The toxicological evaluation of repetitive 2- and 4-week intravenous injection of Activin A/BMP-2 chimera (AB204) into rats

Yoon, Byung Hak; Lee, Jae Hyup; Na, Kyuheum; Cho, Jongho; Choe, Senyon

doi:10.1016/j.yrtph.2015.06.007

Cited by 8 publications

(1 citation statement)

References 26 publications

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“…Lee et al (37) reported that direct intravenous injection of rhBMP2 at a dosage of 0.5 mg/kg did not lead to adverse effect to healthy rats within 2 weeks of observation. Yoon et al (38) evaluated the toxicological effect of repetitive intravenous injection of Activin A/BMP-2 in rats, and no observed adverse effects were found. Those studies suggested that rhBMP2 within blood may not have systemic toxicity to normal rats.…”

Section: Discussionmentioning

confidence: 99%

High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells

Huang

Chen

et al. 2020

Front. Oncol.

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Bone morphogenetic protein 2 (BMP2) signaling had significant roles in diverse pathological processes, such as cancer. Nevertheless, the interaction between BMP2 and carcinoma development remained largely unknown. In particular, the roles that BMP2 play in the development of liver cancer remained controversial, and mechanisms were unclear. BMP2 with strong osteogenic potential had been manufactured into various bone materials. However, cancer risk concerns were raised in recent years. Thus, we focused on analyzing the effects of exogenous BMP2 on the growth of liver cancer and the detailed mechanisms. We found that both intravenous injection of rhBMP2 and in vivo implantation of rhBMP2 materials could lead to the expansion of myeloid-derived suppressor cells (MDSCs) in peripheral blood and subsequently enhanced the infiltration of MDSCs into tumor in vivo. Furthermore, BMP2 signaling-activated MDSCs could secrete IL6 to enhance cell proliferation of liver cancer cells in vitro and facilitate liver cancer growth in vivo. Our study indicated that increased concentration of BMP2 within the peripheral blood could enhance liver cancer growth via the activation of MDSCs. In this study, the roles that BMP2 played in liver cancer growth were further confirmed and the detailed mechanisms about how BMP2 enhanced liver cancer growth were also elucidated.

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Section: Discussionmentioning

confidence: 99%

High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells

Huang

Chen

et al. 2020

Front. Oncol.

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The Cardiovascular Effect of Single Injection and Toxicologic Effects of Repetitive 2-Week Intravenous Administration of Activin A/BMP-2 Chimera in Beagle Dog

2017

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This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R-R interval, QT interval and QTcV interval on the electrocardiography. Also, when administered AB204 at the doses of 0.25 and 0.5 mg/kg/day via repetitive intravenous injection for 2 weeks, it did not cause any significant changes in general symptoms, weight, food intake, ophthalmologic abnormality, urine, hematology, serum biochemistry, organ weight and autopsy values. Therefore, AB204 did not affect cardiovascular functions including blood pressure, pulse rate and ECG, when administered at the dose of ≤0.32 mg/kg via single intravenous injection in male beagle dogs. When it was administered at the dose of 0.5 mg/kg repetitive intravenous injection for 2 weeks, it did not show any toxicity.

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miR-122–5p targets GREM2 to protect against glucocorticoid-induced endothelial damage through the BMP signaling pathway

Huang

Jie

et al. 2022

Molecular and Cellular Endocrinology

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The toxicological evaluation of repetitive 2- and 4-week intravenous injection of Activin A/BMP-2 chimera (AB204) into rats

Cited by 8 publications

References 26 publications

High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells

High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells

The Cardiovascular Effect of Single Injection and Toxicologic Effects of Repetitive 2-Week Intravenous Administration of Activin A/BMP-2 Chimera in Beagle Dog

miR-122–5p targets GREM2 to protect against glucocorticoid-induced endothelial damage through the BMP signaling pathway

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