Effect of HER2/neu expression on survival in non-small-cell lung cancer

Major prognostic factors for early-stage non-small-cell lung cancer (NSCLC) are tumor size and nodal status. It has been suggested that HER2/neu overexpression may be related to poor prognosis in NSCLC. We evaluated the significance of HER2/neu overexpression on survival in patients with NSCLC. Data were collected on 239 patients treated surgically for stage I/II NSCLC between 1987 and 1996. None of the patients received adjuvant chemotherapy or radiation. Formalin-fixed, paraffin-embedded tumor tissue samples were stained with p185/HER2 receptor antibody. Results were reported as positive (2+, 3+) or negative (0, 1+) (Group A). A separate analysis considered only 3+ as positive (Group B). HER2/neu overexpression was seen in 18% in Group A (43 of 239) and 6% in Group B (15 of 239). HER2/neu overexpression was highest in bronchoalveolar cell carcinoma and adenocarcinoma. More stage I tumors were positive than stage II in both groups, but this was significant only in Group A (21% vs. 7%, P = 0.02). No difference was seen with age, gender, or grade for either group. In Group A, the relapse rate was 55% for HER2/neu-overexpressing tumors and 31% for HER2/neu-negative tumors (P = 0.003). Median time to relapse in patients with HER2/neu-positive tumors was 2.9 years; it was not reached in patients with HER2/neu-negative tumors. Median survival of patients with HER2/neu-positive tumors was 3.6 years compared to 5 years in patients with HER2/neu-negative tumors (P = 0.66). In Group B, the relapse rate was 60% for HER2/neu-overexpressing tumors and 33% for negative tumors (P = 0.036). Median time to relapse was 3.4 years in HER2/neu positive and had not been reached in negative tumors. There was no difference in 5-year survival rates for both groups (47% for HER2/neu positive and 50% for negative, P = 0.66).     

Physiological concentrations of gangliosides GM1, GM2 and GM3 differentially modify basic-fibroblast-growth-factor-induced mitogenesis and the associated signalling pathway in endothelial cells.

It has been suggested that gangliosides can influence the growth of cells by modulation of growth-factor-receptor signalling. The activation of endothelial cells (EC) during angiogenesis is crucial for tumour growth and for metastasis, also for numerous other physiological and pathological situations. Pre-treatment of bovine aortic endothelial cells (BAEC) with GM1 or GM2 (5-20 microM) inhibited basic-fibroblast-growth-factor (bFGF)-induced mitogenesis, but GM3 (0.1-20 microM) acted synergistically, increasing proliferation above that of bFGF alone (p < 0.05). The mitogenic effect of all 3 gangliosides was markedly reduced if the cells were washed to remove excess gangliosides from the medium before addition of bFGF. We further show that GM1 and to a lesser extent GM2 modify bFGF binding to its receptor and inhibit the associated mitogenic signal-transduction pathway of protein-tyrosine phosphorylation of 40 to 120 kDa, PLCgamma1, MAP kinase and protein-kinase-C activation. In contrast, GM3 increased tyrosine phosphorylation and MAP kinase activity, as compared with bFGF alone. The observed differential modulation of bFGF-induced mitogenesis by GM1, GM2 and GM3 was at concentrations routinely occurring in the serum of cancer patients. The results suggest that circulating gangliosides may have a role in regulating solid-tumour growth by modulating angiogenesis.     

Comparative efficacy of behavioral stress management versus propranolol in reducing psychophysiological reactivity in post-myocardial infarction patients

The present study compared the relative efficacy of a behavioral stressmanagement procedure versus a pharmacologic method (the beta-blocker propranolol) in reducing psychophysiological reactivity in post-myocardial infarction (MI) patients. A pretreatment-posttreatment assessment design was used, with 10 patients participating in six separate sessions. The first session involved evaluating psychophysiological reactivity to an emotional stressor (a public-speaking task). The subsequent five sessions involved the administration of the respective treatments, either stress management or drug. The patients were randomly assigned to each treatment group. The public-speaking stressor was readministered after the last treatment session. Results demonstrated that behavioral stress management reduced psychophysiological reactivity to public speaking to the same level seen with propranolol. The findings suggest that this nonpharmacological approach could be of use when beta-blocker therapy is not desired, not practical, or medically contraindicated.This research was supported by a grant to the first author from the American Heart Association, Texas Affiliate.     

Competency-based education in thrombolytic therapy: a modular approach

Continuing education of nurses in therapeutic advancements poses a challenge to nurse educators and managers. The competency-based educational method is a way to prepare nurses and subsequently evaluate performance based on derived standards. In this article a competency-based education approach to the use of thrombolytic therapy in acute myocardial infarction is examined.     

A cross-sectional analysis of reported corporate environmental sustainability practices

The concept of sustainability evolved throughout the 1970s and 1980s, but was formally described by the 27 principles of the Rio Declaration on Environment and Development in 1992. Despite the passage of nearly 20 years, to date there are no uniform set of federal rules, regulations, or guidelines specifically governing the environmental aspects of sustainability practices or related requirements in the United States. In this benchmark analysis, we have collected information on the sustainability programs of the five largest US companies in each of the 26 industrial sectors [based on the Forbes Global 2000 through 2009 (n = 130)]. For each company, we reviewed the most recent corporate sustainability, citizenship, or responsibility report, limiting our scope to environmental components, if available. Ten criteria were identified and analyzed, including leadership, reporting, external review, certification, and individual components of environmental sustainability programs. With respect to the prevalence of sustainability components between various business sectors, we found that the Drugs and Biotechnology (87%), Household and Personal Products (87%) and Oil and Gas Operations (87%) industries had the most comprehensive environmental sustainability programs. Using the nine components of environmental sustainability as a benchmark, we identified four key components as the characteristics of the most comprehensive environmental sustainability programs. These were (1) empowering leadership with a commitment to sustainability (80%), (2) standardized reporting (87%), (3) third-party evaluation of the sustainability programs (73%), and (4) obtaining ISO 14001 certification (73%). We found that many firms shaped their own definition of sustainability and developed their associated sustainability programs based on their sector, stakeholder interests, products or services, and business model. We noted an emerging area that we have called product sustainability – one in which toxicologists and environmental scientists can play a vital role helping to ensure that a manufactured item will indeed be considered acceptable for distribution now, as well as in the coming years. Numerous examples or case studies are presented.     

Lipoblastomatosis: Ultrastructure of Two Cases and Relationship to Human Fetal White Adipose Tissue

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polyponal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal “white” adipose tissue.