Molecular Study on Differentiation-Associated Genes Involved in Both Malignant Progression of Glioma and Differentiation of Human Fetal Neural Stem Cells

OBJECTIVE It is unclear whether differentiation disturbances or deregulation of neural stem cells (NSCs) are the early key steps for gliomagenesis and tumor development. Furthermore, relevant molecular changes and gene-regulation pathways are unknown. This study focused on screening and validating differentiation-associated genes from both human NSCs and glioma cells with malignant progression, for the purpose of offering an experimental basis for the cellular origin of gilomas and molecular pathology of gliomagenesis. METHODS The differential-gene expression profiles of malignant progression of gliomas were established, then the differentiation related genes were screened out with a bioinformatics analysis. Expression levels of these genes was further analyzed in cultured human fetal NSCs undergoing differentiation processes with a semi-quantitative RT-PCR assay. RESULTS Eight genes were screened out from the gene-expression profiling of which the expression levels were associated with the differentiation processes of NSCs, namely CXCR4, TN-C, GLT1, IL1-RI, EGFR-8, CDC2, Ndr3 and MAPKK4. Three of them, ie., GLT1, CDC2 and MAPKK4, were further analyzed, showing that expression levels decreased with the differentiation processes of NSCs, and increased with the malignant progression of ganglioglioma. CONCLUSION Three differentiation associated genes were found negatively associated with NSCs differentiation and positively associated with malignant progression of gliomas, suggesting that differentiation disturbances of neural stem cells may be involved in oncogenesis, and that further studies on their roles in gliomagenesis should be conducted.

GENE EXPRESSION PROFILING OF GANGLIOGLIOMA MALIGNANT PROGRESSION BY cDNA ARRAY

Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.

Effect of Juzentaihoto/Shi-Quan-Da-Bu-Tang on Malignant Progression and Metastasis of Tumor Cells

A Japanese herbal(Kampo,汉方)medicine,十全大补汤(juzentaihoto/Shi-Quan-Da-Bu-Tang),is one of the nourishing agents, a so-called"补剂(Hozai/Bu-Ji)," that is used for improving disturbance and imbalances in the homeostatic condition of the body. This formulation is orally administered to patients in various weakened states, including postsurgery patients and patients with chronic illness, where it can alleviate general symptoms such as extreme fatigue, pale complexion, loss of appetite, dry or scaly skin, night sweating, and dryness of the mouth.Recently, juzentaihoto/Shi-Quan-Da-Bu-Tang has been shown to have a variety of biological activities, including activation of natural killer cells and macrophages, cytokine induction, antibody production, antitumor effects in combination with surgical excision or other drugs, and protection against the adverse effects of anticancer drugs and radiation, including immunosuppression and bone marrow toxicity. This article focuses on the antitumor and antimetastatic properties of some Kampo medicines and mainly describes the effects of juzentaihoto and its related formulations on tumor development, progression, and metastasis in vivo. We also discuss the inhibitory mechanism of action and the importance of the prescription and constituent crude drugs in determining the efficacy.