ABSTRACT
Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (≥18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P<0.0002) and decreased survival probability (P=0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P<0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.
Subject(s)
DNA-Binding Proteins/metabolism , Genes, Tumor Suppressor , Neuroblastoma/genetics , Transcription Factors/metabolism , Cell Adhesion , Cell Differentiation , Cell Line, Tumor , Cell Movement , Cellular Reprogramming , Chromosomes, Human, Pair 1 , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , Infant , Kaplan-Meier Estimate , N-Myc Proto-Oncogene Protein , Neuroblastoma/metabolism , Neuroblastoma/pathology , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Oncogene Proteins/genetics , Oncogene Proteins/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Retinoids/pharmacology , Transcription Factors/antagonists & inhibitors , Transcription Factors/geneticsABSTRACT
The destructive effect of high pressure (615 MPa) combined with low temperature (15 degrees C) on various strains of Escherichia coli O157:H7 and various serovars of Salmonella in grapefruit, orange, apple, and carrot juices was investigated. The three-strain cocktail of E. coli O157:H7 (SEA13B88, ATCC 43895, and 932) was found to be most sensitive in grapefruit juice (8.34-log reduction) and least in apple juice (0.41-log reductions) when pressurized at 615 MPa for 2 min at 15 degrees C. Correspondingly, no injured survivor was detected in grapefruit and carrot juices under similar treatment conditions. No Salmonella spp. were detected in a 2-min pressure treatment (615 MPa, 15 degrees C) of grapefruit and orange fruit juices. Except for Enteritidis, all four serovars tested in the present study have viability loss of between 3.92- and 5.07-log reductions when pressurized in apple juice at 615 MPa for 2 min at 15 degrees C. No injured cells were recovered from grapefruit and orange juices, whereas the same treatment demonstrated reduction in numbers of Salmonella serovars Agona and Muenchen in apple juices and to a lesser extent with Typhimurium, Agona, and Muenchen in carrot juice. The present study demonstrated that low-temperature, high-pressure treatment has the potential to inactivate E. coli O157:H7 strains and different Salmonella spp. in different fruit juices.
