Distinction between familial and sporadic forms of colorectal cancer showing DNA microsatellite instability

Attempts to classify colorectal cancer into subtypes based upon molecular characterisation are overshadowed by the classical stepwise model in which the adenoma-carcinoma sequence serves as the morphological counterpart. Clarity is achieved when cancers showing DNA microsatellite instability (MSI) are distinguished as sporadic MSI-low (MSI-L), sporadic MSI-high (MSI-H) and hereditary non-polyposis colorectal cancer (HNPCC). Divergence of the 'methylator' pathway into MSI-L and MSI-H is at least partly determined by the respective silencing of MGMT and hMLH1. Multiple differences can be demonstrated between sporadic and familial (HNPCC) MSI-H colorectal cancer with respect to early mechanisms, evolution, molecular characterisation, demographics and morphology. By acknowledging the existence of multiple pathways, rapid advances in the fields of basic and translational research will occur and this will lead to improved strategies for the prevention, early detection and treatment of colorectal cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

Valuing of firm's prior knowledge: A measure of knowledge distance

Knowledge, especially scientific and technological knowledge, grows according to knowledge trajectories and guideposts that make up the prior knowledge of an organization. We argue that these knowledge structures and their specific components lead to successful innovation. A firm's prior knowledge facilitates the absorption of new knowledge, thereby renewing a firm's systematic search, transfer and acquisition of knowledge and capabilities. In particular, the exponential growth in biotechnology is characterized by the convergence of disparate scientific and technological knowledge resources. This paper examines the shift from protein-based to DNA-based diagnostic technologies as an example, to quantify the value of a firm's prior knowledge using relative values of knowledge distance. The distance between core prior knowledge and the rate of transition from one knowledge system to another has been identified as a proxy for the value a firm's prior knowledge. The overall difficulty of transition from one technology paradigm to another is discussed. We argue this transition is possible when the knowledge distance is minimal and the transition process has a correspondingly high value of absorptive capacities. Our findings show knowledge distance is a determinant of the feasibility, continuity and capture of scientific and technological knowledge. Copyright © 2003 John Wiley & Sons, Ltd.