Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 4/2015

01.04.2015 | Original Article

Serum metallothionein in patients with testicular cancer

verfasst von: Blanka Tariba, Tanja Živković, Nesrete Krasnići, Vlatka Filipović Marijić, Marijana Erk, Marija Gamulin, Mislav Grgić, Alica Pizent

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
Literatur
2.
Zurück zum Zitat Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Møller H (2006) Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 118:3099–3111. doi:10.1002/ijc.21747 CrossRefPubMed Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Møller H (2006) Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 118:3099–3111. doi:10.​1002/​ijc.​21747 CrossRefPubMed
5.
Zurück zum Zitat Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2013) SEER cancer statistics review, 1975–2011. National Cancer Institute, Bethesda. http://seer.cancer.gov/csr/1975_2011/. Accessed 1 Dec 2014 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2013) SEER cancer statistics review, 1975–2011. National Cancer Institute, Bethesda. http://​seer.​cancer.​gov/​csr/​1975_​2011/​. Accessed 1 Dec 2014
6.
Zurück zum Zitat García-Velasco A, Durán I, García E, Tarón M, Ballestín C, Castellanos D, Cortés-Funés H, Paz-Ares L (2012) Biological markers of cisplatin resistance in advanced testicular germ cell tumours. Clin Transl Oncol 14:452–457. doi:10.1007/s12094-012-0823-1 CrossRefPubMed García-Velasco A, Durán I, García E, Tarón M, Ballestín C, Castellanos D, Cortés-Funés H, Paz-Ares L (2012) Biological markers of cisplatin resistance in advanced testicular germ cell tumours. Clin Transl Oncol 14:452–457. doi:10.​1007/​s12094-012-0823-1 CrossRefPubMed
7.
Zurück zum Zitat American Joint Committee on Cancer (AJCC) (2010) Cancer staging manual, 7th edn. Springer Science and Business Media LLC (SBM), BerlinCrossRef American Joint Committee on Cancer (AJCC) (2010) Cancer staging manual, 7th edn. Springer Science and Business Media LLC (SBM), BerlinCrossRef
9.
Zurück zum Zitat Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101:513–523. doi:10.1111/j.1572-0241.2006.00467.x CrossRefPubMed Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101:513–523. doi:10.​1111/​j.​1572-0241.​2006.​00467.​x CrossRefPubMed
10.
Zurück zum Zitat Kim HS, Lee HE, Yang H-K, Kim WH (2014) High lactate dehydrogenase 5 expression correlates with high tumoral and stromal vascular endothelial growth factor expression in gastric cancer. Pathobiology 81:78–85. doi:10.1159/000357017 CrossRefPubMed Kim HS, Lee HE, Yang H-K, Kim WH (2014) High lactate dehydrogenase 5 expression correlates with high tumoral and stromal vascular endothelial growth factor expression in gastric cancer. Pathobiology 81:78–85. doi:10.​1159/​000357017 CrossRefPubMed
13.
Zurück zum Zitat Schmitz KJ, Müller CI, Reis H et al (2009) Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma. Int J Colorectal Dis 24:1287–1296. doi:10.1007/s00384-009-0753-8 CrossRefPubMed Schmitz KJ, Müller CI, Reis H et al (2009) Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma. Int J Colorectal Dis 24:1287–1296. doi:10.​1007/​s00384-009-0753-8 CrossRefPubMed
14.
Zurück zum Zitat Pontes HAR, de Aquino Xavier FC, da Silva TSP, Fonseca FP, Paiva HB, Pontes FSC, Jr Dos Santos Pinto D (2009) Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study. J Oral Pathol Med 38:644–650. doi:10.1111/j.1600-0714.2009.00787.x CrossRefPubMed Pontes HAR, de Aquino Xavier FC, da Silva TSP, Fonseca FP, Paiva HB, Pontes FSC, Jr Dos Santos Pinto D (2009) Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study. J Oral Pathol Med 38:644–650. doi:10.​1111/​j.​1600-0714.​2009.​00787.​x CrossRefPubMed
15.
Zurück zum Zitat Fabrik I, Krizkova S, Huska D, Adam V, Hubalek J, Trnkova L, Eckschlager T, Kukacka J, Prusa R, Kizek R (2008) Employment of electrochemical techniques for metallothionein determination in tumor cell lines and patients with a tumor disease. Electroanalysis 20:1521–1532. doi:10.1002/elan.200704215 CrossRef Fabrik I, Krizkova S, Huska D, Adam V, Hubalek J, Trnkova L, Eckschlager T, Kukacka J, Prusa R, Kizek R (2008) Employment of electrochemical techniques for metallothionein determination in tumor cell lines and patients with a tumor disease. Electroanalysis 20:1521–1532. doi:10.​1002/​elan.​200704215 CrossRef
16.
