Cases reported "Melanoma"

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1/5. Effects of transpupillary thermotherapy on immunological parameters and apoptosis in a case of primary uveal melanoma.

    Transpupillary thermotherapy (TTT) is a new treatment modality for uveal melanoma. We studied whether application of TTT influences the immunogenicity of the tumour cells in vivo or the expression of molecules related to apoptosis. immunohistochemistry using monoclonal antibodies directed against HLA molecules, HMB45, P53, Fas ligand (FasL), Fas, Bcl-2 and tumour-infiltrating cells was applied to sections of an enucleated eye containing a uveal melanoma that received TTT 1 week before enucleation. The innermost part of the tumour which had been exposed directly to the laser treatment showed no staining for hla antigens, nor for Fas or FasL epitopes. The intermediate part of the tumour showed a wet necrosis and HLA expression similar to the expression in the peripheral tumour. A large number of macrophages were observed in the necrotic as well as the intact tumour tissue, especially bordering the wet necrotic area. FasL and Bcl-2 were only expressed in the viable, outer part of the tumour. This immunological evaluation of one case of uveal melanoma treated with TTT revealed that TTT may not only have a direct destructive effect on the primary tumour, but may also influence the immunogenicity of uveal melanoma cells, induce infiltration of macrophages into the tumour, and induce apoptosis. The presence of many macrophages suggests that they play a role in the removal of the TTT-treated tumour tissue by phagocytosis.
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keywords = apoptosis
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2/5. A case of acral lentginous melanoma: the correlation between CD95L expression on melanoma cells and apoptosis of tumor infiltrating lymphocytes.

    There is an increasing amount of evidence that melanoma cells express the ligand for CD95 (CD95L), a potent inducer of apoptosis which contributes to creating the immune privileged circumstances of tumor sites. However, it still remains to be demonstrated whether the capacity of melanoma cells to express CD95L is acquired during the progression. We addressed this question with a case of acral lentiginous melanoma by employing immunostaining using an antibody directed against CD95L as well as by in situ TUNEL staining. H&E-staining of tumor specimens revealed that there were two different growth patterns. The central part of the tumor showed a deeper invasion into the dermis (Breslow thickness >4 -mm). The horizontally growing edge of the tumor proliferated more superficially (Breslow thickness<3-mm). Relatively fewer lymphocytes were observed around the melanoma nests in central areas, which expressed detectable amounts of CD95L. In contrast, more lymphocytes were observed among the melanoma cells in the peripheral lesion, where CD95L was not detected. To evaluate the relevance of the CD95L expression, in situ TUNEL staining was performed. This indicated a significant correlation of lymphocyte apoptosis with CD95L expression on melanoma cells. Together the data suggest that expression of CD95L is turned on depending on the level of melanoma, and that it may tribute to creating immune privileged circumstances by initiating apoptosis of tumor filrating lymphocytes.
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keywords = apoptosis
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3/5. melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destruction.

    The identification of antigens associated with tumor destruction is a major goal of cancer immunology. vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor generates potent, specific, and long-lasting antitumor immunity through improved tumor antigen presentation by dendritic cells and macrophages. A phase I clinical trial of this immunization strategy in patients with disseminated melanoma revealed the consistent induction in distant metastases of dense T and B cell infiltrates that effectuated substantial tumor necrosis and fibrosis. To delineate the target antigens of this vaccine-stimulated tumor destruction, we screened a melanoma cDNA expression library with postimmunization sera from a long-term responding patient (K030). High-titer IgG antibodies recognized melanoma inhibitor of apoptosis protein (ML-IAP), a caspase antagonist containing a single baculoviral IAP repeat and a COOH-terminal RING domain. Although K030 harbored antibodies to ML-IAP at the time of study entry, multiple courses of vaccination over 4 years increased antibody titers and elicited isotype switching. Moreover, lymphocyte infiltrates in necrotic metastases included CD4 and CD8 T cells specific for ML-IAP, as revealed by proliferation, tetramer, enzyme-linked immunospot, and cytotoxicity analysis. Whereas melanoma cells in densely infiltrated lesions showed strong ML-IAP expression by immunohistochemistry, lethal disease progression was associated with the loss of ML-IAP staining and the absence of lymphocyte infiltrates. These findings demonstrate that ML-IAP can serve as a target for immune-mediated tumor destruction, but that antigen-loss variants can accomplish immune escape.
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keywords = apoptosis
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4/5. High levels of sFas and PBMC apoptosis before and after excision of malignant melanoma--case report.

    In our study we investigated the level of apoptosis in PBMCs and the serological level of sFas (CD95/APO-1) in 22 patients with malignant melanoma (12 patients with unique cutaneous primary tumour and 10 patients with unique brain metastasis). The first determination was performed before tumour excision and the second at 6-7 months after excision. Results in patients with primary tumour in the first determination: 6 patients with over normal values in PBMCs apoptosis and 5 patients with increased values of sFas. In the second determination: apoptosis was increased in 5 patients and sFas level was increased in 4 cases. In patients with metastases in the first determination apoptosis of PBMC was increased in 7 cases and sFas in 5 cases. In the second determination apoptosis was increased in 4 cases and sFas was increased in 4 cases. Our results show that half of the investigated patients presented elevated values of PBMCs apoptosis and Fas receptor both before and 6-7 months after tumour excision. apoptosis values for PBMCs and sFas values were with 1/4 higher than normals. There was no difference in clinical evolution of the patients with normal or increased values for studied parameters. Clinical evolution was performed for 1 year. The presence of increased values for PBMCs and sFas after tumour excision, primary or metastasis is surprising and hard to explain. It is possible that tumoral evolution induces a disregulation at PBMCs level or other cells level that persists unexpectedly, after tumour excision or apoptotic processes, in a certain level to be independent and anterior to tumour development.
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ranking = 1.6666666666667
keywords = apoptosis
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5/5. Pagetoid Merkel cell carcinoma: epidermal origin of the tumor.

    We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal merkel cells or its precursors (stem cells).
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ranking = 0.16666666666667
keywords = apoptosis
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