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  • 1
    Electronic Resource
    Electronic Resource
    Synthesis, mechanism of action, and biological evaluation of mitosenes (1989)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 32 (1989), S. 1612-1620 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00127a035
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  • 2
    Electronic Resource
    Electronic Resource
    Influence of site on the chemosensitivity of transplantable murine colon tumours to flavone acetic acid (LM975, NSC 347512) (1989)
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 87-94 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A number of experimental studies have demonstrated significant responses of s. c. solid tumours to flavone acetic acid (FAA). Clinical studies to date have been disappointing, with no objective responses being seen. The present study demonstrated that the tumour site is important for the anit-tumour action of FAA against two transplantable adenocarcinoma lines (MAC) in NMRI mice. Responses were achievable only when the tumours were implanted s. c. Ascitic or systemic tumours did not respond to FAA. Experimentally achievable plasma levels of FAA were not sufficient to induce significant cell kills in either MAC 15A or MAC 26 cell lines in vitro. A poor correlation exists between in vitro and in vivo responses, as the clonogenic assay could not predict the respose of the solid MAC tumours grown s. c. The in vitro data indicated that the length of exposure to FAA was important, with long exposure times being necessary for cytotoxicity to develop, in these tumour cell lines. These studies imply that more than one mechanism is involved, and it is likely that the activity of FAA against s. c. tumours relies at least in part on a specific biological feature of tumours in this site. However, it may still be possible to achieve systemic tumour cell kill in vivo by increasing drug-exposure times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00263126
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of the tissue distribution of ThioTEPA and its metabolite, TEPA, on the response of murine colon tumours (1987)
    Springer
    Cancer chemotherapy and pharmacology 20 (1987), S. 203-206 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Disposition studies in the same animals as those used for assessment of antitumour and toxic effects could increase understanding of the variation in response to cytotoxic drugs. Tissue and plasma levels of ThioTEPA and triethylenephosphoramide (TEPA) were measured to see if any correlation existed between them and the effects of the drug on a series of mouse colon tumours (MAC). The tumour panel included an ascitic form (MAC 15A), an anaplastic (MAC 13) and a well-differentiated (MAC 26) solid tumour, all grown subcutaneously. The maximum tolerated dose of ThioTEPA was 20 mg kg-1 in females bearing MAC 13 and 15 mg kg-1 in males having MAC 15A or 26. The diverse growth characteristics of the tumour cell lines necessitated the use of different methods for assessment of response. After administration of the maximum tolerated dose, the greatest response was observed in MAC 26, in which a growth delay of 15 days — twice the doubling time of the tumour volume — occurred. ThioTEPA produced 58% inhibition of MAC 13 tumour weight, but MAC 15A was unresponsive. One hour after intraperitoneal administration of ThioTEPA (20 mg kg-1), ratios of tissue to plasma concentration were 1.13, 0.87 and 1.17 in tumours and 0.80, 0.75 and 0.73 in spleens of mice bearing MAC 13, 15A and 26 respectively. These data show greater accumulation of drug in neoplastic than in normal tissues. The pattern of distribution of the metabolite was similar, but there was a lesser degree of tissue accumulation than by the drug. Concentrations of drug and metabolite in neoplastic tissues related to their protein content were 116.0, 126.3 and 183.3 μg ThioTEPA/g and 57.5, 83.1 and 78.6 μg TEPA/g in MAC 13, 15A and 26 respectively. Combination of these chemosensitivity and pharmacokinetic data indicates that differences in response of these tumours to ThioTEPA cannot be explained by the availability of the drug and metabolite. The therapeutic effects of ThioTEPA cannot be predicted purely from a knowledge of drug and metabolite disposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570485
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  • 4
    Electronic Resource
    Electronic Resource
    Experimental correlations of in vitro drug sensitivity with in vivo responses to ThioTEPA in a panel of murine colon tumours (1988)
    Springer
    Cancer chemotherapy and pharmacology 21 (1988), S. 168-172 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cell lines derived from three histologically different murine colon tumours (MAC) were used to assess whether or not a tumour colony-forming assay could have retrospectively predicted the wide range of in vivo responses to the alkylating agent, ThioTEPA. Tumour responses ranged from sensitive (MAC 26) to resistant (MAC 15A), with MAC 13 showing only moderate sensitivity. In vitro chemosensitivity studies, in conjunction with pharmacokinetic data, suggest that plasma levels of the drug's primary metabolite, TEPA, should be sufficient to induce significant cell kills in all three tumour lines in vivo. Preliminary studies on the effect of pH on the cytotoxic properties of ThioTEPA in vitro have demonstrated an improved cell kill when cells were exposed to the drug under acidic conditions. As these tumours differ histologically in terms of vascularisation, tumoural pH may play an important part in determining drug efficacy and go some way towards explaining the poor in vitro/in vivo correlation in this model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257366
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  • 5
    Electronic Resource
    Electronic Resource
    Activity of N-[N′-(2-chloroethyl)-N′-nitrosocarbamoyl]-alanine and derivatives against transplantable adenocarcinomata of the mouse colon (MAC) (1986)
    Springer
    Journal of cancer research and clinical oncology 112 (1986), S. 47-49 
    Details
    ISSN: 1432-1335
