a patient specific basis, antineoplastic agents that avoid at least some of the fetal risk involved while maintaining efficacy in the treatment of the patient.

  13. Mycelial antineoplastic activity of Agaricus blazei.

    PubMed

    Bertéli, Míria Benetati Delgado; Umeo, Suzana Harue; Bertéli, André; do Valle, Juliana Silveira; Linde, Giani Andrea; Colauto, Nelson Barros

    2014-08-01

    Basidiocarp of Agaricus blazei (=Agaricus brasiliensis; =Agaricus subrufescens) is used as teas or capsules due to its antineoplastic effect but there are few reports of using mycelium for this purpose. The objective of this study was to evaluate the antineoplastic activity on sarcoma 180 cells implanted in mice of two forms of preparation of the mycelium from two A. blazei strains grown in culture medium with different concentrations of isolated soy protein. Mycelia were grown in Pontecorvo medium with different concentrations of isolated soybean protein (ISP). Mycelial hot water extract, moistened mycelial powder, hot water extract of green tea, Ifosfamida(®) (ifosfamide drug), and saline solution were administered daily by gavage in mice with sarcoma 180 cells to evaluate antineoplastic activity. It was concluded that antineoplastic activity was the same for both strains, except when used as moistened mycelial powder, which rules out the use of mycelial powder in capsules. Mycelial hot water extract had high antineoplastic activity with lower metabolic demand on the spleen and maintenance of normal blood parameters. Mycelial growth in different ISP concentrations had the same antineoplastic activity. Also the vegetative mycelium was as effective as the basidiocarp for sarcoma 180 tumor inhibition. Green tea was as effective as mycelial hot water extract.

  14. 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

  15. [Preparation of antineoplastic agents].

    PubMed

    Descoutures, J-M

    2006-01-01

    In the last fifteen years, the preparation of antineoplastic agents has tended to be centralized in the hospital pharmacy for two main reasons: to enable better protection for the staff, to enable better safety for the patient. The consequences of this organization have led to standardization of techniques, implementation of a quality system and also a better use of antineoplastic agents. After protocols have been standardized by the physician and validated by the pharmacist, four main steps are necessary: phamaceutical validation of the prescription, preparation of IV admixtures according to a production file, control of the final product, dispatching of the preparation to the patient. Computer-controlled processes guarantee the safety of these different steps. The centralized preparations are made either with a vertical laminar flow hood or with an isolator. With the implementation of the National Cancer Plan, antineoplastic agents for patients on home treatments will also be prepared in centralized hospital pharmacies.

  16. Procedures for handling antineoplastic injections in comprehensive cancer centers.

    PubMed

    LeRoy, M L; Roberts, M J; Theisen, J A

    1983-04-01

    The procedures for handling injectable antineoplastic drugs in comprehensive cancer centers in the U.S. are summarized. In May 1982, a survey was sent to directors of pharmacy at 27 institutions designated as comprehensive cancer centers. Some questions duplicated a 1979 survey, while others addressed points in recently published guidelines on handling antineoplastic medications. Representatives of 21 institutions responded. These institutions represented 13,638 beds, 1,848 of which were oncology beds. Seventeen institutions had written policies for the preparation of antineoplastics, but only nine had a training program. The pharmacist or pharmacy technician prepared these medications in 12 institutions. Ten institutions prepared antineoplastics in a vertical laminar-flow hood. Gloves and masks were worn by employees in 20 and 13 of the institutions, respectively. Six institutions in some way assessed the health of employees handling antineoplastics. Eleven institutions had written policies on disposal of antineoplastics; 13 institutions disposed of this waste separately. Ten institutions had a training program for administration of antineoplastics. Compared with 1979, the trend is toward increased protection of persons handling injectable antineoplastic agents, but the procedures used at comprehensive cancer centers are not uniform.

  17. 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

  18. [Gonadal disorder as a result of adverse reaction to antineoplastic drugs--diagnosis, symptoms, prevention and treatment].

    PubMed

    Kowalska, A

    The past three decades have shown the increasing success of chemotherapy as the treatment of malignancies. This therapeutic success has focused attention on the associated gonadal toxicity. Cytotoxic agents may induce infertility and endocrine disfunction. Data for analysis were provided by studies on gonadal function after chemotherapy for: Hodgkin's disease, acute lymphocytic leukemia, non-Hodgkin's lymphoma, breast cancer; renal disease, bone-marrow transplantation. The likelihood of developing chemotherapy-induced damage depended on the chemotherapeutic regimen and prescribed dose, illness, sex and degree of gonadal activity at the time of treatment. Despite of the high frequency of chemotherapy-induced gonadal damage its prevention has received a little attention. LH-RHA and oral contraceptive therapy and testosterone have been tested to a limited extent of gonadal toxicity. Usually in male endocrine disfunction of testis does not need to be treated because it is moderate and does not cause any clinical symptoms. In female hormonal substitution seems to be necessary to decrease unpleasant feelings connected with menopause induced by chemotherapy. Further investigations should considered use of new cytotoxic agents without gonadal toxicity or use of new drugs which can better protect gonadal function.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. Antineoplastic activity of zoledronic acid and denosumab.

    PubMed

    Zwolak, Pawel; Dudek, Arkadiusz Z

    2013-08-01

    Cancer patients suffer from cancer-induced bone pain, hypercalcemia, and reduced quality of life caused by pathological fractures. Many of these complications related to cancer can be treated, or at least controlled, using new anticancer agents. Recently, two agents used initially to treat osteoporosis demonstrated direct and indirect anticancer activity. In this review, we summarize current knowledge about direct and indirect anticancer activity of zoledronic acid (a third-generation bisphosphonate), and denosumab antibody against RANKL. Zoledronic acid influences the proliferation and viability of tumor cells in vitro, and effectively reduces tumor burden, tumor-induced pain, and tumor growth in vivo. Denosumab is a fully human monoclonal antibody preventing the binding of RANKL to its receptor on osteoclasts' membrane, and through this mechanism inhibits the resorption of the bone. Furthermore, this agent demonstrates direct anticancer activity through the RANKL signaling pathway. Because of these features both drugs may gain broader application for the treatment of cancer patients. However, further pre-clinical and clinical evaluation is needed for both agents to fully assess the antineoplastic mechanisms of activity of both agents.

  7. Pharmacy program for improved handling of antineoplastic agents.

    PubMed

    Scott, S A; Schrott, D B; Loesch, G A

    1983-07-01

    A pharmacy program to improve the handling of antineoplastic drug products in a pediatric hospital is described. To correct deficiencies in the preparation and administration of cancer chemotherapy, the pharmacy department in conjunction with pediatric hematology-oncology physicians prepared a cancer chemotherapy manual. Included in the manual were (1) policies and procedures for the ordering, preparation, delivery, administration, and disposal of chemotherapy; (2) a flow sheet to facilitate ordering of daily chemotherapy doses and allow pharmacists to double-check dosage calculations of physicians; (3) drug information monographs on various antineoplastic agents used in the hospital; and (4) a reference chart containing information about the reconstitution, dilution, stability, storage, administration, and special-handling precautions for chemotherapy. Upon the recommendation of the hematology-oncology staff and with the approval of the hospital administration, the pharmacy obtained a vertical laminar-airflow hood and expanded its services to include preparation of all cancer chemotherapy for inpatients. Procedures were implemented to document delivery of chemotherapy to the nursing unit and to ensure proper acquisition and charting of chemotherapy doses given by physicians. Pharmacy involvement has improved control of the handling and administration of cancer chemotherapy in the hospital and has increased the safety of patients and hospital personnel.

  8. 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

  9. Antineoplastic Effects of Honokiol on Melanoma

    PubMed Central

    Guillermo-Lagae, Ruth; Santha, Sreevidya; Thomas, Milton; Zoelle, Emily; Stevens, Jonathan

    2017-01-01

    Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma. PMID:28194418

  10. 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.

  11. The antineoplastic effect of low-molecular-weight heparins – a literature review

    PubMed Central

    Püsküllüoğlu, Mirosława; Krzemieniecki, Krzysztof

    2013-01-01

    There is some evidence for the antitumor effect of heparins, especially the low-molecular-weight ones. The authors discuss the potential mechanism of this antineoplastic effect and present results from several in vitro and in vivo experiments. The clinical trials concerning the impact of low-molecular-weight heparins on the tumor and on the patients’ survival are described. The objective was to find out if heparins could be administered as an antitumor drug, independently of their anticoagulatory properties. The antitumor role of tissue factor, heparinase, chemokines, stromal proteins, cellular interactions as well as angiogenesis and immunology seems certain. The results of the available studies seem promising but large clinical trials are necessary in order to confirm the antineoplastic effect of the low-molecular-weight heparins and to approve them for standard anticancer treatment. It could be a breakthrough in modern oncology. PMID:23788954

  12. 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.

  13. From bacteria to antineoplastic: epothilones a successful history.

    PubMed

    Kaiser, Samuel; Muller, Joseane John; Froehlich, Pedro Eduardo; Baggio Gnoatto, Simone Cristina; Bergold, Ana Maria

    2013-09-01

    Malignancies are a major cause of morbidity and mortality worldwide. Cancer is a cell disease, characterized by a deviation of the control mechanisms of proliferation and differentiation of cells. Among the treatments available, chemotherapy is often the first choice. Epothilones are a new class of anticancer drugs that act by interacting with cellular microtubules interrupting the proliferation of cancer cells. Many synthetic and semi-synthetic analogues of epothilones have been prepared aiming improvement in effectiveness and tolerability, based on QSAR studies. These analogues have been effective for treatment of tumors resistant to first-line treatments. Six new epothilones are being subjected to clinical trials. Ixabepilone (Ixempra®) was approved by FDA in 2007, patupilone is in phase III clinical trial for ovarian and peritoneum cancer. Sagopilone, desoxiepothilone and KOS-1584 are in phase II clinical trials, for the treatment of recurrent glioblastoma and advanced metastatic breast cancer, metastasic breast cancer and metastatic pulmonary cancer, respectively. Desoxiepothilone reached only phase II trials and BMS-310705 reached phase III/IV trials, but were not approved for clinical use due to adverse effects such as neurotoxicity and severe diarrhea, which were dose-limiting. Furthermore, the low t1/2 (40h) in comparison with other class analogues, does not recommend the clinical use of this derivative. Some other synthetized epothilones presented antineoplastic activity in vitro, but are not yet submitted to clinical studies. Neuropathies and diarrhea are adverse effects presented by some substances of this class of anticancer drugs.

  14. Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics.

    PubMed

    Burgaz, S; Karahalil, B; Bayrak, P; Taşkin, L; Yavuzaslan, F; Bökesoy, I; Anzion, R B; Bos, R P; Platin, N

    1999-02-02

    In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.

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

    PubMed

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

    2004-10-15

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

  16. Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds.

    PubMed

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

    2015-03-06

    Antineoplastic compounds are used in the treatment of a variety of cancers. The effectiveness of an antineoplastic compound to exert its activity is largely dependent on transport proteins involved in the entry of the compound into the cells, and those which drive it out of the cell. Organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), belonging to the SLCO family of proteins, are specifically expressed in the sinusoidal membranes of the liver, and are known to interact with a variety of drugs. The present study deals with the interaction of these proteins with antineoplastic compounds routinely used in cancer chemotherapy. The proteins OATP1B1 and OATP1B3 were functionally characterized in stably transfected human embryonic kidney cells using [(3)H] labeled estrone 3-sulfate and [(3)H] labeled cholecystokinin octapeptide (CCK-8) as substrates, respectively. Substrate uptake experiments performed in the presence of antineoplastic compounds showed that vinblastine and paclitaxel strongly interacted with the OATP1B1 with Ki values of 10.2 μM and 0.84 μM, respectively. OATP1B3 showed highly significant interactions with a variety of antineoplastic compounds including chlorambucil, mitoxantrone, vinblastine, vincristine, paclitaxel and etoposide, with Ki values of 40.6 μM, 3.2 μM, 15.9 μM, 30.6 μM, 1.8 μM and 13.5 μM, respectively. We report several novel interactions of the transporter proteins OATP1B1 and OATP1B3 highlighting the need to investigate their role in drug-drug interactions and cancer chemotherapy.

  17. A Systematic Review of Adherence to Oral Antineoplastic Therapies

    PubMed Central

    Amoyal, Nicole; Nisotel, Lauren; Fishbein, Joel N.; MacDonald, James; Stagl, Jamie; Lennes, Inga; Temel, Jennifer S.; Safren, Steven A.; Pirl, William F.

    2016-01-01

    Background. Oral antineoplastic therapies not only improve survival but also reduce the burden of care for patients. Yet patients and clinicians face new challenges in managing adherence to these oral therapies. We conducted a systematic literature review to assess rates and correlates of adherence to oral antineoplastic therapies and interventions aimed at improving adherence. Methods. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of the Ovid MEDLINE database from January 1, 2003 to June 30, 2015, using relevant terminology for oral antineoplastic agents. We included observational, database, and intervention studies. At least two researchers evaluated each paper to ensure accuracy of results and determine risk of bias. Results. We identified 927 records from the search and screened 214 abstracts. After conducting a full-text review of 167 papers, we included in the final sample 51 papers on rates/correlates of adherence to oral antineoplastic therapy and 12 papers on intervention studies to improve adherence. Rates of adherence varied widely, from 46% to 100%, depending on patient sample, medication type, follow-up period, assessment measure, and calculation of adherence. Of the intervention studies, only 1 of the randomized trials and 2 of the cohort studies showed benefit regarding adherence, with the majority suffering high risk of bias. Conclusions. Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer. Implications for Practice: Given the tremendous growth and development of oral antineoplastic therapies in the last decade, significant

  18. 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.

  19. Cleaning of Residues from Equipment Surfaces After Demilitarization of Arsenical-Based Munitions and Fill Materiels

    DTIC Science & Technology

    2007-10-01

    demilitarization process for the destruction of recovered arsenical-based munitions. Presently, this includes the use of PMNSCM’s Explosive Destruction...as the surfaces must be clean in order to achieve a good seal to prevent leaks during operations. A field-useable process for removing the residues was...data generated from the present study will be used to support operation of a non-stockpile demilitarization process for the destruction of recovered

  20. Methanol extract of the ethnopharmaceutical remedy Smilax spinosa exhibits anti-neoplastic activity.

    PubMed

    Seelinger, Mareike; Popescu, Ruxandra; Giessrigl, Benedikt; Jarukamjorn, Kanokwan; Unger, Christine; Wallnöfer, Bruno; Fritzer-Szekeres, Monika; Szekeres, Thomas; Diaz, Rene; Jäger, Walter; Frisch, Richard; Kopp, Brigitte; Krupitza, Georg

    2012-09-01

    Plants have been the source of several effective drugs for the treatment of cancer and over 60% of anticancer drugs originate from natural sources. Therefore, extracts of the rhizome of Smilax spinosa, an ethnomedicinal plant from Guatemala which is used for the treatment of inflammatory conditions, were investigated regarding their anti-neoplastic activities. By using several solvents the methanol extract was by far the most potent against HL60 cell proliferation (50% inhibition at 60 µg/ml). Furthermore, fractionation of this extract yielded fraction F2, which exhibited enforced pro-apoptotic activity, and activated CYP1A1. Proteins that are relevant for cell cycle progression and apoptosis, as well as proto-oncogenes were investigated by western blotting. This revealed that the methanol extract increased the levels of p21 and this may have caused cell cycle attenuation. The derivative fraction F2 induced apoptosis through the intrinsic pathway, which correlated with the inhibition of Stat3 phosphorylation and concomitant induction of caspase 9, then caspase 8 and caspase 3. In summary, the methanol extract and the derivative fraction F2 of S. spinosa showed anti-neoplastic effects in HL-60 cells and CYP1A1 activation in estrogen receptor-positive MCF-7 breast cancer cells but not in estrogen-negative MDA-MB231 breast cancer cells. Based on our data Smilax spinosa may be a promising source for novel anticancer agents.

  1. Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

    SciTech Connect

    Testa, Antonella Giachelia, Manuela; Palma, Selena; Appolloni, Massimo; Padua, Luca; Tranfo, Giovanna; Spagnoli, Mariangela; Tirindelli, Donatella; Cozzi, Renata

    2007-08-15

    The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p < 0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.

  2. Carcinogenicity of antineoplastic agents in man.

    PubMed

    Rieche, K

    1984-03-01

    Review of the literature shows that: Anticancer drugs are in all probability mostly also carcinogenic. Alkylating agents such as melphalan, chlorambucil and cyclophosphamide seem to lead to the highest rate of second malignancies. Second malignancies after antitumour drugs are mostly acute leukaemias. Conditions which could influence the carcinogenicity of an antitumour drug are (a) its carcinogenic potency; (b) long-term administration; (c) the total dose used and (d) long-term survival of the patient. Irradiation and chemotherapy seem to have the greatest carcinogenic potential, e.g. in malignant lymphomas. The role of immunosuppression as a co-carcinogenic factor is difficult to estimate. Although transplant patients on anticancer drugs for immunosuppression have a higher risk of reticulosarcomas, but not of solid tumours, there is no evidence to suppose that in general immunosuppression and carcinogenicity are directly related. There is no reason to abandon intensive chemotherapy regimes if they lead to significant therapeutic results on the grounds of possible carcinogenicity of these drugs.

  3. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma.

    PubMed

    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-G(1) 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.

  4. Arsenic-based Life: An active learning assignment for teaching scientific discourse.

    PubMed

    Jeremy Johnson, R

    2017-01-02

    Among recent high profile scientific debates was the proposal that life could exist with arsenic in place of phosphorous in its nucleic acids and other biomolecules. Soon after its initial publication, scientists across diverse disciplines began to question this extraordinary claim. Using the original article, its claims, its scientific support, and the ensuing counterarguments, a two-day, active learning classroom exercise was developed focusing on the presentation, evaluation, and discussion of scientific argumentation and discourse. In this culminating assignment of a first semester biochemistry course, undergraduate students analyze the scientific support from the original research articles and then present and discuss multiple scientific rebuttals in a lively, civil classroom debate. Through this assignment, students develop a sense of skepticism, especially for the original arsenic-based life claims, and learn to clearly articulate their counterarguments with scientific support and critical reasoning. With its direct integration into first-semester biochemistry curriculum and the excitement surrounding arsenic based life, this assignment provides a robust, simple, and stimulating framework for introducing scientific discourse and active learning into the undergraduate molecular science curriculum. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):40-45, 2017.

  5. 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.

  6. A new monitoring method using solid sorbent media for evaluation of airborne cyclophosphamide and other antineoplastic agents.

    PubMed

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

    2003-02-01

    Cyclophosphamide is a known human carcinogen. In July 1999, in a report at a conference on cytotoxic drugs in Sweden, it was indicated that cyclophosphamide (CP) was not effectively controlled by high efficiency particulate air (HEPA) filters.((1)) This then raised a concern that the existing air monitoring methods, which utilize polytetrafluoroethylene (a.k.a. PTFE, or Teflon) or glass fiber filters for evaluation of antineoplastics such as CP in air may also be ineffective for collection and quantification of such agents. It was decided that further evaluation of the existing filter method for monitoring antineoplastics in air be conducted. This evaluation determined that the filter method of monitoring was minimally effective for some antineoplastic agents, and that an alternate method of monitoring should be sought. The method subsequently developed utilizes a solid sorbent tube, Anasorb 708, a methacrylic acid polymer. Evaluation of this sorbent tube for adsorption and desorption properties found it had a greater than 90 percent recovery for both CP and ifosfamide. Other agents evaluated included 5-fluorouracil, doxorubicin, and paclitaxel. All three agents were able to be detected and measured by use of Anasorb 708 solid sorbent tube. Validation of the method was then conducted with air pulled through the tubes via attachment to an air manifold system at air flows ranging from 1.5 to approximately 4.0 liters per minute for up to 24 hours. This evaluation did validate the Anasorb 708 tube as an effective media for collection of airborne concentrations of CP from less than 1 microgram up to approximately 2 mg (2000 microgram) per tube. This corresponds to a concentration range of approximately 0.7 microgram/m(3) (0.0007 mg/m(3)) to 0.7 mg/m(3) in a 5.76 m(3) volume of air. This method can provide accurate information on airborne concentrations of CP for purposes of conducting risk assessments or evaluation of risk management methods.

  7. 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

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

    PubMed

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

    2016-01-16

    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.

  9. 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.

  10. 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.

  11. 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.

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

    PubMed

    Canello, Tamar; Ovadia, Haim; 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.

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

    PubMed

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

    2016-01-01

    Objetivo: evaluar el impacto del uso de dos sistemas cerrados sobre el proceso de preparación de quimioterapia parenteral, con respecto al sistema estándar, en términos de contaminación local y ambiental, y tiempos de preparación. Método: estudio observacional prospectivo. Se compararon dos proveedores distintos de sistemas cerrados, Icu Medical® y Care Fusion®, frente al sistema estándar de preparación de quimioterapia parenteral. Quince enfermeros del Servicio de Farmacia elaboraron cada uno de ellos 5 preparaciones, una siguiendo el procedimiento estándar y cuatro usando los sistemas cerrados. Para evaluar la aparición de contaminación se elaboró una solución de fluoresceína al 0,5%. Se evaluaron dos tipos de contaminación: local (en tres puntos: sistema acoplado a vial, jeringa y envase final) y ambiental (guantes y mesa de trabajo), obteniéndose el porcentaje de preparaciones contaminadas en cada uno de ellos. Se registró el tiempo empleado por cada enfermero en cada una de las preparaciones. Resultados: se elaboraron 75 preparaciones. Se produjo una reducción global de la contaminación local para los SC Icu Medical® y Care Fusion® del 24% y 74%, respectivamente. En el sistema cerrado Care Fusion® la contaminación local fue significativamente menor que en el sistema estándar en vial, jeringa y envase final; mientras que en el sistema cerrado Icu Medical® solo fue significativamente menor en la conexión al vial. Se produjo un incremento significativo del tiempo de preparación con la utilización de sistemas cerrados de los entre 23,4 y 30,5 segundos. Conclusiones: ambos sistemas cerrados han mostrado un beneficio con respecto a la utilización del sistema estándar. Sin embargo, se han visto incrementados significativamente los tiempos de preparación con ambos sistemas.

  14. PPAR-γ Agonists As Antineoplastic Agents in Cancers with Dysregulated IGF Axis

    PubMed Central

    Vella, Veronica; Nicolosi, Maria Luisa; Giuliano, Stefania; Bellomo, Maria; Belfiore, Antonino; Malaguarnera, Roberta

    2017-01-01

    It is now widely accepted that insulin resistance and compensatory hyperinsulinemia are associated to increased cancer incidence and mortality. Moreover, cancer development and progression as well as cancer resistance to traditional anticancer therapies are often linked to a deregulation/overactivation of the insulin-like growth factor (IGF) axis, which involves the autocrine/paracrine production of IGFs (IGF-I and IGF-II) and overexpression of their cognate receptors [IGF-I receptor, IGF-insulin receptor (IR), and IR]. Recently, new drugs targeting various IGF axis components have been developed. However, these drugs have several limitations including the occurrence of insulin resistance and compensatory hyperinsulinemia, which, in turn, may affect cancer cell growth and survival. Therefore, new therapeutic approaches are needed. In this regard, the pleiotropic effects of peroxisome proliferator activated receptor (PPAR)-γ agonists may have promising applications in cancer prevention and therapy. Indeed, activation of PPAR-γ by thiazolidinediones (TZDs) or other agonists may inhibit cell growth and proliferation by lowering circulating insulin and affecting key pathways of the Insulin/IGF axis, such as PI3K/mTOR, MAPK, and GSK3-β/Wnt/β-catenin cascades, which regulate cancer cell survival, cell reprogramming, and differentiation. In light of these evidences, TZDs and other PPAR-γ agonists may be exploited as potential preventive and therapeutic agents in tumors addicted to the activation of IGF axis or occurring in hyperinsulinemic patients. Unfortunately, clinical trials using PPAR-γ agonists as antineoplastic agents have reached conflicting results, possibly because they have not selected tumors with overactivated insulin/IGF-I axis or occurring in hyperinsulinemic patients. In conclusion, the use of PPAR-γ agonists in combined therapies of IGF-driven malignancies looks promising but requires future developments. PMID:28275367

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

    PubMed

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

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

  16. Antineoplastic chemotherapy and congenital tooth abnormalities in children and adolescents

    PubMed Central

    Brożyna, Agnieszka; Dembowska-Bagińska, Bożenna; Olczak-Kowalczyk, Dorota

    2016-01-01

    Aim of the study Chemotherapeutic treatment in children and adolescents carries a risk of congenital tooth disorders and dentinoma. Study objective is to assess the correlation between tooth abnormalities, early complications of multidrug chemotherapy, and chemotherapeutics used in different antineoplastic therapies in children and adolescents. Material and methods Enamel defects (developmental defects of enamel index – DDE index) and defects in tooth number, size, and structure were assessed clinically and radiologically in 60 patients who underwent chemotherapy on average 4.9 ±3.4 years earlier (PCH), and 60 generally healthy subjects (control group – CG), aged 6–18 years. Höltta’s defect index (DeI) was calculated. Medical files provided information on neoplasm type, age at treatment start and chemotherapy duration, chemotherapeutic type and dose, vomiting, and mucositis (CTCAE v4.0). Statistical significance of differences between groups was assessed with the Mann-Whitney U test and the correlation between dental defects and chemotherapy with Spearman’s rank correlation coefficient (significance p ≤ 0.05). Results Enamel defects, tooth agenesis, microdontia, root resorption, taurodontism, and dentinoma occurred statistically significantly more often in the PCH group. A correlation was established between vincristine use and dose and all types of dental defects; cyclophosphamide, doxorubicin, and isophosphamide and hypodontia; microdontia, root resorption, and enamel defects; etoposide and cisplatin and microdontia, root resorption, and enamel defects; methotrexate root resorption and enamel defects; carboplatin and dentinoma and enamel defects. Mucositis and vomiting promoted root resorption, microdontia, and enamel defects. Conclusions Dental defects are related to both the use of respective chemotherapeutics, especially vincristine, cyclophosphamide, doxorubicin, and isophosphamide, and to early complications in multidrug chemotherapy

  17. Terminal arbor degeneration (TAD): a novel lesion produced by the antineoplastic agent, paclitaxel

    PubMed Central

    Bennett, Gary J.; Liu, Guo Kai; Xiao, Wen Hua; Jin, Hai Wei; Siau, Chiang

    2011-01-01

    The anti-neoplastic agent, paclitaxel, causes a dose-limiting distal, symmetrical, sensory peripheral neuropathy that is often accompanied by a neuropathic pain syndrome. In a low-dose model of paclitaxel-evoked painful peripheral neuropathy in the rat, we have shown that the drug causes degeneration of intraepidermal nerve fibers (IENFs), i.e., the fibers which give rise to the sensory afferent’s terminal receptor arbour. However, we did not find any evidence for axonal degeneration in samples taken at the mid-nerve level. Here we aimed to determine whether the absence of degenerating peripheral nerve axons was due to sampling a level that was too proximal. We used electron microscopy to study the distal-most branches of the nerves innervating the hind paw glabrous skin of normal and paclitaxel-treated rats. We confirmed that we sampled at a time when IENF degeneration was prominent. Because degeneration might be easier to detect with higher paclitaxel doses, we examined a four-fold cumulative dose range (8–32 mg/kg). We found no evidence of degeneration in the superficial subepidermal axon bundles (sSAB) that are located just a few microns below the epidermal basal lamina. Specifically, for all three dose groups there was no change in the number of sSAB per mm of epidermal border, no change in the number of axons per sSAB, and no change in the diameter of sSAB axons. We conclude that paclitaxel produces a novel type of lesion that is restricted to the afferent axon’s terminal arbor; we name this lesion “terminal arbor degeneration (TAD)”. PMID:21395870

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

    PubMed

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

    2017-02-01

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

  19. [Antineoplastic effect of hydrogel prospidin on Seidel ascites hepatoma used as a model].

