ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Human melanoma represents the principal cause of death in patients with skin cancer in the United States and Europe. Tumour infiltrating lymphocytes recognizing melanoma have been used to identify the tumour antigens recognized by T-cells in the context of MHC class I or class II molecules. Such antigens include MAGE-1, MAGE- 3, MART-1/Melan-A, gp100, tyrosinase, the tyrosinaserelated antigen gp75, the antigen gp15 and the mutated CDK4 and β-catenin gene-products. The identification of these T-cell epitopes provides us with novel reagents for the development of state-of-the-art treatments and for the (Immuno-)monitoring of patients with melanoma. In order for treatments, including peptide-based vaccines, to be successful, several conceptual criteria must be met: (1) The patient's tumour must present the relevant epitope(s) integrated into the vaccine, (2) the tumour should express the appropriate restricting major histocompatibility complex (MHC) molecule(s) required for patient cytotoxic T lymphocyte (CTL) reactivity, and (3) the patient's T-cell repertoire should be able to react productively against the melanoma antigens present in the vaccine. Clinical trials implementing peptide-based vaccines or whole protein therapies have been initiated in the United States and Europe. We suggest that such treatments should include the careful monitoring of anti-tumour T-cell responses. This should include examination of melanoma antigen and MHC class I allele expression in the individual patient's tumour, assessment of the status of the peptide transporter molecules TAP1/TAP2 and evaluation of T-cell mediated immune responses reactive against peptides and autologous melanoma. Evaluation of clinical parameters (such as disease-free survival) in conjunction with an examination of immunological parameters may facilitate our understanding of the immune responses against T-cell antigens that are shared among melanoma and normal melanocytes, and may ultimately help to identify the most effective immunoptherapy for patients with melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To investigate the role of c-KIT receptor in melanocytic tumour development and progression, we analysed the expression and localization of c-KIT by immunohistochemistry and Western blotting. In contrast to the positive staining shown by melanocytes and naevus cells in the epidermis of common naevi (n=20), all dysplastic naevi (n=13) were negative, as were dermal melanocytic cells of blue naevi (n=4) and common naevi (n=26). Three out of four superficial spreading melanomas lost c-KIT expression both in the epidermal and dermal parts, while nodular melanomas showed no expression of c-KIT except in partially positive cells, and six out of seven metastatic melanomas were negative. In acral lentiginous melanomas (n=8), in contrast to other types of melanoma, all cases with melanoma cells growing basally in the epidermis showed strong c-KIT positivity, but melanoma cells growing at the upper layers of the epidermis and vertically into the dermis lost c-KIT expression. Using the Western blot method on cultured pigment cells, human epidermal melanocytes, junctional naevus cells and one out of three metastatic melanoma cell lines showed 125 and 145 kDa bands corresponding to c-KIT, whereas dermal naevus cells did not. These results suggest that dysplastic naevi are distinct from ordinary naevi in terms of c-KIT expression and that basally growing cells in acral lentigenous melanomas could be at an initial stage of tumour progression, before c-KIT loss occurs.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In cutaneous melanoma, the standard CD44 molecule is abundantly expressed, whereas the expression of certain splice variants is related to tumour progression and to the metastatic potential of the cell line. In the present study we have investigated the expression of CD44 and the pattern of CD44 alternative splicing in uveal melanoma in relation to the cell type, diameter and invasiveness of the tumour. All uveal melanomas strongly stained with antibodies to the standard portion of CD44. No expression of the CD44 variant (v) exon CD44v7 was found, whereas v5, v6 and v10 were expressed (in 2/12, 5/12 and 8/12 cases, respectively). No correlation was observed between expression of particular splice variants and cell type, tumour diameter or invasion of the sclera or Bruch's membrane. All three uveal melanoma cell lines tested were strongly CD44 positive and expressed low levels of v6-containing isoforms at the cell surface, but v5, v7 and v10 were absent. Our results show that CD44 is strongly expressed in uveal melanoma and that the pattern of CD44 alternative splicing is similar to that observed in cutaneous melanoma. However, in uveal melanoma this alternative splicing does not appear to be related to prognostic parameters.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Nuclear DNA content was assessed, using image cytometry, in adult melanocytes in normal skin and in 20 intradermal naevi, 60 junction naevi, 107 compound naevi, 61 dysplastic naevi, 17 melanomas in situ and 101 primary malignant melanomas. Proliferation was estimated using mitotic counting and immunohistochemical staining by anti-Ki-67 (clone MIB1) monoclonal antibodies. All normal adult melanocytes and intradermal naevi (97% junction naevi, 98% compound naevi, 66% dysplastic naevi) were diploid. Thirty-four percent of the dysplastic naevi, 88% of the melanomas in situ and 96% of the malignant melanomas were clearly aneuploid. Proliferation, as assessed by mitotic counting and MIB1 index, was significantly higher in aneuploid invasive malignant melanomas than in aneuploid dysplastic naevi (P< 0.0001). The results indicate that histomorphologically defined entities of melanocytic lesions are characterized by typical DNA distribution patterns. Distinct aneuploidy combined with high proliferation rates generally seem to be well correlated to an increased malignancy potential of the lesion. In dysplastic naevi, the clonic expansion of aneuploid naevus cells may be limited by host defence mechanisms. Thus, DNA aneuploidy seems to indicate increased risk of malignant transformation, but has to be combined with other data, such as proliferation, in order to differentiate more precisely between different melanocytic lesions.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

