Somatic RET proto-oncogene mutations in sporadic C-cell carcinoma of the thyroid

Summary. Germline mutations of the RET proto-oncogene localized on chromosome 10q11.2 are the underlying cause of hereditary medullary thyroid carcinoma. In MEN 2A and FMTC, mutations can be found in exons 10, 11, 13 or 14. MEN 2B is characterized by a specific mutation in exon 16. In a significant number of sporadic MTC somatic mutations in codon 918 (exon 16) are detectable. Some rare sporadic MTC present somatic mutations in codons 611, 634, 768 and 883. Recently, deletion-insertion of the RET proto-oncogene in exon 11 and a deletion in exon 10 has been found. RET proto-oncogene mutations are not only responsible for the development of the familial MTC, but may also play an important role in the pathogenesis of sporadic MTC. However, the prognostic relevance of these somatic events is still unclear.      

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

Thoraco-abdominal wound in peaceful time

The results of treatment of 63 injured persons with thoracicoabdominal trauma were analyzed. Injured persons with severe trauma and pronounced infringements of hemodynamic (41.25%); with severe injury of inferior organs and stable hemodynamical indexes (47.62%), light injury (11.12%) were detailed. Algorithm of curative-diagnostical measures for every group was elaborated. Among the injured persons 11 (17.46%) died.     

Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour

Aims:  Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene ( HMOX-1 ) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.
Methods and results:  Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P  < 0.0001). On multivariate Cox regression analysis, GTn polymorphism was identified as an independent prognostic factor for survival ( P  = 0.001).
Conclusions:  HMOX-1 promoter GTn polymorphism is a potential prognostic marker and may help to allocate patients to different risk groups, customized therapy and follow-up. Haeme oxygenase-1 could represent an important candidate gene in the pathogenesis and growth of GIST.