    PubMed

    Bychkovskiĭ, P M; Iurkshtovich, T L; Kladiev, A A; Revtovich, M Iu

    2012-01-01

    Antineoplastic effect of hydrogel dextran phosphate, hydrogel prospidin, and prospidin in an injectable preparation has been assessed using Seidel ascites hepatoma as a model. Injectable and hydrogel prospidin in doses from 250, 500 to 1000 mg/kg and hydrogel phosphate dextran in doses of 500 and 1000 mg/kg were administered to rats intraperitoneally in a single dose in a volume of 1 or 2 ml per each 100 g of animal body weight. The study has shown that irrespective of rats with Seidel ascites hepatoma and significantly increase in the dosage of prospidin preparations and hydrogel dextran phosphate results in a longer average life expectancy of rats Compared with its injectable variant, hydrogel prospidin appears to produce more than twice as high antineoplastic effect, and is found to provide prolonged therapeutic effects, as well as cure of animals in more than 60 % of cases.

  20. 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

  1. 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.

  2. 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

    2015-10-22

    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

  3. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

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

    PubMed

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

    2015-05-01

    Objetivo: Describir la implantación de un robot para la elaboración de antineoplásicos en el Servicio de Farmacia y evaluar el valor añadido al proceso farmacoterapéutico. Método: La implantación se llevó a cabo en Junio 2012 en un hospital de tercer nivel, realizándose en dos períodos: 1-Período de pruebas con la instalación del robot, configuración técnica del equipo, validación de 29 principios activos e integración con el software de prescripción electrónica (9 meses); 2-Período de utilización (22 meses). Se impartieron cursos de formación a farmacéuticos y personal de enfermería. Para su funcionamiento el robot emplea reconocimiento fotográfico, identificación por código de barras y controles gravimétricos, que proporcionaron datos de error cometido por preparación, tolerando ±10% y restringiéndolo, tras un estudio piloto, a un intervalo de tolerancia de ±4%. El robot fue programado para reconocer bolsas, infusores, jeringas y viales. El valor añadido se evaluó durante 31 meses con la identificación de los errores de preparación. Resultados: Se realizaron 11.865 preparaciones en el robot, que correspondieron al 40% del global de antineoplásicos elaborados, de 29 principios activos diferentes. Se identificaron y evitaron errores de dosificación en el 1,12% (n=133) de las preparaciones, que no alcanzaron al paciente al ser identificadas por el robot como preparaciones con desviación negativa (-4%) y ser corregidas manualmente. Conclusiones: La implantación de un robot en la elaboración de antineoplásicos permite identificar los errores de elaboración y evitar que lleguen al paciente, promoviendo la seguridad y calidad del proceso farmacoterapéutico de antineoplásicos y reduciendo la exposición del manipulador a los mismos.

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

    PubMed

    Zounkova, Radka; Kovalova, Lubomira; Blaha, Ludek; Dott, Wolfgang

    2010-09-01

    In spite of growing scientific concern about pharmaceuticals in the environment, there is still a lack of information especially with regard to their metabolites. The present study investigated ecotoxicity and genotoxicity of three widely used cytostatic agents 5-fluorouracil (5-FU), cytarabine (CYT) and gemcitabine (GemC) and their major human metabolites, i.e. alpha-fluoro-beta-alanine (FBAL), uracil-1-beta-D-arabinofuranoside (AraU) and 2',2'-difluorodeoxyuridine (dFdU), respectively. Effects were studied in acute immobilization and reproduction assays with crustacean Daphnia magna and growth inhibition tests with alga Desmodesmus subspicatus and bacteria Pseudomonas putida. Genotoxicity was tested with umu-test employing Salmonella choleraesius subsp. chol. Toxicity was relatively high at parent compounds with EC(50) values ranging from 44 microg L(-1) (5-fluorouracil in the P. putida test) to 200 mg L(-1) (cytarabine in D. magna acute test). In general, the most toxic compound was 5-FU. Studied metabolites showed low or no toxicity; only FBAL (metabolite of 5-FU) showed low toxicity to D. subspicatus and P. putida with EC(50) values 80 and 140 mg L(-1), respectively. All parent cytostatics showed genotoxicity with minimum genotoxic concentrations (MGC) ranging from 40 to 330 mg L(-1). From metabolites, only FBAL was genotoxic in high concentrations. To our knowledge, the present study provides some of the first ecotoxicity data for both cytostatics and their metabolites, which might further serve for serious evaluation of ecological risks. The observed EC(50) values within the microg L(-1) range were fairly close to concentrations reported in hospital sewage water, which indicates further research needs, especially studies of chronic toxicity.

  6. [Risk assessment concerning hospital personnel participating in the preparation and administration of antineoplastic drugs].

    PubMed

    Minoia, C; Turci, R; Sottani, C; Schiavi, A; Perbellini, L; Angeleri, S; Frigerio, F; Draicchio, F; Apostoli, P

    1999-01-01

    24 workers (10 involved in the preparation and 14 in administration) exposed to cyclophosphamide (CP) and ifosfamide (IF) in two Italian hospitals were monitored. The extent of exposure was assessed by the analysis of air samples, wipe samples, pads and gloves. Urinary excretion at the beginning and at the end of the work shift was also measured by liquid-liquid extraction and analysis by HPLC-MS/MS. 3 out of 24 air samples resulted to be positive for CP or IF. In wipe samples, CP concentrations ranging from < 0.001 to 82.4 micrograms/dm2 in Hospital A (32 samples) and from 0.2 to 383.3 micrograms/dm2 in Hospital B (17 samples), were found. IF concentrations varied from < 0.001 to 90.9 micrograms/dm2 in Hospital A and from 0.01 to 141.5 micrograms/dm2 in Hospital B. Pads (from 11 to 13 for each operator) were contaminated with CP and IF especially on arms, legs and chest. The use of a plastic-backed liner on the working tray in the laminar flow hoods was demonstrated to compromise the containment properties of the hood. Urine samples were positive for CP in 50% of the workers (range: 0.1-2.1 micrograms/L), whereas IF was detected in 2 subjects only (range: 0.1-0.8 microgram/L). The results from this investigation demonstrated that vertical laminar airflow hoods, when incorrectly used, might represent a source of contamination and that higher risk may depend on lack of educational programmes and observance of preventive guidelines.

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

    MedlinePlus

    ... not pulled back into the building by the heating, ventilating, and air conditioning (HVAC) systems or by the windows, doors, or other points ... American National Standards Institute American Society of Health-System Pharmacists (before ... ventilating, and air conditioning International Agency for Research ...

  8. 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.

  9. 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

  10. Pyrazolopyrimidine Derivatives as Antineoplastic Agents: with a Special Focus on Thyroid Cancer.

    PubMed

    Ferrari, Silvia Martina; La Motta, Concettina; Sartini, Stefania; Baldini, Enke; Materazzi, Gabriele; Politti, Ugo; Ruffilli, Ilaria; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) are molecules that compete with ATP on tyrosine kinase receptors (TKRs), blocking tyrosine kinase (TK) activation and then oncogenic pathways; they have been studied, and some of them are right approved for the treatment of many types of cancer. Among TKIs, one of the most explored chemical template is the pyrazolo[3,4-d]pyrimidine (PP) heterocyclic core, which proved to be a useful scaffold for the obtainment of effective compounds. Actually, derivatives belonging to this structural class show a large spectrum of activity, thus standing out as multi-target agents. Different PP compounds have been shown to act as: a) ABL inhibitors and antiproliferative agents against human leukemia cell lines; b) Src kinase inhibitors in neuroblastoma, medulloblastoma and osteosarcoma; c) Phospholipase D inhibitors in different neoplasias; d) Urokinase plasminogen activator inhibitors, in breast cancer. In thyroid cancer (TC), PP1 and PP2 (inhibitors of RET, Hck, lck, and fynT kinases, and a good inhibitor of c-Src and platelet-derived growth factor receptor) showed antineoplastic actvity in human papillary TC cell lines that carry spontaneous RET/PTC1 rearrangements. More recently, new derivatives, (R)-1-phenethyl-N-(1-phenylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4- amine, namely, CLM3 and CLM29, have been demonstrated to exert a multiple signal transduction inhibition (including the RET-TK, BRAF, EGFR, and with antiangiogenic activity), showing antineoplastic activity, in vitro and in vivo, in papillary dedifferentiated, medullary and anaplastic TC. These data have shown the antineoplastic activity of PP in different neoplasias, opening the way to a future clinical evaluation in human cancers.

  11. Trabectedin, a drug acting on both cancer cells and the tumour microenvironment

    PubMed Central

    D'Incalci, M; Badri, N; Galmarini, C M; Allavena, P

    2014-01-01

    Trabectedin is the first marine-derived anti-neoplastic drug approved for the treatment of advanced soft tissue sarcoma and, in combination with pegylated liposomal doxorubicin, for the treatment of patients with relapsed platinum-sensitive ovarian cancer. From the beginning of its development, trabectedin showed some peculiar properties that clearly distinguished it from other anti-cancer drugs. In this mini-review, we will outline the current state of knowledge regarding the mode of action of trabectedin, which appears to represent a new class of anti-neoplastic drugs acting both on cancer cells and on the tumour microenvironment. PMID:24755886

  12. Regression of a glioblastoma multiforme: spontaneous versus a potential antineoplastic effect of dexamethasone and levetiracetam

    PubMed Central

    Peddi, Prakash; Ajit, Nisha Elizabeth; Burton, Gary Von; El-Osta, Hazem

    2016-01-01

    Patients with grade IV astrocytoma or glioblastoma multiforme (GBM) have a median survival of <12 months, increased to 14.6 months by maximal safe resection with radiation and temozolamide. In the absence of chemotherapy, radiotherapy or chemoradiotherapy, spontaneous regression of GBM or regression while only being on dexamethasone (DEX) and levetiracetam (LEV) have seldom been reported. Here, we present a case of a patient who had significant regression of the GBM with DEX and LEV alone. In this study, we hypothesise a plausible antineoplastic role of DEX and or LEV in GBM and highlight molecular, preclinical and clinical studies supporting this role. PMID:28011886

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

    PubMed

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

    2010-04-01

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

  14. Chitosan-tripolyphosphate nanoparticles functionalized with a pH-responsive amphiphile improved the in vitro antineoplastic effects of doxorubicin.

    PubMed

    Nogueira-Librelotto, Daniele R; Scheeren, Laís E; Vinardell, M Pilar; Mitjans, Montserrat; Rolim, Clarice M B

    2016-11-01

    Delivery systems with pH-responsiveness behavior are of particular interest because they could allow exploring the various pH gradients within the body, for example, between healthy tissue and tumor tissue, or between extracellular tissue and some cell compartments. Likewise, modifications in nanocarriers with polyethylene glycol (PEG) and poloxamer could be a potential approach to improve the effectiveness of cancer treatments. On these premises, we prepared pH-responsive DOX-loaded chitosan-tripolyphosphate nanoparticles (NPs), modified or not with PEG or poloxamer, and incorporating an anionic dyacyl lysine-based surfactant with sodium counterion (77KS) as a pH-sensitive adjuvant. Owing to its pH-sensitivity, the CS-NPs showed membranolytic behavior upon reducing the pH value of surrounding media to 6.6 and 5.4, which are characteristic of the endosomal compartments. The in vitro antiproliferative assays with MCF-7 and HeLa tumor cells indicated that the NPs themselves had no associated significant cytotoxicity, while DOX-loaded NPs induced higher cytotoxicity than free drug. Additionally, DOX-loaded CS-NPs displayed greater selectivity to tumor cells than to the non-tumor 3T3 fibroblasts. The feasibility of using these NPs to target tumor microenvironment was proven, as cytotoxicity against cancer cell models was higher in a mildly acidic environment. Finally, the hemocompatibility of NPs was demonstrated, indicating their suitability for intravenous administration. Altogether, the results suggest that the combination of endosomal acidity with the potential endosomolytic capability of these pH-responsive nanocarriers could increase the intracellular delivery of DOX and, thus, might enhance its antineoplastic efficacy.

  15. 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

  16. Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

    PubMed Central

    Jiang, Guojun; Dong, Shuying; Yu, Meiling; Han, Xi; Zheng, Chao; Zhu, Xiaoguang; Tong, Xuhui

    2017-01-01

    Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy). In Hs578T and MCF-7 cells, where GJ could be formed, the function of GJ was modulated by a pharmacological potentiators [retinoid acid (RA)]/inhibitors [oleamide and 18-α-glycyrrhetinic acid (18-α-GA)] and small interfering RNA (siRNA). In high-density cells (where GJ was formed), enhancement of GJ function by RA increased the cytotoxicity of adriamycin, while inhibition of GJ function by oleamide/18-α-GA and siRNA decreased the cytotoxicity caused by adriamycin. Notably, the modulation of GJ did not affect the survival of cells treated with adriamycin when cells were in low density (no GJ was formed). The present study illustrated the association between GJIC and the antitumor effect of adriamycin in breast cancer cells. The cytotoxicity of adriamycin on breast cancer cells was increased when the function of gap junctions was enhanced. PMID:28356970

  17. Kojic acid--a new leading molecule for a preparation of compounds with an anti-neoplastic potential.

    PubMed

    Novotný, L; Rauko, P; Abdel-Hamid, M; Váchalková, A

    1999-01-01

    Kojic acid as a molecule of natural origin may serve as template for the synthesis of new biologically active compounds. The synthetic KA (pyranone) derivatives possess various kinds of biological activities which are related by their similarity to flavonoids. The most important property is the antifungal and antineoplastic activity and capability of chelating metals. It is shown that the antineoplastic activity of kojic acid derivatives is based on various mechanisms of action on different levels of cellular metabolism and functions what makes this compound interesting for future investigation as cytotoxic agent.

  18. [Immunomodulatory drugs (IMiDs)].

    PubMed

    Oshima, Kumi; Ichinohe, Tatsuo

    2014-06-01

    Immunomodulatory drugs (IMiDs) are a new class of anti-inflammatory and antineoplastic agents that have structural and functional similarities with their prototype compound, thalidomide. Although thalidomide and its derivatives, lenalidomide and pomalidomide, are widely used as an essential component in the treatment of selected hematologic neoplasms including multiple myeloma, the precise mechanisms by which these agents exert anti-tumor effects have yet to be clarified. Recently, a component of E3 ubiquitin ligase complex, cereblon (CRBN), has been identified as a direct molecular target for anti-neoplastic activities of IMiDs. CRBN has also been shown to be involved in IMiDs-mediated T-cell co-stimulation and cytokine production. Further studies are necessary to elucidate the CRBN-related molecular pathways that are essential for antitumor and immunomodulatory activities of IMiDs.

  19. [Emetogenic potential of antineoplastic agents based on clinical trials in Japan].

    PubMed

    Watanabe, Tomoki; Handa, Satoko; Kato, Yasuhisa

    2015-03-01

    Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects of chemotherapy that decreases patients' quality of life and motivation for treatment. Therefore, prevention and treatment of CINV are essential for motivating patients to continue chemotherapy. International societies such as American Society of Clinical Oncology (ASCO), Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) have published guidelines for using antiemetics, and these guidelines were published in Japan in May 2010. However, both the Japananese and international guidelines do not provide sufficient clinical trial-based evidence for antiemetic use in the Japanese population. In this study, we attempted to evaluate and clarify the frequency of CINV in clinical trials in Japan. We found that thet guidelines specify different emetogenic potentials of some antineoplastic agents such as gemcitabine. Therefore, we believe that it is necessary to reevaluate the emetogenic risk of such antineoplastic agents and to develop a practical and standard antiemetic therapy so that in the future, patients do not hesitate to undergo chemotherapy because of side effects.

  20. Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation

    PubMed Central

    Meixensberger, Jürgen; Gaunitz, Frank

    2016-01-01

    Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry. ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613. In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production. PMID:27811375

  1. 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

  2. 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

  3. [Example of safety measures for antineoplastic agents immediately after market launch--a case of TS-1 capsule all example use result investigation that executes safety monitoring--].

    PubMed

    Ito, Kunio

    2006-01-01

    As a measure to ensure safe use of TS-1 during the early marketing period, a drug use investigation was conducted on an all-case basis. Extra safety monitoring,rarely included in the use investigation,was also planned for patients who began therapy with this agent. Of the 4,177 subjects registered during the year beginning in March 1999, 3,882 started TS-1 therapy. Aside from 74 dropouts, 3,808 cases were evaluable for safety. The overall incidence of adverse reactions, with high frequencies of myelosuppression and gastrointestinal disorders, was 74.3%: a result similar to an incidence of 77.5% (100/129) found in the early phase II trial with gastric cancer patients. Safety monitoring made it possible to check if a given patients was eligible for proper use before treatment is begun. During TS-1 administration,collaboration was formed between physicians and medical representatives to ensure regular laboratory testing and to check the test findings. Measures were considered necessary to secure the safe use of drugs with manifest risk of serious adverse reactions, such as antineoplastic agents, during the initial period of market introduction. Our present approach proved effective as one of such measures.

  4. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy 1

    PubMed Central

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

    2016-01-01

    ABSTRACT Objective: to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. Method: integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. Results: only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. Conclusion: this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. PMID:27737380

  5. Evaluation of an electrolysis apparatus for inactivating antineoplastics in clinical wastewater.

    PubMed

    Kobayashi, Toyohide; Hirose, Jun; Sano, Kouichi; Hiro, Naoki; Ijiri, Yoshio; Takiuchi, Hiroya; Tamai, Hiroshi; Takenaka, Hiroshi; Tanaka, Kazuhiko; Nakano, Takashi

    2008-06-01

    We recently reported a system for inactivating antineoplastics in which sodium hypochlorite is supplied by the electrolysis of sodium chloride solution. In this study, we designed an electrolysis apparatus for inactivating the cytotoxicity of antineoplastics in clinical wastewater using the system. The apparatus consists of an electrolysis cell with platinum-iridium electrodes, a pool tank, a circulating system for wastewater, a safety system for explosive gas and overflow, and an exhaust duct. The free chlorine concentration increased linearly up to 6500 mg l(-1), and pH also increased to 9.0-10.0 within 2h, when 0.9% sodium chloride solution was electrolyzed. We examined its efficacy with model and clinical wastewaters. The reciprocal of dilution factor for disappearance of cytotoxicity using Molt-4 cells was compared before and after electrolysis. In the model wastewater, that was 9.10 x 10(4) before electrolysis, and 3.56 x 10(2) after 2h of electrolysis. In the clinical wastewater (n=26), that was 6.90 x 10(3)-1.02 x 10(6) before electrolysis, and 1.08 x 10(2)-1.45 x 10(4) after 2h of electrolysis. Poisonous and explosive gases released by the electrolysis were measured; however, they were found to be negligible in terms of safety. The environmental load was evaluated by carbon dioxide generation as an index and it was found that the carbon dioxide generated by the electrolysis method was 1/70 lower than that by the dilution method with tap water. Moreover, the cost of the electrolysis method was 1/170 lower than that of the dilution method. This method was found to be both effective and economically valuable.

  6. Anticancer Alkaloids from Trees: Development into Drugs

    PubMed Central

    Isah, Tasiu

    2016-01-01

    Trees have made an enormous phytochemical contribution in anticancer drugs' development more than any other life form. The contributions include alkaloids that are biosynthesized in various ways and yield. Lead alkaloids isolated from the trees are taxol and camptothecins that currently have annual sales in billion dollars. Other important alkaloids isolated from these life forms include rohitukine, harringtonine, acronycine, thalicarpine, usambarensine, ellipticine, and matrines. Studies on their mechanism of action and target on the DNA and protein of cancerous cells aided the development of potent hemisynthesized congeners. The molecules and their congeners passed/are passing a long period of historical development before approved as antineoplastic drugs for cancer chemotherapy. Some of them did not find the application as anticancer drugs due to ineffectiveness in clinical trials; others are generating research interest in the antineoplastic activity at the present and have reached clinical trial stages. Potentials in antineoplastic molecules from trees are high and are hoped to be commensurate with cancer types afflicting human society in the future. PMID:28082790

  7. Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study†

    PubMed Central

    Fiorelli, Alfonso; Pentimalli, Francesca; D'Urso, Vittorio; Di Marzo, Domenico; Forte, Iris Maria; Giordano, Antonio; Di Domenico, Marina; Accardo, Marina; Di Serio, Umberto; Santini, Mario

    2014-01-01

    OBJECTIVE Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines. METHODS Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death. RESULTS The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines. CONCLUSIONS Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural

  8. Incidence of infusion reactions to anti-neoplastic agents in early phase clinical trials: The MD Anderson Cancer Center experience.

    PubMed

    Bupathi, Manojkumar; Hajjar, Joud; Bean, Stacie; Fu, Siqing; Hong, David; Karp, Daniel; Stephen, Bettzy; Hess, Kenneth; Meric-Bernstam, Funda; Naing, Aung

    2017-02-01

    Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.

  9. Synthesis and Characterization with Antineoplastic, Biochemical, Cytotoxic, and Antimicrobial Studies of Schiff Base Cu(II) Ion Complexes

    PubMed Central

    Haque, M. M.; Kudrat-E-Zahan, Md.; Banu, Laila Arjuman; Islam, Md. Shariful; Islam, M. S.

    2015-01-01

    Copper(II) complexes containing two Schiff base ligands derived from 2-hydroxybenzaldehyde with 2-aminophenol and 3-aminophenol have been synthesized and characterized by means of analytical, magnetic, and spectroscopic methods. Bacteria, fungus, Entamoeba histolytica, and antineoplastic activities of the synthesized complexes have been determined by monitoring the parameters cell growth inhibition, survival time of tumour mice, time-body relation, causing of intraperitoneal cells and macrophages, alkaline phosphatase activity, hematological effect, and biopsy of tumour. PMID:26294901

  10. [Antineoplastic profile assessment for the evaluation of occupational exposure in hospital personnel involved in handling cytotoxic agents].

    PubMed

    Sottani, C; Fugnoli, L; Businaro, J; Poma, P; Ronchi, A; Micoli, G; Minoia, C

    2012-01-01

    Environmental and biological monitoring performed in health care settings during a 14-year period allowed numerous data to be obtained by using the HPLC coupled with tandem mass spectrometry (HPLC-MS/MS). Data was stored in a specific data-base for the assessment of risk exposure to antineoplastic agents (CA). The strategy of analysis was based on the simultaneous determination of different active substances with a lower limit of quantification (LOQ) optimized in the range of sub-units of microg/L. In the present study, the MRM-ESI-MS/MS profiles of seven antineoplastic agents in both environmental and biological matrices are reported. These methods validated according to FDA guidelines allowed our lab to define a profile of antineoplastic agents that was representative of the four IARC classes, such as cyclophosphamide (group 1), cisplatin and doxorubicin (group 2A), daunorubicin (group 2B), 5-fluorouracil, ifosfamide (group 3), taxol, and gemcitabine (group 4). Moreover, contamination levels on a number of work surfaces and trends over a 14-year period are presented. The evaluation of occupational exposure to CA has been based on ALARA principle for most of the past decades but this principle is nowadays overwhelmed by the fast development of technology. The assessment of a possible in-take of CA in hospital personnel, when the sources of environmental contamination are identified, has become possible by the defining of a limit of exposure close to the limit of detection of the analytical method.

  11. Early Diagnosis and Prediction of Anticancer Drug-induced Cardiotoxicity: From Cardiac Imaging to "Omics" Technologies.

    PubMed

    Madonna, Rosalinda

    2017-02-25

    Heart failure due to antineoplastic therapy remains a major cause of morbidity and mortality in oncological patients. These patients often have no prior manifestation of disease. There is therefore a need for accurate identification of individuals at risk of such events before the appearance of clinical manifestations. The present article aims to provide an overview of cardiac imaging as well as new "-omics" technologies, especially with regard to genomics and proteomics as promising tools for the early detection and prediction of cardiotoxicity and individual responses to antineoplastic drugs.

  12. Bryostatins trigger human polymorphonuclear neutrophil and monocyte oxidative metabolism: association with in vitro antineoplastic activity.

    PubMed

    Esa, A H; Warren, J T; Hess, A D; May, W S

    1995-01-01

    Bryostatin-1-but not bryostatin-13-a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, triggered human polymorphonuclear neutrophil (PMN) and monocyte release of reactive oxygen radicals, as measured by the generation of lucigenin chemiluminescence and by the ferricytochrome c reduction assay. The release of oxygen radicals by bryostatins was sensitive to inhibitors of protein kinases, but resistant to the inhibition of phospholipase A2 activity and arachidonic acid metabolism (prior treatment with mepacrine or indomethacin). Comparison of the effect of protein kinase (PK) inhibitors H-8, H-7 and staurosporine on bryostatin-1-induced neutrophil oxygen radical release further suggested a requirement for activation of phospholipid-dependent PKC, but not for cGMP- or cAMP-dependent PK. In cytostatic assays, PMNs treated with bryostatin-1 inhibited the growth of the erythroleukaemic cell line K562 in a concentration-dependent manner. These findings suggest that the reported antineoplastic effect of bryostatins may result at least in part from activation of PMNs and monocytes.

  13. 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.

  14. Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity

    PubMed Central

    Costa, Iris Munhoz; Schultz, Leonardo; de Araujo Bianchi Pedra, Beatriz; Leite, Mariana Silva Moreira; Farsky, Sandra H. P.; de Oliveira, Marcos Antonio; Pessoa, Adalberto; Monteiro, Gisele

    2016-01-01

    L-asparaginase (L-ASNase) (EC 3.5.1.1) is an important enzyme for the treatment of acute lymphoblastic leukaemia. Currently, the enzyme is obtained from bacteria, Escherichia coli and Erwinia chrysanthemi. The bacterial enzymes family is subdivided in type I and type II; nevertheless, only type II have been employed in therapeutic proceedings. However, bacterial enzymes are susceptible to induce immune responses, leading to a high incidence of adverse effects compromising the effectiveness of the treatment. Therefore, alternative sources of L-ASNase may be useful to reduce toxicity and enhance efficacy. The yeast Saccharomyces cerevisiae has the ASP1 gene responsible for encoding L-asparaginase 1 (ScASNase1), an enzyme predicted as type II, like bacterial therapeutic isoforms, but it has been poorly studied. Here we characterised ScASNase1 using a recombinant enzyme purified by affinity chromatography. ScASNase1 has specific activity of 196.2 U/mg and allosteric behaviour, like type I enzymes, but with a low K0.5 = 75 μM like therapeutic type II. We showed through site-directed mutagenesis that the T64-Y78-T141-K215 residues are involved in catalysis. Furthermore, ScASNase1 showed cytotoxicity for the MOLT-4 leukemic cell lineage. Our data show that ScASNase1 has characteristics described for the two subfamilies of l-asparaginase, types I and II, and may have promising antineoplastic properties. PMID:27824095

  15. Comprehensive Evaluation of the Anti-Angiogenic and Anti-Neoplastic Effects of Endostar on Liver Cancer through Optical Molecular Imaging

    PubMed Central

    Xue, Zhenwen; Chi, Chongwei; Jia, Xiaohua; Tian, Jie

    2014-01-01

    Molecular imaging enables non-invasive monitoring of tumor growth, progression, and drug treatment response, and it has become an important tool to promote biological studies in recent years. In this study, we comprehensively evaluated the in vivo anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer based on the optical molecular imaging systems including micro-computer tomography (Micro-CT), bioluminescence molecular imaging (BLI) and fluorescence molecular tomography (FMT). Firefly luciferase (fLuc) and green fluorescent protein (GFP) dual labeled human hepatocellular carcinoma cells (HCC-LM3-fLuc-GFP cells) were used to establish the subcutaneous and orthotopic liver tumor model. After the tumor cells were implanted 14∼18 days, Endostar (5 mg/kg/day) was administered through an intravenous tail vein injection for continuous 14 days. The computer tomography angiography (CTA) and BLI were carried out for the subcutaneous tumor model. FMT was executed for the orthotopic tumor model. The CTA data showed that tumor vessel formation and the peritumoral vasculature of subcutaneous tumor in the Endostar treatment group was significantly inhibited compared to the control group. The BLI data exhibited the obvious tumor inhibition day 8 post-treatment. The FMT detected the tumor suppression effects of Endostar as early as day 4 post-treatment and measured the tumor location. The above data confirmed the effects of Endostar on anti-angiogenesis and tumor suppression on liver cancer. Our system combined CTA, BLI, and FMT to offer more comprehensive information about the effects of Endostar on the suppression of vessel and tumor formation. Optical molecular imaging system enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer. PMID:24416426

  16. Significance of targeting polyamine metabolism as an antineoplastic strategy: unique targets for polyamine analogues.

