| dc.contributor.advisor | Conradi, Lena-Christin PD Dr. | |
| dc.contributor.author | Fan, Shuang | |
| dc.date.accessioned | 2024-09-16T09:36:18Z | |
| dc.date.available | 2024-10-09T00:50:10Z | |
| dc.date.issued | 2024-09-16 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/15488 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-10703 | |
| dc.format.extent | V, 81 | de |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Tumor vessel normalization through inhibition of glycolysis in colorectal carcinoma | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Conradi, Lena-Christin PD Dr. | |
| dc.date.examination | 2024-09-11 | de |
| dc.description.abstracteng | The current treatment approach for CRC involves a combination of surgery and neoadjuvant
chemo- and RT. However, drug resistance and recurrence remain significant challenges,
emphasizing the need for new and more effective treatments. Recent research has suggested
that inhibiting the glycolytic activator PFKFB3 to promote TVN may improve tumor
hypoxia and enhance tumor response to therapy. In this research, we performed in vivo and
in vitro assays with PDOs, PDXs and CRC cells to evaluate the impact of 3PO, a PFKFB3
inhibitor on cell survival, clonogenicity, migration, invasion and metabolism. Our findings
demonstrate that 3PO enhances radiation-induced CRC cell death, diminishes the metastatic
and invasive abilities, and alters the transcriptional metabolism of PDOs, promoting a
metabolic shift towards oxidative phosphorylation. Importantly, our results show that 3PO
can induce TVN in RC, reducing the tumors’ hypoxic environment and enhancing its
sensitivity to RT. Collectively, these outcomes point to the conclusion that inhibiting
PFKFB3 to facilitate TVN for improve tumor hypoxia, which could represent a compelling
new direction for the treatment of CRC. This research might improve to the exploitation of
new therapeutic approaches for CRC patients, potentially improving their outcomes. | de |
| dc.contributor.coReferee | Kube, Dieter Prof. Dr. | |
| dc.contributor.thirdReferee | Schön, Margarete Prof. Dr. | |
| dc.subject.eng | Colorectal Cancer | de |
| dc.subject.eng | PFKFB3 Inhibition | de |
| dc.subject.eng | Tumor Vessel Normalization | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-15488-2 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Abdominalchirurgie (PPN619875976) | de |
| dc.description.embargoed | 2024-10-09 | de |
| dc.identifier.ppn | 1902788745 | |
| dc.creator.birthname | Shuang Fan | de |
| dc.identifier.orcid | 0000-0002-7720-4912 | de |
| dc.notes.confirmationsent | Confirmation sent 2024-09-16T09:45:01 | de |