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Title: Development of a new recombinant fusion protein with pro-apoptotic and anti-angiogenic properties for targeted anti-cancer therapy
Abstract:
For almost three decades tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been under intense scientific evaluation because of its remarkable ability to induce apoptosis in cancer cells while omitting normal cells. However, its effectiveness was insufficient to become a single therapy agent. Targeting tumor angiogenesis may be a valuable addition to the TRAIL/DR-based anti-tumor strategy. Vascular endothelial growth factor (VEGF) is essential for vascular development and neovascularization both in physiological and pathological processes. Blockade of VEGF pathway has been shown to inhibit pathological angiogenesis and tumor growth. A proposed new fusion protein consists of a recombinant TRAIL variant that is linked to a duplicated sequence of effector peptides linked by flexible linkers. The effector peptide is derived from the VEGF ligand and is able to bind to VEGF receptors but lack angiogenic effect. The VCTR4.0 fusion variant shows specific in vitro cytotoxic activity against various tumor cell lines with an IC50 level of less than 1 nM. Additionally, its a very strong inducer of apoptosis in the TRAIL-resistant line, and its direct anti-angiogenic activity was confirmed in the HUVEC nodular test. The strong anti-tumor activity of the new fusion molecule was also confirmed in the MES-SA / Dx5 drug-resistant human uterine sarcoma xenograft model. A simi ; lar effect was observed in the Colo205 human colorectal adenocarcinoma, the MIA PaCa-2 human pancreatic carcinoma,and the HepG2 human liver cancer model. All these results show that a very promising molecule with a high potential for anti-cancer activity has been developed.
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Rada Dyscypliny Nauki farmaceutyczne
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Last modified:
Apr 8, 2024
In our library since:
Mar 31, 2022
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7
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0
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http://dl.cm-uj.krakow.pl:8080/publication/4590
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| Edition name | Date |
|---|---|
| ZB-134097 | Apr 8, 2024 |
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