No abstract

Renal cell carcinoma (RCC) representing the most common neoplasia of the kidney in Western countries is a histologic diverse disease with an often unpredictable course. The prognosis of RCC is worsened with the onset of metastasis, and the therapies currently available are of limited success for the treatment of metastatic RCC. Although gene expression analyses and other methods are promising tools clarifying and standardizing the pathological classification of RCC, novel innovative molecular markers for the diagnosis, prognosis, and for the monitoring of this disease during therapy as well as potential therapeutic targets are urgently needed. Using proteome-based strategies, a number of RCC-associated markers either over-expressed or down-regulated in tumor lesions in comparison to the normal epithelium have been identified which have been implicated in tumorigenesis, but never linked to the initiation and/or progression of RCC. These include members of the fatty acid binding protein family, which have the potential to serve as diagnostic or prognostic markers for the screening of RCC patients.

Low oxygen tension was proposed to be one of the environmental parameters characteristic of the patho-physiological conditions of natural infections by Brucella suis. We previously showed that various respiratory pathways may be used by B. suis in response to microaerobiosis and anaerobiosis. Here, we compare the whole proteome of B. suis exposed to such low-oxygenated conditions to that obtained from bacteria grown under ambient air using 2-D DIGE. Data showed that the reduction of basal metabolism was in line with low or absence of growth of B. suis. Under both microaerobiosis and anaerobiosis, glycolysis and denitrification were favored. In addition, fatty acid oxidation and possibly citrate fermentation could also contribute to energy production sufficient for survival under anaerobiosis. When oxygen availability changed and became limiting, basic metabolic processes were still functional and variability of respiratory pathways was observed to a degree unexpected for a strictly aerobic microorganism. This highly flexible respiration probably constitutes an advantage for the survival of Brucella under the restricted oxygenation conditions encountered within host tissue.

Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approximately 40% of RCC cell lines, but not in the normal kidney epithelium cell lines. G250 expression levels significantly varied thereby distinguishing between low, medium and high G250 expressing cell lines. Comparisons of two-dimensional gel electrophoresis expression profiles of untreated RCC cell lines versus RCC cell lines treated with a mAb directed against G250 and the characterization of differentially expressed proteins by mass spectrometry and/or Edman sequencing led to the identification of proteins such as chaperones, antigen processing components, transporters, metabolic enzymes, cytoskeletal proteins and unknown proteins. Moreover, some of these differentially expressed proteins matched with immunoreactive proteins previously identified by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, a technique called PROTEOMEX. Immunohistochemical analysis of a panel of surgically removed RCC lesions and corresponding normal kidney epithelium confirmed the heterogeneous expression pattern found by proteome-based technologies. In conclusion, conventional proteome analysis as well as PROTEOMEX could be successfully employed for the identification of markers which may allow the selection of patients prior to specific immunotherapy.

According to terror management theory, individuals defend their cultural beliefs following mortality salience. The current research examined whether naturally occurring instances of death (i.e., Ebola) correspond to results found in laboratory studies. The results of two experiments demonstrated that participants experienced a greater accessibility of death-related thoughts in response to an Ebola prime during a regional outbreak. Study 2 also showed that increased mortality awareness following an Ebola manipulation was associated with greater worldview defense (i.e., religious fundamentalism). Together, these results suggest that reminders of death in the form of a disease threat operate similarly to a mortality salience manipulation.