Metallothionein expression in epithelial ovarian cancer: effect of chemotherapy and prognostic significance

Wrigley, E; Verspaget, H. W.; Jayson, Gordon C; McGown, Alan T.

doi:10.1007/pl00008477

Cited by 14 publications

(15 citation statements)

References 17 publications

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“…We have noted also that in samples obtained after chemotherapy (secondary cytoreductions), MT expression has been significantly higher than in samples originating from the period before chemotherapy (primary laparotomies) [14]. The data on the relationship between MT expression in ovarian cancer and survival of patients treated with platinum-containing drugs are divergent, with some investigators noting the relationship and the other failing to detect it [12][13][14]16].…”

Section: Discussionmentioning

confidence: 93%

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Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome

Surowiak

Materna

Maciejczyk³

et al. 2007

Virchows Arch

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Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug.

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Section: Discussionmentioning

confidence: 93%

“…The relationship between MT expression and resistance to platinum-containing drugs is used to be explained by the potential of MT to bind molecules of the drug [6]. Data on predictive value of immunohistochemical estimation of MT have been divergent [12,13,16].…”

Section: Introductionmentioning

confidence: 99%

Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome

Surowiak

Materna

Maciejczyk³

et al. 2007

Virchows Arch

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“…Almost all methods used for detection of metallothionein in tissues are based on immunohistochemical principles [27,59,61,64]. These procedures require biopsy tissues and labor and time consuming sample handling and can not be used for exact quantification of the protein of interest.…”

Section: Electroanalytical Methods In Metallothionein Analysismentioning

confidence: 99%

Employment of Electrochemical Techniques for Metallothionein Determination in Tumor Cell Lines and Patients with a Tumor Disease

et al. 2008

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In the present paper we employed adsorptive transfer stripping technique coupled with chronopotentiometric stripping analysis for determination of metallothionein (MT) in tumor cell lines and differential pulse voltammetry Brdicka reaction for determination of MT in blood serum of patients with head and neck cancer or retinoblastoma, and of rats treated with cisplatin with respect to discuss the role of MT in formation of resistance on treatment with heavy metal based cytostatics. The cisplatin or carboplatin sensitive and resistant neuroblastoma cell lines were derived from the maternal cell line isolated from the bone metastasis of patients with neuroblastoma. Based on the results obtained it can be concluded that level of MT increases with higher dose of platinum based cytostatics at cells. Further we focused on determination of MT in blood serum of rats treated with cisplatin (two doses 1.05 mg and/or 2.1 mg of cisplatin per kg). The highest level of MT at rats treated with 1.05 mg cisplatin was determined after four hours as 4.9 mmol/L. In the case of the second experimental group the maximum was reached even after two hours of the treatment as 4.8 mmol/L. In addition we were interested in the effect of cisplatin or carboplatin treatment of patients with a tumor disease. At patients with tumor in head and neck area treated with cisplatin we observed that the level of MT was going higher due to administration of the drug. This phenomenon was observed at all patients. However at patients with retinoblastoma treated with carboplatin we observed various phenomena including decreasing, increasing or no changes in MT level. Progression of MT levels was therefore individual and probably depended on tumor resistance to carboplatin.

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“…On the other hand, in vitro studies suggested participation of the proteins in detoxication of the tumor cells from platinum-containing compounds [5,12,32]. Moreover, expression of MT and GST-pi has not been analyzed in ovarian cancer samples originating from first-look laparotomies (FLLs) and second-look laparotomies (SLLs) in the same patients.…”

Section: Introductionmentioning

confidence: 93%

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

et al. 2005

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Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.

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Metallothionein expression in epithelial ovarian cancer: effect of chemotherapy and prognostic significance

Cited by 14 publications

References 17 publications

Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome

Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome

Employment of Electrochemical Techniques for Metallothionein Determination in Tumor Cell Lines and Patients with a Tumor Disease

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

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