    PubMed

    Casero, Robert A; Frydman, Benjamin; Stewart, Tracy Murray; Woster, Patrick M

    2005-01-01

    The polyamines, putrescine, spermidine, and spermine, are naturally occurring polycationic alkylamines that are absolutely required for eukaryotic cell growth. Importantly, the polyamine metabolic pathway, as well as the requirement of polyamines for cell growth, is frequently dysregulated in cancer cells, thus providing a unique set of targets for therapeutic intervention. Ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis, is frequently up-regulated in preneoplastic cells, and has been implicated as an oncogene in multiple tumor types. Several model systems have demonstrated that inhibition of ODC's enzymatic activity and down-regulation of its expression are rational strategies for both chemotherapy and chemoprevention. Specific inhibitors of ODC, most notably 2-difluoromethylornithine (DFMO), have been used experimentally to validate polyamine metabolism as an antineoplastic strategy. However, multiple biochemical and clinical limitations to these ODC-targeting strategies minimize their value as therapeutic tools. Included among these limitations are poor bioavailability of the inhibitor, and the compensatory up-regulation of polyamine metabolism and transport that allow tumor cells to escape the growth inhibitory effects of blockers specifically targeting ODC. As a strategy to overcome the limitations of direct enzyme inhibition, several groups have pursued the design of polyamine analogues that specifically target the dysregulated polyamine metabolism found in tumors. These analogues have been developed specifically to target the specific polyamine transporter, thus competing with circulating natural polyamines. Additionally, most of the analogues examined thus far maintain the regulatory function of the natural polyamines, but are unable to functionally substitute for them in promoting growth. Specifically, individual analogues have demonstrated the ability to down-regulate each of the biosynthetic enzymes without causing

  17. Strong antineoplastic effects of metformin in preclinical models of liver carcinogenesis.

    PubMed

    Cauchy, François; Mebarki, Mouniya; Leporq, Benjamin; Laouirem, Samira; Albuquerque, Miguel; Lambert, Simon; Bourgoin, Pierre; Soubrane, Olivier; Van Beers, Bernard E; Faivre, Sandrine; Bedossa, Pierre; Paradis, Valérie

    2017-01-01

    Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices. Visceral fatty acid composition was analysed by magnetic resonance imaging (MRI). Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways. Tumour engraftment rates were higher in HFD mice than SC mice (hepatic: 79% compared with 25%, P=0.02) and FR mice (subcutaneous: 86% compared with 50%, P=0.04). Subcutaneous tumour volume was increased in HFD mice (+64% compared with FR and SC, P=0.03). Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis. In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9). Metformin caused qualitative changes in visceral fat composition of HFD mice, with decreased proportions of polyunsaturated fatty acids (14.6% ± 2.3% compared with 17.9% ± 3.0%, P=0.04). The potent antitumoral effects of metformin in multiple preclinical models implicating several molecular mechanisms provide a strong rationale for clinical trials including combination studies in HCC patients.

  18. 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

  19. Drug-induced diarrhoea.

    PubMed

    Chassany, O; Michaux, A; Bergmann, J F

    2000-01-01

    Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several

  20. [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.

  1. Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

    PubMed Central

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

    2015-01-01

    The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10−12 M and 10−6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine

  2. Intravenous bisphosphonate-related osteonecrosis of the jaws: Influence of coadjuvant antineoplastic treatment and study of buccodental condition

    PubMed Central

    Bagán, José; Poveda-Roda, Rafael

    2013-01-01

    Objectives: To determine whether coadjuvant antineoplastic treatment can influence the number and size of bone exposures among patients with intravenous bisphosphonate-related osteonecrosis of the jaws (iBRONJ), and to analyze the buccodental condition of these patients. Material and methods: The study sample comprised 67 patients with iBRONJ, 53 patients without iBRONJ receiving treatment with intravenous bisphosphonates, and 36 healthy subjects. In all three groups, measurements were made of the CAO index and of resting whole saliva and stimulated whole saliva. In the patients with iBRONJ, the size (cm) and number of bone exposures were recorded. The data obtained were subjected to analysis of variance (ANOVA), the Mann-Whitney U-test, and multivariate logistic regression analysis. Results: A total of 57.6% of the patients presented single bone exposure, 25.4% presented two, and 17% more than two exposures. The mean exposure size was 2.3±1.9 cm. Neither the bivariate analysis nor the multivariate multiple regression analysis found coadjuvant antineoplastic treatment to exert a statistically significant effect upon the number and size of bone exposures. On the other hand, there were statistically significant differences among the three study groups in relation to the CAO index (p=0.02) and the number of missing teeth (p=0.00). The resting whole saliva and stimulated whole saliva levels were similar in the three groups, though the patients with osteonecrosis of the jaws showed comparatively lower SWS levels. Conclusions: Coadjuvant antineoplastic treatment alone appears to exert no influence upon the size and number of bone exposures in iBRONJ. The patients with this disease show a higher CAO index and a larger number of missing teeth. Key words:Osteonecrosis of the jaws, bisphosphonates, bone exposure, CAO index, resting whole saliva, stimulated whole saliva. PMID:23229272

  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.

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

    PubMed

    Orrego Escobar, Eduardo Freddy

    2015-04-13

    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.

  5. Evaluation of Antibacterial, Antineoplastic, and Immunomodulatory Activity of Paullinia cupana Seeds Crude Extract and Ethyl-Acetate Fraction.

    PubMed

    Carvalho, Lidiane Vasconcelos do Nascimento; Cordeiro, Marina Ferraz; E Lins, Thiago Ubiratan Lins; Sampaio, Maria Clara Pinheiro Duarte; de Mello, Gabriela Souto Vieira; da Costa, Valécia de Cassia Mendonça; Marques, Leila Larisa Medeiros; Klein, Traudi; de Mello, João Carlos Palazzo; Cavalcanti, Isabella Macário Ferro; Pitta, Ivan da Rocha; Galdino da Rocha Pitta, Maira; Rêgo, Moacyr Jesus Barreto de Melo

    2016-01-01

    Paullinia cupana (Guarana) is a native plant of Amazon region that has very traditional importance. Its seeds are rich in bioactive compounds, including tannins, which exhibit relevant properties. Objective. This study aimed to evaluate antibacterial, antineoplastic, and immunomodulatory activity of P. cupana seeds crude extract (CE) and ethyl-acetate fraction (EAF). Methods. Antibacterial activity was evaluated by determination of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Antineoplastic activity was evaluated by MTT assays in hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7), ductal carcinoma (T47-D), non-Hodgkin's B cell lymphoma (Toledo), T cell leukemia (Jukart), and Acute Leukemia (HL-60) cell lines. BALB/c mice splenocytes were treated to assess IFN-γ, IL-6, IL-17, and IL-10 levels by sandwich ELISA. Results. CE and EAF were not toxic to peripheral blood cells and splenocytes. CE and EAF fractions showed a bacteriostatic activity (MIC = 250 μg/mL) and presented IC50 values of 70.25 μg/mL and 61.18 μg/mL in HL-60 leukemia cell line. All cytokines evaluated had their levels reduced after treatment, following dose-response model. Discussion and Conclusion. Different biological activities were observed for both CE and EAF, suggesting P. cupana as a source of bioactive substances, especially tannins that may be used for several diseases treatments.

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

    PubMed

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

    2000-11-01

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

  7. Evaluation of Antibacterial, Antineoplastic, and Immunomodulatory Activity of Paullinia cupana Seeds Crude Extract and Ethyl-Acetate Fraction

    PubMed Central

    Carvalho, Lidiane Vasconcelos do Nascimento; Cordeiro, Marina Ferraz; e Lins, Thiago Ubiratan Lins; Sampaio, Maria Clara Pinheiro Duarte; de Mello, Gabriela Souto Vieira; da Costa, Valécia de Cassia Mendonça; Marques, Leila Larisa Medeiros; Klein, Traudi; de Mello, João Carlos Palazzo; Cavalcanti, Isabella Macário Ferro; Pitta, Ivan da Rocha

    2016-01-01

    Paullinia cupana (Guarana) is a native plant of Amazon region that has very traditional importance. Its seeds are rich in bioactive compounds, including tannins, which exhibit relevant properties. Objective. This study aimed to evaluate antibacterial, antineoplastic, and immunomodulatory activity of P. cupana seeds crude extract (CE) and ethyl-acetate fraction (EAF). Methods. Antibacterial activity was evaluated by determination of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Antineoplastic activity was evaluated by MTT assays in hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7), ductal carcinoma (T47-D), non-Hodgkin's B cell lymphoma (Toledo), T cell leukemia (Jukart), and Acute Leukemia (HL-60) cell lines. BALB/c mice splenocytes were treated to assess IFN-γ, IL-6, IL-17, and IL-10 levels by sandwich ELISA. Results. CE and EAF were not toxic to peripheral blood cells and splenocytes. CE and EAF fractions showed a bacteriostatic activity (MIC = 250 μg/mL) and presented IC50 values of 70.25 μg/mL and 61.18 μg/mL in HL-60 leukemia cell line. All cytokines evaluated had their levels reduced after treatment, following dose-response model. Discussion and Conclusion. Different biological activities were observed for both CE and EAF, suggesting P. cupana as a source of bioactive substances, especially tannins that may be used for several diseases treatments. PMID:28053639

  8. The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine.

    PubMed

    Letzien, Ulrike; Oppermann, Henry; Meixensberger, Jürgen; Gaunitz, Frank

    2014-04-01

    Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide that shows antineoplastic effects in cell culture as well as in animal experiments. Since its mode of action and the targets at the molecular level have not yet been elucidated, we performed qRT-PCR experiments with RNA isolated from glioblastoma cell lines treated with carnosine, β-alanine, L-alanine, L-histidine and the dipeptide L-alanine-L-histidine. The experiments identified a strong induction of expression of the gene encoding pyruvate dehydrogenase 4 (PDK4) under the influence of carnosine and L-histidine, but not by the other substances employed. In addition, inhibition of cell viability was only detected in cells treated with carnosine and L-histidine, with the latter showing a significantly stronger effect than carnosine. Since the tumor cells expressed the tissue form of carnosinase (CN2) but almost no serum carnosinase (CN1), we conclude that cleavage by CN2 is a prerequisite for the antineoplastic effect of carnosine. In addition, enhanced expression of PDK4 under the influence of carnosine/L-histidine opens a new perspective for the interpretation of the ergogenic potential of dietary β-alanine supplementation and adds a new contribution to a growing body of evidence that single amino acids can regulate key metabolic pathways important in health and disease.

  9. 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

  10. The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod

    PubMed Central

    Patmanathan, Sathya Narayanan; Yap, Lee Fah; Murray, Paul G; Paterson, Ian C

    2015-01-01

    Almost all drugs approved for use in humans possess potentially beneficial ‘off-target’ effects in addition to their principal activity. In some cases this has allowed for the relatively rapid repurposing of drugs for other indications. In this review we focus on the potential for re-purposing FTY720 (also known as fingolimod, Gilenya™), an immunomodulatory drug recently approved for the treatment of multiple sclerosis (MS). The therapeutic benefit of FTY720 in MS is largely attributed to the immunosuppressive effects that result from its modulation of sphingosine 1-phosphate receptor signalling. However, this drug has also been shown to inhibit other cancer-associated signal transduction pathways in part because of its structural similarity to sphingosine, and consequently shows efficacy as an anti-cancer agent both in vitro and in vivo. Here, we review the effects of FTY720 on signal transduction pathways and cancer-related cellular processes, and discuss its potential use as an anti-cancer drug. PMID:26171944

  11. Assessment of chromosomal aberrations, micronuclei and proliferation rate index in peripheral lymphocytes from Tunisian nurses handling cytotoxic drugs.

    PubMed

    Bouraoui, Sana; Brahem, Aicha; Tabka, Faten; Mrizek, Najib; Saad, Ali; Elghezal, Hatem

    2011-01-01

    Anti-neoplastic agents are widely used in the treatment of cancer and some non-neoplastic diseases. These drugs have been proved to be mutagens, carcinogens and teratogens. To check the eventual effects of anti-cancer drugs on occupationally exposed Tunisian nurses, we used chromosomal aberration assay and micronucleus assay. Both parameters have been used to evaluate cellular DNA damage in the biological monitoring of occupationally exposed workers and each assay has its own aim .We used the proliferation rate index to evaluate the cytotoxic effect of antineoplastic drugs in exposed nurses. The frequency of binucleated micronucleated cells was significantly higher in nurses handling cytostatic drugs than in control. We detected also a significant increase of structural chromosomal aberrations. Control subjects generally had significantly higher values of proliferation rate index compared to expose ones. Our results confirm the genotoxic and the cytotoxic effects of antineoplastic drugs in blood lymphocytes circulation. This study points to the necessity to work under more safe and controlled conditions during the preparation and the administration of anti-cancer drugs.

  12. Plasma protein binding of phenylacetate and phenylbutyrate, two novel antineoplastic agents.

    PubMed

    Boudoulas, S; Lush, R M; McCall, N A; Samid, D; Reed, E; Figg, W D

    1996-12-01

    Phenylacetate and phenylbutyrate, two novel inducers of tumor cytostasis and differentiation, are currently in clinical trials for the treatment of cancer in adults. The purpose of our study was to evaluate the plasma protein-binding characteristics of phenylacetate and phenylbutyrate in the plasma of normal volunteers and that of patients with cancer. Drug plasma protein-binding analysis was examined using three separate devices: a micropartition system and two equilibrium dialysis systems, all of which exhibited similar results. Phenylacetate and phenylbutyrate concentrations were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Our results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (> 0.442 +/- 0.008 and > 0.188 +/- 0.001, respectively). Plasma pH did not greatly affect protein binding of either drug. As albumin concentration decreased, an increase in free fraction of both drugs was observed, however alpha 1-acid glyco-protein showed no change in free fraction as its concentration increased. Patients with cancer with lower levels of albumin showed an increase in free fraction with both phenylacetate and phenylbutyrate. When phenylacetate and phenylbutyrate were added together in plasma, the free fraction of phenylacetate increased, whereas the phenylbutyrate free fraction slightly decreased. We conclude that phenylacetate and phenylbutyrate have high free fractions that change with varying albumin levels and when both phenylacetate and phenylbutyrate are present together in plasma.

  13. Somatostatin receptor expression in vivo and response to somatostatin analog therapy with or without other antineoplastic treatments in advanced medullary thyroid carcinoma.

    PubMed

    Vainas, I; Koussis, Ch; Pazaitou-Panayiotou, K; Drimonitis, A; Chrisoulidou, A; Iakovou, I; Boudina, M; Kaprara, A; Maladaki, A

    2004-12-01

    The long-term treatment of metastatic medullary thyroid carcinoma (MTC) with somatostatin (SST) analogs was evaluated in 22 patients with persistant or relapsed disease and with in vivo positive SST receptor (SSTR) tumors. After surgical intervention all patients but one, initially or at a later time, had persistenly (15) or after relapse (7) elevated serum calcitonin (CT, 252-69482 pg/ml) and carcinoembryonic antigen (CEA, 8-1130 ng/ml) concentrations; also, all of them showed positive uptake in 111In-pentetreotide scanning. Daily doses of 0.4-1.0 mg octreotide subcutaneously, or monthly doses of 20-30 mg long-acting octreotide (LAR) intramuscularly for 3-21 months were administered. Systemic chemotherapy (Ch) with or without external radiotherapy (eRT) was given to 13 patients simultaneously. A beneficial effect on pre-existing diarrhea was observed in 8 patients (subjective partial remmission, sPR 36.4%); 10 other patients showed stable disease, while in 4 a worsening of pre-existing diarrhea was observed. CT and CEA concentrations decreased more than 25% in 4 out of 22 patients (18%) and 11 patients showed a decrease of less than 25% (biological SD). No objective response in tumour growth was demonstrated. Patients (10 survivors in group B) treated with Ch+eRT plus Octerotide showed higher sR (92.5%), lower mortality (23.1%), longer mean time to death (130 months) and longer mean total survival (mts) time (145 months) in comparison to group A patients who had 66.7% sR, 33.3% mortality, only 88.5 months mean time to death and 101 months mts-time. Long-term octreotide and octreotide-LAR treatment offers a subjective and biological partial remission in one third and in one fourth of the MTC patients respectively, but it does not improve the natural course of the tumor. It remains to be answered if these drugs, combined with other antineoplastic therapies, have a synergistic effect relating to treatment response and to patient survival and mortality.

  14. Targeted sustained delivery of antineoplastic agent with multicomponent polylactide stereocomplex micelle.

    PubMed

    Shen, Kexin; Li, Di; Guan, Jingjing; Ding, Jianxun; Wang, Zhongtang; Gu, Jingkai; Liu, Tongjun; Chen, Xuesi

    2017-01-05

    A c(RGDfC)-decorated polylactide stereocomplex micelle (cRGD-SCM) was prepared through the stereocomplex and hydrophobic interactions among 4-arm poly(ethylene glycol)-block-poly(D-lactide) (4-arm PEG-b-PDLA), methoxy poly(ethylene glycol)-block-poly(L-lactide) (mPEG-b-PLLA), and c(RGDfC)-poly(ethylene glycol)-block-poly(L-lactide) (cRGD-PEG-b-PLLA) for targeted treatment of αvβ3 integrin-positive C26 colon cancer. Doxorubicin (DOX), a model antitumor drug, was loaded into cRGD-SCM with a diameter of approximately 100nm, and the drug loading efficiency was 45.9wt.%. cRGD-SCM/DOX with a sustained release pattern exhibited prolonged circulation time, upregulated accumulation in tumor, enhanced tumor inhibition, and decreased side effects compared with free DOX and non-targeting SCM/DOX in vivo. More interestingly, the targeting ligand in the terminal of PEG can be easily replaced with other targeting groups according to the different types of malignancies. Therefore, the cRGD-decorated platform might be a promising targeted drug delivery system for personal chemotherapy clinically.

  15. In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

    PubMed Central

    Pierelli, L.; Scambia, G.; Fattorossi, A.; Bonanno, G.; Battaglia, A.; Perillo, A.; Menichella, G.; Panici, P. B.; Leone, G.; Mancuso, S.

    1998-01-01

    We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity. PMID:9792145

  16. 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.

  17. Antineoplastic and cytogenetic effects of chlorpromazine on human lymphocytes in vitro and on Ehrlich ascites tumor cells in vivo.

    PubMed

    Lialiaris, Theodore S; Papachristou, Fotini; Mourelatos, Constantine; Simopoulou, Maria

    2009-09-01

    The inhibitory effect of phenothiazines in tumor growth and cancer cell proliferation in vitro and in vivo has been established. These reports motivated us to investigate the genotoxic, cytotoxic, and cytostatic potential of chlorpromazine, alone or in combination with mitomycin C, in vitro and in vivo. Sister chromatid exchange levels were assessed providing a quantitative index of genotoxicity. In-vitro studies were performed on human lymphocyte cultures and in-vivo studies involved Ehrilch ascites tumor (EAT) cells. An antitumour study was also conducted on the survival time and the ascitic volume in EAT-bearing Balb/C mice. The combination of chlorpromazine plus caffeine and mitomycin C exerted cytostatic and cytotoxic actions in human lymphocytes. The combination of chlorpromazine plus mitomycin C exerted cytostatic and cytotoxic actions in EAT cells, significantly increased the survival span of the mice inoculated with EAT cells, and suppressed the expected tumor growth increase. The findings of this basic study illustrate that high chlorpromazine concentrations increase chemotherapeutic effectiveness of mitomycin C. Chlorpromazine concentrations within the observed human plasma concentration range need to be tested along with antineoplastic agents in vitro for its synergistic action so as to evaluate a potential clinical application. Further investigation including other phenothiazines, biological systems, and cancer models is required.

  18. Organotypic culture of breast tumor explants as a multicellular system for the screening of natural compounds with antineoplastic potential.

    PubMed

    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.

  19. Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

    PubMed Central

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition. PMID:24651472

  20. 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

  1. [Activity of nonspecific hepatic oxidases and the biological effects of the antineoplastic antibiotic adriamycin].

    PubMed

    Bogush, T A; Syrkin, A B; Donenko, F V

    1981-10-01

    It was shown in male CBA mice that toxic doses (15 and 20 mg/kg) of adriamycin (AD) inhibited the activity of nonspecific liver oxidases and noticeably increased the duration of the animals' sleep after injection of hexenal which is a substrate of this enzymatic system. The inhibitory effect of AD remained unchanged in the course of 9 days of the experiment. The nontoxic dose of AD (5 mg/kg) inhibited the activity of the enzymatic system on the 2nd--3rd days after the injection of the drug. Meanwhile the activity of the enzymatic system returned to the level seen in intact animals by days 5--6. The toxic action of AD declined on activation of nonspecific liver oxidases with phenobarbital and rose as a result of administering the inhibitor SKF 525-A. The authors discuss whether it is possible to use the data obtained for clinical application of AD.

  2. pH-Responsive Reversible PEGylation Improves Performance of Antineoplastic Agent.

    PubMed

    Sun, Diankui; Ding, Jianxun; Xiao, Chunsheng; Chen, Jinjin; Zhuang, Xiuli; Chen, Xuesi

    2015-04-22

    The reversible PEGylation endows antitumor drugs with various fascinating advantages, including prolonged circulation time in blood, enhanced accumulation in tumor tissue, increased cellular uptake, and promoted intracellular drug release, to improve the therapeutic efficacy and security. Here, the obtained succinic anhydride (SA)-functionalized DOX (SAD) (i.e., insensitive succinic anhydride-functionalized doxorubicin (DOX)) and aconitic anhydride (CA)-modified DOX (CAD) (i.e., acid-sensitive cis-aconitic anhydride-modified DOX) are conjugated to the terminal of poly(ethylene glycol) (PEG) yielding the unresponsive SAD-PEG-SAD and pH-responsive CAD-PEG-CAD prodrugs, respectively. The prepared prodrugs can self-assemble into micelles in aqueous solution. Both micelles are sufficiently stable at normal physiological pH (i.e., 7.4), while CAD-PEG-CAD micelle gradually swells and finally disassembles at intratumoral (i.e., 6.8) and especially endosomal pHs (i.e., 5.5). DOX release from CAD-PEG-CAD at pH 7.4 is efficiently inhibited, whereas it is significantly accelerated by the rapid cleavage of amide bond at pH 5.5. In addition, CAD-PEG-CAD exhibits more efficient cellular uptake and potent cytotoxicity in vitro, as well as improved tissue distribution and superior tumor suppression in vivo than free DOX and SAD-PEG-SAD. More importantly, the PEGylated DOX exhibits favorable security in vivo. In brief, the smart CAD-PEG-CAD with enhanced antitumor efficacy and decreased side effects shows as a promising powerful platform for the clinical chemotherapy of malignancy.

  3. The Application of Pattern Recognition to Screening Prospective Anti-Cancer Drugs: Adenocarcinoma 775 Biological Activity Test.

    DTIC Science & Technology

    A novel application of pattern recognition to the screening of potential anti-cancer drugs is presented. Structural features of 200 drugs previously tested by the National Cancer Institute for activity in the solid tumor adenocarcinoma 755 screening test are input to a master program of pattern recognition methods. The programs were 93.5% accurate in discriminating drugs with positive anti-neoplastic activity versus those with no anti-cancer activity. Extensions to a more rational approach to ’ drug design ’ are also discussed. (Author)

  4. 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.

  5. Soil DNA libraries for anticancer drug discovery.

    PubMed

    Pettit, Robin K

    2004-07-01

    Soil has the largest population of microbes of any habitat, but only about 0.3% of soil microbes are cultivable with current techniques. Cultured soil microbes have been an incredibly productive source of drugs, for example the cancer chemotherapeutics doxorubicin hydrochloride, bleomycin, daunorubicin and mitomycin. Unfortunately, the current yield of new drugs from soil microbes is low due to repeated cultivation of the same small fraction of cultivable microbes. Uncultured soil species represent a tremendous untapped resource of new antineoplastic agents. Methods have recently been developed to access the diversity of secondary metabolites from uncultured soil microbes. Briefly, total DNA is extracted from soil samples, purified, partially digested, and fragments inserted into vectors for expression in readily fermented microbes such as Escherichia coli. Clones expressing enzymatic and antibiotic activities that are encoded by novel sequences have been reported.

  6. Physiological characterization of human ovarian cancer cells in a rat model of intraperitoneal antineoplastic therapy.

    PubMed

    Flessner, Michael F; Choi, Jaehwa; He, Zhi; Credit, Kimberly

    2004-10-01

    Destruction of cancer cells by therapies directed against new molecular targets requires their effective delivery to the tumor. To study diffusion and convection of intraperitoneal (ip) therapy to ip tumors, we established a new athymic rat (RNU) model with ovarian tumor cells (SKOV3 and OVCAR3) implanted in the abdominal wall. The model simulates metastatic tumor and facilitates the measurement of physiological parameters that govern transport forces. CD31 immunohistochemistry revealed unique patterns of angiogenesis, with a tissue-averaged vascular volume of approximately 0.01 ml/g for each tumor. The extracellular volume (SKOV3: 0.54 +/- 0.11 ml/g, n=5; OVCAR3: 0.61 +/- 0.03, n=5) was over twice that of the adjacent normal muscle (0.22 +/- 0.06 ml/g, n=5). Intravenous-injected antibody tumor clearance was two to three times that of muscle. Interstitial pressures were higher than normal tissue with a median of 10-15 mmHg. Quantitative autoradiography of frozen tissue slices from rats exposed to ip solutions containing [14C]mannitol or 125I-immunoglobulin G (trastuzumab) was performed to determine transport of small and large molecules. With ip pressure of 0-6 mmHg, both mannitol and immunoglobulin G displayed steep concentration profiles close to the tumor surface with limited penetration deeper within the tumor tissue; antibody penetration was significantly affected by ip pressure. These results demonstrated effects of molecular size, ip pressure, the limited but highly permeable tumor vasculature, and the expanded interstitium on drug penetration from the peritoneal cavity. In conclusion, we have characterized physical and chemical parameters that determine transport of therapeutic agents in our unique tumor-bearing rat model.

  7. Influence of pain severity on the quality of life in patients with head and neck cancer before antineoplastic therapy

    PubMed Central

    2014-01-01

    Background The aim of this study was to assess the severity of pain and its impact on the quality of life (QoL) in untreated patients with head and neck squamous cell carcinoma (HNSCC). Methods A study group of 127 patients with HNSCC were interviewed before antineoplastic treatment. The severity of pain was measured using the Brief Pain Inventory (BPI) questionnaire, and the QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and the head and neck module (QLQ-H&N35). Results The mean age of the patients was 57.9 years, and there was a predominance of men (87.4%). The most frequent site of the primary tumor was the oral cavity (70.6%), and the majority of the patients had advanced cancers (stages III and IV). QoL in early stage of cancer obtained better scores. Conversely, the patients with advanced stage cancer scored significantly higher on the symptom scales regarding fatigue, pain, appetite loss and financial difficulties, indicating greater difficulties. Regard to the severity of pain, patients with moderate-severe pain revealed a significantly worse score than patients without pain. Conclusions The severity of pain is statistically related to the advanced stages of cancer and directly affects the QoL. An assessment of the quality of life and symptoms before therapy can direct attention to the most important symptoms, and appropriate interventions can then be directed toward improving QoL outcomes and the response to treatment. PMID:24460780

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

    PubMed Central

    Coppola, Carmela; Riccio, Gennaro; Barbieri, Antonio; Monti, Maria Gaia; Piscopo, Giovanna; Rea, Domenica; Arra, Claudio; Maurea, Carlo; De Lorenzo, Claudia; Maurea, Nicola

    2016-01-01

    Objective Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue. PMID:27843329

  9. Synergistic antineoplastic effect of DLC1 tumor suppressor protein and histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), on prostate and liver cancer cells: perspectives for therapeutics.

