Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this investigation was to characterize non-cloned neuroblastoma cells immunohistochemically. In this study, the cholinergic cells in three mouse tumors were identified by using a choline acetyltransferase (CAT) antibody. Different cholinergic cell distribution patterns were found in the three tumors by using a fluorescence-activated cell sorter (FACS). An antibody to CAT was prepared by immunization of guinea pigs with CAT-antigen from bovine brain. The specificity of the antibody obtained was examined with mouse cervical spinal cord. Identification of the cholinergic cells was performed in three types of non-cloned tumor culture cells, neuroblastoma C-1300 in A/J mice, glioblastoma 203GL in C57BL6 mice and lymphosarcoma 6C3HED in CBA mice. The CAT content and distribution were determined by radiochemical assay, immunohistochemical staining, and individual cell counting with a FACS. The results of radiochemical assay and immunohistochemical staining were in agreement with the CAT distribution pattern determined by cell counting with FACS IV.
 ...
PMID:Immunohistochemical identification of cholinergic cells in non-cloned tumor cells. 635 20

For an immunohistochemical analysis of cellular function of tumors, as related to acetylcholine, the antibody to choline acetyltransferase from bovine brain was obtained in guinea pigs. The specificity of the antibody was immunohistochemically studied in the cervical spinal cord of the mouse. And the findings coincided well with the biochemically and histochemically data on the distribution of choline acetyltransferase or acetylcholinesterase in the spinal cord. The choline acetyltransferase activity in the tumor cells at 6-10 days after subculture was 2.26 nmol/1 x 10(5) cells/hr in glioblastoma, 1.77 nmol/1 x 10(5) cells/hr in C-1300 and 1.45 nmol/1 x 10(5) cells/hr in sarcoma and the difference was statistical. In the immunohistochemical cell staining of these tumors, the rate of fluorescence-positive cells was 82.0% in glioblastoma, 37.3% in C-1300 and 4.2% in sarcoma. These findings coincide well with data on the enzymatic activity. The antibody is applicable not only in the field of the immunohistochemistry, but also for a mechanical analysis of cells at the single cell level, as demonstrated by Fluorescence Activated Cell Sorter (FACS).
 ...
PMID:[Immunohistochemical analysis of tumor cells using choline acetyltransferase (author's transl)]. 703 12

Grade IV astrocytomas, or glioblastomas (GBMs), are the most common malignant primary brain tumor in adults. The median GBM patient survival of 12-15 months has remained stagnant, in spite of treatment strategies, making GBMs a tremendous challenge clinically. This is at least in part due to the complex interaction of GBM cells with the brain microenvironment and their tendency to aggressively infiltrate normal brain tissue. GBMs frequently invade supratentorial brain regions that are richly innervated by neurotransmitter projections, most notably acetylcholine (ACh). Here, we asked whether ACh signaling influences the biology of GBMs. We examined the expression and function of known ACh receptors (AChRs) in large GBM datasets, as well as, human GBM cell lines and patient-derived xenograft lines. Using RNA-Seq data from the "The Cancer Genome Atlas" (TCGA), we confirmed the expression of AChRs and demonstrated the functionality of these receptors in GBM cells with time-lapse calcium imaging. AChR activation did not alter cell proliferation or migration, however, it significantly increased cell invasion through complex extracellular matrices. This was due to the enhanced activity of matrix metalloproteinase-9 (MMP-9) from GBM cells, which we found to be dependent on an intracellular calcium-dependent mechanism. Consistent with these findings, AChRs were significantly upregulated in regions of GBM infiltration in situ (Ivy Glioblastoma Atlas Project) and elevated expression of muscarinic AChR M3 correlated with reduced patient survival (TCGA). Data from the Repository for Molecular Brain Neoplasia Data (REMBRANDT) dataset also showed the co-expression of choline transporters, choline acetyltransferase, and vesicular acetylcholine transporters, suggesting that GBMs express all the proteins required for ACh synthesis and release. These findings identify ACh as a modulator of GBM behavior and posit that GBMs may utilize ACh as an autocrine signaling molecule.
 ...
PMID:Acetylcholine Receptor Activation as a Modulator of Glioblastoma Invasion. 3159 Mar 60