Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype.

Hypoxia confers resistance to common cancer therapies, however, it has also has been shown to result in genetic alterations which may allow a survival advantage and increase the tumorigenic properties of cancer cells. Additionally, it may exert a selection pressure, allowing expansion of tumor cells with a more aggressive phenotype. To further assess the role of hypoxia in malignant progression in prostate cancer we exposed human androgen dependent prostate cancer cells (LNCaP) to cycles of chronic hypoxia and isolated a subline, LNCaP-H1. This article describes the partial characterization of this cell line. The LNCaP-H1 subline showed altered growth characteristics and exhibited androgen independent growth both in vitro and in vivo. Furthermore, these cells were resistant to mitochondrial-mediated apoptosis, probably since the endogenous levels of Bax was lower and Bcl-2 higher than in the parental LNCaP cells. Microarray analysis revealed that a complex array of pathways had differential gene expression between the 2 cell lines, with LNCaP-H1 cells exhibiting a genetic profile which suggests that they may be more likely metastasize to distant organs, especially bone. This was supported by an in vitro invasion assay, and an in vivo metastasis study. This study shows that hypoxia can select for androgen independent prostate cancer cells which have a survival advantage and are more likely to invade and metastasize.

Annotated Chromosome Maps for Renal Disease

A combination of linkage analyses and association studies are currently employed to promote the identification of genetic factors contributing to inherited renal disease. We have standardized and merged complex genetic data from disparate sources, creating unique chromosomal maps to enhance genetic epidemiological investigations. This database and novel renal maps effectively summarize genomic regions of suggested linkage, association, or chromosomal abnormalities implicated in renal disease. Chromosomal regions associated with potential intermediate clinical phenotypes have been integrated, adding support for particular genomic intervals. More than 500 reports from medical databases, published scientific literature, and the World Wide Web were interrogated for relevant renal-related information. Chromosomal regions highlighted for prioritized investigation of renal complications include 3q13-26, 6q22-27, 10p11-15, 16p11-13, and 18q22. Combined genetic and physical maps are effective tools to organize genetic data for complex diseases. These renal chromosome maps provide insights into renal phenotype-genotype relationships and act as a template for future genetic investigations into complex renal diseases. New data from individual researchers and/or future publications can be readily incorporated to this resource via a user-friendly web-form accessed from the website: www.qub.ac.uk/neph-res/CORGI/index.php.

Deflation based nonlinear canonical correlation analysis

This paper introduces two new techniques for determining nonlinear canonical correlation coefficients between two variable sets. A genetic strategy is incorporated to determine these coefficients. Compared to existing methods for nonlinear canonical correlation analysis (NLCCA), the benefits here are that the nonlinear mapping requires fewer parameters to be determined, consequently a more parsimonious NLCCA model can be established which is therefore simpler to interpret. A further contribution of the paper is the investigation of a variety of nonlinear deflation procedures for determining the subsequent nonlinear canonical coefficients. The benefits of the new approaches presented are demonstrated by application to an example from the literature and to recorded data from an industrial melter process. These studies show the advantages of the new NLCCA techniques presented and suggest that a nonlinear deflation procedure should be considered. (c) 2006 Elsevier B.V. All rights reserved.