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Combination therapy can significantly delay the growth of malignant brain tumors in children
Medical Network May 30, medullary cell tumor (MB) is the most common malignant brain tumor in children. The MYC gene is usually overexpressed and is associated with poor prognosis in MB. The BET bromodomain recognizes acetylated lysine residues and generally promotes and maintains MYC gene transcription. And some special cyclin-dependent kinases (CDKs) can promote the stability of MYC genes in cancer cells.
In search of better treatments for MB, scientists from universities such as Uppsala University, led by Professor Fredrik J. Swartling, discovered the use of BET bromodomain inhibitors and CDK2 inhibitors to target MYC expression and MYC stabilizing factors. It can inhibit the growth of MB cells. The related research results were recently published in Oncogene, entitled "Combined BET bromodomain and CDK2 inhibition in MYC-driven medulloblastoma".
The researchers found that this combination therapy can work synergistically, causing the cancer cell cycle to be blocked and large-area apoptosis. The researchers used RNA-Seq to characterize the changes in transcription levels that this combined MYC inhibition method brings to cancer cells, and they found that the transcriptional level of this method was caused by their MYCN-induced Group 3 MB animal model. The changes were similar to those caused by the use of doxycycline to shut down MYCN.
In addition, the researchers found that combination therapy significantly prolonged the survival of orthogonally transplanted MYC-expressing Group 3 MB tumor-bearing mice compared to monotherapy.
Overall, this study shows that simultaneous inhibition of the CDK2 and BET bromodomains may be a novel approach to the treatment of MYC-driven medulloblastoma.