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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Chemical reviews 87 (1987), S. 1137-1152 
    ISSN: 1520-6890
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 337-341 
    ISSN: 1432-0851
    Keywords: Key words: Tumor necrosis factor – Cell-cycle dependence – In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Several in vitro studies have demonstrated that tumor cells arrested in the G2 and M phases of the cell cycle expressed an increased sensitivity to the tumor necrosis factor (TNF). The scope of the present study was to investigate whether this cycle dependence of TNF effects also exists in vivo. The experiments were performed by using the Lewis lung carcinoma (LLC), which had been allotransplanted to nude mice. In order to induce delays of the tumor cell cycle in G2, the animals were treated with etoposide (40 mg/kg body weight i. p.) or with local radiation (15 Gy), each increasing the G2 fraction of the LLC from 10% to 35% and 50% respectively. For combination therapy with recombinant (r)TNF, the tumor was transplanted to four groups of six mice each, one of them serving as a control group the others being treated either with a G2 inductor alone, with rTNF alone, or with rTNF and a G2 inductor combined. Administration of rTNF (125 or 250 μg/kg body weight i. v.) was always carried out 24 h after therapy with etoposide or radiation when the maximum of G2 accumulation had developed. The growth behavior of the treated tumors revealed that the response of the LLC to rTNF in vivo was not improved by pretreatment with a G2 inductor and, thus, obviously lacked cell-cycle specificity. It is supposed that direct interactions of TNF with the tumor cells, which are a basic requirement for cell-cycle-linked phenomena, play a minor role in the therapeutic outcome of the LLC under in vivo conditions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 29 (1992), S. 227-235 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study, the influence of carboplatin [diammine(cyclobutane-1,1-dicarboxylato)platinum(II)], the main and most active representative of second-generation antitumour platinum complexes, on the morphology of the testes of male CF1 mice was investigated histologically by examining semithick sections. Carboplatin was administered in doses of 30, 60 or 120 mg/kg and applied as a single intraperitoneal injection. For comparison purposes, the parent compound cisplatin [cis-diamminedichloroplatinum(II)] was administered at equitoxic doses (3, 6 or 12 mg/kg). At various intervals between days 1 and 28 after treatment, the testes were removed and embedded in Epon. Both compounds effected severe structural alterations of Sertoli cells, disrupted the blood/testis barrier, and impaired the processes both of spermatogenesis and spermiohistogenesis. The structural damage in the testes following treatment with carboplatin was at least as pronounced as that occurring under the influence of equitoxic doses of cisplatin. Within a few days, the intercellular spaces around Sertoli cells widened, the tight contacts with neighbouring cells were disrupted, the cytoplasm of Sertoli cells disintegrated and their nuclei shrank. Numerous necroses, abnormal mitotic figures of spermatogenic cells and malformed spermatozoa appeared. Severe damage was evident on days 10–21 after treatment with carboplatin, the strength of the symptoms being clearly dependent on the dose applied. The first indications of ongoing recovery processes were detected on day 21 in the case of the low dose (30 mg/kg) or on day 28 following treatment with 60 mg/kg or 120 mg/kg. These results confirm that carboplatin is at least as toxic to the testes as cisplatin and that its substitution for cisplatin in clinical therapy does not diminish the problem of drug-induced infertility following platinum-based chemotherapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Keywords: 19F-NMR spectroscopy ; 5-FU ; Combined treatment modality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The metabolism of 5-fluorouracil (5-FU) was monitored non-invasively in two xenografts, a hypopharynx carcinoma and a colon carcinoma (CSM) by19F-magnetic resonance spectroscopy following an i. v. bolus injection of 130 mg kg−1 5-FU. Both the level of fluoronucleotides (FNuc) and the tumour growth delay were significantly higher in the CSM colon carcinoma than in the hypopharynx carcinoma (both parameters,P〈0.001). Administration of 100 mg kg−1 methotrexate (MTX) at 15 h before treatment with 5-FU caused a significantly