Suppression of Metastatic Melanoma Growth in Lung by Modulated Electro-Hyperthermia Monitored by a Minimally Invasive Heat Stress Testing Approach in Mice
Modulated electro-hyperthermia (mEHT) is a novel complementary therapy in oncology which is based on the higher conductivity and permittivity of cancerous tissues due to their enhanced glycolytic activity and ionic content compared to healthy normal tissues. We aimed to evaluate the potential of mEHT, inducing local hyperthermia, in the treatment of pulmonary metastatic melanoma. Our primary objective was the optimization of mEHT for targeted lung treatment as well as to identify the mechanism of its potential anti-tumor effect in the B16F10 mouse melanoma pulmonary metastases model while investigating the potential treatment-related side effects of mEHT on normal lung tissue. Repeated treatment of tumor-bearing lungs with mEHT induced significant anti-tumor effects as demonstrated by the lower number of tumor nodules and the downregulation of Ki67 expression in treated tumor cells. mEHT treatment provoked significant DNA double-strand breaks indicated by the increased expression of phosphorylated H2AX protein in treated tumors, although treatment-induced elevation of cleaved/activated caspase-3 expression was insignificant, suggesting the minimal role of apoptosis in this process. The mEHT-related significant increase in p21waf1 positive tumor cells suggested that p21waf1-mediated cell cycle arrest plays an important role in the anti-tumor effect of mEHT on melanoma metastases. Significantly increased CD3+, CD8+ T-lymphocytes, and F4/80+CD11b+ macrophage density in the whole lung and tumor of treated animals emphasizes the mobilizing capability of mEHT on immune cells. In conclusion, mEHT can reduce the growth potential of melanoma, thus offering itself as a complementary therapeutic option to chemo- and/or radiotherapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Cancers - 12(2020), 12 vom: 21. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Thomas, Mbuotidem Jeremiah [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
B16F10 melanoma |
|---|
| Anmerkungen: |
Date Revised 01.01.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/cancers12123872 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM319356957 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM319356957 | ||
| 003 | DE-627 | ||
| 005 | 20231225171257.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cancers12123872 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1064.xml |
| 035 | |a (DE-627)NLM319356957 | ||
| 035 | |a (NLM)33371498 | ||
| 035 | |a (PII)E3872 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Thomas, Mbuotidem Jeremiah |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Suppression of Metastatic Melanoma Growth in Lung by Modulated Electro-Hyperthermia Monitored by a Minimally Invasive Heat Stress Testing Approach in Mice |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 01.01.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Modulated electro-hyperthermia (mEHT) is a novel complementary therapy in oncology which is based on the higher conductivity and permittivity of cancerous tissues due to their enhanced glycolytic activity and ionic content compared to healthy normal tissues. We aimed to evaluate the potential of mEHT, inducing local hyperthermia, in the treatment of pulmonary metastatic melanoma. Our primary objective was the optimization of mEHT for targeted lung treatment as well as to identify the mechanism of its potential anti-tumor effect in the B16F10 mouse melanoma pulmonary metastases model while investigating the potential treatment-related side effects of mEHT on normal lung tissue. Repeated treatment of tumor-bearing lungs with mEHT induced significant anti-tumor effects as demonstrated by the lower number of tumor nodules and the downregulation of Ki67 expression in treated tumor cells. mEHT treatment provoked significant DNA double-strand breaks indicated by the increased expression of phosphorylated H2AX protein in treated tumors, although treatment-induced elevation of cleaved/activated caspase-3 expression was insignificant, suggesting the minimal role of apoptosis in this process. The mEHT-related significant increase in p21waf1 positive tumor cells suggested that p21waf1-mediated cell cycle arrest plays an important role in the anti-tumor effect of mEHT on melanoma metastases. Significantly increased CD3+, CD8+ T-lymphocytes, and F4/80+CD11b+ macrophage density in the whole lung and tumor of treated animals emphasizes the mobilizing capability of mEHT on immune cells. In conclusion, mEHT can reduce the growth potential of melanoma, thus offering itself as a complementary therapeutic option to chemo- and/or radiotherapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B16F10 melanoma | |
| 650 | 4 | |a DNA double-strand breaks | |
| 650 | 4 | |a cell cycle arrest | |
| 650 | 4 | |a immune cell mobilization | |
| 650 | 4 | |a modulated electro-hyperthermia | |
| 650 | 4 | |a pulmonary metastases | |
| 700 | 1 | |a Major, Enikő |e verfasserin |4 aut | |
| 700 | 1 | |a Benedek, Anett |e verfasserin |4 aut | |
| 700 | 1 | |a Horváth, Ildikó |e verfasserin |4 aut | |
| 700 | 1 | |a Máthé, Domokos |e verfasserin |4 aut | |
| 700 | 1 | |a Bergmann, Ralf |e verfasserin |4 aut | |
| 700 | 1 | |a Szász, Attila Marcell |e verfasserin |4 aut | |
| 700 | 1 | |a Krenács, Tibor |e verfasserin |4 aut | |
| 700 | 1 | |a Benyó, Zoltán |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancers |d 2009 |g 12(2020), 12 vom: 21. Dez. |w (DE-627)NLM198667213 |x 2072-6694 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2020 |g number:12 |g day:21 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cancers12123872 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2020 |e 12 |b 21 |c 12 | ||