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Sample records for antimetabolites antineoplastic

  1. Antimetabolite Treatment for Pancreatic Cancer

    OpenAIRE

    Valenzuela, Malyn May Asuncion; Neidigh, Jonathan W.; Wall, Nathan R.

    2014-01-01

    Pancreatic cancer is a deadly and aggressive disease. Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4–8 months. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine and 5-fluorouracil are used clinically. Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improve...

  2. Antineoplastic Drugs.

    Science.gov (United States)

    Morris, Sara; Michael, Nancy, Ed.

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

  3. Targeting one carbon metabolism with an antimetabolite disrupts pyrimidine homeostasis and induces nucleotide overflow

    OpenAIRE

    Ser, Zheng; GAO, XIA; Johnson, Christelle; Mehrmohamadi, Mahya; Liu, Xiaojing; Li, SiQi; Locasale, Jason W.

    2016-01-01

    Anti-metabolite agents that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used anti-metabolite therapeutic with varying efficacy, induces specific alterations to nucleotide metabolism by disrupting pyrimidine homeostasis. An integrative metabolomics analysis of ...

  4. Antibacterial activities of antineoplastic agents.

    OpenAIRE

    Bodet, C A; Jorgensen, J H; Drutz, D J

    1985-01-01

    Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities.

  5. Handling of injectable antineoplastic agents.

    OpenAIRE

    Knowles, R S; Virden, J E

    1980-01-01

    Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents.

  6. Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites.

    Science.gov (United States)

    Weinreich, Jürgen; Struller, Florian; Küper, Markus; Hack, Anita; Königsrainer, Alfred; Schott, Timm C

    2013-04-01

    The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'→5')ECyd. The drug and metabolites of the assays and medium were determined semiquantitatively using high-performance liquid chromatography. The sensitivity of cancer and nonmalignant cell lines was clearly different against the duplex drug. A measure of 0.65 µmol/l 5FdU(5'→5')ECyd, for example, reduced the growth of MKN-45 or 23132/87 gastric cancer cells from 100% on day 0 to about 50 or 20% on day 10, respectively. However, under the same conditions, the growth of the nonmalignant NHDF and CCL-241 cell lines was not markedly inhibited. The cytostatic activity of the duplex drug is based on the active metabolites in and outside the cell formed by the degradation of 5FdU(5'→5')ECyd. The sensitivity of cell lines against the duplex drug depended on its ability to metabolize the duplex drug. 5FdU(5'→5')ECyd should be more advantageous for specific and efficient polychemotherapy of gastric cancer than the corresponding equimolar mixture of 5FdU+ECyd or a standard combination regime of single drugs.

  7. Chemical and Metabolic Aspects of Antimetabolite Toxins Produced by Pseudomonas syringae Pathovars

    Directory of Open Access Journals (Sweden)

    Eva Arrebola

    2011-08-01

    Full Text Available Pseudomonas syringae is a phytopathogenic bacterium present in a wide variety of host plants where it causes diseases with economic impact. The symptoms produced by Pseudomonas syringae include chlorosis and necrosis of plant tissues, which are caused, in part, by antimetabolite toxins. This category of toxins, which includes tabtoxin, phaseolotoxin and mangotoxin, is produced by different pathovars of Pseudomonas syringae. These toxins are small peptidic molecules that target enzymes of amino acids’ biosynthetic pathways, inhibiting their activity and interfering in the general nitrogen metabolism. A general overview of the toxins’ chemistry, biosynthesis, activity, virulence and potential applications will be reviewed in this work.

  8. Hematological Changes in Nurses Handling Antineoplastic Drugs

    OpenAIRE

    Ansari-Lari, M; M.Saadat

    2002-01-01

    A cross-sectional study to determine whether occupational exposure to antineoplastic drugs can cause hematologic changes was performed. Blood samples were collected from a group of 24 hematology/oncology nurses who were exposed to antineoplastic drugs during a mean preiod of 5.5 years (standard error =1.1). The control group, matched by sex, and age, consisted of 18 nurses, worked on other sections. Within the normal range we found significant differences between the exposed and the control g...

  9. Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery vehicle.

    Science.gov (United States)

    McEwan, Conor; Kamila, Sukanta; Owen, Joshua; Nesbitt, Heather; Callan, Bridgeen; Borden, Mark; Nomikou, Nikolitsa; Hamoudi, Rifat A; Taylor, Mark A; Stride, Eleanor; McHale, Anthony P; Callan, John F

    2016-02-01

    In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1), cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the potential of combined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but also the capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance the efficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBs to facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility to activate the sensitiser using externally applied ultrasound, provides a more targeted approach with improved efficacy and reduced side effects when compared with conventional systemic administration of antimetabolite drugs alone.

  10. Antineoplastic Drugs : Treatment Principles and Toxicity

    Directory of Open Access Journals (Sweden)

    Bibu John Kariyil

    Full Text Available The therapy of cancer has improved dramatically during the past half century. This improvement can be traced to a number of factors: a better understanding of cancer's cause and natural history, better technologies for early detection and diagnosis, improved control of primary tumors through surgery and radiation therapy and more effective drugs. The evolution of drug therapy for cancer has progressed rapidly from alkylating agents and antimetabolites to natural products, and most recently, molecular targeted drugs such as imatinib and gefitinib. As our understanding of the biology of cancer improves, new targets for therapy are being identified daily. [Vet. World 2011; 4(8.000: 380-382

  11. Hematological Changes in Nurses Handling Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    M Ansari-Lari

    2002-08-01

    Full Text Available A cross-sectional study to determine whether occupational exposure to antineoplastic drugs can cause hematologic changes was performed. Blood samples were collected from a group of 24 hematology/oncology nurses who were exposed to antineoplastic drugs during a mean preiod of 5.5 years (standard error =1.1. The control group, matched by sex, and age, consisted of 18 nurses, worked on other sections. Within the normal range we found significant differences between the exposed and the control group in the absolute mean number of the total white blood cells (t=-2.50; df=40; P<0.05 and neutrophils (t=-1.72; df=40; P<0.05; one tailed test. The findings suggested, that the hematologic changes can serve as biological markers for medical surveillance and early detection of health problems due to handling antineoplastic drugs.

  12. Occupational rhinosinusitis due to etoposide, an antineoplastic agent

    DEFF Research Database (Denmark)

    Meyer, Harald W; Skov, Per Stahl

    2010-01-01

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

  13. Antineoplastic drugs: Occupational exposure and health risks

    NARCIS (Netherlands)

    Fransman, W.

    2006-01-01

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

  14. Biosynthesis of the antimetabolite 6-thioguanine in Erwinia amylovora plays a key role in fire blight pathogenesis.

    Science.gov (United States)

    Coyne, Sébastien; Chizzali, Cornelia; Khalil, Mohammed N A; Litomska, Agnieszka; Richter, Klaus; Beerhues, Ludger; Hertweck, Christian

    2013-09-27

    Sulfur for fire: The molecular basis for the biosynthesis of the antimetabolite 6-thioguanine (6TG) was unveiled in Erwinia amylovora, the causative agent of fire blight. Bioinformatics, heterologous pathway reconstitution in E. coli, and mutational analyses indicate that the protein YcfA mediates guanine thionation in analogy to 2-thiouridylase. Assays in planta and in cell cultures reveal for the first time a crucial role of 6TG in fire blight pathogenesis.

  15. Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps

    Directory of Open Access Journals (Sweden)

    Chih-Chia Su

    2015-04-01

    Full Text Available Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.

  16. Tumor targeting using liposomal antineoplastic drugs

    OpenAIRE

    Jörg Huwyler; Jürgen Drewe; Stephan Krähenbühl

    2008-01-01

    Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles) have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of applicatio...

  17. Antineoplastic drugs: Occupational exposure and health risks

    OpenAIRE

    Fransman, W.

    2006-01-01

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

  18. Serine deprivation enhances antineoplastic activity of biguanides.

    Science.gov (United States)

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

    2014-12-15

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

  19. The combination effects of bendamustine with antimetabolites against childhood acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Goto, Shoko; Goto, Hiroaki; Yokosuka, Tomoko

    2016-05-01

    Bendamustine combined with other drugs is clinically efficacious for some adult lymphoid malignancies, but to date there are no reports of the use of such combinatorial approaches in pediatric patients. We investigated the in vitro activity of bendamustine combined with other antimetabolite drugs on B cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines established from pediatric patients with refractory or relapsed ALL. We also developed a mathematically drown improved isobologram method to assess the data objectively. Three BCP-ALL cell lines; YCUB-2, YCUB-5, and YCUB-6, were simultaneously exposed to various concentrations of bendamustine and cladribine, cytarabine, fludarabine, or clofarabine. Cell growth inhibition was determined using the WST-8 assay. Combinatorial effects were estimated using our improved isobologram method with IC80 (drug concentration corresponding to 80 % of maximum inhibition). Bendamustine alone inhibited ALL cell growth with mean IC80 values of 11.30-18.90 μg/ml. Combinations of bendamustine with other drugs produced the following effects: (1) cladribine; synergistic-to-additive on all cell lines; (2) cytarabine; synergistic-to-additive on YCUB-5 and YCUB-6, and synergistic-to-antagonistic on YCUB-2; (3) fludarabine; additive-to-antagonistic on YCUB-5, and synergistic-to-antagonistic on YCUB-2 and YCUB-6; (4) clofarabine; additive-to-antagonistic on all cell lines. Flow cytometric analysis also showed the combination effects of bendamustine and cladribine. Bendamustine/cladribine or bendamustine/cytarabine may thus represent a promising combination for salvage treatment in childhood ALL. PMID:26886449

  20. Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations

    Directory of Open Access Journals (Sweden)

    Tourkova Irina L

    2009-07-01

    Full Text Available Abstract The dose-delivery schedule of conventional chemotherapy, which determines its efficacy and toxicity, is based on the maximum tolerated dose. This strategy has lead to cure and disease control in a significant number of patients but is associated with significant short-term and long-term toxicity. Recent data demonstrate that moderately low-dose chemotherapy may be efficiently combined with immunotherapy, particularly with dendritic cell (DC vaccines, to improve the overall therapeutic efficacy. However, the direct effects of low and ultra-low concentrations on DCs are still unknown. Here we characterized the effects of low noncytotoxic concentrations of different classes of chemotherapeutic agents on human DCs in vitro. DCs treated with antimicrotubule agents vincristine, vinblastine, and paclitaxel or with antimetabolites 5-aza-2-deoxycytidine and methotrexate, showed increased expression of CD83 and CD40 molecules. Expression of CD80 on DCs was also stimulated by vinblastine, paclitaxel, azacytidine, methotrexate, and mitomycin C used in low nontoxic concentrations. Furthermore, 5-aza-2-deoxycytidine, methotrexate, and mitomycin C increased the ability of human DCs to stimulate proliferation of allogeneic T lymphocytes. Thus, our data demonstrate for the first time that in low noncytotoxic concentrations chemotherapeutic agents do not induce apoptosis of DCs, but directly enhance DC maturation and function. This suggests that modulation of human DCs by noncytotoxic concentrations of antineoplastic drugs, i.e. chemomodulation, might represent a novel approach for up-regulation of functional activity of resident DCs in the tumor microenvironment or improving the efficacy of DCs prepared ex vivo for subsequent vaccinations.

  1. Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes.

    NARCIS (Netherlands)

    Fransman, W.; Roeleveld, N.; Peelen, S.J.M.; Kort, W. de; Kromhout, H.; Heederik, D.

    2007-01-01

    BACKGROUND: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive. METHODS: Self-administered q

  2. Nurses with dermal exposure to antineoplastic drugs: Reproductive outcomes

    NARCIS (Netherlands)

    Fransman, W.; Roeleveld, N.; Peelen, S.; Kort, W.de; Kromhout, H.; Heederik, D.

    2007-01-01

    BACKGROUND: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive. METHODS: Self-administered q

  3. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

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

  4. Liposomes as delivery systems for antineoplastic drugs

    Science.gov (United States)

    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.

  5. Hospital surfaces contamination with antineoplastic drugs: influence of cleaning procedures

    OpenAIRE

    Oliveira, Ana Cebola; Pádua, Mário; Viegas, Susana

    2016-01-01

    Introduction: The raising frequency of cancer diseases is leading to a widespread application of antineoplastic drugs, thus increasing the probability of workplace surfaces contamination. Most of these drugs are classified by the International Agency for Research on Cancer as known or suspected human carcinogens. Skin absorption is the main route for antineoplastic drugs exposure in occupational settings, therefore cleaning protocols have paramount influence in surfaces contamination and, con...

  6. Antineoplastic Effects of Honey Bee Venom

    Directory of Open Access Journals (Sweden)

    Mohammad Nabiuni

    2013-08-01

    Full Text Available Background: Bee venom (BV, like many other complementary medicines, has been used for thousands of years for the treatment of a range of diseases. More recently, BV is also being considered as an effective composition for the treatment of cancer. Cancer is a major worldwide problem. It is obvious that the identification of compounds that can activate apoptosis could be effective on the treatment of cancer. BV is a very complicated mixture of active peptides, enzymes, and biologically active amines. The two main components of BV are melittin and phospholipase A2 (PLA2. Of these two components, melittin, the major active ingredient of BV, has been identified to induce apoptosis and to possess anti-tumor effects. We tried to review antineoplastic effects of BV in this study. Materials and Methods: The related articles were derived from different data bases such as PubMed, Elsevier Science, and Google Scholar using keywords including bee venom, cancer, and apoptosis.Results: According to the results of this study, BV can induce apoptosis and inhibit tumor cell growth and metastasis. Results of in vivo experiments show that the anti-tumor effect of the BV is highly dependent on the manner of injection as well as the distance between the area of injection and the tumor cells.Conclusion: The results obtained from the reported studies revealed that BV has anti-cancer effects and can be used as an effective chemotherapeutic agent against tumors in the future.

  7. Efficacy, safety, and lack of interactions with the use of raltegravir in HIV-infected patients undergoing antineoplastic chemotherapy

    Directory of Open Access Journals (Sweden)

    Sara Bañón

    2014-11-01

    Full Text Available Introduction: Concomitant use of combination antiretroviral regimen (cART and cancer chemotherapy is difficult due to complex interactions and increased toxicity. Raltegravir could be an adequate option through its favourable drug-drug interaction profile. Methods: Prospective longitudinal study of HIV patients with cancer, AIDS related or not, undergoing chemotherapy. Patients without resistance or previous failure were switched or initiated raltegravir plus two nucleoside analogues. Plasma trough levels of raltegravir were measured. Results: Overall, 28 patients receiving a raltegravir-based regimen (4 naive with tenofovir-emtricitabine (18 cases or abacavir-lamivudine (10 cases were included. Mean age was 46.2 years (IQR, 39–52.7, and 79% were male. Median time of HIV was 201.7 months, CD4+ nadir was 268 cells/mm3, and 75% had previous AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with efavirenz. Ten patients had a non-HIV-related cancer (three breast, two pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one parotid adenocarcinoma, one lung, and 18 had an HIV-related cancer (nine non-Hodgkin lymphoma, seven Hodgkin disease, two anal. Overall, 43% of patients received more than one line of chemotherapy, including antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine, alkylating agents in 12 cases (ciclophosphamide, iphosphamide, vinca alkaloids in 20 patients (vincristine, vinblastine, vindesine, antitumor antibiotics in 16 cases (adriamycin, cisplatin o carboplatin in six and monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab. Six patients modified the doses of antineoplastic agents due to toxicity (four neutropenia, not related to raltegravir. During a median follow up of 12.7 patients-year in concomitant therapy, there was only 1 case of virological failure and no patient discontinued raltegravir. Plasma concentrations of raltegravir in eight

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

    Science.gov (United States)

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

    2016-08-01

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

  9. Approval of antineoplastic agents in India: comparison with the US and EU regions

    OpenAIRE

    Bhaven C. Kataria; Dimple S. Mehta; Sunita B Chhaiya

    2012-01-01

    Background: The antineoplastic drugs are prescribed for the treatment of cancer, which is an important cause of mortality in India; therefore, a drug lag in the availability of antineoplastic drugs is a direct threat to life. The present study was undertaken to assess the drug lag for new antineoplastic agents in India compared with that in the United States (US) or European Union (EU). Methods: The new antineoplastic agents approved in the United States, European Union and India between 1999...

  10. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-06-27

    ... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 AGENCY: National Institute for Occupational... Prevention (CDC) announces the publication of the following document entitled ``NIOSH List of Antineoplastic... Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings...

  11. Metabolic activation and antineoplastic-selective mechanism of action of two novel fluoropyrimidines

    International Nuclear Information System (INIS)

    The coadministration of tetrahydrouridine (H4Urd) diverted the metabolism of 3H-5-fluoro-2'-deoxycytidine (FdCyd) in human epidermoid laryngeal carcinoma (HEp-2) cells through the deoxycytidine kinase-deoxycytidylate deaminase (dCK-dCMPD) pathway to the formation of 5-fluorodeoxyuridylate (FdUMP) without the incorporation of 5-fluorouridylate (FUMP) into RNA or the formation of RNA-level antimetabolite pools. Antimetabolite pool sizes, as assayed by HPLC, following treatment of BD2F1 mice bearing ascitic mammary adenocarcinoma-755 (ADC-755) or Lewis lung carcinoma (LLC) with 3H-FdCyd + H4 Urd resulted in pool sizes indicative of a tumor-selective, dual pathway metabolism of FdCyd via both the cytidine deaminase-deoxythymidine kinase (CD-dTK) and dCK-dCMPD pathways. In contrast to the high levels of all RNA- and DNA-level antimetabolites derived from FdCyd found in tumor tissue, in normal tissues (bone marrow, intestine, liver and spleen) and in serum, FdCyd was metabolized to only a small extent, all antimetabolite pools were markedly lower. 3H-FdCyd + H4Urd exposure resulted in selective incorporation of antimetabolites into tumor RNA and DNA. dCMPD and CD enzyme assays have confirmed that H4Urd administration effectively inhibited the low CD activity in normal, but not the elevated levels found in tumor tissue

  12. Genotoxic assessment in different exposure groups working with antineoplastic agents

    OpenAIRE

    Ladeira, Carina; Viegas, Susana; Pádua, Mário; Carolino, Elisabete; Gomes, Manuel C.; Brito, Miguel

    2015-01-01

    Antioneoplastic drugs are widely used in treatment of cancer, and several studies suggest acute and long-term effects associated to antineoplastic drug exposures, namely associating workplace exposure with health effects. Cytokinesis blocked micronucleus (CBMN) assay is one promising short-term genotoxicity assays for human risk assessment and their combination is recommended to monitor populations chronically exposed to genotoxic agents. The aim of this investigation is the genotoxicity asse...

  13. The Effect of Genetic Polymorphism upon Antineoplastic Sensitivity

    Institute of Scientific and Technical Information of China (English)

    Jun Liang

    2006-01-01

    In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.

  14. Oral Antineoplastic Agents: Assessing the Delay in Care

    Directory of Open Access Journals (Sweden)

    Brandi Anders

    2015-01-01

    Full Text Available The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additional information, including prescribed medication, indication, insurance coverage, patient assistance program use, dispensing pharmacy, and prior authorization requirements. The data was analyzed through multivariate statistical analysis and used to identify risk factors that may significantly increase the time to medication receipt. A total of 58 patients were included in the study. A median of 8 days elapsed between when the medication was prescribed and when it was received by the patient. Medication prescribed, absence of a Risk Evaluation Mitigation Strategies (REMS program, and insurance type are factors that increased time to medication receipt. An understanding of the median time involved, as well as factors affecting the time to delivery of prescriptions, will help healthcare providers better plan and prepare for the use of oral antineoplastic agents.

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

    Science.gov (United States)

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

    2002-02-01

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

  16. A pooled analysis to study trends in exposure to antineoplastic drugs among nurses.

    NARCIS (Netherlands)

    Fransman, W.; Peelen, S.J.M.; Hilhorst, S.; Roeleveld, N.; Heederik, D.; Kromhout, H.

    2007-01-01

    OBJECTIVES: Several studies have shown that exposure to antineoplastic drugs can cause toxic effects on reproductive health as well as carcinogenic effects. Numerous studies have corroborated that hospital workers are exposed to these drugs. This study focused on trends in exposure to antineoplastic

  17. 78 FR 33097 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014: Proposed...

    Science.gov (United States)

    2013-06-03

    ... HUMAN SERVICES Centers for Disease Control and Prevention NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014: Proposed Additions and Deletions to the NIOSH Hazardous Drug... following draft document for public comment entitled ``NIOSH List of Antineoplastic and Other...

  18. 76 FR 46299 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012: Proposed...

    Science.gov (United States)

    2011-08-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012: Proposed Additions and Deletions to the NIOSH Hazardous Drug... following draft document for public comment entitled ``NIOSH List of Antineoplastic and Other...

  19. Approval of antineoplastic agents in India: comparison with the US and EU regions

    Directory of Open Access Journals (Sweden)

    Bhaven C. Kataria

    2012-02-01

    Full Text Available Background: The antineoplastic drugs are prescribed for the treatment of cancer, which is an important cause of mortality in India; therefore, a drug lag in the availability of antineoplastic drugs is a direct threat to life. The present study was undertaken to assess the drug lag for new antineoplastic agents in India compared with that in the United States (US or European Union (EU. Methods: The new antineoplastic agents approved in the United States, European Union and India between 1999 and 2011 were identified and information was gathered primarily from the websites of regulatory agencies of the three regions. We assessed absolute and relative drug lag for new antineoplastic agents approved in the three regions. Results: Of the 70 new antineoplastic agents, 64 (91.42% were approved in the United States, 54 (77.14% in the European Union and 44 (62.85% in India. The US was the first to approve 59 (84.28% out of the 70 new antineoplastic agents, the EU was the first to approve 9 (12.85% and India was the first to approve 2 (2.85%. The median approval lag for India (26.35 months was higher as compared to the United States (0 month and European Union (7.3 months. Conclusions: This study confirms that India's drug lag in the case of new antineoplastic agents is higher as compared to the US and EU. Further detailed analyses are necessary to find the reasons and impacts of drug lag for antineoplastic agents in India. [Int J Basic Clin Pharmacol 2012; 1(1.000: 13-21

  20. Autophagy process is associated with anti-neoplastic function

    Institute of Scientific and Technical Information of China (English)

    Chong Wang; Yachen Wang; Michael A. McNutt; Wei-Guo Zhu

    2011-01-01

    Autophagy is a highly conserved process of cellular degradation, which is present in yeast, plants, and mammals.Under normal physiological conditions, autophagy acts to maintain cellular homeostasis and regulate the turnover of organelles.In response to cellular stresses, autophagy prevents the accumulation of impaired proteins and organelles, which serves to inhibit carcinogenesis.On this basis,it is widely accepted that most tumor suppressors, such as beclin 1 associated proteins, forkhead box class O (FoxO)family proteins, multiple mammalian target of Rapamycin (mTOR) inactivators, and nuclear p53 play a role in indu cing autophagy.Here, we focus on how the process of autophagy is associated with anti-neoplastic function.

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

    Science.gov (United States)

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

    2015-05-01

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

  2. "Sister Chromatid Exchanges and Micronuclei in Lymphocyte of Nurses Handling Antineoplastic Drugs"

    Directory of Open Access Journals (Sweden)

    M Ansari-Lari

    2001-07-01

    Full Text Available Individuals handling antineoplastic drugs or their wastes may absorb these potent genotoxic agents. The effects of handling antineoplastic drugs were examined in a group of 24 nurses working in the hematology and oncology departments of two different university hospitals in Shiraz (Iran and in a group of 18 unexposed nurses as control group. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs and micronuclei (Mn in circulating lymphocytes. A significant increased frequencies of SCE and Mn is observed in circulating lymphocytes. A significant increased frequencies of SCE and Mn is observed in nurses in daily contact with antineoplastic drugs as compared to control group.

  3. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-07-12

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

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

    Science.gov (United States)

    ... 68:16.04 Estrogens Not in AHFS (nonsteroidal synthetic estrogen) 76:00 Oxytocics 10:00 Antineoplastic agents ... Raltitrexed Ribavirin Streptozocin Tacrolimus Tamoxifen Temozolomide Teniposide Testolactone Testosterone Thalidomide Thioguanine Thiotepa Topotecan Toremifene citrate Tositumomab Tretinoin ...

  5. The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    Wanli Liu; Zhongyao Wu

    2005-01-01

    Purpose: To study cyclosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs.Methods: To study the growth curve of cyclosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyclosporine A combined with seven antineoplastic drugs.Results: The average IC50 of cyclosporine A on the 27 retinoblastoma cells is 67.81μg/ml and the average inhibitive rate of these samples is 26.1% when cyclosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyclosporine A and the increasing average inhibitive rate is more than 5.Conclusion: Cyclosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells.

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

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-05-01

    The study population consisted of 46 exposed subjects working as pharmacists, pharmacy technicians, and nurses that handle antineoplastic drugs of two hospital units, and 46 unexposed control subjects. Isolated lymphocytes were cryopreserved following the protocols of Duthie et a

  7. 392 Lung Toxicity Induced by Novel Antineoplastic Therapies in Cancer Patients

    OpenAIRE

    Syrigos, Kostas N.; Vassos, Dimitrios; Makrilia, Nektaria; Tsimpoukis, Sotirios; Politi, Ekaterini; Dannos, Ioannis; Syrigou, Ekaterini

    2012-01-01

    Background Pulmonary toxicity and respiratory failure are major adverse events complicating the use of novel antineoplastic agents in the treatment of lung cancer. We aim to investigate the risk and characteristics of cytostatic-induced pulmonary toxicity caused by agents currently used to treat lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results Almost all categories of antineoplastic agents have been associated wit...

  8. Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations

    OpenAIRE

    Feng, Y.; Tsao, S; Tang, J; Wang, N.; Curtain, R; Wang, Y.

    2009-01-01

    Ethnopharmacological relevance: Coptidis Rhizoma (Huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of Huangliang in treating diseases by removing damp-heat and purging fire and counteracting toxicity. Aim of the review: To trace the long history of the traditional use of Huanglian from folk medicines, especially from Chinese medic...

  9. Interactive effects of antifungal and antineoplastic agents on yeasts commonly prevalent in cancer patients.

    OpenAIRE

    Ghannoum, M. A.; Motawy, M S; Abu Hatab, M A; Abu Elteen, K H; Criddle, R. S.

    1989-01-01

    The effects of combinations of antifungal and antineoplastic drugs on inhibition of the growth of yeasts which commonly infect cancer patients have been analyzed. It was shown that (i) inhibitory drug combinations could be selected in which all drugs were at levels far below their individual MICs; (ii) interactive effects among antineoplastic and antifungal drugs may be very large; (iii) optimum combinations of drugs for inhibition of yeast growth depended upon both the relative and absolute ...

  10. "Sister Chromatid Exchanges and Micronuclei in Lymphocyte of Nurses Handling Antineoplastic Drugs"

    OpenAIRE

    Ansari-Lari, M; M.Saadat; Shahryari, M.; DD Farhud

    2001-01-01

    Individuals handling antineoplastic drugs or their wastes may absorb these potent genotoxic agents. The effects of handling antineoplastic drugs were examined in a group of 24 nurses working in the hematology and oncology departments of two different university hospitals in Shiraz (Iran) and in a group of 18 unexposed nurses as control group. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs) and micronuclei (Mn) in circulating lymphocytes. ...

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

    OpenAIRE

    MÖHLER, HANS; PFIRMAN, ROLF W.; Frei, Karl

    2014-01-01

    Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the...

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

    Science.gov (United States)

    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

  13. Dental anomalies in children submitted to antineoplastic therapy

    Directory of Open Access Journals (Sweden)

    Camila Merida Carrillo

    2014-06-01

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

  14. Antineoplastic mechanisms of Iodine in cancers that take up Iodine

    Directory of Open Access Journals (Sweden)

    Carmen Aceves

    2015-12-01

    Full Text Available Purpose: In addition to being a component of thyroid hormone (TH, iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine.Methods and Results: Studies from our laboratory shown that in preclinical (cell culture, induced animal cancer and xenographs and clinical studies (mammary cancer protocol, molecular iodine (I2 supplementation exerts suppressive effects on implantation, development, and progression of cancer neoplasias. These effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine modulates the immune/tumor response and through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma (PPARγ triggering apoptotic and/or differentiation pathways.Conclusion: The absence of side effects and the easy availability and handling of I2 have allowed the establishment of clinical protocols to utilize I2 supplementation as an adjuvant in therapies against cancers that take up iodine.-----------------------------------------Cite this article as:  Aceves C, Anguiano B. Antineoplastic mechanisms of Iodine in cancers that take up Iodine. Int J Cancer Ther Oncol 2015; 3(4:3401.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.

  15. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

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

    2014-01-01

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

  16. Antineoplastic effects of mammalian target of rapamycine inhibitors.

    Science.gov (United States)

    Salvadori, Maurizio

    2012-10-24

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

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

    Directory of Open Access Journals (Sweden)

    Panagiota Papanagnou

    2016-05-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Tamar Canello

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

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

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

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

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

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

    On dispensing powdered antineoplastic medicines, it is important to prevent cross-contamination and environmental exposure. Recently, we developed a method for blending powdered medicine in a disposable ointment container using a planetary centrifugal mixer. The disposable container prevents cross-contamination. In addition, environmental exposure associated with washing the apparatus does not arise because no blending blade is used. In this study, we aimed to confirm the uniformity of the mixture and weight loss of medicine in the blending procedure. We blended colored lactose powder with Leukerin(®) or Mablin(®) powders using the new method and the ordinary pestle and mortar method. Then, the blending state was monitored using image analysis. Blending variables, such as the blending ratio (1:9-9:1), container size (35-125 mL), and charging rate (20-50%) in the container were also investigated under the operational conditions of 500 rpm and 50 s. At a 20% charging rate in a 35 mL container, the blending precision of the mixtures was not influenced by the blending ratio, and was less than 6.08%, indicating homogeneity. With an increase in the charging rate, however, the blending precision decreased. The possible amount of both mixtures rose to about 17 g with a 20% charging rate in a 125 mL container. Furthermore, weight loss of medicines with this method was smaller than that with the pestle and mortar method, suggesting that this method is safer for pharmacists. In conclusion, we have established a precise and safe method for blending powdered medicines in pharmacies. PMID:24790050

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

    Directory of Open Access Journals (Sweden)

    Kwak TW

    2015-04-01

    Full Text Available Tae Won Kwak,1,* Hee Jae Shin,2,* Young-Il Jeong,1 Myoung-Eun Han,3 Sae-Ock Oh,3 Hyun-Jung Kim,4 Do Hyung Kim,5 Dae Hwan Kang1 1Biomedical Research Institute, Pusan National University Hospital, Busan, 2Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 3Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, 4Genewel Co Ltd. Gyeonggi-do, 5School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea *These authors contributed equally to this work Background: The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods: The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results: Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight

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

    Science.gov (United States)

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

    2001-09-15

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

  3. Off-Label and Off-NCCN Guidelines Uses of Antineoplastic Drugs in China

    OpenAIRE

    Weilan Wang; Man Zhu; Daihong Guo; Chao Chen; Dongxiao Wang; Fei Pei; Liang Ma

    2013-01-01

    Background To evaluate off-label and off-NCCN guidelines uses of antineoplastic drugs in a major Chinese hospital. Methods: Totally 1122 patients were selected from July to December 2011. Then, the off-label and off-NCCN guidelines uses of antineoplastic drugs were analyzed. Results: In 798 of 1122 patients (71.12%), drugs were used for off-label. In 317 of 1122 patients (28.25%), the drugs were prescribed for off-label and off-NCCN guidelines. 2591 medical orders for 1122 patients, 1051/2591...

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

    Directory of Open Access Journals (Sweden)

    Bobbak Vahid

    2008-01-01

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

  5. Anti-neoplastic efficacy of Haimiding on gastric carcinoma and its mechanisms

    Institute of Scientific and Technical Information of China (English)

    Yu-Bin Ji; Shi-Yong Gao; Hong-Rui Ji; Qi Kong; Xiu-Juan Zhang; Bao-Feng Yang

    2004-01-01

    AIM: To study the anti-neoplastic effect of Haimiding and its mechanisms of action.METHODS: Experiments using MTT and colony formation were carried out to study thein vitro anti-neoplastic action of Haimiding, its in vivo anti-neoplastic action was studied by observing its effect on the weight of tumors in FC mice and S180, H22 tumor bearing mice, as well as their life spans.The effect of Haimiding on cell apoptosis and different stages of cell cycles in human gastric carcinoma cells were studied by flow cytometry. Its effect on [Ca2+]i of human gastric carcinoma cells and the source of Ca2+ during the change of [Ca2+]i were observed by confocal laser scanning technique.RESULTS: Haimiding showed a definite cytotoxicity to 8 human tumor cell lines, which was most prominent against BGC-823, Eca-109 and HCT-8 tumor cells. It also exhibited an obvious inhibition on colony formation of the above tumor cell lines, which was most prominent in Eca-109 tumor cells. It showed obvious inhibition on the growth of tumor in FC mice and S180 bearing mice as well as prolonged the life span of H22 bearing mice. It was able to induce apoptosis and elevate intracellular [Ca2+]i concentration of tumor cells.The source of Ca2+ came from both extracellular Ca2+ influx and intracellular Ca2+ release.CONCLUSION: Haimiding is composed of a TCM preparation and 5-flurouracil. Its anti-neoplastic potency is highly enhanced by synergism as compared with either one of its components. Its mechanisms of anti-neoplastic action can be attributed to its action to initiate apoptosis of tumor cells by opening the membrane calcium channel and inducing intracellular Ca2+ release to elevate [Ca2+]i of the tumor cells.

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

    Science.gov (United States)

    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

  7. Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the "Apact" Study)

    Science.gov (United States)

    2016-06-22

    Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Digestive System Diseases; Endocrine System Diseases; Gemcitabine; Antimetabolites, Antineoplastic

  8. Drug lag for antineoplastic and immunomodulating agent approvals in India compared with the US and EU approvals

    Directory of Open Access Journals (Sweden)

    Bhaven C. Kataria

    2016-04-01

    Conclusions: This study confirms that India lag behind the US and EU regions in terms of total number of new drug approvals for antineoplastic and immunomodulating agents. There is a substantial approval delay in India compared to the US and EU regions. Further detailed analyses are necessary to find the reasons and impacts of drug lag for new antineoplastic and immunomodulating agents in India. [Int J Basic Clin Pharmacol 2016; 5(2.000: 335-340

  9. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    OpenAIRE

    Chavez-Blanco, Alma; Perez-Plasencia, Carlos; Perez-Cardenas, Enrique; Carrasco-Legleu, Claudia; Rangel-Lopez, Edgar; Segura-Pacheco, Blanca; Taja-Chayeb, Lucia; Trejo-Becerril, Catalina; Gonzalez-Fierro, Aurora; Candelaria, Myrna; Cabrera, Gustavo; Duenas-Gonzalez, Alfonso

    2006-01-01

    Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazi...

  10. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    OpenAIRE

    Candelaria Myrna; Gonzalez-Fierro Aurora; Trejo-Becerril Catalina; Taja-Chayeb Lucia; Segura-Pacheco Blanca; Rangel-Lopez Edgar; Carrasco-Legleu Claudia; Perez-Cardenas Enrique; Perez-Plasencia Carlos; Chavez-Blanco Alma; Cabrera Gustavo; Duenas-Gonzalez Alfonso

    2006-01-01

    Abstract Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results ...

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

    OpenAIRE

    Carina Ladeira; Susana Viegas; Gomes, Manuel C.

