Receptors for sheep erythrocytes (E) and erythrocyte-antibody-complement complexes (EAC) on the lymphoblasts of childhood acute lymphoblastic leukemia

Two cell-surface markers, rosette formation with sheep erythrocytes (E-rosette) as a T-cell marker and rosette formation with bovine erythrocyte-antibody-complement complex (EAC-rosette) as a B-cell marker were determined on peripheral blood lymphocytes and lymphoblasts from normal and 89 children with acute lymphoblastic leukemia (ALL). In the majority of the patients (12/15 untreated patients and 6/11 patients in relapse), lymphoblasts exhibited neither E- nor EAC-rosette formation. Lymphoblasts from one untreated patient with mediastinal mass displayed E-(50%) and EAC-rosette formation (15%). In 3 of 11 patients in relapse, lymphoblasts displayed an increase in EAC-rosette formation with progressive disease. In the remaining patients with active disease, a small and variable proportion of lymphoblasts expressed E and/or EAC-rosette formation. In 63 patients in remission, percentages of E- and/or EAC-rosette were similar (p > 0.05) to those of control. The results indicate a wide heterogeneity with respect to expression of lymphocyte membrane markers in lymphoblasts and in normal lymphocytes in patients with active ALL.     

Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors

Although the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's-associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty-nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real-time methylation-specific PCR. CDH13 hypermethylation showed discriminative receiver-operator characteristic curve profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma (ESCC) and normal esophagus (NE) (p < 0.0001). CDH13 normalized methylation values (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE (D) and EAC than in NE (p < 0.0000001). CDH13 hypermethylation frequency was 0% in NE but increased early during neoplastic progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13 hypermethylation frequency and its mean NMV were significantly higher in BE with than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D vs. ESCC. Interestingly, mean CDH13 NMV was significantly lower in short-segment than in long-segment BE, a known clinical risk factor for neoplastic progression. Similarly, BE segment length was significantly lower in specimens with unmethylated than with methylated CDH13 promoters. 5-aza-2'-deoxycytidine treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and increased CDH13 mRNA expression. These findings suggest that hypermethylation of CDH13 is a common, tissue-specific event in human EAC, occurs early during BE-associated neoplastic progression, and correlates with known clinical neoplastic progression risk factors.     

Systems Biology Analyses Show Hyperactivation of Transforming Growth Factor-β and JNK Signaling Pathways in Esophageal Cancer

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El polimorfismo de un solo nucleótido PLAU P141L se asocia con el grado de circulación colateral en pacientes con enfermedad arterial coronaria

Introduction and objectives

Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease.

Methods

The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation.

Results

Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio =1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio =1.73 [95% confidence interval, 1.14-2.62]; P = .009).

Conclusions

An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.Full English text available from: www.revespcardiol.org/en     

Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms

BACKGROUND & AIMS: The luminal microenvironment including acid and nitric oxide (NO) has been implicated in Barrett's esophagus carcinogenesis. We investigated the ability of acid and NO to induce DNA damage in esophageal cells. METHODS: Transformed and primary Barrett's esophagus and adenocarcinoma cells were exposed to either acid, (pH 3.5), +/- antioxidant or NO from a donor or generated by acidification of nitrite in the presence of ascorbate +/- NO scavenger. Phosphorylation of histone H2AX and the neutral comet assay were used to detect DNA double-strand breaks (DSBs). Intracellular levels of reactive oxygen species and NO were detected with fluorescent dyes. Mitochondrial viability was measured with a rhodamine dye. Long-term survival was assessed by clonogenic assay. RESULTS: Exposure to acid (pH 3.5) for > or =15 minutes induced DSBs in all cell lines (P < .05). There was a concomitant increase in intracellular reactive oxygen species in the absence of mitochondrial damage, and pretreatment with antioxidants inhibited DNA damage. Exposure to physiologic concentrations of NO produced from the NO donor or acidification of salivary nitrite induced DSBs in a dose- (>25 micromol/L) and cell-dependent manner (adenocarcinoma >Barrett's esophagus, P < .05). This occurred preferentially in S-phase cells consistent with stalled replication forks and was blocked with a NO scavenger. NO also induced DSBs in primary Barrett's esophagus cells treated ex vivo. Cells were able to survive when exposed to acid and NO. CONCLUSIONS: Both acid and NO have the potential to generate DSBs in the esophagus and via distinct mechanisms.     

