Oxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP) : local study in murine tumors

2023
journal article
article
dc.abstract.enHypoxia, an inevitable feature of locally advanced solid tumors, has been known as an adverse prognostic factor, a driver of an aggressive phenotype, and an unfavorable factor in therapies. Myo-inositol trispyrophosphate (ITPP) is a hemoglobin modifier known to both increase $O_{2}$ release and normalize microvasculature. Our goal was to measure the tumor oxygen partial pressure dynamic changes and timing of the therapeutic window after ITPP systemic administration. Two syngeneic tumor models in mice, B16 melanoma and 4T1 breast carcinoma, were used, with varying ITPP dose schedules. Tissue oxygenation level was measured over several days in situ in live animals by Electron Paramagnetic Resonance oximetry with implanted OxyChip used as a constant sensor of the local $pO_{2}$ value. Both B16 and 4T1 tumors became more normoxic after ITPP treatment, with $pO_{2}$ levels elevated by 10-20 mm Hg compared to the control. The increase in $pO_{2}$ was either transient or sustained, and the underlying mechanism relied on shifting hypoxic tumor areas to normoxia. The effect depended on ITPP delivery intervals regarding the tumor type and growth rate. Moreover, hypoxic tumors before treatment responded better than normoxic ones. In conclusion, the ITPP-generated oxygen therapeutic window may be valuable for anti-tumor therapies requiring oxygen, such as radio-, photo- or immunotherapy. Furthermore, such a combinatory treatment can be especially beneficial for hypoxic tumors.pl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Biofizyki i Biologii Nowotworówpl
dc.affiliationSzkoła Doktorska Nauk Ścisłych i Przyrodniczychpl
dc.contributor.authorKrzykawska-Serda, Martyna - 104137 pl
dc.contributor.authorSzczygieł, Dariusz - 255556 pl
dc.contributor.authorGaweł, Szymon - 217720 pl
dc.contributor.authorDrzał, Agnieszka - 178679 pl
dc.contributor.authorSzczygieł, Małgorzata - 200073 pl
dc.contributor.authorKmieć, Maciej M.pl
dc.contributor.authorMackiewicz, Andrzejpl
dc.contributor.authorKieda, Claudinepl
dc.contributor.authorElas, Martyna - 127873 pl
dc.date.accession2023-05-16pl
dc.date.accessioned2023-05-16T12:15:44Z
dc.date.available2023-05-16T12:15:44Z
dc.date.issued2023pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number5pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume18pl
dc.identifier.articleide0285318pl
dc.identifier.doi10.1371/journal.pone.0285318pl
dc.identifier.eissn1932-6203pl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/311382
dc.identifier.weblinkhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285318pl
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeotwarte czasopismo
dc.subtypeArticlepl
dc.titleOxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP) : local $pO_{2}$ study in murine tumorspl
dc.title.journalPLoS ONEpl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Hypoxia, an inevitable feature of locally advanced solid tumors, has been known as an adverse prognostic factor, a driver of an aggressive phenotype, and an unfavorable factor in therapies. Myo-inositol trispyrophosphate (ITPP) is a hemoglobin modifier known to both increase $O_{2}$ release and normalize microvasculature. Our goal was to measure the tumor oxygen partial pressure dynamic changes and timing of the therapeutic window after ITPP systemic administration. Two syngeneic tumor models in mice, B16 melanoma and 4T1 breast carcinoma, were used, with varying ITPP dose schedules. Tissue oxygenation level was measured over several days in situ in live animals by Electron Paramagnetic Resonance oximetry with implanted OxyChip used as a constant sensor of the local $pO_{2}$ value. Both B16 and 4T1 tumors became more normoxic after ITPP treatment, with $pO_{2}$ levels elevated by 10-20 mm Hg compared to the control. The increase in $pO_{2}$ was either transient or sustained, and the underlying mechanism relied on shifting hypoxic tumor areas to normoxia. The effect depended on ITPP delivery intervals regarding the tumor type and growth rate. Moreover, hypoxic tumors before treatment responded better than normoxic ones. In conclusion, the ITPP-generated oxygen therapeutic window may be valuable for anti-tumor therapies requiring oxygen, such as radio-, photo- or immunotherapy. Furthermore, such a combinatory treatment can be especially beneficial for hypoxic tumors.
dc.affiliationpl
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biofizyki i Biologii Nowotworów
dc.affiliationpl
Szkoła Doktorska Nauk Ścisłych i Przyrodniczych
dc.contributor.authorpl
Krzykawska-Serda, Martyna - 104137
dc.contributor.authorpl
Szczygieł, Dariusz - 255556
dc.contributor.authorpl
Gaweł, Szymon - 217720
dc.contributor.authorpl
Drzał, Agnieszka - 178679
dc.contributor.authorpl
Szczygieł, Małgorzata - 200073
dc.contributor.authorpl
Kmieć, Maciej M.
dc.contributor.authorpl
Mackiewicz, Andrzej
dc.contributor.authorpl
Kieda, Claudine
dc.contributor.authorpl
Elas, Martyna - 127873
dc.date.accessionpl
2023-05-16
dc.date.accessioned
2023-05-16T12:15:44Z
dc.date.available
2023-05-16T12:15:44Z
dc.date.issuedpl
2023
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
5
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
18
dc.identifier.articleidpl
e0285318
dc.identifier.doipl
10.1371/journal.pone.0285318
dc.identifier.eissnpl
1932-6203
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/311382
dc.identifier.weblinkpl
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285318
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subtypepl
Article
dc.titlepl
Oxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP) : local $pO_{2}$ study in murine tumors
dc.title.journalpl
PLoS ONE
dc.typepl
JournalArticle
dspace.entity.type
Publication

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