    2015-01-01

    Antineoplastic drugs are a heterogeneous group of chemicals used in the treatment of cancer, and have been proved by IARC to be mutagens, carcinogens and teratogens agents (Fucic et al., 1998; Burgaz et al., 1999; Sessink & Bos, 1999; Bouraoui et al., 2011; Gulten et al., 2011; Buschini et al., 2013). In general, chemicals that interact directly with DNA by biding covalently or by intercalating, or indirectly by interfering with DNA synthesis, were among the first chemotherapeutics developed ...

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

    OpenAIRE

    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 ...

  13. Can occupational exposure to antineoplastic drugs increase levels of an inflammatory trigger?

    OpenAIRE

    T. Kamalasundar; Padmaja Udaykumar; Prabin Shah

    2015-01-01

    Background: Antineoplastic drugs (AND) are known to cause collateral damage to normal cells by oxidative stress. This study was conducted to check for oxidative stress in occupational exposure to these drugs using advanced oxidation protein products (AOPP). Methods: Cross-sectional comparison of serum AOPP levels of 33 nurses occupationally exposed and serum AOPP levels of 30 nurses not exposed using modified AOPP method. Results: Serum AOPP levels were significantly increased (p

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

    OpenAIRE

    Soriano-Hernandez, Alejandro D; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; Martinez-Fierro, Margarita L; Laura L. Valdez-Velazquez; 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 ...

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

    OpenAIRE

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

  16. Reversible posterior leukoencephalopathy syndrome and anti-neoplastic agents: a review

    OpenAIRE

    Farheen M. Shah-Khan; Prabodh Shah; Daryl Pinedo

    2011-01-01

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS) is a well recognized entity with a variety of benign and malignant conditions. Recently it has been found to be associated with the use of anti-neoplastic agents including targeted therapies. RPLS occurs rapidly with the use of some drugs and more slowly with others. Combined therapies are associated with a more frequent and more rapid presentation. This review was based on a literature search for English Language articles concerning RP...

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

    OpenAIRE

    Sima, Peter; Vetvicka, Vaclav

    2011-01-01

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed....

  18. Monitoring of Oxidative Stress in Nurses Occupationally Exposed to Antineoplastic Drugs

    OpenAIRE

    Mahboob, M.; Rahman, M. F.; Rekhadevi, P. V.; Sailaja, N.; Balasubramanyam, A; Prabhakar, P. V.; Singh, Shailendra Pratap; Reddy, Utkarsh A.; Rao, G. Sankara; Grover, Paramjit

    2012-01-01

    Antineoplastic drugs (ANDs) have been in clinical usage for more than five decades. The nonselective mechanism of action of ANDs between cancerous and noncancerous cells had well documented side effects such as acute symptoms, reproductive health issues, and potential cancer development in healthcare workers as a result of occupational exposure. The anticancer mechanism of ANDs is the generation of reactive oxygen species (ROS) which are responsible for various side effects in patients underg...

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

    OpenAIRE

    Hon, Chun-Yip; Teschke, Kay; Chua, Prescillia; Venners, Scott; Nakashima, Lynne

    2011-01-01

    Objectives Studies examining healthcare workers' exposure to antineoplastic drugs have focused on the drug preparation or drug administration areas. However, such an approach has probably underestimated the overall exposure risk as the drugs need to be delivered to the facility, transported internally and then disposed. The objective of this study is to determine whether drug contamination occurs throughout a facility and, simultaneously, to identify those job categories that are potentially ...

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

    OpenAIRE

    Lars Tatenhorst; Eric Hahnen; Heneka, Michael T

    2008-01-01

    The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studie...

  1. Cancer incidence and adverse pregnancy outcome in registered nurses potentially exposed to antineoplastic drugs

    OpenAIRE

    Le Nhu D; Teschke Kay; Chow Yat; Lorenzi Maria; Beking Kris; Spinelli John J; Ratner Pamela A; Gallagher Richard P; Dimich-Ward Helen

    2010-01-01

    Abstract Background To determine the relationships of potential occupational exposure to antineoplastic drugs with cancer incidence and adverse pregnancy outcomes in a historical prospective cohort study of female registered nurses (RNs) from British Columbia, Canada (BC). Methods Female RNs registered with a professional regulatory body for at least one year between 1974 and 2000 formed the cohort (n = 56,213). The identifier file was linked to Canadian cancer registries. An RN offspring coh...

  2. Low Concentration of Quercetin Antagonizes the Cytotoxic Effects of Anti-Neoplastic Drugs in Ovarian Cancer

    OpenAIRE

    Na Li; Chaoyang Sun; Bo Zhou; Hui Xing; Ding Ma; Gang Chen; Danhui Weng

    2014-01-01

    OBJECTIVE: The role of Quercetin in ovarian cancer treatment remains controversial, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of Quercetin in combination with Cisplatin and other anti-neoplastic drugs in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. METHODS: Quercetin treatment at various concentrations was examined in combination with Cisplatin, taxol, Pirarubicin and 5-Fu in human epithelial...

  3. Study on Chromosome Damage Among Nurses Occupationally Exposed to Antineoplastic Drugs in an Oncology Department

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ INTRODUCTION Many antineoplastic agents have been shown to be mutagenic, teratogenic and carcinogenic in experimental animals and in vitro test systems. Epidemiological data on the association of secondary neoplasms with a specific chemotherapeutic treatment are available on some 30 agents. Several previous studies concerning hospital personnel have indicated that occupational exposure to cytostatic drugs may be detected by genotoxicological biomonitoring methods, e.g., comet assay, SCEs, chromosomal aberration and micronucleus test.

  4. Isolation and Characterization of Antineoplastic Alkaloids from Catharanthus Roseus L. Don. Cultivated in Egypt

    OpenAIRE

    Shams, Khaled A; Nazif, Naglaa M; Abdel Azim, Nahla S; Abdel Shafeek, Khaled A; El-Missiry, Mostafa M.; Ismail, Shams I; Seif El Nasr, Medhat M

    2009-01-01

    Vinblastine and vincristine (the antileukemic agents) were isolated, in a pure form, from Catharanthus roseus L. Don., cultivated in Egypt, by several chromatographic techniques. Five modified methods for the preparation of total alkaloids were carried out. All the isolated mixtures were evaluated by HPLC and HPTLC analyses. The antineoplastic alkaloids; vinblastine and vincristine, were isolated by the use of vacuum liquid chromatographic column on silica gel : aluminium oxide (1:1) mixed be...

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

    Science.gov (United States)

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

    2014-10-01

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

  6. Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer

    Directory of Open Access Journals (Sweden)

    Velazquez-Torres Guermarie

    2010-02-01

    Full Text Available Abstract Background Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women. Results The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination. Conclusions It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.

  7. Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available OBJECTIVE: The role of Quercetin in ovarian cancer treatment remains controversial, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of Quercetin in combination with Cisplatin and other anti-neoplastic drugs in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. METHODS: Quercetin treatment at various concentrations was examined in combination with Cisplatin, taxol, Pirarubicin and 5-Fu in human epithelial ovarian cancer C13* and SKOV3 cells. CCK8 assay and Annexin V assay were for cell viability and apoptosis analysis, immunofluorescence assay, DCFDA staining and realtime PCR were used for reactive oxygen species (ROS-induced injury detection and endogenous antioxidant enzymes expression. Athymic BALB/c-nu nude mice were injected with C13*cells to obtain a xenograft model for in vivo studies. Immunohistochemical analysis was carried out to evaluate the ROS-induced injury and SOD1 activity of xenograft tumors. RESULTS: Contrary to the pro-apoptotic effect of high concentration (40 µM-100 µM of Quercetin, low concentrations (5 µM-30 µM of Quercetin resulted in varying degrees of attenuation of cytotoxicity of Cisplatin treatment when combined with Cisplatin. Similar anti-apoptotic effects were observed when Quercetin was combined with other anti-neoplastic agents: Taxol, Pirarubicin and 5-Fluorouracil (5-Fu. Low concentrations of Quercetin were observed to suppress ROS-induced injury, reduce intracellular ROS level and increase the expression of endogenous antioxidant enzymes, suggesting a ROS-mediated mechanism of attenuating anti-neoplastic drugs. In xenogeneic model, Quercetin led to a substantial reduction of therapeutic efficacy of Cisplatin along with enhancing the endogenous antioxidant enzyme expression and reducing ROS-induced damage in xenograft tumor tissue. CONCLUSION: Taken together, these data suggest that Quercetin at low concentrations

  8. Can the clinical course of cancer be influenced by non-antineoplastic drugs?

    OpenAIRE

    Brandes, L. J.; Friesen, L A

    1995-01-01

    Laboratory and anecdotal clinical evidence suggests that some common non-antineoplastic drugs may affect the course of cancer. The authors present two cases that appear to be consistent with such a possibility: that of a 63-year-old woman in whom a high-grade angiosarcoma of the forehead improved after discontinuation of lithium therapy and then progressed rapidly when treatment with carbamazepine was started, and that of a 74-year-old woman with metastatic adenocarcinoma of the colon that re...

  9. Inhibitions of Several Antineoplastic Drugs on Serum Sialic Acid Levels in Mice Bearing Tumors

    OpenAIRE

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

    2012-01-01

    Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, ...

  10. The Effect of Antineoplastic Drugs in a Male Spontaneous Mammary Tumor Model

    OpenAIRE

    Shishido, Stephanie N.; Faulkner, Emma B.; Beck, Amanda; Thu A. Nguyen

    2013-01-01

    Male breast cancer is a rare disease. The limited number of clinical cases has led to the primary treatments for men being derived from female breast cancer studies. Here the transgenic strain FVB/N-Tg(MMTV-PyVT)634Mul/J (also known as PyVT) was used as a model system for measuring tumor burden and drug sensitivity of the antineoplastic drugs tamoxifen, cisplatin, and paclitaxel on tumorigenesis at an early stage of mammary carcinoma development in a male mouse model. Cisplatin treatment sign...

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

    Directory of Open Access Journals (Sweden)

    Subhasis Das

    Full Text Available 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.

  12. Effect of implementing a cancer chemotherapy order form on prescribing habits for parenteral antineoplastics.

    Science.gov (United States)

    Pastel, D A; Fay, P; Lee, D

    1993-12-01

    Effect of implementing a cancer chemotherapy order form on prescribing habits for parenteral antineoplastics. The purpose of this study was to determine whether the use of a cancer chemotherapy order form improved prescriber inclusion of necessary prescription information to minimize errors for parenteral antineoplastics when compared to orders written on standard treatment-order forms. Standard treatment order forms and the newly developed chemotherapy order forms were examined for differences in completeness of the following 13 prescription components: diagnosis, height, weight, body surface area, start date and time, dosage (e.g., mg/m2), dose (mg), solution diluent (drips only) and volume (drips only), infusion rate (drips only), route (i.e., IV push or IV drip), frequency of administration, and total number of scheduled doses. The results demonstrate a significant improvement in completeness of necessary prescription information when cancer chemotherapy was ordered by physicians using a chemotherapy order form compared to a standard treatment order form. Importantly, the availability of various prescription components such as height, weight, and dosage may be used by the pharmacist to verify physicians' calculations of body surface area and dose and thereby reduce the chance of serious medication dosage errors. An additional benefit of the new form is a reduction in the time pharmacists spend clarifying orders.

  13. Computerized cyclic voltammetric detection after HPLC of the antineoplastic agents etoposide, teniposide, adriamycin and its metabolite adriamycinol in urine samples

    OpenAIRE

    Ploegmakers, H. H. J. L.; Moritz, P. A.; Toll, P. J. M. M.; Oort, W.J. van

    1989-01-01

    A computerized electrochemical detection system for application after HPLC, provided with a cyclic voltammetric oxidative and reductive module, is described for the on-line qualitative determination of electroactive antineoplastic agents and metabolites in urine samples, collected from cancer patients, following intravenous administration. The application of two cyclic voltammetric detection modes provides an insight into both oxidative and reductive electrode reactions of compounds, passing ...

  14. Off-Label and Off-NCCN Guidelines Uses of Antineoplastic Drugs in China

    Directory of Open Access Journals (Sweden)

    Weilan Wang

    2013-05-01

    Full Text Available Background: To evaluate off-label and off-NCCN guidelines uses of antineoplastic drugs in a major Chinese hospital.Methods: Totally 1122 patients were selected from July to December 2011. Then, the off-label and off-NCCN guidelines uses of antineoplastic drugs were analyzed.Results: In 798 of 1122 patients (71.12%, drugs were used for off-label. In 317 of 1122 patients (28.25%, the drugs were prescribed for off-label and off-NCCN guidelines. 2591 medical orders for 1122 patients, 1051/2591 (40.56% medical orders were off-label; 445/2591(17.17% medical orders were off-label and off-NCCN guidelines. In 445 off-label and off-NCCN medical orders, 399 (89.66% were unapproved indications, 38 (8.54% were unapproved drug concentration and 12 (2.70% were unapproved route of administration. Percentage of off-label and off-NCCN guidelines drug uses in male was higher than that in female (21.92% vs. 11.39%, P<0.01. Compared with other lines of treatment, percentage of off-label and off-NCCN guidelines drug uses in postoperative adjuvant was the smallest (P<0.01 and percentage in three or multi-line treatments was the highest (P<0.01. The pancreatic cancer possessed the highest percentage (38.74% of off-label and off-NCCN guidelines drug uses among all types of cancer (P<0.01.Conclusion: Off-label uses of antineoplastic drugs are generally common in China hospitals based on NCCN guidelines. The fact suggests that anti-tumor treatment was relatively standard in China. Off-label and off-NCCN guidelines drug uses were mainly for individual treatment. Doctors should fully consider the adverse drug reaction, contraindication, cautions and increase the drug security monitoring. Uncorrected drug concentration should be avoided for drug risk

  15. Experimental study on anti-neoplastic activity of epigallocatechin-3-gallate to digestive tract carcinomas

    Institute of Scientific and Technical Information of China (English)

    RAN Zhi-hua; ZOU Jian; XIAO Shu-dong

    2005-01-01

    Background Epigallocatechin-3-gallate (EGCG) has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers. Methods Methyl thiazolyl tetrazolium (MTT) analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA) protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, c-myc, p53 and mad1 genes in sensitive cancer cell line. Results EGCG exhibited dose-dependent killing effects on all eight disgestive tract cancer cell lines. The 50% inhibitory concentration (IC50) of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 μmol/L, 55.9 μmol/L, 68.5 μmol/L, 79.1 μmol/L, 83.8 μmol/L, 119.8 μmol/L, 183.2 μmol/L and 194.6 μmol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the mad1 gene increased, and that of the p53 gene unchanged. Conclusions EGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available 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.

  20. Drug lag for antineoplastic and immunomodulating agent approvals in India compared with the US and EU approvals

    OpenAIRE

    Bhaven C. Kataria; Ashna S. Pandya; Ashwin K. Panchasara; Pavan J. Panchal; Mitul R. Parmar

    2016-01-01

    Background: There is a tremendous amount of research being conducted on development of new drugs for cancer therapies. The drug development of cancer therapies has dramatically increased over the past few decades. The present study was undertaken to assess the drug lag for new antineoplastic and immunomodulating agents in India compared with that in the United States (US) or European Union (EU). Methods: The new drugs approved in the US, EU and India between 2011 and 2015 were identified a...

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

    OpenAIRE

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

    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 stud...

  2. Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth.

    OpenAIRE

    Ghannoum, M. A.; Motawy, M S; Abu Hatab, M A; Ibrahim, A.S.; Criddle, R. S.

    1989-01-01

    Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations o...

  3. Identification of Knowledge Gaps Regarding Healthcare Workers' Exposure to Antineoplastic Drugs: Review of Literature, North America versus Europe

    OpenAIRE

    Hon, Chun-Yip; Barzan, Cris; Astrakianakis, George

    2014-01-01

    We have been examining the issue of healthcare workers' exposure to antineoplastic drugs for nearly a decade and have observed that there appears to be more publications on the subject matter originating from Europe than from North America. The concern is that findings from Europe may not be generalizable to North America because of differences in handling practices, regulatory requirements, and training. Our objective was to perform a literature review to confirm our observation and, in turn...

  4. Inhibition of basal and TGF beta-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing.

    OpenAIRE

    Hendricks, T.; Martens, M F; Huyben, C M; Wobbes, T.

    1993-01-01

    Antineoplastic drugs, given in the perioperative period, are thought to be a hazard to wound repair. Since fibroblast collagen synthesis is crucial to healing, we examined the effects of bleomycin, cisplatin and 5-fluorouracil on collagen synthesis in confluent cultures of fibroblasts from human colon and skin. The drugs were added in final concentrations between 0.1 and 50 microM. Bleomycin did not affect collagen synthesis in colon fibroblasts but inhibited synthesis in skin fibroblasts. Co...

  5. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs

    OpenAIRE

    D’Angelo, Daniela; Mussnich, Paula; De Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-01-01

    Background Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcino...

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

    International Nuclear Information System (INIS)

    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

  7. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Candelaria Myrna

    2006-01-01

    Full Text Available Abstract Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.

  8. A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode

    Directory of Open Access Journals (Sweden)

    Rong Zheng

    2011-08-01

    Full Text Available The main functional components of green tea, such as epigallocatechin gallate (EGCG, epigallocatechin (EGC, epicatechin gallate (ECG and epicatechin (EC, are found to have a broad antineoplastic activity. The discovery of their targets plays an important role in revealing the antineoplastic mechanism. Therefore, to identify potential target proteins for tea polyphenols, we have taken a comparative virtual screening approach using two reverse docking systems, one based on Autodock software and the other on Tarfisdock. Two separate in silico workflows were implemented to derive a set of target proteins related to human diseases and ranked by the binding energy score. Several conventional clinically important proteins with anti-tumor effects are screened out from the PDTD protein database as the potential receptors by both procedures. To further analyze the validity of docking results, we study the binding mode of EGCG and the potential target protein Leukotriene A4 hydrolase in detail. We indicate that interactions mediated by electrostatic and hydrogen bond play a key role in ligand binding. EGCG binds to the enzyme with certain orientation and conformation that is suitable for nucleophilic attacks by several electrical residues inside the enzyme’s activity cavity. This study provides useful information for studying the antitumor mechanism of tea’s functional components. The comparative reverse docking strategy presented generates a tractable set of antineoplastic proteins for future experimental validation as drug targets against tumors.

  9. The effect of antineoplastic drugs in a male spontaneous mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Stephanie N Shishido

    Full Text Available Male breast cancer is a rare disease. The limited number of clinical cases has led to the primary treatments for men being derived from female breast cancer studies. Here the transgenic strain FVB/N-Tg(MMTV-PyVT634Mul/J (also known as PyVT was used as a model system for measuring tumor burden and drug sensitivity of the antineoplastic drugs tamoxifen, cisplatin, and paclitaxel on tumorigenesis at an early stage of mammary carcinoma development in a male mouse model. Cisplatin treatment significantly reduced tumor volume, while paclitaxel and tamoxifen did not attenuate tumor growth. Cisplatin treatment was shown to induce apoptosis, grossly observed by reduced tumor formation, through reduced Bcl-2 and survivin protein expression levels with an increase in caspase 3 expression compared to control tumors. Tamoxifen treatment significantly altered the hormone receptor expression levels of the tumor, while additionally upregulating Bcl-2 and Cyclin D1. This suggests an importance in hormonal signaling in male breast cancer pathogenesis. The results of this study provide valuable information toward the better understanding of male breast cancer and may help guide treatment decisions.

  10. A preliminary analysis of antineoplastic activity of parvovirus MVMp NS—1 proteins

    Institute of Scientific and Technical Information of China (English)

    SHENXIZHONG; HSIAOCHIENTSUNG; 等

    1997-01-01

    Human gastric cancer MKN-45 cells were transfected with pULB 3238,a plasmid carrying MVMp MS-1 gene with its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR.After the integration and expression of NS-1 gene,some of the transfectants died,while others remained alive,but the growth features of survived cells were changed.For further study on the antineoplastic function of parvoviral NS-1 protein in vivo,transgenic mice carrying NS-1 genes were established by conventional method.Among 4 founders,one of them was found to be able to transmit the transgene to around 50% of their offsprings.RT-PCR was performed to indicate the expression of NS-1 gene in transgenic mice and its mRNA appeared in a variety of tissues.The expression of integrated NS-1 gene may correlate with the decreased incidence of tumor induced in vivo by chemical carcinogens.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-04

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

  14. Reversible posterior leukoencephalopathy syndrome and anti-neoplastic agents: a review

    Directory of Open Access Journals (Sweden)

    Farheen M. Shah-Khan

    2011-12-01

    Full Text Available Reversible Posterior Leukoencephalopathy Syndrome (RPLS is a well recognized entity with a variety of benign and malignant conditions. Recently it has been found to be associated with the use of anti-neoplastic agents including targeted therapies. RPLS occurs rapidly with the use of some drugs and more slowly with others. Combined therapies are associated with a more frequent and more rapid presentation. This review was based on a literature search for English Language articles concerning RPLS and chemotherapeutic agents published from June 1996 to March 2007. We used the PubMed database with keywords: “RPLS”, “Posterior reversible encephalopathy syndrome”, “(PRES”, “Chemotherapy” and “MRI”. This syndrome has classical Clinical-Radiologic features that are easy to recognize. Early recognition and withdrawal of the offending agent is all that is needed in most cases. This review highlights the features of the syndrome. It draws our attention to an entity which is being more frequently recognized and whose exact pathologic mechanisms need to be further studied. This syndrome is associated with the use of neurotoxic as well as non-neurotoxic agents and usually runs a benign course if there is an early diagnosis and management.

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

    Science.gov (United States)

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

    1997-03-01

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

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

    Directory of Open Access Journals (Sweden)

    P.R. Koschek

    2007-10-01

    Full Text Available In the present study, we investigated the in vitro anti-tumoral activities of fractions from aqueous extracts of the husk fiber of the typical A and common varieties of Cocos nucifera (Palmae. Cytotoxicity against leukemia cells was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay. Cells (2 x 104/well were incubated with 0, 5, 50 or 500 µg/mL high- or low-molecular weight fractions for 48 h, treated with MTT and absorbance was measured with an ELISA reader. The results showed that both varieties have almost similar antitumoral activity against the leukemia cell line K562 (60.1 ± 8.5 and 47.5 ± 11.9% for the typical A and common varieties, respectively. Separation of the crude extracts with Amicon membranes yielded fractions with molecular weights ranging in size from 1-3 kDa (fraction A to 3-10 kDa (fraction B and to more than 10 kDa (fraction C. Cells were treated with 500 µg/mL of these fractions and cytotoxicity was evaluated by MTT. Fractions ranging in molecular weight from 1-10 kDa had higher cytotoxicity. Interestingly, C. nucifera extracts were also active against Lucena 1, a multidrug-resistant leukemia cell line. Their cytotoxicity against this cell line was about 50% (51.9 ± 3.2 and 56.3 ± 2.9 for varieties typical A and common, respectively. Since the common C. nucifera variety is extensively cultured in Brazil and the husk fiber is its industrial by-product, the results obtained in the present study suggest that it might be a very inexpensive source of new antineoplastic and anti-multidrug resistant drugs that warrants further investigation.

  17. An evaluation of the anti-neoplastic activity of curcumin in prostate cancer cell lines

    Directory of Open Access Journals (Sweden)

    Camila B. Piantino

    2009-06-01

    Full Text Available OBJECTIVE: The aim of our study is to investigate the anti-neoplastic effect of curcumin in prostate cancer cell lines. Specifically, we are using the LNCaP cell line and another prostate cell line developed in our laboratory, PcBra1. The PcBra1 cells were derived from a localized, obstructive prostate cancer with a Gleason score of 9 (4+5. MATERIAL AND METHODS: A prostate cancer cell line was isolated from a localized, obstructive prostate cancer with a Gleason score of 9 (4+5, and it was characterized using immunohistochemistry. After six passages, the new cell line was treated with varying doses of curcumin: 10 µM, 25 µM or 50 µM. Apoptosis was detected by flow cytometry using Annexin V FITC. For comparison, the same experiment was performed using the well-established metastatic prostate cancer cell line, LNCaP. RESULTS: Increasing concentrations of curcumin promoted more apoptosis in the PcBra1 cells. Exposure to 10 and 25 µM curcumin induced apoptosis in 31.9% and 52.2% of cells, respectively. Late apoptosis was induced in 37% of cells after treatment with 10 µM curcumin and 35% of cells with a 25 µM treatment. Necrosis accounted for less than 10% of the death in these cells at those two concentrations. When curcumin was used at 50 µM, apoptosis was observed in 64.3% of the cells. Including late apoptosis and necrosis, 98.6% of the cells died in response to 50 µM curcumin. Results with the LNCaP cells were similar although late apoptosis was the main phenomenon at 25 µM. CONCLUSION: We have shown that curcumin acts on localized prostate cancer to induce apoptosis and may therefore be an option as a future therapeutic agent.

  18. Somatostatin Enhances the Antineoplastic Effects of Tamoxifen on Breast Carcinoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    ZENGXizhi; YAOZhenxiang

    2002-01-01

    Objective:To study the antineoplastic effects of tamoxifen(TAM) in combination with a somatostain analogue(octreotide,OCT) on breast cancer.Methods:Estrogen receptor(ER)-positive(MCF-7) and ER-negative(MDA-MB-435S)human breast carcinoma cell lines were treated with TAM or OCT,or combination of both agents in vitro.Cell proliferation was evaluated by MTT assay,distribu-tion of cell cycle and rate of apoptosis were detemined by flow cytometry.Results:The inhibitory effect of OCT or TAM on proliferation of MCF-7 cells was associated with cell arrest in G0/G1 phase and induction of apoptosis.The inhibitory effect on proliferation of MCF-7 cells enhanced when treatment of TAM combined with OCT.The increased rate of apoptosis induced by combination of TAM and OCT was much higher than use of either TAM or OCT alone.TAM or OCT also had weak inhibitory effect on MDA-MB435S cell.The cells were arrested at S phase by TAM and at G0/G1 phase by OCT, but the induction of apoptosis was not identified.However,the rate of apoptosis was 22.7% if combined treatment of TAM and OCT applied.Conclusion:TAM and OCT can synergistically inhibit proliferation and induce apoptosis of ER-positive and ER-negative breast cancer cells.The synergism of TAM and OCT may be of interest in the clinical treatment of breast carcinoma.

  19. Antineoplastic effects of octreotide on human gallbladder cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing-Hua Wang; Quan-Tai Xing; Meng-Biao Yuan

    2004-01-01

    AIM: To investigate whether octreotide can inhibit the growth of human gallbladder cancer cells in vitro and to elucidate the antineoplastic mechanism of octreotide in gallbladder cancer.METHODS: A human gallbladder cancer cell line, GBC-SD,was cultured in vitro. The antiproliferative effects of octreotide were examined by means of an MTT assay and a colony forming ability assay. Morphological variation was investigated under scanning electron microscopy and transmission electron microscopy. Cell cycle analysis and apoptosis rate was evaluated by flow cytometry (FCM) after staining by propidium iodide. DNA fragmentation was assayed by agarose gel electrophoresis. Tmmunohistochemical staining was performed to evaluate the expressions of mutant-type p53 and bcl-2.RESULTS: The growth curve and colony forming ability assay showed significant inhibition of octreotide to the proliferation of GBC-SD cells in culture in a time- and dosedependent manner. After exposure to octreotide, GBC-SD cells showed typically apoptotic characteristics, including morphological changes of chromatin condensation, vacuolar degeneration, nucleus fragmentation and apoptotic body formation. In FCM profile apoptotic cells showed increased sub-G1 peaks in the octreotide group, significantly higher than the control group (P=0.013). There was also an augmentation in the cell proportion of G0/G1 phase (P=0.015), while the proportion of S phase and G2/M phase remained unchanged (P=0.057 and P=0.280, respectively).DNA agarose gel electrophoresis displayed a ladder after exposure to 1 000 nmol/L octreotide. After being treated with octreotide, the expressions of both mutant-type p53 and bcl-2 decreased considering the percentage of positive cells (P<0.05).CONCLUSION: Octreotide has a negative action to the proliferation of GBC-SD cells, and the mechanism may be related to cytostatic and cytotoxic effects. The reduction of mutant-type p53 and bcl-2 expressions may be associated with the apoptosis

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

    International Nuclear Information System (INIS)

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

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

    Directory of Open Access Journals (Sweden)

    Qu D

    2014-04-01

    Full Text Available Ding Qu,1,* Wenjie Sun,1,2,* Yan Chen,1,2 Jing Zhou,1 Congyan Liu11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department of Pharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: 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.Keywords: rapid synthesis, Agrimoniae herba extract, silver nanoparticles, A549 cells, antitumor

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

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

  4. Simultaneous detection of three antineoplastic drugs on gloves by liquid chromatography with diode array detector

    Directory of Open Access Journals (Sweden)

    Adélia Maria Pimenta de Pádua Alcântara

    2010-12-01

    Full Text Available The aim of this study was to develop a method for simultaneous detection of antineoplastic drugs on gloves since, in occupational exposure, the main contamination route is through dermal contact, which may occur via prolonged contact with contaminated surfaces or materials. The assay was performed by liquid chromatography using the following conditions for the detection of 5-fluorouracil (5-FU, methotrexate (MTX and paclitaxel (TAX: diode array detection and UV quantification at 195 nm for TAX, at 265 nm for 5-FU and at 302 nm for MTX; ODS column (250 x 4 mm, 5 μm with a similar guard column; mobile phase consisted of water (pH 4-methanol-acetonitrile (35:15:50, v/v/v with a flow rate of 1 mL min-1. The method presented a linear range from 0.25 to 20 μg mL-1 with r² higher than 0.99. Repeatability was 0.25 μg mL-1 in samples, although detection was possible in samples that presented values of around 0.1 μg mL-1. The results obtained suggest that the method developed can be applied for the simultaneous determination of the drugs studied and can be considered useful in exposure assessment for health care workers.O objetivo deste estudo foi desenvolver um método para a detecção simultânea de antineoplásicos em luvas, uma vez que, em exposições ocupacionais, a principal via de introdução é a dérmica, por meio de contato prolongado com superfícies e/ou materiais contaminados com tais fármacos. A tecnica de detecção utilizada foi a cromatografia líquida de alta eficiência, com detector de aranjo de diodos, nas seguintes condições: para a detecção de 5-fluorouracila (5-FU, metotrexato (MTX e paclitaxel (TAX: detecção e quantificação de TAX a 195 nm, de 5-FU a 265 nm e de MTX a 302 nm; coluna ODS (250 x 4 mm, 5 μm, com pré-coluna similar; fase móvel constituída de água (pH 4-metanol-acetonitrila (35:15:50, v/v/v, na vazão de 1 mL min-1. O método apresentou uma faixa linear de 0,25-20 mg mL-1, com r² > 0,99. O desvio

  5. An Experience with Managing Cancer Patients Reportedly Previously Informed of the Absence of Additional Available Antineoplastic Therapeutic Options

    Directory of Open Access Journals (Sweden)

    George River

    2014-09-01

    Full Text Available Over the past 5 years, a small group of cancer patients who stated their physicians had determined there were no additional available antineoplastic therapeutic options (including potential investigational strategies were seen for a ‘second opinion' in a cancer hospital-based oncology program and subsequently experienced what can reasonably be characterized as having achieved meaningful ‘clinical benefit' (functioning at a fairly high level for a minimum 1 year in the work, home, and/or family environments following the further delivery of a variety of treatment approaches. While recognized to be limited (or even simply ‘anecdotal', this experience emphasizes several clinically relevant conclusions, including the overall utility of a ‘second-opinion' strategy and the potential that the reported statement of an individual practitioner or cancer program that all rational options have been attempted may be inaccurate.

  6. Regulatory and logistical issues influencing access to antineoplastic and supportive care medications for children with cancer in developing countries.

    Science.gov (United States)

    Wiernikowski, John T; MacLeod, Stuart

    2014-08-01

    Globally there are numerous impediments, both logistical, regulatory and more recently global drug shortages, hindering pediatric access to therapeutic drugs of all types. Efforts to reduce barriers are ongoing and are especially important in low and middle income countries and for children requiring treatment of conditions such as those encountered in pediatric oncology characterized by the risk of life threatening treatment failures. Progress has been made through the efforts of the World Health Organization and regulators in the US and Europe to encourage the development of therapeutic agents for use in pediatrics and measures taken have fostered the availability of stronger pediatric data to guide therapeutic decisions. Nonetheless, pharmaceuticals remain a global commodity, subject to regulation by the World Trade Organization and this has often had detrimental effects in low and middle income countries. This article emphasizes the need for closer international collaboration to address the barriers currently impeding access to antineoplastic and supportive care medicines for children.

  7. Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-09-01

    Full Text Available Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG enzyme, it specifically detects DNA oxidative damage. The aim of this study was to investigate genotoxic effects in workers occupationally exposed to cytostatics (n = 46, as compared to a control group with no exposure (n = 46 at two Portuguese hospitals, by means of the alkaline comet assay. The potential of the OGG1 Ser326Cys polymorphism as a susceptibility biomarker was also investigated. Exposure was evaluated by investigating the contamination of surfaces and genotoxic assessment was done by alkaline comet assay in peripheral blood lymphocytes. OGG1 Ser326Cys (rs1052133 polymorphism was studied by Real Time PCR. As for exposure assessment, there were 121 (37% positive samples out of a total of 327 samples analysed from both hospitals. No statistically significant differences (Mann-Whitney test, p > 0.05 were found between subjects with and without exposure, regarding DNA damage and oxidative DNA damage, nevertheless the exposed group exhibited higher values. Moreover, there was no consistent trend regarding the variation of both biomarkers as assessed by comet assay with OGG1 polymorphism. Our study was not statistically significant regarding occupational exposure to antineoplastic drugs and genetic damage assessed by comet assay. However, health professionals should be monitored for risk behaviour, in order to ensure that safety measures are applied and protection devices are used correctly.

  8. Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-09-01

    Full Text Available Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG enzyme, it specifically detects DNA oxidative damage.The aim of this study was to investigate genotoxic effects in workers occupationally exposed to cytostatics (n = 46, as compared to a control group with no exposure (n = 46 at two Portuguese hospitals, by means of the alkaline comet assay. The potential of the OGG1 Ser326Cys polymorphism as a susceptibility biomarker was also investigated. Exposure was evaluated by investigating the contamination of surfaces and genotoxic assessment was done by alkaline comet assay in peripheral blood lymphocytes. OGG1 Ser326Cys (rs1052133 polymorphism was studied by Real Time PCR.As for exposure assessment, there were 121 (37% positive samples out of a total of 327 samples analysed from both hospitals. No statistically significant differences (Mann-Whitney test, p > 0.05 were found between subjects with and without exposure, regarding DNA damage and oxidative DNA damage, nevertheless the exposed group exhibited higher values. Moreover, there was no consistent trend regarding the variation of both biomarkers as assessed by comet assay with OGG1 polymorphism.Our study was not statistically significant regarding occupational exposure to antineoplastic drugs and genetic damage assessed by comet assay. However, health professionals should be monitored for risk behaviour, in order to ensure that safety measures are applied and protection devices are used correctly.

