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  • 1
    ISSN: 1432-0843
    Keywords: Key words Mitoxantrone ; Intratumoral injections ; Experimental liver tumors ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The intratumoral (i.t.) delivery of anticancer drugs aims at controlling tumor growth and thereby provides palliative treatment for liver neoplasms. Mitoxantrone is a good candidate for local or regional administration because (1) its metabolism is mainly hepatic, (2) it has a steep dose-response curve for multiple solid tumors, and (3) its fixation in tissues is sustained without vesicant effects after extravasation. We compared the tolerance, pharmacokinetics, and antitumor effects of mitoxantrone on hepatic VX2 tumors in rabbits treated with i.t. intraarterial hepatic (i.a.h.) or i.v. mitoxantrone, i.t. ethanol; or i.t. 0.9% NaCl and in control animals. Tumor growth rates (TGRs) were evaluated at 9 days after treatment. Myelosuppression was the limiting toxicity of i.v. mitoxantrone at 1.5 mg/kg (maximal tolerated dose, MTD), but neither i.t. nor i.a.h. administration led to hematologic toxicity at the same dose. The mitoxantrone retained in tumors after i.t. administration was seen as blue-stained areas of complete necrosis according to histologic analysis. Pharmacokinetic parameters showed a significantly decreased systemic exposure to the drug after both regional treatments, although the i.a.h. route appeared to have an edge over the i.t. route. TGRs were significantly reduced after i.t. mitoxantrone (81±62%), i.a.h. mitoxantrone (337±110%), and i.t. ethanol treatments (287±117%) as compared with control values (886±223%; p〈0.01). Treatment with i.v. mitoxantrone (816±132%) had no antitumor effect, nor did NaCl injections (868±116%). Mitoxantrone given i.t. induced the highest antitumor effects, resulting in a 3.5-fold reduction in TGRs as compared with i.a.h. mitoxantrone and i.t. ethanol treatments (p〈0.02). Treatment with i.t. mitoxantrone provided efficient antitumor therapy without producing major side effects. This method should be considered as palliative treatment for nonresectable liver tumors and other localized malignancies.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0942-0940
    Keywords: Infant ; brain tumours ; irradiation ; sequelae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between 1975 and 1989, 98 children with brain tumours under the age of three at time of diagnosis were entered into a retrospective study. Twenty of them are alive and free of tumour more than five years after treatment and were evaluated in this study. Thirteen tumour localizations were infratentorial and 7 were supratentorial. A histological examination was performed in 15 patients: 5 ependymomas, 6 medulloblastomas and 4 astrocytomas were identified. Fifteen patients underwent surgical removal of tumour, all but one received radiotherapy and 8 were given chemotherapy. Only two children have not late effects. Analysis of long-term sequelae in survivors showed central endocrinopathies in 14 (70%), a neurological handicap in 13 (65%) and impaired cognitive functions in 17 (85%). Irradiation was clearly responsible for mental sequelae in 7 patients and endocrinopathies in 6 patients. The other possible causes are tumour injury, hydrocephalus or surgery. The risks incurred with radiotherapy and advances in infant brain tumour therapy are discussed.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0749-503X
    Keywords: Saccharomyces cerevisiae ; chromosome IV ; POL3 (CDC2) ; KIN28 ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The nucleotide sequence of a 5 kb EcoRI-NcoI fragment of chromosome IV, contiguous to gene POL3 (CDC2), has been determined. It contains three open reading frames: QRI1, QRI2 and QRI7. Two of them are essential genes. QRI7 is homologous to the Escherichia coli orfx gene. Accession number to EMBL/Genbank Data Library is X79380.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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