ABSTRACT
The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differentiation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen (BS), a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD4-CD8+ T lymphocytes and the secretion of downstream cytokines in mice via down-regulating the expression of programmed death-ligand 1 (PD-L1) on the tumor cells' surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.
Subject(s)
Animals , Humans , Male , Mice , Antineoplastic Agents/pharmacology , B7-H1 Antigen/antagonists & inhibitors , Benzene Derivatives/therapeutic use , CD8-Positive T-Lymphocytes/drug effects , Hep G2 Cells , Liver Neoplasms/pathology , Organoselenium Compounds/therapeutic use , STAT3 Transcription Factor/physiology , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Tumor Burden/drug effectsABSTRACT
Objective To explore the clinical significance of the brain natriuretic peptide(BNP) in evaluating the cardiotoxicity caused by daunorubicin(DNR) through studying the changes of the plasma BNP levels in children with acute leukemia who accepted the chemotherapy with DNR.Methods Thirty-one children with acute lymphoblastic leukemia(ALL) admitted in the year of 2002-2004 underwent the chemotherapy in DVLP project.The plasma level of BNP was measured by enzyme linked immunosorbent assay(ELISA) and the left ventricular end diastolic diameter(LVEDD) by color Doppler respectively before and after the administration of DNR.Simultaneously,electrocardiography(ECG) and cardiac muscle enzymes(LDH1,CK-MB) were measured as routine.Results The plasma level of BNP increased from(3.97?2.41) ng/L to(18.25?7.63) ng/L(P
ABSTRACT
Objective To observe the transformation features of children with complete atrioventricular block(CAVB), and to improve the diagnosis and treatment of this disease.Methods Seventeen children with primary diagnosis of CAVB were reviewed by retrospective and follow-up study and the clinical characteristics, treatment schemes and prognosis were evaluated.Results Four cases of congenital CAVB lived normally without obvious symptoms in the tracing period from 6 months to 9 years;1 case had the onset of Adams-Stokes syndrome induced by diarrhea;3 cases of the CAVB caused by virus myocarditis turned into sinus rhythm after comprehensive therapy;2 cases persistently presented with the CAVB Complicated with enlarged heart;1 case gave up treatment after deterioration, and one case died.Three cases of temporary CAVB after the open heart operation turned to sinus rhythm in transitory time, while other two cases presented with permanent CAVB and treated with epicardium pacemaker,among whom one had the pacemaker replaced for one time in the 8-year follow-up,and the follow-up of other cases were intermitted.Conclusions The congenital CAVB in the study group with normal QRS interphase and no obvious symptom might not require treatment but follow-up is needed. While infants with heart malformation and wide QRS wave could not endure the low ventricular rhythm are in high risk. Virus myocarditis induced CAVB children tend to present the Adams-Stokes syndrome, and require effective treatments. Partial cases of the CAVB caused by open heart operation may turn to normal sinus rhythm in 2-4 weeks after surgery. cases has persistent CAVB for over 4 weeks, or Adams-Stokes syndrome onset after the surgery demand epicardium pacemaker treatment.