Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma Article Swipe
Martine Wyrich
,
Henning Ohlig
,
Michael Wessolly
,
Elena Mairinger
,
Julia Steinborn
,
Luka Brčić
,
Balázs Hegedűs
,
Thomas Hager
,
Kristina Greimelmaier
,
Jeremias Wohlschlaeger
,
Fabian Mairinger
,
Sabrina Borchert
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21037/tcr-22-2651
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21037/tcr-22-2651
BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth. METHODS: In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction. RESULTS: Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity. CONCLUSIONS: MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.21037/tcr-22-2651
- https://tcr.amegroups.org/article/viewFile/77074/pdf
- OA Status
- diamond
- Cited By
- 3
- References
- 33
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386162956
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386162956Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21037/tcr-22-2651Digital Object Identifier
- Title
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Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesotheliomaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-08-01Full publication date if available
- Authors
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Martine Wyrich, Henning Ohlig, Michael Wessolly, Elena Mairinger, Julia Steinborn, Luka Brčić, Balázs Hegedűs, Thomas Hager, Kristina Greimelmaier, Jeremias Wohlschlaeger, Fabian Mairinger, Sabrina BorchertList of authors in order
- Landing page
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https://doi.org/10.21037/tcr-22-2651Publisher landing page
- PDF URL
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https://tcr.amegroups.org/article/viewFile/77074/pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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diamondOpen access status per OpenAlex
- OA URL
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https://tcr.amegroups.org/article/viewFile/77074/pdfDirect OA link when available
- Concepts
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Metallothionein, Mesothelioma, Zinc, Cancer research, Medicine, Internal medicine, Oncology, Pathology, Chemistry, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
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3Total citation count in OpenAlex
- Citations by year (recent)
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2024: 2, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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33Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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