Effect of BCG on Concanavalin A-induced Suppressor Cell Activity and Lymphocyte Stimulation in Stage I Melanoma

Suppressor cell activity was determined in 14 patients with stage I melanoma, treated with or without adjuvant Bacillus Calmette-Guerin (BCG) immunotherapy, and in 27 normal healthy volunteers. An in vitro test system was used in which peripheral blood mononuclear cells when stimulated with concanavalin A (ConA) significantly suppress proliferative responses of fresh autologous mononuclear cells. In addition, lymphocyte stimulation capacity to optimal and suboptimal concentrations of phytohemagglutinin (PHA) was determined in 44 BCG treated or not BCG treated melanoma patients and in 40 normal individuals.ConA induced suppressor cell activity was significantly (p < 0.02) impaired in BCG treated melanoma patients (21.3 ± 3.1% suppression) when compared to not BCG treated patients (39.8 ± 5.6%) or to normals (38.3 ± 9.3%). Lymphocyte stimulation capacity was depressed in all melanoma patients when suboptimal concentrations of PHA were used but was found to be not significantly altered at optimal concentration of PHA.The present study reveals that BCG immunotherapy impairs ConA induced suppressor cell activity in melanoma patients but does not influence lymphocyte stimulation capacity

Bullous Pemphigoid, Herpes Gestationis and Linear Dermatitis Herpetiformis: Circulating Anti-Basement Membrane Zone Antibodies; in Vitro Studies

It is well established that suprabasal acantholysis can be produced in tissue culture of normal human skin in the presence of pemphigus IgG autoantibody. In this study, bullous pemphigoid, herpes gestationis and linear dermatitis herpetiformis anti-basement membrane zone antibodies failed to produce dermoepidermal separation in a tissue culture model in spite of the presence of complement. The binding of the antibodies was demonstrated by immunofluorescence and immunoelectron microscopy; ultrastructurally, identical binding sites of anti-basement membrane zone antibodies could be demonstrated in vitro, as has been observed in vivo previously. Tissue culture is a suitable model for studying the binding sites of circulating anti-basement membrane zone antibodies but the functional activity (blister formation) of these antibodies cannot be assessed thereby

In Vivo Epiluminescence Microscopy: Improvement of Early Diagnosis of Melanoma

The majority of pigmented skin lesions can be diagnosed correctly on the basis of clinical criteria; however, there remain a surprisingly high number of small pigmented lesions in which the distinction between melanocytic and non-melanocytic and benign and malignant lesions, and thus between melanoma and non-melanoma, is difficult or impossible to make with the naked eye. Epiluminescence microscopy is a non-invasive technique that, by use of oil immersion, makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented lesions. The technique of epiluminescence microscopy is reviewed, and the significant improvement in the clinical diagnosis of pigmented skin lesions and, in particular, melanoma by this technique is documented

Etretinate Improves Localized Porokeratosis of Mibelli

A 60-year-old woman with plaque-type psoriasis of 30 years' duration was treated with etretinate. The lesion resolved while the patient was on the drug and continued to resolve after she had discontinued therapy. The continuation of resolution after the patient had discontinued the drug is probably due to its long half-life.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65498/1/j.1365-4362.1985.tb05777.x.pd

Combination of Dacarbazine and Dimethylfumarate Efficiently Reduces Melanoma Lymph Node Metastasis

Dimethylfumarate (DMF) has been shown to reduce melanoma growth and metastasis in animal models. We addressed the question of whether DMF is as effective in its antitumor activity as the US Food and Drug Administration–approved alkylating agent dacarbazine (DTIC). We also tested the possibility of an improved antitumoral effect when both therapeutics were used together. Using our severe combined immunodeficiency (SCID) mouse model, in which xenografted human melanoma cells metastasize from primary skin sites to sentinel nodes, we show that these treatments, alone or in combination, reduce tumor growth at primary sites. Our main finding was that metastasis to sentinel nodes is significantly delayed only in mice treated with a combination of DTIC and DMF. Subsequent experiments were able to show that a combination of DTIC/DMF significantly reduced lymph vessel density in primary tumors as examined by real-time PCR and immunohistochemistry. In addition, DTIC/DMF treatment significantly impaired melanoma cell migration in vitro. In vivo, DTIC/DMF therapy significantly reduced mRNA expression and protein concentration of the promigratory chemokines CXCL2 and CXCL11. In addition, our data suggest that this xenotransplantation model is suitable for preclinical testing of various combinations of antimelanoma agents

Specificity of Mimotope-Induced Anti-High Molecular Weight-Melanoma Associated Antigen (HMW-MAA) Antibodies Does Not Ensure Biological Activity

Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes