Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences.

Tumour-associated fibroblasts (TAFs) are part of the tumour stroma, providing functional and structural support for tumour progression and development. The origin and biology of TAFs are poorly understood, but within the tumour environment, TAFs become activated and secrete different paracrine and autocrine factors involved in tumorigenesis. It has been shown that bone marrow mesenchymal stem cells (MSCs) can be recruited into the tumours, where they proliferate and acquire a TAF-like phenotype. We attempted to determine to what extent TAFs characteristics in vitro juxtapose to MSCs' definition, and we showed that TAFs and MSCs share immunophenotypic similarities, including the presence of certain cell surface molecules [human leukocyte antigen-DR subregion (HLA-DR), CD29, CD44, CD73, CD90, CD106 and CD117]; the expression of cytoskeleton and extracellular matrix proteins, such as vimentin, α-smooth muscle actin, nestin and trilineage differentiation potential (to adipocytes, chondrocytes and osteoblasts). When compared to MSCs, production of cytokines, chemokines and growth factors showed a significant increase in TAFs for vascular endothelial growth factor, transforming growth factor-ß1, interleukins (IL-4, IL-10) and tumour necrosis factor α. Proliferation rate was highly increased in TAFs and fibroblast cell lines used in our study, compared to MSCs, whereas ultrastructural details differentiated the two cell types by the presence of cytoplasmic elongations, lamellar content lysosomes and intermediate filaments. Our results provide supportive evidence to the fact that TAFs derive from MSCs and could be a subset of 'specialized' MSCs.

GADA and islet cell antibodies in Romanian children and adolescents with diabetes mellitus.

UNLABELLED: Childhood type 1 diabetes is defined by autoimmunity and insulinopenia. Etiopathogenic definition based on biochemical characteristics has recently replaced the clinical definition based on insulin requirement for treatment. The aim of this study was to describe biochemical and clinical characteristics of children with clinically diagnosed type 1 diabetes, hospitalized at the "Cristian Serban" Center in Buzias. PATIENTS AND METHODS: Fasting C peptide, HbA1c, islet cell autoantibodies (ICA) and antibodies against glutamic acid decarboxylase (GADA) were measured in 278 subjects aged (mean +/- SD; range) 15.1 +/- 4.8 (4-28) years, with a disease duration of 2.1 +/- 0.7 (1.1-3.1) years. GADA and ICA positivity was defined by values higher than the 95th percentile in 99 age-matched non-diabetic controls (0.4 units for ICA and 1.4 for GADA). RESULTS: As many as 66.2% of all patients had positive GADA and 10.1% had positive ICA. While 68.7% had at least one positive antibody, only 7.6% had both antibodies positive. As expected, most of the children (79.9%) had fasting C peptide values in the low range (<0.5 ng/ml), but 3 patients (1.1%) had biochemical signs of insulin resistance (C peptide concentrations >3 ng/ml). Two of the three insulin resistant children had positive GADA and one of them had positive ICA, therefore showing "mixed" features of both type 1 (autoimmunity) and type 2 diabetes (insulin resistance). CONCLUSIONS: Childhood diabetes is now acknowledged to be a complex disorder with heterogeneity in its pathogenesis, clinical course and outcomes. While type 1 diabetes is the most frequent form of diabetes among Caucasian children, measurement of diabetes autoantibodies and C peptide is necessary to better define the types of diabetes in youth.

Clinical and Immunological Aspects in Hashimoto's Thyroiditis.

We propose to establish the relationship between the clinical, functional and immunological parameters in a cohort of women with Hashimoto's thyroiditis. The study included 68 patients between 19 and 70 who were hospitalized for two years in the Endocrinology Clinic of the Hospital in Timisoara. The thyroidal dimensions and the aspects of the thyroidal stroma were shown by echography examinations. The functional parameters like the serum TSH and free T4 concentrations were determined by chemiluminescent methods. The immunological investigations (antithyroglobulin and antiperoxidase antibodies) were performed by the ELISA method. Comparisons were performed by the t test and the Pearson correlation analysis. The correlation between the aspects of thyroidal stroma and thyroid function revealed hypothyroidism in most cases with moderate (++) or severe (+++) echogenity. Another researched aspect was that of correlation of the serum levels of TSH with the thyroidal dimension. The following correlations were obtained: r= - 0.14 in patients with clinical hypothyroidism and r= - 0.3055 in those with subclinical hypothyroidism. The Pearson coefficients for the level of TSH in um and those of the antiperoxidase antibodies, according to clinical and functional categories, revealed the following results: r= - 0.1580 in patients with clinical hypothyroidism and r= - 0.1961 in those with subclinical hypothyroidism. Patients with clinical hypothroidism have significant higher serum level of TSH as compared with those of the patients with subclinical hypothyroidism (p=0.0001). We established a relation between the severe hypoechogenity and hypothyroidism status in patients with positive serum antibodies (r= 0.5695).