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Abstract Background Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses. Methods In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes in vitro with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent in vivo experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators. Results Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-α and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001–1 μM. We also demonstrate that in vitro neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner. Conclusion These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.

Biomarkers in the clinical oncology field can have tremendous therapeutic impact especially if the marker is detected before clinical symptoms. This impact can be extended to the evaluation of clinical oncology treatments allowing evaluation of potential compounds to determine their efficacy in the disease treatment. The discovery of clinical biomarkers can consume time, resources and costs. Therefore, it is important that the most effective strategies are employed to discover these biomarkers. These strategies may include the integration of available genomic, proteomic and histopathological technologies, which could reduce the costs and aid in the validation of the biomarker. Certainly the type of biomarker needed to address a particularly defined problem will drive the type of technology. However, a single biomarker to diagnose a specific cancer can be as elusive as relying on a single technology. This review examines some of the technologies used to discover biomarkers and presents the use of combinatorial technical synergies to discover and validate potential clinical oncology biomarkers.

Progression of immature CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint to the CD4(+)CD8(+) stage requires activation of the pre-TCR complex; however, few of the DNA-binding proteins that serve as molecular effectors of those pre-TCR signals have been identified. We demonstrate in this study that members of the early growth response (Egr) family of transcription factors are critical effectors of the signals that promote this developmental transition. Specifically, the induction of three Egr family members (Egr1, 2, and 3) correlates with pre-TCR activation and development of CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint. Enforced expression of each of these Egr factors is able to bypass the block in thymocyte development associated with defective pre-TCR function. However, Egr family members may play somewhat distinct roles in promoting thymocyte development, because there are differences in the genes modulated by enforced expression of particular Egr factors. Finally, interfering with Egr function using dominant-negative proteins disrupts thymocyte development from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage. Taken together, these data demonstrate that the Egr proteins play an essential role in executing the differentiation program initiated by pre-TCR signaling.