Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0017636 (glioblastoma)
18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention.
...
PMID:Cinnamic acid: a natural product with potential use in cancer intervention. 762 77

Expression of c-Met, the receptor for hepatocyte growth factor (HGF), and the biological roles of HGF were examined in cultured human glioma cells. All of the 5 glioma cell lines examined expressed c-Met protein as well as the c-met gene. Expression of the c-met gene was also confirmed in a glioblastoma tissue. Three cell lines (MGM-3, U251, KG-1-C) demonstrated chemotactic response to HGF in a dose-dependent manner. The response was not only chemotactic but also chemokinetic as judged by a checkerboard analysis. The amounts of c-Met mRNA and protein were abundant in the cell lines which showed a migratory response to HGF. Moreover, c-Met protein expression was highest in U251 with the highest migratory response to HGF. Among the cell lines, KG-1-C produced notable amounts of HGF protein as well as of c-Met, suggesting that HGF may act in an autocrine fashion in this case. HGF did not act as an apparent growth factor in the glioma cell lines examined. Furthermore, HGF stimulated the production of metalloproteinase, probably gelatinase A, in U251 cells.
...
PMID:Effects of hepatocyte growth factor (HGF) on human glioma cells in vitro: HGF acts as a motility factor in glioma cells. 864 32

To elucidate possible mechanisms of phorbol 12-myristate 13-acetate (PMA) induced in vitro invasiveness of glioblastoma cells, we examined expression levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using Western blotting and gelatin zymography assay, and found that PMA induced the secretion of MMP-9, activated MMP-2 proenzyme to fully active form of 59 kDa, down-regulated the TIMP-1 and TIMP-2 secretion, and increased MT1-MMP on the cell surface. However, PKC inhibitor Go 6983 reversed all of these effects brought about by PMA. We, therefore, conclude the activation of PKC by PMA in these cells plays a critical role in the regulation of MMPs/TIMPs system, which has a major role in tumor invasion and metastasis.
...
PMID:Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells. 1096 98

Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real-time RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-beta induces ADAMTS4, but less ADAMTS5, and interleukin-1beta ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential.
...
PMID:Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas. 1600 58

Selective cleavage of the Glu395-Ser396 bond of brevican, one of the major proteoglycans in adult brain tissues, is thought to be important for glioma cell invasion. Our previous biochemical study demonstrated that ADAMTS-4, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, has such an activity. In the present study, we examined brevican-degrading activities of ADAMTS-1, -4 and -5 at the cellular level, and their expression and localization in human glioma tissues. In 293T transfectants expressing ADAMTS-4 or ADAMTS-5, brevican was cleaved into two major fragments in an identical pattern, but no such degradation was observed with ADAMTS-1 transfectants. When the expression levels of these ADAMTS species were examined by real-time quantitative PCR, only ADAMTS-5 was found to be overexpressed in glioblastoma tissues compared to control normal brain tissues (P <0.05). In situ hybridization and immunohistochemistry demonstrated that ADAMTS-5 is expressed predominantly in glioblastoma cells. Forced expression of ADAMTS-5 in glioma cell lines stimulated cell invasion. These results demonstrate for the first time that ADAMTS-5 is capable of degrading brevican and is overexpressed in glioblastoma cells, and suggest that ADAMTS-5 may play a role in glioma cell invasion through the cleavage of brevican.
...
PMID:Human glioblastomas overexpress ADAMTS-5 that degrades brevican. 1613 47

In an earlier study, we reported that nitric oxide is involved in lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate-induced malignant transformation via increases in metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression in rat glioma C6 cells, however the mechanism has remained undefined. Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate alone, induced transformation in glioma C6 cells (but not in human glioblastoma cells GBM-8401 cells) without affecting their viability. An increase in inducible nitric oxide synthase protein expression, nitric oxide production, and metalloproteinase 9 enzyme activity is identified lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-treated C6 cells, however lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate and 12-o-tetradecanoylphorbol 13-acetate (but not lipopolysaccharide) addition shows the similar inductive pattern on metalloproteinase 9 enzyme activity without affecting inducible nitric oxide synthase protein expression and nitric oxide production in GBM-8401 cells. Treatment of C6 cells with lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate increases the expression of phosphorylated extracellular regulated protein kinases and Jun N-terminal kinases, but not p38, proteins, and an addition of the extracellular regulated protein kinases inhibitor PD98059 or Jun N-terminal kinases inhibitors SP600125, but not the p38 inhibitor SB203580, significantly blocked lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced inducible nitric oxide synthase protein expression and metalloproteinase 9 enzyme activity accompanied by blocking morphological transformation in C6 cells. Among 19 structurally related flavonoids, kaempferol and wogonin exhibit significant inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced morphological transformation and colony formation, and attenuation of inducible nitric oxide synthase, phosphorylated extracellular regulated protein kinases protein expression, and metalloproteinase 9 enzyme activity was observed. 2'-OH flavone at a dose of 100 microM inhibition of lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events via apoptosis induction is identified. Furthermore, lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate, induces tumoral invasion and migration in vitro and in vivo, and those are blocked by kaempferol and wogonin addition. These data suggest that combination of lipopolysaccharide and 12-o-tetradecanoylphorbol 13-acetate promotes tumoral progression via activating metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression, which is located downstream of mitogen-activated protein kinases activation, in rat glioma cells C6. Kaempferol and wogonin exhibit effective inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events, and thus possess the potential for further development.
...
PMID:Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate induction of migration and invasion of glioma cells in vitro and in vivo: Differential inhibitory effects of flavonoids. 1658 Jul 79