    PubMed

    Zhou, Xiaoling; Yang, Xu-Yu; Popescu, Nicholas C

    2010-04-01

    Inactivation of tumor suppressor genes is a major contributing alteration in the initiation or progression of cancer. The human tumor suppressor gene DLC1 (deleted in liver cancer 1) is frequently downregulated or silenced in multiple cancers, predominantly by epigenetic mechanisms. With the current considerable interest and progress in epigenetic therapy, a number of promising antineoplastic agents, particularly histone deacetylase (HDAC) inhibitors, have been developed and used successfully in clinical trials. Both DLC1 and HDAC inhibitors exert antineoplastic functions, and their combined action could be exploited for a more effective cancer therapy. To evaluate the potential benefits of this approach, we examined the antineoplastic effects of adenoviral (Ad)-DLC1-mediated transduction and exposure to suberoylanilide hydroxamic acid (SAHA), a powerful HDAC inhibitor, in two human cancer cell lines that lack intrinsic DLC1 expression, 22Rv1 prostate cancer cells and 7703K human hepatocellular carcinoma cells. Consistent with the oncosuppressive function of DLC1 in several cancers, including prostate and liver cancer, transduction of 22Rv1 and 7703K cells with an Ad-DLC1 expression vector resulted in alterations of cell morphology, induction of apoptosis, and inhibition of cell proliferation, migration, and anchorage-independent growth. A low concentration of SAHA (5 microM) efficiently restored the expression of DLC1 in 22Rv1 cells that lack DLC1 expression due to histone deacetylation but had a minimal effect in 7703K cells in which silencing of the DLC1 gene is due mainly to promoter hypermethylation. Regardless of the epigenetic mechanism of DLC1 inactivation, SAHA treatment of DLC1-transduced cells had a synergistic inhibitory effect on tumor cell proliferation and tumorigenesis in both cell lines. In 22Rv1 cells, this combination regimen nearly abolished the formation of colonies in semisolid media as a measure of tumorigenicity in vitro. Current in vitro

  10. Use of liposomes as injectable-drug delivery systems.

    PubMed

    Ostro, M J; Cullis, P R

    1989-08-01

    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  11. Highly sensitive high-performance liquid chromatography/selective reaction monitoring mass spectrometry method for the determination of cyclophosphamide and ifosfamide in urine of health care workers exposed to antineoplastic agents.

    PubMed

    Sottani, Cristina; Tranfo, Giovanna; Faranda, Paolo; Minoia, Claudio

    2005-01-01

    In recent years, the potential for exposure of health care workers to antineoplastic agents has led to the establishment of more restrictive government and professional standards and procedures for handling cytotoxic drugs. Therefore, the detection of low exposure levels is a new and important aim of biological monitoring. In the present paper we report an assay for the simultaneous determination of cyclophosphamide (CP) and ifosfamide (IF) in urine, using electrospray ionization liquid chromatography/tandem mass spectrometry with selective reaction monitoring (HPLC/SRM-MS). A rapid sample preparation procedure uses a solid-phase extraction stage with C18 columns. The urine assay is linear over the range 0.02 to 0.4 microg/L, with lower limits of quantification (LLOQs) of 0.02 and 0.04 microg/L for CP and IF. The accuracy and precision have been carried out through the validation study. The intra-day precision, expressed as relative standard deviation (RSD), is found to be always less than 14.7% for both analytes. The overall precision, assessed on three different days, is less than 15.0%. The recovery of ozaxaphosphorines ranges from 83.5% (CP) to 88.5% (IF) with a RSD always less than 14.6%. The uncertainty of the overall method was also evaluated, to identify possible sources of error. The combined uncertainty was less than 25% over all the days of the validation study. This method is selective and sensitive enough to determine trace levels of CP and IF in a range of urine concentrations relevant to performing low exposure assessment.

  12. Controllable synthesis and adjustable antineoplastic activity of bovine serum albumin-conjugated PbS/Ag2S core/shell nano-composites.

    PubMed

    Wang, Hua-Jie; Yu, Xue-Hong; Cao, Ying; Zhou, Bei; Wang, Cai-Feng

    2012-08-01

    Series of mono-dispersed bovine serum albumin (BSA)-conjugated PbS/Ag(2)S core/shell nano-composites with different Pb/Ag ratios had been successfully synthesized by an ion-exchange method under the gentle conditions using BSA-conjugated PbS nano-crystals as precursors, which were prepared by a biomimetic method. Fourier transform infrared spectra analysis and transmission electron microscopy (TEM) observation demonstrated that BSA was a key factor to control the morphology and size of final products. Additionally, the real-time TEM observation, X-ray powder diffraction and atomic absorption spectroscopy analysis were applied to monitor the synthesis process. The results indicated that the shell thickness and ratio of Pb to Ag could be controlled by adjusting the ion-exchange time. Both metabolic and morphological methods revealed that the proliferation of rat pheochromocytoma (PC 12) cells could be inhibited by BSA-conjugated PbS/Ag(2)S core/shell nano-composites, and the antineoplastic activity was Pb/Ag ratio-dependent. It might be explained by a Trojan horse-type mechanism. Summarily, the present study would be helpful to find a new core/shell nano-composite with higher and controllable antineoplastic activity due to the synergistic reaction of different metal ions.

  13. Reduced Expression of the Retinoblastoma Protein Shows That the Related Signaling Pathway Is Essential for Mediating the Antineoplastic Activity of Erufosine

    PubMed Central

    Zaharieva, Maya M.; Kirilov, Milen; Chai, Minquang; Berger, Stefan M.; Konstantinov, Spiro; Berger, Martin R.

    2014-01-01

    Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by eru-fosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status. PMID:24987858

  14. [Safety notice for the use of drugs for intravesical instillations and cost analysis].

    PubMed

    Zanni, Giuseppe

    2013-01-01

    Among the objectives outlined in the National Health Plan 1998-2000 are some interventions to improve the safety of public and private health-care facilities. One of the significant risks in the health sector is the one resulting from exposure to chemotherapy drugs. The Health Surveillance must take into account that anticancer drugs are cytotoxic compounds, which can cause cancer. It is necessary that occupational exposure to antineoplastic agents be kept within the lowest possible level. The potential absorption due to exposure to chemotherapy may be significantly reduced by adopting preventive measures specific to particular concern in a centralization of structures and activities. To ensure an adequate system of protection for people who use these substances in professional health-care settings, there should be the establishment of a specific "Anticancer Drugs Unit" to entrust the working cycle. The places reserved for the preparation of cytotoxic chemotherapy must be equipped with floor and walls up to heights of appropriate plastic material easily washable. Inside the room there must be a "point of decontamination" for washing hands and eyes. The preparation of antineoplastic agents should be performed under hoods positioned away from heat sources and any air currents. It is advisable to use disposable surgical gowns with long sleeves with elastic cuffs or knitted sleeve to allow the gloves sticking above the gown itself. In the preparation of drugs the vial opening procedure must be implemented after verifying that no liquid is left at the top, and by wrapping the neck of the vial with a sterile gauze. Any accidental contamination must be reported to the Physician. All waste materials produced from the handling of cytotoxic chemotherapy should be considered as special hospital waste. To achieve high standards of safety and prevention for the personnel exposed to antineoplastic agents, it is necessary that workers are adequately informed about the risks and

  15. Paradoxical and bidirectional drug effects.

    PubMed

    Smith, Silas W; Hauben, Manfred; Aronson, Jeffrey K

    2012-03-01

    -dimensional architectural constraints; pharmacokinetic competing compartment effects; disruption and non-linear effects in oscillating systems, systemic overcompensation, and other higher-level feedback mechanisms and feedback response loops at multiple levels. Here we review and provide a compendium of multiple class effects and individual reactions, relevant mechanisms, and specific clinical toxicological considerations of antibiotics, immune modulators, antineoplastic drugs, and cardiovascular, CNS, dermal, endocrine, musculoskeletal, gastrointestinal, haematological, respiratory, and psychotropic agents.

  16. Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery.

    PubMed

    Aldea, Mihaela; Craciun, Lucian; Tomuleasa, Ciprian; Berindan-Neagoe, Ioana; Kacso, Gabriel; Florian, Ioan Stefan; Crivii, Carmen

    2014-06-01

    After sitting many years on the shelves of drug stores as a harmless antidiabetic drug, metformin comes back in the spotlight of the scientific community as a surprisingly effective antineoplastic drug. Metformin targets multiple pathways that play pivotal roles in cancer progression, impacting various cellular processes, such as proliferation, cell death, metabolism, and even the cancer stemness features. The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin's anticancer efficiency. This could indicate a need for tumor genetic profiling in order to identify patients most likely to benefit from metformin treatment. Considering that the majority of experimental models suggest that higher, supra-clinical doses of metformin should be used in order to obtain an antineoplastic effect, new ways of drug delivery could be developed, such as metformin-loaded nanoparticles or incorporation of metformin into microparticles used in transarterial chemoembolization, with the aim of obtaining higher intratumoral drug concentrations and a targeted therapy which will ultimately maximize metformin's efficacy.

  17. The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling.

    PubMed

    Lång, Emma; Grudic, Amra; Pankiv, Serhiy; Bruserud, Oystein; Simonsen, Anne; Bjerkvig, Rolf; Bjørås, Magnar; Bøe, Stig Ove

    2012-07-26

    Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL). The mechanism by which this agent cures this disease was previously shown to involve direct interactions between ATO and the promyelocytic leukemia protein (PML), as well as accelerated degradation of the APL-associated fusion oncoprotein PML/retinoic acid receptor α (RARA). Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. We found that ATO inhibits formation of progeny PML bodies while it stabilizes cytoplasmic precursor compartments, referred to as cytoplasmic assemblies of PML and nucleoporins (CyPNs), after cell division. This block in PML body recycling is readily detected at pharmacologic relevant ATO concentrations (0.02-0.5μM) that do not cause detectable cell-cycle defects, and it does not require modification of PML by SUMOylation. In addition, PML and PML/RARA carrying mutations previously identified in ATO-resistant APL patients are impeded in their ability to become sequestered within CyPNs. Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration.

  18. Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database.

    PubMed

    Colin, Olivier; Favrelière, Sylvie; Quillet, Alexandre; Neau, Jean-Philippe; Houeto, Jean-Luc; Lafay-Chebassier, Claire; Pérault-Pochat, Marie-Christine

    2017-04-01

    Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period. To assess the association between PML and drug intake, we calculated an adverse drug report odds ratio (ROR) with its 95% confidence interval. We have studied the delay of onset of PML for each drug concerned. Among the 101 cases of PML, 39 drugs were mentioned as suspect. The main therapeutic classes suspected with significant ROR were antineoplastic agents (n = 85), immunosuppressants (n = 67), and corticosteroids. A latent interval from the time of drug initiation to the development of PML is established: the median time to onset was 365 days (123-1095 days). The onset of PML is highly variable and differs among drug classes [from 1 to 96 months (IQR: 39.0-126)]. An association between PML and some immunosuppressant drugs was found as expected, but also with antineoplastic agents and glucocorticoids. An important delay of PML onset after stopping treatment is suspected and should alert prescribers. Prescribers but also patients should be informed about the potential associations with all these drugs. Monitoring could be necessary for many drugs to early detect PML.

  19. 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.

  20. 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

  1. A sensitive electrochemical DNA biosensor for antineoplastic drug 5-fluorouracil based on glassy carbon electrode modified with poly(bromocresol purple).

    PubMed

    Koyuncu Zeybek, Derya; Demir, Burcu; Zeybek, Bülent; Pekyardımcı, Şule

    2015-11-01

    This paper describes an electrochemical sensor for the first time based on poly(bromocresol purple) (P(BCP)) developed to observe the interaction between 5-fluorouracil (5-FU) and fish sperm double strand DNA (dsDNA). The P(BCP) film was electrosynthesized by cyclic voltammetry method on the glassy carbon electrode (GCE). The dsDNA was electrochemically immobilized on the surface of P(BCP) modified GCE and the DNA biosensor was prepared. The interaction mechanism of dsDNA with 5-FU was investigated by differential pulse voltammetry using this biosensor. A decrease in the guanine oxidation peak current of the biosensor was observed after the interaction of dsDNA and 5-FU in 0.5 mol L(-1) acetate buffer (pH 4.8) containing 0.02 mol L(-1) NaCl. The accumulation time and dsDNA concentration were optimized to obtain the best peak current response. Under optimum conditions, the linear response on the guanine signal decreasing curve was observed in the 5-FU concentration range of 1.0-50 mg L(-1). The interaction mechanism between dsDNA and 5-FU was further investigated by UV-vis spectroscopy and viscometer. The results reveal that intercalation is the primary mode of interaction between 5-FU and dsDNA.

  2. 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

    2016-05-26

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

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

    PubMed

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

    2016-02-24

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

  4. Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug.

    PubMed Central

    Lemaire, L.; Malet-Martino, M. C.; de Forni, M.; Martino, R.; Lasserre, B.

    1992-01-01

    The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that are formed in the basic medium employed to dissolve this compound. To avoid chemical degradation of this antineoplastic drug, the solution of FU that will be injected should be prepared immediately before use. PMID:1637660

  5. Unusual case of desmotropy. Combined spectroscopy (¹H-¹⁴N NQDR) and quantum chemistry (periodic hybrid DFT/QTAIM and Hirshfeld surface-based) study of solid dacarbazine (anti-neoplastic).

    PubMed

    Latosińska, Jolanta Natalia; Latosińska, Magdalena; Seliger, Janez; Žagar, Veselko; Burchardt, Dorota V; Derwich, Katarzyna

    2015-01-01

    Antineoplastic chemo-therapeutic drug 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide (Dacarbazine, DTIC), has been studied experimentally in solid state by ¹H-¹⁴N NQDR double resonance at 295 K and theoretically by the Density Functional Theory (DFT)/Quantum Theory of Atoms in Molecules (QTAIM) and Hirshfeld surfaces analysis. Only one set of eighteen resonance frequencies was found in the experiment. This indicates the presence of six inequivalent nitrogen sites: -N(CH₃), -NH₂, -NH- and three -N= (of which one is a ring, two are from triazene) in the DTIC molecule. This contradicts the X-ray data which revealed the multiplication of nitrogen sites due to unusual desmotropism. The averaging of NQR frequencies caused by the fast in NQR time-scale exchange of protons in a double-well potential combined with the oscillations of twisted supramolecular synthons was proposed as a potential mechanism responsible for this apparent contradiction. An effective improvement in the quality of the spectrum reproduction was achieved when the calculations were performed assuming the periodic boundary conditions, BLYP functional, the DNP basis set and taking the 3×3×3 k-point separation. The ordering of the nitrogen sites according to the increasing quadrupole coupling constant (QCC): N(3)

  6. Cross-comparison of cancer drug approvals at three international regulatory agencies

    PubMed Central

    Samuel, N.; Verma, S.

    2016-01-01

    Background The primary objective of the present study was to examine the drug approval process and the time to approval (tta) for cancer drugs by 3 major international regulatory bodies—Health Canada, the U.S. Food and Drug Administration (fda), and the European Medicines Agency (ema)—and to explore differences in the drug approval processes that might contribute to any disparities. Methods The publicly available Health Canada Drug Product Database was surveyed for all marketed antineoplastic agents approved between 1 January 2005 and 1 June 2013. For the resulting set of cancer drugs, public records of sponsor submission and approval dates by Health Canada, the fda, and the ema were obtained. Results Overall, the tta for the 37 antineoplastic agents that met the study criteria was significantly less for the fda than for the ema (X̄ = 6.7 months, p < 0.001) or for Health Canada (X̄ = 6.4 months, p < 0.001). The tta was not significantly different for Health Canada and the ema (X̄ = 0.65 months, p = 0.89). An analysis of the review processes demonstrated that the primary reason for the identified discrepancies in tta was the disparate use of accelerated approval mechanisms. Summary In the present study, we systematically compared cancer drug approvals at 3 international regulatory bodies. The differences in tta reflect several important considerations in the regulatory framework of cancer drug approvals. Those findings warrant an enhanced dialogue between clinicians and government agencies to understand opportunities and challenges in the current approval processes and to work toward balancing drug safety with timely access. PMID:27803605

  7. 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 ...

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

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

  10. Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo

    NASA Astrophysics Data System (ADS)

    Lynchak, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Kyzyma, O. A.; Soloviov, D.; Kostjukov, V. V.; Evstigneev, M. P.; Ritter, U.; Scharff, P.

    2017-01-01

    The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

  11. 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

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. 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.

  17. 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.

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

    PubMed

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

    2011-01-01

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

  19. Clinically relevant drug–drug interactions in oncology

    PubMed Central

    McLeod, Howard L

    1998-01-01

    Although anticancer agents are one of the most toxic classes of medication prescribed today, there is relatively little information available about clinically relevant drug–drug interactions. Pharmacokinetic drug interactions have been described, including alterations in absorption, catabolism, and excretion. For example, an increased bioavailability of 6-mercaptopurine has been observed when combined with either allopurinol or methotrexate, leading to increased toxicity in some patients. Induction of etoposide or teniposide clearance by anticonvulsants has also been described, resulting in a lower systemic exposure and risk for lower anticancer activity. Alterations in elimination of methotrexate has been observed with probenecid, presumably through competition for renal secretion. There are also several examples of pharmacodynamic interactions. The combination of 5-fluorouracil plus folinic acid results in more efficient inhibition of thymidylate synthase, a finding which is now utilized routinely in the treatment of colorectal cancer. Improvements in the in vitro and early clinical testing now allow a relatively high degree of prediction of potential clinical drug interactions, prior to observations of untoward drug effects. In conclusion, drug interactions among commonly used anticancer agents have been identified. Their clinical significance can have more impact than many other classes of medications due to the narrow therapeutic index of antineoplastic agents and the potential for lethal side-effects. It is only through prospective, preclinical and early clinical evaluation that the presence of clinically significant drug interactions can be identified and the information used to provide better therapy for this significant health problem. PMID:9663808

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

    PubMed

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

    2017-03-15

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

  1. Determination of MKT-077, a novel antineoplastic agent, in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats.

    PubMed

    Tatsuta, N; Suzuki, N; Koya, K; Kawakami, M; Shishido, T; Chen, L B

    1999-03-01

    A simple high-performance liquid chromatographic method was developed for determination of a novel antineoplastic agent MKT-077 in plasma. MKT-077 was extracted from 50 microl of plasma with acetonitrile containing 1 ml trifluoroacetic acid per liter. Chromatographic separation was achieved within 13.5 min using a reverse-phase Puresil C18 analytical column. A visible detector operated at 490 nm was used. The linearity of the calibration curve was obtained (r2 = 0.99986) over the analytical range of 10-500 ng/ml(-1). The intra- and inter-assay precision was in the range of 0.9-11.1 and 0.3-4.4%, respectively. The intra- and inter-assay bias ranged from -7.3 to 11.1% and from 0.4 to 11.6%, respectively. The utility of this assay was demonstrated after the administration of a single dose of MKT-077 to rats. The plasma elimination half-life of MKT-077 was 1.8-4 h.

  2. Effect of Nutritional Supplementation Enriched with Eicosapentaenoic Acid on Inflammatory Profile of Patients With Oral Cavity Cancer in Antineoplastic Pretreatment: A Controlled and Randomized Clinical Trial.

    PubMed

    Carvalho, Thayana C; Cruz, Bruna C S; Viana, Monica S; Martucci, Renata B; Saraiva, Danúbia C A; Reis, Patrícia F

    2017-04-01

    The objective of the study is to investigate the effect of nutritional supplementation with eicosapentaenoic acid (EPA)-enriched formula on the inflammatory profile of patients with oral cavity cancer. The study was conducted with 53 patients with oral cavity cancer in antineoplastic pretreatment who were randomized into two groups: the control group received a powdered supplement without EPA during 4 wk and the intervention group received a liquid supplement enriched with EPA (2 g/day) during the same period. In the baseline and after 4 wk of supplementation, serum concentrations of albumin, prealbumin, C-reactive protein (CRP), and interleukin-6 (IL-6) were measured. Values of CRP and of CRP/albumin ratio were lower in the intervention group than those in the control group. However, when the two groups were compared to each other after intervention, any significant difference was not observed. There was a significant negative correlation between levels of CRP and albumin, and IL-6 and albumin, both in the control and in the intervention groups. In both groups, a positive correlation between concentrations of IL-6 and CRP was observed. No significant difference was encountered in the assessed parameters between the group that received standard supplement and the group that received EPA-enriched supplement.

  3. Anti-Neoplastic Therapy Use in Advanced Cancer Patients Admitted to an Acute Palliative Care Unit at a Comprehensive Cancer Center: A Simultaneous Care Model

    PubMed Central

    Hui, David; Elsayem, Ahmed; Li, Zhijun; De La Cruz, Maxine; Palmer, J Lynn; Bruera, Eduardo

    2010-01-01

    BACKGROUND Cancer patients admitted to a palliative care unit generally have a poor prognosis. The role of antineoplastic therapy (ANT) in these patients is controversial. We examined the frequency and predictors associated with ANT use in hospitalized patients who required an acute palliative care unit (APCU) stay. METHODS We included all 2604 patients admitted over a five-year period to a 12-bed APCU located within a National Cancer Institute comprehensive cancer center, where patients can access both palliative care and ANT. We retrospectively retrieved from institutional databases patient demographics, cancer diagnosis, ANT use, length of hospital stay, and survival from time of admission. RESULTS The median hospital stay was 11 days and the median survival was 22 days. During hospitalization, 435 patients (17%) received ANT, including chemotherapy (N=297, 11%), hormonal agents (N=54, 2%) and targeted therapy (N=155, 6%). No significant change in frequency of ANT use was detected over the 5 year period. Multivariate logistic regression analysis revealed that younger age, specific cancer diagnoses and longer admissions were independently associated with ANT use. CONCLUSION The use of ANT during hospitalization that included an APCU stay was limited to a small percentage of patients, and did not increase over time. ANT use was associated with younger age, specific cancer diagnoses and longer admissions. The APCU facilitates simultaneous care where patients access palliative care while on ANT. PMID:20162701

  4. 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.

  5. 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).

  6. NSAIDs: Old Drugs Reveal New Anticancer Targets.

    PubMed

    Piazza, Gary A; Keeton, Adam B; Tinsley, Heather N; Whitt, Jason D; Gary, Bernard D; Mathew, Bini; Singh, Raj; Grizzle, William E; Reynolds, Robert C

    2010-05-25

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

  7. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  8. 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

  9. Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines.

    PubMed

    George, V Cijo; Kumar, D R Naveen; Rajkumar, V; Suresh, P K; Kumar, R Ashok

    2012-01-01

    Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of Annona muricata L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and DPPH* radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 μg when compared with those obtained for cancerous cells (IC50 values of 29.2 μg for MDA-MB-435S and 30.1 μg for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of Annona muricata. Isolation of the active metabolites from the extract is in prospect.

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

    PubMed

    Coyne, Cody P; Narayanan, Lakshmi

    2016-08-25

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

  11. 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

  12. Generic Drugs

    MedlinePlus

    Generic Drugs: The Same Medicine for Less Money What is a generic drug? A generic is a copy of a brand-name drug. A brand- name drug has a patent. When ... benefit to your health, and you will save money. 7KH IHGHUDO )RRG DQG 'UXJ $GPLQLVWUDWLRQ )'$ UHJXODWHV ERWK ...

  13. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

    Drug hypersensitivity represents an immune-mediated reaction to a drug. Although several drug hypersensitivity reactions are confined to the skin and rather mild, some may be life threatening and also involve further organs such as liver, kidney and bone marrow. The exact pathogenesis of many drug hypersensitivity reactions is still obscure. In this review the concepts on how small molecular drugs can activate the immune system are discussed and the hapten, prohapten and p-i concept are explained. Furthermore, the classification of drug hypersensitivity reactions and some common and severe clinical manifestations of drug-induced T cell mediated reactions are presented.

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

    SciTech Connect

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

    1989-11-01

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

  15. Assay of anti-cancer drugs in tissue culture: conditions affecting their ability to incorporate 3H-leucine after drug treatment.

    PubMed

    Freshney, R I; Paul, J; Kane, I M

    1975-01-01

    An attempt has been made to construct an assay potentially suitable for use with primary cultures of human tumours to measure the survival of exponentially growing monolayer cultures after exposure to anti-neoplastic drugs. Cell survival was assessed using their protein synthetic capacity after removal of drugs. HeLa cells were employed to avoid the ingerent variability and heterogeneity of primary cultures from human tumours, and an assay has been constructed using microtitration trays to provide large numbers of replicate cultures without the requirement of a large number cells. An increase in the duration of the exposure to drug increased sensitivity in nearly all cases examined. Similarly, an increase in the period of culture following drug removal produced increased sensitivity to alkylating agents but allowed recovery from exposure to certain cycle-dependent drugs. Some of the drugs used were shown to be unstable under culture conditions and vinblastine was actively metabolized, although this instability was not necessarily reflected in the time course of the drug's effect. Mustine sensitivity was shown to be reduced by an increase in cell density at a level where density limitation of 3H-thymidine incorporation becomes apparent. These variations and possible methods of minimizing their effects are discussed.

  16. Assay of anti-cancer drugs in tissue culture: conditions affecting their ability to incorporate 3H-leucine after drug treatment.

    PubMed Central

    Freshney, R. I.; Paul, J.; Kane, I. M.

    1975-01-01

    An attempt has been made to construct an assay potentially suitable for use with primary cultures of human tumours to measure the survival of exponentially growing monolayer cultures after exposure to anti-neoplastic drugs. Cell survival was assessed using their protein synthetic capacity after removal of drugs. HeLa cells were employed to avoid the ingerent variability and heterogeneity of primary cultures from human tumours, and an assay has been constructed using microtitration trays to provide large numbers of replicate cultures without the requirement of a large number cells. An increase in the duration of the exposure to drug increased sensitivity in nearly all cases examined. Similarly, an increase in the period of culture following drug removal produced increased sensitivity to alkylating agents but allowed recovery from exposure to certain cycle-dependent drugs. Some of the drugs used were shown to be unstable under culture conditions and vinblastine was actively metabolized, although this instability was not necessarily reflected in the time course of the drug's effect. Mustine sensitivity was shown to be reduced by an increase in cell density at a level where density limitation of 3H-thymidine incorporation becomes apparent. These variations and possible methods of minimizing their effects are discussed. PMID:1156513

  17. Poorly water-soluble drug nanoparticles via solvent evaporation in water-soluble porous polymers.

    PubMed

    Roberts, Aled D; Zhang, Haifei

    2013-04-15

    A generic method is described to form poorly water-soluble drug nanoparticles within water-soluble porous polymer by solvent evaporation. The simple dissolution of porous polymer with drug nanoparticles results in stable aqueous drug nanoparticle suspension under the optimized conditions. The porous polymers were prepared by freeze-drying aqueous solutions of polyvinyl alcohol, polyethylene glycol, and a surfactant. They were then used as scaffolds for the formation of nanoparticles by initially soaking them in an organic drug solution, followed with removing the solvent via evaporation under ambient conditions. This process was optimized for an antifungal drug griseofulvin, before being translated to anticonvulsant carbamazepine and antineoplastic paclitaxel via a similar procedure, with an aim to improve the loading of drug nanoparticles. By varying certain process parameters a degree of control over the particle size and surface charge could be attained, as well as the drug to stabilizer ratio (drug payload). Noticeably, aqueous paclitaxel nanoparticles (500 nm) were prepared which used the equivalent of 46% less stabilizer than the formulation Taxol.

