Potential oncogenic action of tenascin-C in tumorigenesis

The prominent expression of tenascin-C in the stroma of most solid tumors, first observed in the mid 1980s, implicates tenascin-C in tumorigenesis. This is also supported by in vitro experiments that demonstrate the capacity of tenascin-C to stimulate tumor growth by various mechanisms including promotion of proliferation, escaping immuno-surveillance and positively influencing angiogenesis. However, tumorigenesis in tenascin-C knock-out mice is not significantly different from that observed in control animals. Perhaps this is not unexpected if one considers that tenascin-C may act as an oncogene. The potential role of tenascin-C in tumorigenesis through its oncogenic action on cellular signaling will be discussed in this review, including how tenascin-C mediated tumor cell detachment might affect genome stability.     

The vagus-inhibiting action of alpha-endorphin]

An intravenous bolus injection of 0.1 ml alpha-endorphin (1 x 10(-8)-1 x 10(-4) g/ml) didn't change the heart rate in frogs. The parasympathetic bradycardia induced by the peripheral vagus stimulation was decreased by alpha-endorphin. This vago-inhibitory action was dose-dependent (1 x 10(-5)-1 x 10(-4) g/ml). The maximal inhibitory action was watched in 4-8 and 9-15 minutes after bolus injection of alpha-endorphin in concentration of 1 x 10(-5) and 1 x 10(-4) g/ml accordingly.     

cAMP-dependent oncogenic action of Rap1b in the thyroid gland

cAMP signaling leads to activation and phosphorylation of Rap1b. Using cellular models where cAMP stimulates cell proliferation, we have demonstrated that cAMP-mediated activation, as well as phosphorylation of Rap1b, is critical for cAMP stimulation of DNA synthesis. To determine whether Rap1b stimulates mitogenesis in vivo, we have constructed a transgenic mouse where a constitutively active G12V-Rap1b, flanked by Cre recombinase LoxP sites, is followed by the dominant negative S17N mutant. Employing this novel mouse model, we have switched, in a tissue-specific (thyroid) and temporally controlled manner, the expression of Rap1b from a stimulatory to an inhibitory form. These experiments provide conclusive evidence that Rap1b is oncogenic in the thyroid in ways linked to transduction of the cAMP mitogenic signal.     

The vasomotor action of carragenine in rats]

In the rat, carrageenan injected intravenously lowers the systemic blood pressure. This activity depends on kininogen-kinin system activation, on prostaglandin release by these kinins and on mechanic pulmonary vascular blockade. Neither histamine nor 5-hydroxytryptamine releases are observed.     

The oncogenic activation of beta-catenin

The activation of beta-catenin to an oncogenic state can result from the inactivation of the tumor suppressor adenomatous polyposis coli (APC), by direct mutation in the beta-catenin gene, or by the activation of wnt receptors. Once activated, beta-catenin most likely promotes tumor progression through its persistent interaction with one or more of its numerous downstream targets.     

The ability of mineral dusts and fibres to initiate lipid peroxidation. Part II: relationship to different particle-induced pathological effects

Abstract

Exposure to pathogenic mineral dusts and fibres is associated with pulmonary changes including fibrosis and cancer. Investigations into aetiological mechanisms of these diseases have identified modifications in specific macromolecules as well as changes in certain early processes, which have preceded fibrosis and cancer. Peroxidation of lipids is one such modification, which is observed following exposure to mineral dusts and fibres. Their ability to initiate lipid peroxidation and the parameters that determine this ability have recently been reviewed.¹ Part II of this review examines the relationship between the capacity of mineral dusts and fibres to initiate lipid peroxidation and a number of pathological changes they produce.

The oxidative modification of polyunsaturated fatty acids is a major contributor to membrane damage in cells and has been implicated in a great variety of pathological processes. In most pathological conditions where an induction of lipid peroxidation is observed it is assumed to be the consequence of disease, without further establishing if the induction of lipid peroxidation may have preceded or accompanied the disease. In the great majority of instances, however, despite the difficulty in proving this association, a causal relationship between lipid peroxidation and disease cannot be ruled out.     

