In a recent paper published online first in October 20th in the Journal of Experimental Medicine a group of French researchers have found a new antigenic protein that can be very important in the immune response against melanoma cells.

They studied a patient that had remained free of melanoma 10 years after the infusion of a clone of tumor-infiltrating lymphocytes (TIL). These T-cells cells are obtained from the tumor of a patient with late-stage melanoma. They are cultured in vivo, expanded in sufficient numbers, and then infused to different melanoma patients. In this patient the researchers found that the T-cell line recognized a specific antigen that could be found in all melanoma cell lines and, to a lower extent, melanocytes. They named this protein MELOE-1 (melanoma-over expressed antigen-1).

Subsequently, they found that 5 out of 9 patients treated with TILs that did not had relapse had been infused with TILs that contained MELOE-1–specific T cells. In contrast none of the 21 patients treated with TILs who relapsed had been infused with MELOE-1–specific T cells.

These interesting findings suggest that MELOE-1 can be a promising antigenic target for immunotherapy of melanoma in the near future. (more…)

Two recent separate studies that have been published on-line in the journal Nature Genetics have identified new genetic risk factors for male-pattern baldness. Both studies have found similar results, and they found that there is a susceptibility locus for male-pattern baldness at chromosome 20p11. These studies add a new candidate gene for androgenetic alopecia. Previous studies had shown that variants in the androgen receptor gene on the X chromosome were associated with androgenetic alopecia. These investigators found that the combination of both gene variants (the one on chromosome X and the new one found in chromosome 20) were present in 1 out of 7 caucasian men, and that this increased seven-fold their risk of having androgenetic alopecia.

The gene on chromosome 20p11 has not been identified but it is probable that it harbors an androgen-independent pathway in androgenetic alopecia that may be the target of future therapies. (more…)

Skin fibrosis is the common hallmark of several systemic diseases that cause major disability to patients. These include systemic sclerosis (scleroderma), sclerodermatous graft-versus-host disease, and nephrogenic systemic fibrosis. Currently there is no standard effective therapy for this group of diseases, as anti-fibrotic therapies are not yet available.

Recently, selective inhibitors of intracellular tyrosine kinases have been evaluated as novel antifibrotic approaches. Imatinib mesylate (Gleevec, Novartis) is a small molecule tyrosine kinase inhibitor that blocks two major pro-fibrotic pathways activated in fiibrosing conditions by inhibiting two important tyrosine kinases: c-Abl, a downstream signal in the TGF-beta and PDGF pathways, and the PDGF receptors. Experimental studies have shown that imatinib inhibits collagen synthesis, prevents experimental fibrosis induced by bleomycin, and i by a reduction in thenhibits the proliferation of normal and scleroderma fibroblasts.

Several case reports suggesting the efficacy of this drug in systemic sclerosis, sclerodermatous graft-versus-host disease, and nephrogenic systemic fibrosis have been published in the last few months. For this reason several clinical trials have been started and we will have to wait for these results to know if we are entering in a promising new era of anti-fibrotic therapies.

1. Sfikakis PP, Gorgoulis VG, Katsiari CG, Evangelou K, Kostopoulos C, Black CM. Imatinib for the treatment of refractory, diffuse systemic sclerosis. Rheumatology (Oxford). 2008; 47:735-7.

2. van Daele PL, Dik WA, Thio HB, van Hal PT, van Laar JA, Hooijkaas H, van Hagen
PM. Is imatinib mesylate a promising drug in systemic sclerosis? Arthritis Rheum 2008; 58:2549-52.

3. Magro L, Catteau B, Coiteux V, Bruno B, Jouet JP, Yakoub-Agha I. Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD.
Bone Marrow Transplant. 2008 Sep 1. [Epub ahead of print]

4. Moreno-Romero JA, Fernández-Avilés F, Carreras E, Rovira M, Martínez C, Mascaró JM Jr. Imatinib as a potential treatment for sclerodermatous chronic graft-vs-host disease. Arch Dermatol 2008; 144:1106-9.

5. Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis.
Arthritis Rheum. 2008; 58:2543-8.

The XXIX Symposium of the International Society of Dermatopathology will be held in Graz (Austria) in October 2008. This meeting will provide several sessions and lectures on particular problems in dermatopathology.