Metatypical basal cell carcinoma: a clinical review

Background. Metatypical cell carcinoma can be considered as a new entity of skin cancer, being an intermediate typology between basal cell carcinomas and squamous cell carcinomas. The behaviour of the metatypical cell carcinoma lies between these two varieties of skin cancer. It is difficult to perform a differential diagnosis based on morphological and clinical features - therefore it is only possible by accurate histology. Methods. The authors have retrospectively analysed clinical records of 240 patients who were affected by metatypical skin cancer and who were treated by surgery, radiotherapy and chemotherapy. Results. MTC affected more males than females (62.5% vs 37.5%) than males. The most affected site was the cervicofacial area, 71.7%; then the trunk, 10%; the limbs, 9.6%; the scalp 3.7%; and other regions 5%. A recurrence occurred in 24 cases (10%), mainly in head and neck area. Conclusion. In this manuscript, the authors have emphasised the importance of conducting a differential diagnosis, and the importance of the specific treatment for metatypical skin cancer, even though more clinical studies and long-term follow-ups are required before establishing specific guidelines. © 2008 Tarallo et al; licensee BioMed Central Ltd

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

Variable Thermal Stress Tolerance of the Reef-Associated Symbiont-Bearing Foraminifera \u3cem\u3eAmphistegina\u3c/em\u3e Linked to Differences in Symbiont Type

Adaptation, acclimatization and symbiont diversity are known to regulate thermal tolerance in corals, but the role of these mechanisms remains poorly constrained in other photosymbioses, such as large benthic foraminifera (LBFs), which are known to bleach at temperatures that are likely to be exceeded in the near future. LBFs inhabit a broad range of shallow-water settings. Within species, differences in thermal tolerance have been found among populations from different habitats, but it is not clear whether such differences occur among LBFs inhabiting similar habitats, but differing in other aspects, such as symbiont type. To this end, we compared responses to thermal stress in specimens from a population of Amphistegina lessonii, an abundant Indo-Pacific species, to specimens of Amphistegina gibbosa, its Atlantic counterpart, from a similar environment but two different water depths (5 and 18 m). Test groups of each species were exposed in a common experiment to three thermal stress scenarios over a four-week period. Growth, respiration, mortality and motility were measured to characterize the holobiont response. Coloration, photosynthesis and chlorophyll a content were measured to determine the response of the endosymbiotic diatoms. The photosymbionts were characterized by genetic fingerprinting. Our results show that, although groups of A. gibbosa were collected from different habitats, their responses were similar, indicating only marginally higher tolerance to thermal peaks in specimens from the shallower site. In contrast, species-specific differences were stronger, with A. lessonii showing higher tolerance to episodic stress and less pronounced impacts of chronic stress on motility, growth and photosymbiont performance. These interspecies variations are consistent with the presence of different and more diverse symbiont assemblages in A. lessonii compared with A. gibbosa. This study demonstrates the importance of considering symbiont diversity in the assessment of intra- and interspecific variations in stress responses in LBFs