  18. JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity.

    PubMed

    Shami, Paul J; Saavedra, Joseph E; Wang, Lai Y; Bonifant, Challice L; Diwan, Bhalchandra A; Singh, Shivendra V; Gu, Yijun; Fox, Stephen D; Buzard, Gregory S; Citro, Michael L; Waterhouse, David J; Davies, Keith M; Ji, Xinhua; Keefer, Larry K

    2003-04-01

    We have previously shown that nitric oxide (NO) inhibits growth and induces differentiation and apoptosis in acute myeloid leukemia cells, with the HL-60 human myeloid leukemia line being particularly sensitive to NO-mediated cytolysis. With the goal of identifying a prodrug that can target NO to the leukemia cells without inducing NO-mediated systemic hypotension, we have screened a series of O(2)-aryl diazeniumdiolates designed to be stable at physiological pH but to release NO upon reaction with glutathione. O(2)-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) proved to be the most active antiproliferative agent among those tested in HL-60 cells, with an IC(50) of 0.2-0.5 microM. After 5 days of exposure to 0.5 micro M JS-K, HL-60 cells had differentiated and acquired some of the phenotypic features of normal monocytes. One- to 2-day treatment with JS-K at concentrations of 0.5-1 microM resulted in apoptosis induction in a concentration- and caspase-dependent manner. JS-K also inhibited the growth of solid tumor cell lines but to a lesser extent than HL-60 cells. JS-K was administered i.v. to nonobese diabetic-severe combined immune deficient mice at doses of up to 4 micromol/kg without inducing significant hypotension. The growth of s.c. implanted HL-60 cells was reduced by approximately 50% when the mice received i.v. injections three times/week with 4 micromol/kg boluses of JS-K. Histological examination of tumor explants from JS-K-treated animals revealed extensive necrosis. Similar results were seen with s.c. human prostate cancer (PPC-1) xenografts. Our data indicate that JS-K is a promising lead compound for the possible development of a novel class of antineoplastic agents.

  19. Drug Allergy

    MedlinePlus

    ... of other allergies, such as food allergy or hay fever Allergic reaction to another drug A family history ... so, what drug was it? Do you have hay fever, food allergy or other allergies? Is there a ...

  20. Drugged Driving

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... in the past year. Middle Figure: Driving after marijuana use is more common than driving after alcohol ...

  1. Drugs (image)

    MedlinePlus

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  2. Drug Abuse

    MedlinePlus

    ... abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a ...

  3. 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)

  4. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    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.

  5. Protection behaviors for cytotoxic drugs in oncology nurses of chemotherapy centers in Shiraz hospitals, South of Iran

    PubMed Central

    Abbasi, Khadijeh; Hazrati, Maryam; Mohammadbeigi, Abolfazl; Ansari, Jasem; Sajadi, Mahboubeh; Hosseinnazzhad, Azam; Moshiri, Esmail

    2016-01-01

    Context: The use of antineoplastic agents for the treatment of cancer is an increasingly common practice in hospitals. As a result, workers involved with handling antineoplastic drugs may be accidentally exposed to these agents, placing them at potential risk for long-term adverse effects. This study aimed to determine the occupational protection status of clinical nursing staff exposed to cytotoxic drugs. Subjects and Methods: The study was designed as an analytic descriptive survey. The research settings took place in six centers of chemotherapy in Shiraz, Iran. The participants were 86 nurses who worked in oncology units and administered cytotoxic drugs. Data were collected using a questionnaire and a checklist which was developed by the investigators to determine occupational protection status of clinical nursing staff exposed to cytotoxic drugs. Percentage calculations and the independent samples t-test were used to see the general distribution and analysis of data. To statistically analyze of the data, SPSS software (version 16) was applied. Results: The mean age of participants was 30.52 ± 6.50 years and 66.27% of the nurses worked on inpatient oncology wards. The mean practice score was 21.1 ± 3.76 that ranged from 12.5 to 31. The independent samples t-test showed the outpatient nurses were weaker in practice (17.2 ± 2.52) in comparison with university hospitals (23.35 ± 3.02, P < 0.001). Occupational protection status of clinical nursing staff exposed to cytotoxic drugs especially during administration and disposal of medicines was poor and rarely trained with this subject and was observed under the standard conditions. Conclusions: There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to cytotoxic drugs. It is recommended that all clinical nursing staff should receive full occupational protection training about these matters and the authorities provide standard conditions of oncology

  6. Cell cycle effects of drugs

    SciTech Connect

    Dethlefsen, L.A.

    1986-01-01

    This book contains 11 chapters. Some of the chapter titles are: Cell Growth and Division Cycle; Cell Cycle Effects of Alkylating Agents; Biological Effects of Folic Acid Antagonists with Antineoplastic Activity; and Bleomycin-Mode of Action with Particular Reference to the Cell Cycle.

  7. [Adherence to oral antineoplastic therapy].

    PubMed

    Olivera-Fernandez, R; Fernandez-Ribeiro, F; Piñeiro-Corrales, G; Crespo-Diz, C

    2014-11-03

    Introducción: Los tratamientos antineoplasicos orales presentan ventajas en cuanto a coste, comodidad y mejora potencial en la calidad de vida respecto al tratamiento endovenoso, pero es mas dificil controlar la adherencia y monitorizar los efectos adversos. El objetivo de este estudio fue conocer la adherencia real en pacientes con antineoplasicos orales en nuestro centro, analizar la influencia de las caracteristicas del paciente y del tratamiento, identificar motivos de no adherencia, oportunidades de mejora en la atencion farmaceutica y evaluar la posible relacion adherencia y respuesta al tratamiento. Método: estudio prospectivo observacional de cuatro meses de duracion, en los pacientes con tratamiento antineoplasico oral dispensado desde la consulta de farmacia oncologica. Para la recogida de datos se utilizaron: orden medica, historia clinica y visita con entrevistas al paciente. Resultados: Se evaluaron un total de 141 pacientes. Un 72% se considero totalmente adherente, mientras que en un 28% se detecto algun tipo de no adherencia. El tiempo desde el diagnostico y la presencia de efectos adversos fueron las variables que afectaron a la adherencia. No se pudo demostrar relacion entre adherencia y respuesta al tratamiento. Conclusiones: La adherencia al tratamiento antineoplasico oral en nuestro centro fue del 72%, identificando oportunidades de mejora en la atencion farmaceutica dirigidas a prevenir los efectos adversos y a potenciar la adherencia de nuestros pacientes.

  8. 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; ...

  9. 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.

  10. Drug Addiction

    MedlinePlus

    ... mental health disorders, several factors may contribute to development of drug addiction and dependence. The main factors are: Environment. Environmental factors, including your family's beliefs and attitudes ...

  11. Drugged Driving

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  12. Club Drugs

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  13. Inhibition of DNA and Histone Methylation by 5-Aza-2′-Deoxycytidine (Decitabine) and 3-Deazaneplanocin-A on Antineoplastic Action and Gene Expression in Myeloid Leukemic Cells

    PubMed Central

    Momparler, Richard L.; Côté, Sylvie; Momparler, Louise F.; Idaghdour, Youssef

    2017-01-01

    Epigenetic alterations play an important role in the development of acute myeloid leukemia (AML) by silencing of genes that suppress leukemogenesis and differentiation. One of the key epigenetic changes in AML is gene silencing by DNA methylation. The importance of this alteration is illustrated by the induction of remissions in AML by 5-aza-2′-deoxycytidine (5-AZA-CdR, decitabine), a potent inhibitor of DNA methylation. However, most patients induced into remission by 5-AZA-CdR will relapse, suggesting that a second agent should be sought to increase the efficacy of this epigenetic therapy. An interesting candidate for this purpose is 3-deazaneplanocin A (DZNep). This analog inhibits EZH2, a histone methyltransferase that trimethylates lysine 27 histone H3 (H3K27me3), a marker for gene silencing. This second epigenetic silencing mechanism also plays an important role in leukemogenesis as shown in preclinical studies where DZNep exhibits potent inhibition of colony formation by AML cells. We reported previously that 5-AZA-CdR in combination with DZNep exhibits a synergistic antineoplastic action against human HL-60 AML cells and the synergistic activation of several tumor suppressor genes. In this report, we showed that this combination also induced a synergistic activation of apoptosis in HL-60 cells. The synergistic antineoplastic action of 5-AZA-CdR plus DZNep was also observed on a second human myeloid leukemia cell line, AML-3. In addition, 5-AZA-CdR in combination with the specific inhibitors of EZH2, GSK-126, or GSK-343, also exhibited a synergistic antineoplastic action on both HL-60 and AML-3. The combined action of 5-AZA-CdR and DZNep on global gene expression in HL-60 cells was investigated in greater depth using RNA sequencing analysis. We observed that this combination of epigenetic agents exhibited a synergistic activation of hundreds of genes. The synergistic activation of so many genes that suppress malignancy by 5-AZA-CdR plus DZNep suggests that

  14. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

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

  15. Compatibility of plastics with cytotoxic drug solutions-comparison of polyethylene with other container materials.

    PubMed

    Beitz, C; Bertsch, T; Hannak, D; Schrammel, W; Einberger, C; Wehling, M

    1999-08-05

    In this study low density polyethylene (LDPE)-containers were compared to glass bottles and polyvinyl chloride (PVC) bags in view of adsorption effects with antineoplastic drugs. The infusion containers were supplemented with therapeutic doses of the nine common cytotoxic drugs carboplatin, carmustine, cytarabine, dacarbazine, fluorouracil, gemcitabine, melphalan, methotrexate and vinorelbine. 0.9% isotonic sodium chloride solution and 5% dextrose served as infusion solutions. The containers were stored at room temperature or at 4 degrees C, protected from light, for periods of up to 168 h. Turbidity, change of colour and visible crystallization were not observed. Samples were collected at different time intervals and drug contents were determined with high-performance liquid chromatography (HPLC). Preparations of carmustine showed no adsorption phenomena when stored in LDPE or in glass at 4 degrees C. At room temperature in LDPE, a slight decrease in concentration due to adsorption was monitored. However the drug loss in PVC bags was greater. Dacarbazine and melphalan showed decreases in concentration, which were independent on the type of container material. The remaining analyzed agents showed no drug loss at all. In conclusion, investigated drugs were stable in all three container types, with the best stability in glass bottles, followed by LDPE and PVC.

  16. Macromolecular Drug Targets in Cancer Treatment and Thiosemicarbazides as Anticancer Agents.

    PubMed

    Küçükgüzel, Ş Güniz; Coşkun, Göknil P

    2016-01-01

    Cancer is known as abnormal cell division and consisting of a group of diseases on various organ tissues. Many therapies are available in cancer treatment such as chemotherapy, radiotherapy etc. Without damaging normal tissue, there is a huge need for specified anticancer drugs which have effect only on abnormal cancer cells. Therefore, advances in anticancer drug discovery in treating cancer in the recent years, directed towards to the macromolecular targets. Heterocyclic molecules, such as fluconazole, acetazolamide, etc., have a significant role in health care and pharmaceutical drug design. Thiosemicarbazides (NH2-NH-CSNH2) are the simplest hydrazine derivatives of thiocarbamic acid and are not only transition compounds, but they are also very effective organic compounds. Thiosemicarbazides possess an amide and amine protons, carbonyl and thione carbons. These structures have attracted the attention of the researchers in the development of novel compounds with anticonvulsant, antiviral, anti-inflammatory, antibacterial, antimycobacterial, antifungal, antioxidant and anticancer activities. Recently, a number of thiosemicarbazides are available commercially as anticancer drugs for novel anticancer drug discovery. Antineoplastic or anticancer drugs prevent or inhibit the maturation and proliferation of neoplasms. These observations have been guiding the researchers for the development of new thiosemicarbazides that possess anticancer activity.

  17. 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…

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

    PubMed

    Edery, E G

    2017-03-07

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

  19. 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

  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. [Drugs and retinal disorders: A case/non-case study in the French pharmacovigilance database].

    PubMed

    Bourgeois, Nicolas; Chavant, François; Lafay-Chebassier, Claire; Leveziel, Nicolas; Pérault-Pochat, Marie-Christine

    2016-09-01

    Retina is the part of the eye suffering most damage from pharmaceutical molecules. Drug-induced retinopathies have been described but data are scarce and sometimes conflicting especially concerning its potential seriousness. The aim of this study was to investigate potential associations between drugs and retinal disorders using the French Pharmacovigilance data. We used the case/non-case method in the French PharmacoVigilance Database (FPVD) to identify drugs able to induce retinopathies. Cases were reports of retinal disorders in the FPVD between January 2008 and December 2012. Non-cases were all other reports during the same period. To assess the association between retinopathy and drug intake, we calculated the odds-ratio (OR) [with their 95% confidence intervals] for all drugs associated with at least 3 cases of retinopathy. Among the 123 687 adverse drug reactions recorded during the studied period, we identified 164 cases of retinal disorders. Significant associations were found for 11 drugs. The main therapeutic classes were antirhumatismals (hydroxychloroquine, chloroquine and etanercept: 18 cases), anti-infective (ribavirine, PEG-interferon-alfa-2a and cefuroxime: 16 cases) and antineoplastic drugs (imatinib and letrozole: 8 cases. Three other drugs were also found: raloxifene (5 cases), erythropoietin beta (4 cases) and ranibizumab (3 cases). Taking into account the limits of the methodology, our study confirmed the association between retinopathy and some expected drugs such as aminoquinolines, interferons, imatinib or ranibizumab. Other drugs like erythropoietin beta, cefuroxime, letrozole and etanercept were significantly associated with retinal disorders although this was not or poorly described in the literature. Thus, further prospective studies are necessary to confirm such associations.

  2. Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma

    PubMed Central

    Terpos, Evangelos; Kanellias, Nikolaos; Christoulas, Dimitrios; Kastritis, Efstathios; Dimopoulos, Meletios A

    2013-01-01

    Multiple myeloma remains an incurable disease despite the introduction of the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib that have improved the outcome of patients with both newly diagnosed and relapsed/refractory disease. However, patients who relapse after treatment with these agents or are refractory to them represent an unmet need and highlight the necessity for the development of novel anti-myeloma agents. Pomalidomide is an IMiD, structurally related to thalidomide, with enhanced antiangiogenic, antineoplastic, and anti-inflammatory properties and exhibiting potent anti-myeloma activity in vitro and in vivo. Pomalidomide has shown remarkable activity in patients who were refractory to both bortezomib and lenalidomide in Phase II and III studies. This paper reviews the chemistry and mechanisms of action of pomalidomide as well as all the available data from clinical trials on pomalidomide use in patients with refractory/relapsed multiple myeloma. PMID:23690693

  3. [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.

  4. Drug dependence

    MedlinePlus

    ... starts using drugs to try to self-treat mental illness. Support Groups Many support groups are available in ... American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. ...

  5. Drug Facts

    MedlinePlus Videos and Cool Tools

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

  6. Drug abuse

    MedlinePlus

    ... 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Weiss RD. Drugs of abuse. In: Goldman L, ... Hospice and Palliative Medicine, Atlanta, GA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  7. Study Drugs

    MedlinePlus

    ... may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The ... some proven ways to boost concentration and beat stress: Meditation . Even a few minutes of meditation each ...

  8. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    PubMed

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  9. 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.

  10. 'One-pot' synthesis of multifunctional GSH-CdTe quantum dots for targeted drug delivery.

    PubMed

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

    2014-06-13

    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.

  11. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  12. Eco-genotoxicity of six anticancer drugs using comet assay in daphnids.

    PubMed

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

    2015-04-09

    The eco-genotoxicity of six anti-neoplastic drugs, 5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib, belonging to five classes of anatomical therapeutic classification (ATC), was studied applying the in vivo comet assay on cells from whole organisms of Daphnia magna and Ceriodaphnia dubia. For the first time, this test was performed in C. dubia. In addition, to have a wider genotoxic/mutagenic profile of the anticancer drugs selected, SOS chromotest and Salmonella mutagenicity assay were performed. The comet results showed that all drugs induced DNA damage, in both Cladocerans, with environmental concern; indeed Doxorubicin induced DNA damage in the order of tens of ng L(-1) in both crustaceans, as well as 5-flurouracil in C. dubia and cisplatin in D. magna. In the SOS Chromotest all drugs, except imatinib, were able to activate the repair system in Escherichia coli PQ37 while in the Salmonella mutagenicity assay, doxorubicin was the only drug able to cause direct and indirect frameshift and base-pair substitution mutations. Comet assay was the most sensitive tool of genotoxic exposure assessment, able to detect in vivo the adverse effects at concentration lower than those evaluated in vitro by bacterial assays.

  13. Application of electrolysis for inactivation of an antiviral drug that is one of possible selection pressure to drug-resistant influenza viruses.

    PubMed

    Kobayashi, Toyohide; Hirose, Jun; Wu, Hong; Sano, Kouichi; Katsumata, Takahiro; Tsujibo, Hiroshi; Nakano, Takashi

    2013-12-01

    The recent development of antiviral drugs has led to concern that the release of the chemicals in surface water due to expanded medical use could induce drug-resistant mutant viruses in zoonosis. Many researchers have noted that the appearance of an oseltamivir (Tamiflu(®))-resistant avian influenza mutant virus, which may spread to humans, could be induced by oseltamivir contamination of surface water. Although past studies have reported electrolysis as a possible method for degradation of antineoplastics and antibacterials in water, the validity of the method for treatment of antiviral drugs is unknown. In this study, electrolysis was used to degrade an antiviral prodrug, oseltamivir, and a stable active form, oseltamivir carboxylate, and the degradation process was monitored with HPLC-UV and the neuraminidase inhibitory assay. HPLC-UV-detectable oseltamivir and oseltamivir carboxylate were decomposed by electrolysis within 60 min, and inhibitory activity of neuraminidase decreased below the detection limit of the assay used. Cytotoxic and genotoxic activity were not detected in electrolyzed fluid. These results indicate that electrolysis is a possible treatment for inactivation of the antiviral drug oseltamivir.

  14. 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...

  15. Invariant NKT cells increase drug-induced osteosarcoma cell death

    PubMed Central

    Fallarini, S; Paoletti, T; Orsi Battaglini, N; Lombardi, G

    2012-01-01

    BACKGROUND AND PURPOSE In osteosarcoma (OS) patients, only a limited number of drugs are active and the regimens currently in use include a combination of at least two of these drugs: doxorubicin, cisplatin, methotrexate and ifosfamide. Today, 30–40% of patients still die of OS highlighting the urgent need for new treatments. Invariant NKT (iNKT) cells are a lymphocyte lineage with features of both T and NK cells, playing important roles in tumour suppression. Our aim was to test whether the cytoxicity induced by cisplatin, doxorubicin and methotrexate against OS cells can be enhanced by iNKT cell treatment. EXPERIMENTAL APPROACH iNKT cells were purified from human peripheral blood mononuclear cells by cell sorting (Vα24Vβ11+ cells) and used as effector cells against OS cells (U2-OS, HOS, MG-63). Cell death (calcein-AM method), perforin/granzyme B and Fas/FasL expressions were determined by flow cytometry. CD1d expression was analysed at both the gene and protein level. KEY RESULTS iNKT cells were cytotoxic against OS cells through a CD1d-dependent mechanism. This activity was specific for tumour cells, because human CD1d+ mesenchymal stem cells and CD1d- osteoblasts were not affected. iNKT cell treatment enhanced drug-induced OS cell death in a concentration-dependent manner and this effect was reduced in CD1d-silenced OS cells. CONCLUSION AND IMPLICATIONS iNKT cells kill malignant, but not non-malignant, cells. iNKT cell treatment enhances the cytotoxicity of anti-neoplastic drugs against OS cells in a CD1d-dependent manner. The present data encourage further studies on the use of iNKT cells in OS therapy. PMID:22817659

  16. 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.

  17. Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications

    PubMed Central

    Hartman, Olga; Zhang, Chu; Adams, Elizabeth L.; Farach-Carson, Mary C.; Petrelli, Nicholas J.; Chase, Bruce D.; Rabolt, John F.

    2009-01-01

    Invasive epithelial tumors form from cells that are released from their natural basement membrane and form 3-D structures that interact with each other and with the microenvironment of the stromal tissues around the tumor, which often contains collagen. Cancer cells, growing as monolayers on tissue culture plastic, do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as models for testing of pharmacologically active compounds, including those that are being tested as anti-neoplastics. This work seeks to create new 3-D cellular materials possessing properties similar to those in native tissues surrounding cancers, specifically electrospun micro- and nanofibrous collagen scaffolds that support tumor growth in 3-D. We hypothesize that a 3-D culture system will provide a better replica of tumor growth in a native environment, and thus better report the bioactivity of anti-neoplastic agents. In addition, we optimized conditions, and identified physical characteristics that support growth of the highly invasive, prostate cancer bone metastatic cell line C4-2B on these matrices for use in anti-cancer drug studies. The effects of matrix porosity, fiber diameter, elasticity and surface roughness on growth of cancer cells were evaluated. Data indicates that while cells attach and grow well on both nano- and microfibrous electrospun membranes, the microfibrous membrane represented a better approximation of the tumor microenvironemt. It was also observed that C4-2B non-adherent cells migrated through the depth of two electrospun membranes and formed colonies resembling tumors on day 3. An apoptosis study revealed that cells on electrospun substrates were more resistant to both anti-neoplastic agents, docetaxel (DOC) and camptothecin (CAM), compared to the cells grown on standard collagen-coated tissue culture polystyrene (TCP). Growth, survival, and apoptosis were measured, as well as the differences in the apoptotic

  18. 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 ...

  19. New drugs from old natural compounds: scarcely investigated sesquiterpenes as new possible therapeutic agents.

    PubMed

    Suta, Stefania; Maggi, Filippo; Nicoletti, Marcello; Baldan, Valeria; Dall Acqua, Stefano

    2017-04-04

    Sesquiterpene are natural products that have been extensively studied for their bioactivities, evidencing their potentiality as useful scaffolds for the development of drugs. Considering the different derivatives, the sesquiterpene lactones have been evaluated, especially on cancer cell and antineoplastic efficacy in in vivo studies. Their bioactivity is strictly related to the presence of the reactive α-methylene-γ-lactone group (αMγL). Nevertheless, several other sesquiterpene lacking of the αMγL are known and have been studied for their biological effects and potential usefulness in the development of new drugs. In this review, we focused on several sesquiterpenes that are not presenting the αMγL moiety and may have future potential as scaffold for the development of new drugs, namely the bicyclic compounds belonging to the carotane type (daucanes) that present significant effect as antiproliferative and estrogenic agents. The monocyclic humulane derivatives correlated to zerumbone, and the bicyclic compound beta-caryophyllene and its derivatives that have been considered in the field of cancer and inflammation. It is noteworthy that published studies on sesquiterpenes, reported in this review, concern on pathologies of increasing importance, like estrogen, anti-proliferative, bone loos, immunity deficiency and anti-tumour activities. Some of the natural "old" sesquiterpenes can be considered for their possible role in drug discovery and in counteracting these "new" challenges.

  20. Repositioning approved drugs for the treatment of problematic cancers using a screening approach.

    PubMed

    Varbanov, Hristo P; Kuttler, Fabien; Banfi, Damiano; Turcatti, Gerardo; Dyson, Paul J

    2017-01-01

    Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over the last four decades. Nevertheless, despite the growing number of new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it is important to ensure that existing drugs used to treat other types of cancers, and potentially other diseases, are not overlooked when searching for new chemotherapy regimens for these problematic cancer types. We describe a screening approach that identifies chemotherapeutics for the treatment of lung and pancreatic cancers, based on drugs already approved for other applications. Initially, the 1280 chemically and pharmacologically diverse compounds from the Prestwick Chemical Library® (PCL) were screened against A549 (lung cancer) and PANC-1 (pancreatic carcinoma) cells using the PrestoBlue fluorescent-based cell viability assay. More than 100 compounds from the PCL were identified as hits in one or both cell lines (80 of them, being drugs used to treat diseases other than cancer). Selected PCL hits were further evaluated in a dose-response manner. Promising candidates for repositioning emanating from this study include antiparasitics, cardiac glycosides, as well as the anticancer drugs vorinostat and topotecan.

  1. Repositioning approved drugs for the treatment of problematic cancers using a screening approach

    PubMed Central

    Kuttler, Fabien; Banfi, Damiano; Turcatti, Gerardo; Dyson, Paul J.

    2017-01-01

    Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over the last four decades. Nevertheless, despite the growing number of new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it is important to ensure that existing drugs used to treat other types of cancers, and potentially other diseases, are not overlooked when searching for new chemotherapy regimens for these problematic cancer types. We describe a screening approach that identifies chemotherapeutics for the treatment of lung and pancreatic cancers, based on drugs already approved for other applications. Initially, the 1280 chemically and pharmacologically diverse compounds from the Prestwick Chemical Library® (PCL) were screened against A549 (lung cancer) and PANC-1 (pancreatic carcinoma) cells using the PrestoBlue fluorescent-based cell viability assay. More than 100 compounds from the PCL were identified as hits in one or both cell lines (80 of them, being drugs used to treat diseases other than cancer). Selected PCL hits were further evaluated in a dose-response manner. Promising candidates for repositioning emanating from this study include antiparasitics, cardiac glycosides, as well as the anticancer drugs vorinostat and topotecan. PMID:28166232

  2. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma.

    PubMed

    Kroiss, Matthias; Quinkler, Marcus; Lutz, Werner K; Allolio, Bruno; Fassnacht, Martin

    2011-11-01

    Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, (o,p'-DDD)] is the only drug approved for the treatment for adrenocortical carcinoma (ACC) and has also been used for various forms of glucocorticoid excess. Through still largely unknown mechanisms, mitotane inhibits adrenal steroid synthesis and adrenocortical cell proliferation. Mitotane increases hepatic metabolism of cortisol, and an increased replacement dose of glucocorticoids is standard of care during mitotane treatment. Recently, sunitinib, a multityrosine kinase inhibitor (TKI), has been found to be rapidly metabolized by CYP3A4 during mitotane treatment, indicating clinically relevant drug interactions with mitotane. We here summarize the current evidence concerning mitotane-induced changes in hepatic monooxygenase expression, list drugs potentially affected by mitotane-related CYP3A4 induction and suggest alternatives. For example, using standard doses of macrolide antibiotics is unlikely to reach sufficient plasma levels, making fluoroquinolones in many cases a superior choice. Similarly, statins such as simvastatin are metabolized by CYP3A4, whereas others like pravastatin are not. Importantly, in the past, several clinical trials using cytotoxic drugs but also targeted therapies in ACC yielded disappointing results. This lack of antineoplastic activity may be explained in part by insufficient drug exposure owing to enhanced drug metabolism induced by mitotane. Thus, induction of CYP3A4 by mitotane needs to be considered in the design of future clinical trials in ACC.

  3. Transporter-mediated drug-drug interactions.

    PubMed

    Müller, Fabian; Fromm, Martin F

    2011-07-01

    Drug-drug interactions are a serious clinical issue. An important mechanism underlying drug-drug interactions is induction or inhibition of drug transporters that mediate the cellular uptake and efflux of xenobiotics. Especially drug transporters of the small intestine, liver and kidney are major determinants of the pharmacokinetic profile of drugs. Transporter-mediated drug-drug interactions in these three organs can considerably influence the pharmacokinetics and clinical effects of drugs. In this article, we focus on probe drugs lacking significant metabolism to highlight mechanisms of interactions of selected intestinal, hepatic and renal drug transporters (e.g., organic anion transporting polypeptide [OATP] 1A2, OATP2B1, OATP1B1, OATP1B3, P-gp, organic anion transporter [OAT] 1, OAT3, breast cancer resistance protein [BCRP], organic cation transporter [OCT] 2 and multidrug and toxin extrusion protein [MATE] 1). Genotype-dependent drug-drug interactions are also discussed.

