Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

<p>Abstract</p> <p>Background</p> <p>Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines.</p> <p>Methods</p> <p>Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch <it>t </it>test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest.</p> <p>Results</p> <p>Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known <it>JUNB</it>, <it>FOS </it>and <it>TP63</it>, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as <it>SERPINE1 </it>and <it>MMP7</it>, are known to regulate metastasis. Twenty-one genes including <it>VEGFA </it>and <it>ID2 </it>have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis.</p> <p>Conclusion</p> <p>The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in the metastatic phenotype induced by hypoxia.</p

Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults

The clinical efficacy and safety of sorivudine as treatment for acute cutaneous tester in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study, A total of 125 patients with laboratory-confirmed tester rash present for less than or equal to 72 h were assigned treatment with either 40 mg of sorivudine once daily or 800 mg of acyclovir five times daily, both taken orally for 7 days, Patients were assessed daily until all lesions crusted and then monthly for 6 months for postherpetic neuralgia (PHN) and for 12 months for recurrent or new episodes of tester, Sorivudine significantly shortened the median period of new vesicle formation from 3.0 to 4.0 days (log rank P = .0001), Sorivudine was effective regardless of duration of rash before treatment, Zoster recurrences and new episodes were experienced by fewer patients assigned sorivudine (11%) than acyclovir (26%, P = .037), No differences were seen in incidence, severity, or duration of either acute neuritis or PHN, Both treatments were well tolerated