ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The current classification of cutaneous melanoma was developed in 1972 and revised in 1982. Since that time new concepts and terminology have evolved that require consideration of a further revision. This paper reviews some of the concepts that will form part of that process. Regional meetings of interested parties have been held to review the classification and there will be an open meeting on the topic at the 1997, 4th World Conference on Melanoma in Sydney, Australia. A questionnaire is included that will allow the interested reader to provide comments on the topic.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Electrochemotherapy (ECT), chemotherapy administered in combination with electric fields, has the potential to be an effective localized treatment for cutaneous malignancies. Bleomycin's cytotoxicity was enhanced by exposing tumour cells to electrical fields following intravenous injection of the chemotherapeutic agent. Two issues associated with this procedure are the existence of a narrow but optimal time-window for effective treatment and the fact that a systemic drug dose is administered for a localized therapy. In order to address these issues, a study was initiated to examine the effectiveness of administering bleomycin by intratumoural injection. A dose–response relationship for intratumoural injection was determined. In addition, the minimal effective field strength necessary for ECT was established. Results of this study indicated drastic reductions in tumour volume for ECT-treated groups. In addition, ECT-treated groups showed increased survival over control groups. The minimum effective dose for the ECT intratumour bleomycin group was 0.025 units. The minimum effective field strength was found to be 1250 V/cm. The results demonstrate that intratumoural injection of bleomycin in combination with electric pulses is effective, and this information will be used to initiate clinical trials.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We have established a surviving model of isolated limb perfusion using xenografts of the human melanoma cell line MM 96L injected subcutaneously into the hindlimb of a nude rat. The femoral artery and vein were cannulated via the left renal artery and vein and the hind limb was isolated using tourniquets. The limb was perfused with Krebs Heinseleit buffer at 37°C containing 4.7% bovine serum albumin at a constant flow rate of 4 ml per min for 30-60 min with 100% survival of the animals. Tumour vascularization and blood flow were demonstrated using vascular casts and [51Cr]-microspheres. Following the addition of melphalan (15 or 100µg/ml), drug concentrations in the perfusate, tissues and systemic circulation were determined using high pressure liquid chromatography (HPLC). Systemic leakage, assessed using [125l]albumin and melphalan and detected by a γ-counter and HPLC respectively, was<0.5%. The melphaian concentration and tissue flow rate in the tumour deposits were 40 and 30% respectively, when compared with the surrounding subcutaneous tissue. At a dose of 15µ<g/ml, melphalan caused a reduction in tumour growth after 60 min perfusion, and a significant reduction in tumour size was seen when the melphalan dose was 100µg/ml. The surviving nude rat model of isolated limb perfusion for recurrent melanoma will allow examination of optimal perfusion conditions, along with the pharmacokinetics, pharmacodynamics and efficacy of melphalan and other drugs.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effects of melatonin on the growth of human uveal melanoma cells were studied invitroThree continuous uveal melanoma cell lines were tested. Cells were plated into multi-well plates. After 24 h, melatonin was added to the medium at concentrations from 0.001 to 1000 nM. Cells were collected and counted after 5 days and compared with the controls. Melatonin inhibited the growth of melanoma cells in a dose-dependent manner (0.1-10 nM) with a mean inhibition rate of 50%. The uptake of bromodeoxyuridine (BrdU) by the melanoma cells was also measured. Melatonin inhibited the uptake of BrdU of melanoma cells at concentrations of 0.1-10 nM with a mean inhibition rate of 40%. These results indicate that melatonin may offer a new treatment for metastatic uveal melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The constitutive and cytokine-mediated expression of MHC class I and II antigens and intercellular adhesion molecule-1 (ICAM-1) was evaluated on eight human melanoma cell lines derived from primary and metastatic malignancies from patients (WM human melanoma series) including three pairs of related cell lines derived from the same individual. The cytokines IL-1β, IL-4, IL-6, TNFα, TGFβ2, IFNγ, and IFNα were assessed for their ability to modulate the expression of cell surface antigens. MHC class I and class II antigen expression was unregulated by IFNγ, IFNα and/or TNFα in cell lines established from primary melanoma. In contrast the cell lines derived from metastatic deposits did not show an increase in expression of MHC antigens in response to these cytokines. Both primary and metastatic WM cell lines were shown to be resistant to spontaneous natural killer cell (NK) activity, but susceptible to effector lymphocytes mediating lymphotine activated killer (LAK) cytotoxicity as a result of activation by IL-2. Although the constitutive and cytokine- induced level of expression of ICAM-1 and MHC antigens varied between paired primary and metastatic cell lines, this did not correlate with susceptibility of the cell line target to NK or LAK cytotoxicity. Whereas the IFNs, TNFα, TGFβ2 and IL-1β differentially modulated the expression of ICAM-1 and MHC class I, treatment with IFNs (but not IL-1β, TNFα or TGFβ2) resulted in a significant reduction in the sensitivity of the melanoma cells to NK and LAK cytotoxicity. Constitutive ICAM-1 expression was positively correlated with the ability of WM cell lines to colonise the lungs of SCID mice upon i.v. injection. The aquisition of cytokine resistance and inability to demonstrate enhanced cell surface expression may represent an important feature associated with the development of the metastatic phenotype.