  9. Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy on hepatocarcinoma-bearing rats,and examine the action between calcium channel blockers and cytotoxic drugs. Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of liver carcinoma-bearing rats.All experimental animals were divided into four groups.On the sixth day post implantation,in group A (control group) 6ml of saline was injected intraperitoneally once a day for 3 days.In group B(single chemotherapy group) 6ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days.In group C(combination of treatment group)both 5-Fu(75mg/kg) and verapamil (25mg/kg) were administered simultaneously as in A and B.In group D(simple verapamil group)only 6ml of verapamil(25mg/kg)was administered as above. Results Compared with groups A, B and D,The volume of cancer and the contents of liver cancer DNA and protein were significantly reduced.The rates of inhibiting cancer(89.9% in group C and 35.4% in group B)were significantly increased in groupC. Group C had significantly long survival time compared to groups A, B and D(P<0.05).By light microscopy, a number of focal necroses were found in cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitonea chemotherapy to liver cancer;The use of verapamil can not increase the toxicity of 5-Fu.

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

    Directory of Open Access Journals (Sweden)

    Gelatti Umberto

    2011-03-01

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

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

    OpenAIRE

    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 ...

  12. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the Chilean population: comparison with Caucasian and Asian populations

    OpenAIRE

    Angela Margarita Roco; Luis Abel Quiñones; Agúndez, José A. G.; Elena eGarcía-Martín; Valentina eSquicciarini; Carla Estefania Miranda; Joselyn eGaray; Nancy eFarfán; Iván Nicolás Saavedra; Dante Daniel Caceres; Carol eIbarra; Nelson Miguel Varela

    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 ...

  13. Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

    OpenAIRE

    Carina Ladeira; Susana Viegas; Mário Pádua; Elisabete Carolino; Gomes, Manuel C.; Miguel Brito

    2015-01-01

    Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG) enzyme, it specifically detects DNA oxidative damage.The aim of this study was to investigate genotoxic effects in workers occupationally e...

  14. Chemosensitivity assay in mice prostate tumor: Preliminary report of flow cytometry, DNA fragmentation, ion ratiometric methods of anti-neoplastic drug monitoring

    OpenAIRE

    Kline Richard; Sharma Rakesh

    2004-01-01

    Abstract Flow cytometry, DNA fragmentation, ion ratiomateric analysis and NMR peaks characterized drug chemosensitivity of antineoplastic drugs. Hypotheses were: 1. The chemosensitive effect of different cancer cell lines is characteristic; 2. DNA fragmentation, ion ratiometric analysis suggest apoptosis status of tumor cells. Methods PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the [Na]i and [Ca]i ion sensing dyes, cell death, NMR peaks and apoptosis staining fo...

  15. Quantitative Analysis of the Anti-Proliferative Activity of Combinations of Selected Iron-Chelating Agents and Clinically Used Anti-Neoplastic Drugs

    OpenAIRE

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

    2014-01-01

    Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, ...

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

    OpenAIRE

    Gelatti Umberto; Sabatini Laura; Dominici Luca; Appolloni Massimo; Buschini Annamaria; Carrieri Mariella; Ceretti Elisabetta; Barbieri Anna; Villarini Milena; Grollino Maria G; Mussi Francesca; Pavanello Sofia; Feretti Donatella; Bonfiglioli Roberta; Moretti Massimo

    2011-01-01

    Abstract Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital n...

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

    OpenAIRE

    Reza Heidari; Akram Jamshidzadeh; Hossein Niknahad; Farshad Safari; Hamdollah Azizi; Narges Abdoli; Mohammad Mehdi Ommati; Forouzan Khodaei; Arastoo Saeedi; Asma Najibi

    2016-01-01

    Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotec...

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Leobardo Manuel Gómez-Oliván

    2014-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China); Bao, Jin-ku, E-mail: jinkubao@yahoo.com [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China)

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-03-10

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Irma Edith Carranza-Torres

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  7. Multicenter study of environmental contamination with antineoplastic drugs in 36 Canadian hospitals: a 2013 follow-up study.

    Science.gov (United States)

    Berruyer, M; Tanguay, C; Caron, N J; Lefebvre, M; Bussières, J F

    2015-01-01

    No occupational exposure limit exists for antineoplastic drugs. The main objective of this study was to describe environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in pharmacy and patient care areas of Canadian hospitals in 2013. The secondary objective was to compare the 2013 environmental monitoring results with previous studies. Six standardized sites in the pharmacy and six sites on patient care areas were sampled in each participating center. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by UPLC-MSMS. The limit of detection (LOD) in pg/cm(2) was 1.8 for cyclophosphamide, 2.2 for ifosfamide, and 7.5 for methotrexate. The 75th percentile of cyclophosphamide concentration was compared between the 2013, 2008-2010, and 2012 studies. Thirty-six hospitals participated in the study and 422 samples were collected. Overall, 47% (198/422) of the samples were positive for cyclophosphamide, 18% (75/422) were positive for ifosfamide, and 3% (11/422) were positive for methotrexate. In 2013, the 75th percentile value of cyclophosphamide surface concentration was reduced to 8.4pg/cm(2) (n = 36), compared with 9.4pg/cm(2) in 2012 (n = 33) and 40pg/cm(2) (n = 25) in 2008-2010. The 75th percentile for ifosfamide and methotrexate concentration remained lower than the LOD. The 2013 study shows an improvement in the surface contamination level, and a plateau effect in the proportion of positive samples.

  8. 碱基切除修复与抗肿瘤药物耐药%Base excision repair and antineoplastic drug resistance

    Institute of Scientific and Technical Information of China (English)

    况里杉; 王宇亮; 周向东

    2013-01-01

    Chemotherapy is one of the main methods to treat malignant tumors in clinical practice. Resistance to antineoplastic agents is one of the important reasons for treatment failure. The antineoplastic mechanism of various chemotherapeutic agents is to cause DNA damage, then result in apoptosis of tumor cells. It is suggested that the function of DNA repair is directly associated with the efficacy of antineoplastic agents. Current studies suggest that there are four major DNA repair pathways including BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair) and DSBR (double strand break repair). Of these four pathways, BER is one of the main mechanisms of DNA repair and its malfunction is closely related to the resistance to antineoplastic agents. Recently, many kinds of agents and strategies targeting BER have been developed to reverse chemoresistance. This review summarizes the progress in research in this area and discusses the mechanism of resistance to antineoplastic agents and the potential preventive and therapeutic strategies.%化疗是目前临床上治疗肿瘤的主要方法之一,抗肿瘤药物耐药则是导致肿瘤治疗失败的重要原因之一.多种化疗药物抗肿瘤的主要机制是引起DNA损伤,进而导致肿瘤细胞凋亡;因此,DNA修复功能状态与抗肿瘤药物疗效有着直接的关系.目前,已知有4种主要的DNA修复途径:碱基切除修复(base excision repair,BER)、核苷酸切除修复(nucleotide excision repair,NER)、错配修复(mismatch repair,MMR)和双键断裂修复(double strand break repair,DSBR).其中,BER是主要的DNA修复机制之一,其修复功能异常与抗肿瘤药物耐药有着密切的联系.近年来,以BER为靶点开发了多种逆转耐药的药物或方法.本文将简要综述相关的研究进展,深入探讨抗肿瘤药物耐药的发生机制及防治措施.

  9. Design and synthesis of highly Water-soluble Platinum antineoplastic drugs%高水溶性铂类抗肿瘤药物的设计与合成

    Institute of Scientific and Technical Information of China (English)

    张启飞; 鲁彦会; 刘朋兴; 王松青; 高清志

    2012-01-01

    目的 设计与合成具有高水溶性的铂类抗肿瘤药物.方法 通过在丙二酸铂结构中偶联糖分子设计出目标化合物并合成取得水溶性抗肿瘤药物.结果 得到了迄今水溶性最好的金属铂类抗肿瘤化合物,其动物模型抗肿瘤活性和安全性均优于顺铂和卡铂.结论 通过糖分子偶联设计取得的新型铂类抗肿瘤药物能够解决一般铂类药物的低水溶性问题.经初步动物模型抗肿瘤药效实验证明该类药物具有理想的抗肿瘤效果.%Objective To design and synthesize Platinum antineoplastic drugs with high water solubility. Methods Sugar molecular was coupled to the malonic acid Platinum structure to design and synthesize Platinum antineoplastic drugs with high water solubility. Results Metal Platinum antineoplastic compound with best water-solubility was produced, and its antineoplastic activity and safety were better than those of Cisplatin and Carboplatin on animal model. Conclusion Neotype Platinum antineoplastic drug, which is produced through the sugar molecule coupling design, can solve low water-solubility problem of general Platinum drugs. Preliminary antineoplastic efficacy experiment on animal model demonstrates that this kind of medicine has ideal antineoplastic effect.

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

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production.

    Science.gov (United States)

    Soriano, Ofelia; Delgado, Guadalupe; Anguiano, Brenda; Petrosyan, Pavel; Molina-Servín, Edith D; Gonsebatt, Maria E; Aceves, Carmen

    2011-08-01

    Several groups, including ours, have reported that iodine exhibited antiproliferative and apoptotic effects in various cancer cells only if this element is supplemented as molecular iodine, or as iodide, to cells that are able to oxidize it with the enzyme thyroperoxidase. In this study, we analyzed the effect of various concentrations of iodine and/or iodide in the dimethylbenz[a]anthracene (DMBA) mammary cancer model in rats. The results show that 0.1% iodine or iodide increases the expression of peroxisome proliferator-activated receptor type γ (PPARγ), triggering caspase-mediated apoptosis pathways in damaged mammary tissue (DMBA-treated mammary gland) as well as in frank mammary tumors, but not in normal mammary gland. DMBA treatment induces the expression of lactoperoxidase, which participates in the antineoplastic effect of iodide and could be involved in the pro-neoplastic effect of estrogens, increasing the formation of DNA adducts. In conclusion, our results show that a supplement of 0.1% molecular iodine/potassium iodide (0.05/0.05%) exert antineoplastic effects, preventing estrogen-induced DNA adducts and inducing apoptosis through PPARγ/caspases in pre-cancer and cancerous cells. Since this iodine concentration does not modify the cytology (histology, apoptosis rate) or physiology (triiodothyronine and thyrotropin) of the thyroid gland, we propose that it be considered as an adjuvant treatment for premenopausal mammary cancer.

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

    Directory of Open Access Journals (Sweden)

    Eliska Potuckova

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

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Chemosensitivity assay in mice prostate tumor: Preliminary report of flow cytometry, DNA fragmentation, ion ratiometric methods of anti-neoplastic drug monitoring

    Directory of Open Access Journals (Sweden)

    Kline Richard

    2004-03-01

    Full Text Available Abstract Flow cytometry, DNA fragmentation, ion ratiomateric analysis and NMR peaks characterized drug chemosensitivity of antineoplastic drugs. Hypotheses were: 1. The chemosensitive effect of different cancer cell lines is characteristic; 2. DNA fragmentation, ion ratiometric analysis suggest apoptosis status of tumor cells. Methods PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the [Na]i and [Ca]i ion sensing dyes, cell death, NMR peaks and apoptosis staining for chemotherapeutic action of different drugs. Results DNA fragmentation, ratiometric ions and fluorescence endlabelling plots were characteristic for cell lines and drug response. 31P-23Na NMR spectra showed characteristic high phospho-choline and sodium peaks. Conclusion Flow cytometry, DNA fragmentation, ion ratiometric methods and NMR peaks indicated apoptosis and offered in vivo drug monitoring method.

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

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

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

  19. 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

    Science.gov (United States)

    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

  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.

    Science.gov (United States)

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

    Science.gov (United States)

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

    2013-01-01

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

  2. Drug: D05134 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05134 Drug Nelarabine (JAN/USAN/INN); Nelzarabine (USAN); Arranon (TN) C11H15N5O5 ...4 Agents affecting cellular function 42 Antineoplastics 422 Antimetabolites 4229 Others D05134 Nelarabine (JAN/USAN/INN); Nelzara...S L01BB Purine analogues L01BB07 Nelarabine D05134 Nelarabine (JAN/USAN/INN); Nelzarabine (USAN) Antineoplas...tics [BR:br08308] Antimetabolites Purine analogues Nelarabine [ATC:L01BB07] D05134 Nelarabine (JAN/USAN/INN); Nelzara

  3. Analysis of the Utilization of Antineoplastic Chinese Patent Medicine in Our Hospital during the Period of 2008-2011%我院2008-2011年抗肿瘤口服中成药使用分析

    Institute of Scientific and Technical Information of China (English)

    郭玉霞; 张磊; 齐伟; 吴志恒

    2012-01-01

    OBJECTIVE: To evaluate the status quo of the utilization of antineoplastic Chinese patent medicine in our hospital and to promote rational use of drugs. METHODS: The consumption sum, DDDs.DDC and DUI of antineoplastic Chinese patent medicine in our hospital during the period of 2008—2010 were analyzed statistically. RESULTS: The variety of antineoplastic Chinese patent medicine in our hospital was stable during 2008—2011, the consumption sum of drugs increased year by year, suitable price and effective therapeutic efficacy of Chinese patent medicine took the lead on the list of DDDs and DDC. CONCLUSION: In our hospital, the utilization of antineoplastic Chinese patent medicine is rational on the whole. Comprehensive considerations including good effect and reasonable cost should be taken into account during clinical drug use.%目的:评价我院抗肿瘤口服中成药的使用现状,促进合理用药.方法:对我院2008-2011年抗肿瘤口服中成药的销售金额、用药频度(DDDs)、日用药金额(DDC)、药物利用指数(DUI)进行排序和分析.结果:我院2008-2011年抗肿瘤口服中成药品种基本固定,销售金额呈逐年上升趋势,疗效确切、价格适中的中成药DDDs、DDC、DUI排序靠前.结论:我院抗肿瘤中成药的应用基本合理,在临床用药过程中要综合考虑疗效和经济两方面.

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

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Coyne CP

    2016-08-01

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

  9. Antineoplastic mechanism of Octreotide in human hepatoma%细胞凋亡-奥曲肽抑制人肝癌生长的机制的探讨

    Institute of Scientific and Technical Information of China (English)

    陈绪军; 刘志苏; 艾中立

    2001-01-01

    目的奥曲肽能抑制人肝癌的生长,其机制尚未明了,本研究旨在观察奥曲肽在体外能否诱导人肝癌细胞凋亡,以从诱导肿瘤细胞凋亡的角度来探讨其抑制人肝癌生长的机制.方法将奥曲肽作用体外培养的人肝癌细胞株,运用细胞化学染色(Hochesst 33 258),透射电子显微镜术,DNA琼脂糖电泳及流式细胞术(flow cytometry,FCM)等方法来检测凋亡.结果经0.2μg/ml的奥曲肽处理后,形态学上,BEL-7402肝癌细胞表现为细胞皱缩,核质浓缩、核碎裂,细胞起泡以及凋亡小体形成等凋亡特征性的形态学改变;生化学上,DNA琼脂糖电泳呈现为梯状带.经FCM定量发现,随着奥曲肽之浓度增高(0~2 μg/ml),凋亡细胞增多,而且凋亡率与奥曲肽的药物浓度呈正相关(r=0.809,P<0.05).结论在体外,奥曲肽可诱导人肝癌细胞凋亡,这可能为奥曲肽抑制人肝癌生长的机制.%Objectives To investigate whether apoptosis can be induced by Octreotide in human hepatoma cells in vitro and elucidate the antineoplastic mechanism of Octreotide in hepatoma.Methods A cultured human hepatoma cell line,BEL-7402,was exposed to Octreotide and apoptosis was evaluated by cytochemical staining(Hochesst 33258),transmission electron microscopy,agarose gel electrophoresis and flow cytometry(FCM).Results After exposure to 0.2 μg/ml Octreotide,apoptosis with nuclear chromatin condensation as well as fragmentation,cell shrinkage and the formation of apoptotic bodies was observed using cytochemical staining and transmission electron microscopy.A DNA ladder in agarose gel electrophoresis was also displayed.FCM showed that the apoptotic cell number rose with an increase in the concentration of Octreotide(0- 2 iμg/ml).There was a positive correlation between Octreotide concentration and apoptotic rate in BEL-7402 cells(r=0.809,P<0.05).Conclusion Apoptosis in human hepatoma cells can be induced by Octreotide,which may be related to the

  10. Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, and its metabolites in rats.

    Science.gov (United States)

    Beal, D D; Skibba, J L; Croft, W A; Cohen, S M; Bryan, G T

    1975-04-01

    Chronic oral administration of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388, DTIC), induced predominantly thymic and mammary tumors as demonstrated previously. Male and female Sprague-Dawley and female Buffalo rats were susceptible to the carcinogenicity of DTIC. A 50% incidence of mammary adenocarcinomas was induced in males within 18 weeks. Type of tumor and tumor incidence were dose dependent. Single and multiple intraperitoneal injections of DTIC did not alter organ specificity. DTIC-induced thymic lymphosarcomas and mammary adenocarcinomas were transplantable. Tissue distribution studies revealed no correlation between uptake of DTIC by a given tissue and its susceptibility to carcinogenicity. Metabolites of DTIC were tested for carcinogenic activity. Animals administered 5-diazoimidazole-4-carboxamide orally, intraperitoneally, or intragastrically developed low incidences of thymic, stomach, bladder, or mammary tumors. A low incidence of mammary tumors developed in rats fed 2-azahypoxanthine. A variety of tumors, including several ependymoblastomas, were induced in rats that received 5-aminoimidazole-4-carboxamide orally. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (MTIC), when fed or given in single or multiple intraperitoneal injections, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Control rats had low incidences of mammary adenocarcinomas and adenofibromas after 52 weeks. These data show that the carcinogenic properties of DTIC resemble those of carcinogenic N-nitroso compounds, hydrazine, azo, and azoxy-alkanes and aryltriazenes and thus suggest similar mechanism(s) of action. These data also indicate that MTIC is involved in the induction of mammary adenofibromas and uterine leiomyosarcomas by DTIC.

  11. Antineoplastic Activity of Compound Recipe Xingqi Preparation%复方星芪制剂抗肿瘤活性的研究

    Institute of Scientific and Technical Information of China (English)

    任小巧; 侯凤飞; 高增平; 胡京红

    2012-01-01

    目的:探讨民间验方复方星芪制剂的抗肿瘤活性.方法:采用小鼠腋下接种肿瘤细胞法测定复方星芪制剂的抗肿瘤活性,MTT法测定复方星芪制剂提取物对小鼠脾细胞的增殖活性.结果:复方星芪方对移植性肿瘤(肉瘤S180和肝癌H22)具有显著的抑制作用,对小鼠脾细胞的增殖具有促进作用,并有较好的剂量依赖关系.结论:复方星芪制剂有抗肿瘤作用,其抗肿瘤作用可能与促进机体免疫有关.%Objective:To study the antineoplastic activity of compound recipe Xingqi preparation. Methods;Use tumor cells vaccination of mice armpit to determine anti-tumor activity and MTT method to determine proliferation activity for spleen cell. Results:The compound recipe Xingqi preparation has significant inhibitory action on portability tumor (sarcoma SI 80 and liver cancer H22) , but promoting effect for spleen cell proliferation and good dose-response relationship. Conclusion: The compound recipe Xingqi preparation has antitu-mor effect and its anti-tumor effects may be concerned with immunization promotion.

  12. Drug: D01223 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01223 Drug Capecitabine (JAN/USAN/INN); Xeloda (TN) C15H22FN3O6 359.1493 359.3501 ...drugs in Japan [BR:br08301] 4 Agents affecting cellular function 42 Antineoplastics 422 Antimetabolites 4223 Fluorouracils D01223 Cap...1B ANTIMETABOLITES L01BC Pyrimidine analogues L01BC06 Capecitabine D01223 Capecitabine (JAN/USAN/INN) Target...hase [HSA:7298] [KO:K00560] Capecitabine [ATC:L01BC06] D01223 Capecitabine (JAN/USAN/INN) Antineoplastics [B...R:br08308] Antimetabolites Pyrimidine analogues Capecitabine [ATC:L01BC06] D01223 Capecitabine (JAN/USAN/INN

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

    Directory of Open Access Journals (Sweden)

    Shadia A. Elsayed

    2010-01-01

    Full Text Available New complexes of dioxovanadium(V, zinc(II, ruthenium(II, palladium(II, and platinum(II with 6-methylpyridine-2-carbaldehyde-N(4-ethylthiosemicarbazone (HmpETSC have been synthesized. The composition of these complexes is discussed on the basis of elemental analyses, IR, Raman, NMR (H1, C13, and P31, and electronic spectral data. The X-ray crystal structures of [VO2(mpETSC] and [Pt(mpETSCCl] are also reported. The HmpETSC and its [Zn(HmpETSCCl2] and [Pd(mpETSCCl] complexes exhibit antineoplastic activity against colon cancer human cell lines (HCT 116.

  14. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the Chilean population: comparison with Caucasian and Asian populations

    Directory of Open Access Journals (Sweden)

    Angela Margarita Roco

    2012-11-01

    Full Text Available 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 compare 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 allele frequency (0.12 and GSTT1null (0.11 and GSTM1null (0.36 genotype frequencies 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 considered

  15. [Adherence to oral antineoplastic therapy].

    Science.gov (United States)

    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.

  16. Liquid-liquid extraction combined with high performance liquid chromatography-diode array-ultra-violet for simultaneous determination of antineoplastic drugs in plasma

    Directory of Open Access Journals (Sweden)

    Ananda Lima Sanson

    2011-06-01

    Full Text Available A liquid-liquid extraction (LLE combined with high-performance liquid chromatography-diode array detection method for simultaneous analysis of four chemically and structurally different antineoplastic drugs (cyclophosphamide, doxorubicin, 5-fluorouracil and ifosfamide was developed. The assay was performed by isocratic elution, with a C18 column (5 µm, 250 x 4.6 mm and mobile phase constituted by water pH 4.0- acetonitrile-methanol (68:19:13, v/v/v, which allowed satisfactory separation of the compounds of interest. LLE, with ethyl acetate, was used for sample clean-up with recoveries ranging from 60 to 98%. The linear ranges were from 0.5 to 100 µg mL-1, for doxorubicin and 1 to 100 µg mL-1, for the other compounds. The relative standard deviations ranged from 5.5 to 17.7%. This method is a fast and simple alternative that can be used, simultaneously, for the determination of the four drugs in plasma, with a range enabling quantification of the drugs in pharmacokinetics, bioequivalence and therapeutic drug-monitoring studies.Um método de extração líquido-líquido (ELL combinado com cromatografia líquida de alta eficiência-detector de arranjo de diodos foi desenvolvido para análise simultânea de quatro fármacos antineoplásicos quimicamente e estruturalmente diferentes (ciclofosfamida, doxorrubicina, fluoruracila e ifosfamida. O estudo foi realizado sob condições isocráticas, com coluna C18 (5µm, 250 x 4.6 mm e fase móvel constituída por água pH 4.0-acetonitrila-metanol (68:19:13, v/v/v, que permitiu separação satisfatória dos analitos de interesse. A ELL, com acetato de etila, foi utilizada para limpeza da amostra, com recuperação variando de 60 a 98%. As faixas foram lineares de 0,5 a 100 µg mL-1 para doxorrubicina e 1 a 100 µg mL-1 para os outros compostos. O desvio padrão relativo variou de 5,5 a 17,7%. Este método é uma alternativa rápida e simples que pode ser usado, simultaneamente, para a determinação dos

  17. 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)

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Eman M Dokla

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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Studies on antineoplastic constituents from marine bryozoan Bugula neritina inhabiting South China Sea:isolation and structural elucidation of a novel macrolide%中国南海总合草苔虫抗癌活性成分研究:一个新的大环内酯的分离鉴定

    Institute of Scientific and Technical Information of China (English)

    林厚文; 刘皋林; 易杨华; 姚新生; 吴厚铭

    2004-01-01

    Objective :To investigate the antineoplastic constituents from marine bryozoan Bugula neritina in South China Sea. Methods:Antineoplastic compounds were screened by bioassay-guided method with partitive extraction and multiple column chromatographies (Sephadex LH-20,ODS and preparative HPLC). Structures of active compounds were determined by high-resolution 2D NMR (600 MHz) and ESI-MS techniques. Results:A new antineoplastic macrolide bryostatin 19 (1) was isolated from this animal. Five known antineoplastic bryostatins: bryostatin 4 (2), bryostatin 5 (3), bryostatin 6 (4), bryostatin 18(5) and bryostatin 10(6),were for the first time obtained from this bryozoan in South China Sea. Bryostatin 19(1) shows strong inhibition activity against U937 cell line with ED50 value being 3.2 nmol/L in vitro. Conclusion : The animal resource of Bugula neritina is abundant in South China Sea. It contains potential antineoplastic new macrolide of bryostatin series and will be developed as potentially useful source of anticancer agents in the future.%目的:研究中国南海总合草苔虫中的抗癌活性成分.方法:通过分级萃取和多种硅胶柱层析(Sephadex LH-20凝胶过滤、ODS反相层析和HPLC)追踪分离抗癌活性成分;利用电喷雾离子质谱(ESI-MS)和高分辨(600 MHz)核磁共振二维谱技术鉴定化合物的结构.结果:分离得到一个新的具有显著抗肿瘤活性的大环内酯bryostatin 19(1).同时还首次自中国海域的该种苔虫中分离鉴定了5个bryostatins类大环内酯抗癌活性化合物:bryostatin 4,5,6,10,18.Bryostatin 19显示很强的体外抗癌活性,对U937细胞的ED50值为3.2 nmol/L.结论:我国南海总合草苔虫资源丰富,并且含有新结构的抗癌活性草苔虫内酯.本研究结果为今后的新药研制与开发提供了参考.

  1. In vitro and in vivo studies of the antineoplastic activity of copper (II) compounds against human leukemia THP-1 and murine melanoma B16-F10 cell lines.

    Science.gov (United States)

    Borges, Layla J H; Bull, Érika S; Fernandes, Christiane; Horn, Adolfo; Azeredo, Nathalia F; Resende, Jackson A L C; Freitas, William R; Carvalho, Eulógio C Q; Lemos, Luciana S; Jerdy, Hassan; Kanashiro, Milton M

    2016-11-10

    We investigated the antineoplastic activities of a previously reported copper (II) coordination compound, [Cu(BMPA)Cl2]CH3OH (1), and a new compound, [Cu(HBPA)Cl2]H2O (2), where BMPA is bis(pyridin-2-ylmethyl)amine and HBPA is (2-hydroxybenzyl)(2-pyridylmethyl)amine, using various cellular models of human leukemia (THP-1, U937, HL60, Molt-4, JURKAT) and human colon cancer (COLO 205), as well as a murine highly metastatic melanoma (B16-F10) cell line. Compound (2) was characterized using several physical and chemical techniques, including X-ray diffraction studies. The IC50 values of the copper coordination complexes in the human leukemia cell lines ranged from 87.63 ± 1.02 to ≥400 μM at high cell concentrations and from 19.17 ± 1.06 to 97.67 ± 1.23 μM at low cell concentrations. Both compounds induced cell death, which was determined by cell cycle analyses and phosphatidylserine exposure studies. THP-1 cells released cytochrome c to the cytoplasm 12 h after treatment with 400 μM of compound (2). To evaluate the apoptosis pathway induced by compound (2), we measured the activities of initiator caspases 8 and 9 and executioner caspases 3 and 6. The results were suggestive of the activation of both intrinsic and extrinsic apoptosis pathways. To investigate the activities of the compounds in vivo, we selected two sensitive cell lines from leukemia (THP-1) and solid tumor (B16-F10) lineages. BALB/c nude bearing THP-1 tumors treated with 12 mg·kg(-1) of compound (2) showed a 92.4% inhibition of tumor growth compared with the control group.

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

    Science.gov (United States)

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

    2004-03-26

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

  3. Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    , but also multiplied the complex interaction of genetic and other laboratory parameters that can be used for therapy adjustments. Thus, with the advances in the laboratory techniques, post laboratory issues have become major obstacles for treatment individualization. Many of these challenges have been......ABSTRACT: Predicting the response to medical therapy and subsequently individualizing the treatment to increase efficacy or reduce toxicity has been a longstanding clinical goal. Not least within oncology, where many patients fail to be cured, and others are treated to or beyond the limit...... adjustments could increase the of risk of relapse or life-threatening complications. In this review we use childhood ALL therapy as a model and discuss these issues, and how they may be addressed....

  4. Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate

    DEFF Research Database (Denmark)

    Niekerk, P.B. van Kooten; Schmiegelow, K.; Schroeder, H.

    2008-01-01

    BACKGROUND AND OBJECTIVE: Through interruption of maintenance treatment with 6-mercaptopurine (6MP), toxicity after high-dose methotrexate (HDMTX) may compromise the efficiency of the treatment of children with acute lymphocytic leukaemia (ALL). We investigated the influence of polymorphisms......-intensity co-treatment (6MP 75 mg/m(2)/d + MTX 20 mg/m(2)/wk) was found associated with increased odds of haematological toxicity (OR's: 3.47-7.88; P's: fever (OR = 2.2; P = 0.004) and interruption maintenance treatment (OR = 15.9; P ....006-0.027), fever (OR = 2.65; P = 0.037) and interruption of maintenance treatment (OR = 3.04; P = 0.032). No convincing associations were found between the MTHFR C677T or A1298C polymorphisms and toxicity. CONCLUSION: Our findings demonstrate that toxicity after HDMTX is influenced by coadministrated...

  5. Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    of acceptable toxicity, an individualized therapeutic approach is indicated. The mapping of the human genome and technological developments in DNA sequencing, gene expression profiling, and proteomics have raised the expectations for implementing genotype-phenotype data into the clinical decision process......, but also multiplied the complex interaction of genetic and other laboratory parameters that can be used for therapy adjustments. Thus, with the advances in the laboratory techniques, post laboratory issues have become major obstacles for treatment individualization. Many of these challenges have been...... illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

  6. Application analysis of antineoplastic molecular targeted drug in 32 hospitals in Wuhan area during 2010-2012%2010-2012年武汉地区32家医院应用抗肿瘤分子靶向治疗药物分析

    Institute of Scientific and Technical Information of China (English)

    桂玲; 费敏; 张程亮; 刘东

    2014-01-01

    目的:分析2010-2012年武汉地区32家医院应用抗肿瘤分子靶向治疗药物状况。方法应用金额排序法和用药频度( DDDs)排序法,对武汉市32家医院近三年临床使用的抗肿瘤分子靶向治疗药物进行回顾性统计和分析。结果武汉地区抗肿瘤分子靶向治疗药物销售金额与DDDs逐年稳定增长,日均费用( DDC)相对稳定。各类药品销售金额与DDDs排序趋势一致,国产新药埃克替尼的销售金额及DDDs增长较快。结论2010-2012年武汉地区应用抗肿瘤分子靶向治疗药物状况符合临床应用特点,销售金额及DDDs排序合理。%Objective To analyse the application of antineoplastic molecular targeted drug in 32 hospitals in Wuhan area during 2010-2012.Methods Applied the amount of sorting and DDDs sorting to count and analyse the situation of an-tineoplastic molecular targeted drug application in 32 hospitals of Wuhan city in recent three years.Results The sales amount and DDDs of antineoplastic molecular targeted drug in the treatment of Wuhan area were increased steadily year by year,DDC was relatively stable.All kinds of the amount of drug sales and DDDs sorted the favorable trend.Sales amount and DDDs of do-mestic new drugs Icotinib were growing faster.Conclusion The application status of antineoplastic molecular targeted drug in Wuhan area during 2010-2012 were conform to the clinical application characteristics,while the sales amount and DDDs were sorted reasonably.

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

    Directory of Open Access Journals (Sweden)

    Verónica González Pardo

    2012-04-01

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

  8. Intestinal and Liver Toxicity of Antineoplastic Drugs

    OpenAIRE

    McDonald, George B.; Tirumali, Nigendra

    1984-01-01

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

  9. Antineoplastic unsaturated fatty acids from Fijian macroalgae.

    Science.gov (United States)

    Jiang, Ren-Wang; Hay, Mark E; Fairchild, Craig R; Prudhomme, Jacques; Roch, Karine Le; Aalbersberg, William; Kubanek, Julia

    2008-10-01

    Phytochemical analysis of Fijian populations of the green alga Tydemania expeditionis led to the isolation of two unsaturated fatty acids, 3(zeta)-hydroxy-octadeca-4(E),6(Z),15(Z)-trienoic acid (1) and 3(zeta)-hydroxy-hexadeca-4(E),6(Z)-dienoic acid (2), along with the known 3(zeta)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (4). Investigations of the red alga Hydrolithon reinboldii led to identification of a glycolipid, lithonoside (3), and five known compounds, 15-tricosenoic acid, hexacosa-5,9-dienoic methyl ester, beta-sitosterol, 10(S)-hydroxypheophytin A, and 10(R)-hydroxypheophytin A. The structures of 1-3 were elucidated by spectroscopic methods (1D and 2D NMR spectroscopy and ESI-MS). Compounds 1, 2, and 4, containing conjugated double bonds, demonstrated moderate inhibitory activity against a panel of tumor cell lines (including breast, colon, lung, prostate and ovarian cells) with IC(50) values ranging from 1.3 to 14.4 microM. The similar cell selectivity patterns of these three compounds suggest that they might act by a common, but unknown, mechanism of action.

