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  • 1
    Digitale Medien
    Digitale Medien
    Synthetic phospholipids as substrates for phospholipase C from Bacillus cereus
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism 1125 (1992), S. 166-170 
    Details
    ISSN: 0005-2760
    Schlagwort(e): Alkylphosphocholine ; Diacylglycerol ; Lysophospholipid ; Phospholipase C ; Synthetic phospholipid
    Quelle: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Thema: Biologie , Chemie und Pharmazie , Medizin , Physik
    Materialart: Digitale Medien
    URL: http://linkinghub.elsevier.com/retrieve/pii/0005-2760(92)90041-S
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  • 2
    Digitale Medien
    Digitale Medien
    Synthese von neuen bifunktionellen Maleinimidverbindungen zur Herstellung von Chemoimmunokonjugaten (1997)
    Springer
    Monatshefte für Chemie 128 (1997), S. 91-102 
    Details
    ISSN: 1434-4475
    Schlagwort(e): Maleimides ; Chemoimmunoconjugates ; Crosslinking reagent
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Bifunctional maleimide compounds are suitable for binding small molecules to carrier proteins in that they bind to the sulfhydryl group of proteins through the double bond of the maleimide group and to molecules of low molecular weight (e.g. anticancer drugs) through a functional groupX. 18 maleimide compounds of the general formula Maleimid-R-X (R=phenylene, benzyl-, methylene-, ethylene, or am-benzoylethylamide group andX=hydroxy-, amino-, hydrazino-, carboxylic acid-, carboxylic anhydride-, carboxylic acid chloride-, carboxylic acid hydrazide-, oxycarbonylchloride-, aldehyde, keto-, orp-toluenesulfonate-group) were synthesized and characterized through1H- and13C-NMR-spectroscopy, elemental analysis, and mass spectrometry.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00807643
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  • 3
    Digitale Medien
    Digitale Medien
    Pharmacokinetic behavior and antineoplastic activity of liposomal hexadecylphosphocholine (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 393-398 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Liposomes ; Alkylphosphocholine ; Pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Hexadecylphosphocholine (HePC) shows remarkable antineoplastic efficacy in Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinoma. Unfortunately, this is accompanied by detrimental side effects that include gastrointestinal damage, body weight loss, and thrombophlebitis after i.v. injection, which has precluded the use of the HePC in humans, where nausea and vomiting can occur at noneffective dose levels. We have developed small unilamellar vesicles (SUVs) composed of HePC, cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, which can be given p. o. and i.v. In contrast to the free drug, the toxicity of liposomal HePC is shown to be greatly reduced, and there is no risk of thrombophlebitis. Single administration of equimolar HePC doses results in differing pharmacokinetic values for free HePC (p. o.) and HePC-SUVs (p. o., i.v.).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685563
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  • 4
    Digitale Medien
    Digitale Medien
    Clinical and pharmacologic phase I study of Cemadotin—HCl (LU103793), a novel antimitotic peptide, given as 24-hour infusion in patients with advanced cancer (1998)
    Springer
    Annals of oncology 9 (1998), S. 1323-1330 
    Details
    ISSN: 1569-8041
    Schlagwort(e): Cematodin–HCL ; Dolastin 15 analog ; phase I study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To determine the maximum tolerable dose (MTD), principal toxicity, and pharmacologic behaviour of Cemadotin—HCl, a novel antimitotic peptide. Patients and methods: Cemadotin—HCl (10.0 to 27.5 mg/m2/day every three weeks) was administered as a 24-hour intravenous (i.v.) continuous infusion to patients with advanced cancer. Pharmacokinetic analyses were performed during the first treatment cycle. Blood samples were taken over 48 hours and analyzed by radioimmunoassay. Results: Hypertension was the dose-limiting toxicity (DLT). This type of toxicity was observed at all dose levels, but grade 3 (CTC) was observed only at dose levels 20.0, 25.0 and 27.5 mg/m2. This effect was reversible but in three patients associated with signs of cardiac ischemia. Other significant toxic effects were neutropenia, asthenia, tumor pain and transient liver enzyme elevation. A linear pharmacokinetics was observed. The best curve fit was obtained with a two-compartment model with a terminal half-life of ≈10 hours at each dose level, a volume of distribution at steady state of ≈9 l/m2 and a total clearance of ≈0.6 l/hour/m2. Neither partial nor complete responses were observed although minor tumor regressions were seen in a patient with carcinoma of unknown primary (CUP) and in another patient with liver metastases from a colon cancer. Conclusions: Hypertension was the dose-limiting toxicity of Cemadotin—HCl administered as a continuous 24-hour infusion. The recommended dose for further evaluation of its anticancer efficacy in disease-oriented phase II studies with this schedule is 15.0 mg/m2. The nature of the principal cardio-vascular toxicity remains unclear. The observed toxicities appeared to be significant but manageable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008430515881
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  • 5
    Digitale Medien
    Digitale Medien
    Clinical phase I study with one-hour paclitaxel infusion (1998)
    Springer
    Annals of oncology 9 (1998), S. 569-572 
    Details
    ISSN: 1569-8041
    Schlagwort(e): paclitaxel (Taxol®) ; phase I study ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Paclitaxel (PAC) is one of the major anti-cancer drugs,effective in different tumors. Studies with 24-hour infusion with 135mg/m2 and a three-hour infusion with 175 mg/m2showed a significant schedule-dependent toxicity. We evaluated a one-hourinfusion schedule within a phase I study to determine the dose limitingtoxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancerefficacy. Patients and methods: Patients with advanced malignant tumors weretreated within cohorts by one-hour infusional paclitaxel starting with 150mg/m2 and stepwise escalation with 25 mg/m2increments. Therapy was repeated in three-week intervals. Cycles wererepeated until progression. Toxicity was closely monitored, anti-cancerefficacy was only evaluated in those patients who received at minimum twotreatment cycles. Results: Thirty-four patients entered the study (11 NSCLC, five SCLC,seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTDwas PAC 250 mg/m2. The DLT was central and peripheralneuropathy (WHO grade 3). Other significant toxicities were fatigue,myalgia/arthralgia and paraesthesia. No significant myelotoxicity wasobserved. Totally twentyone patients were evaluable for response. A partialresponse was observed in five (24%) patients (two NSCLC, two ovariancancer, one head and neck cancer). Three (14%) patients had stabledisease and in 13 (62%) patients progressive disease was observed. Conclusions: Paclitaxel 225 mg/m2 on day 1 administered asone-hour infusion and repeated every three weeks can be given safely, featuredno relevant myelotoxicity, and is the recommended dose for phase II studies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1008217429971
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