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 beta-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.

Concomitant Xeroderma pigmentosum and disseminated small plaque psoriasis: first case of an antinomic association.

We present the case of an eighteen-year-old Caucasian white boy who was diagnosed with xeroderma pigmentosum type A at age 5 and who experienced over the past year disseminated small plaque psoriasis confirmed with skin punch biopsy. The psoriatic lesions were successfully treated with multipotent topical corticosteroids and systemic retinoids. To our knowledge, the association between psoriasis and xeroderma pigmentosum has not been previously reported and may be regarded as unlikely when considering the pathogenesis of both diseases.

Lymphomatoid contact dermatitis to an exotic wood: a very harmful toilet seat.

We report the case of a 58-year-old man who experienced a 2-year history of arciform rash of the buttocks associated with an intense pruritus. The lesion worsened despite several multipotent topical steroid courses. Punch biopsy with immunohistochemistry of the lesion was suggestive of lymphomatoid contact dermatitis, and extensive screening for cutaneous T-cell lymphoma (CTCL) remained totally negative. Lymphomatoid contact dermatitis is an inflammatory disease that can clinically simulate malignant lymphoma. Although the course of the disease is considered to be benign, it should be regarded with attention as it has been hypothesized that the condition could be a precursor of CTCL.

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

Malignant melanoma has been extensively studied concerning methods of predicting progression and clinical outcome. The maximum tumor thickness as measured by Breslow's 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.

Onchocerciasis-associated limb swelling in a traveler returning from Cameroon.

Travelers to West Central Africa are at risk for infection with Onchocerca volvulus. We describe the case of an adventurous traveler who became infected with O volvulus after a 10-day stay in rural Cameroon. Two years after his return, he was diagnosed with a 3-month history of limb swelling with pruritus and fixed edema of the right arm. He was successfully treated by a single dose of ivermectin, with an additional treatment with doxycycline. The patient was followed-up during 1 year after therapy without relapse. Such travelers experiencing unusual dermatitis syndromes should prompt evaluation for onchocerciasis.

Immune characterization of clinical grade-dendritic cells generated from cancer patients and genetically modified by an ALVAC vector carrying MAGE minigenes.

Gene delivery into dendritic cells (DC) is most efficiently achieved by viral vectors. Recombinant canarypox viruses (ALVAC) were validated safe and efficient in humans. We aimed firstly to evaluate DC transduction by ALVAC vectors, then to investigate if such infection induced or not the maturation of the DC, and finally to assess the efficiency of ALVAC-MAGE-transduced DC to activate specific CTL clones. Clinical grade DC from melanoma patients were generated from blood monocytes and infected with a recombinant ALVAC virus encoding either a marker gene (EGFP) or the MAGE-1-MAGE-3 minigenes. According to the patient-donor, 22+/-16% of immature DC were successfully transduced. Flow cytometry analysis of surface markers expressed on DC after ALVAC infection did not reveal a mature phenotype. Moreover, ALVAC transduction did not interfere with the capacity of the DC to further mature under poly:IC stimulation. But most importantly, our results demonstrated that DC from HLA-A1 patient-donors infected with the recombinant ALVAC MAGE-1-MAGE-3 minigenes virus were capable of activating a MAGE 3/A1 CTL clone more efficiently than same DC loaded with MAGE 3/A1 peptide, as shown by increased IFN-gamma secretion. These results could be the basis for the development of a new clinical strategy in melanoma patient's immunotherapy.

Expression of galectin-3 in primary and metastatic melanoma: immunohistochemical studies on human lesions and nude mice xenograft tumors.