  10. Exposição ocupacional a medicamentos antineoplásicos em clínicas veterinárias no município do Rio de Janeiro / Occupational risks in the manipulation of antineoplastic in clinical veterinarians in the of Rio de Janeiro city

    Directory of Open Access Journals (Sweden)

    Mônica Faria da Silva

    2013-02-01

    Full Text Available Médicos veterinários estão expostos constantemente a riscos químicos, físicos e biológicos durante a prática de sua profissão. Médicos veterinários, de 78 dos 88estabelecimentos registrados no Conselho Regional de Medicina Veterinária do Rio de Janeiro e com mais de cinco anos de funcionamento, foram entrevistados sobre o uso de medicamentos antineoplásicos, medidas de proteção individual e efeitos tóxicos associados. A vincristina (100% é o antineoplásico mais utilizado, seguido da ciclofosfamida (27,02%. Nenhuma das clínicas visitadas possuía capela de fluxo laminar; 58,10% dos profissionais não utilizavam máscaras, 16,20% não usavam luvas e 14,85% nenhum tipo de Equipamento de Proteção Individual (EPI; 30% relataram não conhecer os efeitos tóxicos decorrentes da exposição aos antineoplásicos. A maioria dos entrevistados relatou que, durante a graduação, não recebeu orientação adequada sobre riscos químicos ocupacionais. Ações de vigilância sanitária devem ser tomadas para diminuir os riscos decorrentes da manipulação de medicamentos antineoplásicos em clínicas veterinárias. -------------------------------------------------------------------------------- Veterinarians are constantly exposed to chemical physical and biological risks during professional practice. Veterinarians from 78 out of 88 fi ve-year functioning establishments in the city of Rio de Janeiro were interviewed about antineoplastics usage and individual protective measures and the associated toxic effects. As informed, vincristine (100% is the most widely used anticancer, followed by cyclophosphamide (27.02%. None of the clinics visited had any laminar fl ow chamber; 58.10% of professionals weren’t using masks to manipulate anticancers; 16.20% weren’t using gloves and 14.85% weren’t using any type of IEP; 30% reported not to be aware of antineoplastics toxicity. Most veterinarians related that during graduation course no proper

  11. Drug: D02115 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02115 Drug Methotrexate sodium; Trexall (TN) C20H21N8O5. Na 476.1533 476.4211 D021...p07050 Antirheumatics - DMARDs and biological agents map04976 Bile secretion Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01B ANTIMETABOLITES L01BA Folic acid analogues L01BA01 Methotrexate D02115 Methotrexate sodium L04 IMMUNOSUPPRESSANTS L04A IMMUNOSUPPRESSANTS L04AX Other immunosuppressants L04AX03 Methotrexate D02115 Methotrexate sodium USP drug classification [BR:br08302] Immunological Agents Immune Suppressants Methotrexate D02115 Methotrexate sodium Target-based classification of drugs [BR:br08310] Enzymes Oxidoredu...ase [HSA:1719 200895] [KO:K00287] Methotrexate...lites Folic acid analogues Methotrexate... [ATC:L01BA01] D02115 Methotrexate sodium CAS: 15475-56-6 PubChem: 78

  12. Factors that affect cancer patient compliance to oral anti-neoplastic therapy Factores que influyen en la adhesión de pacientes con cáncer a la terapia antineoplásica oral Fatores que influenciam a adesão de pacientes com câncer à terapia antineoplásica oral

    Directory of Open Access Journals (Sweden)

    Patrícia Andréa Crippa Marques

    2008-01-01

    Full Text Available OBJECTIVES: To identify factors that can affect compliance to treatment with neoplastic oral drugs in a group of cancer patients. METHODS: Interviews were performed on 61 patients diagnosed with cancer and under anti-neoplastic oral therapy in a private hospital. The interviews were carried out using instruments to assess compliance. RESULTS: Most patients (95% reported the oral treatment was not difficult. The Morisky and Green Test were positive in 28% of the patients. Factors that may affect following the treatment were significantly (pOBJETIVOS: Identificar los factores asociados a la adhesión al tratamiento con drogas de acción antineoplásica por vía oral en pacientes con cáncer. MÉTODOS: Fueron entrevistados 61 pacientes con cáncer sometidos a terapia antineoplásica por vía oral en un hospital particular, con la aplicación de instrumentos para evaluar la adhesión. RESULTADOS: La mayoría de los pacientes (95% refirió que el tratamiento oral no es difícil. El test Morisky y Green fue positivo en el 28% de los pacientes. Los factores que pueden influir en la realización del tratamiento se asociaron de forma significativa (pOBJETIVOS: Identificar fatores associados à adesão ao tratamento com drogas de ação antineoplásica por via oral em pacientes com câncer. MÉTODOS: Foram entrevistados 61 pacientes com câncer sob terapia antineoplásica via oral em hospital particular, com a aplicação de instrumentos para avaliar a adesão. RESULTADOS: A maioria dos pacientes (95% referiu que o tratamento oral não é difícil. O Teste Morisky e Green foi positivo em 28% dos pacientes. Os fatores que podem influenciar a realização do tratamento se associaram de forma significativa (p<0,05 com a variável tempo, os pacientes que apresentaram mais dificuldade, tinham mais tempo de tratamento. CONCLUSÕES: Os pacientes apresentaram atitudes positivas frente ao tratamento com medicamentos antineoplásicos orais, porém foram

  13. Genotoxicity biomarkers for monitoring occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Hilda M. Rodríguez-Montero

    2016-06-01

    Full Text Available Context: The Institute of Oncology and Radiobiology (INOR is the leading institution for the diagnosis, treatment and follow-up of cancer in Cuba. The main methods used in cancer treatment are surgery, radiotherapy and chemotherapy. The last one involves the handling of hazardous substances, such as cytostatics, which implies a health risk to persons occupationally exposed to it. There are two sites where a considerable among of cytostatic is handled (Ambulatory Chemotherapy Room (ACR and the Central Unit of Cytostatic Mixture Preparation (CUCM. Genotoxicity biomarkers of exposure and effects have been widely used to detect occupational environment hazards. Aims: To evaluate genotoxicity biomarkers indicative of exposure and effects to cytostatics. Methods: In this study were tested samples taken from the surfaces of biological safety cabinets located in the Central Unit of Cytostatic Mixture using SOS – Chromotest. We also evaluated samples of oral mucosa exfoliated cells from exposed and control subjects, by micronucleus test. Results: All subjects were exposed and subjects who administered the mixes in the institution had an increased of DNA damage in comparison with the pharmaceutical staff that prepared it and wear the primary protection barriers properly. Conclusions: These results underline the efficiency of genotoxicological biomarkers in detecting the exposure levels and the deleterious effect of cytostatics on occupationally exposed personal.

  14. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renee L.; van Dalen, Elvira C.; Van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Background Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood ca

  15. Thermodynamics of molecular recognitions between antineoplastic drug taxol and phosphatidylcholine

    Directory of Open Access Journals (Sweden)

    Erhan Süleymanoglu

    2010-12-01

    Full Text Available The aim of this study was to study the basic features of Taxol recognition with phospholipids by applying the thermodynamic and spectroscopic measurements. The obtained information could be used further for deductions on its precise cellular and pharmacological mechanisms of action, on improvements of its solubility properties by phospholipids, as well as for designing the novel lipidic carriers for drug delivery.

  16. Multifunctional CD40L: pro- and anti-neoplastic activity

    OpenAIRE

    Korniluk, Aleksandra; Kemona, Halina; Dymicka-Piekarska, Violetta

    2014-01-01

    The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its ...

  17. Multifunctional CD40L: pro- and anti-neoplastic activity.

    Science.gov (United States)

    Korniluk, Aleksandra; Kemona, Halina; Dymicka-Piekarska, Violetta

    2014-10-01

    The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer. Although CD40L has a major contribution to anti-cancer activity, many reports point at its ambivalent nature. CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis. CD40L involvement in the inhibition of tumor progression has led to the emergence of not only therapy using recombinant forms of the ligand and vaccines in the treatment of cancer but also therapy consisting of inhibiting platelets-main source of CD40L. This article is a review of studies on the ambivalent role of CD40L in neoplastic diseases. PMID:25117071

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

    OpenAIRE

    Ralph, Stephen John

    2008-01-01

    Arsenic-based compounds have become accepted agents for cancer therapy providing high rates of remission of some cancers such as acute promyelocytic leukemia (APL). The mechanisms by which arsenic-containing compounds kill cells and reasons for selective killing of only certain types of cancer cells such as APLs have recently been delineated. This knowledge was gained in parallel with increasing understanding and awareness of the importance of intracellular redox systems and regulation of the...

  19. Enhanced cytotoxicity of antineoplastic agents following prolonged exposure to misonidazole.

    OpenAIRE

    Roizin-Towle, L. A.; Hall, E. J.

    1981-01-01

    Chinese hamster V79 cells cultured in vitro were used to investigated the cytotoxicity of various anti-cancer drugs subsequent to a prolonged treatment of the cells with Misonidazole (MISO). The sensitivity of the cells to Bleomycin (BLM), Melphalan or cis-Platinum (cis-DDP) was significantly increased by prior incubation with MISO under hypoxic conditions. When cysteamine, a radical scavenger, was present during the pretreatment with MISO, this enhancement of cytotoxicity was greatly reduced...

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

    OpenAIRE

    Panagiota Papanagnou; Theodora Stivarou; Maria Tsironi

    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...

  1. Cytotoxicity and Antineoplastic Activities of Alkylamines and Their Borane Derivatives

    OpenAIRE

    Hall, Iris H.; Tse, Elaine Y.; Muhammad, Rosallah A.

    1996-01-01

    The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition r...

  2. PCNA Damage Caused by Anti-Neoplastic Drugs

    OpenAIRE

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

    2008-01-01

    Structurally diverse chemotherapeutic and chemopreventive drugs, including camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian cells exposed to fluorescent light. This PCNA damage was caused by both nuclear and cytoplasmically localizing drugs. For some drugs, the PCNA crosslinking was evident even with very brief exposures to laboratory room lighting. In the absence of drugs, there wa...

  3. Hypersensitivity Reactions Associated with Platinum Antineoplastic Agents: A Systematic Review

    OpenAIRE

    Makrilia, Nektaria; Syrigou, Ekaterini; Kaklamanos, Ioannis; Manolopoulos, Leonidas; Saif, Muhammad Wasif

    2010-01-01

    Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal...

  4. Malignant melanoma-The cradle of anti-neoplastic immunotherapy.

    Science.gov (United States)

    Koller, Kristian M; Wang, Wenge; Schell, Todd D; Cozza, Eugene M; Kokolus, Kathleen M; Neves, Rogerio I; Mackley, Heath B; Pameijer, Colette; Leung, Anna; Anderson, Bryan; Mallon, Carol A; Robertson, Gavin; Drabick, Joseph J

    2016-10-01

    One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options. PMID:27637351

  5. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    OpenAIRE

    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) wi...

  6. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    R.L. Mulder; E.C. van Dalen; M. van den Hof; D. Bresters; B.G.P. Koot; S.M. Castellino; Y. Loke; E. Leclercq; P.N. Post; H.N. Caron; A. Postma; L.C.M. Kremer

    2011-01-01

    Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. Howev

  7. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon

    Directory of Open Access Journals (Sweden)

    Astha Varma

    2011-01-01

    Full Text Available Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer agents. In this regard, Andrographis paniculata Nees, a well-known plant of Indian and Chinese traditional system of medicines, has drawn attention of researchers in recent times. Andrographolide, the principal bioactive chemical constituent of the plant has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Andrographolide also shows potent immunomodulatory and anti-angiogenic activities in tumorous tissues. Synthetic analogues of the compound have also been created and analyzed, which have also shown similar activities. Although it is too early to predict its future in cancer chemotherapy, the prologue strongly recommends further research on this molecule to assess its potential as a prospective anticancer agent.

  8. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon

    OpenAIRE

    Neeta Shrivastava; Harish Padh; Astha Varma

    2011-01-01

    Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer ag...

  9. On/off-switchable anti-neoplastic nanoarchitecture

    Science.gov (United States)

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

    2015-09-01

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

  10. Comparative study between trabeculectomy with photodynamic therapy (BCECF-AM and trabeculectomy with antimetabolite (MMC in the treatment of primary open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Saeed AM

    2012-10-01

    Full Text Available Ahmed M SaeedOphthalmology Department, Benha University, Benha, EgyptBackground: Various methods have been investigated to avoid postoperative scarring of the filtering bleb in modern glaucoma surgery. Most deal with the application of antimetabolic drugs such as mitomycin C (MMC. 2’,7’-bis-(2-carboxyethyl-5-(and-6-carboxyfluorescein, acetoxymethyl ester (BCECF-AM is a locally acting intracellular photosensitizer which could control and decrease postoperative fibrosis at the trabeculectomy site.Purpose: To compare the effect of photodynamic therapy in combination with trabeculectomy to the effect of MMC combined with the same procedure in controlling postoperative intraocular pressure (IOP in patients with medically uncontrolled primary open angle glaucoma (1ry OAG.Methods: A randomized controlled clinical trial was conducted on 76 eyes of 76 patients divided into three groups undergoing trabeculectomy, trabeculectomy with BCECF-AM (group A, trabeculectomy with MMC (group B, and trabeculectomy only as a control group (group C. Patients were reviewed postoperatively for clinical evaluation and photo documentation of the blebs with a fundus camera and ultrasonic biomicroscopy (UBM. The desirable effect of the adjunctive material was evaluated according to the clinical efficacy, tolerability, and safety by comparison with the control group.Setting: Benha University Hospital, Benha, Egypt.Results: After a mean follow-up of 24 months, all procedures succeeded in lowering IOP. The cumulative probability of complete success at the 24 month follow-up was 91% for group B, compared to 82% and 81.5% for group A and group C, respectively. The percentage of complete success was highest for group B, second highest for group A, and lowest for group C over the follow-up period; however, these differences were not statistically significant (P > 0.05. Regarding the bleb morphology and UBM reflectivity, the differences were not statistically significant (P > 0.05. The mean bleb height and breadth were larger in groups A and B in comparison to group C over the study period. The mean aqueous drainage route was similar in groups A and C, but less than in group B at 3 and 12 months postoperatively. Complications were generally mild and less marked in group A and C than group B.Conclusion: Cellular photoablation using BCECF-AM seems to be a feasible new method to use in combination with glaucoma filtration surgery. Although MMC might be considered a more potent adjunctive to trabeculectomy in promoting IOP reduction, photodynamic therapy carries relatively less risk of adverse effects and complications. Cellular photoablation using BCECF-AM could be considered efficient, tolerable and relatively safer in managing patients with 1ry OAG. Further studies are necessary to determine the safety and the reliability of this therapy.Keywords: photodynamic therapy, mitomycin C, trabeculectomy, open angle glaucoma, ultrasonic biomicroscopy

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

    Directory of Open Access Journals (Sweden)

    Fernanda Ludmilla Rossi Rocha

    2004-06-01

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

  12. The effect of antineoplastic drug NSC631570 on immunogenicity of B16 melanoma

    Directory of Open Access Journals (Sweden)

    Larysa M.Skivka

    2014-06-01

    Full Text Available Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melanoma B16 after treatment with NSC631570. Methods: Two melanoma B16 sublines with different metastatic potentials were used. For in vivo growth cells were inoculated intravenously into C57BL/6 mice. The anticancer effect was calculated according to the growth inhibition index. Cell viability was determined by the MTT test. Cell apoptosis and necrosis were assessed by flow cytometry. HMGB1 expression, the serum level of cytokines and cytokine profile in tumor tissue were determined by ELISA. TAP1 and TAP2 expression was evaluated in RT-PCR and by Western blot. Results: Treatment of melanoma B16 cells with NSC631570 at apoptogenic concentrations induced tumor cell death accompanied by dose-dependent HMGB1 release in vitro. At the non-apoptogenic concentration the preparation caused an increase in TAP expression. The therapeutic efficacy of NSC631570 was also associated with strong release of HMGB1 in the serum of tumor-bearing mice and was more expressed in the case of the high-metastatic tumor variant. The therapeutic effect was accompanied by an increase of levels of Th1 cytokines in the serum and in tumor tissue of treated animals. Conclusion: In addition to the direct induction of tumor cell apoptosis, the preparation can increase the tumor immunogenicity. [J Exp Integr Med 2014; 4(2.000: 93-105

  13. The effect of antineoplastic drug NSC631570 on immunogenicity of B16 melanoma

    OpenAIRE

    Skivka, Larysa M.; Olexander G. Fedorchuk; Natalia O. Bezdeneznykh; Olexanrda O. Lykhova; Nadija I. Semesiuk; Yuri I. Kudryavets; Oksana M. Malanchuk

    2014-01-01

    Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melan...

  14. Green Production of Indolylquinones, Derivatives of Perezone, and Related Molecules, Promising Antineoplastic Compounds

    Directory of Open Access Journals (Sweden)

    René Gerardo Escobedo-González

    2016-01-01

    Full Text Available A green approach to produce the indolyl derivatives from four natural quinones (perezone, isoperezone, menadione, and plumbagin was performed; in this regard, a comparative study was accomplished among the typical mantle heating and three nonconventional activating modes of reaction (microwave, near-infrared, and high speed ball milling or tribochemical, under solventless conditions and using bentonitic clay as a catalyst. In addition, the tribochemical production of isoperezone from perezone is also commented on. It is also worth noting that the cytotoxicity of the synthesized indolylquinones in human breast cancer cell was tested by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay, with the 3-indolylisoperezone being the most active. The structural attribution of the target molecules was performed by typical spectroscopic procedures; moreover, the experimental and computed 1H and 13C NMR chemical shifts data, with previous acquisition of the corresponding minimum energetic structures, were in good agreement.

  15. Components in Antineoplastic Actinomycete Strain(N2010-37)of Bottom Mud in Mangrove

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhong-liu; JIN Bei; YIN Wen-qing; FU Chun-yan; FENG Hua-fen

    2011-01-01

    Objective To study the antitumor components from an actinomycete strain(N2010-37)of bottom mud in Zhanjiang Mangrove,South China Sea.Methods The components were isolated and purified by chromatographic techniques and recrystallization,and the structures were identified by spectral methods together with physicochemical analyses.The antitumor effects of these components were tested in vitro by MTT method.Results Three compounds were identified including two anthrones and one novel lactone.They are(3S,4R,7R,8R,9S)-3,8-dihydroxy-4,7,9-trimethyl-2,6-cyclononanediolacetone(1),2-hydroxy-l-methoxy-3-methylanthraquinone(2),and 1,6,8-thihydroxy-3-methyl-anthraquinone(3).Conclusion Compound 1 is a new compound,and compounds 1 and 3 show the favorablecytotoxic activities against human chronic granulocytic leukemia cell line K562 strain by MTT method in vitro.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Magnetic resonance spectroscopy detectable metabolomic fingerprint of response to antineoplastic treatment.

    Directory of Open Access Journals (Sweden)

    Alessia Lodi

    Full Text Available Targeted therapeutic approaches are increasingly being implemented in the clinic, but early detection of response frequently presents a challenge as many new therapies lead to inhibition of tumor growth rather than tumor shrinkage. Development of novel non-invasive methods to monitor response to treatment is therefore needed. Magnetic resonance spectroscopy (MRS and magnetic resonance spectroscopic imaging are non-invasive imaging methods that can be employed to monitor metabolism, and previous studies indicate that these methods can be useful for monitoring the metabolic consequences of treatment that are associated with early drug target modulation. However, single-metabolite biomarkers are often not specific to a particular therapy. Here we used an unbiased 1H MRS-based metabolomics approach to investigate the overall metabolic consequences of treatment with the phosphoinositide 3-kinase inhibitor LY294002 and the heat shock protein 90 inhibitor 17AAG in prostate and breast cancer cell lines. LY294002 treatment resulted in decreased intracellular lactate, alanine fumarate, phosphocholine and glutathione. Following 17AAG treatment, decreased intracellular lactate, alanine, fumarate and glutamine were also observed but phosphocholine accumulated in every case. Furthermore, citrate, which is typically observed in normal prostate tissue but not in tumors, increased following 17AAG treatment in prostate cells. This approach is likely to provide further information about the complex interactions between signaling and metabolic pathways. It also highlights the potential of MRS-based metabolomics to identify metabolic signatures that can specifically inform on molecular drug action.

  19. Synthesis, characterization and in vitro anti-neoplastic activity of gypsogenin derivatives.

    Science.gov (United States)

    Emirdağ-Öztürk, Safiye; Babahan, İlknur; Özmen, Ali

    2014-04-01

    Gypsogenin (L(1); 3-hydroxy-23-oxoolean-12-en-28-oic acid), a natural saponin, was isolated from the boiling water extract of Gypsophila arrostii roots. In addition, the derivatives gypsogenin thiosemicarbazone (L(2); 23-[(aminocarbonothioyl)hydrazono]-3-hydroxolean-12-en-28-oic acid) and gypsogenin thiosemicarbazone glyoxime (L(3)H2; (3β)-3-hydroxy-23-[({[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]amino}carbonothioyl)hydrazono] olean-12-en-28-oic acid) as well as the Cu(II) and Co(II) complexes of L(3)H2 were prepared. The structures were established on NMR analysis ((1)H, (13)C NMR, HMBC, HMQC, and NOESY), FT-IR and completed by analysis of LC/MS. Furthermore, the antiproliferative effects of the Co(II) and Cu(II) complexes of the gypsogenin derivatives were assayed in human promyelocytic leukemia (HL 60) cells. These complexes were found to be potent anticancer agents with concentrations that inhibited 50% of proliferation (IpC50) between 5μM and 40μM. Cell death was distinguished by HO/PI double staining. The Co(II) complex of L(3)H2 has shown approximately %50 apoptotic effect at 10μM concentration. Paclitaxel has been used as positive control. PMID:24463219

  20. Antineoplastic and Cytotoxic Activities of Nickel(II) Complexes of Thiosemicarbazones

    OpenAIRE

    Hall, Iris H.; Miller, Merrill C.III; West, Douglas X.

    1997-01-01

    Nickel(II) complexes of thiosemicarbazons were observed to be potent cytotoxic agents in human and rodent tissue cultured tumor cells. Each compound demonstrated a slightly different profile in the various histological types of tumors. The nickel complex of Appip demonstrated the most potent in vivo activity in the Ehrlich ascites carcinoma. This agent selectively inhibited L1210 DNA and purine syntheses, and DNA polymerase α, PRPP-amido transferase, IMP-dehydrogenase, dihydrofolate reductase...

  1. Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

    Directory of Open Access Journals (Sweden)

    Kretzer IF

    2016-03-01

    Full Text Available Iara F Kretzer,1,2 Durvanei A Maria,3 Maria C Guido,1 Thaís C Contente,1 Raul C Maranhão1,2 1Laboratory of Metabolism and Lipids, Heart Institute of the Medical School Hospital, 2Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo, 3Biochemistry and Biophysics Laboratories, Butantan Institute, São Paulo, Brazil Purpose: Lipid nanoemulsions (LDEs that bind to low-density lipoprotein (LDL receptors used as carriers of paclitaxel (PTX can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva, which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX. Materials and methods: B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls, Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 µmol/kg (three intraperitoneal injections, 3 alternate days: Simva 50 mg/kg/day by gavage, 9 consecutive days. Results: Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion: Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX. Keywords: lipid nanoparticles, drug delivery, statins, cancer treatment, B16F10 melanoma

  2. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment. PMID:26996021

  3. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study.

    Science.gov (United States)

    Boehrer, Simone; Adès, Lionel; Braun, Thorsten; Galluzzi, Lorenzo; Grosjean, Jennifer; Fabre, Claire; Le Roux, Génèviève; Gardin, Claude; Martin, Antoine; de Botton, Stéphane; Fenaux, Pierre; Kroemer, Guido

    2008-02-15

    Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), induces differentiation, cell-cycle arrest, and apoptosis of EGFR-negative myeloblasts of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as in EGFR-negative cell lines representing these diseases (P39, KG-1, and HL 60). This off-target effect can be explained by inhibitory effects on JAK2. Apoptosis induction coupled to mitochondrial membrane permeabilization occurred independently from phenotypic differentiation. In apoptosis-sensitive AML cells, erlotinib caused a rapid (within less than 1 hour) nucleocytoplasmic translocation of nucleophosmin-1 (NPM-1) and p14(ARF). Apoptosis-insensitive myeloblasts failed to manifest this translocation yet became sensitive to apoptosis induction by erlotinib when NPM-1 was depleted by RNA interference. Moreover, erlotinib reduced the growth of xenografted human AML cells in vivo. Erlotinib also killed CD34(+) bone marrow blasts from MDS and AML patients while sparing normal CD34(+) progenitors. This ex vivo therapeutic effect was once more associated with the nucleocytoplasmic translocation of NPM-1 and p14(ARF). One patient afflicted with both MDS and non-small cell lung cancer manifested hematologic improvement in response to erlotinib. In summary, we here provide novel evidence in vitro, ex vivo, and in vivo for the potential therapeutic efficacy of erlotinib in the treatment of high-risk MDS and AML.

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

    Science.gov (United States)

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

    2016-01-01

    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.

  5. Identification of sirna of p53 family members to develop new antineoplastic drugs

    International Nuclear Information System (INIS)

    During the three years of the project we have identified a crucial role for miR-92, a micro RNA that is part of the miR-17 cluster, in controlling 32D myeloid cells proliferation. We have demonstrated that miR-92 is expressed in myeloid cells and it induces proliferation of these cells. We demonstrated that miR-92 acts by repressing one of the p63 isoforms expressed in these cells, whose 3'UTR contains a miR-92 consensus site conserved across species. P63 is a p53 homolog whose activity is critical for proper cell differentiation during development, by regulating the proliferative potential of the cells

  6. 75 FR 57044 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010

    Science.gov (United States)

    2010-09-17

    ... published for comment in NIOSH Docket Number 105. After expert panel review, public review and comment, input from stakeholders and review of the scientific literature NIOSH proposed a second, draft list...

  7. Efficacy of antineoplastic treatment is associated with the use of antibiotics that modulate intestinal microbiota.

    Science.gov (United States)

    Pflug, Natali; Kluth, Sandra; Vehreschild, Jörg J; Bahlo, Jasmin; Tacke, Daniela; Biehl, Lena; Eichhorst, Barbara; Fischer, Kirsten; Cramer, Paula; Fink, Anna-Maria; von Bergwelt-Baildon, Michael; Stilgenbauer, Stephan; Hallek, Michael; Cornely, Oliver A; Vehreschild, Maria J G T

    2016-06-01

    Reduced anticancer efficacy of cyclophosphamide and platinum salts has been reported in animals treated with anti-Gram-positive antibiotics. These effects were related to translocation of Gram-positive bacteria during mucositis with subsequent induction of cytotoxic oxygen reactive species and tumor invasion by pathogenic Th17 cells. To assess these hypotheses in a clinical setting, we identified patients receiving cyclophosphamide for chronic lymphocytic leukemia (CLL) and cisplatin for relapsed lymphoma. Data originated from the CLL8 trial (NCT00281918) and the Cologne Cohort of Neutropenic Patients (NCT01821456). Relevant antibiotics were defined as compounds with primary activity against Gram-positive bacteria. We evaluated their impact on response, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier methodology and Cox proportional hazards regression analysis. Among 800 available CLL patients, those receiving anti-Gram-positive antibiotics (n = 45/800) achieved a significantly lower overall response rate (OR 74.3% vs. 90.2%, p = 0.007). Patients with anti-Gram-positive antibiotics progressed significantly earlier, had a reduced OS (median PFS 14.1 vs. 44.1 mo, p administration of anti-Gram-positive antibiotic treatment was independently associated with reduced PFS (Hazard ratio (HR) 2.090, p = 0.001) and OS (HR 2.966, p HR 2.237, p = 0.012) and OS (HR 7.831, p < 0.001). Our data supports a potential negative impact of anti-Gram-positive antibiotics on the anticancer activity of cyclophosphamide and cisplatin in a clinical setting. PMID:27471619

  8. The antineoplastic agent α-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes.

    Science.gov (United States)

    Rigo, Antonella; Vinante, Fabrizio

    2016-08-01

    The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuses on the relevant steps in the cytotoxic cascade triggered by α-BSB: (1) the lipid rafts through which α-BSB enters the cells, (2) the opening of pores in the mitochondria and lysosomes, (3) the activation of both caspase-dependent and caspase-independent cell death pathways, (4) the induction of autophagy and (5) apoptosis. The effectiveness of α-BSB as an agent against tumor cells is grounded on its capability to act on different layers of cell regulation to elicit different concurrent death signals, thereby neutralizing a variety of aberrant survival mechanisms leading to treatment resistance in neoplastic cell. PMID:27278818

  9. Antineoplastic Effects of 5-Aminosalicylates and Potential Cancer Preventive Role in Inflammatory Bowel Disease

    OpenAIRE

    2004-01-01

    Early studies from tertiary referral centers in the United States and Europe showed that patients with long-standing and extensive inflammatory bowel disease (IBD) have an increased risk of colon cancer. It was subsequently appreciated that the degree of risk depended on the population being studied and on both genetic and environmental factors (eg diet, drugs and prior surgical treatment). Indeed, over the past decade or so, the effects of chronically administered medications, including 5-am...

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

    Science.gov (United States)

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

    1992-04-01

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

  11. 5-Azacytidine and 5-aza-2'-deoxycytidine behave as different antineoplastic agents in B16 melanoma.

    OpenAIRE

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

    1987-01-01

    The antiproliferative effects of 5-azacytidine (acaCyd) and 5-aza-2'-deoxycytidine (azadCyd) were studied in murine B16 melanoma and a series of B16 melanoma derived mutant strains with selective resistances to the respective drugs. The in vitro cytotoxicities of azaCyd and azadCyd on B16 wild type, expressed in terms of IC50 values, were found to be 5 microM and 0.2 microM, respectively. The in vitro cytotoxicity of both drugs was dependent on the duration of exposure. Uridine and cytidine w...

  12. 5-Azacytidine and 5-aza-2'-deoxycytidine behave as different antineoplastic agents in B16 melanoma.

    Science.gov (United States)

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

    1987-01-01

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

  13. PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2007-11-01

    Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

  14. Antineoplastic agents; I. Three spirostanol glycosides from rhizomes of Dioscorea collettii var. hypoglauca.

    Science.gov (United States)

    Hu, K; Dong, A; Yao, X; Kobayashi, H; Iwasaki, S

    1996-12-01

    By activity-guided fractionation, three known steroidal saponins, prosapogenin A of dioscin, dioscin and gracillin, were isolated from the total saponin fraction of Dioscorea coiletti var. hypoglauca as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic activity against the cancer cell line K562 in vitro. The structures of the compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H-NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis. PMID:9000889

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

    Directory of Open Access Journals (Sweden)

    Chen Li

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

    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.

  18. In silico ADME and Toxicity Study of Some Selected Antineoplastic Drugs

    OpenAIRE

    Chandra Shekhar Sharma; Shashank Shekher Mishra; Hamendra Pratap Singh; Neeraj Kumar

    2016-01-01

    Cancer is a serious health problem that recognized as a group of diseases involving uncontrolled cell growth. Majority of cancer chemotherapeutic agents have serious toxicity profile. Due to this use of these agents are limited. Therefore, it is essential requirement for developing new chemotherapeutic agents to devoid toxicity. In this research work, we study the pharmacokinetic, toxicity and bioactivity profile of few selected chemotherapeutic agents by In silico method. These research inve...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  1. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    Science.gov (United States)

    El-Merahbi, Rabih; Liu, Yen-Nien; Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs. PMID:25380390

  2. Protein-polyamine conjugates by transglutaminase 2 as potential markers for antineoplastic screening of natural compounds.

    Science.gov (United States)

    Lentini, A; Provenzano, B; Tabolacci, C; Beninati, S

    2009-04-01

    The role of post-translational modification of cell proteins with polyamines, a reaction catalyzed by a tissue tranglutaminase (TG, EC 2.3.2.13), in the induction of cell differentiation, represents an intriguing strategy to control cell proliferation and metastatic ability of different tumor cell lines. In this review, we focus our attention on the metabolic aspects of some natural compounds (methylxantines, retinoids and flavonoids) responsible of their antitumor effects exerted through the induction of TG activity in cancer cells.

  3. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Rabih El-Merahbi

    Full Text Available Cancer stem cells (CSCs, including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1 in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS. Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  4. Anti-neoplastic activity of two flavone isomers derived from Gnaphalium elegans and Achyrocline bogotensis.

    Directory of Open Access Journals (Sweden)

    Christan M Thomas

    Full Text Available Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic effects of two flavone isomers on human cancer cells from breast (MCF7, SK-BR-3, colon (Caco-2, HCT116, pancreas (MIA PaCa, Panc 28, and prostate (PC3, LNCaP that vary in differentiation status and tumorigenic potential. These flavones are derived from plants of the family Asteraceae, genera Gnaphalium and Achyrocline reputed to have anti-cancer properties. Our studies indicate that 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone displays potent activity against more differentiated carcinomas of the colon (Caco-2, and pancreas (Panc28, whereas 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone cytototoxic action is observed on poorly differentiated carcinomas of the colon (HCT116, pancreas (Mia PaCa, and breast (SK-BR3. Both flavones induced cell death (>50% as proven by MTT cell viability assay in these cancer cell lines, all of which are regarded as highly tumorigenic. At the concentrations studied (5-80 µM, neither flavone demonstrated activity against the less tumorigenic cell lines, breast cancer MCF-7 cells, androgen-responsive LNCaP human prostate cancer line, and androgen-unresponsive PC3 prostate cancer cells. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone displays activity against more differentiated carcinomas of the colon and pancreas, but minimal cytotoxicity on poorly differentiated carcinomas of these organs. On the contrary, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone is highly cytotoxic to poorly differentiated carcinomas of the colon, pancreas, and breast with minimal activity against more differentiated carcinomas of the same organs. These differential effects suggest activation of distinct apoptotic pathways. In conclusion, the specific chemical properties of these two flavone isomers dictate mechanistic properties which may be relevant when evaluating biological responses to flavones.

  5. [Antineoplastic treatment impact on nutritional status in patients with breast cancer].

    Science.gov (United States)

    Monroy Cisneros, Karina; Astiazarán García, Humberto; Esparza Romero, Julián; Guevara Torres, Alfonso Genaro; Valencia Juillerat, Mauro E; Méndez Estrada, Rosa Olivia; Tortoledo Ortiz, Orlando; Pacheco Moreno, Bertha Isabel

    2014-10-01

    Presentación: El cáncer de mama es el tipo de tumor más frecuentemente diagnosticado entre las mujeres de México y también el de más alta mortalidad. Aunque el tratamiento ha mejorado significativamente, puede afectar al estado nutricional del paciente. Objetivo: El objetivo de este estudio era evaluar el impacto de la fase inicial de la terapia antineoplásica sobre el estado nutricional en pacientes con cáncer de mama. Métodos: Cuarenta sujetos con diagnóstico primario de cáncer de mama invasivo fueron estudiados antes y después de la intervención (con seis meses de desfase) usando un diseño quasi-experimental. Las mediciones al inicio y seis meses después de la intervención incluyeron antropometría, composición corporal mediante absorciometría dual de rayos X (DEXA), cuestionario de recopilación de dieta en 24 horas y frecuencia de comidas, y suero beta-caroteno y retinol. El efecto de la terapia fue analizado empleando mediciones repetidas y regresión lineal mixta. Resultados: El tejido magro disminuyó tras el periodo de estudio (p=0.032). Además, se dio una interacción entre los parámetros de peso, IMC y grasa corporal con el estado de menopausia, aumentando en estas variables debido a la terapia solo en pacientes premenopáusicas (p=0.005, 0.006 y 0.001, respectivamente). Descenso de retinol sérico (p=0.049) a pesar de la mejoría en el estado de beta-caroteno (p=0.03). En general hubo un aumento en el consumo de verdura y un descenso de productos animales. Conclusión: El tratamiento antineoplásico del cáncer de mama tuvo un efecto negativo sobre el peso y la grasa corporal, especialmente en mujeres jóvenes. Aunque se observaron algunos cambios positivos en la dieta, el consumo de verdura siguió siendo insuficiente, lo que también se reflejó en los biomarcadores séricos.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-04-01

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

  8. The association between the antineoplastic drug daunomycin and iron. Evidence for polynuclear aggregates

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    1996-08-01

    A series of new compounds containing a 9,10-anthracenedione moiety and one or two peptide chains at position 1 and/or 4 have been synthesized. The amino acid residues introduced are glycine (Gly), lysine (Lys), and tryptophan (Trp), the latter two in both the L- and D-configurations. The peptidyl anthraquinones maintain the ability of intercalating efficiently into DNA, even though the orientation within the base-pair pocket may change somewhat with reference to the parent drugs mitoxantrone (MX) and ametantrone (AM). The interaction constants of the mono-, di-, and triglycyl derivatives are well comparable to those found for AM but 5-10 times lower than the value reported for MX. On the other hand, the glycyl-lysyl compounds bind DNA to the same extent as (L-isomer) or even better than (D-isomer) MX. As for the parent drugs without peptidyl chains, the new compounds prefer alternating CG binding sites, although to different extents. The bis-Gly-Lys derivatives are the least sensitive to base composition, which may be due to extensive aspecific charged interactions with the polynucleotide backbone. As far as redox properties are concerned, all peptidyl anthraquinones show a reduction potential very close to that of AM and 60-80 mV less negative than that of MX; hence, they can produce free-radical-damaging species to an extent similar to the parent drugs. The biological activity has been tested in human tumor and murine leukemia cell lines. Most of the test anthraquinones exhibit cytotoxic properties close to those of AM and considerably lower than those of MX. Stimulation of topoisomerase-mediated DNA cleavage is moderately present in representatives of the glycylanthraquinone family, whereas inhibition of the background cleavage occurs when Lys is present in the peptide chain. For most of the test anthraquinones, the toxicity data are in line with the DNA affinity scale and the topoisomerase II stimulation activity. However, in the lysyl derivatives, for which lack of cytotoxicity cannot be related to poor binding to DNA, the steric and electronic properties of the side-chain substituent must impair an effective recognition of the cleavable complex. PMID:8759632

  10. In silico ADME and Toxicity Study of Some Selected Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Chandra Shekhar Sharma

    2016-01-01

    Full Text Available Cancer is a serious health problem that recognized as a group of diseases involving uncontrolled cell growth. Majority of cancer chemotherapeutic agents have serious toxicity profile. Due to this use of these agents are limited. Therefore, it is essential requirement for developing new chemotherapeutic agents to devoid toxicity. In this research work, we study the pharmacokinetic, toxicity and bioactivity profile of few selected chemotherapeutic agents by In silico method. These research investigations provide the lead for the development of new cancer chemotherapeutic agents with lesser toxicity and more effectiveness.

