Monitoring antiangiogenesis of bevacizumab in zebrafish

Zhang, Jing; Gao, Beili; Zhang, Wenchao; Qian, Zhiliang; Xiang, Yi

doi:10.2147/dddt.s166330

Cited by 22 publications

(15 citation statements)

References 37 publications

(41 reference statements)

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“…It starts as early as 30 hpf with the migration of cells from the posterior cardinal vein (PCV), and it is completed by 72 hpf with the formation of a complete SIV basket connected with intercapillary branches. Changes in the formation of this structure represent a typical readout for treatments with pro or anti-angiogenic effects [ 8 , 9 ]. Recently, experimental approaches, such as zebrafish yolk membrane (ZFYM) angiogenesis assay and tumor xenotransplantation (TX) assays [ 10 , 11 ], have been developed to exploit the potential of SIVP for the study of the impact of small molecules and growth factors on developmental vascularization.…”

Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Basnet

Zizioli

Muscò

et al. 2021

IJMS

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In this study, we report the effects of caffeine on angiogenesis in zebrafish embryos both during normal development and after exposure to Fibroblast Growth Factor 2 (FGF2). As markers of angiogenesis, we measured the length and width of intersegmental vessels (ISVs), performed whole-mount in situ hybridization with fli1 and cadh5 vascular markers, and counted the number of interconnecting vessels (ICVs) in sub-intestinal venous plexus (SIVP). In addition, we measured angiogenesis after performing zebrafish yolk membrane (ZFYM) assay with microinjection of fibroblast growth factor 2 (FGF2) and perivitelline tumor xenograft assay with microinjection of tumorigenic FGF2-overexpressing endothelial (FGF2-T-MAE) cells. The results showed that caffeine treatment causes a shortening and thinning of ISVs along with a decreased expression of the vascular marker genes and a decrease in the number of ICVs in the SIVP. Caffeine was also able to block angiogenesis induced by exogenous FGF2 or FGF2-producing cells. Overall, our results are suggestive of the inhibitory effect of caffeine in both direct and indirect angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Basnet

Zizioli

Muscò

et al. 2021

IJMS

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“…According to our knowledge, this is the first study investigating the linker effect on scFv antibodies by using a zebrafish model. Zebrafish SIV development is induced by VEGF, and previous studies showed that human anti-VEGF antibodies can inhibit this process 38 . Due to the transparency of the zebrafish and, the robustness of the embryo and larvae for micromanipulation, zebrafish is an advantageous model for in vivo testing of anti-VEGF antibodies 39 , 40 .…”

Section: Discussionmentioning

confidence: 99%

Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv

Arslan

Karadag

Onal

et al. 2022

Sci Rep

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Single chain antibody fragments (scFvs) are favored in diagnostic and therapeutic fields thanks to their small size and the availability of various engineering approaches. Linker between variable heavy (VH) and light (VL) chains of scFv covalently links these domains and it can affect scFv’s bio-physical/chemical properties and in vivo activity. Thus, scFv linker design is important for a successful scFv construction, and flexible linkers are preferred for a proper pairing of VH–VL. The flexibility of the linker is determined by length and sequence content and glycine-serine (GS) linkers are commonly preferred for scFvs based on their highly flexible profiles. Despite the advantage of this provided flexibility, GS linkers carry repeated sequences which can cause problems for PCR-based engineering approaches and immunogenicity. Here, two different linkers, a repetitive GS linker and an alternative non-repetitive linker with similar flexibility but lower immunogenicity are employed to generate anti-Vascular Endothelial Growth Factor scFvs derived from bevacizumab. Our findings highlight a better in vitro profile of the non-repetitive linker such as a higher monomer ratio, higher thermal stability while there was no significant difference in in vivo efficacy in a zebrafish embryonic angiogenesis model. This is the first study to compare in vivo efficacy of scFvs with different linkers in a zebrafish model.

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“…Several anti-angiogenic agents have been successfully tested in zebrafish [ 48 ]. Zebrafish embryos are permeable to small molecules, which can be dissolved in their culture medium; moreover, it is well known that some aspects of the physiological development of the sub-intestinal vein (SIV) and intersomitic and retinal vessels can simulate tumor-induced angiogenesis and be an important platform to test and quantify the effect of anti-angiogenic compounds [ 49 ]. Moreover, a zebrafish tumor-xenograft is a suitable platform to study neovascularization occurring with cancer progression in live animals.…”

Section: Discussionmentioning

confidence: 99%

Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

Carra

Gaudenzi

Dicitore

et al. 2021

IJMS

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Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.

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Monitoring antiangiogenesis of bevacizumab in zebrafish

Cited by 22 publications

References 37 publications

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Caffeine Inhibits Direct and Indirect Angiogenesis in Zebrafish Embryos

Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv

Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

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