摘要:

The appearance of macrophages in human tumours, the so called tumour-infiltrating or tumour-associated macrophages (TIM or TAM) has suggested a role for these cells in host defence mechanisms against cancer.1–4in this review we discuss monocyte-mediated cytotoxic activity against melanoma, as reported by a number of different authors. Although most studies described in this review have used melanoma cell lines as targets for monocyte/macrophage cytotoxicity, it would be incomplete if cytotoxicity against other target cells such as K562 or WEHI-164 is not discussed. At least two distinct mechanisms of killing by monocytes/macrophages can be distinguished; direct recognition and cytotoxicity by the effector cells and antibody-mediated lysis of the tumour cells (antibody-dependent cellular cytotoxicity, ADCC). Both types of cytotoxicity will be discussed.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The increased incidence of disease, the relative unresponsiveness of advanced tumour to conventional therapies, and high socioeconomic costs make the malignant melanoma an aggressive cancer. During the last decade, several new biological agents have been developed, some of which have shown significant activity in the treatment of disease. However, the impact on the management of melanoma patients is still far from being conclusive. Among biological response modifiers (BRMs), interferons (IFNs) have generated a great deal of interest and have been extensively employed, although incorrectly. IFNs have been used without a specific rationale and at antiproliferative rather than biologically active doses; no extensive laboratory monitoring has been performed. In this paper data available in the current literature are reviewed and the efficacies of the different IFNs, used alone or in combination and in various treatment regimens, are compared in order to understand what is the place of IFNs in the management of patients with metastatic melanoma. Results are encouraging but still disappointing with the most effective treatment, with an overall response rate of 28.5% (10.5% complete responses). However, these results need confirmation. In conclusion, IFN is effective in the therapy of advanced melanoma, but improved response rates are necessary before it may be suitable for general, rather than investigative, use. Alternative biothera-peutical approaches and strategies are suggested.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We measured the glutathione content of a panel of human malignant melanoma cell lines by flow cytometry after staining with mercury orange, using visible light (488 nm) excitation, and compared the values obtained with those measured biochemically using a modified Tietze assay. Glutathione levels were depleted by culturing cells with various concentrations of buthionine sulphoximine to provide a suitable spread of glutathione concentrations. The two assays showed good correlation (r=0.93). We found a number of technical factors to be critically important. In particular, the conditions of staining, cell number, and method of mixing media, cells and stain were responsible for wide variations in fluorescence intensity. We applied the flow cytometric technique to cell suspensions obtained by fine needle aspiration biopsy of human malignant melanoma deposits, and observed a proportion of cells with high glutathione levels in many samples. The results confirm the feasibility of measuring glutathione content by visible light flow cytometry, and raise the possibility of monitoring glutathione content as an indicator of drug resistance in clinical therapy of human malignant melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The metastasis of malignant tumour cells depends on their rapid replication, and their ability to adhere to the matrix of a biological barrier such as basement membrane, to degrade the matrix, and to migrate through this more permeable barrier. Secreted enzymes, including the cysteine proteinases cathepsins B and L, are known to degrade basement membrane components. Using a barrier-free substratum we studied the possible role of cysteine proteinases in influencing the motilityper seof metastatic cells. We found that stefins, the natural inhibitors of cysteine proteinases, markedly decreased the stimulated motility of both human melanoma cells and W256 carcinosarcoma cells at low concentrations (0.5 μM). A stefin also inhibited melanoma cell adherence, but to a lesser extent than motility. Additionally, synthetic inhibitors (E-64, diazomethyl ketones) of cysteine proteinases were found to depress stimulated motility of W256 cells. These results suggest that cysteine proteinases and their inhibitors may have a direct role in the development of a migratory responseper sein tumour cells.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