increased conversion of 5-FU to FNuc in both tumours (P〈0.05) as compared with the application of 5-FU alone. However, only in the CSM tumour was a significantly increased growth delay (P〈0.01) observed. Pre-treatment of both xenografts with 400 mg kg−1 thymidine enhanced the conversion of 5-FU to FNuc in both tumours. In the CSM tumour this treatment modality caused a significantly (P〈0.05) higher growth delay as compared with the results obtained with 5-FU alone, whereas in the hypopharynx carcinoma the additional application of thymidine caused no significant change in tumour growth. It is known that both thymidine and MTX can reduce the DNA-directed cytotoxicity of 5-FU, whereas the RNA-directed cytotoxicity is increased. It is concluded that the DNA-mediated toxicity may be more important in the hypopharynx carcinoma than in the CSM colon carcinoma. As a consequence, pre-treatment with MTX or thymidine enhances FNuc formation, although only in the CSM carcinoma is there an increased tumour growth delay. Thus, in the hypopharynx carcinoma the measurement of FNuc did not serve as a predictor for the treatment efficacy of the combined treatment modality. Pre-treatment with MTX did not influence the catabolism of 5-FU, whereas thymidine actually prolonged the half-life of 5-FU without α-fluoro-β-alanine becoming detectable.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 5 (1981), S. 237-241 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vitro growth-inhibiting potencies of titanocene dichloride (TDC), zirconocene dichloride (ZDC), hafnocene dichloride (HDC), vanadocene dichloride (VDC), and molybdocene dichloride (MDC) against Ehrlich ascites tumor (EAT) cells cultured in vitro as permanently growing suspension cultures were determined. The most striking growth-suppression activity was detected for VDC. A VDC concentration as low as 5 · 10-6 mol/l effects a highly significant diminution of cell proliferation. TDC and MDC inhibit cellular growth only in concentrations of 5 · 10-4 or 10-3 mol/l, respectively, whereas ZDC and HDC, which are ineffective against EAT cells in vivo, require higher concentration levels. The growth inhibition is caused by a cytotoxic action of the metallocene dichlorides, as is demonstrated in the case of VDC and TDC by differentiation of live and dead EAT cells by means of the dye lissamine green.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 337-341 
    ISSN: 1432-0851
    Keywords: Tumor necrosis factor ; Cell-cycle dependence ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several in vitro studies have demonstrated that tumor cells arrested in the G2 and M phases of the cell cycle expressed an increased sensitivity to the tumor necrosis factor (TNF). The scope of the present study was to investigate whether this cycle dependence of TNF effects also exists in vivo. The experiments were performed by using the Lewis lung carcinoma (LLC), which had been allotransplanted to nude mice. In order to induce delays of the tumor cell cycle in G2, the animals were treated with etoposide (40 mg/kg body weight i.p.) or with local radiation (15 Gy), each increasing the G2 fraction of the LLC from 10% to 35% and 50% respectively. For combination therapy with recombinant (r)TNF, the tumor was transplanted to four groups of six mice each, one of them serving as a control group the others being treated either with a G2 inductor alone, with rTNF alone, or with rTNF and a G2 inductor combined. Administration of rTNF (125 or 250 μg/kg body weight i.v.) was always carried out 24 h after therapy with etoposide or radiation when the maximum of G2 accumulation had developed. The growth behavior of the treated tumors revealed that the response of the LLC to rTNF in vivo was not improved by pretreatment with a G2 inductor and, thus, obviously lacked cell-cycle specificity. It is supposed that direct interactions of TNF with the tumor cells, which are a basic requirement for cell-cycle-linked phenomena, play a minor role in the therapeutic outcome of the LLC under in vivo conditions.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 122 (1996), S. 596-602 
    ISSN: 1432-1335
