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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 23 (1984), S. 1312-1322 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 17 (1978), S. 5598-5604 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Effects of a combination chemotherapy using cis-diamminedichloroplatinum (II) (DDP) and its antidote, sodium thiosulfate (STS), on metastatic lung tumour in rats were studied. Rats were given an upper hemibody infusion (UHI) of 15 mg/kg DDP immediately after occlusion of the abdominal aorta and i.v. administration of 1581 mg/kg STS (200-fold molar ratio to DDP) 10 min later. The aortic clamp was released at approximately 11 min after the beginning of UHI when a half volume of STS solution was infused. Antitumour and side effects in this group were compared with those in the respective control groups given 5 mg/kg DDP alone by UHI or by systemic administration. In the group given UHI of DDP (DDP-UHI) in combination with STS, there was a significantly better antitumour effect than seen in the group given DDP alone, as evaluated by the number of lung tumour nodules and survival time after inoculation of the transitional cell carcinoma into the lung. Nephrotoxicity, as assessed by increase in BUN levels, was completely avoided. Haematological toxicity effects assessed by decreases in WBC were slight but body-weight loss due to anorexia was severe.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary “Two-route chemotherapy” (TRC) using cis-diamminedichloroplatinum(II) (DDP) and its antidote, sodium thiosulfate (STS), combined with the angiotensin II (AT-II)-induced hypertension method was evaluated for its efficacy against peritoneally disseminated tumors in rats. A bolus i.p. injection of DDP (15 mg/kg) was given 1 min after the initiation of an AT-II (16.5 μg/kg) i.v. infusion lasting 11 min. Immediately after the termination of the AT-II infusion, 1,580 mg/kg STS was injected i.v. over a further 5 min. This modified TRC significantly improved the antitumor effect, evaluated by survival (increase in life span, 273%), compared with that achieved with other treatments, as follows: 15 mg/kg DDP i.p. and the concomitant i.v. infusion of 1,580 mg/kg STS (conventional TRC), 153% increase in life span; 5 mg/kg DDP i.p. with or without AT-II i.v. (167% and 107% increases in life span, respectively). As an index of nephrotoxicity, blood urea nitrogen (BUN) levels seen after modified TRC (21.1 mg/dl) were as low as those observed after conventional TRC (19.1 mg/dl), despite the postadministration of STS, and were much lower than those seen after DDP alone or DDP plus AT-II (35.6 and 35.7 mg/dl, respectively). Further evaluation of the effectiveness of modified TRC using various doses of DDP gave similar results. The feasibility of the administration of STS 10 min after DDP treatment was explained by the significant inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. Thus, TRC combined with AT-II has a superior therapeutic effect against peritonitis carcinomatosa induced in rats.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mode of inactivation of cis-diamminedichloroplatinum(II) (DDP) in the bloodstream and protection from its toxicity by sodium thiosulfate (STS) were investigated in rabbits. Plasma ultrafiltrate in rabbits given 5 mg/kg DDP IV and various excess molar ratios of STS IV were assayed for the active platinum levels with a new microbiological assay system using an E. coli strain. The active platinum species in the plasma were inactivated completely by coadministration of a 400-fold excess of STS IV. The rabbits were almost completely protected against both BUN increase and body weight loss normally caused by DDP when 400-fold doses of STS were given. Diuretic effects were also observed. Our data provide evidence for the basis of optimum use of STS to protect against DDP toxicity. [6, 9]. This TRC with DDP and STS is now in clinical trial [7, 8], but the precise mode of protective action of STS against DDP toxicity has not been determined. We now present evidence that this protective effect is due to inactivation of biologically active DDP in the bloodstream.