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  • 1
    Electronic Resource
    Electronic Resource
    Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall (2005)
    Oxford, UK : Blackwell Science Ltd
    Histopathology 47 (2005), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on morphological features and KIT (CD117) immunoreactivity. Most patients with advanced GISTs show a major clinical response after treatment with imatinib mesylate. The histopathological features of GISTs in patients on prolonged imatinib treatment have, thus far, not been addressed in detail. In this report, we present three patients with metastatic GISTs, who received more than 1 year of therapy with imatinib, and whose tumours changed their morphological and immunohistochemical characteristics during continued treatment with the drug.Methods and results : All three primary GISTs from these patients were classical spindle-type tumours, showing diffuse, strong CD117, CD34, and focal α-smooth muscle actin expression. During treatment, two clinically progressive and one clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary epithelioid growth pattern, characterized by rounded cells with eosinophilic cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably, two of these tumours also became CD34 immunonegative and in one case the progression was accompanied by desmin expression. KIT mutational analysis revealed the presence of distinct exon 11 mutant isoforms in all cases examined, while the same genotype was sustained in the base line and on-therapy tumour specimens, proving the common origin of analysed specimens.Conclusions : GISTs subject to imatinib treatment can undergo striking (immuno)phenotypic changes, which are not necessarily corroborated by new genotypic modifications. Because these may mimic other tumour types, this feature creates a differential diagnostic challenge, of which the pathologist should be aware.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.2005.02179.x
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  • 2
    Electronic Resource
    Electronic Resource
    Prof. Dr. E. van der Schueren (1998)
    Springer
    Annals of oncology 9 (1998), S. 343-343 
    Details
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008213132408
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  • 3
    Electronic Resource
    Electronic Resource
    Control of anticoagulation in rats (1974)
    Springer
    Cellular and molecular life sciences 30 (1974), S. 953-955 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Résumé La méthode d'analyse à l'aide du réactif Normotest du contrôle en laboratoire de l'anticoagulation par les dérivés des cumarines montre chez les rats une sensibilité propre pour la diminution de l'activité des facteurs de coagulation et aussi pour l'action inhibitrice des PIVKA, lesquels se manifestent dans le sang avec un certain délai. Un traitement de longue durée à moins du 15% en moyenne de l'activité des facteurs de coagulation est déconseillé à cause des très grands risques d'hémorragie.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01938383
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  • 4
    Electronic Resource
    Electronic Resource
    Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: A key to study an angiogenic marker in vivo? (1999)
    Springer
    Annals of oncology 10 (1999), S. 965-971 
    Details
    ISSN: 1569-8041
    Keywords: angiogenesis ; biological monitoring ; platelets ; vascular endothelial growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Serum VEGF levels are elevated in cancer patients and are used as a tumor marker in different malignancies. We have measured VEGF levels in different blood compartments in cancer patients and healthy volunteers in order to assess the most suitable way of processing blood for measuring VEGF as a marker of tumor-angiogenesis. Patients and methods: VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay in serum (VEGFS), EDTA plasma (VEGFEDTA), citrated plasma (VEGFC), CTAD-plasma (VEGFCTAD), platelet poor plasma (VEGFPPP), platelet rich plasma after induction of platelet activation (VEGFPRP). Platelet activation was assessed by measuring PF4 concentrations in different plasma samples. Results: We observed higher VEGFS (P = 0.0027), VEGFEDTA (P = 0.003) and VEGFPPP (P = 0.0007) levels in cancer patients than in volunteers; VEGFPRP concentrations showed no significant difference (P = 0.208). Analysis of the correlation between VEGFplt and VEGFS in cancer patients showed a similar correlation in a comparable VEGFS concentration range as in the volunteers. When comparing VEGFC to VEGFCTAD, we find significantly higher VEGF and PF4 levels in citrated plasma (VEGF: P = 0.00019; PF4: P = 0.00023). Conclusions: It is likely that VEGFS in cancer patients encompass platelet-delivered VEGF and VEGF from other sources, notably from (neo)-angiogenesis in tumoral tissue. The best discrimination between volunteers and cancer patients was observed in PPP. As generating plasma can induce platelet activation, with consequent VEGF release from platelets, we suggest that to assess free circulating VEGF, CTAD plasma should be used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008377921886
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  • 5
    Electronic Resource
    Electronic Resource
    Activated oxazaphosphorines are transported predominantly by erythrocytes (1997)
    Springer
    Annals of oncology 8 (1997), S. 1139-1144 
    Details
    ISSN: 1569-8041
    Keywords: biological transport ; blood specimen collection ; erythrocytes ; ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Oxazaphosphorines are metabolised by a variety of pathways, one of which leads to activation and the formation of alkylating compounds. However, the transport forms conveying activated oxazaphosphorines to the tumour cell have not been fully characterised. There is increasing recognition of the importance of the erythrocyte as a carrier of compounds in the circulation, and we have recently described higher concentrations of 4-hydroxycyclophosphamide within the erythrocyte compartment compared to plasma. We have now determined the concentrations of ifosfamide and seven of its metabolites in the plasma and erythrocytes of patients receiving a six-hour intravenous infusion of ifosfamide. Patients and methods: Red cells from five patients, receiving a total of eight cycles of ifosfamide, were separated from plasma using the MESED instrument, and analysis of red cells and plasma performed using Gas Chromatography-Mass Spectrometry (GC/MS). Results: The concentration of all compounds in the erythrocyte compartment was higher than or equal to those in plasma, and isophosphoramide mustard and carboxyifosfamide showed a particular affinity for the erythrocyte. The red cell fraction can contain as much as 77% of the total blood concentration of isophosphoramide mustard. Conclusions: Erythrocyte associated isophosphoramide mustard is an important transport form of activated ifosfamide. Red cells may have a role in the delivery of activated oxazaphosphorines to tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008261203803
