Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

CHIC-CDR: A repository for managing multi-modality clinical data and its application to in-silico oncology

<p>Access to high-quality clinical data is a prerequisite for medical data analysis and in-silico medicine. Data drives the development of research questions, feeds computational algorithms, and provides the evidence base for validating complex disease models which form the basis for personalized simulations in the future. However, provision of uniform access to, and secondary use of, clinical treatment or study data is hampered by the data's intrinsic characteristics: its confidential nature, and its heterogeneity in terms of sources, quality and information.</p> <p>The clinical data repository (CDR) has been designed to address these critical issues by providing a unique access-point to clinical data in compliance with the European medico-legal framework. CDR has been initiated as an exchange platform for medical images, but was quickly extended to other health-related data, in particular clinical treatment & follow-up, histological and genetic information. Data access is granted based on a role-based policy within a single-sign-on security framework. CDR also supports the (pseudo-)anonymization process and provides facilities for semantic annotation of data during and after the upload process, enabling semantically mediated queries for improved data discovery.<br> CDR has been developed by SICAS (http://www.si-cas.com) and the University of Bern (http://www.istb.unibe.ch/) with support from the EU CHIC (http://chic-vph.eu/) and Co-Me (http://co-me.ch) projects.<br>  <br> This presentation outlines the principal requirements and main challenges related to the sharing of heterogeneous clinical data for research purposes, discusses properties of a generic solution, and details implementation and application in the CHIC context.</p

The Virtual Skeleton Database: An Open Access Repository for Biomedical Research and Collaboration

Background: Statistical shape models are widely used in biomedical research. They are routinely implemented for automatic image segmentation or object identification in medical images. In these fields, however, the acquisition of the large training datasets, required to develop these models, is usually a time-consuming process. Even after this effort, the collections of datasets are often lost or mishandled resulting in replication of work. Objective: To solve these problems, the Virtual Skeleton Database (VSD) is proposed as a centralized storage system where the data necessary to build statistical shape models can be stored and shared. Methods: The VSD provides an online repository system tailored to the needs of the medical research community. The processing of the most common image file types, a statistical shape model framework, and an ontology-based search provide the generic tools to store, exchange, and retrieve digital medical datasets. The hosted data are accessible to the community, and collaborative research catalyzes their productivity. Results: To illustrate the need for an online repository for medical research, three exemplary projects of the VSD are presented: (1) an international collaboration to achieve improvement in cochlear surgery and implant optimization, (2) a population-based analysis of femoral fracture risk between genders, and (3) an online application developed for the evaluation and comparison of the segmentation of brain tumors. Conclusions: The VSD is a novel system for scientific collaboration for the medical image community with a data-centric concept and semantically driven search option for anatomical structures. The repository has been proven to be a useful tool for collaborative model building, as a resource for biomechanical population studies, or to enhance segmentation algorithms