Zurück zum Zitat Krejcova L, Fabrik I, Hynek D, Krizkova S, Gumulec J, Ryvolova M, Adam V, Babula P, Trnkova L, Stiborova M, Hubalek J, Masarik M, Binkova H, Eckschlager T, Kizek R (2012) Metallothionein electrochemically determined using Brdicka reaction as a promising blood marker of head and neck malignant tumours. Int J Electrochem Sci 7:1767–1784 Krejcova L, Fabrik I, Hynek D, Krizkova S, Gumulec J, Ryvolova M, Adam V, Babula P, Trnkova L, Stiborova M, Hubalek J, Masarik M, Binkova H, Eckschlager T, Kizek R (2012) Metallothionein electrochemically determined using Brdicka reaction as a promising blood marker of head and neck malignant tumours. Int J Electrochem Sci 7:1767–1784
17.
Zurück zum Zitat Krizkova S, Ryvolova M, Gumulec J, Masarik M, Adam V, Majzlik P, Hubalek J, Provaznik I, Kizek R (2011) Electrophoretic fingerprint metallothionein analysis as a potential prostate cancer biomarker. Electrophoresis 32:1952–1961. doi:10.1002/elps.201000519 CrossRefPubMed Krizkova S, Ryvolova M, Gumulec J, Masarik M, Adam V, Majzlik P, Hubalek J, Provaznik I, Kizek R (2011) Electrophoretic fingerprint metallothionein analysis as a potential prostate cancer biomarker. Electrophoresis 32:1952–1961. doi:10.​1002/​elps.​201000519 CrossRefPubMed
18.
Zurück zum Zitat Krizkova S, Masarik M, Majzlik P, Kukacka J, Kruseova J, Adam V, Prusa R, Eckschlager T, Stiborova M, Kizek R (2010) Serum metallothionein in newly diagnosed patients with childhood solid tumours. Acta Biochim Pol 57:561–566PubMed Krizkova S, Masarik M, Majzlik P, Kukacka J, Kruseova J, Adam V, Prusa R, Eckschlager T, Stiborova M, Kizek R (2010) Serum metallothionein in newly diagnosed patients with childhood solid tumours. Acta Biochim Pol 57:561–566PubMed
20.
Zurück zum Zitat Thirumoorthy N, Manisenthil Kumar KT, Shyam Sundar A, Panayappan L, Chatterjee M (2007) Metallothionein: an overview. World J Gastroenterol 13:993–996CrossRefPubMedCentralPubMed Thirumoorthy N, Manisenthil Kumar KT, Shyam Sundar A, Panayappan L, Chatterjee M (2007) Metallothionein: an overview. World J Gastroenterol 13:993–996CrossRefPubMedCentralPubMed
22.
Zurück zum Zitat Raspor B (2001) Elucidation of the mechanism of the Brdicka reaction. J Electroanal Chem 503:159–162CrossRef Raspor B (2001) Elucidation of the mechanism of the Brdicka reaction. J Electroanal Chem 503:159–162CrossRef
23.
Zurück zum Zitat Martinčič A, Cemazar M, Sersa G, Kovač V, Milačič R, Ščančar J (2013) A novel method for speciation of Pt in human serum incubated with cisplatin, oxaliplatin and carboplatin by conjoint liquid chromatography on monolithic disks with UV and ICP-MS detection. Talanta 116:141–148. doi:10.1016/j.talanta.2013.05.016 CrossRefPubMed Martinčič A, Cemazar M, Sersa G, Kovač V, Milačič R, Ščančar J (2013) A novel method for speciation of Pt in human serum incubated with cisplatin, oxaliplatin and carboplatin by conjoint liquid chromatography on monolithic disks with UV and ICP-MS detection. Talanta 116:141–148. doi:10.​1016/​j.​talanta.​2013.​05.​016 CrossRefPubMed
25.
Zurück zum Zitat Peleg-Shulman T, Najajreh Y, Gibson D (2002) Interactions of cisplatin and transplatin with proteins. Comparison of binding kinetics, binding sites and reactivity of the Pt-protein adducts of cisplatin and transplatin towards biological nucleophiles. J Inorg Biochem 91:306–311CrossRefPubMed Peleg-Shulman T, Najajreh Y, Gibson D (2002) Interactions of cisplatin and transplatin with proteins. Comparison of binding kinetics, binding sites and reactivity of the Pt-protein adducts of cisplatin and transplatin towards biological nucleophiles. J Inorg Biochem 91:306–311CrossRefPubMed
26.
Zurück zum Zitat Hsu M, Wang W, Li L (2014) Lower level of serum metallothionein I/II in patients with atopic dermatitis. Austin J Dermatol 1:2–3 Hsu M, Wang W, Li L (2014) Lower level of serum metallothionein I/II in patients with atopic dermatitis. Austin J Dermatol 1:2–3
27.
28.
Zurück zum Zitat Krizkova S, Fabrik I, Adam V, Kukacka J, Prusa R, Chavis GJ, Trnkova L, Strnadel J, Horak V, Kizek R (2008) Utilizing of adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum and tissues. Sensors 8:3106–3122. doi:10.3390/s8053106 CrossRefPubMedCentral Krizkova S, Fabrik I, Adam V, Kukacka J, Prusa R, Chavis GJ, Trnkova L, Strnadel J, Horak V, Kizek R (2008) Utilizing of adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum and tissues. Sensors 8:3106–3122. doi:10.​3390/​s8053106 CrossRefPubMedCentral
30.
