Pierre Vereecken

Cell migration-The role of integrin glycosylation

BACKGROUND Cell migration is an essential process in organ homeostasis, in inflammation, and also in metastasis, the main cause of death from cancer. The extracellular matrix (ECM) serves as the molecular scaffold for cell adhesion and migration; in the first phase of migration, adhesion of cells to the ECM is critical. Engagement of integrin receptors with ECM ligands gives rise to the formation of complex multiprotein structures which link the ECM to the cytoplasmic actin skeleton. Both ECM proteins and the adhesion receptors are glycoproteins, and it is well accepted that N-glycans modulate their conformation and activity, thereby affecting cell-ECM interactions. Likely targets for glycosylation are the integrins, whose ability to form functional dimers depends upon the presence of N-linked oligosaccharides. Cell migratory behavior may depend on the level of expression of adhesion proteins, and their N-glycosylation that affect receptor-ligand binding. SCOPE OF REVIEW The mechanism underlying the effect of integrin glycosylation on migration is still unknown, but results gained from integrins with artificial or mutated N-glycosylation sites provide evidence that integrin function can be regulated by changes in glycosylation. GENERAL SIGNIFICANCE A better understanding of the molecular mechanism of cell migration processes could lead to novel diagnostic and therapeutic approaches and applications. For this, the proteins and oligosaccharides involved in these events need to be characterized.

High serum galectin-3 in advanced melanoma: preliminary results

Background.  Galectin‐3 (Gal‐3) is a member of the family of β‐galactoside‐binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo.

A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients.

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-β and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.

Interferon alpha as adjuvant postsurgical treatment of melanoma: a meta-analysis

Background: The literature on the benefit of α-interferon (IFN-α) as adjuvant postsurgical treatment of melanoma reports discordant results. Objective: With the published data so far, we performed a meta-analysis in order to evaluate the effect of IFN-α on the relapse rate (RR) and the overall survival (OS). Methods: Published randomised trials were identified by Medline search. Stage IV melanoma was not considered. Results: Nine published studies were included, with a total of 2,880 patients. Both the per protocol and the intention-to-treat analysis show that IFN-α significantly decreased the RR (OR = 0.74; 95% CI = 0.64–0.86). Subgroup analyses show that, for all stages, high and low doses decreased the RR (OR = 0.71, 95% CI = 0.54–0.92, and OR = 0.76, 95% CI = 0.63–0.91, respectively). No difference has been evidenced on OS. Conclusions: High and low doses of IFN-α significantly decrease the RR, but the OS does not seem to be improved.

Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage Iii and stage Iv melanoma patients

Galectin-3 (Gal-3) is a member of the &bgr;-galactoside-binding lectins family and has been implicated in angiogenesis, tumor invasion, and metastatic process in vitro and in vivo. As we showed recently that advanced melanoma patients presented high serum level of Gal-3, we investigated the association of this protein with the outcome of melanoma patients. Whether this protein could be a biomarker has not been assessed, and we compared the prognostic value of serum Gal-3 in multivariate analysis with lactate dehydrogenase, C-reactive protein and S100B. We conclude that Gal-3 could be of prognostic value in melanoma patients; more precisely, this protein has a strong independent prognostic signification with a cut-off value of 10 ng/ml. After these data, we believe that serum Gal-3 measurement can have an important role in the follow-up and management of advanced American Joint Commission on Cancer stage III and stage IV melanoma patients. Further studies will uncover whether Gal-3 will be able to open new therapeutic perspectives.

Management of Merkel tumours: An evidence-based review

(1) Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer of neuroendocrine origin generally seen in patients over 50 years of age. It has a high propensity for recurrence post-treatment; 5-year overall survival rates range from 23% to 80%. (2) The rarity of MCC means that there is a lack of prospective controlled trials in these patients. Patients are generally treated with surgery as a first-line therapy, supplemented with adjuvant radiotherapy and chemotherapy if required. (3) The use of adjuvant therapies in MCC remains controversial. Data from case series and meta-analyses of case series suggest that the addition of radiotherapy to surgery in patients with MCC can confer significant benefits with regard to reducing local and regional recurrence rates and prolonging disease-free survival. Generally, the current literature tends not to support the use of chemotherapy in these patients. (4) Stage-specific treatment regimens have been outlined involving various combinations of surgery, radiation and chemotherapy for International Union Against Cancer (UICC) stage I to III disease, while the emphasis of treatment in patients with UICC stage IV disease is on palliative care with or without radio- or chemotherapy. There is a need for more structured clinical research to better illuminate the most effective treatments for this disease.

A Case of Pyoderma gangrenosum Stabilized with Lymecycline, Topical Benzoyl Peroxide and Treated by Autograft

Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown etiology, often associated with various systemic disorders such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus and hematologic malignancies. The ulcers are characterized by their undermined violaceous borders. The disease remains a therapeutic challenge. Corticosteroids are the mainstay of therapy; however, side effects from this treatment and recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the case of a large subacute pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and successfully treated by an autograft. This observation supports the opinion that the risk of pathergy of a graft can be avoided by the stabilization of the disease.

Topical application of imiquimod for the treatment of high‐risk facial basal cell carcinoma in Gorlin syndrome

Sir, Gorlin syndrome is an autosomal dominant disease characterized by early in life apparition of numerous basal cell carcinomas (BCC). More than 100 other different anomalies have been described in this disorder including odontogenic keratocysts of jaws, palmar and plantar pits, calcified falx cerebri, skeletal abnormalities, ectopic calcification, etc. The BCC lesions are predominantly distributed on the face, the back, but can be seen elsewhere on the body, even within palmar and plantar pits. Sun exposure, radiotherapy and immunodepression (HIV) have been reported as precipitating factors. The gene for Gorlin syndrome has been mapped to locus 9q22.3–q31, with expression of a mutation of a tumour suppressor gene analogous to the patched gene (PTC) of Drosophila involved in other cancers, notably breast carcinomas. Topical imiquimod is an immune enhancer whose efficacy has been shown in treating anogenital warts and different skin preneoplasic and neoplasic conditions i.e. actinic keratoses, intraepidermal carcinomas, superficial and nodular basal cell carcinomas and melanoma metastases. Its mechanism of action seems to be related, at least partly, to induction of

Significance of cell kinetic parameters in the prognosis of malignant melanoma: a review

Abstract:  Malignant melanoma has been extensively studied concerning methods of predicting progression and clinical outcome. The maximum tumor thickness as measured by Breslows method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB‐1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings.

Black Skin Dermatology Online, from the project to the website: a needed collaboration between North and South.

Background  Whereas teledermatology is an emerging discipline, to date, no teledermatology service has been developed, which is specifically dedicated to black skins.