Establishment and Thorough Characterization of Xenograft (PDX) Models Derived from Patients with Pancreatic Cancer for Molecular Analyses and Chemosensitivity Testing.

Patient-derived xenograft (PDX) tumor models are essential for identifying new biomarkers, signaling pathways and novel targets, to better define key factors of therapy response and resistance mechanisms. Therefore, this study aimed at establishing pancreas carcinoma (PC) PDX models with thorough molecular characterization, and the identification of signatures defining responsiveness toward drug treatment. In total, 45 PC-PDXs were generated from 120 patient tumor specimens and the identity of PDX and corresponding patient tumors was validated.

Immunohistochemical distinction of ABC and GCB in extranodal DLBCL is not reflected in mutation patterns.

Gene expression profiling (GEP) separated diffuse large B-cell lymphoma (DLBCL) in two different entities, i.e. activated B cell-like (ABC) and germinal center B cell-like (GCB) lymphomas with ABC lymphomas demonstrating a less favorable outcome.

BCL9L expression in pancreatic neoplasia with a focus on SPN: a possible explanation for the enigma of the benign neoplasia.

Background: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors affecting mainly women. They show an activating mutation in CTNNB1, the gene for β-catenin, and consequently an overactivation of the Wnt/β-catenin pathway. This signaling pathway is implied in the pathogenesis of various aggressive tumors, including pancreatic adenocarcinomas (PDAC).

A new type of MAML2 fusion in mucoepidermoid carcinoma.

The present study reports for the first time a CRTC3-MAML2 fusion gene in a mucoepidermoid carcinoma, as determined by RT-PCR and sequencing. We screened a total of 67 formalin-fixed, paraffin-embedded mucoepidermoid carcinomas for the presence of chimeric genes. In one of these samples, a CRTC3-MAML2 fusion gene was detected.

Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism.

The adenoviral protein E3-14.7K (14.7K) is an inhibitor of TNF-induced apoptosis, but the molecular mechanism underlying this protective effect has not yet been explained exhaustively.

TNF-receptor I defective in internalization allows for cell death through activation of neutral sphingomyelinase.

The cytoplasmic tail of the tumor necrosis factor receptor I (TNF-RI) contains several functionally distinct domains involved in apoptotic signaling. Mutants of TNF-RI carrying deletions of the death domain (DD), internalization domain (TRID), and neutral sphingomyelinase domain (NSD), respectively, retransfected in cells devoid of TNF-RI and TNF-RII, constituted distinct tools to evaluate the specific role of each domain in downstream apoptotic signaling events. Deletion of DD abolishes activation of caspase-3 and -9 and apoptosis following treatment with TNF because of blocked assembly of the DISC.

The role of receptor internalization in CD95 signaling.

Activation of the cell surface CD95 receptor triggers a cascade of signaling events, including assembly of the death-inducing signaling complex (DISC), that culminate in cellular apoptosis. In this study, we demonstrate a general requirement of receptor internalization for CD95 ligand-mediated DISC amplification, caspase activation and apoptosis in type I cells. Recruitment of DISC components to the activated receptor predominantly occurs after the receptor has moved into an endosomal compartment and blockade of CD95 internalization impairs DISC formation and apoptosis.

Targeting mature T cell leukemia: new understanding of molecular pathways.

The best studied T cell leukemia/lymphoma from a genetic and biochemical point of view is T-cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL). This neoplasia commonly shows chromosomal rearrangements at 14q32.1 including translocations [t(14;14)(q11;q32), t(7;14)(q35;q32)], and inversions [inv(14)(q11;q32)].