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.
...
PMID:The role of chemotherapy in the treatment of malignant astrocytomas. 1673 21

Cytokines play important roles in the growth and growth arrest of cancer cells. IL-13 via an IL-4R alpha/IL-13R alpha 1 heterocomplex receptor inhibits the growth of renal cell carcinoma cells (RCC). However, it does not inhibit the growth of glioblastoma cells that express the IL-13R alpha 2 chain. In the present studies we investigated whether melanoma cells express IL-13R alpha 1 and IL-13R alpha 2 chains as well as whether they respond to IL-13. Membrane IL13R alpha 2 was co-expressed with IL-4R alpha and IL-13R alpha 1 chains in three of six tested melanoma cell lines. Furthermore, the IL-13R alpha 2 positive cell lines, release a soluble form of IL-13R alpha 2, specifically under IL-13 but not IL-4 stimulation. The release of soluble IL-13R alpha 2 was inhibited by various metalloproteinase inhibitors and EDTA inhibits the biological response to IL-13.
...
PMID:Human melanoma cells release soluble and functional receptors. 1868 68

Glioblastoma multiforme is highly aggressive and is the most common glial tumor type. Although there have been advances in treatment, the average survival expectancy is 12-15 months. Several genes have been shown to influence glioblastoma progression. In the present work, we demonstrate that the RhoGTPase Activating Protein 21 (ARHGAP21) is expressed in the nuclear and perinuclear regions of several cell lines. In T98G and U138MG, glioblastoma derived cell lines, ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (FAK). ARHGAP21 depletion by shRNAi in T98G cells alters cellular morphology and increases: FAK phosphorylation states and activation of downstream signaling; the activity state of Cdc42; the production of metalloproteinase 2 (MMP-2) and cell migration rates. These modifications were found to be mainly due to the loss of ARHGAP21 action on FAK and, consequently, the activation of downstream effectors. These results suggest not only that ARHGAP21 might act as a tumor suppressor gene, but also indicate that ARHGAP21 might be a master regulator of migration having a crucial role in controlling the progression of different tumor types.
...
PMID:ARHGAP21 modulates FAK activity and impairs glioblastoma cell migration. 1926 1

A disintegrin and metalloproteinase 19 (ADAM19, or adamalysin 19) is a cell surface glycoprotein with a signal sequence, a prodomain, a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, a epidermal growth factor-like domain, a transmembrane domain, and a cytoplasmic domain. It is an endopeptidase that cleaves extracellular matrix proteins and sheds growth factors and cytokines such as neuregulins, heparin-binding epidermal growth factor, tumor necrosis factor (TNF)-alpha, and TNF-related activation-induced cytokine. The ADAM19 gene was cloned from human, monkey, and mouse. It is expressed in multiple organs and tissues including heart, lung, bones, brain, spleen, liver, skeletal muscle, kidney, and testes. ADAM19 plays essential roles in embryo implantation, cardiovascular morphogenesis, neurogenesis, and other developmental processes. It has constitutive alpha-secretase activity associated with processing Alzheimer's disease amyloid precursor protein (APP) to non-amyloidogenic fragments; thus, it is neuroprotective. Those observations indicate that inhibition of ADAM19 activity is undesirable during embryo development and morphogenesis, and during the development of Alzheimer's disease. On the contrary, in adults, ADAM19 is upregulated in human brain tumors such as astrocytoma and glioblastoma and is correlated with the invasiveness of glioma. It is also over-expressed by many human cancerous cell lines including cancers of the colon, ovary, lung, and brain. Abnormally high expression of ADAM19 is also linked to inflammation and fibrosis of the lung and kidney. Targeted inhibition of ADAM19 may be crucial for the treatment of certain types of tumors and inflammatory diseases.
...
PMID:ADAM19/adamalysin 19 structure, function, and role as a putative target in tumors and inflammatory diseases. 1960 35


1 2 3 4 Next >>

---