  11. Histologic evaluation of wound healing in experimental intestinal anastomoses: effects of antineoplastic agents.

    OpenAIRE

    de Roy van Zuidewijn, D. B.; Schillings, P. H.; Wobbes, T; De Boer, H. H. (Hans)

    1992-01-01

    Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to impr...

  12. Use of the radiometric method at creation cell test-systems for pre-screening of anticancer preparations

    International Nuclear Information System (INIS)

    Full text: Development of cancer chemotherapy is tightly bound with investigation of biological activity of different compounds on in vitro test systems. Our research has been directed on definition of sensitivity of the cell line KML removed by us from passed of mice melanoma B-16. We had been investigated action of 18 clinical antineoplastic preparations of different classes: alkylating - sarcolysinum, thiophosphamide, dopan, fhthordopan; antimetabolites - cytararibinum, methotrexatum, 6-mercaptopurinum, 5-fhthorouracilum, fhthorafur; antineoplastic antibiotics- adriamycinum, neomycinum, rubomycinum, bruneomycinum, carminomycinum, olivomycinum; plant substances - vinblastinum, colchaminum (component of ointment which used at treatment of skin cancer) and other - carboplatin. Cytotoxic effect of preparations estimated two methods - radiometric on inclusion of 3H - timidine in cells and spectrophotometric by definition of total amount nucleic acids and protein. For this purpose KML cells passed in quantity of 120 thousand in 3 ml of nutrient medium RPMI 1640, 10 % calf embryo serum in bottles and after 24 hours entered substances in dozes from 0,01 up to 100 μg/ml. Contact of substances to cells was 24 hours, then 10 μ Ci 3H - timidine was injected on bottles at 1 hour. Cells transferred on GFC-filters, washed from not connected label. Filters transferred in scintillation liquid and a level of a radio-activity determined on β-counter. All tested clinical preparations appeared active within the criteria of activity, thus the radiometric method was more sensitive, than spectrophotometric. Thus, testing results of model have shown that stable cell line KML was sensitive to action of 18 clinical preparations with various mechanisms of action by different estimations of damaging action. This model can be used for biological activity of new potential cancerolytics pre-screening. This work was supported by the Center of Science and Technology of the Republic of

  13. Drug: D03150 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available :br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineo...plastic agents L01XX32 Bortezomib D03150 Bortezomib (JAN

  14. Drug: D04862 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX10 Masoprocol D04862... Masoprocol (USAN/INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents Masproc

  15. Drug: D02168 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineop...lastic agents L01XX17 Topotecan D02168 Nogitecan hydroch

  16. Drug: D05387 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available HER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX24 Pegaspargase ...D05387 Pegaspargase (USAN/INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents

  17. The Occupational Exposure which Medical Staff Handling Antineoplastic Agents Make in Antineoplastic Therapeutic Process and Protective Measure%医护人员对抗肿瘤药物的职业暴露及防护措施

    Institute of Scientific and Technical Information of China (English)

    艾建红; 张志娟; 王家彦; 刘俏; 王桂森

    2012-01-01

    Configuration and input chemotherapy drugs are one ofthe main jobs ofthe nurse, so it caused great threat to the health of the nursing staff. Occupational protection has already become our topic of high attention in recent years. Although many hospitals has established Pharmacy Intravenous Admixture Services, at work there are still a lot of temporary chemotherapy which need clinical nurses to dispose and contact antitumor drugs. This may lead to personal health risk. This paper reviewed common occupational exposure pathways during the anti-tumor therapy process, and put forward corresponding protective measures to provide medical personnel security information.%配置和输入化疗药物是护士的主要工作之一,故对护理人员的健康造成了很大的威胁.职业防护已成我们近年来高度关注的话题.虽很多医院现已改为中心配液,但在工作中仍有很多临时化疗医嘱需要临床护士,接触抗肿瘤药物可能导致个人健康风险.本文综述了抗肿瘤治疗过程中常见的职业暴露途径,并提出了针对性的防护措施,以期为医护人员提供安全保障信息.

  18. Biochemical, computer, and spectroscopic techniques applied to the study of prions and of combinations of antineoplastic drugs

    OpenAIRE

    Perra, Daniela

    2015-01-01

    This thesis collects the work I have done during the three-year PhD Course. The results obtained are divided according to the research topics addressed: · Drug discovery of anticancer agents and development of synergistic associations (Part I); · Studies on the prion structure and the pathogenesis of prion diseases (Part II). Studies referring to the Part I have been carried out at the University of Cagliari and were focalized on the evaluation and experimental validation of th...

  19. THE IMPORTANCE OF CONTINUING EDUCATION IN THE PREVENTION OF OCCUPATIONAL RISKS FOR NURSES WHO HANDLE ANTINEOPLASTIC DRUGS

    Directory of Open Access Journals (Sweden)

    Evelyn Nascimento Morais

    2011-04-01

    Full Text Available Objetivos: evidenciar e analisar, a partir do discurso dos enfermeiros, a atuação da Educação Continuada voltada a prevenção dos riscos ocupacionais oriundos do manuseio de quimioterápicos antineoplásicos. Método: trata-se de um estudo descritivo-exploratório, com abordagem qualitativa, utilizando entrevistas semi-estruturadas. Vinte enfermeiros estiveram inseridos nesta dinâmica. Resultados: as informações coletadas permitiram-nos a abordagem de pontos relevantes sobre a educação ocupacional dos trabalhadores que manuseiam/administram quimioterápicos antineoplásicos, traçando contribuições para o gerenciamento prevencional das doenças ocasionadas pelo trabalho. Conclusão: Os dados foram capazes de fornecer subsídios para o aperfeiçoamento e/ou aplicação de técnicas corretas e seguras voltadas a otimização do serviço prestado ao cliente oncológico em terapia antineoplásica. Descritores: Enfermagem do trabalho. Riscos ocupacionais. Saúde do trabalhador.

  20. Effect of lithium chloride and antineoplastic drugs on survival and cell cycle of androgen-dependent prostate cancer LNCap cells

    OpenAIRE

    Vajihe Azimian-Zavareh; Ghamartaj Hossein; Ehsan Janzamin

    2012-01-01

    Objective: Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs. Materials and Methods: Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with lo...

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

    NARCIS (Netherlands)

    Janssens, T.

    2012-01-01

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

  2. Stability of Antineoplastic Drugs after Preparation%抗肿瘤药物配制后稳定性探讨

    Institute of Scientific and Technical Information of China (English)

    杜洪全; 方英立

    2014-01-01

    检索中英文数据库,查阅有关文献,综述临床常用静脉用抗肿瘤药物配制后稳定的条件及时间,为临床安全用药提供参考。%Relevant literature in both English and Chinese database was retrieved. The time and conditions of medicine in stable state in prepared fluid of common clinical antitumor drugs were reviewed to provide reference for safe medication in clinic.

  3. How to deal with uncertainties regarding the occupational exposure to antineoplastic mixtures: additive effect should always be considered?

    OpenAIRE

    Ladeira, Carina; Viegas, Susana; Veiga, Ana Costa

    2016-01-01

    Risk assessment considerations - The concept that “safe levels of exposure” for humans can be identified for individual chemicals is central to the risk assessment of compounds with known toxicological profiles. Selection of agents for combination chemotherapy regimens involves minimize overlapping of mechanisms of action, antitumor activity and toxicity profile. Although the toxicological profile and mechanism of action of each individual drug is well characterized, the toxicological interac...

  4. The effects in mice of combined treatments to X-rays and antineoplastic drugs in the Comet assay

    International Nuclear Information System (INIS)

    The Comet assay is a rapid, easy and reproducible method to detect genotoxic activity of chemical and physical agents in vitro and in vivo. In the present study the effects of exposure to irradiation or chemicals: cyclophosphamide (CP) and mitomycin C (MMC) or combined exposure to low doses of both agents (0.25 Gy + 3.15 mg/kg bw CP and 0.25 Gy + 0.25 mg/kg bw MMC) were examined for the induction of DNA damage in the Comet assay measured simultaneously in somatic (bone marrow lymphocytes) and haploid germ cells. The male mice were treated in vivo and sacrificed at 24 h after exposure. The percentage contents of DNA in the 'comet tail' increased with increasing doses of X-rays and chemicals. After combined exposure to X-rays and CP and to X-rays and MMC weak increases of DNA damage in bone marrow lymphocytes and in germ cells were observed by comparison with the results obtained for each agent acting alone. There were slightly different responses in bone marrow lymphocytes and in germ cells, but effects were observed over a similar dose range

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

    OpenAIRE

    Janssens, T.

    2012-01-01

    Anticancer drugs themselves can cause adverse health effects when administered to human patients. In addition, it has become apparent that personnel in human medicine, occupationally exposed to these anticancer drugs, may also be at risk. The past decades, the use of chemotherapy in veterinary medicine has been gaining popularity. Consequently, an increasing number of people in veterinary medicine may be exposed to anticancer drugs. This raises the question whether veterinary personnel and ow...

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

    Science.gov (United States)

    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).

  7. Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes

    OpenAIRE

    Yamaguchi, Hiroaki; KOBAYASHI, Minako; Okada, Masahiro; Takeuchi, Toshiko; Unno, Michiaki; ABE, Takaaki; Goto, Junichi; Hishinuma, Takanori; Mano, Nariyasu

    2008-01-01

    A rapid screening system has been established to extract novel candidates that exhibit potent inhibition of the transport of fluorescent substrate by organic anion transporting polypeptide (OATP) 1B3. OATP1B3 is abundantly expressed in solid digestive organ cancers. Thus, the identification of new substrates leads to novel strategies for effective cancer chemotherapy with minimal adverse effects. We used an automated image acquisition and analysis system (IN Cell Analyzer 1000) to visualize ...

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

    OpenAIRE

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

    2011-01-01

    Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, ...

  9. Inhibition of SIRT2 Potentiates the Anti-motility Activity of Taxanes: Implications for Antineoplastic Combination Therapies12

    OpenAIRE

    Bonezzi, Katiuscia; Belotti, Dorina; North, Brian J.; Ghilardi, Carmen; Borsotti, Patrizia; Resovi, Andrea; Ubezio, Paolo; Riva, Antonella; Giavazzi, Raffaella; Verdin, Eric; Taraboletti, Giulia

    2012-01-01

    Taxanes are potent inhibitors of cell motility, a property implicated in their antiangiogenic and antimetastatic activity and unrelated to their antiproliferative effect. The molecular mechanism of this anti-motility activity is poorly understood. In this study, we found that paclitaxel induced tubulin acetylation in endothelial and tumor cells, at concentrations that affected cell motility but not proliferation (10-8 to 10-9 M, for 4 hours). Induction of tubulin acetylation correlated with i...

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

    Directory of Open Access Journals (Sweden)

    Eduardo Freddy Orrego Escobar

    2015-04-01

    Full Text Available Resumen El cáncer es una de las pandemias más relevantes. Existe una clara predominancia de esta patología con características epidemiológicas entre países en vías de desarrollo y países desarrollados. Es necesario diseñar estrategias de tratamiento y profilaxis efectivas, de bajo costo y mínimos efectos secundarios. El presente trabajo se enfoca en una breve revisión de las investigaciones que han dado luz del gran potencial que albergan las plantas, destacando aquellas realizadas en y con plantas de Latinoamérica considerando que es un universo de estudio aún incipiente. La gran batería de compuestos orgánicos y otras sustancias como proteínas indican que siguen siendo una alternativa confiable en la búsqueda de nuevos actores en la batalla contra el cáncer.

  11. Antineoplastic effects of deoxyelephantopin,a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells

    Institute of Scientific and Technical Information of China (English)

    Farha A.Kabeer; Geetha B.Sreedevi; Mangalam S.Nair; Dhanya S.Rajalekshmi; Latha P.Gopalakrishnan; Sujathan Kunjuraman; Remani Prathapan

    2013-01-01

    OBJECTIVE:Deoxyelephantopin,a sesquiterpene lactone from Elephantopus scaber,showed inhibition of the growth of various tumor cells in vitro.In the present study,we investigated the cytotoxicity and apoptosis-inducing capacity of deoxyelephantopin on lung adenocarcinoma (A549) cells.METHODS:The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined.The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay.Cellular morphology of deoxyelephantopin-treated cells was observed using phasecontrast microscopy.The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining,Hoechst 33342 staining,terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay,DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry.Activation of caspases was detected using fluorogenic substrate specific to caspases 2,3,8 and 9 and flow cytometric analysis.The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was also analyzed.RESULTS:Deoxyelephantopin exhibited cytotoxicity to A549 cells (IC5o =12.287 μg/mL),however,there was no toxicity towards normal human lymphocytes.Deoxyelephantopin suppressed the colony-forming ability of A549 cells in a dose-dependent manner.Acridine orange,ethidium bromide and Hoechst 33342 staining showed cell shrinkage,chromosomal condensation and nuclear fragmentation,indicating induction of apoptosis.Deoxyelephantopin increased apoptosis of A549 cells,as evidenced by more TUNEL-positive cells.DNA fragmentation and Annexin V staining revealed late-stage apoptotic cell population.Deoxyelephantopin inhibited A549 cell growth by cell cycle arrest at G2/M phase and induced apoptosis through both extrinsic and intrinsic pathways.CONCLUSION:These results suggest that deoxyelephantopin has great potential as a new chemotherapeutic agent to be developed further for the treatment of lung cancer.

  12. Validated Spectrophotometric Methods for the Determination of Mycophenolate: An Anti-Neoplastic Agent in Bulk and Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    A. Narendra

    2013-01-01

    Full Text Available Three simple, precise and cost-effective spectrophotometric methods have been developed for the determination of Mycophenolate in bulk and its pharmaceutical formulations. Mycophenolate shows max at 250.0 nm in zero-derivative spectrum (method A, 258.0 nm in first-derivative spectrum (method B and method C is based on the calculation of area under curve (AUC for analysis of Mycophenolate in the wavelength range of 240.0–260.0 nm. The drug follows the Beer-Lambert's law in the concentration range of 1.0–150.0 μg/mL for all the methods. The methods were validated by following the analytical performance parameters suggested by the International Conference on Harmonization. All validation parameters were within the acceptable range. The developed methods were successfully applied to estimate the amount of Mycophenolate in bulk and pharmaceutical dosage forms.

  13. Biocompatibility and in vitro antineoplastic drug-loaded trial of titania nanotubes prepared by anodic oxidation of a pure titanium

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    TiO2 nanotube (NT) arrays have been prepared by anodic oxidation of a Ti sheet,and carbon-deposited TiO2 NT arrays have been prepared by annealing TiO2 NT arrays in carbon atmosphere. The biocompatibility of the as-prepared NT arrays was investigated by observing the growth of osteosarcoma (MG-63) cells on the NT arrays. The application of the TiO2 NT arrays as a drug delivery vehicle was investigated. Both the TiO2 NTs and the carbon-modified TiO2 NTs have good biocompatibility supporting the normal growth and adhesion of MG-63 cells with no need of extracellular matrix protein coating. The one end-opened TiO2 NTs can be easily filled with drugs,working as an efficient drug delivery vehicle.

  14. Drug: D06130 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic...ne (INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents Tiazofurine [ATC:L01X

  15. Drug: D06320 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents Vorino...08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineopla...stic agents L01XX38 Vorinostat D06320 Vorinostat (JAN/US

  16. Drug: D08290 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents... L01XX36 Oblimersen D08290 Oblimersen (INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agen...ts Oblimersen [ATC:L01XX36] D08290 Oblimersen (INN) PubChem: 96024977 ...

  17. Drug: D07258 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX16 Mi...toguazone D07258 Mitoguazone (INN) Antineoplastics [BR:br08308] Miscellaneous agents... Other antineoplastic agents Mitoguazone [ATC:L01XX16] D07258 Mitoguazone (INN) CAS: 459-86-9 PubChem: 51

  18. Drug: D03259 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available LATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC05...ombination) (JAN); Gemtuzumab ozogamicin (USAN); Gemtuzumab (INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal

  19. Norspermidine and novel Pd(II and Pt(II polynuclear complexes of norspermidine as potential antineoplastic agents against breast cancer.

    Directory of Open Access Journals (Sweden)

    Tânia Magalhães Silva

    Full Text Available BACKGROUND: New strategies are needed for breast cancer treatment and one initial step is to test new chemotherapeutic drugs in breast cancer cell lines, to choose candidates for further studies towards clinical use. METHODOLOGY AND FINDINGS: The cytotoxic effects of a biogenic polyamine analogue - norspermidine - and its trinuclear Pd(II and Pt(II complexes - Pd(3NSpd(2 and Pt(3NSpd(2, respectively - were investigated in one immortalized normal-like and three breast cancer cell lines. The normal-like MCF-10A cells were least sensitive to the compounds, while growth inhibition and cell death was observed in the cancer cell lines. Norspermidine and its Pd(II complex were generally shown to have stronger antiproliferative effects than the corresponding Pt(II complex. Moreover, both norspermidine and the Pd(II complex reduced the cellular activity of the growth-related enzyme, ornithine decarboxylase (ODC to a lower level than the Pt(II complex in most of the cell lines examined. Treatment with norspermidine or the Pd(II complex reduced the number of colonies formed in a soft agar assay performed with the breast cancer cell lines, indicating that these compounds reduced the malignancy of the breast cancer cells. The effect of norspermidine or the Pd(II complex on colony formation was much stronger than that observed for the Pt(II complex. The results from a new mammalian genotoxicity screen together with those of a single cell gel electrophoresis assay indicated that none of the drugs were genotoxic at a 25 µM concentration. MAIN CONCLUSIONS: Overall, norspermidine and its Pd(II complex were shown to have strong antiproliferative effects. In comparison, the effects obtained with the Pd(II complex were much stronger than that of the Pt(II complex. The results obtained in the present study demonstrate that the trinuclear Pd(II complex of norspermidine (Pd(3NSpd(2 may be regarded as a potential new metal-based drug against breast cancer, coupling a significant efficiency to a low toxicity.

  20. The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

    Directory of Open Access Journals (Sweden)

    Mei-Han Huang

    2015-10-01

    Full Text Available Oxaliplatin (OXAL is a third-generation organoplatinum which is effective against advanced cancer cells including glioma cells. How this agent and other related compounds interacts with ion channels in glioma cells is poorly understood. OXAL (100 µM suppressed the amplitude of whole-cell K+ currents (IK; and, either DCEBIO or ionomycin significantly reversed OXAL-mediated inhibition of IK in human 13-06-MG glioma cells. In OXAL-treated cells, TRAM-34 did not suppress IK amplitude in these cells. The intermediate-conductance Ca2+-activated K+ (IKCa channels subject to activation by DCEBIO and to inhibition by TRAM-34 or clotrimazole were functionally expressed in these cells. Unlike cisplatin, OXAL decreased the probability of IKCa-channel openings in a concentration-dependent manner with an IC50 value of 67 µM. No significant change in single-channel conductance of IKCa channels in the presence of OXAL was demonstrated. Neither large-conductance Ca2+-activated K+ channels nor inwardly rectifying K+ currents in these cells were affected in the presence of OXAL. OXAL also suppressed the proliferation and migration of 13-06-MG cells in a concentration- and time-dependent manner. OXAL reduced IKCa-channel activity in LoVo colorectal cancer cells. Taken together, the inhibition by OXAL of IKCa channels would conceivably be an important mechanism through which it acts on the functional activities of glioma cells occurring in vivo.

  1. Tumor Destruction and In Situ Delivery of Antigen Presenting Cells Promote Anti-Neoplastic Immune Responses: Implications for the Immunotherapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Manfredi AA

    2004-07-01

    Full Text Available Antigen presenting cells (APCs activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2014-09-15

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

  4. Intensification of the influence of the antineoplastic medicines of the local application through their concentration with the generators of the electrons of the internal conversion

    International Nuclear Information System (INIS)

    Full text : This article offers a technology using the accelerators of the electrons for the generators of the electrons of the internal conversion only with the lower kinetic energy but the higher degree of the local ionization of the medium molecules particularly for the deep ionized destructions of the biological activity of the cancerous growth of tissues in the visible part of the human body

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

    OpenAIRE

    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+ cel...

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

    Science.gov (United States)

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

    2014-01-01

    Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors. PMID:24741306

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

    Directory of Open Access Journals (Sweden)

    Yurgel VC

    2014-03-01

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

  8. A Comparative Docking Strategy to Identify Polyphenolic Derivatives as Promising Antineoplastic Binders of G-quadruplex DNA c-myc and bcl-2 Sequences.

    Science.gov (United States)

    Costa, Giosuè; Rocca, Roberta; Moraca, Federica; Talarico, Carmine; Romeo, Isabella; Ortuso, Francesco; Alcaro, Stefano; Artese, Anna

    2016-09-01

    Polyphenols are compounds ubiquitously expressed in plants and used for their multiple healthy effects in humans as anti-inflammatory, antimicrobial, antiviral, anticancer and immunomodulatory agents. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis, polyphenols can be employed to inhibit the growth of cancer cells. Several studies reported their high affinity to different G-quadruplex DNA structures, including the oncogene promoters c-myc and bcl-2. In this work we applied a structure-based virtual screening approach in order to screen a database of polyphenolic derivatives and human metabolites against both c-myc and bcl-2 DNA G-quadruplex structures. A Delphinidine derivative was identified as the best "dual" candidate and, after molecular dynamics simulations, resulted able to well stabilize both receptors. PMID:27546043

  9. A study of Nigella sativa induced growth inhibition of MCF and HepG2 cell lines: An anti-neoplastic study along with its mechanism of action

    Directory of Open Access Journals (Sweden)

    Y Padmanabha Reddy

    2015-01-01

    Full Text Available Objective: To evaluate the anticancer potential of seeds of Nigella sativa using MCF and HepG2 cell lines along with its mechanism of action. Materials and Methods: (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and acridine orange/ethidium bromide nuclear staining technique were selected to evaluate anticancer potential and mechanism of action of test extract. Results: Aqueous extract of N.sativa at a test dose of 180 mg and 300 mg was identified to be the best as anticancer agent against MCF and HepG2 cell lines among different solvent test extract where doxorubicin and cisplatin were employed as standard references. Discussion: Further study including separation and characterization of active principles in the aqueous extract shall prove beneficial.

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

    Science.gov (United States)

    Bosanquet, A G

    1985-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

    The objective of the present investigation was to develop and validate a 'green' reversed phase high-performance liquid chromatography (RP-HPLC) method for rapid analysis of a cytotoxic drug 5-fluorouracil (5-FU) in bulk drug, marketed injection, water-in-oil (w/o) nanoemulsion, double water-in-oil-in-water (w/o/w) nanoemulsion and bacterial ghost (BG) matrix. The chromatography study was carried out at room temperature (25±1°C) using an HPLC system with the help of ultraviolet (UV)-visible detector. The chromatographic performance was achieved with a Nucleodur 150mm×4.6mm RP C8 column filled with 5µm filler as a static phase. The mobile phase consisted of ethyl acetate: methanol (7:3% v/v) which was delivered at a flow rate of 1.0mLmin(-1) and the drug was detected in UV mode at 254nm. The developed method was validated in terms of linearity (r(2)=0.998), accuracy (98.19-102.09%), precision (% RSD=0.58-1.17), robustness (% RSD=0.12-0.53) and sensitivity with satisfactory results. The efficiency of the method was demonstrated by the assay of the drug in marketed injection, w/o nanoemulsion, w/o/w nanoemulsion and BG with satisfactory results. The successful resolution of the drug along with its degradation products clearly established the stability-indicating nature of the proposed method. Overall, these results suggested that the proposed analytical method could be effectively applied to the routine analysis of 5-FU in bulk drug, various pharmaceutical dosage forms and BG. PMID:27154677

  12. Antineoplastic effect of a novel chemopreventive agent, neokestose, on the Caco-2 cell line via inhibition of expression of nuclear factor-κB and cyclooxygenase-2.

    Science.gov (United States)

    Lee, Shun-Mei; Chang, Jan-Yi; Wu, Jiann-Shing; Sheu, Dey-Chyi

    2015-07-01

    Neokestose is a 6G-fructooligosaccharide (FOS) and an important prebiotic. When FOS are ingested by patients with colorectal cancer, they may come into contact with cancer cells prior to being fermented by bifidobacteria in the colon. In the present study, the effects of neokestose on cell proliferation, cell cycle and apoptosis of the colorectal cancer cell line Caco-2 were investigated to evaluate its anti-cancer effect. An MTT assay showed that neokestose-treated Caco-2 cells exhibited a significant and dose-dependent loss of viability. Flow cytometric analysis indicated that the sub-G1 population of Caco-2 cells was significantly increased following treatment with neokestose, and the percentage of Caco-2 cells in the stage of late apoptosis was also significantly increased in a dose-dependent manner. Western blot analysis showed that the overexpression of nuclear factor-κB, a central molecule responsible for the transition from inflammation to cancer, and cyclooxygenase-2, an important enzyme in colorectal tumorigenesis, in colorectal carcinoma cells was inhibited by neokestose. Accordingly, the present study provided in vitro evidence that neokestose may be used as a dietary chemopreventive agent, whose application is more rational than that of COX-2 inhibitors or aspirin for preventing colorectal cancer. PMID:25815878

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

    Science.gov (United States)

    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 (PAnnona muricata. Isolation of the active metabolites from the extract is in prospect.

  14. Drug: D08956 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01...oplastic agents Omacetaxine [ATC:L01XX40] D08956 Omaceta...XX40 Omacetaxine mepesuccinate D08956 Omacetaxine mepesuccinate (USAN) Antineoplastics [BR:br08308] Miscellaneous agents Other antine

  15. Drug: D07257 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available NTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic...tics [BR:br08308] Miscellaneous agents Other antineoplastic agents Lonidamine [ATC:L01XX07] D07257 Lonidamin

  16. Drug: D02494 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available PLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic... [BR:br08308] Miscellaneous agents Other antineoplastic agents Miltefosine [ATC:L01XX09] D02494 Miltefosine

  17. Drug: D05216 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX36 Oblimersen D05216 Oblimersen sod...ium (USAN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents Oblimersen [ATC:L01XX36] D05216 Oblimersen sodium (USAN) CAS: 190977-41-4 PubChem: 47206935 ...

  18. Drug: D06066 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available porfin (USAN/INN) Antineoplastics [BR:br08308] Miscellaneous agents Sensitizers used in photodynamic/radiati...dynamic/radiation therapy L01XD05 Temoporfin D06066 Temo...ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XD Sensitizers used in photo

  19. Drug: D03257 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ptide Antineoplastic [DS:H00031] Therapeutic category: 4291 ATC code: L01XC03 breast cancer treatment Monoclonal... IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibod...57 Trastuzumab (genetical recombination) (JAN); Trastuzumab (INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal

  20. Deoxycytidine kinase modulates the impact of the ABC transporter ABCG2 on clofarabine cytotoxicity

    OpenAIRE

    Nagai, Shinjiro; Takenaka, Kazumasa; Nachagari, Deepa; Rose, Charles; Domoney, Kali; Sun, Daxi; Sparreboom, Alex; Schuetz, John D.

    2011-01-01

    Purine nucleoside antimetabolites, such as clofarabine, are effective antileukemic agents. However, their effectiveness depends on an initial activation step in which they are monophosphorylated by deoxycytidine kinase (dCK). Some purine nucleoside antimetabolites and their monophosphate derivatives are exported by the ABC transporter ABCG2. Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK ...

  1. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer

    OpenAIRE

    Boulware, Stephen B.; Christensen, Laura A.; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M.; Finch, Rick A.

    2013-01-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly-proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene,...

  2. Drug: D08880 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available STIC AGENTS L01XX Other antineoplastic agents L01XX45 Carfilzomib D08880 Carfilzomib (INN/USAN) Target-based...ASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLA

  3. Drug: D03455 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC06 Cetuximab D03455 Cetuximab (...; Cetuximab (USAN/INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Cetuxima

  4. Drug: D09587 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC12 B...587 Brentuximab vedotin (USAN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal

  5. Drug: D09217 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09217 Drug Sitimagene ceradenovec (INN) gene-based drug [DS:H00042] ATC code: L01X...GENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX37 Sitimagene ceradenovec D09217 Sitimagen...e ceradenovec (INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplastic agents Sitimagen...e ceradenovec [ATC:L01XX37] D09217 Sitimagene ceradenovec (INN) CAS: 898830-54-1 PubChem: 96025897 ...

  6. Drug: D05350 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ctibix (TN) Antineoplastic; Treatment of EGF expressing tumors [DS:H00020] Therapeutic category: 4291 ATC code: L01XC08 Monoclonal...N/INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Panitumumab [ATC:L01XC08...oclonal antibodies L01XC08 Panitumumab D05350 Panitumumab (genetical recombination)...EOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Mon

  7. Drug: D03106 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX25 Bexarotene D03106 Bexarotene (USAN/INN...5 K06258] Bexarotene [ATC:L01XX25] D03106 Bexarotene (USAN/INN) Antineoplastics [BR:br08308] Miscellaneous agents Other antineoplasti

  8. Drug: D02908 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XD Sensitizers used in photodynamic/radiation therapy...ydrochloride (JAN/USAN) Antineoplastics [BR:br08308] Miscellaneous agents Sensitizers used in photodynamic/radiation therapy

  9. Drug: D03958 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03958 Drug Edrecolomab (USAN/INN); Panorex (TN) Monoclonal antibody [antineoplasti...MODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal...58 Edrecolomab (USAN/INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal

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

    Directory of Open Access Journals (Sweden)

    N. V. Jiménez Torres

    2009-06-01

    Full Text Available Introducción: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA. Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los alimentos con medicamentos antineoplásicos orales y establecer recomendaciones para su administración. Métodos: Se realizó una búsqueda bibliográfica en Medline y The Cochrane Library para el periodo comprendido entre enero de 1966 a marzo de 2008, enfocada a identificar las publicaciones sobre interacciones fármaco alimento con antineoplásicos orales. El análisis bibliográfico consta de dos fases. En la primera fase se excluyeron los artículos que por título y contenido del resumen no se correspondían con el objetivo planteado; en la segunda fase se eliminaron las referencias duplicadas en ambas bases de datos. Los criterios de inclusión para seleccionar los artículos fueron: diseño (revisiones sistemáticas, metaanálisis, ensayos clínicos randomizados Fase I y II, población (pacientes adultos; >19 años de edad, intervención evaluada (administración de antineoplásicos orales bajo condiciones de ayuno o con alimentos y medida del resultado de la iFA (cálculo del IC90% de la razón entre la media geométrica de valores del área bajo la curva de concentraciones plasmáticas (ABC o la concentración plasmática máxima (Cmax con y sin alimentos. Se excluyeron las publicaciones que como medida de resultado no hacían referencia al dictamen de bioequivalencia establecido por la Food and Drugs Administration (FDA. La valoración crítica de los artículos seleccionados se realizó según las recomendaciones que de acuerdo con la FDA deben cumplir estos estudios. Resultados: En la búsqueda inicial se obtuvieron 850 referencias (98,5% Medline + y 1,4% Cochrane. En la primera fase se excluyeron el 87,7% (746 de los artículos, correspondiendo el 100% a la búsqueda en Medline. En la segunda fase, quedaron 40 artículos (5,2% de los iniciales para su lectura crítica a texto completo, a los que se añadieron cuatro más no indexados en Medline. De la lectura crítica de los 44 artículos finales, se excluyeron 25 artículos (20 artículos originales, 4 comunicaciones cortas y 1 metanálisis por no incluir como medida de resultado el dictamen de bioequivalencia. Los 19 (2,2% artículos restantes proporcionaron información sobre 19 fármacos antineoplásicos orales, en 210 pacientes y 146 voluntarios sanos. De estos 19 fármacos, el 63% no presentan iFA o interacciones fármaco-alimento, pudiéndose administrar indistintamente con/sin alimentos; el 21% se deben administrar con alimentos y sólo el 16% presentan interacción fármaco alimento, por lo que se deben administrar sin alimentos. Discusión: Actualmente, la importancia clínica de las interacciones fármaco alimento con antineoplásicos orales se identifica más directamente con la seguridad del paciente que con la efectividad del tratamiento. Ante el desarrollo de estos agentes orales, su irrupción en la terapia oncológica desplazando a la terapia parenteral, con costes mensuales de miles de euros, hay necesidad de realizar estudios farmacocinéticos y farmacodinámicos bien diseñados. Su objetivo debe de ser comparar su biodisponibilidad en presencia o ausencia de alimentos con la respuesta clínica. Mientras tanto, establecer recomendaciones para su administración en relación con los alimentos, es inconsistente para algunos de estos fármacos y su resultado incierto por la falta de estudios fundamentados en el dictamen de bioequivalencia establecido por la FDA.Introduction: studies on bioavailability are part of the clinical development of drugs for oral use in order to identify potential drug-food interactions. For oral antitumor drugs, their clinical importance is currently recognized although regrettably the information available presents variability concerning the scientific evidence. Objectives: To review the available scientific evidence about oral anti-tumor medications and establish the recommendations for their administration with foods. Methods: We carried out a bibliographic search in Medline and The Cochrane Library for the period January of 1966 to March of 2008, focused on identifying those publications about drug-food interactions with oral antitumor medications. The bibliographical analysis was made in two steps. During the first phase, we excluded those articles in which the title or their content did not correspond with the objective settled; during the second phase, we deleted all the references duplicated in both databases. The inclusion criteria to select the articles were: design (systematic reviews, meta-analysis, Phase I and Phase II randomized clinical trials, population (adult patients; >19 years of age, intervention evaluated (administration of oral anti-tumor drugs under fasting conditions or with food and measurement of the iFA results (calculation of the 90% CI of the odds ratio between the geometric mean of the values under the curve of the plasma concentrations (ABC or the maximal plasma concentration (Cmax with and without foods. We excluded those publications that did not make reference to the bioequivalence dictamen established by the Food and Drugs Administration (FDA in their outcomes measurement. A critical appraisal of the selected articles was done according to the recommendations that the FDA established to be met by these studies. Results: At the initial search we obtained 850 references (98.5% Medline + and 1.4% Cochrane. During the first phase, we excluded 87.7% (746 of the articles, 100% of them corresponding to the search in Medline. During the second phase, 40 studies remained (5.2% of the initial ones for full-text critical appraisal, to which four studies were added not indexed in Medline. From the critical appraisal of the 44 final articles, 25 were excluded (20 original articles, 4 short communications, and 1 meta-analysis because they did not include as an outcome measure the bioequivalence dictamen. The 19 (2.2% remaining articles provided information on 19 oral anti-tumor drugs in 210 patients and 146 healthy volunteers. Of these 19 drugs, 63% did not present drugfood interactions, with the possibility of administering them either with or without food; 21% have to be administered with foods and only 16% present drug-food interactions, so they have to be administered without foods. Discussion: Currently, the clinical importance of drugfood interactions with oral anti-tumor drugs is identified more directly with the patient's safety than with the efficacy of the therapy. Given the development of these oral agents, their incorporation into the oncologic strategy displacing parenteral therapy, with monthly costs of thousands of Euros, it is necessary to perform well-designed studies on pharmacokinetics and pharmacodynamics. Their goal has to be comparing their bioavailability in the presence or absence of foods with the clinical response. In the meanwhile, to establish recommendations for their administration in relation to foods is inconsistent for some of these drugs and their results is uncertain given the lack of studies based on the FDAbioequivalence dictamen.

