Expression of SODD and P65 in ALL of children and its relationship with chemotherapeutic drugs.
ABSTRACT The expression of silence of death domains (SODD) and its clinical significance and relationship with phospho-NF-kappaB-p65 proteins in bone marrow cells of childhood acute lymphoblastic leukaemia (ALL) were explored, and the expression of SODD and phospho-NF-kappaB-p65 in Jurkat cells treated with chemotherapeutic drugs was detected in order to find a new chemotherapeutic target. The expression of SODD and phospho-NF-kappaB-p65 proteins in bone marrow cells was detected by immunohistochemistry in 25 children with ALL. The apoptosis rate was measured by Annexin-V-Fluorescence/PI double-labeling flow cytometry and the expression of SODD and phospho-NF-kappaB-p65 proteins determined by Western blotting in the Jurkat cells. It was found that the expression of SODD and active P65 in ALL was significantly higher than that in normal control group (P<0.05). The expression of the SODD and phospho-NF-kappaB-p65 proteins in the high-risk (HR) group was significantly higher than that in the standard-risk (SR) group (P<0.05). The Pearson rank correlation analysis revealed that there was a positive correlation between SODD and phospho-NF-kappaB-p65 expression (P<0.01, r=0.69). VCR could effectively induce the apoptosis of Jurkat cells, and down-regulate the expression of SODD and phospho-NF-kappaB-p65 proteins in a time-dependent manner, but DNR could not down-regulate the expression of SODD effectively. It was concluded that SODD may be closely related to the clinical classification and prognosis of ALL in children. The expression of SODD and phospho-NF-kappaB-p65 had a definite synergistic relationship with the onset and development of ALL. VCR could down-regulate the expression of SODD and inhibit the NF-kappaB activation, which could recover the sensibility of apoptosis in leukemic cells.
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ABSTRACT: Melanoma is frequently lethal and its global incidence is steadily increasing. Despite the rapid development of different modes of targeted treatment, durable clinical responses remain elusive. A complete understanding of the molecular mechanisms that drive melanomagenesis is required, both genetic and epigenetic, in order to improve prevention, diagnosis, and treatment. There is increased appreciation of the role of microRNAs (miRNAs) in melanoma biology, including in proliferation, cell cycle, migration, invasion, and immune evasion. Data are also emerging on the role of long non-coding RNAs (lncRNAs), such as SPRY4-IT1, BANCR, and HOTAIR, in melanomagenesis. Here we review the data on the miRNAs and lncRNAs implicated in melanoma biology. An overview of these studies will be useful for providing insights into mechanisms of melanoma development and the miRNAs and lncRNAs that might be useful biomarkers or future therapeutic targets.Archives of Biochemistry and Biophysics 12/2014; DOI:10.1016/j.abb.2014.07.022 · 3.04 Impact Factor
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ABSTRACT: This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.Genetics and molecular research: GMR 01/2014; 13(1):2020-2031. DOI:10.4238/2014.March.24.6 · 0.85 Impact Factor
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ABSTRACT: Resistance to apoptosis remains a significant problem in drug resistance and treatment failure in malignant disease. NO-aspirin is a novel drug that has efficacy against a number of solid tumours, and can inhibit Wnt signaling, and although we have shown Wnt signaling to be important for acute lymphoblastic leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does not appear to be involved in the induction of ALL cell death. Treatment of B lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-α in response to NO-aspirin, suggesting that the process was ligand-independent. Consistent with this, expression of silencer of death domain (SODD) was reduced following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD suppressed expansion of transduced cells confirming the importance of SODD for ALL cell survival. Considering that SODD and caspase-10 are frequently over-expressed in ALL, interfering with these proteins may provide a new strategy for the treatment of this and potentially other cancers.PLoS ONE 07/2014; 9(7):e103383. DOI:10.1371/journal.pone.0103383 · 3.53 Impact Factor