  4. Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs?

    PubMed

    Besse, Jean-Philippe; Latour, Jean-François; Garric, Jeanne

    2012-02-01

    This study considers the implications and research needs arising from anticancer (also referred to as antineoplastic) drugs being released into the aquatic environment, for the entire therapeutic classes used: cytotoxic, cytostatic and endocrine therapy drugs. A categorization approach, based on French consumption amounts, allowed to highlight parent molecules and several metabolites on which further occurrence and ecotoxicological studies should be conducted. Investigations of consumption trends at a national and a local scale show an increase in the use of anticancer drugs between 2004 and 2008, thus leading to increased levels released in the environment. It therefore appears necessary to continue surveying their presence in surface waters and in wastewater treatment plant (WWTP) effluents. Furthermore, due to the rise of anticancer home treatments, most of the prescribed molecules are now available in town pharmacies. Consequently, hospital effluents are no longer the main expected entry route of anticancer drugs into the aquatic environment. Concerning ecotoxicological risks, current knowledge remains insufficient to support a definitive conclusion. Risk posed by cytotoxic molecules is still not well documented and it is not possible to conclude on their long-term effects on non-target organisms. To date, ecotoxicological effects have been assessed using standardized or in vitro assays. Such tests however may not be suitable for anticancer drugs, and further work should focus on full-life cycle or even multigenerational tests. Environmental significance (i.e. occurrence and effects) of cytostatics (protein kinases inhibitors and monoclonal antibodies), if any, is not documented. Protein kinases inhibitors, in particular, deserve further investigation due to their universal mode of action. Finally, concerning endocrine therapy drugs, molecules such as antiestrogen Tamoxifen and its active metabolites, could be of concern. Overall, to accurately assess the

  5. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole

    PubMed Central

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Aims Delineate the feasibility of simultaneous, dual selective “targeted” chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively “targeted” for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma. Methodology Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it’s potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu]. Results Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with

  6. The anti-histaminic cyproheptadine synergizes the antineoplastic activity of bortezomib in mantle cell lymphoma through its effects as a histone deacetylase inhibitor.

    PubMed

    Paoluzzi, Luca; Scotto, Luigi; Marchi, Enrica; Seshan, Venkatraman E; O'Connor, Owen A

    2009-09-01

    Cyproheptadine, an inhibitor of the H1 histamine receptors, has recently shown activity in models of leukaemia and myeloma, presumably through inhibition of cyclin-D expression. Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin-D1. We investigated the effect of cyproheptadine alone and in combination with the proteasome inhibitor bortezomib in models of MCL. The combination of these drugs was mathematically synergistic, producing significant reductions in the mitochondrial membrane potential leading to apoptosis. In a severe combined immunodeficient beige mouse model, cyproheptadine plus bortezomib demonstrated a statistically significant advantage compared to either agent alone.

  7. 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.

  8. Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy

    PubMed Central

    Sooriyaarachchi, Melani; George, Graham N.; Pickering, Ingrid J.; Narendran, Aru

    2016-01-01

    Numerous in vivo studies have shown that the severe toxic side-effects of intravenously administered cisplatin can be significantly reduced by the co-administration of sulfur-containing ‘chemoprotective agents’. Using a metallomics approach, a likely biochemical basis for these potentially useful observations was only recently uncovered and appears to involve the reaction of chemoprotective agents with cisplatin-derived Pt-species in human plasma to form novel platinum–sulfur complexes (PSC's). We here reveal aspects of the structure of two PSC's and establish the identification of an optimal chemoprotective agent to ameliorate the toxic side-effects of cisplatin, while leaving its antineoplastic activity largely intact, as a feasible research strategy to transform cisplatin into a safer and more effective anticancer drug. PMID:27722429

  9. Anticancer drug detection using a highly sensitive molecularly imprinted electrochemical sensor based on an electropolymerized microporous metal organic framework.

    PubMed

    Florea, Anca; Guo, ZhenZhong; Cristea, Cecilia; Bessueille, François; Vocanson, Francis; Goutaland, François; Dzyadevych, Sergiy; Săndulescu, Robert; Jaffrezic-Renault, Nicole

    2015-06-01

    A simple and highly sensitive approach for the detection of the anti-neoplastic drug gemcitabine is presented, based on a one-step electropolymerized molecularly imprinted microporous-metal-organic-framework. The sensitive layer was prepared by electropolymerization of the aniline moieties of p-aminothiophenol- gold nanoparticles on the surface of gold electrodes tethered with p-aminothiophenol, in the presence of gemcitabine as a template molecule. Experimental parameters that control the performance of the sensor were investigated and optimized. Under optimal conditions a calibration curve was obtained in the linear range from 3.8 fM to 38 nM with a limit of detection of 3 fM. The obtained imprinted sensor has the advantages of easy manufacture, high sensitivity and selectivity and good reproducibility. Furthermore the feasibility of the proposed technique has been investigated on spiked serum samples and infusion solution containing gemcitabine.

  10. 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

  11. 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.

  12. An efficient, convenient synthesis of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides as anticipated antineoplastic agents.

    PubMed

    Abdel-Hafez, Atef Abdel-Monem

    2002-07-01

    A series of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides (18-27, 30, 32) were synthesized in an ongoing effort to develop new antineoplastic agents. The synthon 2-(2-aminobenzoylamino)-benzoic acid (7), for preparation of the target compounds, was prepared via the reaction of isatoic anhydride 5 and anthranilic acid 6. Nine compounds (18-20, 24-27, 30, 32) were subjected to National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay. Among the compounds tested, 6-benzyl-13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione (26, NSC 721327), bearing the benzyl group at position 6, showed cytotoxic activity and subpanel selectivity against leukemia (CCRF-CEM), colon (HCC-2998), CNS (SNB-75) and melanoma (UACC-257) panels at log(10) GI(50) (M), compound concentration that inhibits 50% of cell growth, ranging from -4.08 to -4.59.

  13. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... by Month Approvals, tentative approvals, and supplements Original New Drug Approvals (NDAs and BLAs) by Month All applications ... FDA. Does not include tentative approvals. Original Abbreviated New Drug Approvals (ANDAs) by Month Generic Drug Approvals. Does ...

  14. ‘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.

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

    PubMed Central

    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

    2015-01-01

    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

  16. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  17. Antinociceptive effect of three common analgesic drugs on peripheral neuropathy induced by paclitaxel in rats.

    PubMed

    Pascual, David; Goicoechea, Carlos; Burgos, Elisa; Martín, María Isabel

    2010-05-01

    Nowadays, there are no validated drugs to control the neuropathic pain induced by paclitaxel, one of the most effective antineoplastic drugs. The aim was to study the involvement of opioid and NMDA receptor on established paclitaxel-induced pain, testing three common analgesics drugs morphine, ketamine and methadone. Animals received four intraperitoneal (i.p.) injections on alternate days of paclitaxel (1mg/kg). Three weeks later, animals showed a mechanical and heat allodynia/hyperalgesia. Morphine (1, 2.5, 5 and 10mg/kg) abolished the reduction in the mechanical and thermal withdrawal thresholds in a dose dependent manner. This effect was blocked by naloxone. Only highest dose of ketamine (50mg/kg) was able to increase the mechanical and thermal threshold and returned to basal values. Subanalgesic doses of morphine (1mg/kg) and ketamine (12.5mg/kg) produced an additive effect on heat hyperalgesia reaching an antinociceptive effect. This combination did not induce any change on tactile allodynia. Methadone (2.5 and 5mg/kg) produced an analgesic effect that was completely antagonized by naloxone in both tests. Our results confirm that: the activation of opioids receptor produced analgesia; the blockade of NMDA receptors produce antinociception but at high doses with motor impairments and low doses of ketamine enhancing the effect of opioids.

  18. Detection of low-quantity anticancer drugs by surface-enhanced Raman scattering.

    PubMed

    Litti, Lucio; Amendola, Vincenzo; Toffoli, Giuseppe; Meneghetti, Moreno

    2016-03-01

    Ultrasensitive detection of low-quantity drugs is important for personalized therapeutic approaches in several diseases and, in particular, for cancer treatment. In this field, surface-enhanced Raman scattering (SERS) can be very useful for its ability to precisely identify analytes from their unique vibrational spectra, with very high sensitivity. Here, we report a study about SERS detection of sunitinib, paclitaxel and irinotecan, i.e. three commonly used antineoplastic drugs, and of SN-38, i.e. the metabolite of irinotecan, dissolved in methanol solutions. By using commercial Klarite substrates, we found that sunitinib, irinotecan and SN-38 have detection limits of 20-70 ng, which is below the threshold for applications in cancer therapy. Conversely, the SERS signal was not appreciable with paclitaxel, and this is explained by the absence of optical resonances in the visible range. Overall, our results show that ultrasensitive SERS detection of sunitinib, irinotecan and SN-38 is feasible, encouraging further development of this technology also for other drugs with similar molecular structure especially for those analytes with absorption bands in the visible range.

  19. 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.

  20. 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.

  1. 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.

  2. Club Drug Use

    MedlinePlus

    ... different from other illicit drugs?What are the dangers of taking club drugs?What can I do ... Drug Use | Gamma-Hydroxybutyrate (GHB)Learn about the dangers of taking gamma-hydroxybutyrate (GHB), an illegal drug ...

  3. Effects of Drug Use

    MedlinePlus

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... and the brain , sometimes forever. Learn more about: how drug use and mental health problems often happen together the link between drug use ...

  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. 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…

  6. DrugCentral: online drug compendium

    PubMed Central

    Ursu, Oleg; Holmes, Jayme; Knockel, Jeffrey; Bologa, Cristian G.; Yang, Jeremy J.; Mathias, Stephen L.; Nelson, Stuart J.; Oprea, Tudor I.

    2017-01-01

    DrugCentral (http://drugcentral.org) is an open-access online drug compendium. DrugCentral integrates structure, bioactivity, regulatory, pharmacologic actions and indications for active pharmaceutical ingredients approved by FDA and other regulatory agencies. Monitoring of regulatory agencies for new drugs approvals ensures the resource is up-to-date. DrugCentral integrates content for active ingredients with pharmaceutical formulations, indexing drugs and drug label annotations, complementing similar resources available online. Its complementarity with other online resources is facilitated by cross referencing to external resources. At the molecular level, DrugCentral bridges drug-target interactions with pharmacological action and indications. The integration with FDA drug labels enables text mining applications for drug adverse events and clinical trial information. Chemical structure overlap between DrugCentral and five online drug resources, and the overlap between DrugCentral FDA-approved drugs and their presence in four different chemical collections, are discussed. DrugCentral can be accessed via the web application or downloaded in relational database format. PMID:27789690

  7. Drug Preferences of Multiple Drug Abusers.

    ERIC Educational Resources Information Center

    Harford, Robert J.

    1978-01-01

    Examined drug preferences of a group of active multiple drug abusers referred for treatment. Nearly half the respondents preferred drugs other than type they most frequently used. Preferences were related to method of administration. Results suggest preference is one among several determinants of drug use. (Author/BEF)

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

    PubMed

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

    2014-04-01

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

  9. Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies.

    PubMed

    Ensslin, A S; Huber, R; Pethran, A; Römmelt, H; Schierl, R; Kulka, U; Fruhmann, G

    1997-01-01

    For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 micrograms/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies. In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 micrograms cyclophosphamide/l urine was measured in two samples, respectively. An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring. In an ongoing project in our department the

  10. 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.

  11. Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors.

    PubMed

    Wang, Chen; Zimmermann, Michael T; Prodduturi, Naresh; Chute, Christopher G; Jiang, Guoqian

    2014-01-01

    Adverse drug events (ADEs) are a critical factor for selecting cancer therapy options. The underlying molecular mechanisms of ADEs associated with cancer therapy drugs may overlap with their antineoplastic mechanisms; an aspect of toxicity. In the present study, we develop a novel knowledge-driven approach that provides an ADE-based stratification (ADEStrata) of tumor mutations. We demonstrate clinical utility of the ADEStrata approach through performing a case study of breast invasive carcinoma (BRCA) patients receiving aromatase inhibitors (AI) from The Cancer Genome Atlas (TCGA) (n=212), focusing on the musculoskeletal adverse events (MS-AEs). We prioritized somatic variants in a manner that is guided by MS-AEs codified as 6 Human Phenotype Ontology (HPO) terms. Pathway enrichment and hierarchical clustering of prioritized variants reveals clusters associated with overall survival. We demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In conclusion, the ADEStrata approach could produce clinically and biologically meaningful tumor subtypes that are potentially predictive of the drug response to the cancer therapy drugs.

  12. Gefitinib-associated vitiligo: report in a man with parotid squamous cell carcinoma and review of drug-induced hypopigmentation.

    PubMed

    Jalalat, Sheila Z; Cohen, Philip R

    2013-10-16

    Gefitinib is a tyrosine kinase inhibitor that targets and inhibits epidermal growth factor receptors. It was initially used to treat non-small cell lung cancer but has increasingly been used for other solid tumors such as those in the breast, colorectal sites, and head and neck, as in our patient. Vitiligo is an autoimmune disorder that results in the destruction of melanocytes and subsequent skin depigmentation and hypopigmentation. Previously described mucocutanous side effects of gefitinib at 250-500 mg/day include alopecia, asteatotic dermatitis, desquamation, hyperpigmentation, papulopustular acneiform eruption, pruritus, seborrheic dermatitis, and skin fragility. A 54-year-old man with metastatic squamous cell carcinoma to the parotid gland developed vitiligo within 1 month of starting gefitinib therapy. We retrospectively reviewed the medical literature using PubMed, searching: (1) gefitinib side effects, (2) drugs and (3) vitiligo. The patient with gefitinib-induced vitiligo continued to receive treatment with the drug during which time areas of skin hypopigmentation persisted and progressed. Etiology of drug-induced vitiligo includes alopecia areata therapies, anticonvulsants, antimalarials, antineoplastics, anti-Parkinson medications, and other miscellaneous drugs. No other individuals have been described with gefitinib-induced vitiligo. Albeit rare, gefitinib may be associated with the development of vitiligo.

  13. Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson’s disease and depression

    PubMed Central

    Lawal, Hakeem O.; Terrell, Ashley; Lam, Hoa A.; Djapri, Christine; Jang, Jennifer; Hadi, Richard; Roberts, Logan; Shahi, Varun; Chou, Man-Ting; Biedermann, Traci; Huang, Brian; Lawless, George M.; Maidment, Nigel T.; Krantz, David E.

    2012-01-01

    Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson’s disease as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or “enhancer/suppressor” screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background, and performed a suppressor screen. We fed dVMAT mutant larvae ~1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for Parkinson’s disease, depression and ADHD and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems. PMID:23229049

  14. Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran.

    PubMed

    Yu, Li; Cai, Lin; Hu, Hao; Zhang, Yi

    2014-05-01

    Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP-OXD-EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP-OXD-EPI was confirmed by analysis of FTIR and (1)H-NMR spectra. To study the bone-seeking potential of AEDP-OXD-EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP-OXD-EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP-OXD-EPI is an ideal bone-targeting anti-tumor drug.

  15. Antineoplastic effects of α-santalol on estrogen receptor-positive and estrogen receptor-negative breast cancer cells through cell cycle arrest at G2/M phase and induction of apoptosis.

    PubMed

    Santha, Sreevidya; Bommareddy, Ajay; Rule, Brittny; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Dwivedi, Chandradhar

    2013-01-01

    Anticancer efficacy and the mechanism of action of α-santalol, a terpenoid isolated from sandalwood oil, were investigated in human breast cancer cells by using p53 wild-type MCF-7 cells as a model for estrogen receptor (ER)-positive and p53 mutated MDA-MB-231 cells as a model for ER-negative breast cancer. α-Santalol inhibited cell viability and proliferation in a concentration and time-dependent manner in both cells regardless of their ER and/or p53 status. However, α-santalol produced relatively less toxic effect on normal breast epithelial cell line, MCF-10A. It induced G2/M cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cells. Cell cycle arrest induced by α-santalol was associated with changes in the protein levels of BRCA1, Chk1, G2/M regulatory cyclins, Cyclin dependent kinases (CDKs), Cell division cycle 25B (Cdc25B), Cdc25C and Ser-216 phosphorylation of Cdc25C. An up-regulated expression of CDK inhibitor p21 along with suppressed expression of mutated p53 was observed in MDA-MB-231 cells treated with α-santalol. On the contrary, α-santalol did not increase the expression of wild-type p53 and p21 in MCF-7 cells. In addition, α-santalol induced extrinsic and intrinsic pathways of apoptosis in both cells with activation of caspase-8 and caspase-9. It led to the activation of the executioner caspase-6 and caspase-7 in α-santalol-treated MCF-7 cells and caspase-3 and caspase-6 in MDA-MB-231 cells along with strong cleavage of poly(ADP-ribose) polymerase (PARP) in both cells. Taken together, this study for the first time identified strong anti-neoplastic effects of α-santalol against both ER-positive and ER-negative breast cancer cells.

  16. 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)…

  17. 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.

  18. Personality, drug preference, drug use, and drug availability.

    PubMed

    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) theories. Drug preference was measured by the method of paired-comparison and personality was measured with the Zuckerman-Kuhlman Personality Questionnaire-50 CC. Contrary to expectations, high compared with low scorers on Sociability and Impulsive-Sensation Seeking preferred depressants. Surprisingly, low compared with high scorers on neuroticism did not differ in preference for alcohol. As in the previous study, drug preference, use, and availability were highly correlated, although ease of availability was slightly more predictive of drug use than drug preference. Clinical and theoretical implications are discussed.

  19. 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…

  20. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    PubMed Central

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention. PMID:23875171

  1. Multifunctional Enveloped Mesoporous Silica Nanoparticles for Subcellular Co-delivery of Drug and Therapeutic Peptide

    PubMed Central

    Luo, Guo-Feng; Chen, Wei-Hai; Liu, Yun; Lei, Qi; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-01-01

    A multifunctional enveloped nanodevice based on mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Mesoporous silica MCM-41 nanoparticles were used as the core for loading antineoplastic drug topotecan (TPT). The surface of nanoparticles was decorated with mitochondria-targeted therapeutic agent (Tpep) containing triphenylphosphonium (TPP) and antibiotic peptide (KLAKLAK)2 via disulfide linkage, followed by coating with a charge reversal polyanion poly(ethylene glycol)-blocked-2,3-dimethylmaleic anhydride-modified poly(L-lysine) (PEG-PLL(DMA)) via electrostatic interaction. It was found that the outer shielding layer could be removed at acidic tumor microenvironment due to the degradation of DMA blocks and the cellular uptake was significantly enhanced by the formation of cationic nanoparticles. After endocytosis, due to the cleavage of disulfide bonds in the presence of intracellular glutathione (GSH), pharmacological agents (Tpep and TPT) could be released from the nanoparticles and subsequently induce specific damage of tumor cell mitochondria and nucleus respectively with remarkable synergistic antitumor effect. PMID:25317538

  2. 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

  3. Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system.

    PubMed

    Feng, Linglin; Zhang, Lei; Liu, Min; Yan, Zhiqiang; Wang, Chenyu; Gu, Bing; Liu, Yu; Wei, Gang; Zhong, Gaoren; Lu, Weiyue

    2010-04-01

    Our aim was to develop a novel liposomal drug delivery system containing dextrans to reduce undesirable retention of antineoplastic agents and thus alleviate local tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the strongest inhibiting effect on liposome uptake by macrophages among tested dextrans. The distribution of radiolabeled liposomes mixed with dextrans in injection site and draining lymph node was investigated in rats after subcutaneous injection. DEAE-Dx substantially reduced the undesired local retention and promoted the draining of liposome into lymphatics, which was further confirmed by confocal microscopy images revealing the substantial prevention of rhodamine B-labelled liposome sequestration by macrophages in normal lymph node in rats. Pharmacokinetic data indicated the accelerated drainage of liposome through lymphatics back to systemic circulation by mixing with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local tissue damage caused by liposomal doxorubicin. In conclusion, dextrans, particularly DEAE-Dx, could efficiently enhanced liposomes drainage into lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted liposomal drug delivery system.

  4. 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.

  5. 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.

  6. Antimicrobial (Drug) Resistance Prevention

    MedlinePlus

    ... Visitor Information Contact Us Research > NIAID's Role in Research > Antimicrobial (Drug) Resistance > Understanding share with facebook share with twitter ... Prevention, Antimicrobial (Drug) Resistance Antimicrobial (Drug) Resistance Antimicrobial ... To prevent antimicrobial resistance, you and your healthcare ...

  7. Drug Plan Coverage Rules

    MedlinePlus

    ... Medication Therapy Management programs Drug plan coverage rules , current page Using your drug plan for the first time Filling a prescription without your new plan card Costs for Medicare drug coverage Joining a health or ...

  8. Drugs Approved for Melanoma

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  9. 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.

  10. 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 ...

  11. National Drug IQ Challenge

    MedlinePlus

    ... National Drug IQ Challenge 2016 National Drug & Alcohol IQ Challenge Print Get Started! Correct/Total Questions: Score: ... accessible version of the 2016 National Drug & Alcohol IQ Challenge , [PDF, 637KB]. Download an accessible version of ...

  12. Prescription Drug Abuse

    MedlinePlus

    ... Whether they're using street drugs or medications, drug abusers often have trouble at school, at home, with ... a short period of time may make a drug abuser aggressive or paranoid. Although stimulant abuse might not ...

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

    PubMed

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

    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

  14. 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

  15. Text mining for drug-drug interaction.

    PubMed

    Wu, Heng-Yi; Chiang, Chien-Wei; Li, Lang

    2014-01-01

    In order to understand the mechanisms of drug-drug interaction (DDI), the study of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) data are significant. In recent years, drug PK parameters, drug interaction parameters, and PG data have been unevenly collected in different databases and published extensively in literature. Also the lack of an appropriate PK ontology and a well-annotated PK corpus, which provide the background knowledge and the criteria of determining DDI, respectively, lead to the difficulty of developing DDI text mining tools for PK data collection from the literature and data integration from multiple databases.To conquer the issues, we constructed a comprehensive pharmacokinetics ontology. It includes all aspects of in vitro pharmacokinetics experiments, in vivo pharmacokinetics studies, as well as drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three-level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK corpus was demonstrated by a drug interaction extraction text mining analysis.The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions.

  16. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  17. 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

  18. Quantum-dot-conjugated graphene as a probe for simultaneous cancer-targeted fluorescent imaging, tracking, and monitoring drug delivery.

    PubMed

    Chen, Mei-Ling; He, Ye-Ju; Chen, Xu-Wei; Wang, Jian-Hua

    2013-03-20

    We report a novel quantum-dot-conjugated graphene, i.e., hybrid SiO2-coated quantum dots (HQDs)-conjugated graphene, for targeted cancer fluorescent imaging, tracking, and monitoring drug delivery, as well as cancer therapy. The hybrid SiO2 shells on the surface of QDs not only mitigate its toxicity, but also protect its fluorescence from being quenched by graphene. By functionalizing the surface of HQDs-conjugated graphene (graphene-HQDs) with transferrin (Trf), we developed a targeted imaging system capable of differential uptake and imaging of cancer cells that express the Trf receptor. The widely used fluorescent antineoplastic anthracycline drug, doxorubicin (DOX), is adsorbed on the surface of graphene and results in a large loading capacity of 1.4 mg mg(-1). It is advantageous that the new delivery system exhibits different fluorescence color in between graphene-HQDs and DOX in the aqueous core upon excitation at a same wavelength for the purpose of tracking and monitoring drug delivery. This simple multifunctional nanoparticle system can deliver DOX to the targeted cancer cells and enable us to localize the graphene-HQDs and monitor intracellular DOX release. The specificity and safety of the nanoparticle conjugate for cancer imaging, monitoring, and therapy has been demonstrated in vitro.

  19. 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.

  20. [Improvement of quality of practices for the preparation of cytotoxic drugs: results of a "before-after" study].

    PubMed

    Gilles, L; Favier, B; Catillon, F; Dussart, C; Peyron, F; Simoens, X; Latour, J-F; Farsi, F; Biron, P

    2009-09-01

    Despite the publication of guidelines for handling antineoplastic agents, measurable amounts of these drugs are still found at various hospital sites. In this context, the French cancer network ONCORA supported the present study to assess the impact of environmental contamination controls on the quality of practices during the preparation of cytotoxic drugs. The first part of the study was conducted at five voluntary hospitals. A total of 65 wipe samples of objects and surfaces were taken in the drug preparation rooms and analyzed for the presence of 5-fluorouracil (5-FU). Measurable amounts of 5-FU were detected in 21 samples (32%). Many surfaces within Biological Safety Cabinets and isolators were found contaminated (36%). The worse results were obtained on gloves and on the outside of infusion bags. The same method was applied during the second part of the study, conducted six months after the end of the first audit. Global contamination was reduced to 17%. This study shows that appropriate handling helps decrease the number of samples contaminated, making it possible to recommend these controls for evaluating and improving the quality of practices. Since 2007, the network's laboratory has extended its activities to all French hospitals interested in this quality assurance programme.

  1. Drugs and pharmaceuticals: management of intoxication and antidotes.

    PubMed

    Smith, Silas W

    2010-01-01

    The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life support--airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant-induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, L-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of

  2. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  3. 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…

  4. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan…

  5. 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 ...

  6. New drug update: 2010.

    PubMed

    Hussar, Daniel A

    2010-10-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  7. 2016 New Drug Update.

    PubMed

    Hussar, Daniel A

    2016-04-01

    Six new drugs marketed within the last year, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. The drugs include a hypnotic, an anticoagulant, two drugs for heart failure, and two drugs to reduce low-density lipoprotein cholesterol.

  8. New drug update: 2011.

    PubMed

    Hussar, Daniel A

    2012-04-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  9. 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

  10. Drug hypersensitivity syndrome.

    PubMed

    Bonnetblanc, J M

    1993-01-01

    Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program.

  11. New drug update: 2012.

    PubMed

    Hussar, Daniel A

    2013-04-01

    Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  12. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    PubMed

    Hansen, J M; Christensen, L K

    1977-01-01

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

  13. Drugs and drug resistance in African trypanosomiasis.

    PubMed

    Delespaux, Vincent; de Koning, Harry P

    2007-01-01

    Despite the many decades of use of most of the current trypanocides, we know little of their mode of action. This may in part be because most of these will act on multiple targets once inside the cell, and they derive their selective action on the parasite from selective accumulation by the pathogen. Loss of this capacity for drug uptake by the trypanosome would thus be a major cause for drug resistance. We here discuss the use of current drugs against human and veterinary African trypanosomiasis, the prevalence, causes and mechanisms of drug resistance and new developments in trypanosomiasis therapy such as the introduction of nifurtimox and DB289.

  14. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  15. 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.

  16. Antineoplastic effects of Bordetella pertussis adenylate cyclase.

    PubMed

    Slungaard, A; Confer, D L; Jacob, H S; Eaton, J W

    1983-01-01

    Urea extracts of B. pertussis, but not B. bronchiseptica, cause large and sustained intracellular cAMP elevation in several neoplastic cell lines. These cAMP elevations are associated with growth inhibition (HL-60, Friend erythroleukemia) and a phenotypic change/differentiation (HL-60, L1210). B. pertussis extract injections prolong survival of L1210 tumor-bearing mice. Pretreatment of L1210 cells with B. pertussis extract both delays mortality and induces growth of solid tumors instead of ascites in subsequently inoculated mice. We conclude that B. pertussis adenylate cyclase is capable of invading a variety of neoplastic cells to catalyze the intracellular formation of large amounts of cAMP. These cAMP elevations are durable and promote growth arrest, differentiation, or phenotypic alterations reflected in altered biologic behavior. B. pertussis adenylate cyclase should prove to be a useful tool for manipulating cAMP levels in neoplastic cells to elucidate the role of cAMP in malignant transformation.