  11. 基因芯片技术在抗肿瘤药物研究和肿瘤诊断中的应用%Applications of genechip technology in antineoplastic and cancer treatment

    Institute of Scientific and Technical Information of China (English)

    曹明楠; 崔俊; 李卫东

    2014-01-01

    Tumorigenesis is the combined effect of environmental and genetic factors on organisms, causing activation of multiple oncogenes, inactivation of tumor suppressor genes through a multistep, mutagenic process whereby cells undergo a series of physiological changes including regulation of apop-tosis and repairs of DNA damages. Gene chip technology is an emerging molecular biology technique developed in the mid-1990s. lt has high-throughput, multifactorial, miniaturized, sensitive, quick and other characteristics in genetic analyses. Application of these features in tumor research which involves a number of genetic changes could shed much light on tumor development so as to facilitate diagnosis and treatment of tumors. ln this paper, progress in gene chip technology for screening antitumor drug reaction mechanisms and antitumor drugs, toxicology of antitumor drugs, pharmacogenomics, tumor diagnosis and the search for tumor related genes were reviewed.%肿瘤的发生发展是遗传因素和环境因素共同作用于机体,通过多步骤诱变过程导致多个癌基因激活和抑癌基因失活,细胞发生包括凋亡调节和DNA修复损伤等一系列生理功能改变的结果。基因芯片技术是20世纪90年代中期发展起来的一种新兴分子生物学技术,在基因分析方面具有高通量、多因素、微型化和快速灵敏等特点,因此将基因芯片技术运用到涉及众多基因改变的肿瘤研究中,可以更全面地了解肿瘤发生发展机制,为肿瘤的诊治打下坚实的基础。本文就近些年来基因芯片技术在抗肿瘤药物的作用机制筛查、药物筛选和毒理学研究、药物基因组学、肿瘤诊断以及寻找肿瘤相关基因等抗肿瘤领域的进展进行综述。

  12. 龙葵生物碱体外抑制肿瘤细胞增殖作用的实验研究%Study of Antineoplastic Effects In Vitro of Solanine Extract on Human Lung Cancer A549 Cells

    Institute of Scientific and Technical Information of China (English)

    黄越燕; 朱琦峰; 周燕; 张莹楠

    2012-01-01

    目的:研究龙葵生物碱提取物对人肺癌A549细胞株增殖的抑制作用.方法:采用盐酸-乙醇混合溶剂加热回流法从龙葵中提取分离生物碱.以MTT法考察龙葵生物碱不同浓度对人肺癌A549细胞株增殖的抑制作用,采用倒置显微镜观察药物对肿瘤细胞株形态的影响.结果:龙葵生物碱提取物对人肺癌A549细胞株具有显著的细胞增殖抑制作用,且呈剂量依赖关系,并可使肿瘤细胞形态发生显著变化.结论:龙葵生物碱具有对肺癌细胞的抑制作用.

  13. 我院2011-2014年结直肠癌患者化疗用药分析%Analysis of the Application of Antineoplastic Drugs in Patients with Colorectal Cancer in Our Hospital during 2011-2014

    Institute of Scientific and Technical Information of China (English)

    邰宵辉; 张玲芳; 张旭霞; 刘乐; 彭艳艳; 杨静; 李红玲

    2015-01-01

    目的:为结直肠癌患者化疗提供方案以及用药参考。方法:查阅我院2011-2014年化疗的结直肠癌住院患者的病历及医嘱,对化疗方案和药物的使用及用药不合理现象进行回顾性统计、分析。结果:共纳入结直肠癌患者593例,化疗频次1940次,主要从化疗的适应证、方案的选择、化疗过程、化疗的时间及周期等方面对化疗方案选择进行分析;用药不合理409例,主要从药物剂量、溶剂选择、药物浓度等方面进行统计分析,不合格率为21.08%。结论:我院结直肠癌患者抗肿瘤药的使用以及化疗方案的选择基本合理,但仍存在一定的不足,在今后的临床应用中,有待进一步改进。%OBJECTIVE:To provide reference for medication and chemotherapy in patients with colorectal cancer. METH-ODS:Through retrospective study,case histories and doctor’s advice of the colorectal cancer patients receiving chemotherapy in our hospital during 2011-2014 were consulted to analyze the chemotherapy,medication and irrational drug use. RESULTS:A total of 593 cases of colorectal cancer patients with chemotherapy frequency of 1 940 times were collected to analyze the choice of che-motherapy regimen mainly from the following aspects:indications of chemotherapy,choice of chemotherapy regimen,chemothera-py process and chemotherapy period. There was 409 cases of irrational drug use according to the analysis of drug dosage,selection of solvents and drug concentration,the unqualified rate was 21.08% . CONCLUSIONS:The medication and chemotherapy in pa-tients with colorectal cancer in our hospital are basically rational,but there are still certain problems and shortcomings. In future clinical applications,the medication and chemotherapy need to be improved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, J

    2007-10-15

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

  15. Action mechanisms of antineoplastics of new synthesis and their possible use in therapy combined with radiation; Mecanismos de accion de antineoplasicos de nueva sintesis y su posible uso en terapia combinada con radiacion

    Energy Technology Data Exchange (ETDEWEB)

    Brena V, M.; Serment G, J. [ININ, Departamento de Biologia, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Ruiz A, L., E-mail: jorge.serment@inin.gob.m [UNAM, Facultad de Quimica, Departamento de Quimica Inorganica y Nuclear, Ciudad Universitaria, 04510 Mexico D. F. (Mexico)

    2010-07-01

    In this work is described one research line of the Molecular Biology Laboratory of the Biology Department of the Instituto Nacional de Investigaciones Nucleares (ININ), in which microorganisms or human cells cultivations are used as model to study the effect of a compounds group of new synthesis that it will be use in the treatment against the cancer, as well as the possible synergism of these pharmaceuticals with the ionizing radiation. The results show that, without to reach discarding other cellular structures, an important target for these substances in the DNA, and to this respect other hypothesis are exposed to explain some possible mechanisms of its action. Also, the preliminary data are presented as for the additive effect with the gamma radiation of two of the compounds that are candidates for their next clinical application. This research is part of a project in collaboration with the Chemistry Faculty of the UNAM. (Author)

  16. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna;

    2015-01-01

    85 antimetabolites that can inhibit growth of, or even kill, any of the cell lines, while at the same time not being toxic for 83 different healthy human cell types. 60 of these antimetabolites were found to inhibit growth in all cell lines. Finally, we experimentally validated one of the predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies.......Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...

  17. Drug: D04988 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available l 181.0506 181.6174 D04988.gif Antineoplastic agent used in photodynamic therapy ATC code: L01XD03 Anatomica...N) Antineoplastics [BR:br08308] Miscellaneous agents Sensitizers used in photodynamic/radiation therapy Meth...TINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XD Sensitizers used in photodynamic/radiation ther...apy L01XD03 Methyl aminolevulinate D04988 Methyl aminolevulinate hydrochloride (USA

  18. Learning about Lymphoma: Glossary of Terms

    Science.gov (United States)

    ... fluorouracil (5-FU), methotrexate, pentostatin, piritrexim, and trimetrexate. antineoplastic antibiotics: A group of chemotherapy drugs including cordycepin and the anthracyclines doxorubicin (Adriamycin, AD ...

  19. Predictive impact of RRM1 protein expression on vinorelbine efficacy in NSCLC patients randomly assigned in a chemotherapy phase III trial

    DEFF Research Database (Denmark)

    Vilmar, A C; Santoni-Rugiu, E; Sørensen, Jens Benn

    2013-01-01

    Platinum-based doublets (PBDs) remain the cornerstone of treatment in non-small-cell lung cancer (NSCLC) and may include gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward. Accordingly, we explored the predictive role of ribonucleotide...

  20. THE EFFECTS OF GAMMA-INTERFERON COMBINED WITH 5-FLUOROURACIL OR 5-FLUORO-2'-DEOXYURIDINE ON PROLIFERATION AND ANTIGEN EXPRESSION IN A PANEL OF HUMAN COLORECTAL-CANCER CELL-LINES

    NARCIS (Netherlands)

    MAAS, IWHM; BOVEN, E; PINEDO, HM; SCHLUPER, HMM; Haisma, Hidde

    1991-01-01

    Gamma-Interferon (IFN-gamma) and the antimetabolites 5-fluorouracil (5-FU) and S-fluoro-2'-deoxyuridine (FUdR) were investigated as individual agents and in combination for their in vitro antiproliferative capacity and for their effect on the expression of HLA class-I antigen, carcinoembryonic antig

  1. Mangotoxin production of Pseudomonas syringae pv. syringae is regulated by MgoA

    NARCIS (Netherlands)

    Carrion, V.J.; Voort, van der M.; Arrebola, E.; Gutiérrez-Barranquero, J.A.; Vicente, de A.; Raaijmakers, J.M.; Cazorla, F.M.

    2014-01-01

    Background The antimetabolite mangotoxin is a key factor in virulence of Pseudomonas syringae pv. syringae strains which cause apical necrosis of mango trees. Previous studies showed that mangotoxin biosynthesis is governed by the mbo operon. Random mutagenesis led to the identification of two other

  2. Systemic Medications for Psoriasis and Psoriatic Arthritis Including Biologics

    Science.gov (United States)

    ... as antimetabolites. It was initially used to treat cancer. Methotrexate was found to be effective in clearing psoriasis ... sold as a generic. The doses administered for cancer are considerably higher than those given for psoriasis ... is prescribed for adults with severe psoriasis or ...

  3. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer.

    Science.gov (United States)

    Boulware, Stephen B; Christensen, Laura A; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M; Finch, Rick A

    2014-09-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene, thereby inducing replication-independent, unscheduled DNA repair synthesis (UDS) preferentially in the TFO-targeted region. The TFO-directed UDS facilitated incorporation of the antimetabolite, gemcitabine (GEM), into the damaged oncogene, thereby potentiating the anti-tumor activity of GEM. Mice bearing COLO 320DM human colon cancer xenografts (containing amplified c-MYC) were treated with a TFO targeted to c-MYC in combination with GEM. Tumor growth inhibition produced by the combination was significantly greater than with either TFO or GEM alone. Specific TFO binding to the genomic c-MYC gene was demonstrated, and TFO-induced DNA damage was confirmed by NBS1 accumulation, supporting a mechanism of enhanced efficacy of GEM via TFO-targeted DNA damage-induced UDS. Thus, coupling antimetabolite chemotherapeutics with a strategy that facilitates selective targeting of cells containing amplification of cancer-relevant genes can improve their activity against solid tumors, while possibly minimizing host toxicity. PMID:23681918

  4. Vitamin D in combination cancer treatment

    OpenAIRE

    Ma,Yingyu; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    As a steroid hormone that regulates mineral homeostasis and bone metabolism, 1α, 25-dihydroxycholecalciferol (calcitriol) also has broad spectrum anti-tumor activities as supported by numerous epidemiological and experimental studies. Calcitriol potentiates the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-distu...

  5. Vitamin D in combination cancer treatment

    OpenAIRE

    Yingyu Ma, Donald L. Trump, Candace S. Johnson

    2010-01-01

    As a steroid hormone that regulates mineral homeostasis and bone metabolism, 1α, 25-dihydroxycholecalciferol (calcitriol) also has broad spectrum anti-tumor activities as supported by numerous epidemiological and experimental studies. Calcitriol potentiates the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-...

  6. The Pseudomonas aeruginosa oxyvinylglycine L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a weak seed germination-arrest factor

    Science.gov (United States)

    The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is demonstrated to share biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproduc...

  7. Leukemia from dermal exposure to cyclophosphamide among nurses in the Netherlands : Quantitative assessment of the risk

    NARCIS (Netherlands)

    Fransman, Wouter; Kager, Hans; Meijster, Tim; Heederik, Dick; Kromhout, Hans; Portengen, Lützen; Blaauboer, Bas J.

    2014-01-01

    Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to cycl

  8. Drug: D08679 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available aloids and analogues L01CA02 Vincristine D08679 Vincristine (INN) Target-based clas... ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01C PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS L01CA Vinca alk

  9. Leukemia from dermal exposure to cyclophosphamide among nurses in the Netherlands: Quantitative assessment of the risk

    NARCIS (Netherlands)

    Fransman, W.; Kager, H.; Meijster, T.; Heederik, D.; Kromhout, H.; Portengen, L.; Blaauboer, B.J.

    2014-01-01

    Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to cycl

  10. Chemoprevention of photocarcinogenesis by selected dietary botanicals.

    OpenAIRE

    Baliga, Manjeshwar S; Santosh K. Katiyar

    2006-01-01

    KEYWORDS - CLASSIFIACATION: adverse effects;Animals;Antineoplastic Agents;Antineoplastic Agents,Phytogenic;Antioxidants;chemistry;Chemoprevention;drug therapy;Dermatology;dietary modulation of cancer & cancer biomarkers;Dietary Supplements;Evaluation;Humans;methods;Neoplasms,Radiation-Induced;prevention & control;Phytotherapy;radiation effects;Research;Skin;Skin Neoplasms;therapeutic use;toxicity;Ultraviolet Rays. Epidemiological, clinical and laboratory studies have implicated solar ultra...

  11. Drug: D08756 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08756 Drug Picibanil (TN) Antineoplastic [DS:H00018 H00032 H00054 H00055] Therapeutic category: 4299 Therap...eutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 42 Antineoplastics 429 Miscellaneous 4299 Others D08756 PubChem: 96025439 ...

  12. Drug: D04603 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available NTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC11 Ipilimuma...oplastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Ipilimumab [ATC:L01XC11] D04603 Ipilimumab (USAN/INN) CAS: 477202-00-9 PubChem: 47206447 ...

  13. Drug: D09980 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available C AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC14 Trastuzumab emtansine D09980 T...tuzumab emtansine (USAN/INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Tr

  14. Insuficiência respiratória aguda causada por pneumonia em organização secundária à terapia antineoplásica para linfoma não Hodgkin Acute respiratory failure caused by organizing pneumonia secondary to antineoplastic therapy for non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Adriell Ramalho Santana

    2012-12-01

    Full Text Available Doenças difusas do parênquima pulmonar pertencem a um grupo de doenças de evolução geralmente subaguda ou crônica, mas que podem determinar insuficiência respiratória aguda. Paciente masculino, 37 anos, em terapia para linfoma não Hodgkin, admitido com tosse seca, febre, dispneia e insuficiência respiratória aguda hipoxêmica. Iniciadas ventilação mecânica e antibioticoterapia, porém houve evolução desfavorável. Tomografia computadorizada de tórax mostrava opacidades pulmonares em "vidro fosco" bilaterais. Devido ao paciente ter feito uso de três drogas relacionadas à pneumonia em organização (ciclofosfamida, doxorrubicina e rituximabe e quadros clínico e radiológico serem sugestivos, iniciou-se pulsoterapia com metilprednisolona com boa resposta. Pneumonia em organização pode ser idiopática ou associada a colagenoses, drogas e neoplasias, e geralmente responde bem a corticoterapia. O diagnóstico é anatomopatológico, mas condições clínicas do paciente não permitiam a realização de biópsia pulmonar. Pneumonia em organização deve ser diagnóstico diferencial em pacientes com aparente pneumonia de evolução desfavorável ao tratamento antimicrobiano.Interstitial lung diseases belong to a group of diseases that typically exhibit a subacute or chronic progression but that may cause acute respiratory failure. The male patient, who was 37 years of age and undergoing therapy for non-Hodgkin's lymphoma, was admitted with cough, fever, dyspnea and acute hypoxemic respiratory failure. Mechanical ventilation and antibiotic therapy were initiated but were associated with unfavorable progression. Thoracic computed tomography showed bilateral pulmonary "ground glass" opacities. Methylprednisolone pulse therapy was initiated with satisfactory response because the patient had used three drugs related to organizing pneumonia (cyclophosphamide, doxorubicin and rituximab, and the clinical and radiological symptoms were suggestive. Organizing pneumonia may be idiopathic or linked to collagen diseases, drugs and cancer and usually responds to corticosteroid therapy. The diagnosis was anatomopathological, but the patient's clinical condition precluded performing a lung biopsy. Organizing pneumonia should be a differential diagnosis in patients with apparent pneumonia and a progression that is unfavorable to antimicrobial treatment.

  15. Raynaud′s phenomenon in a child with medulloblastoma as a late effect of chemotherapy

    Directory of Open Access Journals (Sweden)

    Erman Atas

    2015-01-01

    Full Text Available There are a lot of early or late side effects of chemotherapies. One of them is Raynaud′s phenomenon (RP. Vascular toxicity associated with antineoplastic agents is notified in bleomycin alone therapy or in combination with cisplatin, vinblastine, and vincristine. The mechanism of RP associated with antineoplastic agents is unknown. All children receiving vinblastine, vincristine, bleomycin and cisplatin therapy, are followed and questioned about their complaint on RP. Long-term follow-up of surviving patients is recommended. Oncologists should be aware of the potential late toxic effects of antineoplastic drugs.

  16. Drug: D09960 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09960 Drug Ruxolitinib phosphate (JAN/USAN); Jakafi (TN) C17H18N6. H3PO4 404.1362 ...LATING AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XE Protein kinase inhibitors L01XE18 Ru...xolitinib D09960 Ruxolitinib phosphate (JAN/USAN) USP drug classification ...[BR:br08302] Antineoplastics Molecular Target Inhibitors Ruxolitinib D09960 Ruxolitinib phosphate (JAN/USAN)... Target-based classification of drugs [BR:br08310] Protein kinases Tyrosine protein kinases JAK family janus

  17. Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy

    OpenAIRE

    Kang, Min H.; Reynolds, C. Patrick

    2009-01-01

    Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic ...

  18. Drug: D07100 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07100 Drug Amrubicin hydrochloride (JAN/USAN); Calsed (TN) C25H25NO9. HCl 519.1296 519.9282 D07100...on 42 Antineoplastics 423 Antibiotics 4235 Anthracycline antibiotics D07100 Amrubicin hydrochloride (JAN/USA... L01DB Anthracyclines and related substances L01DB10 Amrubicin D07100 Amrubicin hydrochloride (JAN/USAN) Tar...4] Amrubicin [ATC:L01DB10] D07100 Amrubicin hydrochloride (JAN/USAN) Antineoplast...ics [BR:br08308] Natural products Antibiotics Amrubicin [ATC:L01DB10] D07100 Amrubicin hydrochloride (JAN/US

  19. Drug: D04066 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04066 Drug Estramustine (USAN/INN) C23H31Cl2NO3 439.1681 440.4031 D04066.gif Antin...er antineoplastic agents L01XX11 Estramustine D04066 Estramustine (USAN/INN) USP drug classification [BR:br0...8302] Antineoplastics Antiestrogens/Modifiers Estramustine D04066 Estramustine (U...SAN/INN) Antineoplastics [BR:br08308] Alkylating agents Nitrogen mustard analogues Estramustine [ATC:L01XX11] D0406...6 Estramustine (USAN/INN) CAS: 2998-57-4 PubChem: 47206023 DrugBank: DB01196 LigandBox: D04066 NIKKAJ

  20. Drug: D10104 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10104 Drug Dabrafenib mesylate (USAN); Tafinlar (TN) C23H20F3N5O2S2. CH4SO3 615.0892 615.6681 D1010...4.gif Antineoplastic ATC code: L01XE23 BRAF inhibitor [HSA:673] [KO:K04365] hsa04010(673) M...ER ANTINEOPLASTIC AGENTS L01XE Protein kinase inhibitors L01XE23 Dabrafenib D10104 Dabrafenib mesylate (USAN...) USP drug classification [BR:br08302] Antineoplastics Molecular Target Inhibitors Dabrafenib D10104 Dabrafe...nib mesylate (USAN) Target-based classification of drugs [BR:br08310] Protein kin

  1. Drug: D09314 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09314 Drug Ofatumumab (genetical recombination) (JAN); Ofatumumab (USAN/INN); Arze... 4 Agents affecting cellular function 42 Antineoplastics 429 Miscellaneous 4291 Other Antitumors D09314 Ofatumumab (genetica...IC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC10 Ofatumumab D09314 Ofatumumab (genetica...R:br08302] Antineoplastics Monoclonal Antibodies Ofatumumab D09314 Ofatumumab (genetical recombination) (JAN...A:931] [KO:K06466] Ofatumumab D09314 Ofatumumab (genetical recombination) (JAN); Ofatumumab (USAN/INN) Antin

  2. Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future.

    Science.gov (United States)

    Burke, Matthew P; Borland, Kayla M; Litosh, Vladislav A

    2016-01-01

    Nucleoside and nucleobase antimetabolites have substantially impacted treatment of cancer and infections. Their close resemblance to natural analogs gives them the power to interfere with a variety of intracellular targets, which on one hand gives them high potency, but on the other hand incurs severe side effects, especially of the chemotherapeutics used against malignancies. Therefore, the development of novel nucleoside analogs with widened therapeutic windows represents an attractive target to synthetic organic and medicinal chemists. This review discusses the current antimetabolite drugs: 5- fluorouracil, 6-mercaptopurine, 6-thioguanine, Cladribine, Vidaza, Decitabine, Emtricitabine, Abacavir, Sorivudine, Clofarabine, Fludarabine, and Nelarabine; gives insight into the nucleoside drug candidates that are being developed; and outlines the approaches to nucleobase modifications that may help discover novel bioactive nucleoside analogs with the mechanism of action focused on termination of DNA synthesis, which is expected to diminish the off-target toxicity in non-proliferating human cells. PMID:26369814

  3. Mycophenolic acid: a drug with a potential beyond renal transplantation

    Directory of Open Access Journals (Sweden)

    Jammula P. Patro

    2016-09-01

    Full Text Available Mycophenolic acid is an anti-metabolite immunosuppressant. It inhibits the enzyme inosine monophosphate dehydrogenase, which is essential for purine synthesis. It is indicated in prevention of rejection after renal transplantation. It is one of the few drugs, which were discovered more than a century ago and still in active use. This review discusses the other current and potential uses of the drug. [Int J Res Med Sci 2016; 4(9.000: 3666-3669

  4. Functional thiamine deficiency in end-stage renal disease: malnutrition despite ample nutrients.

    Science.gov (United States)

    Moradi, Hamid; Said, Hamid M

    2016-08-01

    Zhang et al. found that plasma concentrations of the thiamine antimetabolite oxythiamine are significantly increased in patients with end-stage renal disease. These investigators discuss the potential sources of oxythiamine and the consequences of its plasma elevation. This commentary addresses the significance of these findings and expands on the potential role of gut microbiome in the generation of this antithiamine metabolite. PMID:27418090

  5. Late-Onset Glaucoma-Filtrating Bleb Leak in a Penetrating Keratoplasty Patient: A Case Report

    OpenAIRE

    Zuleyha Yalniz-Akkaya; Ayse Burcu; Firdevs Ornek

    2012-01-01

    Introduction. Late-onset bleb leaks occur more frequently after the use of adjunctive antimetabolites and require surgical management to seal and preserve filtrating bleb. Case Presentation. A 48-year-old female presented with decreased visual acuity for five days in her left eye. She had a left penetrating keratoplasty one year earlier and two trabeculectomies 7 years earlier. Visual acuity was hand motions, intraocular pressure was 3 mmHg, corneal graft was clear, mature cataract was presen...

  6. Removal of antinutritional factors from bean (Phaseolus vulgaris L.) seeds

    OpenAIRE

    Bollini R.; Carnovale E.; Campion B.

    1999-01-01

    Phytohemagglutinin and the lectin-related proteins present in bean seeds are toxic to monogastric animals and lower the nutritional value of beans. Since these antimetabolites are present in substantial amounts, a breeding program aimed to the removal ofphytohemagglutinin was developed. The character ""absence of phytohemagglutinin"" was transferred into a bean cultivar by backcrossing. The lines obtained maintained the agronomic performance of the recurrent parent. Preliminary results show t...

  7. Post-transplantation diabetes mellitus

    OpenAIRE

    N Zbiti; K Souly; Z Errami; L Guendouz; L Benamar; F Ezaitouni; N Ouzeddoun; R Bayahia; A Chabraoui; H Rhou

    2012-01-01

    To determine the prevalence of post-kidney transplantation diabetes (PTDM) and to assess its risk factors, we retrospectively studied 92 non-diabetic kidney transplant patients. The immunosuppressive drugs used to prevent rejection included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antimetabolite (azathioprine or mycofenolate mofetil). Diabetes was defined according to the WHO criteria and the American Diabetes Association. The mean age of our patients was 35.8 ±...

  8. Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2

    OpenAIRE

    LI, QIONGYU; Wang, Xiangfeng; SHEN, ALING; Zhang, Yuchen; Chen, Youqin; Sferra, Thomas J.; LIN, JIUMAO; Peng, Jun

    2015-01-01

    Previous studies have demonstrated that Hedyotis diffusa Willd (HDW), a traditional Chinese herbal medicine, exhibits potent anticancer activity in models of colorectal cancer (CRC). Aggressive forms of CRC exhibit resistance to widely used chemotherapeutic drugs, including the antimetabolite, 5-fluorouracil (5-FU); however, less is known with regard to the activity of HDW against 5-FU-resistant cancer. In the present study, the mechanism of action and the potency of ethanol extracts of HDW (...

  9. Role of hydroxycarbamide in prevention of complications in patients with sickle cell disease

    OpenAIRE

    NM Wiles; Howard, J.

    2009-01-01

    NM Wiles, J HowardDepartment of Haematology, St Thomas’ Hospital, Westminster, Bridge Road, London, SE1 7EH, UKAbstract: Sickle cell disease (SCD) is a genetically inherited condition caused by a point mutation in the beta globin gene. This results in the production of the abnormal hemoglobin, sickle hemoglobin (HbS). Hydroxycarbamide, is an antimetabolite/cytotoxic which works by inhibiting ribonucleotide reductase, blocking the synthesis of DNA and arresting cells in the S phase. ...

  10. Drug: D05338 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available oxifying agents for antineoplastic treatment V03AF08 Palifermin D05338 Palifermin (USAN/INN) USP drug classification [BR:br08302] Den...tal and Oral Agents Palifermin D05338 Palifermin (USAN/I

  11. Piattaforma PharmacoWikilance - Studio Alexandros

    OpenAIRE

    Pieroni, Stefania; Knezevic, Tamara; De Nes, Michele; Molinaro, Sabrina

    2015-01-01

    PharmacoWikilance (acronym PhiWi) web platform user guide. PhiWi platform supports the management and storage of digital data for pharmacovigilance studies. The Alexandros study is about adverse reactions to antineoplastic drugs.

  12. Drug: D05266 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available AAHAILGGLH LTLDWAVRGL LLLKTRL Peptide Hematopoietic stimulant ATC code: L03AC02 i...R:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L03 IMMUNOSTIMULANTS L03A IMMUNOSTIMULANTS L03AC Int

  13. Drug: D10507 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available LANTS L03A IMMUNOSTIMULANTS L03AX Other immunostimulants L03AX18 Cridanimod D10507 Cridanimod...tomical Therapeutic Chemical (ATC) classification [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L03 IMMUNOSTIMU

  14. Drug: D09032 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available L PRODUCTS L01CA Vinca alkaloids and analogues L01CA05 Vinflunine D09032 Vinflunine ditartrate (USAN) Antine...MODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01C PLANT ALKALOIDS AND OTHER NATURA

  15. Drug: D09190 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ective immunosuppressants L04AA04 Antithymocyte immunoglobulin (rabbit) D09190 Anti...TC) classification [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L04 IMMUNOSUPPRESSANTS L04A IMMUNOSUPPRESSANTS L04AA Sel

  16. Irinotecan Lipid Complex Injection

    Science.gov (United States)

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  17. Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Parner, Vibeke Kirk; Tuxen, Malgorzata K.;

    2015-01-01

    PURPOSE: Despite improved anti-neoplastic treatment the prognosis for patients with liver metastases from metastatic breast cancer remains poor. MATERIALS AND METHODS: Thirty-two consecutive patients with metastatic breast cancer treated with radiofrequency ablation (RFA) at the Department...

  18. Drug: D05702 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available the treatment of solid tumors ribonuclease CAS: 196488-72-9 PubChem: 47207363 ... ...CKYKLK KSTNKFCVTC ENQAPVHFVG VGSC (Disulfide bridge: 19-68; 30-75; 48-90; 87-104) Peptide Antineoplastic for

  19. A Review of Cancer Chemotherapy for Pet Animals

    OpenAIRE

    Norris, A. M.; Withrow, S.J.

    1984-01-01

    A review of the principles of cancer chemotherapy for pet animals is presented. The various pharmacological classes of antineoplastic drugs are described with specific references to those drugs that have been widely used in veterinary medicine.

  20. Drug: D00574 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available e inhibitor Indication: Cushing's syndrome aromatase inhibitor [HSA:1588] [KO:K07434] hsa00140(1588) Steroid... D00574.gif Adrenocortical suppressant; Antineoplastic Same as: C07617 ATC code: L02BG01 Reversible aromatas

  1. Drug: D07974 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 98) Pyrimidine metabolism hsa00670(7298) One carbon pool by folate Enzyme: DPYD [HSA:1806] Genomic biomark...er: DPYD [HSA:1806] map07041 Antineoplastics - antimetabolic agents Anatomical Ther

  2. Drug: D03204 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0080] ATC code: L04AA22 Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] L ANTINEOPLASTIC A....9736 Treatment of systemic lupus erythematosus and diseases-associated nephritis [immunosuppressant] [DS:H0

  3. Drug: D07928 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available te USP drug classification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Sex Hormones/Modif...stradiol propanesulfonate Antineoplastics [BR:br08308] Hormones and hormone antag

  4. Drug: D00327 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rug classification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Sex Hormones...(JP16/USP/INN) Antineoplastics [BR:br08308] Hormones and hormone antagonist Androgen Fluoxymesterone [ATC:G0

  5. Drug: D01011 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available plastics - hormones Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 24 Hormones... Liothyronine sodium (JP16/USAN) Antineoplastics [BR:br08308] Hormones and hormone antagonist Thyroid hormon

  6. Drug: D07434 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 2 [HSA:2100] [KO:K08551] Polyestradiol phosphate [ATC:L02AA02] D07434 Polyestradiol phosphate (INN) Antineoplastics [BR:br08308] Horm...ones and hormone antagonist Estrogen Polyestradiol phosp

  7. Drug: D04187 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L04 IMMUNOSUPPRESSANTS L04A IMMUNOSUPPRESSANTS L04AA Selective immunosuppressan...ts L04AA27 Fingolimod D04187 Fingolimod hydrochloride (JAN/USAN) USP drug classific

  8. Drug: D09966 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09966 Drug Talimogene laherparepvec (USAN); Talminogene laherparepvec; Oncovex (TN) Antineoplastic gene the...rapy drug (oncolytic HSV1, GM-CSF [HSA:1437] [KO:K05427]) CAS: 1187560-31-1 PubChem: 124490634 ...

  9. Drug: D02259 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 259.gif Antineoplastic; Diagnostic aid [thyroid function determination]; Radioactive agent [DS:H00032] Thera... affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  10. Drug: D08128 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available onal Agents, Stimulant/Replacement/Modifying (Thyroid) Liothyronine D08128 Liothyronine (INN) Target-based c...ion map07043 Antineoplastics - hormones USP drug classification [BR:br08302] Horm

  11. Longitudinal trends in use of targeted therapies for treatment of malignant neoplasms of the eye: a population-based study in Taiwan

    OpenAIRE

    Hsu, Jason C.; Gonzalez-Gonzalez, Luis A; Lu, Vicky H; Christine Y Lu

    2016-01-01

    Objectives: This study examined the recent trend in use and costs of antineoplastic agents for treatment of eye malignancies in Taiwan from 2009 to 2012. We also forecasted use and costs of targeted therapies up to and including year 2016 based on the current patterns. Design: Retrospective observational study focusing on the usage of targeted therapies for treatment of eye malignancy. Setting: The monthly claims data for eye malignancy-related antineoplastic agents were retrieved from Taiwan...

  12. Raynaud′s phenomenon in a child with medulloblastoma as a late effect of chemotherapy

    OpenAIRE

    Erman Atas; Nadir Korkmazer; Hatice A Artik; Oguzhan Babacan; Vural Kesik

    2015-01-01

    There are a lot of early or late side effects of chemotherapies. One of them is Raynaud′s phenomenon (RP). Vascular toxicity associated with antineoplastic agents is notified in bleomycin alone therapy or in combination with cisplatin, vinblastine, and vincristine. The mechanism of RP associated with antineoplastic agents is unknown. All children receiving vinblastine, vincristine, bleomycin and cisplatin therapy, are followed and questioned about their complaint on RP. Long-term follow-up of...

  13. Wound healing suppressant effect of vincristine reversed by vitamin A: an experimental study

    OpenAIRE

    Venkatadri T.V.; Afzal Khan A. K.

    2016-01-01

    Background: Use of antineoplastic drugs pre and postoperatively have shown to adversely affect the healing of surgical wounds. Vincristine is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that vincristine impairs skin wound healing. Methods: In this study we investigated the effect of vitamin A on vincristine induced suppression of healing in two wound models, viz: incision and dead space in rats. Hydroxyproline (measure of collagen) was es...

  14. Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10)

    OpenAIRE

    Deng, Wen; Dai, Chun-ling; Chen, Jun-Jiang; KATHAWALA, RISHIL J.; SUN, YUE-LI; CHEN, HAI-FAN; Fu, Li-wu; Chen, Zhe-Sheng

    2013-01-01

    It is well established that ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) is one of the major mechanisms that causes resistance to antineoplastic drugs in cancer cells. ABC transporters can significantly decrease the intracellular concentration of antineoplastic drugs by increasing their efflux, thereby lowering their cytotoxic activity. One of these transporters, the multidrug resistance protein 7 (MRP7/ABCC10), has already been shown to produce resistance to ant...

  15. Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening

    OpenAIRE

    Nilubol Naris; Zhang Lisa; Shen Min; Zhang Ya-Qin; He Mei; Austin Christopher P; Kebebew Electron

    2012-01-01

    Abstract Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation a...

  16. Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth

    OpenAIRE

    Shishido, Stephanie N.; Nguyen, Thu A.

    2012-01-01

    Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increa...

  17. L-Asparaginaz Allerjisi Sürekli Adrenalin ?nfüzyonu E?li?inde Yapılan Desensitizasyonla A??labilir miş

    OpenAIRE

    2, Semra KARA; 1, Nurullah ÇEL?K; 2, Ömer CEV?T; 2, Hayri B. TOKSOY 2 Dilara ?ÇA?ASIO?LU

    2010-01-01

    ABSTRACT May L-asparaginase allergies be removed by desen-sitization with continous adrenaline infusion? The allergic reactions related to chemotherapeutic drugs represent a very significiant problem in clinical practice as all these antineoplastic drugs must be used in a phase associated schedule. L-asparaginase is an anti-neoplastic drug in which hypersensitivity reactions can be seen commonly. It is estimated that hyper-sensitivity reactions may occur in 5-35% and life threatening a...

  18. Novel polysaccharide anti-tumour drug delivery system for active targeting and controlled release to breast cancer bone metastases

    OpenAIRE

    Bonzi, Gwénaëlle A.M.

