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  • 1
    ISSN: 1432-1335
    Keywords: Colon cancer ; Multidrug resistance ; Flow cytometry ; P-glycoprotein ; DNA ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In many cell systems, resistance to cytotoxic drugs is acquired by the amplification and/or overexpression of the multidrug resistance (mdr) gene, which codes for the glycoprotein, p170 (P-glycoprotein). Moreover, in a variety of malignant tumours there is increasing evidence of the relationship between the DNA ploidy pattern of patients and their prognosis. In this study we aimed to evaluate these two potential indicators of constitutive drug resistance in human colorectal tumours. We employed a method to quantify simultaneously, on a per cell basis,mdr gene expression (using the C219 monoclonal antibody for P-glycoprotein) and nuclear DNA content with high-resolution bivariate flow cytometry. The study was performed on a human coloncarcinoma-derived cell line (LoVo) and its doxorubicinresistant variant (LoVo/Dx) and on tumour samples and adjacent normal mucosa from 35 untreated patients with colon cancer. The P-glycoprotein was found in both LoVo and LoVo/Dx cells with levels slightly lower in the parental than in the resistant subline (P, NS). A multidrug-resistant specific probe for mRNA expression and Western blot assay confirmed the specificity of p170 expression. All of the colon cancer with unimodal diploid DNA distribution and all the normal colonic mucosa samples showed P-glycoprotein expression, without a statistically significant difference in median values between tumours and normal samples. Tumours with bimodal DNA distribution showed median values of P-glycoprotein expression of their hyperdiploid cell clones significantly higher than those of their diploid clones and of the tumours with unimodal DNA distribution (P〈0.005). Our results show the feasibility of bivariate flow-cytometric analysis of P-glycoprotein expression and DNA content on clinical material and support the hypothesis that the MDR phenotype and DNA ploidy together may influence the biological behaviour of colon cancer in vivo.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Folinic acid ; 5-Fluorouracil ; Cisplatin ; Head/neck cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A group of 60 patients with advanced head/neck cancer were treated with high-dose folinic acid (500 mg/m−2/week−1) plus 5-fluorouracil (400 mg/m−2/week−1 on day 1, and cisplatin (20 mg/m−2/week−1) 24 h after folinic acid infusion was completed. Out of 55 evaluable patients, 10 patients (18%) experienced a complete response with a mean duration of 11.4+ months, 25 patients had a partial response (45%) of 6.7+ months, 6 patients (11%) showed a stabilization of 4.8+months, and 14 (25%) progressed. The overall response rate was 63.6% (95% confidence limits 56.5%–69.5%). Patients pretreated with radiotherapy had a 67% overall response rate, while those pretreated with chemotherapy showed a 54% overall response rate. All patients with cancer of the oropharynx had a major response, while patients with cancer of the oral cavity had the lowest response rate. The mean survival of patients who attained a complete response was 14.5+ months. Partial responders had a mean survival of 10.6+ months, while patients who progresses survived a mean of 3.6+months. The treatment has been very well tolerated with few cases of grade 3 gastrointestinal toxicity. Grade 1–2 leukopenia was recorded in 64% of cases, grade 1–2 nausea/vomiting in 85%. In one case therapy was stopped because of persistent diarrhoea.
    Type of Medium: Electronic Resource
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