Renal primitive neuroectodermal tumor: does age at diagnosis impact outcomes?

Primitive neuroectodermal tumor (PNET) of the kidney is a rare and highly malignant neoplasm. The median age for renal PNET is 27 years but it can be seen also in a wide age range between 3 and 78 years. We performed a Medline search for the term renal PNET and identified 79 cases up till December of 2010. We report here a new case of renal PNET and a literature review for published data for evaluation of clinicopathological prognostic factors, with an emphasis on prognosis in two groups of adults and children-adolescents: 18 years of age or under and over 18 years

Attenuated p53 activation in tumour-associated stromal cells accompanies decreased sensitivity to etoposide and vincristine

Alterations in the tumour suppressor p53 have been reported in tumour-associated stromal cells; however, the consequence of these alterations has not been elucidated. We investigated p53 status and responses to p53-activating drugs using tumour-associated stromal cells from A375 melanoma and PC3 prostate carcinoma xenografts, and a spontaneous prostate tumour model (TRAMP). p53 accumulation after treatment with different p53-activating drugs was diminished in tumour-associated stromal cells compared to normal stromal cells. Tumour-associated stromal cells were also less sensitive to p53-activating drugs – this effect could be reproduced in normal stromal cells by p53 knockdown. Unlike normal stromal cells, tumour stromal cells failed to arrest in G2 after etoposide treatment, failed to upregulate p53-inducible genes, and failed to undergo apoptosis after treatment with vincristine. The lower levels of p53 in tumour stromal cells accompanied abnormal karyotypes and multiple centrosomes. Impaired p53 function in tumour stroma might be related to genomic instability and could enable stromal cell survival in the destabilising tumour microenvironment

EigenTHREADER: analogous protein fold recognition by efficient contact map threading

Motivation: Protein fold recognition when appropriate, evolutionarily-related, structural templates can be identified is often trivial and may even be viewed as a solved problem. However in cases where no homologous structural templates can be detected, fold recognition is a notoriously difficult problem (Moult et al., 2014). Here we present EigenTHREADER, a novel fold recognition method capable of identifying folds where no homologous structures can be identified. EigenTHREADER takes a query amino acid sequence, generates a map of intra-residue contacts, and then searches a library of contact maps of known structures. To allow the contact maps to be compared, we use eigenvector decomposition to resolve the principal eigenvectors these can then be aligned using standard dynamic programming algorithms. The approach is similar to the Al-Eigen approach of Di Lena et al. (2010), but with improvements made both to speed and accuracy. With this search strategy, EigenTHREADER does not depend directly on sequence homology between the target protein and entries in the fold library to generate models. This in turn enables EigenTHREADER to correctly identify analogous folds where little or no sequence homology information is. Results: EigenTHREADER outperforms well-established fold recognition methods such as pGenTHREADER and HHSearch in terms of True Positive Rate in the difficult task of analogous fold recognition. This should allow template-based modelling to be extended to many new protein families that were previously intractable to homology based fold recognition methods. Availability and implementation: All code used to generate these results and the computational protocol can be downloaded from https://github.com/DanBuchan/eigen_scripts. EigenTHREADER, the benchmark code and the data this paper is based on can be downloaded from: http://bioinfadmin.cs.ucl.ac.uk/downloads/eigenTHREADER/

Intermediate filament proteins and actin isoforms as markers for soft tissue tumor differentiation and origin: II. Rhabdomyosarcomas

A series of 15 rhabdomyosarcomas was examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE) and indirect immunofluorescence, the latter using monoclonal or affinity-purified polyclonal antibodies to desmin, vimentin, α-smooth muscle and α-sarcomeric (α-sr) actins. By light microscopy, the authors diagnosed 1 botrioid, 1 alveolar, and 7 embryonal rhabdomyosarcomas, 4 pleomorphic spindle cell sarcomas, and 2 spindle cell sarcomas, one nondistinct, the other with a hemangiopericytomatous pattern. By transmission electron microscopy, 13 neoplasms disclosed rhabdomyoblastic differentiation; the remaining 2, myogenic differentiation. By immunofluorescence microscopy, all neoplasms expressed vimentin and α-sr actin, 12 expressed, in addition, desmin, and 1 expressed α-smooth muscle actin. Among the 11 neoplasms studied by means of 2D-GE, 7 demonstrated an α-actin spot, while 4 showed only β and γ spots. One tumor disclosed, in addition to α, β, and γ spots, a spot with a molecular weight corresponding to actin, but more acidic than α-actins. This study demonstrates that α-sr actin antibody represents a valuable marker for the diagnosis of rhabdomyosarcoma, because it was present in all neoplasms, including the one negative for desmin. This antibody further allowed the recognition of pleomorphic variants and morphologically atypical forms of rhabdomyosarcomas. The presence of α-smooth muscle actin in 1 case of rhabdomyosarcoma suggests that this actin isoform may be expressed during skeletal muscle differentiation