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Histological evaluation of epidermal melanocytes on routine staining is difficult and cannot be made with accuracy. Widely known antibodies such as S-100 and HMB-45 are unreliable for normal epidermal melanocytes. Furthermore, S-100 stains other cells including Langerhans' cells. Results of incubation with DOPA are inconsistent and the procedure is time-consuming. We have evaluated the use of Mel-5, an antibody that was developed against melanoma and melanocytes. This antibody is a mouse monoclonal antibody that specifically detects a 75 kDa glycoprotein usually expressed by normal melanocytes, naevi and melanoma cells in routinely fixed paraffin sections. Histological differentiation between pigmented actinic keratosis in photodamaged skin and lentigo maligna can be difficult. The atypical keratinocytes, particularly in the basal layer, can be confused with atypical melanocytes, especially if they are pigmented. Similarly, distinctions between lichen planus-like keratosis and lichenoid melanoma in situ and lentigo maligna and lentigo may be difficult. Use of Mel-5 in such cases has shown consistent results in separating melanocytic from non-melanocytic lesions. This antibody is also helpful in evaluating biopsies of patients with vitiligo, post-inflammatory pigmentary alteration and regressed or regressing melanocytic lesions. Furthermore, Mel-5 is an invaluable tool in quantification of epidermal melanocytes in research projects.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Spitz naevi and halo naevi are benign melanocytic lesions that share many histological features with malignant melanoma. All lesions are characterized by a brisk infiltration of lymphocytes, mainly of the T cell subtype, and halo naevi are known to undergo spontaneous regression. Since the benign nature of Spitz naevi and halo naevi might therefore be caused by specific T cell responses against tumour-associated antigens, it was found of interest to characterize this T cell response in detail. A reverse transcriptase-polymerase chain reaction (RTPCR)- based method adapted for analysis of paraffin-embedded material combined with Southern blot analysis has been used to analyse the T cell receptor (TCR) AV and BV repertoires of infiltrating lymphocytes in 14 different melanocytic lesions. The results have shown that only a few particular TCRAV and TCRBV regions are expressed in each lesion. To evaluate the T cell response, it is of interest to know the HLA-type of the analysed lesions, since most melanoma-specific effector lymphocytes are CD8+ cytotoxic T cells and therefore HLA class l-restricted. As blood samples were not available from any of these patients, an RT-PCR method using HLA-A2-specific primers was used to analyse for the presence of this allele. The preferentially expressed TCRAV genes were sequenced, and this analysis showed that the high expression of these TCRAV genes was due to a clonal or oligoclonal expansion of T cells. In summary, the expression of relatively few TCR variable regions indicates a clonal expansion of T cells.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The serum levels of the soluble form of intercellular adhesion molecule-1 (slCAM-1) and 5-S-cysteinyldopa (5-S-CD) were determined by double determinant immunoassay and high-performance liquid chromatography, respectively. Fifty-three melanoma patients (stage 1, 12 patients; stage II, 11; stage III, 19; and stage IV, 11; total number of samples, 116) and 31 age- and sex-matched healthy control subjects were analysed. Both the slCAM-1 and 5-S-CD levels were significantly higher in stage IV patients than those in stage I, II and III patients (slCAM-1; all P<0.001; 5-S-CD; all P<0.05). The serum levels of 5-S-CD were elevated only in stage IV patients. slCAM-1 levels elevated gradually with disease progression. Testing of sequential bleedings showed that both slCAM-1 and 5-S-CD levels were elevated in most of the patients whose disease had progressed. However 5- S-CD levels were not elevated in those patients whose metastases were amelanotic. There was a statistically significant correlation between slCAM-1 and 5-S-CD levels (R=0.6 55,P< 0.001). Serum levels of 5-S-CD may be a useful parameter for monitoring the clinical course of the disease in patients whose metastases are melanotic. Analysis of both slCAM-1 and 5-S-CD levels in serum will contribute greatly to monitoring the clinical course of melanoma patients.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Childhood melanoma is a rare disease with an estimated incidence of one per million per year. Careful study of childhood melanoma patients is critical due to the limited data currently available pertaining to this disease. Twenty-two children 15 years of age or under with malignant melanoma were treated at the Pigmented Lesion Clinic of Massachusetts General Hospital over a 33-year period. The medical records of all patients were reviewed, as well as the histologic characteristics of the lesions. Patients who were initially diagnosed with malignant melanoma but on review found to have Spitz naevi were not included in our study. Ten patients were boys and 12 were girls. The median ages of the boys and girls in our study were 12.9 and 13.6 years, respectively. Among the classified primary melanomas, 10 were superficial spreading, three were borderline/minimal deviation, two were nodular and one was melanoma in situ. Four of 22 patients had a documented family history of melanoma, and two additional patients had a family history of dysplastic naevi. A majority of lesions (14/22) arose in association with a precursor lesion. Two children died of disease at 1 and at 7 years following initial diagnosis. Eight patients had documented metastases. Since the majority of melanomas arose in association with a precursor lesion, follow-up of children with congenital and/ or dysplastic naevi is recommended. An interesting finding was the sometimes paradoxical behaviour of relatively thin lesions with metastases. Thus, a high index of suspicion is needed by the clinician confronted with melanocytic lesions of childhood. We found children from age 12 to 15 to be more at risk for the development of melanoma than younger children. Melanoma presenting before the age of 10 is very unusual.

ISSN:0960-8931    

出版商:OVID    

年代:1997

数据来源: OVID