Cutaneous melanoma is an aggressive tumor with increasing incidence worldwide. Recent development of promising treatments based on immune checkpoints blockade in cancer immunotherapy or signal transduction inhibitors (B-Raf enzyme inhibitor and MEK inhibitor) requires identification of new biomarkers predictive of either prognosis and/or therapeutic response. Dynamic interaction between melanoma and normal host cells influences tumor progression; proteins regulating connections between melanoma cells and extracellular matrix facilitate tumor invasion and dissemination. We discuss the various functions of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in melanoma and their possible role as prognostic and/or predictive biomarkers. We also studied the correlation with regression of expression of several MMPs and TIMPs in melanoma; regressed and nonregressed components are in fact different tumor subclones; in some cases of melanoma with regression (with a specific morphology), the biologic aggressiveness of the tumor and implicitly the overall prognosis may be more favorable than that of melanoma without regression thus offering the possibility of a supplemental stratification of these patients beyond AJCC staging.
Part of the book: The Role of Matrix Metalloproteinase in Human Body Pathologies
Diagnosis of autoimmune diseases is crucial for the clinician and the patient alike. The immunoassay techniques most commonly used for this purpose are immunohistochemistry, ELISA, and Western blotting. For the detection of more specific biomarkers or the discovery of new ones for diagnostic purposes and as therapeutic targets, microarray techniques are increasingly used, for example, protein microarray, Luminex, and in recent years, surface plasmon resonance imaging. All of these technologies have undergone changes over time, making them easier to use. Similar technologies have been invented but responding to specific requirements for both diagnostic and research purposes. The goals are to study more analytes in the same sample, in a shorter time, and with increased accuracy. The reproducibility and reliability of the results are also a target pursued by manufacturers. In this chapter, we present these technologies and their utility in the diagnosis of immunogenetic diseases.
Part of the book: Immunogenetics
In the normal peripheral nervous system, Schwann cells (SCs) are present in two different states of differentiation: myelinating SCs that surround large-caliber axons, forming myelin sheath, and non-myelinating SCs that surround more small-caliber axons forming Remak bundles. Under pathological conditions (injury or inflammation), SCs, with a remarkable plasticity, undergo phenotypic transformations, downregulating the production of myelin proteins mRNAs, upregulating neurotrophic factors and cytokines, thus promoting the axonal regeneration. Dedifferentiated SCs activate the protein degradation, participating in the demyelination process and clearance of myelin debris; attract macrophages helping wound healing; proliferate to replace lost cells; guide axonal growth; and protect against secondary axonal damage. Thus, SC functions have a critical contribution to regeneration processes that occur in peripheral nerve after injury.
Part of the book: Demyelination Disorders