ABSTRACT
OBJECTIVE@#To study the association between S100A8 expression and prognosis in children with acute lymphoblastic leukemia (ALL).@*METHODS@#The clinical data of 377 children with ALL who were treated with the CCLG-2008-ALL regimen were retrospectively reviewed. ELISA and PCR were used to measure serum protein levels and mRNA expression of S100A8. The Kaplan-Meier method was used for survival analysis and a Cox regression analysis was also performed.@*RESULTS@#The children were followed up for 56 months, and the overall survival rate of the 377 children was 89.1%. The prednisone good response group had significantly lower S100A8 protein and mRNA levels than the prednisone poor response group (P<0.01). In the children with standard or median risk, both S100A8 protein and mRNA levels were associated with event-free survival rate (P<0.05). There were significant differences in S100A8 protein and mRNA levels between the children with different risk stratifications (P<0.01). The children who experienced events had significantly higher S100A8 protein and mRNA levels than those who did not (P<0.01). The Kaplan-Meier survival analysis and the Cox regression model suggested that S100A8 overexpression was an independent risk factor for the prognosis of children with ALL.@*CONCLUSIONS@#High S100A8 expression may be associated with the poor prognosis of children with ALL and is promising as a new marker for individualized precise treatment of children with ALL.
Subject(s)
Child , Humans , Calgranulin A , Metabolism , Disease-Free Survival , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Retrospective StudiesABSTRACT
Scutellarin (SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction (ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and -independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU (10-1 000 μmol·L(-1)) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-cGMPS (PKGI-rp, 4 μmol·L(-1)), significantly blocked SCU (10-1 000 μmol·L(-1))-induced relaxation. The NO synthase (NOS) inhibitor, NO-nitro-L-arginine methylester (L-NAME, 100 μmol·L(-1)), did not significantly change the effects of SCU (10-1 000 μmol·L(-1)). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU (500 μmol·L(-1)), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp (4 μmol·L(-1)) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein (p-VASP, phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.
Subject(s)
Animals , Rats , Apigenin , Pharmacology , Cell Adhesion Molecules , Cell Hypoxia , Coronary Vessels , Cyclic GMP , Metabolism , Pharmacology , Cyclic GMP-Dependent Protein Kinases , Glucuronates , Pharmacology , Microfilament Proteins , NG-Nitroarginine Methyl Ester , Metabolism , Pharmacology , Phosphoproteins , Rats, Sprague-Dawley , Reperfusion Injury , Signal Transduction , Thionucleotides , Metabolism , Pharmacology , Vasodilation , PhysiologyABSTRACT
A 7-year-old girl was admitted to Xiangya Hospital due to systemic lymphadenectasis for 2 months and skin ecchymosis for 3 days. Nine months ago, the girl experienced painless nodules in the left lower extremity with no apparent causes. Three months later, dermatorrhagia and ecchymosis occurred in many regions such as the periocular areas, conjunctiva, oral mucosa, perineal area, and groin, with a "raccoon sign" in both eyes; superficial lymphadenectasis and hepatosplenomegaly were also observed in many regions. The pathological sections for the skin nodules showed malignant tumors in lymphohematopoietic cells, and in combination with clinical manifestations, immunohistochemistry, and positive results for CD4, CD56, and CD123 by bone marrow flow cytometry, the girl was diagnosed with blastic plasmacytoid dendritic cell neoplasm. Then high-risk ALL regimen was applied as the chemotherapy for this girl. At present, the girl has been followed up for 3 months; ecchymosis has disappeared, and the enlarged lymph nodes have shrunk. No abnormal cells have been found in bone marrow morphological examination, and bone marrow flow cytometry has shown that primitive precursor cells account for 1.5% and express CD33, CD34, CD123, and CD117.