Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis.

There is a fine balance between inflammation and tumorigenesis. While environmentally induced inflammatory condition can precede a malignant transformation, in other cases an oncogenic change of unknown origin can induce an inflammatory microenvironment that promotes the development of tumors. Regardless of its origin, maintaining the inflammation milieu has many tumor-promoting effects. As a result, inflammation can aid the proliferation and survival of malignant cells, can promote angiogenesis and metastasis, can down-regulate innate/adaptive immune responses, and can alter responses to hormones and chemotherapeutic agents. There is an abundance of studies unveiling molecular pathways of cancer-related inflammation; this wealth of information brings new insights into biomarkers domain in the diagnosis and treatment improvement pursue. In cutaneous tissue there is an established link between tissue damage, inflammation, and cancer development. Inflammation is a self-limiting process in normal healthy physiological conditions, while tumorigenesis is a complex mechanism of constitutive pathway activation. Once more, in cutaneous melanoma, there is an unmet need for inflammatory biomarkers that could improve prognostication. Targeting inflammation and coping with the phenotypic plasticity of melanoma cells represent rational strategies to specifically interfere with metastatic progression. We have shown that there is a prototype of intratumor inflammatory infiltrate depicting a good prognosis, infiltrate that is composed of numerous T cells CD3+, Langerhans cells, few/absent B cells CD20+ and few/absent plasma cells. Circulating immune cells characterized by phenotype particularities are delicately linked to the stage melanoma is diagnosed in. Hence circulatory immune sub-populations, with activated or suppressor phenotype would give the physician a more detailed immune status of the patient. A panel of tissue/circulatory immune markers can complete the immune status, can add value to the overall prognostic of the patient and, as a result direct/redirect the therapy choice. The future lies within establishing low-cost, affordable/available, easily reproducible assays that will complete the pre-clinical parameters of the patient.

Proteomics focusing on immune markers in psoriatic arthritis.

The immune-pathogenesis of psoriatic arthritis represents a subject of intense research, as a still unknown factor can trigger the chronic inflammation that, upon a defective immune terrain, generates this auto-immune/auto-inflammatory condition. The pathogenesis complexity of psoriatic arthritis resides in the psoriatic synovitis milieu, where intricate immune relations are emerging during disease development. Innate immune response generates inflammatory cytokines driving effectors functions for immune and non-immune cells that sustain the chronical character of the synovitis. Herein, we review the updated information regarding biomarkers/immune markers that sustain the heterogeneity and complexity of psoriatic arthritis pathogenesis, this complexity leading to multifaceted methodological approaches for disease investigation. New immune proteomic or genomic biomarkers can enlarge and identify new therapeutic targets.

Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy.

BACKGROUND: Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential. RESULTS: The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude. CONCLUSIONS: Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.

Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy

BACKGROUND: Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential. RESULTS: The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude. CONCLUSIONS: Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.

Critical physiological and pathological functions of Forkhead Box O tumor suppressors.

The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases.

Serum markers in skin melanoma--preliminary study.

Skin melanoma presents the strongest metastatic capacity and the highest mortality rate of all types of skin cancer, being one of the most aggressive forms of human cancer. Although melanoma represents only 4% of skin cancers, it accounts for 80% of skin cancer deaths. The aim of this study was the investigation of two specific serum markers for melanoma: S100B and melanoma inhibitory activity in relation to disease development. The longitudinal study was performed on 51 patients diagnosed with skin melanoma and 72 healthy volunteers. For serum S100B and MIA measurement standard ELISA was used. The serum concentration of S100B was found significantly different from normal values only in patients in stage IV, in contrast to MIA, where significant differences occurred as early as stage II. The dynamics of the studied serum markers was in accordance with the skin melanoma evolution, especially for serum MIA. Only both increased S100B and MIA serum levels can indicate the disease evolution towards advanced stages and appearance of the metastatic processes.