顺铂与阿霉素合用的抗瘤活性与剂量的关系

以体外培养瘤细胞集落形成率、荷瘤小鼠生命延长率(ILS)和小鼠实体瘤的抑瘤率作为药效的评价指标,观察顺铂(DDP)与阿霉素(ADM)合用的剂量效应关系。小剂量DDP与ADM的联用时相加作用明显。一种药已达有效量再与另一药小剂量合用其效应与单药足量的效应无显著差异;若两药有效量联合,虽能提高ILS,但表现出毒性增强。     

Performance Evaluation and Structure Optimization of Low-Emission Mixed Epoxy Asphalt Pavement

Epoxy asphalt concrete (EAC) has excellent properties such as high strength, outstanding thermal stability, and great fatigue resistance, and is considered to be a long-life pavement material. Meanwhile, the low initial viscosity of the epoxy components provides the possibility to reduce the mixing temperature of SBS-modified asphalt. The purpose of this study is to verify the feasibility of low-emission mixing of SBS-modified epoxy asphalt and to compare the mechanical responses in several typical structures with EAC, in order to perform structure optimization for practical applications of EAC. In this paper, the Brookfield rotational viscosity test was conducted to investigate the feasibility of mixing SBS-modified epoxy asphalt at a reduced temperature. Subsequently, the dynamic modulus tests were carried out on EAC to obtain the Prony series in order to provide viscoelastic parameters for the finite element model. Six feasible pavement structures with EAC were proposed, and a finite element method (FEM) model was developed to analyze and compare the mechanical responses with the conventional pavement structure. Additionally, the design life was predicted and compared to comprehensively evaluate the performance of EAC structures. Finally, life cycle assessment (LCA) on carbon emissions was developed to explore the emission reduction effect of the epoxy asphalt pavement. The results indicate that the addition of epoxy components could reduce the mixing temperature of SBS-modified asphalt by 30 °C. The proper use of EAC can significantly improve the mechanical condition of the pavement and improve its performance and service life. It is recommended to choose S5 (with EAC applied in the middle-lower layer) as the optimal pavement structure, whose allowable load repetitions to limit fatigue cracking were more than 1.7 times that of conventional pavements and it has favorable rutting resistance as well. The LCA results show that in a 25-year life cycle, the carbon emissions of epoxy asphalt pavements could be reduced by 29.8% in comparison to conventional pavements.     

Presence of hBD-1 and hBD-2 in human cerumen and external auditory canal skin

Conclusion. Human β-defensin-1 (hBD-1) and human β-defensin-2 (hBD-2) antimicrobial peptides present in the cerumen, which is composed of exfoliated epithelial keratin and gland secretion, might provide the first line of defense against microbes in external auditory canal (EAC) skin. Objectives. Cerumen (earwax) plays a primary role in protecting the EAC skin and tympanic membrane. Even though the protection by antimicrobial peptides present in the skin secretion has been well established, little is known about the intrinsic role of the peptides in the EAC skin and cerumen. The aim of this study was to examine the presence of important antimicrobial peptides, hBD-1 and hBD-2, in the cerumen and EAC skin. Materials and methods. Cerumen was collected from 20 healthy adults, and the EAC skins were obtained from 12 patients who underwent middle ear surgery with canaloplasty. The presence of hBD-1 and hBD-2 was analyzed using immunohistochemistry and Western blotting. Results. In the immunohistochemical study of the EAC skin, expression of hBD-1 and hBD-2 was observed in both the epithelium and the glands. The presence of hBD-1 and hBD-2 peptides in the cerumen was confirmed by Western blotting.