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  • 1
    ISSN: 1569-8041
    Keywords: breast cancer ; MDR1 gene ; multidrug resistance ; P-glycoprotein ; rhodamine 123
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The discovery of the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp) has been widely seen as an important milestone in our understanding of the mechanisms underlying the clinical phenomenon of the emergence of resistant cells. MDR1 expression has been shown for numerous solid tumors and for virtually all hematologic malignancies. Nevertheless, results regarding MDR1/P-gp expression in human breast cancer have been controversial and the results of clinical trials on modulation of P-gp activity have not been encouraging. Patients and methods: MDR1/P-gp expression and the function of the P-gp pump were investigated in 61 tumor samples from patients with primary breast cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with two MAbs (UIC2 and MRK 16) and the rhodamine 123 (Rh123) efflux assay. The cellular composition of the tumor cell suspension was analyzed by using specific MAbs against the P-gp expressing lymphocyte subsets CD4, CD8 and CD56, as well as against the HER-2/neu gene product, which was used to identify breast carcinoma cells. Results: UIC2 and MRK16 revealed a staining positivity in 72% and 75% of samples, respectively. A positive MDR1-RT-PCR signal was detected in 62% of the samples. Nevertheless, no correlation between immunohistochemistry and RT-PCR could be established. Furthermore, there was no correlation between HER-2/neu expression and MDR1-RT-PCR or P-gp immunohistochemical assays. A contamination by CD8+ and CD4+ lymphocytes was established in 100% and 84% of tumor cell suspensions, respectively. As assessed by the Rh123 efflux assay CD8+ and the CD4+ lymphocytes exhibited marked P-glycoprotein activity, whereas such activity was not detectable in a single instance for the breast carcinoma cells. In MDR1-RT-PCR positive samples, contamination by CD8 lymphocytes averaged 4.3%, while the contamination of CD8 cells in the MDR1 mRNA-negative samples was only 2.4% (P = 0.007). This signal vanished after elimination of the lymphocyte subpopulations by T-cell rosetting. Conclusions: In primary breast cancer detection of MDR1 gene expression by means of RT-PCR or immunohistochemical assays is not indicative for the MDR phenotype, since there is no evidence of significant activity of the P-gp pump.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2013-04-19
    Description: Background The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. Patients and methods Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18–20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. Results Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. Conclusions Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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