Background: Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST) have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome.
Resveratrol (RSV), a plant-derived stilbene, induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner (IC50 5 27 lM, trypan blue exclusion assay). At a lower range (25 lM), RSV treatment for 48 hr causes arrest in the S-phase of the cell cycle, while at a higher concentration range (50 lM), apoptosis can be detected, with activation of caspase-3. The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial. Here we show that RSV, at both concentration ranges, leads to a marked increase in p53, while a decrease of SIRT1 expression level, as well as enzyme activity, only occurred at the higher concentration range. Concomitantly, however, treatments at both concentration ranges resulted in a marked increase in K373-acetylated p53 and lysine-acetylated FOXO3a. Immunohistochemical stainings of human lymph nodes show a preferential distribution of SIRT1 in the germinal center of the follicles while the mantle zone shows nearly no staining to few positive cells. The classical HL-affected lymph nodes show a strong positivity of the diagnostic Hodgkin Reed-Sternberg cells. Notably, both the HL-derived cell lines and the Hodgkin Reed-Sternberg cells of the affected lymph nodes derive from germinal center-derived B cells. The study of SIRT1 distribution and expression on a larger number of biopsies might disclose a novel role for this histone/protein deacetylase as therapeutic target.Plant polyphenols are a class of natural molecules well known for their wide range of beneficial properties. [1][2][3] Resveratrol (RSV) is a polyphenol belonging to the class of the stilbenes present in many vegetables and fruits including grapes. The manifold properties of RSV span from chemopreventive action to antioxidant activity, promotion of tissue differentiation, modulation of adipogenesis and antiproliferative effect in several tumoral experimental models.
4-15The information currently available concerning the effects of this natural chemopreventive agent on human lymphoma cells and experimental models is limited. Although there are reports on the antiproliferative activity of RSV on different leukemia and lymphoma cell lines, [16][17][18] no data are available to date in the literature concerning the effects of RSV on Hodgkin lymphoma (HL) cell lines. HL is a tumor frequently affecting adolescents and young adults and represents about 11% of all the diagnosed lymphomas in the United States. 19,20 Furthermore, no studies addressed the involvement of the histone/protein deacetylase SIRT1 (one of the key RSV targets) and of its downstream substrates in lymphomas.Therefore, the initial aims of our work have been the assessment of the potential antiproliferative activity of RSV in the HL-derived L-428 cell line. Next, we examined various apoptosis criteria and cell cycle changes following the RSV treatment. We demonstrate the dose-dependent increase of the proportion of early and late apopto...
Our study failed to demonstrate that the 25G is more effective than the 22G needle in EUS-FNA of solid lesions. However, targeting of lesions in the distal duodenum may be simplified by using the 25G needle.
Immunostaining with PDGFR-alpha is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-alpha previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-beta in GISTs.
This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n ¼ 34), primary myelofibrosis (n ¼ 44) and polycythaemia vera (n ¼ 25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement (Z70%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic 40.40). In conclusion, our results support the use of the histological criteria proposed by the WHO
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