    Keywords: Cell cycle ; Cisplatin ; Flow cytometry ; Head and neck cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies performed with xenografted human head and neck carcinomas in vivo have demonstrated that the cytokinetic phenomena occurring under the influence of cisplatin closely correlate with the response of the tumors to therapy. The present paper analyses whether this correlation also exists in vitro. Four human head and neck carcinoma cell lines showing different degrees of sensitivity to cisplatin, as determined by the trypan blue exclusion assay, were investigated by flow cytometry at various intervals after administration of cisplatin. Early cell-cycle blockades in the S phase always reflected a high degree of cytostatic potency of cisplatin and were usually succeeded by a pronounced inhibition of tumor cell proliferation and a reduction of cell viability. In the case of a minimal response to therapy and in untreated control cultures of all four tumor lines, the relative number of S-phase cells continuously diminished during the observation period. These findings point to the S-phase blockade as the crucial cytokinetic effect of cisplatin preceding relevant growth reductions. This knowledge might support the development of a drugresponse assay that could predict the sensitivity of individual patient tumors in vitro before the beginning of clinical cancer chemotherapy.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1335
    Keywords: Key words31P NMR spectroscopy ; Hypopharynx carcinoma ; Radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: An early indicator of tumor sensitivity to irradiation could provide useful information on the effectiveness of therapy and may facilitate more individual designs of treatment protocols. The aim of the present study was to evaluate the potential of in vivo 31P nuclear magnetic resonance spectroscopy in predicting the response of a xenografted human hypopharynx carcinoma to radiotherapy. Methods: The tumor had been serially heterotransplanted to athymic mice. 31P NMR spectra were collected before and at four intervals (24, 48, 72, and 120 h) after irradiation with 15 Gy or 30 Gy. Alterations of phosphorus metabolism were compared with the growth delays, the histological appearance, and the mitotic activity of the treated tumors. Results: Radiation with 30 Gy induced increases of the phosphodiester level (P 〈 0.001) as well as of the tumor pH (P 〈 0.05) and decreases of the phosphomonoester level (P 〈 0.001) within 48 h. The changes clearly preceded measurable tumor responses and were accompanied by severe histological destruction and marked depression of mitotic indices. However, none of these spectral alterations was significantly correlated with individual delays of tumor growth. The only parameters allowing a prediction of radiation-induced tumor responses were the pre-treatment levels of phosphomonoesters and -diesters. The 31P NMR spectroscopic changes observed after therapy with 15 Gy were either unsystematic or insignificant. Conclusions: Pre-treatment levels of tumor phospholipids were indicative of radiosensitivity in the xenografted human hypopharynx carcinoma investigated here. However, since phosphorus metabolism varies considerably among different tumor lines, it seems unlikely that there exists a uniform 31P NMR spectroscopic parameter predicting tumor response to radiation therapy.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 73 (1986), S. 239-247 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 74 (1987), S. 374-382 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Notes: Schlußfolgerungen Für eine Reihe verschiedenartiger, anorganischer und metallorganischer Nicht-Platinmetall-Verbindungen wurden in den letzten Jahren zum Teil ausgeprägte tumorhemmende Eigenschaften nachgewiesen. Damit hat sich den bereits klinisch bewährten Platinmetall-Komplexen eine neue, chemisch heterogene Gruppe tumorhemmender Verbindungen zugesellt, die durch folgende biologische Eigenschaften gekennzeichnet sind: • Das Wirkungsspektrum der meisten Nicht-Platinmetall-Verbindungen gegenüber experimentellen tierischen und menschlichen Tumoren ist nicht identisch mit dem von Cisplatin. Dementsprechend dürfte auch das klinische Aktivitätsspektrum unterschiedlich sein. Für einige Gallium- und Germanium-Verbindungen konnte dies in klinischen Studien bereits belegt werden. • Die organschädigenden Eigenschaften der meisten tumorhemmenden Nicht-Platinmetall-Verbindungen, insbesondere derer, die weniger schwere Metallatome wie Titan oder Eisen enthalten, weichen grundlegend von dem für Cisplatin bekannten Toxizitätsmuster ab. Theoretisch dürfte es daher • Tumorhemmende Nicht-Platinmetall-Verbindungen verhalten sich somit in biologischer Hinsicht nicht analog den cytostatischen Platin-Komplexen und sind daher als eigenständige Gruppen cytostatisch wirksamer Substanzen anzusehen und abzugrenzen.
    Type of Medium: Electronic Resource
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