Winston Patrick Kuo

The ubiquitous cytokine transforming growth factor-beta1 (TGF-beta1) is one of the most potent metastatic inducers. Functional interactomic mapping using high-throughput proteomic and genomic data provides valuable insights into the regulation of tumor suppressive and metastatic attributes of TGF-beta1. Polarity changes of the TGF-beta1 interactome at a given time contributes to these contrasting effects. Differential expression profiles of pivotal interactomic nodes contribute to these polarity changes. These insights are of immense value in the development of effective cancer therapeutics. Moreover, TGF-beta1 interactomic nodes are useful in discovering novel cancer biomarkers. This review describes an initial version of the TGF-beta1 interactome in relation to tumor progression and metastasis. Thus, this review embodies an important step towards the mapping of comprehensive and individualized TGF-beta1 interactomes that will assist in the development of personalized cancer therapeutics.

Background: Peripheral arterial disease (PAD), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. However, mechanisms underlying the genesis and progression of the disease are far from clear. Genome-wide gene expression profiling of clinical samples may represent an effective approach to gain relevant information. Results: After histological classification, a total of 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions and 5 normal femoral arteries, were profiled using Affymetrix microarray platform. Following real-time RT-PCR validation, different algorithms of gene selection and clustering were applied to identify differentially expressed genes. Under a stringent cutoff, i.e., a false discovery rate (FDR) <0.5%, we found 366 genes were differentially regulated in intermediate lesions and 447 in advanced lesions. Of these, 116 genes were overlapped between intermediate and advanced lesions, including 68 up-regulated genes and 48 down-regulated ones. In these differentially regulated genes, immune/inflammatory genes were significantly up-regulated in different stages of PAD, (85/230 in intermediate lesions, 37/172 in advanced lesions). Through literature mining and pathway analysis using different databases such as Gene Ontology (GO), and the Kyoto Encyclopedia of Gene and Genomics (KEGG), genes involved in immune/inflammatory responses were significantly enriched in up-regulated genes at different stages of PAD(p < 0.05), revealing a significant correlation between immune/inflammatory responses and disease progression. Moreover, immune-related pathways such as Toll-like receptor signaling and natural killer cell mediated cytotoxicity were particularly enriched in intermediate and advanced lesions (P < 0.05), highlighting their pathogenic significance during disease progression. Conclusion: Lines of evidence revealed in this study not only support previous hypotheses, primarily based on studies of animal models and other types of arterial disease, that inflammatory responses may influence the development of PAD, but also permit the recognition of a wide spectrum of immune/inflammatory genes that can serve as signatures for disease progression in PAD. Further studies of these signature molecules may eventually allow us to develop more sophisticated protocols for pharmaceutical interventions.

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy. The five-year survival rate remains largely unchanged for the past 40 years. Early diagnosis has been shown to correlate with increased survival, based on cytologic changes. In order to improve our current treatment strategies for OSCC, it is necessary to understand the genetic and molecular networks underlying this disease. In this preliminary study, we illustrate the application of DNA microarrays to study OSCC. Using computational and statistical algorithms, we were able to differentiate (or classify) "cancer" and "normal" samples based on the behavior of the gene expression profiles. We found 651 genes to be associated with cancer. This article describes a preliminary study of current developments from the Human Genome Project (HGP) and its application to OSCC.