Dobesilate diminishes activation of the mitogen-activated protein kinase ERK1/2 in glioma cells.

Fibroblast growth factors (FGFs) and their receptors, regularly expressed at high levels in gliomas, are further upregulated during the transition of the tumor from low- to high-grade malignancy, and are essential for glioma progression. FGFs induce upregulation of the mitogen-activated protein kinase (MAPK) signaling cascade in cultured glioma cells, which suggests that MAPK pathway participates in the FGF-dependent glioma development. Recently, it has been shown that dobesilate, an inhibitor of FGF mitogenic activity, shows antiproliferative and proapoptotic activities in glioma cell cultures.

Synthesis of the blood circulating C-terminal fragment of insulin-like growth factor (IGF)-binding protein-4 in its native conformation. Crystallization, heparin and IGF binding, and osteogenic activity.

Insulin-like growth factor-binding proteins play a critical role in a wide variety of important physiological processes. It has been demonstrated that both an N-terminal and a C-terminal fragment of insulin-like growth factor-binding protein-4 exist and accumulate in the circulatory system, these fragments accounting for virtually the whole amino acid sequence of the protein. The circulating C-terminal fragment establishes three disulfide bridges, and the binding pattern of these has recently been defined.

Differentiation-inducing activity of neomycin in cultured rat glioma cells.

Induction of cellular differentiation is an attractive therapeutic strategy against glioma cell proliferation and tumorigenicity. Preliminary in vitro studies have indicated that neomycin inhibits the proliferation of cultured glioma cells and induces changes in cellular morphology, making it potentially useful as a therapeutic agent for gliomas. The purpose of this work was to expand on the preliminary research by investigating the differentiation effect of neomycin in rat C6 glioma cells, using glial fibrillary acidic protein (GFAP) staining as a reliable marker of differentiation for normal astrocytes and for tumors of astrocytic lineage.

Neomycin inhibits glioma cell migration.

Blocking migration is an attractive strategy to inhibit glioma tumorigenesis. Previous studies have indicated that neomycin inhibits glioma cells proliferation. The purpose of this study was to expand on the preliminary research by investigating the antimigratory effect of neomycin.

Antiproliferative action of neomycin is associated with inhibition of cyclin D1 activation in glioma cells.

The progression of mammalian cells through G1 phase of the cell cycle is governed by the D-type cyclins (D1, D2, D3). These proteins are induced at the beginning of the G1 phase and associate with serine/threonine cyclin-dependent kinases to form holoenzymes. Overexpression of cyclin D1 in human cancers as well as in several cancer cell lines has been reported.

Glioma cell-associated sustained activation of the transcription factor, nuclear factor-kappa B, was inhibited by neomycin.

Experimental evidence suggests that the transcription factor nuclear factor-Kappa B (NF-kappa B) plays an important role in tumor cell invasion, apoptosis suppression and growth. Malignant glioma is one of the most intractable tumors because of its invasiveness to surrounding brain tissue. Our study investigated the role of neomycin on NF-kappa B activity in glioma cell cultures.

Dual blockade of mitogen-activated protein kinases ERK-1 (p42) and ERK-2 (p44) and cyclic AMP response element binding protein (CREB) by neomycin inhibits glioma cell proliferation.

Several growth factors and their receptors are expressed in inappropriately high abundance in gliomas and are further upregulated during the transition from low- to high-grade malignancy. In glioma cells growth factors induce expression of mitogen-activated protein kinase (MAPK) pathways. Here we report that neomycin restrained glioma cell proliferation in vitro by inhibition of p42/44 MAPK and the cyclic AMP element binding protein (CREB)-directed transcription pathways.

Peripheral nerve regeneration by bone marrow stromal cells.

Adult bone marrow contains stem cells that have attracted interest through their possible use for cell therapy in neurological diseases. Bone marrow stromal cells (MSCs) were harvested from donor adult rats, cultured and pre-labeled with bromodeoxyuridine (BrdU) previously to be injected in the distal stump of transected sciatic nerve of the rats. Distal nerve stump of control rats received culture medium solution.

Inhibition of rat glioma growth by neomycin. Preliminary report.

Tumor development is known to largely depend on angiogenesis, and nuclear translocation of angiogenic factors is one of the crucial steps in tumor angiogenesis. This preliminary study was designed to investigate the suppression of tumor growth by neomycin, an inhibitor of nuclear translocation of several angiogenic factors overexpressed in gliomas. We found that intratumoral osmotic pump delivery of 10 mM neomycin caused significant inhibition of C6 glioma tumor development (85%) in rats.

Antiproliferative effect of neomycin in glioma cells.

The angiogenic growth factor (AGF) family of signaling molecules has been implicated in normal development and in physiological process as well as in human malignancy. Since blockage of nuclear translocation of AGF in endothelial cells with neomycin resulted in inhibition of the growth factor capacity to induce angiogenesis, we treated glioma cells with neomycin and assessed its effects on cell proliferation. Administration of 10mM neomycin during two days resulted in a 56% inhibition of glioma cells proliferation.