Zurück zum Zitat Kontozoglou TE, Banerjee D, Cherian MG (1989) Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch A Pathol Anat Histopathol 415:545–549CrossRefPubMed Kontozoglou TE, Banerjee D, Cherian MG (1989) Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch A Pathol Anat Histopathol 415:545–549CrossRefPubMed
31.
Zurück zum Zitat Eid H, Géczi L, Bodrogi I, Institoris E, Bak M (1998) Do metallothioneins affect the response to treatment in testis cancers? J Cancer Res Clin Oncol 124:31–36CrossRefPubMed Eid H, Géczi L, Bodrogi I, Institoris E, Bak M (1998) Do metallothioneins affect the response to treatment in testis cancers? J Cancer Res Clin Oncol 124:31–36CrossRefPubMed
32.
Zurück zum Zitat Chin JL, Banerjee D, Kadhim SA, Kontozoglou TE, Chauvin PJ, Cherian MG (1993) Metallothionein in testicular germ cell tumors and drug resistance. Clin Correl Cancer 72:3029–3035 Chin JL, Banerjee D, Kadhim SA, Kontozoglou TE, Chauvin PJ, Cherian MG (1993) Metallothionein in testicular germ cell tumors and drug resistance. Clin Correl Cancer 72:3029–3035
33.
Zurück zum Zitat Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer D, Mulder NH (2000) Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer 85:777–781CrossRefPubMed Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer D, Mulder NH (2000) Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer 85:777–781CrossRefPubMed
35.
Zurück zum Zitat Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Pérez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7:3–18CrossRefPubMed Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Pérez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7:3–18CrossRefPubMed
36.
Zurück zum Zitat Desoize B, Madoulet C (2002) Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol 42:317–325CrossRefPubMed Desoize B, Madoulet C (2002) Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol 42:317–325CrossRefPubMed
37.
Zurück zum Zitat DeConti RC, Toftness BR, Lange RC, Creasey WA (1973) Clinical and pharmacological studies with cis-diamminedichloroplatinum(II). Cancer Res 33:1310–1315PubMed DeConti RC, Toftness BR, Lange RC, Creasey WA (1973) Clinical and pharmacological studies with cis-diamminedichloroplatinum(II). Cancer Res 33:1310–1315PubMed
39.
Zurück zum Zitat Hagrman D, Goodisman J, Dabrowiak JC, Souid AK (2003) Kinetic study on the reaction of cisplatin with metallothionein. Drug Metab Dispos 31:916–923CrossRefPubMed Hagrman D, Goodisman J, Dabrowiak JC, Souid AK (2003) Kinetic study on the reaction of cisplatin with metallothionein. Drug Metab Dispos 31:916–923CrossRefPubMed
40.
Zurück zum Zitat Huska D, Fabrik I, Baloun J, Adam V, Masarik M, Hubalek J, Vasku A, Trnkova L, Horna A, Zeman L, Kizek R (2009) Study of interactions between metallothionein and cisplatin by using differential pulse voltammetry Brdicka reaction and quartz crystal microbalance. Sensors 9:1355–1369. doi:10.3390/s90301355 CrossRefPubMedCentralPubMed Huska D, Fabrik I, Baloun J, Adam V, Masarik M, Hubalek J, Vasku A, Trnkova L, Horna A, Zeman L, Kizek R (2009) Study of interactions between metallothionein and cisplatin by using differential pulse voltammetry Brdicka reaction and quartz crystal microbalance. Sensors 9:1355–1369. doi:10.​3390/​s90301355 CrossRefPubMedCentralPubMed
41.
Zurück zum Zitat Ossipov K, Scaffidi-Domianello YY, Seregina IF, Galanski M, Keppler BK, Timerbaev AR, Bolshov MA (2014) Inductively coupled plasma mass spectrometry for metallodrug development: albumin binding and serum distribution of cytotoxic cis- and trans-isomeric platinum(II) complexes. J Inorg Biochem 137:40–45. doi:10.1016/j.jinorgbio.2014.04.008 CrossRefPubMed Ossipov K, Scaffidi-Domianello YY, Seregina IF, Galanski M, Keppler BK, Timerbaev AR, Bolshov MA (2014) Inductively coupled plasma mass spectrometry for metallodrug development: albumin binding and serum distribution of cytotoxic cis- and trans-isomeric platinum(II) complexes. J Inorg Biochem 137:40–45. doi:10.​1016/​j.​jinorgbio.​2014.​04.​008 CrossRefPubMed
Metadaten
Titel
Serum metallothionein in patients with testicular cancer
verfasst von
Blanka Tariba
Tanja Živković
Nesrete Krasnići
Vlatka Filipović Marijić
Marijana Erk
Marija Gamulin
Mislav Grgić
Alica Pizent
Publikationsdatum
01.04.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 4/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2702-2

Weitere Artikel der Ausgabe 4/2015

Cancer Chemotherapy and Pharmacology 4/2015 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.