[What´s new in Ewing-like sarcoma family? Soft tissue and bone sarcomas with CIC/BCOR rearrangement. Review of the literature and first personal experience]. / Co nového v Ewing-like family aneb malobunecné/kulatobunecné sarkomy mekkých tkání a kostí s rearanzí genu CIC a BCOR. Prehled problematiky a nase prvotní zkusenosti.

The literature is reviewed regarding of a rare molecularly defined group of sarcomas with rearrangement of both CIC and BCOR genes, which were originally placed into the EWSR1wt Ewing-like category. Personal experience with three cases demonstrating difficulties of this issue is added. Both groups of lesions differ not only by age and topography, but also vary in both the prognostic and the predictive parameters. CIC-rearranged tumors are very aggressive and almost never occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly bone tumors in young males behaving even better than classical Ewing sarcoma. From the morphologic point of view, it turned out to be a salient finding that these types of neoplasm might leave canonical morphotype of small blue round cell sarcoma. Instead of it, they are not uncommonly characterized as a relatively uniform spindle cell proliferation with prevailing myxoid transformation deserving much broader differential diagnosis. Our three cases reports display difficulties in reaching the correct diagnosis even by implementing sophisticated molecular techniques in routine practice. Notwithstanding of exhaustive molecular assays used, one may still encounter a lesion where original descriptive term Ewing-lie sarcoma remains uncorrected.

Red wine polyphenols correct vascular function injured by chronic carbon tetrachloride intoxication.

The aim of the study was to evaluate the effect of red wine polyphenols extract Provinols™ on the development of cardiovascular injury in the model of carbon tetrachloride (CCl4) intoxication. We followed the thoracic aorta vasoactivity and left ventricle nitric oxide (NO) synthase activity in male Wistar rats. In the preventive experiment lasting for 12 weeks the control group, the group receiving CCl4 (0.5 ml/kg) two times a week subcutaneously, the group receiving Provinols™ (30 mg/kg/day) in drinking water and the group receiving CCl4+Provinols™ was used. In the recovery experiment, the initial 12 weeks of CCl4 treatment were followed by 3 weeks of spontaneous recovery or recovery with Provinols™. CCl4-intoxication resulted in the injury of vasoactivity which was demonstrated by the inhibition of acetylcholine-induced relaxation as well as noradrenaline-induced contraction. In the preventive as well as recovery experiment administration of polyphenols refreshed endothelium-dependent relaxant response and normalized inhibited contraction to adrenergic stimuli. Provinols™ treatment significantly increased NO-synthase activity in all groups. The results revealed beneficial effects of red wine polyphenols on vascular function injured by chronic CCl4 intoxication. The correction of endothelial function seems to be attributed to the activation of NO pathway by polyphenols.

Neoplastic transformation of the thyroid gland is accompanied by changes in cellular sialylation.

Cancer of the thyroid gland is one of the most common endocrine diseases. Histological evaluation is often complicated by difficulty in distinguishing between benign and malignant lesions. Abnormal glycosylation of cell structures, including changes in sialylation, is a feature of the neoplastic transformation process. The aim of this study was to evaluate associations between neoplastic changes in the thyroid gland and changes in sialylation, with reference to its terminal linkage type. Lectin histochemistry using three sialic acid-binding lectins: Tritrichomonas mobilensis lectin (TML), which recognizes sialic acid without linkage preference; Maackia amurensis leukoagglutinin (MAL), which preferentially binds alpha-2,3-linked sialic acid; and Sambucus nigra agglutinin (SNA), which preferentially binds alpha-2,6-linked sialic acid, were used for detection of sialylated glycoconjugates in 50 human thyroid gland specimens. These included papillary, follicular, oncocytic, medullary and anaplastic carcinomas, follicular adenomas and benign follicular and parenchymatous goiter. The luminal surface of follicular cells in normal thyroid glands, adenomas and goiters showed weak or absent labelling for sialic acid. Malignant transformation of the gland was accompanied by an increase of sialic acid positivity on follicular epithelial cells, especially of alpha-2,3-linked sialic acid. Strong luminal positivity for sialic acid was found in papillary carcinomas, whereas moderate positivity was seen in follicular carcinomas. Inconsistent, weak positivity for sialic acid was documented in medullary and anaplastic carcinomas. Increased membrane sialic acid on thyroid gland cells may be an important diagnostic pathological finding, that could be useful in distinction of malignant from benign thyroid lesions, especially with respect to aspiration cytology diagnostics.

