Plasma Level of Tumor Necrosis Factor-alpha (TNF-α) Correlates with Leukocytosis and Biological Features of Leukemic Cells, but not Treatment Response of Children with Acute Lymphoblastic Leukemia

2003 ◽  
Vol 44 (6) ◽  
pp. 1077-1079 ◽  
Author(s):  
M. P. Potapnev ◽  
N. V. Petyovka ◽  
M. V. Belevtsev ◽  
V. P. Savitskiy ◽  
N. V. Migal
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2477-2477 ◽  
Author(s):  
Hayato Tamai ◽  
Koichi Miyake ◽  
Hiroki Yamaguchi ◽  
Masahiro Okabe ◽  
Kazuo Dan ◽  
...  

Abstract Abstract 2477 Mixed-lineage leukemia (MLL)/AF4 positive acute lymphoblastic leukemia (ALL), which is common in infant leukemia, is associated with a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The resistance to graft versus leukemia (GVL) effect may be the possible reason of the poor effect of allo-HSCT on MLL/AF4 positive ALL. Cytotoxic effector mechanisms, which are mediated by tumor necrosis factor-alpha (TNF-alpha), Fas ligand (FasL), or perforin were reported to contribute to GVL effect. We analyzed the sensitivity to TNF-alpha of MLL/AF4 positive ALL cell lines (SEM and RS4;11) together with MLL/AF4 negative leukemia cell lines (MOLT4, Raji and K562) and found that the growth inhibition by TNF-alpha of MLL/AF4 positive ALL cell lines group was significantly lower than those of another MLL/AF4 negative leukemia cell lines group (P<0.01). To examine the possible mechanism of resistance to TNF-alpha of MLL/AF4 positive leukemia, we focused on S100A6 as a possible factor, since it was reported that expression of S100A6, which is a calcium-binding protein implicated in many cellular processes and often up-regulated in cancers limits apoptosis induced by TNF-alpha through p53 inactivation in cardiac myocytes. Western Blot analysis showed that significant up-regulation of S100A6 expression and inhibition of acetyl p53/p53 expression were observed only in MLL/AF4 positive ALL cell lines in the presence of TNF-alpha (5ng/ml)(P<0.01 for S100A6 and P<0.01 for acetyl-P53/p53). To confirm the effect of S100A6 on the resistance to TNF-alpha of MLL/AF4 positive ALL cell lines, we examined the apoptosis rate of MLL/AF4 positive ALL cell lines treated with small interfering RNA (siRNA) against S100A6. TUNEL assay showed that significantly increased rate of apoptosis under s100A6 siRNA in the presence of TNF-alpha (control siRNA VS s100A6 siRNA; 42.5%&mnplus;4.5% VS 90.0%&mnplus;5.0%, P<0.01 for SEM, 32.5%&mnplus;3.5% VS 87.5%&mnplus;5.0%, P<0.01 for RS4;11). Western Blotting also showed that these apoptosis were mediated by p53-Caspase8 pathway. Up-reguration of S100A6 and inhibition of p53-Caspase8 pathway were also confirmed in previously established MLL/AF4 transgenic mice. These results suggest that MLL/AF4 positive ALL escapes from TNF-alpha mediated apoptosis by up-regulation of S100A6 expression followed by interfering with p53 acetylation. Our present results suggest that S100A6 may be a promising therapeutic target for MLL/AF4 positive ALL by combinating with allo-HSCT. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Jennifer Surja Pariaputra ◽  
Sarworini Bagio Budiardjo ◽  
Margaretha Suharsini

 Objective: The aim of this study was to investigate the effects of the short-term use of a probiotic milk drink on salivary tumor necrosis factor-alpha (TNF-α) in children with acute lymphoblastic leukemia (ALL) during the induction phase of chemotherapy.Methods: A randomized, case-controlled clinical trial was carried out. The samples of the study were collected from 11 children with ALL and 11 healthy children as the control. Both groups received a probiotic milk drink. The probiotic milk drink contained Lactobacillus casei (6.5×109 colony forming unit/mL). The subjects were instructed to rinse 5 mL of probiotic milk drink for 30 s over the course of 2 weeks. Unstimulated saliva samples were collected from patients at baseline and 1 and 2 weeks after rinsing with the probiotic milk drink. The levels of TNF-α were determined using a human TNF-α enzyme-linked immunosorbent assay kit.Results: The salivary TNF-α levels in the experimental group decreased but not to a statistically significant degree (p>0.05) when comparing the baseline with weeks 1 and 2 after rinsing. There was a significant decrease of salivary TNF-α levels in the control group (p<0.05) when comparing the baseline with 1 and 2 weeks after rinsing. The concentration of salivary TNF-α in the experimental group was higher than in the control group (p<0.05).Conclusion: This study demonstrates the effect of a short-term intake of a probiotic milk drink on children with ALL during the induction phase of chemotherapy. The results show a reduction of salivary TNF-α after taking the probiotic milk drink after 1 week and 2 weeks, although the results were not statistically significant.


2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.


2005 ◽  
Vol 60 (4) ◽  
pp. 471-475 ◽  
Author(s):  
Barbara Orzeszko ◽  
Tomasz Świtaj ◽  
Anna B. Jakubowska-Mućka ◽  
Witold Lasek ◽  
Andrzej Orzeszko ◽  
...  

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active


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