1,3-Dipolar cycloaddition reactions can be considered a powerful synthetic tool in the building of heterocyclic rings, with applications in different fields. In this review we focus on the synthesis of biologically active compounds possessing the 1,2,3-triazole core through 1,3-dipolar cycloaddition reactions. The 1,2,3-triazole skeleton can be present as a single disubstituted ring, as a linker between two molecules, or embedded in a polyheterocycle. The cycloaddition reactions are usually catalysed by copper or ruthenium. Domino reactions can be achieved through dipolarophile anion formation, generally followed by cyclisation. The variety of attainable heterocyclic structures gives an illustration of the importance of the 1,2,3-triazole core in medicinal chemistry

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Molecular dynamics simulations and quantum mechanics/molecular mechanics calculations provided a mechanism for G-quadruplex binding of three transition metal complexes.

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near‐total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real‐time, allele‐specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E mutation was significantly higher than that of patients without mutations. A significant association was found between low p27Kip1 protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAFV600E mutation in the metastatic tumor and presented a wider diameter of the largest metastatic area, a higher number of involved LNs, and a higher percentage of metastatic lesions with extracapsular extension of LN (ECE‐LN). A significantly lower mean value of p27Kip1 was observed in LNs harboring the BRAFV600E mutation and in ECE‐LN; an inverse correlation was found between p27Kip1 and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN. CONCLUSIONS. The authors' data suggested that BRAFV600E mutation and p27Kip1 down‐regulation in cancer cells of PTC ≤1 cm may be factors that facilitate tumor‐cell growth and progression once these are seeded in the LNs. Cancer 2007. © 2007 American Cancer Society.

The purpose of this work was to determine in colon mucosa of Crohn's disease (CD) and ulcerative colitis (UC) in relapse: a) the levels of the chaperonins Hsp60 and Hsp10; b) the quantity of inflammatory cells; and c) if the levels of chaperonins parallel those of inflammation cells. Twenty cases of CD and UC and twenty normal controls (NC) were studied using immunohistochemistry, Western blotting and immunofluorescence. Immunohistochemically, Hsp60 and Hsp10 were increased in both inflammatory bowel diseases (IBD) compared to NC. These results were confirmed by Western blotting. Hsp60 and Hsp10 occurred in the cytoplasm of epithelial cells in CD and UC but not in NC. Hsp60 and Hsp10 co-localised to epithelial cells of mucosal glands but not always in connective tissue cells of lamina propria, where only Hsp60 or, less often, Hsp10 was found. Cells typical of inflammation were significantly more abundant in CD and UC than in NC. Since chaperonins are key factors in the activation of the immune system leading to inflammation, we propose that they play a central role in the pathogenesis of the two diseases, which, consequently, ought to be studied as chaperonopathies.