A method for the quantitation of tyrosinase mRNA in the bloodstream of melanoma patients has been developed by using competitive polymerase chain reaction (PCR) with a heterologous DNA (PCR MIMIC) as an internal standard. The method was validated by demonstration of similar amplification efficiencies for both molecules and by accurate quantitation of an artificial fourfold difference in the level of tyrosinase mRNA. The ratio of amplified target to amplified standard (At/Asratio) was determined for a range of melanoma patients who had previously tested positive for tyrosinase. Sequential samples were also analysed to examine the level of tyrosinase in individual patients over time. When tyrosinase levels in melanoma cell lines were compared for a constant amount of total RNA, or for a constant number of cells, tyrosinase mRNA was found to vary more than a thousand-fold between cell lines. Because of this, the At/Asratio of patients was compared with the At/Asratios obtained when 10-fold serial dilutions of cells from a control melanoma cell line (MM200) were added to 2 ml of packed blood. An MM200 equivalence' value was thus calculated, giving the equivalent number of MM200 cells in the bloodstream of melanoma patients. Prolonged follow-up will be needed to determine the prognostic significance of the detection and levels of tyrosinase mRNA in the bloodstream of melanoma patients.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In vivocutaneous surface microscopy, epiluminescence microscopy, dermoscopy, dermatoscopy and magnified oil immersion diascopy, are terms that describe the use of an incident light magnification system to examine cutaneous lesions, usually with immersion oil at the skinmicroscope interface. The result is the visualization of a multitude of morphological features, not visible with the naked eye, that enhance the clinical diagnosis of nearly all pigmented lesions. Sixty-two invasive melanomas and 159 randomly selected non-melanoma pigmented lesions were used in the study. The non-melanomas, while randomly selected from a large data base, were all clinically atypical. Using the × 10 magnification of hand-held surface microscopes (Dermatoscope, Episcope), we present an analysis of 72 surface microscopic variables (constituting over 15,000 single observations) for the diagnosis of invasive melanoma. Forty of the 72 features studied were shown to differ significantly between invasive melanoma and non-melanoma pigmented lesions. Blue-white veil, multiple brown dots, radial streaming and pseudopods had a specificity greater than 95% for melanoma. Two features, symmetrically irregular pigment (non-uniform pigmentation with point and axial symmetry) and the presence of a single colour, had a sensitivity of 0%, i.e. were absent, in melanoma. The other significant features are presented, with their sensitivity and specificity for melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1–7 months, and six remain alive with evidence of disease after a follow-up of 2–7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+and CD4+. The CD4+cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8' and CD4+lymphoid cells. The role of TP5 may be an activation of CD4+and CD8+lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0960-8931    

出版商:OVID    

年代:1996

数据来源: OVID