The ability of mineral dusts and fibres to initiate lipid peroxidation. Part II: relationship to different particle-induced pathological effects

Exposure to pathogenic mineral dusts and fibres is associated with pulmonary changes including fibrosis and cancer. Investigations into aetiological mechanisms of these diseases have identified modifications in specific macromolecules as well as changes in certain early processes, which have preceded fibrosis and cancer. Peroxidation of lipids is one such modification, which is observed following exposure to mineral dusts and fibres. Their ability to initiate lipid peroxidation and the parameters that determine this ability have recently been reviewed. Part II of this review examines the relationship between the capacity of mineral dusts and fibres to initiate lipid peroxidation and a number of pathological changes they produce. The oxidative modification of polyunsaturated fatty acids is a major contributor to membrane damage in cells and has been implicated in a great variety of pathological processes. In most pathological conditions where an induction of lipid peroxidation is observed it is assumed to be the consequence of disease, without further establishing if the induction of lipid peroxidation may have preceded or accompanied the disease. In the great majority of instances, however, despite the difficulty in proving this association, a causal relationship between lipid peroxidation and disease cannot be ruled out.     

The mechanism of the diuretic action of chlorazicin]

Diuretic and natriuretic action of chloracizine in rats was not associated with its direct influence on the kidney and was accompanied by increase in the plasma volume, by a fall of the hematocrite index and of the total plasma proteins. A study of endogenous creatinine and of osmotic-free water clearance showed the diuretic action of chloracizine to be mainly due to the increase of glomerular filtration and to reduction of the relative proximal reabsorption.     

The mechanism of action of a reinforcing stimulus]

Experiments on alert non-immobilized rabbits revealed that electrical cutaneous stimulation of a limb, used as a reinforcing agent in elaboration of a conditioned reflex to photic flashes, weakened slow polyrhythmic oscillations of background EEG and late components of evoked potentials in the visual cortex to photic flashes. Against this background, the connection between slow potentials and spike activity in both the visual and sensorimotor cortical areas considerably diminished. During EEG activation, induced by the reinforcing stimulus, inhibitory pauses and post-inhibitory activation in the firing of the neocortical units weakened and protracted, ordered spike activity appeared. The data obtained are in agreement with the hypothesis that weakening of the recurrent inhibition system is one of the basic mechanisms in the action of the reinforcing stimulus in conditioning.     

The mechanism of the radioprotective action of sulfolane]

As a result of radiolysis of sulfolane, that has a radioprotective action, sulfonyl anion-radicals and hydrosulfonyl radicals are produced, subsequent transformations of which lead to complete regeneration of sulfolane. On the other hand, some other five-membered cyclic sulfones, that have no radioprotective action, are irreversibly depleted in reactions with water radiolysis products. Sulfolane is suggested to protect from the effect of e(-)aq and H. and to be ineffective in protecting against OH. radicals.     

The role of oxidative stress in diseases caused by mineral dusts and fibres: Current status and future of prophylaxis and treatment

Inhalation of silica and asbestos fibres by humans can lead to fibrosis of the lung and cancer. Different mechanistic approaches, including oxidative stress, are used for prophylactic and therapeutic interventions to attenuate the fibrogenic and carcinogenic effects of these particles. Thus far, most of these therapeutic interventions have been only partly successful. A review of the mechanisms which are thought to be involved in mineral particle-induced toxicity and the relevant therapeutic interventions used to date to counteract these mechanisms, will help formulate better prophylactic and treatment intervention strategies in the future.     

A clinico-physiological study of the mechanism of the cholecystokinetic action of medicinal mineral waters of the naftusia type]

It is stated that the cholecystokinetic action of curative waters of naftusia type is due to the interaction of its organic substances, particularly bitumens, with mucous membrane of gastroduodenal zone by the intramural reflex mechanism with participation of humoral factor. It is indicated by attenuation or suppression of the effect by pharmacons interrupting the work of interchemoreception, N- and M-cholinoreceptors, beta-adrenoreceptors; intensification of the effect by blockade of alpha-adrenoreceptors; its reversion by nonselective stimulation of adrenoreceptors; release of gastrin, glucagon and insulin into blood.     

The antiviral action of a modified bacterial ribonuclease]

The antiviral activity of a bacterial ribonuclease conjugate with chitosane of Kamchatka crab (in a form of water soluble chito-oligosaccharides) has been studied. The conjugate inhibitory activity for A and B viruses as well as to Sindbis arbovirus in tissue cultures is shown. The preparation efficiency at intramuscular and intranasal administration was observed at experimental influenza infection of white mice.