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 13 (1984), S. 82-85 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To elucidate the mechanisms of inactivation of cis-diamminedichloroplatinum(II) (DDP) toxicity by its antidote sodium thiosulfate (STS), we studied the effects of STS on plasma concentrations of platinum (Pt) in vivo, binding of Pt to serum protein in vitro, and uptake of Pt by bacterial cells (E. coli, WP 2 uvrA strain) or cultured mouse tumor cells (FM3A) in vitro. STS did not significantly affect either plasma levels of total Pt or non-protein-bound Pt in vivo, but did inhibit binding of Pt to serum protein and cellular uptake of Pt in vitro. These results suggest that when DDP is given in combination with STS in vivo, the binding to macromolecules and entry of DDP into the cells are prevented due to formation of the Pt-thiosulfate complex in the extracellular fluid.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effect of “two-route chemotherapy” (TRC) with intra-arterial (IA) neocarzinostatin (NCS) and IV N-(2-mercaptopropionyl)-glycine (tiopronin), its antidote, on rat limb tumors. Chemotherapy experiments were carried out on day 9 after the inoculation of 106 syngeneic transitional carcinoma cells into the hind limb in female Wistar King A rats. In the group given TRC, 3500 units/kg NCS and 800 mg/kg tiopronin were given via the femoral artery and the femoral vein, respectively. The antitumor effect was evaluated by the tumor weight on day 12 after the treatment. Compared with the weight of tumors in untreated controls, TRC reduced tumor weight to one-tenth, while 700 units/kg IA NCS alone reduced tumor weight to one-third and 700 units/kg systemic NCS alone reduced tumor weight to three-fourths of the control weight. In the group given TRC, WBC and nucleated bone marrow cells were completely protected and loss of body weight was slight.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. 98-100 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Utilizing the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM), the protective effect of sodium thiosulfate (STS) on the antiproliferative action of cis-diamminedichloroplatinum (II) (DDP) against human cells was investigated. DDP alone significantly inhibited the proliferation of PBM over the concentration range of 10-7 to 5x10-5 M. The antiproliferative effect of DDP was significantly blocked when STS was added to the stimulation culture at the time of exposure to DDP at molar STS/DDP ratios of more than 500. However, STS at molar ratios of less than 100 induced minimal protection. Then, STS was added at various times after DDP exposure with a molar STS/DDP ratio of 1000. The protection was effective within 10 min after exposure to DDP at a concentration of 5x10-5 M, whereas it was not effective beyond 30 min after the exposure. The results indicate that effective protection against DDP cytotoxicity in human cells can be achieved by the concurrent presence of STS with molar STS/DDP ratios of more than 500, but not when a molar STS/DDP ratio of less than 100 is used.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1436-2813
    Keywords: intra-hepatic arterial infusion ; DDP ; STS ; metastatic liver tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of combination chemotherapy of an antitumor drugcis-diamminedichloroplatinum (II) (DDP) and its potent antidote, sodium thiosulfate (STS) in rat liver tumor systems. This therapy was given to female WKA rats with metastatic liver tumors 13 days after inoculation of syngeneic hepatoma cells through the mesenteric vein. DDP and STS were administeredvia two different routes, hepatic artery and femoral vein, respectively (we call this treatment “two route infusion chemotherapy”). The antitumor effects were evaluated 21 days after the treatment by calculating the tumor weight from the total weight of the liver. Tumor weights of rats treated with 20 mg/kg of intra-arterial DDP plus 1,054 mg/kg of systemic STS (group A), 5 mg/kg of intra-arterial DDP alone (group B), and 5 mg/kg of systemic DDP alone (group C) were, about one fifth two fifths and three fifths of the tumor weights in the untreated controls, respectively. In group A, no rats died despite administration of a 4-fold higher DDP dose than in the latter two groups B and C in which 14–18 per cent of the rats died, due to DDP-induced toxicity. The patterns of body weight gain in the three groups after the chemotherapy were much the same. Our results clearly indicate that the antitumor effect of DDP on metastatic liver tumors in rats can remarkably be enhanced by the “two route infusion chemotherapy” of DDP and STS.
    Type of Medium: Electronic Resource
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