The functional cancer map: A systems-level synopsis of genetic deregulation in cancer

<p>Abstract</p> <p>Background</p> <p>Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies.</p> <p>Methods</p> <p>Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors.</p> <p>Results</p> <p>We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'.</p> <p>Conclusion</p> <p>The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.</p

The smear layer:a phenomenon in root canal therapy.

WOS: A1995RM09200005PubMed ID: 8626198When the root canals are instrumented during endodontic therapy, a layer of material composed of dentine, remnants of pulp tissue and odontoblastic processes, and sometimes bacteria, is always formed on the canal walls. This layer has been called the smear layer. It has an amorphous, irregular and granular appearance under the scanning electron microscope. The advantages and disadvantages of the prescence of smear layer, and whether it should be removed or not from the instrumented root canals, are still controversial. It has been shown that this layer is not a complete barrier to bacteria and it delays but does not abolish the action of endodontic disinfectants. Endodontic smear layer also acts as a physical barrier interfering with adhesion and penetration of sealers into dentinal tubules, in turn, it may affect the sealing efficiency of root canal obturation. When it is not removed, the durability of the apical and coronal seal should be evaluated over a long period. If smear layer is to be removed, EDTA and NaOCl solutions have been shown to be effective, among various irrigation solutions and techniques, including ultrasonics, that have been tested. Once this layer is removed, it should be borne in mind that there is a risk of reinfecting dentinal tubules if the seal fails. Further studies are needed to establish the clinical importance of the absence or presence of smear layer