Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug. However, it causes cardiotoxicity and also a few negative effects on skeletal muscle as well. As a result, cancer treatment might actually worsen cancer-induced cachexia and consequently the prognosis of the disease. Inhibiting myostatin/activin signaling is known to increase muscle size. This pathway blockade by soluble activin receptor IIB (sAcvR2B-Fc) has also prolonged survival in cancer, even of animals in which tumor growth is not inhibited. It is not known, however, whether blocking this pathway affects chemotherapy-induced muscle wasting. We found that doxorubicin induces muscle atrophy which is prevented by a blocker for activin receptor 2B ligands (sAcvR2B-Fc).
Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug. However, it causes cardiotoxicity and also a few negative effects on skeletal muscle as well. As a result, cancer treatment might actually worsen cancer-induced cachexia and consequently the prognosis of the disease. Inhibiting myostatin/activin signaling is known to increase muscle size. This pathway blockade by soluble activin receptor IIB (sAcvR2B-Fc) has also prolonged survival in cancer, even of animals in which tumor growth is not inhibited. It is not known, however, whether blocking this pathway affects chemotherapy-induced muscle wasting. We found that doxorubicin induces muscle atrophy which is prevented by a blocker for activin receptor 2B ligands (sAcvR2B-Fc)
Project description:Analyzed differentially expressed genes among FOP- or resFOP-iMSCs treated by several ligands: Activin-A, 100 ng/mL; BMP-7, 100 ng/mL; TGF-B3, 10 ng/mL Comparison of gene expressions among FOP- or resFOP-iMSCs treated 16h by several ligands
Project description:This study was to compare the gene expression of our anti-GDF8 (i.e. anti-myostatin) and anti-activin A antibody combination to that of the activin receptor type IIB (ActRIIB.hFc) trap in SCID mice. The study was conducted in tibialis anterior muscle that is a common muscle type for the hypertrophy study. The combination treatment produces very similar muscle growth in tibialis muscle as the ActRIIB.hFc trap, however our combination blocks two specific ligands compared to the many ligands the receptor trap will inhibit. The difference in gene expression between these groups demonstrates that despite producing similar muscle growth, the trap affecting more genes in muscle without producing additional muscle hypertrophy.