Galectins are a large family of proteins which bind galactoside-containing glycans. Their role in cancer seems to be important since members of the family may mediate cell adhesion and modulate cell growth. Galectin-3 (Gal-3) is expressed in the nucleus, in the cytoplasm and on the cell surface, and can also be secreted into the extracellular matrix. A series of experimental and clinical data have been reported which indicate that Gal-3 may play a putative role in carcinogenesis, cancer progression and the process of metastasis. To study the possible correlation between Gal-3 expression and malignant potential in primary melanoma lesions, we conducted an immunohistochemical study with monoclonal anti-Gal-3 antibody in a series of primary and metastatic melanoma lesions as well as benign skin pigmented lesions. We also developed a xenograft melanoma model in nude mice with two melanoma cell lines (ATCC G-361 and ATCC HT-144) and assessed staining with the Gal-3 antibody in the xenografts and the metastases. The expression of anti-Gal-3 staining was determined semiquantitatively. The expression of Gal-3 was higher in thin primary melanoma lesions than in benign pigmented skin lesions or metastases and seemed to correlate inversely with the aggressiveness as estimated by the Breslow index which is recognized as the main prognostic factor in melanoma. We propose Gal-3 expression in melanoma as a diagnostic and/or a prognostic parameter and suggest that further studies of such a role for Gal-3 are warranted.

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

BACKGROUND: The literature on the benefit of alpha-interferon (IFN-alpha) 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-alpha 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-alpha 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-alpha significantly decrease the RR, but the OS does not seem to be improved.

Expression of the fibroblast/macrophage marker 1B10 by spindle cells in Kaposi's sarcoma lesions and by Kaposi's sarcoma-derived tumor cells.

BACKGROUND: Kaposi's sarcoma (KS) is a tumor whose ontogenic origin remains a matter of contention. KS tissues are characterized by predominant expression of endothelial markers, while KS-derived cell cultures are usually characterized by expression of mesenchymal non-endothelial cell markers. AIMS: In order to clarify the ontogenic origin of KS cells, we investigated the expression of the fibroblast/macrophage marker 1B10 in KS tissues (AIDS-associated KS, n = 9; classic KS, n = 6; iatrogenic KS, n = 6) and in KS-derived cell cultures. RESULTS: 1B10 was expressed by loosely distributed spindle-shaped cells in early 'patch-stage' KS and by a variable proportion of spindle cells in late 'plaque- and nodular-stage' KS. Using immunohistochemistry and immunoblot analysis, we found that, in vitro, reactivity for 1B10 was uniformly evidenced in fibroblasts and in KS-derived spindle cell cultures, irrespective of their histological or epidemiological setting. By contrast, vascular smooth muscle cells and endothelial cells were negative for 1B10. CONCLUSIONS: These results suggest that the KS spindle cells isolated in vitro may represent a particular subpopulation of the KS spindle cell compartment.

Desferrioxamine enhances AIDS-associated Kaposi's sarcoma tumor development in a xenograft model.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, we have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS). We have also shown that the iron chelator desferrioxamine (DFO) has a potent anti-KS activity in vitro, suggesting that it may represent a potential therapeutic approach for the treatment of KS. The present study was designed to investigate the effect of DFO on the growth of human KS xenografts in immunodeficient mice. Unexpectedly, we found that mice treated with DFO (400 mg/kg, 3 times weekly) (n = 30) exhibited a marked enhancement of tumor growth compared with control mice (n = 33) (230 +/- 134 mm(2) versus 143 +/- 70 mm p < 0.01). No enhancement of tumor growth was seen in mice treated with iron-saturated DFO. At least 2 findings suggest that this paradoxic pro-KS activity occurred independently of mice iron stores. First, treatment with DFO had only a marginal effect on ferritin and hematocrit levels. Second, induction of effective iron depletion by an iron-poor diet (6.7 mg iron/kg diet) (n = 23) did not have a deleterious effect on the growth of the KS xenografts. The lesions obtained from the DFO-treated animals exhibited a significantly decreased apoptotic index (p < 0.05), indicating that some antiapoptotic mechanism induced by DFO may be operating in vivo to favour tumor growth. In conclusion, our data show that DFO has a stimulatory effect on KS growth in immunodeficient mice, suggesting that this drug is not indicated in patients with KS.