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Antineoplastic Drugs (antineoplastic + drug)
Selected AbstractsLenalidomide, an antineoplastic drug, and its hemihydrateACTA CRYSTALLOGRAPHICA SECTION C, Issue 10 2009Krishnan Ravikumar The crystal structures of lenalidomide [systematic name: (RS)-3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione], C13H13N3O3, (I), an antineoplastic drug, and its hemihydrate, C13H13N3O3·0.5H2O, (II), have been determined by single-crystal X-ray diffraction analysis. The overall conformation of the molecule defined by the orientation of the two ring portions, viz. pyridinedione and isoindolinone, is twisted in both structures. The influence of the self-complementary pyridinedione ring is seen in the crystal packing of both structures through its involvement in forming hydrogen-bonded dimers, although alternate dione O atoms are utilized. An extensive series of N,H...O hydrogen bonds link the dimers into two-dimensional supramolecular arrays built up from infinite chains. The water molecule in (II) has a cohesive function, connecting three lenalidomide molecules by hydrogen bonds. The significance of this study lies in the analysis of the interactions in these structures and the aggregations occurring via hydrogen bonds in the hydrated and dehydrated crystalline forms of the title compound. [source] Determination of carboplatin in canine plasma by high-performance liquid chromatographyBIOMEDICAL CHROMATOGRAPHY, Issue 8 2010Nicolas Villarino Abstract Carboplatin is an antineoplastic drug administered to treat different tumoral conditions in canine oncology. The objective of this study was to validate a high-performance chromatographic (HPLC) method which could be applied in canine pharmacokinetic studies. Following ultrafiltration using a Centrifree device, standards, quality controls and plasma samples were separated by isocratic reversed-phase HPLC on an Inertsil ODS-2 (250 × 4.6,mm i.d.) analytical column and quantified using UV detection at 220,nm. The mobile phase was potassium phosphate (pH 4.5), with a flow-rate of 1.0,mL/min. The procedure produced a linear curve (r2 > 0.999) over the concentration range 1,200,,g/mL. The lower limit of quantification was 1,,g/mL. The intra-assay and inter-assay precision was ,90%. The overall recovery was ,90%. The method was illustrated with a preliminary pharmacokinetic analysis on nine dogs treated with carboplatin at our hospital. Carboplatin disposition followed a monocompartmental structure in dogs and was characterized by a short half-life (50,min). Copyright © 2009 John Wiley & Sons, Ltd. [source] Thalidomide for the treatment of multiple myelomaCONGENITAL ANOMALIES, Issue 3 2004Yutaka Hattori ABSTRACT Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan. [source] ABCG2 (BCRP) expression in normal and malignant hematopoietic cellsHEMATOLOGICAL ONCOLOGY, Issue 3 2003Brian L. Abbott Abstract ABCG2 (BCRP) is a member of the ATP-binding cassette (ABC) family of cell surface transport proteins. ABCG2 expression occurs in a variety of normal tissues, and is relatively limited to primitive stem cells. ABCG2 expression is associated with the side population (SP) phenotype of Hoechst 33342 efflux. The substrate profile of ABCG2 includes the antineoplastic drugs primarily targeting topoisomerases, including anthracyclines and camptothecins. More recently, pheophorbide, a chlorophyll-breakdown product, and protoporhyrin IX have been described as ABCG2 substrates, perhaps indicating a physiologic role of cytoprotection of primitive cells. Also, mice lacking ABCG2 expression have no intrinsic stem cell defects, although there is a remarkable increase in toxicity with antineoplastic drugs that are ABCG2 substrates, and also a photosensitivity resembling protoporphyria. Like other members of the ABC family, such as MDR1 and MRP1, ABCG2 is expressed in a variety of malignancies. Despite numerous reports of ABCG2 expression in AML, there is little evidence that ABCG2 expression is correlated with an adverse clinical outcome. This review will focus on the potential usefulness of ABCG2 as a marker primitive stem cells and possible physiologic roles of ABCG2 in protection of primitive stem cell populations, and potential methods of overcoming ABCG2-associated drug resistance in anticancer therapy. Copyright © 2003 John Wiley & Sons, Ltd. [source] Personal imports of drugs to Japan in 2005 , an analysis of import certificatesJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2008K. Tsuji MS Summary Background:, Personal imports of unapproved drugs are made by physicians and patients in Japan. Such imports require submission of a request for an import certificate from the Regional Bureau of Health and Welfare (RBHW). So far, there have been few reports on personal imports of drugs in Japan. Objective:, To assess the extent and nature of personal imports of drugs in Japan. Methods:, The date, product name and amount of drug imported were provided by RBHW for each personal import made by physicians in 2005. All imports were classified into several groups including whether they were for ,prescription drugs for non-cosmetic use (PDNC)' or ,prescription drugs for cosmetic use (PDC)'. Identification of PDNC was made by International Non-proprietary Name (INN). All drugs were classified under therapeutic groups. For the most frequently imported unapproved drugs, the approval year in the US/EU and development status in Japan were recorded. Results:, A total of 12 196 personal imports were initiated by physicians in 2005. 