  17. Mechanism of Antineoplastic Action of Bisperoxovanadium Compound

    DTIC Science & Technology

    2005-05-01

    bisperoxovanadium ( bpVs ) compounds and into the basic biology and regulation of Cdc25A phosphatase. The bpVs cause phase-specific cell cycle arrest (G1/S...that: p53 is not induced by bpV (Me2Phen); p53 and p21 status do not affect IC50; depletion of glutathione or supplementation with antioxidants does...the scale of specific subnuclear and mitotic structures. 15. SUBJECT TERMS Cdc25A, bisperoxovanadium compounds, bpVs 16. SECURITY CLASSIFICATION OF

  18. Food-drug interactions.

    PubMed

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

    2011-03-01

    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.

  19. Understanding Drug Use and Addiction

    MedlinePlus

    ... Publications » DrugFacts » Understanding Drug Use and Addiction Understanding Drug Use and Addiction Email Facebook Twitter Revised August ... drug addiction and lead productive lives. What Is drug addiction? Addiction is a chronic disease characterized by ...

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

    PubMed

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

    2017-04-14

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

  1. [Bullous drug reactions].

    PubMed

    Hertl-Yazdi, M S; Hertl, M

    2005-01-01

    Bullous drug exanthems are clinically characteristic, usually severe cutaneous and mucosal drug hypersensitivity reactions. Commonly, they appear 5-14 days after onset of drug treatment. Therapy of choice is to avoid the culprit drug and systemic administration of glucocorticoids. A key element in the immune pathogenesis of bullous drug exanthems is presumably the activation of cytotoxic CD8(+) T lymphocytes which recognize drug metabolites as nominal antigens. These compounds form spontaneously (e.g. penicillins) or are metabolized by cytochrome P450-dependent enzymes (sulfonamides). The diagnosis of bullous drug exanthems is primarily based on skin tests and in vitro-techniques. Among the skin tests, prick as well as patch tests are important. Patch tests can be also applied at the former skin lesion in fixed drug eruption. In vitro techniques include analysis of drug-specific IgE (only available for anti-penicillin, anti-sulfamethoxazole) and cellular tests with the patients' lymphocytes (lymphocyte transformation test-LTT).

  2. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions."

  3. Drugs in breast milk.

    PubMed

    1974-03-15

    Data on the pharmacology of drugs in breast milk are incomplete. The concentration in milk of drugs present in maternal blood depends on the lipid solubility of the drug and its degree of ionization. The immature renal and hepatic functions in the nursing infant can delay excretion of drugs. There has been no documented harm to nursing infants due to maternal use of oral contraceptives although long-term studies are unavailalbe. Breast feeding is contraindicated if the mother uses therapeutic doses of radioactive iodine, is a severe chronic alcoholic, or takes corticosteroids, phenobarbitone, and anticancer drugs. During lactation, drugs should be avoided as much as possible.

  4. Drug Monographs: Cabozantanib and Omacetaxine

    PubMed Central

    Solimando, Dominic A.; Ho, Kristin V.; Waddell, J. Aubrey

    2013-01-01

    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@aol.com; 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:24421492

  5. Drug monographs: cabozantanib and omacetaxine.

    PubMed

    Solimando, Dominic A; Ho, Kristin V; Waddell, J Aubrey

    2013-05-01

    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@aol.com; 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.

  6. Drug Monographs: Daratumumab and Osimertinib.

    PubMed

    Solimando, Dominic A; Waddell, J Aubrey

    2016-04-01

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

  7. Drug monographs: afatinib and obinutuzumab.

    PubMed

    Mancheril, Benjamin G; Aubrey Waddell, J; Solimando, Dominic A

    2014-03-01

    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 Boulevard #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.

  8. The drug cocktail network

    PubMed Central

    2012-01-01

    Background Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations. Results In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (Drug Combination Predictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach. Conclusions The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations. PMID:23046711

  9. Physiologically-based Pharmacokinetic Modeling of Target-Mediated Drug Disposition of Bortezomib in Mice

    PubMed Central

    Zhang, Li; Mager, Donald E.

    2015-01-01

    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 hours, 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/m2) 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

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

    PubMed Central

    Fernandes, Natália Martinez; Pelissari, Isadora Gonçalves; Cogo, Licia Assunção; Santos Filha, Valdete Alves Valentins dos

    2016-01-01

    Introduction The manipulation of antineoplastic drugs presents high risk for accidents and occupational diseases. Objective To evaluate the auditory and vestibular systems of workers who are exposed to chemotherapeutic treatment in the University Hospital of Universidade Federal de Santa Maria, Brazil, and to identify the use of individual protection equipment, related to the obtained results. Methods This study is a cross-sectional study using a quantitative method. We evaluate 33 male and female workers, ranging from 21–60 years old, of the nursing and pharmacy sectors. The workers underwent conventional Audiologic Assessment; Transient Evoked Otoacoustic Emissions; and Computerized Vectoelectronystagmography. Results The majority of the sample was female (90.9%). Individual protection equipment was used by 90.9% of the workers. Complaints of dizziness were reported by 56.25% of nursing workers and 52.94% of pharmacy workers. Audiological and vestibular assessment results were within normal limits, 96.97% and 74.20%, respectively. However, audiometric configuration of notch type was identified in 75.75% of all workers. Audiometric notches (76%) and altered caloric test (100%) were often associated with decreased use of coal masks. Conclusion Among the workers evaluated, the vestibulocochlear system was within the normal limits. The presence of notch configuration indicates the need to use individual protection equipment. PMID:27746836

  11. 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.

  12. Vinca alkaloid drugs promote stress-induced translational repression and stress granule formation

    PubMed Central

    Szaflarski, Witold; Fay, Marta M.; Kedersha, Nancy; Zabel, Maciej; Anderson, Paul; Ivanov, Pavel

    2016-01-01

    Resistance to chemotherapy drugs is a serious therapeutic problem and its underlying molecular mechanisms are complex. Stress granules (SGs), cytoplasmic ribonucleoprotein complexes assembled in cells exposed to stress, are implicated in various aspects of cancer cell metabolism and survival. SGs promote the survival of stressed cells by reprogramming gene expression and inhibiting pro-apoptotic signaling cascades. We show that the vinca alkaloid (VA) class of anti-neoplastic agents potently activates a SG-mediated stress response program. VAs inhibit translation initiation by simultaneous activation of eIF4E-BP1 and phosphorylation of eIF2α, causing polysome disassembly and SG assembly. VA-induced SGs contain canonical SG components but lack specific signaling molecules. Blocking VA-induced SG assembly by inactivating eIF4EBP1 or inhibiting eIF2α phosphorylation decreases cancer cell viability and promotes apoptosis. Our data describe previously unappreciated effects of VAs on cellular RNA metabolism and illuminate the roles of SGs in cancer cell survival. PMID:27083003

  13. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis.

    PubMed

    Singh Kanwar, S; Vaish, V; Nath Sanyal, S

    2011-01-01

    The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action.

  14. In vivo imaging of cell proliferation for a dynamic, whole body, analysis of undesired drug effects.

    PubMed

    Rizzi, Nicoletta; Manni, Isabella; Vantaggiato, Cristina; Delledonne, Giacomo Andrea; Gentileschi, Maria Pia; Maggi, Adriana; Piaggio, Giulia; Ciana, Paolo

    2015-06-01

    Noninvasive in vivo imaging offers a novel approach to preclinical studies opening the possibility of investigating biological events in the spatiotemporal dimension (eg, in any district of the body in time). Toxicological analysis may benefit from this novel approach through precise identification of the time and the target organs of toxicity manifestations, and assessment of the reversibility of toxic insults. The current limitation for routine application of this technology is the lack of appropriate surrogate markers for imaging toxicological events. Here, we demonstrate that in vivo imaging of a proliferation marker is capable of measuring the reduction of cell proliferation due to genotoxic/apoptotic agents, γ rays or antineoplastic drugs, or the increased proliferation associated with the inflammatory and regenerative reactions occurring after a toxic insult. A number of tools are currently available for imaging proliferation in preclinical and clinical settings, however our data provide a novel way to translate the evidence of toxic effects obtained in preclinical animal studies, by the direct, noninvasive measure of dividing cells in humans.

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

    PubMed

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

    2016-01-01

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

  16. Corneal Limbal Stem Cell Deficiency Associated with the Anticancer Drug S-1

    PubMed Central

    Kim, Kyeong Hwan; Kim, Wan Soo

    2015-01-01

    ABSTRACT Purpose An oral antineoplastic drug, S-1, is known to be more effective with less toxicity and fewer gastrointestinal side effects than the conventional intravenous 5-fluorouracil. We report a case of limbal stem cell deficiency that occurred in a patient receiving chemotherapy using S-1 alone for gastric cancer. Case Report A 65-year-old woman with symptoms of grittiness and epiphora in both eyes for several months was referred to the ophthalmology clinic. She had been receiving S-1 orally after total gastrectomy for advanced gastric cancer. Slit lamp examination revealed an irregular hazy corneal epithelium in both eyes that extended to the center of the cornea overlying the pupil and showed late staining with fluorescein dye. Palisades of Vogt at the superior limbus were absent in both eyes. Best-corrected distance vision was 20/50 in both eyes with all other structures of the anterior and posterior segment unremarkable including a patent lacrimal drainage system. There was no change in the corneal lesions of either eye despite 3 months of topical therapy. The lesions did resolve in 4 months after discontinuation of S-1 therapy owing to acute renal failure. Conclusions Early detection of this adverse reaction before significant visual loss through regular follow-up appears to be important in patients receiving S-1 therapy. PMID:25756340

  17. Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent literature.

    PubMed

    Martín Lancharro, Pablo; De Castro-Acuña Iglesias, Nuria; González-Barcala, Francisco-Javier; Moure González, José Domingo

    2016-11-01

    Objetivo: Disponer de la evidencia mas actual y conocer las medidas a aplicar para evitar la exposicion laboral a citostaticos. Método: Se realizo una busqueda bibliografica en las bases de datos MEDLINE, COCHRANE PLUS y WEB OF SCIENCE con los terminos “surface contamination”, “antineoplastic drug”, “drug preparation”, “occupational exposure”, “safe handling” y “closed-system transfer device” para el periodo 2010- 2015. Resultados: Se seleccionaron 13 articulos para la revision. Estos articulos corresponden a hospitales de USA, Canada, Japon, Australia, Espana, Portugal y Alemania. En todos ellos se ha encontrado contaminacion por farmacos citostaticos en mas de 15 superficies distintas con concentraciones que van desde los 1,69 ng/cm2 hasta 4,784 μg/cm2. Los farmacos determinados han sido ciclofosfamida, ifosfamida, 5-fluorouracilo, metotrexato, paclitaxel, cisplatino, gemcitabina y docetaxel. El sistema cerrado reduce la contaminacion de las superficies de trabajo significativamente, pero no la elimina. Conclusiones: Se verifica la presencia de contaminacion por farmacos citostaticos en numerosos hospitales de los 5 continentes. En todos los casos se ha encontrado contaminacion en la cabina, en el suelo frente a la cabina y en otros lugares de la farmacia. El farmaco mas frecuentemente encontrado es la ciclofosfamida. El sistema empleado mas eficaz para reducir la contaminacion es el uso de dispositivos cerrados de transferencia (CSTD-closed system transfer device).

  18. Drug use first aid

    MedlinePlus

    ... gait ( ataxia ) Sweating or extremely dry, hot skin Violent or aggressive behavior Death Drug withdrawal symptoms also ... own safety in danger. Some drugs can cause violent and unpredictable behavior. Call for medical help. Do ...

  19. 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.

  20. 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.

  1. 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)

  2. Prescription Drug Abuse

    MedlinePlus

    ... from what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that was prescribed for someone else Taking a ... at higher doses or when taken with other medicines. NIH: National Institute on Drug Abuse

  3. Drugs: Shatter the Myths

    MedlinePlus

    ... Enter Search Term(s): National Drug and Alcohol Facts Week® Print NEW 2018 DATE! You Host an NDAFW ... could not have done National Drug & Alcohol Facts Week ® without you! 2,174 events were registered for ...

  4. Stereoselectivity in drug metabolism.

    PubMed

    Lu, Hong

    2007-04-01

    Many chiral drugs are used as their racemic mixtures in clinical practice. Two enantiomers of a chiral drug generally differ in pharmacodynamic and/or pharmacokinetic properties as a consequence of the stereoselective interaction with optically active biological macromolecules. Thus, a stereospecific assay to discriminate between enantiomers is required in order to relate plasma concentrations to pharmacological effect of a chiral drug. Stereoselective metabolism of drugs is most commonly the major contributing factor to stereoselectivity in pharmacokinetics. Metabolizing enzymes often display a preference for one enantiomer of a chiral drug over the other, resulting in enantioselectivity. The structural characteristics of enzymes dictate the enantiomeric discrimination associated with the metabolism of chiral drugs. The stereoselectivity can, therefore, be viewed as the physical property characteristic that phenotypes the enzyme. This review provides a comprehensive appraisal of stereochemical aspects of drug metabolism (i.e., enantioselective metabolism and first-pass effect, enzyme-selective inhibition or induction and drug interaction, species differences and polymorphic metabolism).

  5. Drug-induced mania.

    PubMed

    Peet, M; Peters, S

    1995-02-01

    Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.

  6. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  7. 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)

  8. Animal Drug Safety FAQs

    MedlinePlus

    ... Animal & Veterinary Safety & Health Frequently Asked Questions Animal Drug Safety Frequently Asked Questions Share Tweet Linkedin Pin ... issues? Additional Information I gave my dog a drug and he got sick. How do I report ...

  9. Street Drugs and Pregnancy

    MedlinePlus

    ... premature birth Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... Is it safe? > Street drugs and pregnancy Street drugs and pregnancy E-mail to a friend Please ...

  10. Drug Facts: Anabolic Steroids

    MedlinePlus

    ... can avoid unwanted side effects or maximize the drugs' effects by taking them in ways that include: cycling— ... despite physical problems, high costs to buy the drugs, and negative effects on their relationships. These behaviors reflect steroids' addictive ...

  11. Access to Investigational Drugs

    MedlinePlus

    ... access to investigational drugs being developed by pharmaceutical companies? Are there specific criteria used to determine whether ... laboratory. If the results are promising, the drug company or sponsor must apply for FDA approval to ...

  12. Food-drug interactions.

    PubMed

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril). In addition, the physiological response to food intake, in particular gastric acid secretion, may reduce the bioavailability of certain drugs (ampicillin, azithromycin capsules, didanosine, erythromycin stearate or enteric coated, and isoniazid). For other drugs, concomitant food intake may result in an increase in drug bioavailability either because of a food-induced increase in drug solubility (albendazole, atovaquone, griseofulvin, isotretinoin, lovastatin, mefloquine, saquinavir and tacrolimus) or because of the secretion of

  13. 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

  14. Drug risk factors associated with a sustained outbreak of Clostridium difficile diarrhea in a teaching hospital

    PubMed Central

    Nath, Swapan K; Salama, Suzette; Persaud, Devia; Thornley, James H; Smith, Ian; Foster, Gary; Rotstein, Coleman

    1994-01-01

    A case-control study was undertaken to identify and quantify antimicrobial and nonantimicrobial drug risk factors associated with a sustained outbreak of Clostridium difficile diarrhea on two medical (teaching and nonteaching) units and an oncology unit. In total, 80 cases associated with an endemic clone of toxigenic C difficile were compared with controls. Eighty controls were selected from a group of 290 controls randomly chosen from the outbreak period. The controls were matched to cases according to age, admitting diagnosis and unit of admission. Seventy (88%) patients in the case group received at least one antibiotic before diarrhea, compared with 37 (46%) patients in the control group. Major risk factors implicated in the development of C difficile diarrhea in hospitalized patients were the following antimicrobial agents: ceftazidime (adjusted odds ratio [aor]=26.01, 95% ci 5.67 to 119.19, P=0.0001); cefuroxime (aor=5.17, ci 1.86 to 14.36, P=0.005); ciprofloxacin (aor=3.81, ci 1.05 to 13.79, P=0.04); and clindamycin (aor=15.16, ci 2.93 to 78.44, P=0.004). This is the first time that the use of ciprofloxacin has been linked to the development of C difficile diarrhea. Use of gastrointestinal drugs (ranitidine, famotidine, cimetidine, omeprazole and sucralfate) was also an added risk (aor=3.20, ci 1.39 to 7.34, P=0.01); however, antineoplastic therapy was not significant (P<0.53). Recognition of the specific high risk drugs may spur more restricted use of these agents, which may help in controlling C difficile diarrhea in hospitalized patients. PMID:22346513

  15. Incidence of hospital admissions due to adverse drug reactions in France: the EMIR study.

    PubMed

    Bénard-Laribière, Anne; Miremont-Salamé, Ghada; Pérault-Pochat, Marie-Christine; Noize, Pernelle; Haramburu, Françoise

    2015-02-01

    To assess the incidence of hospital admissions related to adverse drug reactions (ADRs) in France and the frequency of preventable ADRs in France, a prospective study was conducted among a representative randomly selected sample of medical wards in public hospitals between December 2006 and June 2007; all patients admitted during a 2-week period were included. An ADR-related hospitalization case was defined as a hospital admission because of an ADR, and an independent committee reviewed and validated all potential cases. Preventability was assessed using the French ADR preventability scale. Data were extrapolated to the population of France. Among 2692 admissions, 97 were related to an ADR (incidence 3.6%, 95% confidence interval, CI [2.8-4.4]). Patients admitted for an ADR were significantly older than those admitted for other reasons (P < 0.001). A third (32.0%) of ADR-related hospitalizations were 'preventable', 16.5% 'potentially preventable'. Drug interactions accounted for 29.9% of ADR-related hospitalizations. The most frequent causes of ADR-related hospitalizations were vascular disorders (20.6%), mainly bleeding complications, central nervous system disorders (11.3%), gastrointestinal disorders, and general disorders (9.3%). Antithrombotic and antineoplastic agents were the most frequently involved (12.6% each), followed by diuretics and analgesics (9.0% each). Vitamin-K-antagonists (VKAs) were the most common drugs associated with admission. The estimated annual number of ADR-related hospitalizations in France was 143 915 (95% CI [112 063-175 766]). ADRs were a significant cause of hospital admission in 2006-2007, in particular those due to VKAs. As new oral anticoagulants (NOACs) have been marketed, more attention needs to be paid to ensure a safe use of antithrombotic agents.

  16. 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…

  17. Intranuclear drug delivery and effective in vivo cancer therapy via estradiol-PEG-appended multiwalled carbon nanotubes.

    PubMed

    Das, Manasmita; Singh, Raman Preet; Datir, Satyajit R; Jain, Sanyog

    2013-09-03

    Cancer cell-selective, nuclear targeting is expected to enhance the therapeutic efficacy of a myriad of antineoplastic drugs, particularly those whose pharmacodynamic site of action is the nucleus. In this study, a steroid-macromolecular bioconjugate based on PEG-linked 17β-Estradiol (E2) was appended to intrinsically cell-penetrable multiwalled carbon nanotubes (MWCNTs) for intranuclear drug delivery and effective breast cancer treatment, both in vitro and in vivo. Taking Doxorubicin (DOX) as a model anticancer agent, we tried to elucidate how E2 appendage influences the cell internalization, intracellular trafficking, and antitumor efficacy of the supramolecularly complexed drug. We observed that the combination of DOX with E2-PEG-MWCNTs not only facilitated nuclear targeting through an estrogen receptor (ER)-mediated pathway but also deciphered to a synergistic anticancer response in vivo. The antitumor efficacy of DOX@E2-PEG-MWCNTs in chemically breast cancer-induced female rats was approximately 18, 17, 5, and 2 times higher compared to the groups exposed to saline, drug-deprived E2-PEG-MWCNTs, free DOX, and DOX@m-PEG-MWCNTs, respectively. While free DOX treatment induced severe cardiotoxicity in animals, animals treated with DOX@m-PEG-MWCNTs and DOX@E2-PEG-MWCNTs were devoid of any perceivable cardiotoxicity, hepatotoxicity, and nephrotoxicity. To the best of our knowledge, this is the first instance in which cancer cell-selective, intranuclear drug delivery, and, subsequently, effective in vivo breast cancer therapy has been achieved using estrogen-appended MWCNTs as the molecular transporter.

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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,…

  3. Drugs and Learning.

    ERIC Educational Resources Information Center

    Werry, John S.

    1981-01-01

    Reviews literature pertinent to studying the effects of drugs upon children's learning and cognitive function. The author concludes such research is in its infancy. He recommends further research focus upon whether drugs enhance the acquisition of new academic skills and upon assessment of the benefits versus side effects of such drug use.…

  4. Drugs, Alcohol and HIV

    MedlinePlus

    ... and drugs can do to your overall health. Drugs and Alcohol: Effects on your immune system Drinking too much alcohol ... getting help and finding the treatment you need. Drugs and Alcohol: ... on short- and long-term effects of drinking, with specific information on people who ...

  5. 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…

  6. 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…

  7. 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

  8. Drug-induced nephropathies.

    PubMed

    Paueksakon, Paisit; Fogo, Agnes B

    2017-01-01

    Drugs are associated frequently with the development of various types of acute and chronic kidney diseases. Nephrotoxicity is associated most commonly with injury in the tubulointerstitial compartment manifested as either acute tubular injury or acute interstitial nephritis. A growing number of reports has also highlighted the potential for drug-induced glomerular disease, including direct cellular injury and immune-mediated injury. Recognition of drug-induced nephropathies and rapid discontinuation of the offending agents are critical to maximizing the likelihood of renal function recovery. This review will focus on the pathology and pathogenesis of drug-induced acute interstitial nephritis and drug-induced glomerular diseases.

  9. The global drug gap.

    PubMed

    Reich, M R

    2000-03-17

    Global inequities in access to pharmaceutical products exist between rich and poor countries because of market and government failures as well as huge income differences. Multiple policies are required to address this global drug gap for three categories of pharmaceutical products: essential drugs, new drugs, and yet-to-be-developed drugs. Policies should combine "push" approaches of subsidies to support targeted drug development, "pull" approaches of financial incentives such as market guarantees, and "process" approaches aimed at improved institutional capacity. Constructive solutions are needed that can both protect the incentives for research and development and reduce the inequities of access.

  10. 2015 new drug update.

    PubMed

    Hussar, Daniel A

    2015-04-01

    Six new drugs approved within the last two years, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating system developed by the author. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. The drugs include two antidiabetic agents, one bronchodilator, one antidepressant, one for erectile dysfunction, and one for menopause-associated conditions.

  11. 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

  12. 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… ...

  13. Rational drug design.

    PubMed

    Mandal, Soma; Moudgil, Mee'nal; Mandal, Sanat K

    2009-12-25

    In this article, current knowledge of drug design is reviewed and an approach of rational drug design is presented. The process of drug development is challenging, expensive, and time consuming, although this process has been accelerated due to the development of computational tools and methodologies. The current target based drug design approach is incomplete because most of the drugs developed by structure guided approaches have been shown to have serious toxic side effects. Otherwise these drugs would have been an ideal choice for the treatment of diseases. Hence, rational drug design would require a multidisciplinary approach. In this regard, incorporation of gene expression technology and bioinformatics tools would be indispensable in the structure based drug design. Global gene expression data and analysis of such data using bioinformatics tools will have numerous benefits such as efficiency, cost effectiveness, time saving, and will provide strategies for combination therapy in addition to overcoming toxic side effects. As a result of incorporation of gene expression data, partial benefit of the structure based drug design is slowly emerging and rapidly changing the approach of the drug development process. To achieve the full benefit of developing a successful drug, multidisciplinary approaches (approaches such as computational chemistry and gene expression analysis, as discussed in this article) would be necessary. In the future, there is adequate room for the development of more sophisticated methodologies.

  14. Abuse of prescription drugs.

    PubMed Central

    Wilford, B B

    1990-01-01

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

  15. Drug Retention Times

    SciTech Connect

    None, None

    2007-05-01

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

  16. Food and Drug Interactions.

    PubMed

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  17. Drug abuse and stroke.

    PubMed

    Fonseca, Ana Catarina; Ferro, José M

    2013-02-01

    Cerebrovascular disorders contribute to the morbidity and disability associated with illicit drug use. Drug abusers have an increased risk of both hemorrhagic and ischemic stroke. In geographic areas with a high prevalence of illicit drug use, drug abuse is a frequent cause of stroke in the young adult. The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis. Toxicology screening for illicit drugs should be done in young patients with stroke with no obvious cause, or if suggested by history or examination. Although in some patients the mechanism of stroke is identified using neuroimaging and other modern diagnostic tools, in a sizeable fraction of cases the mechanism of stroke remains unclear. Further studies are needed to elucidate the role of hemodynamic and immunologic mechanisms in these cases.

  18. 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.

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

    PubMed

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

    2012-03-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. National Institute on Drug Abuse

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... HIV/AIDS research New resources available for criminal justice and drug treatment counselors Medication plus ongoing care ...

  12. Health Consequences of Drug Misuse

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... in education level, employment, housing, relationships, and criminal justice involvement. For more information on how various drugs ...

  13. Drugs + HIV, Learn the Link

    MedlinePlus Videos and Cool Tools

    ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction ...

  14. [Drug-drug interactions: interactions between xenobiotics].

    PubMed

    Haen, E

    2014-04-01

    Drug-drug interactions (DDI) are a major topic in programs for continuous medical education (CME). Many physicians are afraid of being trapped into charges of malpractice; however, DDI cannot be avoided in many cases. They belong to routine medical practice and it is often impossible to avoid them. Moreover, they do not just occur between drugs but between any kind of foreign substance (xenobiotica), such as food (e.g. grapefruit juice, broccoli, barbecue) as well as legal (e.g. tobacco smoke, caffeine and alcohol) and illegal drugs. Therefore, the medical challenge is not just to avoid any interaction. Instead the physician faces the question of how to proceed with drug treatment in the presence of such interactions. Based on the medical education a physician has to judge first of all whether there is a risk for interactions in the prescription being planned for an individual patient. The classification of interactions proposed in this article (PD1-PD4, PK1-PK3) might help as a sort of check list. For more detailed information the physician can then consult one of the many databases available on the internet, such as PSIAConline (http://www.psiac.de) and MediQ (http://www.mediq.ch). Pharmacokinetic interactions can be easily assessed, monitored and controlled by therapeutic drug monitoring (TDM). Besides these tools it is important to keep in mind that nobody knows everything; even physicians do not know everything. So take pride in asking someone who might help and for this purpose AGATE offers a drug information service AID (http://www.amuep-agate.de). Just good for nothing, without being based on any kind of medical approach are computer programs that judge prescriptions without taking into account a patient's individual peculiarities. In case these types of programs produce red exclamation marks or traffic lights to underline their judgment, they might even work in a contrapuntal way by just eliciting insecurity and fear.

  15. 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.

  16. Drug availability in Jamaica.

    PubMed

    Lee, M G; Henry, G L

    1989-06-01

    The availability of drugs and the supply system in Jamaica were examined. The Jamaica Commodity Trading Company imports all drugs through an international tendering system for the public health sector, and vital drugs for private distributors. For the 18-month period from January 1988, 652 awards were made, consisting of 426 (65%) brand and 226 (35%) generic drugs. There were several strengths and formulations for many drugs, including 19 preparations of 2 antibiotics. The University Hospital of the West Indies (UHWI) has been experiencing recurrent delays in the supply of several important drugs. In contrast, the private hospitals and pharmacies surveyed were adequately supplied. Many brands of several classes of drugs were available, including 51 antibiotics and 18 different anti-inflammatory analgesic and anti-hypertensive agents. However, several drugs used in special situations were only available at the UHWI. There is a need for the supply of drugs to be a priority in the public health sector and for the use of several drugs to be rationalized.

  17. Recreational drugs of abuse.

    PubMed

    Albertson, Timothy E

    2014-02-01

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

  18. Drug-induced hypokalaemia.

    PubMed

    Ben Salem, Chaker; Hmouda, Houssem; Bouraoui, Kamel

    2009-01-01

    Hypokalaemia (defined as a plasma potassium concentration<3.5 mEq/L) is a common electrolyte abnormality in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hypokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic disease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diagnosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.

