Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant glioma comprises the majority of primary human brain tumors with 16,800 new cases reported each year in the USA. Its prognosis remains dismal despite numerous attempts to improve conventional therapeutic modalities. Therefore, much effort is devoted to the exploration of alternative forms of treatment such as immunotherapy. The identification of potential target structures highly overexpressed in brain tumors is a crucial prerequisite for the activation of the immune defense against malignant glioma cells. By screening an expression database for genes highly expressed in glioblastoma multiforme (GBM), we identified the Pit-Oct-Unc (POU) cooperating transcription factor SOX11 that is known to be crucially involved in brain development. Analysis of the expression pattern of SOX11 in different normal adult and fetal tissues by multiple tissue dot blot and by a highly sensitive quantitative PCR assay confirmed the selective overexpression of SOX11 in fetal brain tissue. Examination of tissue specimens obtained from malignant gliomas and from normal brain by quantitative real-time PCR (Q-RT-PCR) revealed upregulation of SOX11 in almost all tumor samples (15/16) as compared to the pooled normal brain. Seventy-five percent of the tumor samples (12/16) showed a 5- to more than 600-fold overexpression. We conclude that, after downregulation of SOX11 in the adult brain, its expression is reactivated during tumorigenesis and that SOX11 therefore represents a promising novel molecular target for adjuvant therapy of malignant gliomas.
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PMID:Highly specific overexpression of the transcription factor SOX11 in human malignant gliomas. 1558 15

The development of T cell-based immunotherapies of cancer depends on the identification of tumor-associated antigens capable of eliciting tumor-directed cytotoxic T cell responses. In malignant glioma the number of well-defined target antigens for cytotoxic T lymphocytes (CTLs) is still very limited. Recently, we demonstrated the abundant and specific overexpression of the transcription factor SOX11 in malignant glioma. Here, we describe the SOX11-derived peptide LLRRYNVAKV which is capable of inducing human leukocyte antigen-A*0201-restricted and tumor-reactive CTLs. This novel CTL epitope may serve as an attractive candidate for a T cell-based immunotherapy of glioma.
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PMID:Identification of a naturally processed T cell epitope derived from the glioma-associated protein SOX11. 1650 79

Recent findings have shown that malignant tumors contain cancer-initiating cells (CIC), which self-renew and are tumorigenic. However, CICs have not been characterized properly due to lack of specific markers. We recently established a mouse glioma cell line, NSCL61, by overexpressing an oncogenic HRas(L61) in p53-deficient neural stem cells. Using limiting dilution assays, we show that only 2 of 24 NSCL61 clones retained their tumorigenicity in vivo, although the others also expressed oncogenic HRas(L61) and could proliferate in culture. A comparison of the gene expression profiles of tumorigenic and nontumorigenic clones showed that the tumorigenic clones had lost Sox11 expression. We show that overexpression of sox11 prevented tumorigenesis of NSCL61s by inducing their neuronal differentiation accompanied with decreased levels of plagl1. We also show that overexpression of plagl1 abolished neuronal commitment of nontumorigenic cells and induced them to become tumorigenic. Moreover, we show that human glioma-initiating cells lost sox11 expression, and overexpression of sox11 prevented their tumorigenesis in vivo. Together with the clinical evidence showing that downregulation of sox11 mRNA correlates with a significant decrease in survival, these findings suggest that Sox11 prevents gliomagenesis by blocking the expression of oncogenic plagl1.
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PMID:Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation. 1980 59