metallothionein and Neoplasms--Germ-Cell-and-Embryonal

Increased levels of metallothionein (MT) have recently been found in the blood serum of men with newly diagnosed testicular germ cell tumors (TGCT). In light of previously published results, the aim of this study was to investigate the difference in serum MT levels among patients with different stages of TGCT and compare MT with commonly used markers (α-fetoprotein, β-human chorionic gonadotropin and lactate dehydrogenase). The concentration of total MT was determined in the serum of 25 men with TGCT (seminoma or non-seminoma) by differential pulse voltammetry. Serum samples were obtained prior to chemotherapy, after two cycles of chemotherapy and 1 year after chemotherapy. A statistically significant difference in MT levels in patients with different stages of TGCT was observed in the serum of patients with non-seminoma obtained before chemotherapy. Although not significant, an increase in serum MT levels commensurate with the disease stage increase was also observed in patients with seminomatous TGCT. The results indicate that, in combination with the existing markers, MT could be useful for the identification of the histological type of tumor and stage of the disease before biopsy diagnosis.

Topics: Adolescent; Adult; alpha-Fetoproteins; Biomarkers, Tumor; Chorionic Gonadotropin, beta Subunit, Human; Humans; L-Lactate Dehydrogenase; Male; Metallothionein; Middle Aged; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Young Adult

Metallothioneins (MTs) have been disclosed as a useful diagnostic factor for tumour progression and drug resistance in a variety of malignancies. Increased levels of MT in blood serum have been found in patients with several types of cancer, but there is no available information on serum MT levels in patients with testicular germ cell tumour (TGCT). The aim of the study was to determine MT levels in serum of patients with TGCT and to evaluate the portion of platinum (Pt) that binds to MT after cisplatin administration since MTs could be involved in drug resistance.. Concentration of total MT was determined in serum of 25 men with newly diagnosed TGCT by differential pulse voltammetry. The fractionation of serum was carried out by size exclusion high-performance liquid chromatography (SE-HPLC), while concentration of Pt in collected fractions was determined by inductively coupled plasma mass spectrometry.. Concentration of serum MT was significantly higher in TGCT patients than in healthy volunteers. The results of SE-HPLC analysis showed that only a small amount of Pt was bound to proteins in the area of MT elution.. Significant increase in MT levels in individuals with TGCT indicates certain health problem and, in combination with other commonly used diagnostic tools, could improve early diagnosis.

Topics: Adolescent; Adult; Antineoplastic Agents; Chromatography, Gel; Cisplatin; Humans; Male; Metallothionein; Middle Aged; Neoplasms, Germ Cell and Embryonal; Platinum; Protein Binding; Testicular Neoplasms; Young Adult

Data on the involvement of elevated metallothionein (MT) expression in resistance to some of the commonly used anticancer treatments are scattered and conflicting. This encouraged us to examine further the contribution of metallothionein expression to the development of this resistance phenotype.. Formalin-fixed, paraffin-embedded blocks of primary untreated germ cell testicular tumor specimens, obtained from 77 patients following radical orchiectomy, were examined for their MT expression using monoclonal antibody and immunohistochemistry. Clinical staging, the chemotherapeutic schedule and evaluation of response to treatment (defining objective response) were performed according to UICC criteria.. All tumor types, including seminomas and nonseminomas, expressed MT, regardless of their histology and clinical stage. The immunoreactivity of MT showed a significant positive correlation with the clinical sensitivity of cancer to antitumor therapy (P = 0.0001).. In patients with germ cell testicular tumors, high MT expression, as detected by immunohistochemistry, predicts a better response rate to chemotherapy whereas tumors lacking or demonstrating low MT expression show a worse prognosis. These data do not support the hypothesis that MT overexpression contributes to cisplatinum resistance, at least in this tumor type.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunohistochemistry; Male; Metallothionein; Middle Aged; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Treatment Outcome

Expression of intracellular metallothionein (MT) has been linked to cis-diamminedichloroplatinum (cDDP) resistance in human germ cell tumor cell lines. To determine whether exposure to cDDP would select for cells with increased MT expression, the MT content of the human teratocarcinoma cell line T7800 was measured after development of resistance to cDDP by exposure to progressively higher drug concentrations (6.25-25 microM). cDDP-resistant cells (T7800R) had significantly higher MT mRNA and MT protein, increased resistance to killing by cDDP and altered in vitro growth kinetics compared to parental T7800 cells. cDDP resistance in a variety of other human tumor cell lines correlated with MT content, with no significant difference in glutathione level. These data indicate that selection in vitro for cDDP resistance in human germ cell tumors coselects for cells with enhanced MT content. However, selected cells differed in characteristics other than MT content. They had a slower growth rate and, although the rank order of MT level in T7800, T7800R and other human tumor cell lines correlated very well with cDDP resistance, differences in the level of MT expression did not correspond with differences in the absolute level of cDDP resistance. These results suggest that increased MT expression is concomitant with increased cDDP resistance in a variety of human tumor cell lines. However, measured differences in MT levels may not accurately reflect the degree of cDDP resistance differences among those cells.

Topics: Cell Division; Cisplatin; Drug Resistance, Neoplasm; Humans; Metallothionein; Neoplasms, Germ Cell and Embryonal; RNA, Messenger; Tumor Cells, Cultured