  19. 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.

  20. New Drugs for CML

    DTIC Science & Technology

    2007-02-01

    AD_________________ Award Number: W81XWH-06-1-0232 TITLE: New Drugs for CML PRINCIPAL...TYPE Final 3. DATES COVERED 1 Feb 2006– 31 Jan 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for CML 5b. GRANT NUMBER W81XWH...Deisseroth A. Use of combinatorial structural variation of top design new drugs for CML. Mol Cancer Ther, 6: 655-666, 2007. Novel compounds with

  1. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  2. 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

  3. [Safety nonsteroidal antiinflammatory drugs].

    PubMed

    Oscanoa-Espinoza, Teodoro Julio

    2015-01-01

    The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drug in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity.

  4. Sublingual drug delivery.

    PubMed

    Goswami, Tarun; Jasti, Bhaskara; Li, Xiaoling

    2008-01-01

    The sublingual route is one of the early modes of administration for systemic drug delivery. This route avoids first-pass metabolism and affords quick drug entry into the systemic circulation. Attempts have been made to deliver various pharmacologically active agents, such as cardiovascular drugs, analgesics, and peptides, across the sublingual mucosa. In this review, the anatomical structure, blood supply, biochemical composition, transport pathways, permeation enhancement strategies, in vitro/in vivo models, and clinical investigations for the sublingual route of drug delivery is discussed.

  5. Drug dangers and reactions.

    PubMed

    WEILERSTEIN, R W

    1961-01-01

    The protection of the consumer against dangerous, adulterated, and misbranded drugs provided by the Federal Food, Drug, and Cosmetic Act has failed in some instances. A general program of reporting adverse drug reactions has been initiated on a pilot basis. Arrangements are being made to extend this program into larger hospitals. Better and more complete reporting of adverse drug reactions together with tightening of the Food and Drug law regarding new drugs will improve this situation. Recently the president of the National Academy of Sciences appointed a committee at the request of the Secretary of Health, Education, and Welfare to review the policies and procedures used by the Food and Drug Administration in reaching decisions and to present recommendations. This committee has completed its work and has made specific recommendations that would give the Food and Drug Administration authority to require proof of efficacy as well as safety of all new drugs, and would provide it with sufficient resources to meet the responsibilities assigned to it.

  6. DRUG DANGERS AND REACTIONS

    PubMed Central

    Weilerstein, Ralph W.

    1961-01-01

    The protection of the consumer against dangerous, adulterated, and misbranded drugs provided by the Federal Food, Drug, and Cosmetic Act has failed in some instances. A general program of reporting adverse drug reactions has been initiated on a pilot basis. Arrangements are being made to extend this program into larger hospitals. Better and more complete reporting of adverse drug reactions together with tightening of the Food and Drug law regarding new drugs will improve this situation. Recently the president of the National Academy of Sciences appointed a committee at the request of the Secretary of Health, Education, and Welfare to review the policies and procedures used by the Food and Drug Administration in reaching decisions and to present recommendations. This committee has completed its work and has made specific recommendations that would give the Food and Drug Administration authority to require proof of efficacy as well as safety of all new drugs, and would provide it with sufficient resources to meet the responsibilities assigned to it. PMID:13783849

  7. 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.

  8. Drug-induced exanthems.

    PubMed

    Yawalkar, Nikhil

    2005-04-15

    Cutaneous adverse reactions to drugs can comprise a broad spectrum of clinical and histopathological features. Recent evidence from immunohistological and functional studies of drug-reactive T cells suggest that distinct T-cell functions may be responsible for this broad spectrum of different clinical reactions. Maculopapular exanthems represent the most commonly encountered cutaneous drug eruption. Previous studies on maculopapular exanthems indicate that drug-specific CD4+ T cells expressing cytotoxic granule proteins such as perforin and granzyme B are critically involved in killing activated keratinocytes. These cells are particularly found at the dermo-epidermal junction and may contribute to the generation of vacuolar alteration and destruction of basal keratinocytes, which are typical found in drug-induced maculopapular exanthems. In contrast to maculopapular exanthems, the preferential activation of drug-specific cytotoxic CD8+ T cells may lead to more severe reactions like bullous drug eruptions. Furthermore, activation of drug-specific T with distinct cytokine and chemokines profiles may also explain the different clinical features of drug-induced exanthems. IL-5 and eotaxin are upregulated in maculopapular exanthems and explain the eosinophilia often found in these reactions.

  9. 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

  10. The relationship between rational drug design and drug side effects.

    PubMed

    Wang, Juan; Li, Zhi-xin; Qiu, Cheng-xiang; Wang, Dong; Cui, Qing-hua

    2012-05-01

    Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.

  11. Drug-nutrient interactions.

    PubMed

    Chan, Lingtak-Neander

    2013-07-01

    Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

  12. Recommunalizing Drug Offenders: The "Drug Peace" Agenda.

    ERIC Educational Resources Information Center

    Arrigo, Bruce A.

    1997-01-01

    Examines the manner in which substance-using shelter tenants, many of them ex-offenders, who lived in an urban, single- room-occupancy neighborhood, engaged in the process of recommunalization. Identifies and describes eight developmental stages of recommunalization, and links recommunalization to proposals for solving the war on drugs. (RJM)

  13. Drug-induced lupus.

    PubMed

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  14. Asthma - control drugs

    MedlinePlus

    ... About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Asthma - control drugs URL of this page: //medlineplus.gov/ency/patientinstructions/000005.htm Asthma - control ...

  15. PRESERVATION OF DRUGS

    PubMed Central

    Rao, R. Bhima; Natarajan, R.K.; Sarma, P.S. Nataraja; Purushothaman, K.K.

    1982-01-01

    In this article the factors likely to cause spoilage of the drugs of the Indian systems of medicine are reviewed. Methods for the prevention of spoilage are discussed. The results of a limited study carried out on the stability of a few selected drug preparations representing the main dosage forms are also presented PMID:22556951

  16. Medicare Prescription Drug Coverage

    MedlinePlus

    ... people also have to pay an additional monthly cost. Private companies provide Medicare prescription drug coverage. You choose the drug plan you like best. Whether or not you should sign up depends on how good your current coverage is. You need to sign up as ...

  17. Drug Education, A Misnomer

    ERIC Educational Resources Information Center

    Edwards, Gerald; Holloway, Janet

    1975-01-01

    Recognizing that behavior is a result of the integration of affective and cognitive factors, drug education must focus on the motivations of students. Article focused on the responsibility for development of drug abuse programs that must be shared by schools as well as students and teachers. (Author/RK)

  18. 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…

  19. Drugs in sport.

    PubMed

    McGrath, J C; Cowan, D A

    2008-06-01

    This themed issue of the British Journal of Pharmacology has been compiled and edited by Ian McGrath, Regius Professor of Physiology at University of Glasgow and David Cowan, Director of the Drug Control Centre at King's College London. It contains 11 articles covering the mechanisms of action of the major groups of drugs used illicitly in sport. The articles, written by experts in how drugs work, set out where drugs can or cannot affect sporting performance, how this relates to their legitimate medicinal use, their other detrimental effects and how they can be detected. Publication coincides with Olympic year, when sport is highlighted in the public mind and much speculation is made concerning the use of drugs. The articles provide a framework of expert, accurate knowledge to inform and facilitate these debates and to help to overcome the ill-informed and dangerous anecdotal information by which sports men and women are persuaded to misuse drugs in the mistaken belief that this will improve their performance without present or future ill effects. A unique article is included by the Spedding brothers, Mike with a long career in drug discovery and Charlie, the 1984 Los Angeles Olympic Marathon Bronze Medallist and still the English National Marathon record holder. From their unique experience, they describe the insidious and unfair way that drug-assisted performance undermines the ethos of sport and endangers the vital place of sport in maintaining the health of the population.

  20. The Drug War.

    ERIC Educational Resources Information Center

    DeCrosta, Anthony

    1989-01-01

    The role of teachers in helping fight against drug abuse is discussed stressing the teacher's ability to see changes in the students and the potential for positive influence. A vital school role involves teaching life skills and wellness principles. Information on commonly abused drugs and their effects is presented. (SM)

  1. 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.…

  2. 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…

  3. Linear drug eruption.

    PubMed

    Alfonso, R; Belinchon, I

    2001-01-01

    Linear eruptions are sometimes associated with systemic diseases and they may also be induced by various drugs. Paradoxically, such acquired inflammatory skin diseases tend to follow the system of Blaschko's lines. We describe a case of unilateral linear drug eruption caused by ibuprofen, which later became bilateral and generalized.

  4. Drug Education Program.

    ERIC Educational Resources Information Center

    Department of Defense, Washington, DC.

    Although designed specifically for schools on overseas military bases, this brief guide for the development of drug education programs for elementary and secondary school students can be used as an outline for any school-related drug education program. The materials in the handbook address the following areas of concern: (1) suggestions of topics…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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'.

  10. 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.

  11. 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.

  12. Antipsychotic drugs and seizures.

    PubMed

    Remick, R A; Fine, S H

    1979-02-01

    The authors examine the clinical problem of which antipsychotic drug to use when antipsychotics are indicated in patients with a seizuire disorder or who are susceptible to seizures. While definitive answers to this problem are still unknown, guidelines are offered for antipsychotic drug use in this situation, based on the author's understanding of psychotropics and epilepsy.

  13. [Immunotherapies for drug addictions].

    PubMed

    Montoya, Ivan

    2008-01-01

    Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders.

  14. Alternative drugs of abuse.

    PubMed

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

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  15. Drug Impact Index.

    ERIC Educational Resources Information Center

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  16. 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

  17. 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

  18. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  19. 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

  20. Targeting drugs to mitochondria.

    PubMed

    Heller, Anne; Brockhoff, Gero; Goepferich, Achim

    2012-09-01

    Mitochondria are of an increasing interest in pharmaceutical and medical research since it has been reported that dysfunction of these organelles contributes to several diseases with a great diversity of clinical appearance. By the fact that mitochondria are located inside the cell and, in turn, origins of mitochondrial diseases or targets of drugs are located inside mitochondria, a drug molecule has to cross several barriers. This is a severe drawback for the selective accumulation of drug molecules in mitochondria. Therefore, targeting strategies such as direct drug modification or encapsulation into nanocarriers have to be applied to achieve an accumulation of drug molecules in these organelles. In this review, it will be demonstrated how properties and dysfunctions of mitochondria are generating a need for the development of mitochondria specific therapies. Furthermore, intracellular targets of mitochondrial diseases, strategies to utilize mitochondrial specificities and targeting approaches will be discussed. Finally, techniques to investigate mitochondrial characteristics and functionality are reviewed.

  1. Ethics and drug resistance.

    PubMed

    Selgelid, Michael J

    2007-05-01

    This paper reviews the dynamics behind, and ethical issues associated with, the phenomenon of drug resistance. Drug resistance is an important ethical issue partly because of the severe consequences likely to result from the increase in drug resistant pathogens if more is not done to control them. Drug resistance is also an ethical issue because, rather than being a mere quirk of nature, the problem is largely a product of drug distribution. Drug resistance results from the over-consumption of antibiotics by the wealthy; and it, ironically, results from the under-consumption of antibiotics, usually by the poor or otherwise marginalized. In both kinds of cases the phenomenon of drug resistance illustrates why health (care)--at least in the context of infectious disease--should be treated as a (global) public good. The point is that drug resistance involves 'externalities' affecting third parties. When one patient develops a resistant strain of disease because of her over- or under-consumption of medication, this more dangerous malady poses increased risk to others. The propriety of free-market distribution of goods subject to externalities is famously dubious--given that the 'efficiency' rationale behind markets assumes an absence of externalities. Market failure in the context of drug resistance is partly revealed by the fact that no new classes of antibiotics have been developed since 1970. I conclude by arguing that the case of drug resistance reveals additional reasons--to those traditionally appealed to by bioethicists--for treating health care as something special when making policy decisions about its distribution.

  2. Development of a Novel In Vitro Human Tissue-Based Angiogenesis Assay to Evaluate the Effect of Antiangiogenic Drugs

    PubMed Central

    Woltering, Eugene A.; Lewis, James M.; Maxwell, P. Johnstone; Frey, Daniel J.; Wang, Yi-Zarn; Rothermel, John; Anthony, Catherine T.; Balster, Douglas A.; O’Leary, J. Patrick; Harrison, Lynn H.

    2003-01-01

    Objective To describe a novel in vitro human tissue-based angiogenic model that can predict an individual tumor’s response to antiangiogenic drugs. Summary Background Data A number of in vitro and in vivo angiogenesis assays exist, but they do not provide potentially useful information for the treatment of an individual patient. Clonogenic assays have been used to evaluate the response of an individual’s tumor to antineoplastic agents, but these tumor fragments are cultured in an environment that does not lead to neovessel growth. The authors have previously demonstrated that human vein disks or human tumor xenograft fragments incorporated into a 0.3% fibrin-thrombin clot will develop angiogenic vessel growth from the cut edge of the vessel disk or xenograft fragment. Methods Fresh human tumor or normal tissue disks (2 × 1 mm) from fresh surgical specimens were incorporated into fibrin-thrombin clots overlain with nutrient medium containing either 20% fetal bovine serum alone or in combination with Epothilone B, a tubulin inhibitor with antiangiogenic properties. Tissue disks were visually assessed over time to determine the percentage of wells that developed an angiogenic response. Neovessel growth, density, and length were graded at intervals using a semiquantitative visual neovessel growth-rating scheme (angiogenic index, 0–16 scale) devised in the authors’ laboratory. Results Epothilone B treatment at doses of 10−6 mol/L and 10−8 mol/L decreased the number of wells that developed an invasive angiogenic response and limited the development of vessels that invaded the matrix. At these doses, Epothilone B also caused regression of vessels in wells that had been allowed to develop an angiogenic response. Treatment of tumors or normal tissues with Epothilone B at doses less than 10−8 mol/L was ineffective. Conclusions Epothilone B may be an effective antiangiogenic agent in a variety of tumor types. The authors speculate that this in vitro model might

  3. Potential Drug - Drug Interactions among Medications Prescribed to Hypertensive Patients

    PubMed Central

    Ganguly, Barna

    2014-01-01

    Context: Drug-drug interactions(DDIs) are significant but avoidable causes of iatrogenic morbidity and hospital admission. Aim: To detect potential drug-drug interactions among medications received by hypertensive patients. Materials and Methods: Patients of both sex and all adult age groups, who were attending medicine out -patient department (OPD) of a tertiary care teaching rural hospital since last six months and were being prescribed antihypertensive drug/s for essential hypertension, were selected for the study. Hypertensive patient with co-morbities diabetes mellitus, ischemic heart diseases, congestive heart failure, and chronic renal diseases were also included in the study. Potential drug drug interactions were checked with medscape drug interaction software. Results: With the help of medscape drug interaction software, 71.50% prescriptions were identified having atleast one drug-drug interaction. Total 918 DDIs were found in between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs were found significant type of DDIs. Drug drug interaction between atenolol & amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88) in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to cause DDIs in our study. Conclusion: We detected a significant number of drug drug interaction in hypertensive patients. These interactions were between antihypertensive agents or between hypertensive and drug for co-morbid condition. PMID:25584241

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. Irreversible enzyme inhibition kinetics and drug-drug interactions.

    PubMed

    Mohutsky, Michael; Hall, Stephen D

    2014-01-01

    This chapter describes the types of irreversible inhibition of drug-metabolizing enzymes and the methods commonly employed to quantify the irreversible inhibition and subsequently predict the extent and time course of clinically important drug-drug interactions.

  12. Artemisinin-derived dimer ART-838 potently inhibited human acute leukemias, persisted in vivo, and synergized with antileukemic drugs

    PubMed Central

    Fox, Jennifer M.; Moynihan, James R.; Mott, Bryan T.; Mazzone, Jennifer R.; Anders, Nicole M.; Brown, Patrick A.; Rudek, Michelle A.; Liu, Jun O.; Arav-Boger, Ravit; Posner, Gary H.

    2016-01-01

    Artemisinins, endoperoxide-containing molecules, best known as antimalarials, have potent antineoplastic activity. The established antimalarial, artesunate (AS), and the novel artemisinin-derived trioxane diphenylphosphate dimer 838 (ART-838) inhibited growth of all 23 tested acute leukemia cell lines, reduced cell proliferation and clonogenicity, induced apoptosis, and increased intracellular levels of reactive oxygen species (ROS). ART-838 was 88-fold more potent that AS in vitro, inhibiting all leukemia cell lines at submicromolar concentrations. Both ART-838 and AS cooperated with several established antileukemic drugs and newer kinase inhibitors to inhibit leukemia cell growth. ART-838 had a longer plasma half-life than AS in immunodeficient NOD-SCID-IL2Rgnull (NSG) mice, remaining at effective antileukemic concentrations for >8h. Intermittent cycles of ART-838 inhibited growth of acute leukemia xenografts and primagrafts in NSG mice, at higher potency than AS. Based on these preclinical data, we propose that AS, with its established low toxicity and low cost, and ART-838, with its higher potency and longer persistence in vivo, should be further developed toward integration into antileukemic regimens. PMID:26771236

  13. Artemisinin-derived dimer ART-838 potently inhibited human acute leukemias, persisted in vivo, and synergized with antileukemic drugs.

    PubMed

    Fox, Jennifer M; Moynihan, James R; Mott, Bryan T; Mazzone, Jennifer R; Anders, Nicole M; Brown, Patrick A; Rudek, Michelle A; Liu, Jun O; Arav-Boger, Ravit; Posner, Gary H; Civin, Curt I; Chen, Xiaochun

    2016-02-09

    Artemisinins, endoperoxide-containing molecules, best known as antimalarials, have potent antineoplastic activity. The established antimalarial, artesunate (AS), and the novel artemisinin-derived trioxane diphenylphosphate dimer 838 (ART-838) inhibited growth of all 23 tested acute leukemia cell lines, reduced cell proliferation and clonogenicity, induced apoptosis, and increased intracellular levels of reactive oxygen species (ROS). ART-838 was 88-fold more potent that AS in vitro, inhibiting all leukemia cell lines at submicromolar concentrations. Both ART-838 and AS cooperated with several established antileukemic drugs and newer kinase inhibitors to inhibit leukemia cell growth. ART-838 had a longer plasma half-life than AS in immunodeficient NOD-SCID-IL2Rgnull (NSG) mice, remaining at effective antileukemic concentrations for >8h. Intermittent cycles of ART-838 inhibited growth of acute leukemia xenografts and primagrafts in NSG mice, at higher potency than AS. Based on these preclinical data, we propose that AS, with its established low toxicity and low cost, and ART-838, with its higher potency and longer persistence in vivo, should be further developed toward integration into antileukemic regimens.

  14. Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member 2 and subfamily C member 10-mediated drug resistance.

    PubMed

    Zhang, Hui; Kathawala, Rishil J; Wang, Yi-Jun; Zhang, Yun-Kai; Patel, Atish; Shukla, Suneet; Robey, Robert W; Talele, Tanaji T; Ashby, Charles R; Ambudkar, Suresh V; Bates, Susan E; Fu, Li-Wu; Chen, Zhe-Sheng

    2014-06-01

    In this study we investigated the effect of linsitinib on the reversal of multidrug resistance (MDR) mediated by the overexpression of the ATP-binding cassette (ABC) subfamily members ABCB1, ABCG2, ABCC1 and ABCC10. Our results indicate for the first time that linsitinib significantly potentiate the effect of anti-neoplastic drugs mitoxantrone (MX) and SN-38 in ABCG2-overexpressing cells; paclitaxel, docetaxel and vinblastine in ABCC10-overexpressing cells. Linsitinib moderately enhanced the cytotoxicity of vincristine in cell lines overexpressing ABCB1, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, linsitinib significantly increased the intracellular accumulation and decreased the efflux of [(3)H]-MX in ABCG2-overexpressing cells and [(3)H]-paclitaxel in ABCC10-overexpressing cells. However, linsitinib, at a concentration that reversed MDR, did not significantly alter the expression levels of either the ABCG2 or ABCC10 transporter proteins. Furthermore, linsitinib did not significantly alter the intracellular localization of ABCG2 or ABCC10. Moreover, linsitinib stimulated the ATPase activity of ABCG2 in a concentration-dependent manner. Overall, our study suggests that linsitinib attenuates ABCG2- and ABCC10-mediated MDR by directly inhibiting their function as opposed to altering ABCG2 or ABCC10 protein expression.

  15. Bioequivalence of generic drugs.

    PubMed

    Andrade, Chittaranjan

    2015-09-01

    Generic drugs are bioequivalent to the original brand; this is a prerequisite for marketing approval. It is theoretically possible that one generic drug may overestimate the pharmacokinetic (PK) parameters of the original and another generic may underestimate these PK parameters; in consequence, these 2 generics may not be bioequivalent between themselves. The result could be loss of efficacy or development of drug-related adverse effects if these generics are interchanged in stable patients. In a recent study involving 292 indirect comparisons of generic formulations of 9 different drugs, mathematical modeling showed that in most cases (87.0% for maximum concentration, 90.1% for area under the curve, and 80.5% for both) generic drugs are bioequivalent to each other. These reassuring findings notwithstanding, prudence dictates that, in stable patients, generic drugs should be interchanged only if there is a good reason for it. This is because bioequivalent brands of drugs may differ in their excipient content, and this can result in variations in safety profiles.

  16. Food and Drug Interactions

    PubMed Central

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions. PMID:28261555

  17. Herb-drug interactions.

    PubMed

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  18. Adverse cutaneous drug reaction.

    PubMed

    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.

  19. Nanomaterials for Drugs Delivery

    DOE PAGES

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction ofmore » the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to

  20. Nanomaterials for Drugs Delivery

    SciTech Connect

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction of the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to solve many

  1. Opioids and designer drugs.

    PubMed

    Ford, M; Hoffman, R S; Goldfrank, L R

    1990-08-01

    Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

  2. Vaccines against drug abuse.

    PubMed

    Shen, X Y; Orson, F M; Kosten, T R

    2012-01-01

    The currently available medications for the treatment of drug abuse have had only limited success. Anti-addiction vaccines, aimed at eliciting antibodies that block the pharmacological effects of drugs, have great potential for treating drug abuse. We review the status of two vaccines that are undergoing clinical trials (for cocaine and nicotine addiction) and two that are still in preclinical development (for methamphetamine and heroin addiction). We also outline the challenges and ethical concerns associated with the development of anti-addiction vaccines and their use as future therapeutics.

  3. Drug-induced gynecomastia.

    PubMed

    Eckman, Ari; Dobs, Adrian

    2008-11-01

    Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

  4. Neonatal drug withdrawal.

    PubMed

    Hudak, Mark L; Tan, Rosemarie C

    2012-02-01

    Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

  5. Drug-specific [sup 19]F NMR and dynamic [sup 18]F PET imaging of the cytostatic agent 5-fluorouracil

    SciTech Connect

    Bellemann, M.E.; Brix, G.; Haberkorn, U.; Ostertag, H.J.; Lorenz, W.J. )

    1994-12-01

    The spatial distribution of the antineoplastic agent 5-fluorouracil (5-FU) has been mapped both with [sup 19]F NMR and [sup 18]F PET imaging techniques. For [sup 19]F NMR imaging of 5-FU and its major catabolite [alpha]-fluoro-[beta]-alanine (FBAL), a fast gradient-echo pulse sequence was employed. A chemical-shift selective saturation pulse was used to suppress either the 5-FU or the FBAL resonance before the other component of the [sup 19]F NMR spectrum was images. This approach yielded selective 5-FU and FBAL NMR images free of chemical-shift artifacts in readout and slice-selection direction. In phantom experiments, [sup 19]F 5-FU and FBAL images with a spatial resolution of 12.5 x 12.5 x 20 mm[sup 3] were obtained in 32 min from model solutions with drug and catabolite concentrations similar to those estimated in animals and patients undergoing i.v. chemotherapy with 5-FU. The biodistribution of 5-[[sup 18]F]FU in rats shortly after administration of the drug demonstrated the good vascularization of the transplanted tumors. The metabolic turnover of the cytostatic agent started about 10--20 min p.i. and was predominant in the tumor and liver tissue. The rapid adjustment of the [sup 18]F metabolite concentrations in the transplanted tumors to a steady state provides evidence of anabolic tumor activity, which supports the hypothesis of 5-FU trapping in malignant cells based on [sup 19]F NMR spectroscopy data. The high uptake of 5-[[sup 18]F]FU in the liver, on the other hand, mainly reflects the catabolization of 5-FU to the noncytotoxic FBAL, which leads to a reduced bioavailability of the drug.

  6. Photocatalytic degradation of selected anticancer drugs and identification of their transformation products in water by liquid chromatography-high resolution mass spectrometry.

    PubMed

    Calza, P; Medana, C; Sarro, M; Rosato, V; Aigotti, R; Baiocchi, C; Minero, C

    2014-10-03

    A study on the fate of two antineoplastic drugs, methotrexate and doxorubicin, in the aquatic environment is presented. The investigation involved a study of their decomposition under dark experiments, homogeneous photolysis and heterogeneous photocatalysis using titanium dioxide, the identification of intermediate compounds, as well as the assessment of acute toxicity over time. The analysis were carried out using LC (ESI positive mode) coupled with LTQ-Orbitrap analyser; accurate mass-to-charge ratios of parent ions were reported with inaccuracy below 10mmu, which guarantee the correct assignment of their molecular formula in all cases, while their MS(2) and MS(3) spectra showed several structural-diagnostic ions that allowed to characterize the different transformation products and to discriminate the isobaric species. Fourteen and eight main species were identified subsequently to doxorubicin or methotrexate transformation. The major transformation processes for doxorubicin involved (poli)hydroxylation and/or oxidation of the molecule, or the detachment of the sugar moiety. Methotrexate transformation involved decarboxylation or the molecule cleavage. Acute toxicity measurements showed that not only the two drugs exhibit high toxicity, but also their initial transformation products are highly toxic.

  7. 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) ...

  8. Prescription Drugs and Cold Medicines

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... and over-the-counter (OTC) drugs are, after marijuana (and alcohol), the most commonly abused substances by ...

  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 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.

  11. 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.

  12. 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.

  13. 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.

  14. Drugs Approved for Thyroid Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  15. List of Confused Drug Names

    MedlinePlus

    ... vaccine Inspra Intuniv INV anz Invega iodine Isordil ISO tretinoin Jantoven Jantoven Janumet Janumet Janumet Januvia Januvia ... Drug Names Drug Name Confused Drug Name tretinoin ISO tretinoin Tricor Tracleer tromethamine Trophamine Trophamine tromethamine tuberculin ...

  16. Commonly Abused Drugs Charts

    MedlinePlus

    ... with long, slender stems topped by caps with dark gills Swallowed (eaten, brewed as tea, or added ... NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home Site Map Accessibility Privacy ...

  17. DrugFacts: Heroin

    MedlinePlus

    ... Badge NIDA TV Spotlight: Heroin in the Twin Cities YouTube embedded video: http://www.youtube-nocookie.com/ ... a highlight on heroin use in the Twin Cities from her June 2013 Report on "Drug Abuse ...

  18. Drug-induced tremor

    MedlinePlus

    ... valproate (Depakene) Asthma medicines such as theophylline and albuterol Immune suppressing medicines such as cyclosporine and tacrolimus Mood stabilizers such as lithium carbonate Stimulants such as caffeine and amphetamines Antidepressant drugs such as selective serotonin reuptake inhibitors ( ...

  19. Cholesterol - drug treatment

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  20. Drug Education for Administrators

    ERIC Educational Resources Information Center

    Hackett, Peter; McKeon, Thomas L.

    1976-01-01

    The formulation of a drug policy and the implementation of that policy in a firm but fair manner are the responsibility of the school administrator. Authors give serious consideration to this responsibility. (Editor/RK)