Melanoma Brain Metastases in the Era of Target Therapies: An Overview.

Malignant melanoma is the third most common type of tumor that causes brain metastases. Patients with cerebral involvement have a dismal prognosis and their treatment is an unmet medical need. Brain involvement is a multistep process involving several signaling pathways such as Janus kinase/signal Transducer and Activator of Transcription (JAK/STAT), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Vascular Endothelial Growth Factor and Phosphatase and Tensin Homolog (PTEN).

BRAF-inhibitors can exert control of disease in BRAF T599I mutated melanoma: a case report.

BRAF signaling is involved in melanoma growth in more than half of metastatic patients. In the last few years, new drugs that block this pathway have significantly improved the outcomes of patients with metastatic melanoma. Ninety percent of BRAF mutations involve exon 15, and the most frequent, V600E, results from the amino acid change from valine (V) to glutamic acid (E).

Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells.

The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses. Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter Their stemness potential was confirmed by limiting dilution assays. We explored the sensitivity of eGFP mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, First, we treated MCs with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells.

Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features.

Purpose: We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC).

Experimental Design: We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4.

In melanocytic lesions the fraction of BRAF V600E alleles is associated with sun exposure but unrelated to ERK phosphorylation.

BRAF(V600E) mutation has been frequently reported in different types of melanocytic lesions, but its role in melanomagenesis is poorly understood, having been associated with either the proliferative-induced MAPK pathway activation or the acquisition of oncogene-driven senescence. The presence of BRAF alterations has been related to sun exposure, although the molecular mechanisms underlying this event are only partly known. To elucidate the relationships among BRAF/NRAS alterations, MAPK pathway activation, and sun exposure, we examined 22 acquired nevi and 18 cutaneus melanomas from 38 patients.

Clear cell sarcoma (malignant melanoma of soft parts) and sentinel lymph node biopsy.

Clear cell sarcoma of the tendons and aponeuroses is an aggressive, rare soft tissue tumour that occurs predominantly in the extremities of young adults. Although it appears to be histogenetically related to melanoma, its clinical behaviour resembles soft tissue sarcoma. Prognosis is reported to be poor due to the great propensity of regional and distant metastases.

Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease.

Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.