Compared to the 19-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in the Ukraine has increased from 4.7 to 9.0 per 100,000 of the total population. Cesium 137 (¹³⁷Cs), which accounts for 90% of the internal radioactivity in the Ukrainian population exposed to long-term low-dose radiation and 90% of the more labile pool of ¹³⁷Cs, is excreted via the kidneys. Our present study aimed to evaluate the status of pro- and anti-apoptotic regulatory molecules in conventional renal cell carcinomas (cRCCs) in Ukrainian patients. To achieve this objective, Bcl-2, Bcl-x, BAX, death receptor (DR5) and transcriptional nuclear factor kappa B (NF-ÎB, with p50 and p65 subunits) were immunohistochemically investigated using a tissue microarray technique in cRCCs from a group of 56 Ukrainian patients, comprising 18 patients living in non-contaminated areas and 41 patients from ¹³⁷Cs-contaminated areas. As a comparison, 19 Spanish patients with analogous tumors were also investigated. It was shown that BAX and DR5-positive cRCCs tended to increase among the Ukrainian patients living in the radio-contaminated areas, along with the suppression of anti-apoptotic molecules (Bcl-2 and Bcl-x) and with p65 and p50 overexpression in the same tumors. This study suggested that chronic long-term, low-dose radiation exposure might result in the alteration of the apoptotic regulatory mechanisms, which, in turn, could lead to enhanced tumor progression and resistance to apoptosis.

The development of malignant tumors is the result of sequential genetic and epigenetic lesions that lead to alterations in a number of gene expressions, which are primarily controlled by transcription factors. A growing body of evidence suggests that early growth response-1 (Egr-1), a transcription factor, may function as a tumor suppressor. Here, the possible role of Egr-1 in the suppression of tumor cell invasion, angiogenesis and metastasis was investigated. Expression of Egr-1 significantly reduced the invasion of human fibrosarcoma cells through matrigel. Mouse embryonic fibroblasts, from Egr-1 knockout mice, also showed increased invasion through matrigel compared with MEFs from wild-type mice. Conditioned medium from Egr-1-transfected cells compared with control transfected cells also reduced proliferation, invasion through matrigel and tube formation of human umbilical cord vein endothelial cells and human microvascular endothelial cells. In addition, Egr-1-transfected cells inhibited vessel formation in mouse skin plug assays. To study the possible molecular mechanisms responsible for this function, the expression of multiple cytokines, chemokines, growth factors and angiogenic factors were examined by using human cytokine antibody array technology it was observed that tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was up-regulated in Egr-1-transfected cells. Addition of Egr-1-transfected cell conditioned medium and TIMP-2 recombinant protein suppressed fibrosarcoma cell invasion. In summary, it was shown that Egr-1 may have novel functions in the suppression of tumor cell invasion and angiogenesis, while TIMP-2 may be involved in the suppression of tumor cell invasion and angiogenesis in Egr-1-transfected cells.

Hematopoietic stem cell (HSC) allograft can be performed with cells of peripheral or medullar origin. Currently, it is the best therapy for certain malignant diseases. The curative power of allografts is based on conditioning and on the graft versus leukemia (GVL) effect. This effect is always associated with a toxic reaction called graft-versus-host disease (GVHD). Numerous studies have been carried out on mouse models, but the pathophysiology of GVHD remains unknown. To evaluate the variation in gene expression during GVHD, a prospective study was performed on two patients with GVHD, using the donors as controls. Blood lymphocytes were isolated by Ficoll gradient. The gene expression levels in total RNA were determined using the Taqman method. The gene expressions of cytokines (TNFα, INFγ, IL4, IL10), major histocompatibility complex class II (MHC II) and class III (BAT2), an adhesion molecule (VCAM) and granzyme M were studied. INFγ, TNFα, BAT2 and IL4 were up-regulated whereas IL10 and VCAM1 were down-regulated.

 Background: In breast cancer treatment, FEC100  (fluorouracil, epirubicin and cyclophosphamide) chemotherapy delivered in a neoadjuvant setting is still applied empirically to all patients. The aim of this study was to establish a multigene classifier of sensitivity to neoadjuvant FEC100. Materials and Methods: cDNA nylon microarrays, containing 15,000 genes, were used to analyze the gene expression profiles of tumour biopsies collected before chemotherapy: 8 were typed as pathological complete responders and 8 as non-responders according to their histological and clinical responses. Results: A classifier was generated by means of Linear Discriminant Analysis and was evaluated by leave-one-out cross-validation. The difference of expression of the NDUFB5 gene (NADH dehydrogenase 1 beta subcomplex, 5), the best discriminating gene, was verified using RT-PCR. Conclusion: This preliminary work requires further investigations, especially in terms of larger cohorts, before the results can be transferred to clinical practice.

The ATP-binding cassette (ABC) transporters are highly conserved genes involved in the translocation of molecules through biological membranes. Several of them are involved in tumor drug resistance, and it is thought that many others may contribute to the development of the tumor phenotype in a still unknown way. A low-density DNA microarray was recently developed for the analysis of 38 ABC-transporter genes and 3 other transporters. In the present pilot study, clinical samples from 16 breast cancer patients were tested. Of the 41 transporters analyzed, 10 were not or very seldom expressed, while 23 were found to be expressed, sometimes at very high levels, in the majority of the tumors. Comparison of the treated and untreated tumors showed an unexpected similarity of results. The signal obtained on the capture probes for ABCC6/8/9 was, however, found to be higher in the treated samples. The microarray data were validated on 15 ABC-transporter genes by real-time PCR. The present results showed that the expression of the majority of the ABC transporters was a clear feature of breast tumors, whether treated or not.

The small heterodimer partner (SHP) is a key regulator of genes involved in cholesterol-bile acid homeostasis and functions as a specific transcription repressor. Differential protein expression in the liver of transgenic mice expressing the human SHP gene was compared with wild-type animals. Liver protein extracts were analyzed by two-dimensional electrophoresis and the proteins were identified by MALDI-TOF-MS. Approximately 30 proteins were differentially-expressed in the livers of transgenic mice, compared to the control mice. Major effects were evident in lipid accumulation, including a fatty acid-binding protein. Overexpression of SHP also triggered alterations in key enzymes involved in the metabolism of amino acids, nucleic acids and urea and was associated with changes in cellular proteins involved in calcium homeostasis, detoxification and protein folding and repair.