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  • 6
    Electronic Resource
    Electronic Resource
    Effects and systemic uptake of the new mitomycin C analogue KW-2149 in beagle dogs after intravesical administration (1995)
    Springer
    Urological research 23 (1995), S. 157-161 
    Details
    ISSN: 1434-0879
    Keywords: Mitomycins ; Bladder ; Systemic uptake ; Toxicity ; Urothelium ; Dogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to evaluate the local effects of the new mitomycin C analogue KW-2149 after intravesical instillation, together with its penetration into the systemic circulation in healthy beagle dogs. Two reference dogs were treated with two instillations of mitomycin C (30 mg in 30 ml phosphate buffer). Four dogs were given two, three, four and six instillations, respectively, of KW-2149 (60 mg in 30 ml phosphate buffer). KW-2149 concentrations measured in the systemic circulation were very low and were frequently found to be below the limit of determination. The number of instillations had no influence on the KW-2149 concentrations measured in the systemic circulation. Blood analysis showed no systemic toxicity. The histopathological findings in the bladder were comparable in both groups. The number of instillations had no influence on the severity of the lesions found in the bladder wall. On the basis of its in vitro activity KW-2149 can be regarded as a promising agent for intravesical treatment of superficial bladder cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00389567
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of mitoxantrone in humans following single-agent infusion or intra-arterial injection therapy or combined-agent infusion therapy (1986)
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. 27-32 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study describes the pharmacokinetics of mitoxantrone determined by a sensitive and specific HPLC-method. The time-concentration curves of i.v.-treated patients (15 mg/m2 over 30 min) correspond to a three-compartment model with a T1/2α of 12 min, a T1/2β of 93 min, and a slow elimination phase of 36 h. The central compartment volume was 26.22 and the distribution volume, 1381.9. The mean urinary excretion was 4.9% of the total dose. The pharmacokinetic parameters were also defined in five patients who were treated with combination chemotherapy (mitoxantrone 12 mg/m2, methotrexate 30 mg/m2 and vincristine 2 mg). These results were not different from those with the single-drug treatment, except for the volume of the central compartment, which was significantly decreased. The peak levels after hepatic arterial infusion of mitoxantrone were three times lower than those after the identical dose given i.v. to the same patient. Pleural fluid sampling showed a six-fold increase compared with the plasma level (12 ng/ml versus 2 ng/ml). A multiple linear regression analysis of the data revealed correlations between the pharmacokinetic results and some of the baseline parameters. It is possible to predict changes in the kinetic behaviour of mitoxantrone on the basis of these relations but on the other hand toxicity is less predictable from the baseline parameters or from the pharmacokinetic results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253059
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  • 8
    Electronic Resource
    Electronic Resource
    Concluding remarks (1986)
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. S57 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647454
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  • 9
    Electronic Resource
    Electronic Resource
    Cooperative studies of systemic chemotherapy (1983)
    Springer
    Cancer chemotherapy and pharmacology 11 (1983), S. S25 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00256713
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  • 10
    Electronic Resource
    Electronic Resource
    In vitro and in vivo chemosensitizing effect of cyclosporin A on an intrinsic multidrug-resistant rat colon tumour (1993)
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 609-614 
    Details
    ISSN: 1432-1335
    Keywords: Cyclosporin A ; Multidrug resistance ; P glycoprotein ; Chemosensitizing ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colon tumours are intrinsically resistant to chemotherapy and most of them express the multidrug transporter P glycoprotein (Pgp). Whether this Pgp expression determines their resistance to anticancer agents in patients is not known. We report here on the reversibility of intrinsic multidrug resistance in a syngeneic, solid tumour model. CC531 is a rat colon carcinoma that expresses Pgp, as was shown with the monoclonal antibody C-219. In vitro the sensitivity to doxorubicin, daunorubicin and colchicine was enhanced by the addition of the chemosensitizers verapamil and cyclosporin A (CsA), while the sensitivity to cisplatin was not enhanced. In a daunorubicin accumulation assay verapamil and CsA enhanced the daunorbicin content of CC531 cells. In vivo CsA was injected intramuscularly for 3 consecutive days at a dose of 20 mg kg−1 day−1. This resulted in whole-blood CsA levels above 2 μmol/l, while intratumoral CsA levels amounted to 3.6 μmol/kg. In a subrenal capsule assay the maximal tolerable dose of doxorubicin (4 mg/kg) significantly reduced tumour growth. Doxorubicin at 3 mg/kg was not effective, but in combination with CsA this dose was as effective as 4 mg/kg doxorubicin. These experiments show that adequate doses of the chemosensitizing drug CsA can be obtained in vivo, resulting in increased antitumoral activity of doxorubicin in vivo. The in vitro and in vivo data together suggest that the chemosensitization by CsA is mediated by Pgp. This finding may have implications for the application of CsA and CsA-like chemosensitizers in the clinical setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01372724
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