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Cytostatic Agent (cytostatic + agent)
Selected AbstractsA Concise and Efficient Synthesis of seco -Duocarmycin SAEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2003Lutz F. Tietze Abstract A short and efficient synthesis of seco -duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5- exo - trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDSBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010D De Forni BACKGROUND AND PURPOSE Antiviral hyper-activation-limiting therapeutic agents (AV-HALTs) are a novel experimental drug class designed to both decrease viral replication and down-regulate excessive immune system activation for the treatment of chronic infections, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. VS411, a first-in-class AV-HALT, is a single-dosage form combining didanosine (ddI, 400 mg), an antiviral (AV), and hydroxyurea (HU, 600 mg), a cytostatic agent, designed to provide a slow release of ddI to reduce its maximal plasma concentration (Cmax) to potentially reduce toxicity while maintaining total daily exposure (AUC) and the AV activity. EXPERIMENTAL APPROACH This was a pilot phase I, open-label, randomized, single-dose, four-way crossover trial to investigate the fasted and non-fasted residual variance of AUC, Cmax and the oral bioavailability of ddI and HU, co-formulated as VS411, and administered as two different fixed-dose combination formulations compared to commercially available ddI (Videx EC) and HU (Hydrea) when given simultaneously. KEY RESULTS Formulation VS411-2 had a favourable safety profile, displayed a clear trend for lower ddI Cmax (P= 0.0603) compared to Videx EC, and the 90% confidence intervals around the least square means ratio of Cmax did not include 100%. ddI AUC, was not significantly decreased compared to Videx EC. HU pharmacokinetic parameters were essentially identical to Hydrea, although there was a decrease in HU exposure under fed versus fasted conditions. CONCLUSIONS AND IMPLICATIONS A phase IIa trial utilizing VS411-2 formulation has been fielded to identify the optimal doses of HU plus ddI as an AV-HALT for the treatment of HIV disease. [source] Corneal and conjunctival findings after mitomycin C application in pterygium surgery: an in-vivo confocal microscopy studyACTA OPHTHALMOLOGICA, Issue 2 2009Andrey Zhivov Abstract. Purpose:, To perform a qualitative assessment of the topical side-effects of mitomycin C on cornea after pterygium surgery. Methods:,In-vivo confocal microscopy (Heidelberg Retina Tomograph II in combination with the Rostock Cornea Module) was performed in 10 patients with unilateral primary pterygium. Mitomycin C 0.02% was applied topically to seven eyes for 5 min intraoperatively and twice daily for 5 days postoperatively. Three eyes underwent surgery without application of cytostatic agent. Patient follow-up was 1 month. Results:, After application of mitomycin C, complete epithelialization of the operated zone was found 2 weeks after surgery. In-vivo confocal microscopy revealed signs of superficial punctate keratitis for 2 weeks in the central cornea only after application of mitomycin C. The presence of epithelial and stromal oedema in this group was noted for up to 2 weeks in the central cornea and for up to 4 weeks in the operated zone. In the control group, complete epithelialization was found after 1 week; there were no signs of oedema after 1 week in the central cornea or after 2 weeks in the operated zone. Leucocyte infiltration and increased Langerhans cell density were noted in both groups in the operated and central zones. Analysis of the conjunctiva revealed a decrease in goblet cell density following cytostatic application. Conclusion:, Local application of mitomycin C delays corneal epithelialization, and prolongs postoperative epithelial and stromal oedema in both the centre and periphery. Moreover, signs of punctate keratitis were noted 2 weeks after surgery in central intact cornea. Nevertheless, in-vivo confocal microscopy shows that these changes are reversible 4 weeks after application of mitomycin C 0.02%. [source] Influence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney functionPEDIATRIC BLOOD & CANCER, Issue 6 2003Lutz Hempel MD Abstract Background The present investigation was intended to further clarify the mechanisms involved in renal dysfunction following high-dose methotrexate (HD-MTX) treatment. Patients and Methods Fifty eight predominately pediatric patients [39 male, 19 female; mean age 12.3 years (range 2.2,34.1)] suffering from acute lymphoblastic leukemia (ALL, n,=,28), Non Hodgkins lymphoma (NHL, n,=,13), osteosarcoma (n,=,8), malignant brain tumor (n,=,6), or an ALL relapse (n,=,3), were prospectively examined. In the course of 220 infusions of HD-MTX, glomerular and tubular renal function was determined by measuring proteinuria and glomerular filtration rate (GFR), as well as renal excretion of alpha-1-microglobulin (AMG) and N -acetyl-,- D -glucosaminidase (NAG). It was investigated whether there were differences in MTX toxicity in dependence on the administered dose (1, 5, or 12 g/m2 BSA), on the combination with other cytostatic agents (ifosfamide or cyclophosphamide), on the metabolism of MTX into 7-OH-MTX, and on pre-treatment with MTX. Results The administration of HD-MTX has no direct tubulotoxic effect. The disturbance in glomerular function was dose dependently and indicated by an increase in proteinuria as well as by a decrease in GFR; all changes were completely reversible and did not correlate to the metabolism of MTX to 7-OH-MTX. Increasing the number of MTX therapeutic cycles did not increase the nephrotoxicity of MTX. Conclusion MTX is not directly tubulotoxic. Its side effects on glomeruli are usually without clinical relevance. Med Pediatr Oncol 2003;40:348,354. © 2003 Wiley-Liss, Inc. [source] Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line,BIOELECTROMAGNETICS, Issue 8 2002M.J. Ruiz-Gómez Abstract The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1cch. The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P,<,0.01), exhibiting 6.1% of survival at 47.5 ,g/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 ,g/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P,<,0.001). Cisplatin showed a significant reduction in the % of survival (44.2,39.1%, P,<,0.05) at 25 Hz and 47.5 ,g/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1cch, with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation. Bioelectromagnetics 23:578,585, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||