    2014-01-01

    ABSTRACT In the late stage of the disease, breast cancer patients often develop bone metastases, a major cause of cancer-related death among women worldwide. The common treatment currently used clinically includes the anti-neoplastic agent paclitaxel combined with the bisphosphonate alendronate. Paclitaxel is an anti-neoplastic drug which cytotoxic effect is mainly attributed to its ability to promote the assembly of microtubules as well as prevent the depolymerisation of these micro...

  19. The role of prophylaxis of bacterial infections in children with acute leukemia/non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Elio Castagnola

    2014-06-01

    Full Text Available Infections represent a well-known complication of antineoplastic chemotherapy that may cause delay of treatment, with alteration of the antineoplastic program and dose-intensity, or even the death of a patient that could heal from his/her neoplasia. Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Therefore a program of antibiotic prophylaxis for febrile neutropenia may be considered in the management strategy of cancer patients.

  20. The Role of Prophylaxis of Bacterial Infections in Children With Acute Leukemia/Non-Hodgkin Lymphoma

    OpenAIRE

    Elio Castagnola

    2014-01-01

    Infections represent a well-known complication of antineoplastic chemotherapy that may cause delay of treatment, with alteration of the antineoplastic program and dose-intensity, or even the death of a patient that could heal from his/her neoplasia. Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Therefore a program of antibiotic prophylaxis for febrile neutropenia may be considered in the management stra...

  1. Drug: D02802 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC04 Alemtuzumab D02802 Alemtuzumab (USAN/INN) Target-...[ATC:L01XC04] D02802 Alemtuzumab (USAN/INN) Antineoplastics [BR:br08308] Molecularly targeted agents Monoc...lonal antibody Alemtuzumab [ATC:L01XC04] D02802 Alemtuzumab (USAN/INN) CAS: 216503-57-0 PubChem: 17396960 DrugBank: DB00087 NIKKAJI: J2.415.690G ...

  2. Exploration on Anti-Multidrug-Resistant Molecular Mechanisms of Salvicine and Characterization of Salvicine-Resistant A549/SAL Cell Line%沙尔威辛抗肿瘤多药耐药分子机制及耐药特性研究

    Institute of Scientific and Technical Information of China (English)

    缪泽鸿; 丁健

    2004-01-01

    Multidrug resistance (MDR) is a major clinical problem in treating human cancers with conventional chemotherapeutic drugs. This study demonstrated that salvicine, a novel antitumor compound under clinical trial, exerted direct cytotoxicity against MDR tumor cells and down-regulated mdr-1/P-glycoprotein (P-gp) expression simultaneously. Salvicine effectively killed MDR sublines, such as K562/A02, KB/VCR and MCF-7/ADR, and parental K562, KB, and MCF-7 cell lines to an equivalent degree. Its cytotoxic activities were much more potent than those of several classical anticancer drugs. Salvicine induced the downregulation of mdr-1 gene and P-gp expression,while not affecting MRP and LRP expression. Anti-MDR mechanism exploration revealed that transcription factor c-Jun played a principal role in downregulation of mdr-1 expression and induction of apoptosis by salvicine. Levels of c-jun expression were enhanced by salvicine prior to reduction of mdr-1 expression in K562/A02 cells. Moreover, c-jun antisense oligodeoxynucleotides (AODs)prevented salvicine-stimulated enhancement of c-Jun protein and reduction of mdr-1 gene expression, but did not affect the increase in c-jun mRNA levels. Salvicine promoted phosphorylation of JNK kinase and c-Jun protein and enhanced DNA binding activity of transcription factor AP1. Additionally, c-jun AODs also inhibited salvicine-induced apoptosis and cytotoxicity. Finally, salvicine was further shown not to induce a tumor MDR phenotype. We established a salvicine-resistant tumor cell subline, A549/SAL, which displayed 8.91-fold resistance to salvicine and an average of 6. 70-fold resistance to the antimetabolites. The subline, however, was not resistant to alkylating agents,platinum compounds, and other naturally-derived antineoplastics.%肿瘤多药耐药(multidrug resistance,MDR)是临床化疗成功最为严重的障碍.首先阐明了新拓扑异构酶Ⅱ抑制剂沙尔威辛对MDR肿瘤细胞直接的细胞毒性作用及下调mdr-1

  3. Avaliação da satisfação de pacientes oncológicos com atendimento recebido durante o tratamento antineoplásico ambulatorial Evaluación de la satisfaccíon de pacientes oncológicos con la atención recibida durante el tratamiento antineoplásico ambulatorial Evaluation of the satisfaction level of cancer patients with the assistance recieved during ambulatory antineoplastic chemoteraphy

    Directory of Open Access Journals (Sweden)

    Selma Montosa da Fonseca

    2006-10-01

    Full Text Available Este estudo descritivo, fundamentado na abordagem de resultados proposta por Donabedian, teve como objetivo avaliar o nível de satisfação de pacientes oncológicos com o atendimento recebido no Ambulatório de Quimioterapia de Adultos do Hospital São Paulo. A amostra incluiu 105 pacientes que aceitaram participar do estudo. A avaliação dos usuários foi positiva, tanto com o atendimento de enfermagem (54% muito bom e 46% bom, quanto com o atendimento global do serviço (50% muito satisfeitos e 46% satisfeitos. O nível de satisfação manifestado pelos usuários relacionou-se, principalmente, com a acessibilidade organizacional, o ambiente acolhedor e o processo assistencial nas dimensões da interação profissional/cliente e do desempenho técnico. No entanto, apontaram como medidas necessárias, evitar a falta de drogas e aumentar o número de vagas.Este estudio descriptivo, fundado en el abordaje de resultados propuesto por Donabedian, tuvo como objetivo evaluar el nivel de satisfacción de pacientes con cáncer con la atención recibida en el Ambulatorio de Quimioterapia de Adultos de Hospital São Paulo. La muestra incluyó 105 pacientes que aceptaron participar de la investigación. La evaluación de los usuarios fue positiva, tanto con la atención de enfermería (54% muy buena y 46% buena, cuanto con la atención general del servicio (50% muy satisfechos y 46% satisfechos.El nivel de satisfacción manifestado por los usuarios se relacionó, principalmente, con la accesibilidad organizacional, el ambiente acogedor y el proceso asistencial en las dimensiones de la interacción profesional/cliente y del desempeño técnico. No obstante, apuntaron como medidas necesarias, evitar la falta de medicinas y aumentar el número de plazas.This descriptive study, grounded upon Donabedian's outcomes approach, had as purpose to evaluate the satisfaction level of cancer patients with the assistance received at the Adult Chemotherapy Ambulatory of Hospital São Paulo. The sample was constituted of 105 patients who accepted to participate in the study. The patients' evaluation was positive both with nursing care (54% very good and 46% good and with the overall care received in that service (50% very satisfied and 46% satisfied. The level of satisfaction manifested by the clients was related mainly to the organization accessibility, the welcoming environment and the assistance process, in its professional/client interaction and the technical performance dimensions. However, they also pointed out the need for measures aimed at preventing drugs shortage and the lack of vacancies for new patients.

  4. Human relations in nursing care towards cancer patients submitted to antineoplastic chemotherapy La relación humana en el cuidado de enfermería al cliente con cáncer sometido a la terapia antineoplásica A relação humana no cuidado de enfermagem junto ao cliente com câncer submetido à terapêutica antineoplásica

    Directory of Open Access Journals (Sweden)

    Conceição Adriana Sales Fontes

    2008-03-01

    Full Text Available OBJECTIVES: To describe the relationship between nurses and cancer patients, in the context of chemotherapy, according to the client's perception; to analyze nursing practice in oncology, based on human healthcare principles. METHODS: This is a qualitative, exploratory and descriptive research. Ten clients undergoing chemotherapy treatment took part in the study. The "Almanac" techniques of creativity and sensitivity were associated to semi-structured interviews. RESULTS: The subjects' discourses revealed that nursing care is supported on principles that are proper of human relations, such as friendship, affection, attention, tolerance and solidarity. It was also highlighted that the nurse's actions join technical and human attributes together, considering life as a fundamental ethical value in relation to human dignity as the main interaction element in healthcare. CONCLUSIONS: The results contributed for the reflection about nursing care within chemotherapy, collaborating with possible changes in the nurse's oncology healthcare practice with this client, who already is very stigmatized by the social construction of the disease.OBJETIVOS: Describir la relación entre la enfermera y el cliente con cáncer, dentro del contexto de la quimioterapia, según la perspectiva del cliente y analizar la práctica de la enfermera en el área de oncología basada en los preceptos del cuidado humano. MÉTODOS: se trata de una investigación cualitativa, exploratoria y descriptiva. Participaron diez clientes que recibían tratamiento de quimioterapia. Se utilizó la técnica de creatividad y sensibilidad "Almanaque" paralelamente a la entrevista semiestructurada. RESULTADOS: El discurso de los sujetos reveló que el cuidado de enfermería se apoya en los principios propios de la relación humana, como la amistad, el cariño, la atención, la tolerancia y la solidaridad. Además, destaca que las acciones de la enfermera involucran atributos técnicos y humanos, considerando la vida un valor ético fundamental en relación a la dignidad humana como base de la interacción en el cuidado. CONCLUSIÓNS: Sus resultados contribuyeron en la reflexión sobre el cuidado de enfermería en el ámbito de esta terapéutica, colaborando con posibles cambios en la práctica de cuidar de la enfermera en oncología junto a este cliente, tan estigmatizado por la propia construcción social de la enfermedad.OBJETIVOS: Descrever a relação entre a enfermeira e o cliente com câncer, no contexto da quimioterapia, segundo a perspectiva do cliente; analisar a prática da enfermeira em oncologia assentada nos preceitos do cuidado humano. MÉTODOS: Pesquisa qualitativa, exploratória e descritiva. Participaram dez clientes sob tratamento quimioterápico. Utilizou-se técnica de criatividade e sensibilidade "Almanaque" conjugada à entrevista semi-estruturada. RESULTADOS: O discurso dos sujeitos revelou que o cuidado de enfermagem sustenta-se em princípios próprios da relação humana, como amizade, carinho, atenção, tolerância e solidariedade. Destacou que as ações da enfermeira conjugam atributos técnicos e humanos, considerando a vida como valor ético fundamental em respeito à dignidade humana como alicerce da interação no cuidado. CONCLUSÕES: Seus resultados contribuíram para a reflexão sobre cuidado de enfermagem no âmbito desta terapêutica, colaborando com possíveis mudanças na prática de cuidar da enfermeira em oncologia junto a este cliente, já tão estigmatizado pela própria construção social da doença.

  5. Effects of methotrexate on rat P-450 cytochrome mono-oxygenases; Action du methotrexate sur les monooxygenases a cytochromes P-450 chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Guitton, J.; Guilluy, R.; Brazier, J.L. [Faculte de Pharmacie, 69 - Lyon (France); Souillet, G. [Hopital Debrousse, 69 - Lyon (France); Riviere, J.L. [INRA, 69 - Marcy l`Etoile (France); Gerard, F. [Institut Pasteur, 69 - Lyon (France)

    1994-12-31

    Methotrexate, an anti-cancerous agent, acts as an anti-metabolite of the nucleic acids which synthesis is then inhibited. Using aminopyrine breath test after methotrexate processing, the effects of the molecule on activities of the hepatocyte P-450 cytochrome mono-oxygenases, are studied. Breath micro-tests with carbon 13-labelled aminopyrine have been carried out to observe the metabolism evolution. Micro-test results have been compared to microsomal enzymatic activities for various substrates, and also to P-450 cytochrome ratio. Results show that methotrexate induces a reduction in the P-450 cytochrome ratio, and thus reduce the hepatic biotransformation process. 1 fig., 30 refs.

  6. Effects of methotrexate on rat P-450 cytochrome mono-oxygenases

    International Nuclear Information System (INIS)

    Methotrexate, an anti-cancerous agent, acts as an anti-metabolite of the nucleic acids which synthesis is then inhibited. Using aminopyrine breath test after methotrexate processing, the effects of the molecule on activities of the hepatocyte P-450 cytochrome mono-oxygenases, are studied. Breath micro-tests with carbon 13-labelled aminopyrine have been carried out to observe the metabolism evolution. Micro-test results have been compared to microsomal enzymatic activities for various substrates, and also to P-450 cytochrome ratio. Results show that methotrexate induces a reduction in the P-450 cytochrome ratio, and thus reduce the hepatic biotransformation process. 1 fig., 30 refs

  7. Removal of antinutritional factors from bean (Phaseolus vulgaris L. seeds

    Directory of Open Access Journals (Sweden)

    Bollini R.

    1999-01-01

    Full Text Available Phytohemagglutinin and the lectin-related proteins present in bean seeds are toxic to monogastric animals and lower the nutritional value of beans. Since these antimetabolites are present in substantial amounts, a breeding program aimed to the removal ofphytohemagglutinin was developed. The character ""absence of phytohemagglutinin"" was transferred into a bean cultivar by backcrossing. The lines obtained maintained the agronomic performance of the recurrent parent. Preliminary results show that removal of phytohemagglutinin results in a higher true protein digestibility. Further modification in the composition of the lectin-related protein family is now under way.

  8. Pemetrexed-Induced Nephrogenic Diabetes Insipidus.

    Science.gov (United States)

    Fung, Enrica; Anand, Shuchi; Bhalla, Vivek

    2016-10-01

    Pemetrexed is an approved antimetabolite agent, now widely used for treating locally advanced or metastatic nonsquamous non-small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed.

  9. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

    Institute of Scientific and Technical Information of China (English)

    Kensuke Matsumoto; Akira Kitanaka; Makiko Uemura; Fusako Waki; Tetsuya Fukumoto; Hiroaki Ohnishi; Yoshitsugu Kubota; Toshihiko Ishida

    2011-01-01

    Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration,and that hematological adverse events were relatively rare. PPyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-Ⅱ inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.

  10. [Juvenile chronic arthritis: therapeutic strategy 1990].

    Science.gov (United States)

    Gerber, N J; Sauvain, M J

    1991-04-27

    Therapeutic strategies based on experience with 119 patients with juvenile chronic arthritis are reviewed. Therapeutic goals are formulated and the means of attaining them (NSAIDs, the so-called disease modifying drugs gold, chloroquine and penicillamine, the antimetabolite methotrexate, intra-articular and systemic corticosteroids, physio- and ergotherapy, technical and orthopedic measures, as well as vocational and medicosocial aspects) are discussed. As the individual prognosis normally depends less on drugs than on preventive and rehabilitative measures, the outcome is largely determined by the quality of a well-coordinated inter-disciplinary team approach. PMID:2047820

  11. Drug: D10019 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10019 Drug Panobinostat lactate (JAN) C21H23N3O2. C3H6O3 439.2107 439.5042 D10019....gif Antitumor ATC code: L01XX42 histone deacetylases (HDACs) inhibitor [HSA:3065 3066 8841 9759 10014 10013 ...GENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XX Other antineoplastic agents L01XX42 Panobinostat D100...s [BR:br08310] Enzymes Hydrolases histone deacetylase [HSA:3065 3066 8841 9759 10014 10013 51564 55869 9734 ...83933] [KO:K06067 K11404 K11405 K11406 K11407 K11408 K11409] Panobinostat [ATC:L01XX42] D10019 Panobinostat

  12. Regression of Hepatocellular Carcinoma Lung Metastases after Guyabano Fruit Extract Consumption.

    Science.gov (United States)

    Gunasekaran, Senthil S; Emmadi, Rajyasree; Landers, Lisa A; Gaba, Ron C

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of worldwide cancer-related mortality, and even with established treatment paradigms, its global burden demands greater research into therapeutic options. In the following case report, a patient suffering from HCC with lung metastasis demonstrated regression of metastatic disease while consuming guyabano fruit extract in the absence of conventional chemotherapy. While the antineoplastic effects of the guyabano fruit is well documented, there is sparse clinical documentation of HCC regression associated with it, and a better understanding of guyabano and its antineoplastic activity may trigger discovery of novel therapeutic options for this deadly disease.

  13. Drug: D09959 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09959 Drug Ruxolitinib (USAN/INN) C17H18N6 306.1593 306.365 D09959.gif Treatment o...C AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XE Protein kinase inhibitors L01XE18 Ruxolitinib D09959 Ruxolitinib (USAN/INN) USP dru...xolitinib D09959 Ruxolitinib (USAN/INN) Target-based classification of drugs [BR:br08310] ...g classification [BR:br08302] Antineoplastics Molecular Target Inhibitors Ru...Protein kinases Tyrosine protein kinases JAK family janus kinase 1 [HSA:3716] [KO:K11217] Ruxolitinib [ATC:L01XE18] D09959 Ru

  14. Drug: D07256 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07256 Drug Etoglucid (INN) C12H22O6 262.1416 262.2995 D07256.gif Same as: C19537 A...NOMODULATING AGENTS L01 ANTINEOPLASTIC AGENTS L01A ALKYLATING AGENTS L01AG Epoxides L01AG01 Etoglucid D07256 Etoglucid... (INN) Antineoplastics [BR:br08308] Alkylating agents Epoxides Etoglucid... [ATC:L01AG01] D07256 Etoglucid (INN) CAS: 1954-28-5 PubChem: 51091594 LigandBox: D07256 NIKKAJI: J54.369A

  15. Drug: D00961 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00961 Drug Bicalutamide (JAN/USP/INN); Casodex (TN) C18H14F4N2O4S 430.061 430.3734... D00961.gif Antineoplastic, Antiandrogen [DS:H00024] Same as: C08160 Therapeutic category: 4291 ATC code: L02BB03 andr...tate cancer Enzyme: CYP3A4 [HSA:1576] map07043 Antineoplastics - hormones map07226 Progesterone, andr...ogen and estrogen receptor agonists/antagonists Therapeutic category of drugs in Japan [...TS AND RELATED AGENTS L02BB Anti-androgens L02BB03 Bicalutamide D00961 Bicalutamide (JAN/USP/INN) USP drug c

  16. 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

    Science.gov (United States)

    Berno, Claudia Rodrigues; Rós, Barbara de Toledo; da Silveira, Ingridhy Ostaciana Maia Freitas; Coelho, Henrique Rodrigues; Antoniolli, Andréia Conceição Milan Brochado; Beatriz, Adilson; de Lima, Dênis Pires; Monreal, Antônio Carlos Duenhas; Sousa, Fabricio Garmus; da Silva Gomes, Roberto; Oliveira, Rodrigo Juliano

    2016-07-01

    The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy. PMID:27402479

  17. The Effects of Benzo(A) Pyrene Doxorubicin and Paclitaxel on P170 Glycoprotein

    OpenAIRE

    COŞAN, Didem

    2001-01-01

    B(a)P is a mutagenic, carcinogenic and teratogenic substance. Paclitaxel and doxorubicin are antineoplastic drugs widely used in cancer treatment. The purpose of this study is to observe the effects of doxorubicin and paclitaxel on p170 glycoprotein in rat liver and kidney tissue after administration of B(a)P. As is well known, p170 glycoprotein is an indicator of drug resistance. We hypothesized that a combination of these antineoplastic drugs would cause lower p170 levels and thus would ha...

  18. Drug: D10137 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10137 Drug Regorafenib hydrate (JAN); Stivarga (TN) C21H15ClF4N4O3. H2O 500.0874 500.8307 D101...Japan [BR:br08301] 4 Agents affecting cellular function 42 Antineoplastics 429 Miscellaneous 4291 Other Antitumors D101...NTINEOPLASTIC AGENTS L01XE Protein kinase inhibitors L01XE21 Regorafenib D10137 Regorafenib hydrate (JAN) US...P drug classification [BR:br08302] Antineoplastics Molecular Target Inhibitors Regorafenib D10137 Regorafeni...e RTK class III (PDGF receptor family) PDGFRB tyrosine kinase [HSA:5159] [KO:K05089] Regorafenib D101

  19. Drug: D01441 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01441 Drug Imatinib mesilate (JAN); Imatinib mesylate (USAN); Gleevec (TN); Glivec... (TN) C29H31N7O. CH4SO3 589.2471 589.7084 D01441.gif Antileukemia and other antitumor agent (tyrosine kinase... L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XE Protein kinase inhibitors L01XE01 Imatinib D0144...cs Molecular Target Inhibitors Imatinib D01441 Imatinib mesilate (JAN); Imatinib mesylate (USAN) Target-base...e RTK class III (PDGF receptor family) PDGFRA tyrosine kinase [HSA:5156] [KO:K04363] Imatinib [ATC:L01XE01] D0144

  20. Drug: D06068 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06068 Drug Temsirolimus (JAN/USAN/INN); Torisel (TN) C56H87NO16 1029.6025 1030.287... function 42 Antineoplastics 429 Miscellaneous 4291 Other Antitumors D06068 Temsirolimus...imus D06068 Temsirolimus (JAN/USAN/INN) Target-based cla...lian target of rapamycin (mTOR) [HSA:2475] [KO:K07203] Temsirolimus [ATC:L01XE09] D06068 Temsirolimus (JAN/U...SAN/INN) Antineoplastics [BR:br08308] Molecularly targeted agents mTOR kinase inhibitor Temsirolimus [ATC:L01XE09] D06068 Temsirolimu

  1. Drug: D06409 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06409 Drug Bevacizumab (genetical recombination) (JAN); Avastin (TN) C6638H10160N1... affecting cellular function 42 Antineoplastics 429 Miscellaneous 4291 Other Antitumors D06409 Bevacizumab (genetica...STIC AGENTS L01XC Monoclonal antibodies L01XC07 Bevacizumab D06409 Bevacizumab (genetical recombination) (JA...[HSA:7422] [KO:K05448] Bevacizumab [ATC:L01XC07] D06409 Bevacizumab (genetical recombination) (JAN) Antineop...lastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Bevacizumab [ATC:L01XC07] D06409 Bevacizumab (genetica

  2. Drug: D05446 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05446 Drug Pertuzumab (genetical recombination) (JAN); Pertuzumab (USAN/INN); Perj... Antitumors D05446 Pertuzumab (genetical recombination) (JAN); Pertuzumab (USAN/I...receptor family) ERBB2 tyrosine kinase [HSA:2064] [KO:K05083] Pertuzumab D05446 Pertuzumab (genetical recombination) (JAN); Pertuzumab (USAN/INN) CAS: 380610-27-5 PubChem: 47207115 ... ...umab D05446 Pertuzumab (genetical recombination) (JAN); Pertuzumab (USAN/INN) Tar...AGENTS L01 ANTINEOPLASTIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC13 Pertuz

  3. Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease.

    Science.gov (United States)

    Young, S P; Johnson, A W; Muller, D P

    2001-12-01

    Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. These two hypotheses were investigated by studying the effects of modulating phytanic acid and alpha-tocopherol concentrations on the fatty acid composition and certain physical parameters of cultured retinal cells. Results showed that (a) the phospholipid fraction of retinal cells readily incorporated phytanic acid, (b) the incorporation of phytanic acid increased membrane fluidity, (c) there was no competition for uptake between phytanic acid and alpha-tocopherol, and (d) the incorporation of phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.

  4. Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort.

    Science.gov (United States)

    Coghill, A E; Johnson, L G; Berg, D; Resler, A J; Leca, N; Madeleine, M M

    2016-02-01

    Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus. PMID:26824445

  5. DNA precursor compartmentation in mammalian cells: metabolic and antimetabolic studies of nuclear and mitochondrial DNA synthesis

    International Nuclear Information System (INIS)

    HeLa cells were used for the quantitation of cellular and mitochondrial deoxyribonucleoside triphosphate (dNTP) and ribonucleoside triphosphate (rNTP) pools and of changes in pools in response to treatment with the antimetabolites methotrexate (mtx) and 5-fluorodeoxyuridine (FUdR). Use of an enzymatic assay of dNTPs and of improved nucleotide extraction methods allowed quantitation of mitochondrial dNTP pools. All four mitochondrial dNTP pools expand following treatment with mtx or FUdR whereas cellular dTTP and dGTP pools are depleted. Mitochrondrial rNTP pools were also found to expand in response to these antimetabolites. Mouse L-cells were used to determine the relative contributions of an exogenously supplied precursor to nuclear and mitochrondrial DNA replication. Cells were labeled to near steady state specific activities with 32P-orthophosphate and subsequently labeled with [3H]uridine, a general pyrimidine precursor, in the continuing presence of 32P. Deoxyribonucleoside monophosphates derived from these DNAs were separated by HPLC and the 3H/32P ratio in each pyrimidine determined. The dCMP residues in mitochondrial DNA (mtDNA) were found to be derived exclusively from the exogenous supplied uridine. The dTMP residues from nuclear and mtDNA and the dCMP residues from nuclear DNA were seen to be synthesized partly from exogenous sources and partly from other sources, presumably de novo pyrimidine synthesis

  6. One year follow-up of the cardio-metabolic profile evolution in renal transplant patients treated with alemtuzumab, cyclosporine, and steroids in a reference hospital in Colombia

    Directory of Open Access Journals (Sweden)

    Nieto-Ríos, John Fredy

    2015-10-01

    Full Text Available Introduction: Cardiovascular events occur 50 times more often in kidney transplant patients than in the general population and are the leading cause of death. The aim of the study was to evaluate the behavior of cardio-metabolic profile and determine the incidence of major cardiovascular events in the first year after transplantation. Methods: This prospective study evaluated the behavior of cardio-metabolic profile in adult patients that were transplanted during 2011. Results: The median age was 44.3 ± 12.05 years, 68.7 % were men and 95.5 %, hypertensive. Alemtuzumab-cyclosporine and steroids were used in 89.6 %, delaying the introduction of the antimetabolite. In the first year after transplantation there were three cases of diabetes mellitus, three major cardiovascular events, and 12 cases of acute rejection. Albumin, hemoglobin, weight, body mass index (BMI, calcium and HbA1C increased (p<0.05, whereas paratohormone, phosphorus, creatinine and uric acid decreased (p<0.05. Glomerular filtration rate (GFR was higher in patients without rejection (p=0.001. Conclusion: This immunosuppressive protocol with alemtuzumab, cyclosporine and steroids, and the delayed introduction of the antimetabolite improved bone mineral metabolism, uric acid, albumin and hemoglobin, but there were negative effects on HbA1c, weight and BMI. There was a low incidence of new onset diabetes mellitus and major ardiovascular events.

  7. Long-term outcomes for children with acute lymphoblastic leukemia (ALL) treated on The Cancer Institute of New Jersey ALL trial (CINJALL).

    Science.gov (United States)

    Drachtman, Richard A; Masterson, Margaret; Shenkerman, Angela; Vijayanathan, Veena; Cole, Peter D

    2016-10-01

    The Cancer Institute of New Jersey Acute Lymphoblastic Leukemia trial (CINJALL) employed a post-induction regimen centered on intensive oral antimetabolite therapy, with no intravenous methotrexate (MTX). Fifty-eight patients enrolled between 2001 and 2005. A high rate of induction death (n = 3) or induction failure (n = 1) was observed. Among those who entered remission, five-year DFS is 80 ± 8.9% for those at standard risk of relapse and 76 ± 7.8% for high-risk patients, with median follow up over six years. The estimated cumulative incidence of testicular relapse among boys was elevated (13 ± 7.2%) compared to the rate observed on contemporary protocols. We conclude that post-induction therapy using intensive oral antimetabolites for children with acute lymphoblastic leukemia (ALL) can result in overall long-term DFS comparable to that observed among children treated with regimens including intravenous MTX. However, an increased risk of late extramedullary relapse among boys was observed, supporting the prevailing opinion that high-dose MTX improves outcome for children with ALL. PMID:26879921

  8. A genetically hard-wired metabolic transcriptome in Plasmodium falciparum fails to mount protective responses to lethal antifolates.

    Directory of Open Access Journals (Sweden)

    Karthikeyan Ganesan

    2008-11-01

    Full Text Available Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210 failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS. This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites.

  9. Control of plant defense mechanisms and fire blight pathogenesis through the regulation of 6-thioguanine biosynthesis in Erwinia amylovora.

    Science.gov (United States)

    Coyne, Sébastien; Litomska, Agnieszka; Chizzali, Cornelia; Khalil, Mohammed N A; Richter, Klaus; Beerhues, Ludger; Hertweck, Christian

    2014-02-10

    Fire blight is a devastating disease of Rosaceae plants, such as apple and pear trees. It is characterized by necrosis of plant tissue, caused by the phytopathogenic bacterium Erwinia amylovora. The plant pathogen produces the well-known antimetabolite 6-thioguanine (6TG), which plays a key role in fire blight pathogenesis. Here we report that YcfR, a member of the LTTR family, is a major regulator of 6TG biosynthesis in E. amylovora. Inactivation of the regulator gene (ycfR) led to dramatically decreased 6TG production. Infection assays with apple plants (Malus domestica cultivar Holsteiner Cox) and cell cultures of Sorbus aucuparia (mountain ash, rowan) revealed abortive fire blight pathogenesis and reduced plant response (biphenyl and dibenzofuran phytoalexin production). In the presence of the ΔycfR mutant, apple trees were capable of activating the abscission machinery to remove infected tissue. In addition to unveiling the regulation of 6TG biosynthesis in a major plant pathogen, we demonstrate for the first time that this antimetabolite plays a pivotal role in dysregulating the plant response to infection.

  10. Improving cancer treatment with cyclotron produced radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Larson, S.M.; Finn, R.D.

    1992-08-04

    Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunology projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.

  11. Improving cancer treatment with cyclotron produced radionuclides. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Larson, S.M.; Finn, R.D.

    1992-08-04

    Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunology projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.

  12. REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

    Science.gov (United States)

    Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

  13. Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

    DEFF Research Database (Denmark)

    Laaksonen, Matti; Ramseier, Adrian; Rovó, Alicia;

    2011-01-01

    Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study...

  14. Drug: D07807 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available on [BR:br08303] V VARIOUS V03 ALL OTHER THERAPEUTIC PRODUCTS V03A ALL OTHER THERAPEUTIC PRODUCTS V03AF Detoxifying agents for antineo...plastic treatment V03AF02 Dexrazoxane D07807 Dexrazoxane

  15. Drug: D10260 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Detoxifying agents for antineoplastic treatment V03AF09 Glucarpidase D10260 Glucarpidase (prop.INN) CAS: 9074-87-7 PubChem: 163312291 ... ...fication [BR:br08303] V VARIOUS V03 ALL OTHER THERAPEUTIC PRODUCTS V03A ALL OTHER THERAPEUTIC PRODUCTS V03AF

  16. Drug: D09816 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09816 Drug Sevriplatin (JAN); Sebriplatin (INN) Pt. C6H6O4. C5H14N2 439.1071 439.3715 D09816.gif antineopla...stic CAS: 110172-45-7 PubChem: 124490556 LigandBox: D09816 ATOM 18 1 N1a N 29.6100

  17. Contemplation on new drug approvals by U.S. FDA, 2011-2015

    Directory of Open Access Journals (Sweden)

    Bhaven C. Kataria

    2016-02-01

    Conclusions: For new drugs approved between 2011 and 2015, the U.S. FDA was first to approve majority of new drugs. There was upward trend of new drug approvals in antineoplastic therapeutic area. [Int J Basic Clin Pharmacol 2016; 5(1.000: 55-59

  18. Drug: D01459 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ineoplastic treatment V03AF01 Mesna D01459 Mesna (JAN/USAN/INN) Antineoplastics [BR...US V03 ALL OTHER THERAPEUTIC PRODUCTS V03A ALL OTHER THERAPEUTIC PRODUCTS V03AF Detoxifying agents for ant

  19. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    Current technology has limited applicability for electroporation based treatment of deep-seated tumors, and is in general, not optimized in terms of compliance with clinically relevant parameters. Here we present a novel electrode device developed for electrotransfer of antineoplastic drugs and...

  20. Epithelial-mesenchymal Transition and Tumor Drug Resistance

    Directory of Open Access Journals (Sweden)

    Linlin ZHANG

    2013-01-01

    Full Text Available Resistance to antineoplastic drugs is a common problem in cancer treatments. Epithelial-mesenchymal transition (EMT, which plays an important role in the process of drug resistance, may provide opportunity to solve this problem. This article reviews the characteristics of EMT, relationship between EMT and drug resistance, mechanism of EMT in tumor drug resistance in details.

  1. Epithelial-mesenchymal Transition and Tumor Drug Resistance

    OpenAIRE

    Zhang, Linlin; Wu, Zhihao; Zhou, Qinghua

    2013-01-01

    Resistance to antineoplastic drugs is a common problem in cancer treatments. Epithelial-mesenchymal transition (EMT), which plays an important role in the process of drug resistance, may provide opportunity to solve this problem. This article reviews the characteristics of EMT, relationship between EMT and drug resistance, mechanism of EMT in tumor drug resistance in details.

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

    OpenAIRE

    Ravi Kant Upadhyay

    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 insi...

  3. Determination of platinum surface contamination in veterinary and human oncology centres using inductively coupled plasma mass spectrometry

    NARCIS (Netherlands)

    Janssens, T.; Brouwers, E. E M; de Vos, J. P.; de Vries, N.; Schellens, J. H M; Beijnen, J. H.

    2015-01-01

    The objective of this study was to determine the surface contamination with platinum-containing antineoplastic drugs in veterinary and human oncology centres. Inductively coupled plasma mass spectrometry was used to measure platinum levels in surface samples. In veterinary and human oncology centres

  4. The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies

    Directory of Open Access Journals (Sweden)

    Sato A

    2015-04-01

    Full Text Available Akinori Sato Department of Urology, National Defense Medical College, Tokorozawa, Japan Abstract: The human immunodeficiency virus protease inhibitor ritonavir has recently been shown to have antineoplastic activity, and its use in urological malignancies is under investigation with an eye toward drug repositioning. Ritonavir is thought to exert its antineoplastic activity by inhibiting multiple signaling pathways, including the Akt and nuclear factor-kappaB pathways. It can increase the amount of unfolded proteins in the cell by inhibiting both the proteasome and heat shock protein 90. Combinations of ritonavir with agents that increase the amount of unfolded proteins, such as proteasome inhibitors, histone deacetylase inhibitors, or heat shock protein 90 inhibitors, therefore, induce endoplasmic reticulum stress cooperatively and thereby kill cancer cells effectively. Ritonavir is also a potent cytochrome P450 3A4 and P-glycoprotein inhibitor, increasing the intracellular concentration of combined drugs by inhibiting their degradation and efflux from cancer cells and thereby enhancing their antineoplastic activity. Furthermore, riotnavir’s antineoplastic activity includes modulation of immune system activity. Therapies using ritonavir are thus an attractive new approach to cancer treatment and, due to their novel mechanisms of action, are expected to be effective against malignancies that are refractory to current treatment strategies. Further investigations using ritonavir are expected to find new uses for clinically available drugs in the treatment of urological malignancies as well as many other types of cancer. Keywords: drug repositioning, novel treatment

  5. Inductively coupled plasma mass-spectrometric determination of platinum in excretion products of client-owned pet dogs

    NARCIS (Netherlands)

    Janssens, T.; Brouwers, E. E M; de Vos, J.P.; de Vries, N.; Schellens, J. H M; Beijnen, J. H.

    2015-01-01

    Residues of antineoplastic drugs in canine excretion products may represent exposure risks to veterinary personnel, owners of pet dogs and other animal care-takers. The aim of this study was to measure the extent and duration of platinum (Pt) excretion in pet dogs treated with carboplatin. Samples w

  6. Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil

    DEFF Research Database (Denmark)

    Ehrnrooth, E; Sørensen, B; Poulsen, J H;

    2000-01-01

    5-fluorouracil (5-FU) is considered the standard antineoplastic drug of choice for metastatic colorectal cancer. It has been suggested that 5-FU administered as bolus infusion is cytotoxic mainly through an RNA damaging effect. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m2 on the 5-FU...

