The impact of operative approach on outcome of surgery for gastro-oesophageal tumours

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.     

Membrane damage and microbial inactivation by chlorine in the absence and presence of a chlorine-demanding substrate

The relationship between cell inactivation and membrane damage was studied in two gram-positive organisms, Listeria monocytogenes and Bacillus subtilis, and two gram-negative organisms, Yersinia enterocolitica and Escherichia coli, exposed to chlorine in the absence and presence of 150 ppm of organic matter (Trypticase soy broth). L. monocytogenes and B. subtilis were more resistant to chlorine in distilled water. The addition of small amounts of organic matter to the chlorination medium drastically increased the resistance of both types of microorganisms, but this effect was more marked in Y. enterocolitica and E. coli. In addition, the survival curves for these microorganisms in the presence of organic matter had a prolonged shoulder. Sublethal injury was not detected under most experimental conditions, and only gram-positive cells treated in distilled water showed a relevant degree of injury. The exposure of bacterial cells to chlorine in distilled water caused extensive permeabilization of the cytoplasmic membrane, but the concentrations required were much higher than those needed to inactivate cells. Therefore, there was no relationship between the occurrence of membrane permeabilization and cell death. The addition of organic matter to the treatment medium stabilized the cytoplasmic membrane against permeabilization in both the gram-positive and gram-negative bacteria investigated. Exposure of E. coli cells to the outer membrane-permeabilizing agent EDTA increased their sensitivity to chlorine and caused the shoulders in the survival curves to disappear. Based on these observations, we propose that bacterial envelopes could play a role in cell inactivation by modulating the access of chlorine to the key targets within the cell.     

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control

Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we first applied the Bayesian formulation of the immigration-death model to the dataset from Egypt. We further analysed data obtained from a cross-sectional parasitological survey that determined the infection prevalence of S. mansoni among 447 individuals in a village in C?te d'Ivoire. Three consecutive stool samples were collected from each participant and analysed by the Kato-Katz technique. In the C?te d'Ivoire study, the observed S. mansoni infection prevalence was 41.6% and varied with age. The immigration-death model was able to correctly predict 50% of the observed age group-specific point prevalences. The model presented here can be utilized to estimate S. mansoni community infection prevalences, which in turn helps in the strategic planning of schistosomiasis control.     

Beyond the metabolic role of ghrelin: a new player in the regulation of reproductive function

Ghrelin is a gastric peptide, discovered by Kojima et al. (1999) [55] as a result of the search for an endogenous ligand interacting with the “orphan receptor” GHS-R1a (growth hormone secretagogue receptor type 1a). Ghrelin is composed of 28 aminoacids and is produced mostly by specific cells of the stomach, by the hypothalamus and hypophysis, even if its presence, as well as that of its receptors, has been demonstrated in many other tissues, not least in gonads. Ghrelin potently stimulates GH release and participates in the regulation of energy homeostasis, increasing food intake, decreasing energy output and exerting a lipogenetic effect. Furthermore, ghrelin influences the secretion and motility of the gastrointestinal tract, especially of the stomach, and, above all, profoundly affects pancreatic functions. Despite of these previously envisaged activities, it has recently been hypothesized that ghrelin regulates several aspects of reproductive physiology and pathology. In conclusion, ghrelin not only cooperates with other neuroendocrine factors, such as leptin, in the modulation of energy homeostasis, but also has a crucial role in the regulation of the hypothalamic–pituitary gonadal axis. In the current review we summarize the main targets of this gastric peptide, especially focusing on the reproductive system.     

T-helper cells as new players in ANCA-associated vasculitides

In anti-neutrophil cytoplasmic autoantibody-associated vasculitides (AAV), several observations support a key role of T-helper cells (CD4⁺ T cells) in disease pathophysiology. An expanded population of effector memory CD4⁺ T cells in AAV patients may contribute to tissue injury and disease progression. In addition, functional impairment of regulatory T cells (T_Regs) is reported in AAV patients. A fraction of T_Regs have the capacity to differentiate into Th17 cells in the context of a proinflammatory environment. Therefore, nonfunctionality of T_Regs described in AAV patients may be caused by their conversion into IL-17-producing cells that may contribute to granulomatous vasculitis. Further investigations directed at the plasticity of T_Regs in AAV patients are warranted.     

What have we learned from clinical trials in primary Sj?gren's syndrome about pathogenesis?

In vitro and in vivo experimental data have pointed to new immunopathogenic mechanisms in primary Sj?gren's syndrome (pSS). The availability of targeted treatment modalities has opened new ways to selectively target these mechanistic pathways in vivo. This has taught us that the role of proinflammatory cytokines, in particular TNFα, is not crucial in the immunopathogenesis of pSS. B cells appear to play a major role, as depletion of B cells leads to restoration of salivary flow and is efficacious for treatment of extraglandular manifestations and mucosa-associated lymphoid tissue lymphoma. B cells also orchestrate T-cell infiltration and ductal epithelial dearrangement in the salivary glands. Gene profiling of salivary gland tissue in relation to B-cell depletion confirms that the axis of IFNα, B-cell activating factor, B-cell activation, proliferation and survival constitutes a major pathogenic route in pSS.