EGFR inhibition in glioma cells modulates Rho signaling to inhibit cell motility and invasion and cooperates with temozolomide to reduce cell growth.

Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib.

Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle of aged rats.

Muscle resistance to insulin plays a key role in the metabolic dysregulation associated to obesity. A pro-inflammatory and pro-oxidant status has been proposed to be the link between dietary obesity and insulin resistance. Given the gender differences previously found in mitochondrial function and oxidative stress, the aim of the present study was to investigate whether this gender dimorphism leads to differences in the development of high-fat-diet-induced insulin resistance in rat skeletal muscle.

Gender related differences in paraoxonase 1 response to high-fat diet-induced oxidative stress.

Objective: To evaluate the influence of the pro-oxidant and proinflammatory state related to dietary obesity on serum paraoxonase 1 (PON1) activity in male and female rats.

Methods And Procedures: Adult Wistar rats of both genders were fed on a high-fat diet to induce weight gain or standard diet for 14 weeks. Body weight was assessed weekly and food intake fortnightly throughout the dietary treatment.

Paraoxonase 1 response to a high-fat diet: gender differences in the factors involved.

Diets consumed in industrialized countries are rich in fat and increase the incidence of atherosclerosis, a process reported to be influenced by gender. Considering the anti-atherogenic role attributed to serum Paraoxonase 1 (PON1) activity, and given the pro-atherogenic effects described for saturated fatty acids (SFA), as opposed to the beneficial ones conferred to monounsaturated fatty acids (MUFA), the aim of this study was to investigate the response of male and female rat serum PON1 activity and its related factors to a high-fat (HF), hypercaloric diet (fat representing 55.2% of the energy) containing similar amounts of SFA and MUFA.

Time-dependent modulation of rat serum paraoxonase 1 activity by fasting.

High-density lipoprotein-associated paraoxonase 1 (PON1) protects the endothelium from the pro-oxidant activity of oxidised low-density lipoprotein. Whereas fasting has been related to increased oxidative stress, intermittent fasting and caloric restriction are associated to increased resistance to oxidative injury. Taking into consideration that serum PON1 activity is modulated by a restriction of caloric intake and because there is no evidence regarding PON1 response to total food deprivation, we investigated whether PON1 activity is involved in the response aimed to counteract the greater oxidative stress associated to fasting and whether serum PON1 activity is altered by the length of food deprivation.

The age-related paraoxonase 1 response is altered by long-term caloric restriction in male and female rats.

Caloric restriction (CR) has been shown to attenuate age-related oxidative damage and to improve major atherosclerotic risk factors. Paraoxonase 1 (PON1), an enzyme specifically associated with HDL containing apolipoproteins A-I and J, has been reported to prevent the proatherosclerotic effects of oxidized LDL. The aim of this study was to evaluate whether modulation of PON1 activity is part of the underlying CR mechanisms that attenuate the age-associated negative effects.

Effects of caloric restriction and gender on rat serum paraoxonase 1 activity.

Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender.