Preferential inhibition of glioblastoma cells with wild-type epidermal growth factor receptors by a novel tyrosine kinase inhibitor ethyl-2,5-dihydroxycinnamate.

Epidermal growth factor receptor (EGFR) gene overexpression and mutations play an important role in the pathogenesis of a variety of malignant human cancers. In this study, we tested the effects of a novel EGFR tyrosine kinase inhibitor, ethyl-2,5-dihydroxycinnamate (EtDHC), against related human glioblastoma cell lines expressing specific forms of EGFR gene mutations. EtDHC more potently inhibited cell growth and DNA synthesis in glioblastoma cells with endogenous or overexpressed wild-type EGFR compared with those with truncated EGFR, by preferentially inhibiting the tyrosine kinase activity and autophosphorylation of the wild-type EGFR.

Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors.

The effects of a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, tyrphostin AG 1478, were tested on three related human glioma cell lines: U87MG, which expressed endogenous wild-type (wt) EGFR, and two retrovirally infected U87MG cell populations which over-expressed either wt (U87MG.wtEGFR) or truncated EGFR (U87MG. delta EGFR).

Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat.

Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive peptide. Previous studies have shown that intraventricularly-administered bFGF reduces the size of cerebral infarcts following focal ischemia. In the current study, we tested the effects of intravenously-administered bFGF in a model of focal ischemia/reperfusion.

Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat.

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain neurons, glia, and endothelial cells. In the current study, we used Northern blotting, in situ hybridization, and immunohistochemical techniques to examine bFGF expression in brain following focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold increase in bFGF mRNA in tissue surrounding focal infarcts at 1 day after ischemia.

Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats.

Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity, and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that pretreatment with basic fibroblast growth factor limits infarct size in a model of focal cerebral ischemia in vivo.

Basic fibroblast growth factor dilates rat pial arterioles.

Basic fibroblast growth factor (bFGF) is a polypeptide that promotes the survival and differentiation of brain neurons, glia, and endothelial cells. It has been shown recently that intravenously administered bFGF lowers blood pressure by systemic vasodilation; this effect is mediated, in part, by nitric oxide (NO)-dependent mechanisms. In the current study, we directly evaluated the effect of bFGF on pial arterioles of pentobarbital-anesthetized Sprague-Dawley rats (n = 18) using the closed cranial window technique.

Basic fibroblast growth factor protects cerebrocortical neurons against excitatory amino acid toxicity in vitro.

Background And Purpose: Previous studies have shown that basic fibroblast growth factor protects against excitatory amino acid toxicity in cultured hippocampal, striatal, and cerebellar neurons. In the current study, we examined the neuroprotective effects of this growth factor on cerebrocortical neurons, which are commonly involved in thromboembolic stroke.

Methods: Dissociated neuron-glia cultures of embryonic rat cerebral cortex (12 days in vitro) were preincubated with basic fibroblast growth factor (0.

Growth factor expression after stroke.

Fibroblast growth factors are polypeptides with potent trophic effects on central nervous system cells. Both acidic and basic forms of fibroblast growth factor are found in the mammalian brain. We have examined the expression of these factors after focal brain injury or stroke.

Fibroblast growth factor (FGF) levels in the developing rat brain.

Acidic and basic fibroblast growth factors (FGF) are polypeptides with potent multipotential trophic effects on central nervous system (CNS) glia, endothelial cells, and neurons. These factors are characterized by strong binding to heparin, and are commonly assayed by their mitogenic activity on Balb/c 3T3 cells in vitro. We found a marked (ca.

Increased levels of basic fibroblast growth factor (bFGF) following focal brain injury.

Focal injury to the mammalian central nervous system (CNS) results in a cascade of cellular responses - including glial and capillary proliferation and neural sprouting - that contribute to the repair of neural tissue and to the recovery of neurological function. Fibroblast growth factors (FGFs) are heparin-binding polypeptides with potent trophic effects on CNS glia, endothelia, and neurons; both acidic and basic forms are found in the mammalian CNS. We used heparin-affinity chromatography coupled to Balb/c 3T3 mitogenic assay to show a marked increase in levels of bioactive FGFs in tissue surrounding focal cortical lesions of the mature rat brain at one week after injury.

Partial purification and characterization of a neurite-promoting factor from the injured goldfish optic nerve.

We have partially purified and characterized a neurite-promoting factor derived from the injured goldfish optic nerve (ON). This factor is secreted into conditioned media (CM) by the injured, but not intact goldfish ON, and has potent outgrowth-promoting effects on neurons of the embryonic mammalian brain. Based on its elution properties on ion-exchange and gel-filtration chromatography, this factor appears to be an acidic protein of Mr ca.

Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds.

Basic fibroblast growth factor (bFGF) is a polypeptide found within the CNS with potent effects on the survival and proliferation of CNS glia and endothelial cells, and on the survival and outgrowth of CNS neurons. Immunohistochemical methods were used to examine relative changes in the levels and distribution of bFGF following focal brain injury. Two monospecific antisera to bFGF were used to immunostain intact mature rat brain, and brain in which a focal mechanical lesion had been made in the dorsolateral cerebral cortex one week previously.

A factor from the injured lower vertebrate CNS promotes outgrowth from human fetal brain neurons.

Unlike mammals, lower vertebrates retain the capacity to regenerate damaged central nervous system (CNS) pathways throughout life. In previous studies, we have used the goldfish optic nerve (ON) as a model for CNS regeneration, and found that the injured goldfish ON selectively secretes a factor that promotes process outgrowth of cultured neurons, including neurons of the developing rodent CNS. In the current study, we found that a factor similarly obtained from the injured goldfish ON also has potent outgrowth-promoting effects on cerebrocortical neurons of the fetal human brain, and that these effects are dependent on the age of fetal neurons.

Different interactions used by Cro repressor in specific and nonspecific DNA binding.

The mode of interaction of Cro repressor with specific and nonspecific sites on DNA was explored by chemical modification and protection of lysine and tyrosine residues. Cro has 8 lysines. In the presence of DNA, lysines 32 and 56 are fully protected and lysines 21, 62, and 63 are partially protected from alkylation.

The interaction of calmodulin with melittin.

Studies utilizing the interaction of melittin with the 1-106 fragment of calmodulin, the protection of calmodulin from tryptic digestion by melittin, and the interaction of the carbocyanine dye Stains-all with the calmodulin-melittin complex have indicated that complex formation of calmodulin with melittin involves the alpha-helical connecting bridge joining the N- and C-terminal lobes of calmodulin.

The interaction of calmodulin with the carbocyanine dye (Stains-all).

The dye "Stains-all" combines with calmodulin to yield a series of complex species whose absorption and circular dichroism spectra are sensitive to the presence of Ca2+ or Mg2+. At high dye:calmodulin ratios, the dominant complex formed is characterized by a strong absorption band at 600-650 nm, which is associated with a biphasic circular dichroism band. These spectral features are abolished in the presence of Ca2+.