Photoinversion of sulfoxides as a source of diversity in dynamic combinatorial chemistry

Photochemical interconversion of the two diastereoisomers cis- and trans-thianthrene dioxide (1) can be considered an example of photodynamic combinatorial chemistry (PDCC) in which the interconversion among diastereomeric equilibrating species is brought about by electromagnetic irradiation. Photoequilibrium can be shifted by irradiation at different wavelengths or by addition of SnCl2 that binds cis-1 more efficiently than trans-1. © 2010 American Chemical Society

Cancer-nerve crosstalk in human cholangiocarcinoma

Cholangiocarcinoma (CCA) is a tumor with high tendency to infi ltrate nerves. Recent stud ies highlighted a key role of Schwann cells (SC) in cancer progression. This aspect is still unin vestigated in CCA We observed through a 3D model of perineural invasion the neurotropism of a CCA cell line (HuCC-T1), towards sciatic nerve explants, while no migration was observed using the cholangiocyte controls (H69). Migration and invasion of HuCC-T1 is fostered by the SC conditioned media. Neither the HuCC-T1 nor the H69 control produce factors capable of modulating neuritogenesis in PC12. Western blots performed on HuCC-T1 cells incubated for 48h with conditioned media from SC show a downregulation of E-Caderin indicative of epithelial-mesenchimal transition (EMT) and an upregulation of the proliferating nuclear antigen (PCNA) as compared to the controls. Our data indicate that SC may regulate EMT, migration, invasion and proliferation in Chol angiocarcinoma. we will further investigate this phenomenon by looking for potential mechanisms and molecular pathways involve

Cholangiocarcinoma Malignant Traits Are Promoted by Schwann Cells through TGFβ Signaling in a Model of Perineural Invasion

The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial–mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFβ receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFβ signaling in regulating this process