  7. Drug: D08562 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available hemical (ATC) classification [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L03 IMMUNOSTIMULANTS L03A IMMUNOSTIMU...LANTS L03AX Other immunostimulants L03AX11 Tasonermin D08562 Tasonermin (INN) CAS: 94948-59-1 PubChem: 96025247 ...

  8. Drug: D10242 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available LANTS L03A IMMUNOSTIMULANTS L03AA Colony stimulating factors L03AA14 Lipegfilgrastim D10242 Lip...d pegylated G-CSF [HSA:1440] [KO:K05423] granulocyte colony stimulating factor (G...(ATC) classification [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L03 IMMUNOSTIMU...ceptors (hematopoietin family receptors) granulocyte colony stimulating factor (G

  9. Cyclophosphamide-induced symptomatic hyponatraemia

    NARCIS (Netherlands)

    Bruining, D M; van Roon, E N; de Graaf, H; Hoogendoorn, M

    2011-01-01

    Cyclophosphamide is an alkylating agent used in antineoplastic and immunosuppressive therapies. Symptomatic hyponatraemia is a rare but life-threatening complication in patients treated with cyclophosphamide. We report the case of a 64-year-old woman with breast cancer who developed severe symptomat

  10. Drug: D03911 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03911 Drug Droloxifene (USAN/INN) C26H29NO2 387.2198 387.514 D03911.gif Antineoplastic Same as: C14296 Sele...ctive estrogen receptor modifier (SERM) estrogen receptor 1 agonist/antagonist [HSA

  11. Drug: D00467 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ENTS L01AX Other alkylating agents L01AX02 Pipobroman D00467 Pipobroman (JAN/USAN.../INN) Antineoplastics [BR:br08308] Alkylating agents Other alkylating agents Pipobroman[ATC:L01AX02] D00467

  12. Drug: D05572 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05572 Drug Porfiromycin (USAN/INN) C16H20N4O5 348.1434 348.3538 D05572.gif Antibac...terial; Antineoplastic Porfiromycin is a Mitomycin C [DR:D00208] derivative. DNA synthesis inhibitor CAS: 80

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

    OpenAIRE

    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.

  14. The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors

    DEFF Research Database (Denmark)

    Møller, P; Knudsen, Lisbeth E.; Loft, S;

    2000-01-01

    of occupational exposures encompassing styrene, vinyl chloride, 1,3-butadiene, pesticides, hair dyes, antineoplastic agents, organic solvents, sewage and waste materials, wood dust, and ionizing radiation. Eleven of the occupational studies were positive, whereas seven were negative. Notably, the negative studies...

  15. Drug: D01695 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available [TAX:5353] Same as: C13156 Therapeutic category: 4299 ATC code: L03AX01 immunostimulants Therapeutic categor...tion [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L03 IMMUNOSTIMULANTS L03A IMMUNOSTIMULANTS L03AX Other immunostimulant

  16. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  17. Pentazocine-induced agranulocytosis.

    OpenAIRE

    Sheehan, Meg; Hyland, Robert H; Norman, Conolly

    1984-01-01

    A 46-year-old man with pentazocine-induced agranulocytosis is described. In previously reported cases of a complete absence of mature neutrophils in the peripheral blood and bone marrow the patients had undergone marrow-depressing treatment with radiation and antineoplastic drugs. This case is unique in that the patient had complete agranulocytosis without predisposing factors.

  18. Drug: D04067 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04067 Drug Esorubicin hydrochloride (USAN) C27H29NO10. HCl 563.1558 563.9808 D0406...7.gif Antineoplastic CAS: 63950-06-1 PubChem: 47206024 LigandBox: D04067 NIKKAJI: J290.162E ATOM 39 1 C8x C

  19. Fertility impairment in radiotherapy.

    Science.gov (United States)

    Biedka, Marta; Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  20. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency

    NARCIS (Netherlands)

    Banka, S.; Blom, H.J.; Walter, J.; Aziz, M.; Urquhart, J.; Clouthier, C.M.; Rice, G.I.; Brouwer, A.P.M. de; Hilton, E.; Vassallo, G.; Will, A.; Smith, D.E.; Smulders, Y.M.; Wevers, R.A.; Steinfeld, R.; Heales, S.; Crow, Y.J.; Pelletier, J.N.; Jones, S.; Newman, W.G.

    2011-01-01

    Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pan

  1. Fractionation of an Extract of Pluchea odorata Separates a Property Indicative for the Induction of Cell Plasticity from One That Inhibits a Neoplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Mareike Seelinger

    2012-01-01

    Full Text Available Introduction. Several studies demonstrated that anti-inflammatory remedies exhibit excellent anti-neoplastic properties. An extract of Pluchea odorata (Asteraceae, which is used for wound healing and against inflammatory conditions, was fractionated and properties correlating to anti-neoplastic and wound healing effects were separated. Methods. Up to six fractionation steps using silica gel, Sephadex columns, and distinct solvent systems were used, and eluted fractions were analysed by thin layer chromatography, apoptosis, and proliferation assays. The expression of oncogenes and proteins regulating cell migration was investigated by immunoblotting after treating HL60 cells with the most active fractions. Results. Sequential fractionations enriched anti-neoplastic activities which suppressed oncogene expression of JunB, c-Jun, c-Myc, and Stat3. Furthermore, a fraction (F4.6.3 inducing or keeping up expression of the mobility markers MYPT, ROCK1, and paxillin could be separated from another fraction (F4.3.7, which inhibited these markers. Conclusions. Wound healing builds up scar or specific tissue, and hence, compounds enhancing cell migration support this process. In contrast, successful anti-neoplastic therapy combats tumour progression, and thus, suppression of cell migration is mandatory.

  2. Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development

    NARCIS (Netherlands)

    Hooser, S.T.; Dijk-Knijnenburg, C.M. van; Waalkens-Berendsen, I.D.H.; Smits-van Prooije, A.E.; Snoeij, N.J.; Baan, R.A.; Fichtinger-Schepman, M.J.

    2000-01-01

    Exposure of males to some genotoxic chemicals causes DNA damage in spermatozoa resulting in embryotoxicity and developmental defects in their offspring. This study demonstrates that cisplatin-DNA adducts could be measured in spermatozoa following treatment with the antineoplastic drug, cisplatin. Th

  3. Drug: D08167 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rol (INN) USP drug classification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Sex Hormones...ptor [HSA:5241] [KO:K08556] Megestrol [ATC:G03AC05 G03DB02 L02AB01] D08167 Megestrol (INN) Antineoplastics [BR:br08308] Hormones

  4. Drug: D01159 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 24 Hormones 247 Estrogen an...G03DA01] D01159 Gestonorone caproate (JAN/USAN) Antineoplastics [BR:br08308] Hormones and hormone antagonist

  5. Drug: D00951 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available agonists/antagonists Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 24 Hormones...lassification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Sex Hormones/Modifiers) Progest... acetate (JAN/USP) Antineoplastics [BR:br08308] Hormones and hormone antagonist P

  6. Drug: D04687 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tion [BR:br08303] L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS L04 IMMUNOSUPPRESSANTS L04A IMMUNOSUPPRESSANTS L04AX Other immunosuppr...essants L04AX04 Lenalidomide D04687 Lenalidomide (USAN/INN) USP drug classification

  7. The quality of chemotherapy and its quality assurance.

    NARCIS (Netherlands)

    Ottevanger, P.B.; Mulder, P.H.M. de

    2005-01-01

    AIMS: Assessment of the quality of chemotherapy care and its quality assurance in clinical trials and daily practice. METHODS: Using Medline, literature was searched combining the following words: quality assurance or quality of care, combined with anti-neoplastic agents. The bibliography of each ar

  8. Understanding the Essential Meaning of Measured Changes in Weight and Body Composition Among Women During and After Adjuvant Treatment for Breast Cancer

    DEFF Research Database (Denmark)

    Pedersen, Birgith; Groenkjaer, Mette; Falkmer, Ursula;

    2016-01-01

    BACKGROUND: Changes in weight and body composition among women during and after adjuvant antineoplastic treatment for breast cancer may influence long-term survival and quality of life. Research on factual weight changes is diverse and contrasting, and their influence on women's perception of body...

  9. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

    DEFF Research Database (Denmark)

    Burn, John; Gerdes, Anne-Marie; Macrae, Finlay;

    2011-01-01

    Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of as...

  10. Drug: D03962 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available cal care conditions; Adjunctive treatment in standard radiation therapy and chemotherapy [synthetic alloster...HER ANTINEOPLASTIC AGENTS L01XD Sensitizers used in photodynamic/radiation therapy L01XD06 Efaproxiral D0396...sitizers used in photodynamic/radiation therapy Efaproxiral [ATC:L01XD06] D03962 Efaproxiral sodium (USAN) C

  11. Drug: D07567 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available AGENTS L01XD Sensitizers used in photodynamic/radiation therapy L01XD04 Aminolevu...photodynamic/radiation therapy Aminolevulinic acid [ATC:L01XD04] D07567 Aminolevulinic acid CAS: 106-60-5 Pu...linic acid D07567 Aminolevulinic acid Antineoplastics [BR:br08308] Miscellaneous agents Sensitizers used in

  12. Drug: D03327 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available R ANTINEOPLASTIC AGENTS L01XD Sensitizers used in photodynamic/radiation therapy L01XD01 Porfimer sodium D03...nts Sensitizers used in photodynamic/radiation therapy Porfimer sodium [ATC:L01XD01] D03327 Porfimer sodium

  13. Drug: D02894 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available raquinone derivative CAS: 70711-40-9 PubChem: 17397051 LigandBox: D02894 NIKKAJI: J...D02894 Drug Ametantrone acetate (USAN) C22H28N4O4. (C2H4O2)2 532.2533 532.586 D02894.gif Antineoplastic anth

  14. Drug: D05510 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 510.gif Antineoplastic anthraquinone derivative CAS: 105118-12-5 PubChem: 47207179 LigandBox: D05510 ATOM 32...D05510 Drug Piroxantrone hydrochloride (USAN) C21H25N5O4. 2HCl 483.144 484.3762 D05

  15. Endophytes : exploiting biodiversity for the improvement of natural product-based drug discovery

    NARCIS (Netherlands)

    Staniek, Agata; Woerdenbag, Herman J.; Kayser, Oliver

    2008-01-01

    Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has y

  16. Pathogenesis of Pneumococcal Pneumonia in Cyclophosphamide-Induced Leukopenia in Mice

    OpenAIRE

    Wang, Erjian; Simard, Marie; Ouellet, Nathalie; Bergeron, Yves; Beauchamp, Denis; Bergeron, Michel G.

    2002-01-01

    Streptococcus pneumoniae pneumonia frequently occurs in leukopenic hosts, and most patients subsequently develop lung injury and septicemia. However, few correlations have been made so far between microbial growth, inflammation, and histopathology of pneumonia in specific leukopenic states. In the present study, the pathogenesis of pneumococcal pneumonia was investigated in mice rendered leukopenic by the immunosuppressor antineoplastic drug cyclophosphamide. Compared to the immunocompetent s...

  17. Factors Affecting Pharmacokinetic Variability of Docetaxel

    NARCIS (Netherlands)

    S.D. Baker (Sharyn)

    2004-01-01

    textabstractIn the early 1960s, the US National Cancer Institute started a program aimed at the discovery of new anticancer drugs by releasing protocols for widespread screening of substances and extracts from various origins for antineoplastic activity. Of the more than 100,000 compounds from 35,00

  18. Drug: D02006 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ron (TN) SrCl2 158.8452 158.526 D02006.gif Antineoplastic; Radioactive agent Therapeutic category: 4300 ATC ...code: V10BX01 Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radio...active drugs 4300 Radioactive drugs D02006 Strontium (89

  19. Drug: D06005 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 04020(5159) Calcium signaling pathway hsa04060(2322+3815+5159) Cytokine-cytokine receptor interaction hsa05200(2322+3815+5159) Pathwa...ys in cancer map07045 Antineoplastics - protein kinases inhibitors Target-based cla

  20. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    Current technology has limited applicability for electroporation based treatment of deep-seated tumors, and is in general, not optimized in terms of compliance with clinically relevant parameters. Here we present a novel electrode device developed for electrotransfer of antineoplastic drugs...

  1. Drug: D08086 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08086 Drug Irinotecan (INN); Biotecan (TN) C33H38N4O6 586.2791 586.678 D08086.gif ...54658] map07042 Antineoplastics - agents from natural products map00983 Drug metabolism - other enzymes map0

  2. Drug: D03220 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03220 Drug Becatecarin (USAN/INN) C33H34Cl2N4O7 668.1805 669.5517 D03220.gif Antin...eoplastic [rebeccamycin analogue] CAS: 119673-08-4 PubChem: 17397373 LigandBox: D03220 ATOM 46 1 C1y C 18.13

  3. Drug: D09321 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 46062.6732 Oncology, treatment of lymphoma [DS:H00005] ATC code: L01XC15 Monoclonal antibody CD20 [HSA:931] ... L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC15 Obinutuzumab D09321 Obinutuzumab (USAN

  4. Drug: D00952 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available xia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodef....gif Antineoplastic Same as: C08151 ATC code: G03AC05 G03DB02 L02AB01 Indication: For the treatment of anore

  5. Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10.

    Directory of Open Access Journals (Sweden)

    Tong Shen

    Full Text Available BACKGROUND: One of the major mechanisms that could produce resistance to antineoplastic drugs in cancer cells is the ATP binding cassette (ABC transporters. The ABC transporters can significantly decrease the intracellular concentration of antineoplastic drugs by increasing their efflux, thereby lowering the cytotoxic activity of antineoplastic drugs. One of these transporters, the multiple resistant protein 7 (MRP7, ABCC10, has recently been shown to produce resistance to antineoplastic drugs by increasing the efflux of paclitaxel. In this study, we examined the effects of BCR-Abl tyrosine kinase inhibitors imatinib, nilotinib and dasatinib on the activity and expression of MRP7 in HEK293 cells transfected with MRP7, designated HEK-MRP7-2. METHODOLOGY AND/OR PRINCIPAL FINDINGS: We report for the first time that imatinib and nilotinib reversed MRP7-mediated multidrug resistance. Our MTT assay results indicated that MRP7 expression in HEK-MRP7-2 cells was not significantly altered by incubation with 5 microM of imatinib or nilotinib for up to 72 hours. In addition, imatinib and nilotinib (1-5 microM produced a significant concentration-dependent reversal of MRP7-mediated multidrug resistance by enhancing the sensitivity of HEK-MRP7-2 cells to paclitaxel and vincristine. Imatinib and nilotinib, at 5 microM, significantly increased the accumulation of [(3H]-paclitaxel in HEK-MRP7-2 cells. The incubation of the HEK-MRP7-2 cells with imatinib or nilotinib (5 microM also significantly inhibited the efflux of paclitaxel. CONCLUSIONS: Imatinib and nilotinib reverse MRP7-mediated paclitaxel resistance, most likely due to their inhibition of the efflux of paclitaxel via MRP7. These findings suggest that imatinib or nilotinib, in combination with other antineoplastic drugs, may be useful in the treatment of certain resistant cancers.

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

    Science.gov (United States)

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

    2013-06-01

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

  7. Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

    Directory of Open Access Journals (Sweden)

    Momparler Richard L

    2008-05-01

    Full Text Available Abstract Background The inactivation of tumor suppressor genes (TSGs by aberrant DNA methylation plays an important role in the development of malignancy. Since this epigenetic change is reversible, it is a potential target for chemotherapeutic intervention using an inhibitor of DNA methylation, such as 5-aza-2'-deoxycytidine (DAC. Although clinical studies show that DAC has activity against hematological malignancies, the optimal dose-schedule of this epigenetic agent still needs to be established. Methods Clonogenic assays were performed on leukemic and tumor cell lines to evaluate the in vitro antineoplastic activity of DAC. The reactivation of TSGs and inhibition of DNA methylation by DAC were investigated by reverse transcriptase-PCR and Line-1 assays. The in vivo antineoplastic activity of DAC administered as an i.v. infusion was evaluated in mice with murine L1210 leukemia by measurement of survival time, and in mice bearing murine EMT6 mammary tumor by excision of tumor after chemotherapy for an in vitro clonogenic assay. Results Increasing the DAC concentration and duration of exposure produced a greater loss of clonogenicity for both human leukemic and tumor cell lines. The reactivation of the TSGs (p57KIP2 in HL-60 leukemic cells and p16CDKN2A in Calu-6 lung carcinoma cells and the inhibition of global DNA methylation in HL-60 leukemic cells increased with DAC concentration. In mice with L1210 leukemia and in mice bearing EMT6 tumors, the antineoplastic action of DAC also increased with the dose. The plasma level of DAC that produced a very potent antineoplastic effect in mice with leukemia or solid tumors was > 200 ng/ml (> 1 μM. Conclusion We have shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer. Our data also show that there is a good correlation between the concentrations of DAC that reduce in vitro clonogenicity, reactivate TSGs and inhibit DNA methylation. These

  8. Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

    International Nuclear Information System (INIS)

    The inactivation of tumor suppressor genes (TSGs) by aberrant DNA methylation plays an important role in the development of malignancy. Since this epigenetic change is reversible, it is a potential target for chemotherapeutic intervention using an inhibitor of DNA methylation, such as 5-aza-2'-deoxycytidine (DAC). Although clinical studies show that DAC has activity against hematological malignancies, the optimal dose-schedule of this epigenetic agent still needs to be established. Clonogenic assays were performed on leukemic and tumor cell lines to evaluate the in vitro antineoplastic activity of DAC. The reactivation of TSGs and inhibition of DNA methylation by DAC were investigated by reverse transcriptase-PCR and Line-1 assays. The in vivo antineoplastic activity of DAC administered as an i.v. infusion was evaluated in mice with murine L1210 leukemia by measurement of survival time, and in mice bearing murine EMT6 mammary tumor by excision of tumor after chemotherapy for an in vitro clonogenic assay. Increasing the DAC concentration and duration of exposure produced a greater loss of clonogenicity for both human leukemic and tumor cell lines. The reactivation of the TSGs (p57KIP2 in HL-60 leukemic cells and p16CDKN2A in Calu-6 lung carcinoma cells) and the inhibition of global DNA methylation in HL-60 leukemic cells increased with DAC concentration. In mice with L1210 leukemia and in mice bearing EMT6 tumors, the antineoplastic action of DAC also increased with the dose. The plasma level of DAC that produced a very potent antineoplastic effect in mice with leukemia or solid tumors was > 200 ng/ml (> 1 μM). We have shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer. Our data also show that there is a good correlation between the concentrations of DAC that reduce in vitro clonogenicity, reactivate TSGs and inhibit DNA methylation. These results suggest that the antineoplastic action of DAC is

  9. Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?

    Science.gov (United States)

    Stocco, Gabriele; Pelin, Marco; Franca, Raffaella; De Iudicibus, Sara; Cuzzoni, Eva; Favretto, Diego; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2014-04-01

    Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease (IBD). In vivo it is active after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of isoforms M and A of the enzyme glutathione-S-transferase (GST) may increase its speed. Indeed, in pediatric patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites. In addition to increase the activation of azathioprine to mercaptopurine, GSTs may contribute to azathioprine effects even by modulating GSH consumption, oxidative stress and apoptosis. Therefore, genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.

  10. Dermatomyositis and polymyositis in childhood.

    Science.gov (United States)

    Gamstorp, I

    1990-01-01

    Personal experience of 30 years work with 40-50 cases of dermatomyositis and polymyositis in childhood is reviewed, stressing the clinical findings of skin eruptions on the knuckles, elbows and knees (except in the 10 per cent of patients without any skin involvement), weakness of particularly proximal muscles and tightness of tendons. Special diagnostic procedures are reviewed as well as treatment. The basic treatment is corticosteroids, which must be started at a high dose and as soon as possible be given at intervals of 48 hours to diminish the side-effects. In many, though not all, patients the treatment must be continued for years. The parents should always know that extended treatment may be necessary. Physiotherapy should be started cautiously and be slowly increased, close co-operation between the physician and the physiotherapist being necessary. If the patient does not respond to corticosteroids, antimetabolites may be added. Most patients survive with no or only minor sequelae.

  11. Cerebral metastases--a therapeutic update.

    Science.gov (United States)

    Cavaliere, Robert; Schiff, David

    2006-08-01

    Cerebral metastases remain a common complication among patients with cancer. Historically, whole-brain radiotherapy has remained the standard of care, with surgery being reserved for selected cases. Recent advances have changed our practice, however. In particular, stereotactic radiosurgery has emerged as a vital treatment modality for this disease. In addition, chemotherapy, including temozolomide, topoisomerase inhibitors and antimetabolites, and treatment sensitizers, such as efaproxiral and motexafin gadolinium, are actively being assessed in clinical trials, and are likely to play an increasing role in the management of cerebral metastases in the future. Nonetheless, many uncertainties remain, such as the optimal combination and timing of therapeutics. As the arsenal of therapeutics expands, it will be increasingly important to select appropriate patients for a particular treatment paradigm. Understanding the efficacy and toxicity of treatment is essential to this task. PMID:16932601

  12. L-canavanine incorporation into vitellogenin and macromolecular conformation.

    Science.gov (United States)

    Rosenthal, G A; Reichhart, J M; Hoffmann, J A

    1989-08-15

    L-Canavanine is a potentially deleterious arginine antimetabolite whose toxicity is expressed in canavanine-sensitive organisms ranging from viruses to humans. Canavanine, a substrate for arginyl-tRNA synthetase, is incorporated into nascent polypeptide chains in place of arginine. This substitution results in the production of structurally aberrant, canavanyl proteins. Chemical, physical, and immunological studies of native and canavanine-containing vitellogenin obtained from female migratory locusts (Locusta migratoria migratorioides (Orthoptera] provide the first experimental evidence that canavanine can disrupt the tertiary and/or quaternary structure that yields the three-dimensional conformation unique to the protein. These findings enhance our understanding of the biochemical basis for canavanine's antimetabolic and potent insecticidal properties. PMID:2760038

  13. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  14. Docking Studies in Target Proteins Involved in Antibacterial Action Mechanisms: Extending the Knowledge on Standard Antibiotics to Antimicrobial Mushroom Compounds

    Directory of Open Access Journals (Sweden)

    Maria José Alves

    2014-01-01

    Full Text Available In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a, alanine racemase (Alr, d-alanyl-d-alanine synthetase (Ddl, isoleucyl-tRNA sinthetase (IARS, DNA gyrase subunit B, topoisomerase IV (TopoIV, dihydropteroate synthetase (DHPS and dihydrofolate reductase (DHFR using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets.

  15. Overview of immunosuppression in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Anjana A Pillai; Josh Levitsky

    2009-01-01

    Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate periand post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.

  16. Takotsubo Cardiomyopathy and 5-Fluorouracil: Getting to the Heart of the Matter

    Directory of Open Access Journals (Sweden)

    Stephanie Hui-Su Lim

    2013-01-01

    Full Text Available Takotsubo cardiomyopathy is a rare but increasingly recognized phenomenon, which can occur as a side-effect of chemotherapeutic agents, in particular, the antimetabolite 5-fluorouracil. We describe a case of delayed Takotsubo cardiomyopathy after 3 weeks of adjuvant 5-fluorouracil for resected rectal adenocarcinoma in a 66-year-old female, supported by angiographic, electrocardiographic, and echocardiographic features. As a complication, she developed an apical mural thrombus with subsequent cerebral thromboembolic events and was successfully anticoagulated to make a full recovery. We present a review of the literature on Takotsubo cardiomyopathy secondary to 5-fluorouracil and the rare occurrence of thromboembolic complications. As this is a significant clinical phenomenon which involves a multispeciality approach to management, oncologists and cardiologists need to recognize it as a potential toxicity of a widely administered chemotherapeutic drug.

  17. Endogenous ethanol--its metabolic, behavioral and biomedical significance.

    Science.gov (United States)

    Ostrovsky YuM

    1986-01-01

    Ethanol is constantly formed endogenously from acetaldehyde, and level of the former can be measured in both human beings and animals. Acetaldehyde can be generated in situ from the metabolism of pyruvate, threonine, deoxyribose-5-phosphate, phosphoethanolamine, alanine and presumably from other substrates. The levels of blood and tissue endogenous ethanol change as a function of various physiologic and experimental conditions such as starvation, aging, stress, cooling, adrenalectomy, etc. and are regulated by many exogenous compounds such as antimetabolites, derivatives of amino acids, lithium salts, disulfiram, cyanamide, etc. Under free choice alcohol selection situations, the levels of endogenous ethanol in rat blood and alcohol preference by the animals are negatively correlated. Similar negative correlations have been found between the levels of blood endogenous ethanol and the frequency of delirium in alcoholic patients undergoing alcohol withdrawal. Endogenous ethanol and acetaldehyde can therefore be regarded as compounds which fulfil substrate, regulatory and modulator functions.

  18. Hippuristanol - A potent steroid inhibitor of eukaryotic initiation factor 4A.

    Science.gov (United States)

    Cencic, Regina; Pelletier, Jerry

    2016-01-01

    Protein synthesis and its regulatory signaling pathways play essential roles in the initiation and maintenance of the cancer phenotype. Insight obtained over the last 3 decades on the mechanisms regulating translation in normal and transformed cells have revealed that perturbed control in cancer cells may offer an Achilles' heel for the development of novel anti-neoplastic agents. Several small molecule inhibitors have been identified and characterized that target translation initiation - more specifically, the rate-limiting step where ribosomes are recruited to mRNA templates. Among these, hippuristanol, a polyhydroxysteroid from the gorgonian Isis hippuris has been found to inhibit translation initiation by blocking the activity of eukaryotic initiation factor (eIF) 4A, an essential RNA helicase involved in this process. Herein, we highlight the biological properties of this compound, its potential development as an anti-cancer agent, and its use to validate eIF4A as an anti-neoplastic target. PMID:27335721

  19. Drug: D10060 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10060 Drug Abexinostat (USAN) C21H23N3O5 397.1638 397.4244 D10060.gif Antineoplast...ic histone deacetylases (HDACs) inhibitor [HSA:3065 3066 8841 9759 10014 10013 51564 55869 9734 83933] [KO:K...n of drugs [BR:br08310] Enzymes Hydrolases histone deacetylase [HSA:3065 3066 8841 9759 10014 10013 51564 55...869 9734 83933] [KO:K06067 K11404 K11405 K11406 K11407 K11408 K11409] Abexinostat D10060 Abexinostat (USAN) ...CAS: 783355-60-2 PubChem: 135626780 LigandBox: D10060 ATOM 29 1 C8y C 11.9700 -15

  20. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists' arsenal.

    Science.gov (United States)

    Papanagnou, Panagiota; Baltopoulos, Panagiotis; Tsironi, Maria

    2015-01-01

    Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. PMID:26056460

  1. DNA vaccines, electroporation and their applications in cancer treatment

    OpenAIRE

    Lee, Si-Hyeong; Danishmalik, Sayyed Nilofar; Sin, Jeong-Im

    2015-01-01

    Numerous animal studies and recent clinical studies have shown that electroporation-delivered DNA vaccines can elicit robust Ag-specific CTL responses and reduce disease severity. However, cancer antigens are generally poorly immunogenic, requiring special conditions for immune response induction. To date, many different approaches have been used to elicit Ag-specific CTL and anti-neoplastic responses to DNA vaccines against cancer. In vivo electroporation is one example, whereas others inclu...

  2. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity

    OpenAIRE

    Ashley Richard A; Saban Ricardo; Saban Marcia R; Azzarello Joseph T; Osban Jeanette; Yang Qing; Frank Mark; Welter Jan C; Fung Kar-Ming; Lin Hsueh-Kung

    2009-01-01

    Abstract Background Originating from Africa, India, and the Middle East, frankincense oil has been important both socially and economically as an ingredient in incense and perfumes for thousands of years. Frankincense oil is prepared from aromatic hardened gum resins obtained by tapping Boswellia trees. One of the main components of frankincense oil is boswellic acid, a component known to have anti-neoplastic properties. The goal of this study was to evaluate frankincense oil for its anti-tum...

  3. Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes

    OpenAIRE

    Barbagallo, Ignazio; Vanella, Luca; Cambria, Maria T.; Tibullo, Daniele; Godos, Justyna; Guarnaccia, Laura; Zappalà, Agata; Galvano, Fabio; Li Volti, Giovanni

    2016-01-01

    Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti-neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM) treatment, either at the beginning or at the end of adipogenic differentiati...

  4. Colorectal Chemoprevention with Calcium and Vitamin D | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION: In this application we propose to complete CA098286, a double-blind, randomized, controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium have anti-neoplastic effects in the large bowel and that these agents interact, each requiring the other for full effect. Despite the strong supporting |

  5. Chemotherapy-induced adverse drug reactions in oncology patients: A prospective observational survey

    OpenAIRE

    Deepti Chopra; Rehan, Harmeet S.; Vibha Sharma; Ritu Mishra

    2016-01-01

    Background: Chemotherapy, a multimodal approach to oncological treatment, involves highly complex regimens and hence accounts to high susceptibility toward adverse drug reactions (ADRs). The present study aims to determine the prevalence of adverse events in patients treated with chemotherapy. Materials and Methods: Spontaneous ADR report of patients on antineoplastic drugs received in the past 2 years (January 2011-January 2013) were studied. These reports were analyzed for various carcinoma...

  6. LIVER SPECIFIC DRUG TARGETING STRATEGIES: A REVIEW

    OpenAIRE

    Ramesh S. Gorad*, Satish K. Mandlik and Kishore N. Gujar

    2013-01-01

    Drug delivery to liver is one of the most challenging research areas in pharmaceutical sciences. The some physiological barrier such as opsonization, mechanical entrapment by pulmonary vascular bed, uptake by RES represents an insurmountable obstacle for a large number of proteins and drugs, including antibiotics, antineoplastic agents and antiviral agents to target liver disorders. Therefore, various strategies have been proposed to improve the delivery of different drugs to liver and hepato...

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

    OpenAIRE

    Sana Abbasi; Arghya Paul; Wei Shao; Satya Prakash

    2012-01-01

    Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The f...

  8. Glycyrrhetinic acid and its derivatives as inhibitors of poly(ADP-ribose)polymerases 1 and 2, apurinic/apyrimidinic endonuclease 1 and DNA polymerase β

    OpenAIRE

    Salakhutdinov N. F.; Schreiber V.; Khodyreva S. N.; Ilina E. S.; Kutuzov M. M.; Sukhanova M. V.; Salomatina O. V.; Zakharenko A. L.; Lavrik O. I.

    2012-01-01

    Aim. For strengthening the efficiency of monofunctional alkylating antineoplastic drugs it is important to lower the capacity of base excision repair (BER) system which corrects the majority of DNA damages caused by these reagents. The objective was to create inhibitors of the key BER enzymes (PARP1, PARP2, DNA polymerase β, and APE1) by the directed modification of glycyrrhetinic acid (GA). Methods. Amides of GA were produced from the GA acetate by formation of the corresponding acyl chlorid...

  9. Local Treatment of Hand-Foot Syndrome with Uridine/Thymidine: In Vitro Appraisal on a Human Keratinocyte Cell Line HaCaT

    OpenAIRE

    Hartinger, J.; Veselý, P.; Matoušková, E.; Argalacsová, S.; L. Petruželka; Netíková, I.

    2012-01-01

    5-fluorouracil (5-FU) is one of the most commonly used antineoplastic drugs in the anticancer therapy. The hand-foot (HF) syndrome (palmar-plantar erythrodysesthesia) is an adverse effect frequently related to long-term i.v. administration of 5-FU or its orally applicable prodrug capecitabine. Its severity can even lead to interruption of the otherwise effective anticancer therapy. Tentative practice in some clinics has shown that topical application of 10% uridine ointment is beneficial for ...

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

    OpenAIRE

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

    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 adv...

  11. Nakládání s odpady ze zdravotnických zařízení se zaměřením na odpady z cytostatik

    OpenAIRE

    Kasalová, Petra

    2014-01-01

    This thesis deals with the management of waste from health care facilities and similar equipment. The first part is processed whole cycle management of waste from health care facilities and waste management legislation are assessed ecological, ecotoxicological and health risks associated with waste management. The work is devoted to a group of drugs whose use is still expanding in the treatment of cancer. It is an antineoplastic . Due to the increasing number of cancer continues to i...

  12. Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance

    OpenAIRE

    Creixell, Mar; Peppas, Nicholas A.

    2012-01-01

    There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti-apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the toxicity to healthy tissues. By encapsulating drugs into nanoparticles that bypass the efflux pumps, drug efflux is reduced, hence i...

  13. Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth.

    Directory of Open Access Journals (Sweden)

    Stephanie N Shishido

    Full Text Available Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control, cisplatin (3.5 mg/kg, PQ (25 mg/kg, or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers.

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

    OpenAIRE

    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...

  15. The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

    OpenAIRE

    Gianluca Farrugia; Rena Balzan

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat pain, fever, and inflammation. However, mounting evidence shows that NSAIDs, such as aspirin, have very promising antineoplastic properties. The chemopreventive, antiproliferative behaviour of NSAIDs has been associated with both their inactivation of cyclooxygenases (COX) and their ability to induce apoptosis via pathways that are largely COX-independent. In this review, the various proapoptotic pathways induced by tr...

  16. Hand, foot and scrotal blisters in a patient with cancer receiving oral chemotherapy

    OpenAIRE

    Guerra, Jose Rodolfo; Suelves, Ana M; Bella, Archie; Lolo, Delatre

    2014-01-01

    Tyrosine kinase inhibitors are novel antineoplastic drugs that make use of the molecular abnormalities that have been discovered in certain types of tumours. These agents are associated with important dermatological side effects. This case report discusses an atypical presentation of the hand–foot syndrome in one patient treated with sorafenib. A 78-year-old man, recently started on sorafenib for the treatment of hepatocarcinoma with lung metastasis, presented to the emergency room with painf...

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

    OpenAIRE

    Evrim eGurpinar; 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...

  18. Colonization of a Central Venous Catheter by the Hyaline Fungus Fusarium solani Species Complex: A Case Report and SEM Imaging

    OpenAIRE

    Alberto Colombo; Giuseppe Maccari; Terenzio Congiu; Petra Basso; Andreina Baj; Antonio Toniolo

    2013-01-01

    The incidence of opportunistic infections by filamentous fungi is increasing partly due to the widespread use of central venous catheters (CVC), indwelling medical devices, and antineoplastic/immunosuppressive drugs. The case of a 13-year-old boy under treatment for acute lymphoblastic leukemia is presented. The boy was readmitted to the Pediatric Ward for intermittent fever of unknown origin. Results of blood cultures drawn from peripheral venous sites or through the CVC were compared. CVC-d...

  19. Cisplatin induced paroxysmal supraventricular tachycardia

    OpenAIRE

    Waseem Raja; M Hussain Mir; Imtiyaz Dar; Muzamil Ahmad Banday; Irfan Ahmad

    2013-01-01

    Cisplatin or cis-diamminedichloroplatinum (CDDP) is the first member of a class of platinum-containing anti-cancer drugs that act by binding to and causing cross-linking of deoxyribonucleic acid, which ultimately triggers apoptosis. Cisplatin has a broad-spectrum antineoplastic activity against various types of human tumors. Unfortunately, the optimal usefulness of Cisplatin is limited secondary to its dose related toxicity especially nephrotoxicity. Cisplatin chemotherapy is also associated ...

  20. Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant Patients Treated with mTOR Inhibitors

    OpenAIRE

    Gianluigi Zaza; Paola Tomei; Paolo Ria; Simona Granata; Luigino Boschiero; Antonio Lupo

    2013-01-01

    The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological cha...