Changes in sialic acid expression in the lung during intrauterine development of the human fetus.

Sialic acid is a component of glycoproteins that influences enzymatic and receptor functions of cells. During proliferation and differentiation of tissues, sialic acid can serve as a recognition determinant in intercellular communication and interactions of cells with the extracellular matrix. In the present study, sialic acid expression in relation to developmental maturity of the lung has been studied. We analyzed 12 necroptic lung specimens from foetuses of different gestational ages from the 15th week to the neonate. Sections were stained histochemically using 3 lectins specific for sialic acid: Tritrichomonas mobilensis lectin (TML), specific for sialic acid without linkage preference, Sambucus nigra agglutinin (SNA), specific for alpha2,6-linked sialic acid, and Maackia amurensis leucoagglutinin (MAL), specific for alpha2,3-linked sialic acid. MAL positivity dominated over SNA positivity showing prevalence of alpha2,3-linked sialic acids to be homogeneously distributed in the lung at the canalicular stage of development. In more mature lungs, well-differentiated bronchial epithelium showed strong sialic acid expression of both linkages. Sialic acid with alpha2,6 linkage dominated in vascular endothelium. Our results showed a slight decrease in sialic acid expression in lungs with gestational age to a relative minimum before birth. Lectin staining of mature lung tissue showed intense sialic acid expression in alveolar epithelial type II cells. Changes in expression of specific sialic acids during differentiation of the lungs may be useful as marker of the degree of maturity of the foetus.

Sialic acid expression in autoimmune thyroiditis.

Autoimmune diseases of the thyroid gland are among the most frequent endocrine disorders. The present study analyzes expression patterns of sialic acids in these diseases. Three lectins specific for sialic acids were used for the histochemical analysis of surgical specimens of the thyroid gland: Tritrichomonas mobilensis lectin that stains all types of sialic acids, Maackia amurensis leukoagglutinin that stains sialic acids with alpha2,3 linkage and Sambucus nigra agglutinin that stains sialic acids with alpha2,6 linkage. In autoimmune thyroiditis, there was a significant increase in sialic acid expression in epithelial cells, especially on luminal membranes of follicular cells. The alpha2,3 linkage dominated over the alpha2,6 linkage. Lymphocytes of patients with Hashimoto thyroiditis, especially in germinal centers, showed strong expression of alpha2,6-linked sialic acids on their cell membrane. Vascular endothelium was positive in all specimens. It can be concluded, that there is a significant increase in sialic acid expression in autoimmune diseases of the thyroid gland, predominantly of sialic acids with alpha2,3 linkage, whereas the sialylation pattern of lymphocytes in Hashimoto thyroiditis was also different.

Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension.

BACKGROUND: Increase of blood pressure is accompanied by functional and morphological changes in the vascular wall. The presented study explored the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension. METHODS: Wistar rats were administered for 6 weeks clear water or L-NAME (40 mg/kg/day) dissolved in water, piperine (20 mg/kg/day), curcumin (100 mg/kg/day) or their combination in corn oil by oral gavage. The systolic blood pressure was measured weekly. Histological slices of thoracic aorta were stained with hematoxylin and eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), orcein, picrosirius red and van Gieson staining and with antibodies against smooth muscle cells actin. Microscopic pictures were digitally processed and morphometrically evaluated. RESULTS: The increase of blood pressure caused by L-NAME was partially prevented by piperine and curcumin, but the effect of their combination was less significant. Animals with hypertension had increased wall thickness and cross-sectional area of the aorta, accompanied by relative increase of PTAH positive myofibrils and decrease of elastin, collagen and actin content. Piperine was able to decrease the content of myofibrils and slightly increase actin, while curcumin also prevented elastin decrease. The combination of spices had similar effects on aortic morphology as curcumin itself. CONCLUSIONS: Administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease.