ErbB1 and prostate cancer: ErbB1 activity is essential for androgen-induced proliferation and protection from the apoptotic effects of LY294002

BACKGROUND: Androgens play a critical role in proliferation and survival of prostate cancer cells, but the mechanisms leading to these effects are poorly understood. ErbB receptor tyrosine kinases have been implicated in the development of prostate cancer. METHODS: We examined the interaction between the ErbB receptors and androgens using the LNCaP androgen-sensitive prostate tumor model. RESULTS: In the absence of androgens, the cells have low levels of ErbB1 and relatively high levels of ErbB2. Addition of androgens to the medium reversed the ratio; ErbB1 levels rose and ErbB2 levels dropped in response to treatment with the synthetic hormone, R1881. Expression of ErbB activating ligands was found to be constitutive and androgen-independent. The androgen-induced proliferation of LNCaP cells was completely inhibited by the addition of the small molecule ErbB1 tyrosine kinase inhibitors CGP59326 and the bispecific inhibitor (PKI166) for ErbB1 and ErbB2 to the culture medium. Furthermore, in the absence of androgens the relatively low proliferative level was further significantly reduced in the presence of CGP59326. Inhibition of PI3K activity by LY294002 led to induction of apoptosis in androgen-deprived LNCaP cells. Androgen-mediated rescue from LY294002-induced apoptosis was inhibited by addition of CGP59326 to the cells. CONCLUSIONS: These results suggest a model whereby androgens promote an increase in the activity of the epidermal growth factor (EGF)-network by increasing ErbB1 levels, and this activity of is essential for androgen-induced proliferation and survival of the prostate cancer LNCaP cell line.     

BAD: a good therapeutic target?

The major goal in cancer treatment is the eradication of tumor cells. Under stress conditions, normal cells undergo apoptosis; this property is fortunately conserved in some tumor cells, leading to their death as a result of chemotherapeutic and/or radiation-induced stress. Many malignant cells, however, have developed ways to subvert apoptosis, a characteristic that constitutes a major clinical problem. Gilmore et al. recently described the ability of ZD1839, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), to induce apoptosis of mammary cells that are dependent upon growth factors for survival. Furthermore, they showed that the major effector of the EGFR-targeted therapy is BAD, a widely expressed BCL-2 family member. These results are promising in light of the role of the EGFR in breast cancer development.     

Atrial fibrillation in patients with heart failure

Atrial fibrillation and heart failure are very common cardiac disorders, and both are associated with symptoms, significant morbidity, and mortality. Studies have attempted to determine the prognostic significance of atrial fibrillation in patients with heart failure. Whether atrial fibrillation is an independent risk factor of mortality remains controversial. Multiple trials using either pharmacologic or nonpharmacologic therapies in an attempt to manage atrial fibrillation have been developed. The purposes of this review are to present an overview of atrial fibrillation in patients with heart failure and to discuss the prevalence, prognostic significance, complications, mechanisms, and trials that have formed the therapies presently used.     

Dynamic external fixation for pilon fractures of the interphalangeal joints

Eight consecutive pilon fractures of the finger proximal interphalangeal joint and one of the interphalangeal joint of the thumb were treated by closed reduction and application of a new dynamic external fixator. The average range of movement achieved was 12 degrees -88 degrees and there were no serious complications. The technique described offers an effective and simple solution for treatment of pilon fractures of the interphalangeal joint.     

A school-based smoking prevention program for adolescent girls in New York City

Teenaged girls comprise the largest percentage of new cigarette smokers in the United States today. Factors contributing to smoking initiation include peer pressure, family and social influences, cigarette availability, and cigarette advertising. Because three-quarters of smokers become dependent on cigarettes by age 20, smoking prevention programs aimed at the adolescent population have great potential. The proposed program outlined is directed at girls 12 to 18 years of age in New York City. Among the objectives are increasing students' knowledge of the short- and long-term health effects of smoking and awareness of the social factors which lead to smoking. Participants would be taught social skills and behaviors which could help them to resist initiating smoking, by such activities as assertiveness training through role playing. Endurance sports activities would be emphasized while learning of the effects of smoking on physical conditioning. The costs of such a program are estimated, and classroom activities are outlined.     

Split-thickness skin grafts and negative-pressure dressings in the treatment of axillary hidradenitis suppurativa.

Although a number of different reconstructive techniques have been described for the treatment of axillary skin defects, split-thickness skin grafting continues to be the most common surgical modality. Here, we present our recent experience of using split-thickness skin grafts together with negative-pressure dressings for the management of defects following wide surgical excision of severe hidradenitis suppurativa. This technique ensures complete skin-graft take whilst allowing full shoulder mobility, thereby minimising the undesirable sequelae associated with split-thickness skin grafting alone.