    Keywords: 2-chloroethylnitrosocarbamoyl ; Amino acids ; Derivatives ; Nitrosoureas ; Experimental chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anti-neoplastic activity of N-[N′-(2-chloroethyl)-N-nitrosocarbamoyl(CNC)]-alanine, CNC-alanyl-alanine, CNC-alanine-methylamide and CNC-glycine-methylamide was examined in murine transplantable colon tumours (MAC). The methylamide derivatives were highly active against a solid adenocarcinoma (MAC 13) and an ascitic adenocarcinoma (MAC 15A). CNC-alanyl-alanine was also highly active against MAC 15A. Responses of the three latter agents against the ascitic tumour were better than for any previously tested drugs including the nitrosoureas but their eventual usefulness cannot be determined without further toxicological studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00394938
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  • 6
    Electronic Resource
    Electronic Resource
    The assessment of response of murine transplantable colon tumors to combination chemotherapy (1982)
    Springer
    Journal of cancer research and clinical oncology 103 (1982), S. 119-126 
    Details
    ISSN: 1432-1335
    Keywords: Mice model ; Colon cancer ; Chemotherapy ; Mäuse ; Adenokarzinom des Colons ; Chemotherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das MAC (murines Adenokarzinom des Colons), das sich als Modell für das menschliche colorectale Karzinom bezüglich seiner Chemosensitivität als gut erwiesen hat, wurde mit zwei weiteren modifizierten Chemotherapieschemate (MeCCNU+5 FU, BCNU+5 FU) untersucht, um seine Eignung auch als Modell zur Entwicklung neuer Kombinationstherapien zu prüfen. Dabei wurden zweierlei Probleme ersichtlich: erstens die verfügbare Zeitspanne, bevor der Tumor in Kontrolltieren und “NonResponders” zu groß wurde und die adäquate Beweglichkeit der Tiere erheblich beeinträchtigte; zweitens die Erfolgsbeurteilung der Medikation. Der Beginn der Medikamentenapplikation 3 Tage nach Transplantation des Tumors und Erfolgsbeurteilung durch Messung der zeitlichen Verzögerung des Tumor-wachstums bis zum Erreichen eines bestimmten Volumens ermöglichten eine vernünftige Evaluation. Die Resultate wurden mit dem Gehan-(verallgemeinerter Wilcoxon)-Test analysiert. Es wird gezeigt, daß die beschriebene Methodik für das Studium transplantabler, solider Tumoren als Modell für ihre Chemosensitivität auf Kombinationstherapien geeignet ist.
    Notes: Summary The mouse adenocarcinoma of the colon (MAC) system, which has been shown to be a good model for human colorectal carcinoma in terms of its chemosensitivity, was tested with two modified human protocols (MeCCNU+5 FU, BCNU+5 FU) in an attempt to evaluate its suitability as a model for developing new regimens of combination chemotherapy for treating patients with colorectal carcinoma. This attempted evaluation raised problems regarding, firstly, the length of time available before tumours became too large in control and non-responding hosts to maintain adequate mobility and, secondly, the assessment of response to the drugs. The commencement of drug administration 3 days after transplantation and the assessment of response by measuring delay in time for tumor growth to reach a given volume, with the results analysed by Gehan's (generalised Wilcoxon) test, gave a workable method of evaluation. This method is presented as being suitable for use in the study of transplantable solid tumor lines as models for combination chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00409642
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and cytotoxicity of B.3839, a molecular combination of 5-fluorouracil and N-(2-chloroethyl)-N-nitrosourea, in a mouse model (1992)
    Springer
    Investigational new drugs 10 (1992), S. 149-158 
    Details
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; cytotoxicity ; molecular combination ; fluorouracil ; nitrosourea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary B.3839 is the prototype compound in a series of novel molecular combinations of chloroethylnitrosoureas and 5-fluorouracil(5-FU) and has been tested against MAC tumours in mice. Previous studies have shown it is moderately active against MAC15A and highly active against MAC13 though this activity is dependent on route of administration. The aim of this study was to determine whether bioavailability could explain this difference in anti-tumour activity. Plasma levels of B.3839 and 5-FU after i.p. and oral administration were measured using HPLC. Non tumour-bearing and MAC26 bearing mice gave almost identical plasma profiles after i.p. administration with the Cmax being 29.8 and 30.4μ gml−1 and t1/2 16 and 15 min. The AUCs were 15.3 and 13.9μg h ml−1 suggesting tumour load had no influence over plasma levels. Oral administration gave a much lower Cmax of 8.0μg ml−1 but an AUC of 15.2μg h ml−1 due to a longer terminal t1/2 (94 min) giving 99% bioavailability. Levels of 5-FU release from B.3839 by either route were considered too small to influence anti-tumour activity. Cytotoxicity assaysin vitro against the MAC lines gave IC70 values of 5.3, 13.8 and 8.6μg ml−1 for MAC 26,13 and 15A respectively after a one hour exposure. Bone marrow toxicity was shown to be less severe than that of TCNU which is currently in clinical trials. The results show bioavailability alone is not enough to explain tumour response. There appears to be a need for a threshold concentration (C) to be maintained for a period of time (t).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00877239
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  • 8
    Electronic Resource
    Electronic Resource
    Antineoplastic activity of alkylphosphocholines (APC) in human breast carcinomasin vivo andin vitro; use of liposomes (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 269-279 
    Details
    ISSN: 1573-7217
    Keywords: alkykphosphocholines ; breast carcinoma ; eicosanylphosphocholine ; hexadecylphosphocholine ; liposomes ; nude mice ; octadecylphosphocholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study examines thein vitro andin vivo activity of alkylphosphocholines (APC) in experimental human breast carcinomas. Three analogs, hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC) were investigated. Three hormone receptor negative cell lines were sensitive to all three APCsin vitro whereas the receptor positive MCF-7 line was more resistant. Sensitivity was seen in 4/6 hormone receptor negative tumorsin vivo, with HPC being the most active analog. There were no antitumor effects in the four receptor positive models. The reasons for these differences in response between hormone receptor negative and -positive lines are not yet understood and require further study. Gastrointestinal toxicity and hemolysis, the major side effects of the APCs, were reduced by the use of liposomal preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666004
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