5428 were for PDNCs corresponding to 242 drugs by INN. 55 PDNCs were each the subject of 10 or more imports. 11 drugs (252 imports) out of the top 55 PDNCs were available on the Japanese market during 2005 and 44 (4713 imports) were not approved. Of the 44 unapproved drugs, 11 (1019 imports) had been approved and 10 (2785 imports) were in the pre-registration phase as of December 31, 2006. Of the 44 unapproved drugs, 12 (1213 imports) were approved during 2000,2004, and 17 (3138 imports), during 1995,1999 in the US or EU. While the majority of imported drugs were antineoplastic drugs, drugs for various kinds of non-serious diseases were also imported. Conclusions:, A substantial number of unapproved drugs were being imported to Japan. A formal system for monitoring the use of those drugs should be established. [source] Antiproliferative, cytotoxic and antitumour activity of coumarins isolated from Calophyllum brasilienseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2007César Ruiz-Marcial Among the eight Calophyllum species found on the American continent, Calophyllum brasiliense is the most widely distributed. Chemical analysis of this species has shown the presence of xanthones with cancer chemopreventive properties and antifungal activity. Recently, three new coumarins with antineoplastic properties have been found. In this study, we have evaluated the biological effects of the antiproliferative activity of coumarins isolated from C. brasiliense on the survival, cell cycle and apoptosis of cells in-vitro and their antitumour effects in mice. The cytological study showed that coumarins from C. brasiliense reduce the survival of BMK cells (baby mouse kidney cells) by inducing apoptosis and, to a lesser degree, necrosis. The cell cycle was arrested in S-phase and the division of BMK cells was inhibited. Coumarins had caused a reduction of experimental tumours in 83% of animals by the end of the treatment. Therefore, coumarins have the potential to be used alone or in combination with other antineoplastic drugs, and they might increase the effectiveness of other treatments for cancer. [source] Intraepidermal innervation and tail nerve conduction velocity in neurotoxicity models: results of a correlation study in normal and pathological conditionsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004M Borgna Animal models of human diseases affecting the peripheral nervous system are widely used to assess the pathogenesis of neurotoxicity and to compare the effect of new agents. Several behavioural, pathological and neurophysiological methods have been used, and each has advantages and disadvantages. A major goal in the study of neurotoxicity would be to assess the damage in the same way in animal models and in humans. In this study we correlated the neurophysiological results obtained in normal rats and in rats treated with cisplatin 2 mg/kg q3d × 8 with the density of intraepidermal fibers (IEF) obtained in skin biopsy specimens. The aim was to investigate the possible role of a minimally invasive procedure such as skin biopsy as an alternative method to assess the peripheral neurotoxicity of antineoplastic drugs. The nerve conduction velocity (NCV) in the tail nerve was assessed in thirty-six young adult female Wistar rats which were left untreated, or treated with erythropoietin (EPO), cisplatin (CDDP) or EPO + CDDP. CDDP and CDDP + EPO-treated rats had a significantly reduced NCV vs. age-matched untreated rats. At sacrifice, skin specimens were obtained. The density of IEF was calculated by 2 independent blinded examiners and the correlation existing between NCV and IEF was highly significant (r = 0.670, p < 0.001). This preliminary result suggests that IEF should be evaluated in other animal models and might represent a useful tool to study peripheral neurotoxicity also in humans. [source] Occupational risk in health care and research,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2003Daniela Vecchio MS Abstract Background Working in the health care and research sectors has been linked to various hazards. Methods Studies published in the peer-reviewed literature that are pertinent to the exposures or diseases