Glycogen Synthase Kinase-3 (GSK-3) was recently implicated in the dysregulated biology of acute myeloid leukemia (AML). Low concentrations of GSK-3 inhibitors, SB216763 and BIO, suppressed the proliferation of AML cells with FLT3-ITD as early as 24 h after treatment. BIO was used in subsequent assays since it exhibited higher inhibitory effects than SB216763. BIO-induced G1 cell cycle arrest by regulating the expression of cyclin D2 and p21 in MV4-11 cells, and promoted apoptosis by regulating the cleaved-caspase3 signaling pathways. In vivo assays demonstrated that BIO suppressed tumor growth, while metabolomics assay showed that BIO reduced the levels of ATP and pyruvate in MV4-11 cells suggesting that it inhibited glycolysis. BIO markedly suppressed cell growth and induced apoptosis of AML cells with FLT3-ITD by partially inhibiting glycolysis, suggesting that BIO may be a promising therapeutic candidate for AML.
Background and objectives: To investigate the feasibility and safety of ultrasoundguided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) in pediatric patients.Methods: A single-institute retrospective review was performed on 35 pediatric patients with predominantly hematological malignancies (88.6%) who underwent TIVAP implantation via ultrasound-guided right BCV approach from July 2018 to June 2021. The catheter tip was adjusted to be positioned at the cavoatrial junction under pulsed fluoroscopic guidance. Technical success rate, procedural information, and TIVAP-related complications were evaluated.Results: All the pediatric TIVAP devices were successfully implanted via right BCV access. Venous access was successful by first attempt in 32 children (91%), two cases (5.7%) required a second attempt, and one patient (2.9%) required a third attempt.The mean procedural time was 44.6 ± 6.4 minutes (range: 34-62 minutes). No intraoperative complications occurred. The average TIVAP indwelling time was 564 ± 208 days (range: 193-1014 days), with a cumulative 19,723 catheter-days. Overall, three patients (8.6%) experienced four postoperative complications (two cases of local hematoma and two catheter dysfunctions) at a rate of 0.2 per 1000 catheterdays. No other complications such as wound dehiscence, delayed incision healing, Abbreviations: BCV, brachiocephalic vein; CRBSI, catheter-related bloodstream infection; CRT, catheter-related thrombosis; CVC, central venous catheter; IJV, internal jugular vein; IQR, interquartile range; PICC, peripherally inserted central catheter; SCV, subclavian vein; TIVAP, totally implantable venous access port.
Glycogen Synthase Kinase-3 (GSK-3) was recently implicated in the dysregulated biology of acute myeloid leukemia (AML). Low concentrations of GSK-3 inhibitors, SB216763 and BIO, suppressed the proliferation of AML cells with FLT3-ITD as early as 24 h after treatment. BIO was used in subsequent assays since it exhibited higher inhibitory effects than SB216763. BIO induced G1 cell cycle arrest by regulating the expression of cyclin D2 and p21 in MV4-11 cells, and promoted apoptosis by regulating the cleaved-caspase3 and AKT signaling pathways. In vivo assays demonstrated that BIO suppressed tumor growth, while metabolomics assay showed that BIO reduced the levels of ATP and pyruvate in MV4-11 cells suggesting that it inhibited glycolysis. BIO markedly suppressed cell growth and induced apoptosis of AML cells with FLT3-ITD by partially inhibiting glycolysis, suggesting that BIO may be a promising therapeutic candidate for AML.
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