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  • 1
    Electronic Resource
    Electronic Resource
    Fibronectin turnover in human mesangial cell cultures as affected by Adriamycin (1993)
    Springer
    Cell biology and toxicology 9 (1993), S. 149-163 
    Details
    ISSN: 1573-6822
    Keywords: Adriamycin ; extracellular matrix expansion ; fibronectin turnover ; human mesangial cells ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2+-0.3% of totalprotein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5–5 μg/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 pglml(7.3+-2.3pg/cell vs. controls: 4.4+-1.9pg/cell; n= 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 μg ADR/ml. In accordance, immunofZuorescence staining revealed an expansion ofpericellular FNfibers in cultures exposed to 2 μg ADR/ml. Concomitant with the accumulation of extracelhlar FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium ofADR-treated HMC. These data suggest thatADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset ofproteinuria in ADR-treated rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00757577
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  • 2
    Electronic Resource
    Electronic Resource
    A Randomized Trial Comparing the Nephrotoxicity of Cisplatin/Ifosfamide-Based Combination Chemotherapy with or without Amifostine in Patients with Solid Tumors (2000)
    Springer
    Investigational new drugs 18 (2000), S. 281-289 
    Details
    ISSN: 1573-0646
    Keywords: nephrotoxicity ; cisplatin ; ifosfamide ; protection ; amifostine ; hypomagnesemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This study evaluates the degree of kidney damageduring cisplatin/ifosfamide-based combinationchemotherapy and its possible prevention byamifostine. Thirty-one patients with solid tumorsstratified according to pretreatment were randomizedto receive VIP- or TIP-chemotherapy with or withoutamifostine (910 mg/m2) given as a short infusion priorto cisplatin. Chemotherapy consisted of cisplatin(50 mg/m2), ifosfamide (4 g/m2) and either etoposide(500 mg/m2) (= VIP) or paclitaxel (175 mg/m2) (= TIP)repeated at 3 weekly intervals. For all patients theglomerular filtration rate (GFR) measured bycreatinine-clearance, serum creatinine, electrolytesand differential urinary protein/enzyme excretion weredetermined prior to, during and after each cycle. Atotal of 62 cycles of chemotherapy were evaluable. Inthe amifostine-group GFR was fully maintained afterapplication of two cycles of chemotherapy, whereas inthe control group a 〉 30%-reduction of median GFR(108 to 80 ml/min) was observed (p 〈 0.001). Patientsreceiving amifostine had a lower degree of highmolecular weight proteins excretion indicating lessglomerular damage. In both groups significantincreases of tubular marker profiles peaking at day 3after chemotherapy were observed with a nearlycomplete reversibility of these changes prior to thenext chemotherapy cycle. The number of patients withlow magnesium serum levels during treatment was 17%after amifostine application versus 69% in controlpatients. The results seem to indicate that treatmentwith amifostine can preserve GFR after application oftwo cisplatin/ifosfamide-based chemotherapy cycles.This may be advantageous if repetitive cycles ofchemotherapy or subsequent administration of high dosechemotherapy is planned.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006490226104
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