An inactive cathepsin B-like enzyme with a molecular mass of 40 kD was found in a human melanoma culture medium. The inactive form of this enzyme was converted into an active form with a molecular mass of 28 kD by pepsin treatment. This activated cathepsin B-like enzyme had almost the same characteristics regarding molecular size, substrate specificity, dependence on chemical reagents, and Kmvalues as intracellular cathepsin B. Sodium dodecylsulphate polyacrylamide gel electrophoresis followed by electroblotting with an antiserum against cathepsin B yielded inactive cathepsin B-like enzyme fractions which showed two immunoreactive bands with molecular masses of 40 and 28 kD, respectively. On the other hand, alkali treatment of the inactive cathepsin B-like enzyme fractions released a cysteine proteinase inhibitor with a molecular mass of 12 kD. These data suggest that these inactive cathepsin B-like enzymes in melanoma culture medium are present not only in the precursor form, but that they are also present as enzyme-inhibitor complexes, both of which can be activated enzymaticallyin vitro.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation; HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two-carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The action of the marine furanoditerpenes, spongiatriol (SP) and epispongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The frequency of melanoma (CMM), and of common and dysplastic naevi (CN and DN) in areas of skin chronically, intermittently and rarely exposed to UV light was investigated in 121 melanoma patients (30–50 years) and 310 controls. Both cases and controls had significantly more CN in intermittently exposed areas than in areas chronically or rarely exposed. The ratio of observed to expected number of CMM was also highest in intermittently exposed skin (1.3 compared to 0.8 in chronically exposed and 0.5 in rarely exposed areas). Thus, intermittent UV exposure seems to have the most potent naevo-genic‘ as well as carcinogenic effect on melanocytes. Nineteen per cent of controls and 56% of cases had naevi fulfilling the clinical criteria for DN. The distribution pattern of DN was clearly different from that of CN and does not accord with the idea that UV light is a major aetiological factor for DN. The probability of CMM significantly increased with the degree of relative clustering of CN (pp

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A total of 761 melanocytic lesions were studied to elucidate the usefulness of clinical features for the diagnosis of dysplastic naevi. Characteristics associated with high (irregular border, irregular pigmentation), intermediate (black coloured areas, largest diameter > 0.5 cm, change of size, change of colour) and low diagnostic efficiency could be defined. Combinations of criteria had high sensitivities: at least one of the following four criteria was positive in 96% of the dysplastic naevi and in all melanomas with less pronounced clinical characteristics: irregular border, irregular pigmentation, greatest diameter >0.5 cm, black coloured areas. A lesion is therefore unlikely to be a dysplastic naevus or a melanoma if all these criteria are absent. When change of size and change of colour were analysed in addition to the features mentioned above a sensitivity of 0.96 was found for at least two of these six criteria. At least three of these six criteria were observed in all melanomas with less pronounced clinical characteristics. However, a rather low specificity (0.19 for at least one of four positive criteria, 0.20 for at least two of six positive criteria) indicated that dysplastic and non-dysplastic naevi cannot be clinically differentiated with acceptable certainty. With less stringent histological criteria approximately twice as high specificities were found. Specificities were about twice as high in a subgroup of patients with at least one proven dysplastic naevus besides the lesion under diagnostic consideration. This facilitates the identification of individuals at risk of developing a melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

From January 1988 to December 1989, 920 patients with pigmented cutaneous lesions, clinically diagnosed as suspected or certain cutaneous melanoma (CM), underwent excision under local anaesthesia as outpatients. Histological examination confirmed CM in 135 patients. Patients in this group whose initial excision was for biopsy purposes only (extending 1–2 mm beyond the lesion margin) underwent a subsequent radical excision (extending >10 mm from the neoplastic margin). The second resection was carried out within 10 to 15 days of the first, on an outpatient basis if the thickness of the CM was <2 mm, and in hospital if it was >2 mm. The clinical diagnosis proved correct in 88 cases (65%) where exeresis was the definitive surgical treatment. Outpatient surgery seems to be the best method for easing a workload dominated by the need to examine a growing number of pigmented skin lesions, without altering the prognosis for CM.

ISSN:0960-8931    

出版商:OVID    

年代:1992

数据来源: OVID