Part of the book: Advancements in Tumor Immunotherapy and Cancer Vaccines
Part of the book: Melanoma
This chapter describes the main deregulated intracellular pathways at both genetic and proteomic levels that are found in three main skin cancers: basal cell carcinoma, squamous cell carcinoma and melanoma. In basal cell carcinoma, the main intracellular signaling pathways is the Sonic Hedgehog pathway, while in squamous cell carcinoma, it is the p53 pathway. However, in both nonmelanoma skin cancers, these major pathways trigger cross-activation with other important ones. In melanoma, mitogen-activated protein kinase pathway and PI3K/Akt pathways are deeply deregulated, and moreover due to the disease complexity, BRAF, RAS (N/H/K), NF1 and Triple-WT melanoma subtypes need additional molecular stratification. The stage in which photodynamic therapies’ clinical application is in the treatment of these diseases is another subject tackled by the chapter. Thus, if basal cell carcinoma and squamous cell carcinoma possess in their therapeutical armamentarium photodynamic therapies approach, melanoma, with its particularities, still needs thorough molecular investigations to adapt this particular therapy. Based on the accumulated knowledge on pathological intracellular pathways, the chapter describes the molecular details that reside in applying photodynamic therapy. In vivo and in vitro models of cutaneous malignancy and photodynamic therapies’ molecular events are further detailed.
Part of the book: Photomedicine
Squamous cell carcinoma (SCC) is the second most frequent non-melanoma skin cancer (NMSC) and carries with it a significant psychosocial and economic burden for both patients and health-care systems. Known risk factors for SCC include chronic ultraviolet (UV) exposure, chronic wounds and inflammation, exposure to certain chemicals and immunosuppression. The considerable risk of SCC recurrence and metastasis has driven the need for the discovery of new molecules that could explain the initiation and biological behavior of this type of NMSC. In this respect, proteomic research techniques have rapidly evolved and adapted in order to connect missing links and single out distinctive skin cancer biosignatures. Proteomic analysis of normal, dysplastic, and malignant keratinocytes appears to be promising in respect to SCC biomarker discovery, with the potential to aid in risk assessment, early detection, disease progression and development of novel targeted therapeutic agents. Identifying changes in the keratinocyte proteome pattern from normal to inflammatory and malignant cells will lead to the discovery of novel SCC biomarkers that could represent valuable tools for patient screening, diagnosis, management and follow-up.
Part of the book: Human Skin Cancers
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
Psoriasis is a chronic inflammatory skin disorder with high immunological background caused by a complex interplay between an altered immune system, genetic factors, autoantigens, lifestyle, and environmental factors. Extensive literature in recent years highlighted the crucial role played by the immune system in the pathogenesis of this pathology. Although it is unequivocally accepted that psoriasis is a T-cell mediated autoimmune condition, both innate and specific immune cells are highly involved in the pathogenesis of psoriasis. The aberrant interactions between immune cells and resident hyper-proliferative keratinocytes are mediated by immune and non-immune related molecules which lead to amplification of the local immune responses, that maintain the chronic inflammatory status. In this chapter, we will highlight the immune molecules resident in the psoriatic tissue or appending to the blood circulation that can indicate the prognosis of this systemic autoimmune disease. Moreover, we will focus on immune cells resident or circulating ones that can pinpoint the clinical evolution of the psoriatic disease. All these data can be developed in immune markers patterns that aid psoriasis diagnosis and/or future (immune)therapies.
Part of the book: Psoriasis