relevant to these fields were reviewed. Results The most important exposures include infectious agents, formaldehyde, anesthetic agents, antineoplastic drugs, and ethylene oxide. The best-documented evidence is that of infectious risk primarily among clinical personnel. Monitoring studies of persons occupationally exposed to anesthetics clearly demonstrate behavioral effects, possible risk of reproductive problems, as well as cytogenetic effects of unknown significance. The latter two impairments are also observed among those exposed to antineoplastic drugs and ethylene oxide. Exposure to formaldehyde appears to be associated with nasopharyngeal tumors. Whereas increased risk of cancer of certain sites, particularly the brain and lymphohematopoietic system, is found among research and health care personnel, no specific exposure has been linked to these neoplasms. Conclusions Although some results are inconsistent, continued environmental and biological monitoring will allow better assessment of exposures and of implemented protection measures. Am. J. Ind. Med. 43:369,397, 2003. © 2003 Wiley-Liss, Inc. [source] Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug aloneBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2001N. Di Gaetano We have shown previously that the anti-CD20 chimaeric monoclonal antibody rituximab exerts its effects on neoplastic B-lymphoma cell lines in part via complement-dependent cytotoxicity. In addition, membrane expression levels of complement inhibitory proteins CD55 and CD59 play a role in determining susceptibility to lysis. We have identified one t(14;18)-positive human B-cell non Hodgkin's lymphoma cell line (Karpas 422) that is resistant to rituximab and complement and used it for subsequent studies on the possible interaction between this novel therapeutic agent and established antineoplastic drugs. We have exposed Karpas to several chemotherapeutic agents (doxorubicin, idarubicin, cisplatin, taxol) for different time periods and subsequently exposed the cells to rituximab and human complement. The combination of these drugs with rituximab induced an additive cytotoxic effect. In contrast, exposure to fludarabine (1 µg/ml for 48,72 h) showed a synergistic effect, with cell lysis increasing from 10% to 20% using fludarabine or rituximab and complement alone to about 70% with both cytotoxic agents. Analysis of the mechanism for this synergistic effect showed that fludarabine downmodulates the membrane expression of CD55 (from 96% to 55% positive cells) without significantly altering CD20 levels. Northern analysis demonstrated that fludarabine induced a general downmodulation of steady state mRNA levels with no change in transcription rate detected in run-off assays. The study of the effect of fludarabine and rituximab in six freshly isolated B-cell chronic lymphocytic leukaemia (B-CLL) samples showed that, in most cases, fludarabine has an additive cytotoxic activity with rituximab and complement. This report gives a rational support for clinical studies with combinations of drugs, including monoclonal antibodies and fludarabine. [source] Commercial taxane formulations induce stomatocytosis and increase blood viscosityBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001Michael Mark Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology. Whole blood was incubated in vitro with increasing concentrations of Taxol®, Taxotere®, paclitaxel (0 , 100 ,M) and the vehicles Cremophor-EL and Tween 80 (0 , 5% vol) for 1 h at 37°C. Plasma and whole blood viscosity (Haematocrit 45%) were measured and erythrocyte morphology was assessed on glutaraldehyde-fixed cells. The same investigations were performed in seven patients before and after a Taxol®-infusion. Taxol® and Taxotere® induced a dose- and time-dependent stomatocytic shape transformation of erythrocytes. Paclitaxel alone had no effect, but the vehicles cremophor-EL and Tween 80, used in Taxol® and Taxotere®, respectively, induced a comparable degree of stomatocytosis. This suggests a preferential intercalation of these substances into the inner hemileaflet of the membrane lipid bilayer. Associated with this shape change a dose-dependent increase in plasma and whole blood viscosity was observed. Neither shape nor viscosity changes were reversible upon removal of the agents. After the infusion of 130 , 300 mg Taxol® in patients a slight shift towards stomatocytosis and an increase in whole blood viscosity at high shear rate from 5.09±0.30 to 5.44±0.38 mPa.s (P<0.05) were confirmed. Commercial taxane drug formulations induce stomatocytosis and increase blood viscosity, which is due to their formulation vehicles. These findings may contribute to the understanding of the cardiovascular side effects of these drugs. British Journal of Pharmacology (2001) 134, 1207,1214; doi:10.1038/sj.bjp.0704387 [source] | ||||||||||||||||||||||