摘要:

This study addressed the impact of exposure to ultraviolet radiation on the risk of cutaneous malignant melanoma (CMM), as well as the behavioural components at stake in its occurrence. We performed a one-to-one unmatched case-control study among subjects aged 20 years or more with naturally non-pigmented skin in Germany, France and Belgium. Fourhundred and twenty consecutive patients with CMM diagnosed from 1 January 1991 on were derived from hospital registries; 447 controls were chosen ramdomly in the same municipality as cases. Subjects unaware of the dangers of exaggerated exposure to sunlight display an estimated CMM risk of 3.72 (95% confidence interval 2.63-5.26). The number of holiday weeks spent annually in sunny resorts and sunbathing during the hot hours of the day are strong risk factors in the three countries, but not the number of years spent outdoors, as farmers or building workers. Multiple logistic adjustments on the host characteristics increases the CMM risk associated with recreational exposure to sunlight, as well as the adjustment on the unawareness of the dangers of exaggerated exposure to sunlight. Recreational exposure to sunlight and sunburn early in life seem capable of fostering the proliferation of pigmented lesions of the skin. Our data support the hypothesis that most CMM develop from pigmented lesions of the skin containing initiated melanocytes, and that the cell proliferation due to brutal, intermittent exposures to solar radiation amplifies the likelihood of a melanocyte entering into a malignant process. These results reinforce the conviction that for controlling the rising incidence of CMM, information about the CMM risk must be widely disseminated, mainly through recommending a prudent attitude towards exposure to sunlight.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Saturation studies of 2-(125l)-iodomelatonin binding to membranes from normal human melanocytes, mouse melanoma cells B16F10 and amelanotic S91 revealed no specific binding. Using 2-(125l)-iodomelatonin in the concentration range of 6 to 566 pM, no high affinity melatonin binding sites were detectable in any of the cell types. Even when the concentration of radioligand was increased up to 2000 pM, specific binding was either low or absent and not reproducible. These results suggest that in the culture conditions used in this study, no high affinity melatonin binding sites are detected in pigmented cells.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Previously we reported that exposure of mice to UV radiation increases the incidence of melanomas arising from injection of syngeneic melanoma cells into the UV-irradiated ears. In this study, we investigated the UV dose-response characteristics, duration, waveband dependence, and role of inflammation in this effect of UV irradiation. The optimal conditions consisted of short term (3-4 weeks), intermittent (twice weekly) exposures to a moderate dose (4.8 kJ/m2) of UVB (280-320 nm) radiation from FS40 sunlamps and the effect lasted only for 3 days after the final UV irradiation. Removal of wavelengths below 315 nm with a Mylar filter abrogated the effect. The UV dose response and the time course of UV-induced inflammation, assessed by ear swelling and microscopic evaluation, did not correlate with that for enhanced melanoma outgrowth, nor did the treatment of the ears with the inflammatory agents turpentine and 12-o-tetradecanoyl phorbol-13-acetate mimic the UV effects on melanoma development. These results indicate that enhancement of melanoma development in UV-irradiated skin is probably unrelated to the inflammatory effects of UV irradiation

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Mouse monoclonal antibodies against tumour-associated gangliosides G02(14.G2a) and G03(MB 3.6) were tested to mediate antibody-dependent cellular cytotoxicity (ADCC) with various effector cells or complement-dependent cytolysis (CDC). We also evaluated the immunomodulating potential of interferons in combination with cellular cytotoxicity. Using effector: target (E/T) ratios of 40: 1, ADCC with effector cells such as granulocytes or mononuclear blood cells was not detectable against melanoma cell lines GR, SK-MEL-28 and G- 361 which preferentially express G03and bind antibody MB 3.6. Neuroblastoma cell line SK-N-LO, which was used for comparative purposes, mainly expressed G02and the tumour cells were killed effectively after labelling with antibody 14.G2a. Granulocytes did not show significant killing of melanoma cells by ADCC, but neuroblastoma cells were killed very efficiently. Peripheral blood mononuclear cells (PBMC) also failed to kill melanoma cells. Interferon-fS slightly stimulated PBMC and increased killing of neuroblastoma cells, but no additive effects with ADCC were detectable. Incubation of target cells with interferons produced no significant differences in susceptibility of the target cells to interferon-activated PBMC cytotoxicity. Despite the lack of effectiveness in mediating cellular cytotoxicity, G03antibody MB 3.6 showed strong complement- dependent cytolysis in the presence of human plasma. There were remarkable differences in individual activity and different susceptibility of the melanoma cell lines. We assume that CDC may have more activity against melanoma cells than cytotoxicity associated with various effector cells

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In the mid- to late-1980s white populations in Australia, New Zealand and Scotland showed a sharp increase in melanoma incidence above preceding long-term trends, in some cases as much as doubling in as little as 2 years. Most of this increase was in thin melanomas, (<1.50 mm thick), and males were more affected than females. Thicker melanomas also generally increased in incidence, particularly in males aged 65 years or older. Examination of Australian Medicare and pathology laboratory data indicated that excision of skin lesions and laboratory diagnosis of pigmented lesions also rose sharply in this period, suggesting that advancement of the time of diagnosis was a likely factor in the increase in melanoma incidence. However the maintenance of new higher incidence levels and the increase in incidence of thicker lesions suggests that advancement of diagnosis cannot explain all of the increase. A real increase in incidence and increasing diagnosis of a preexisting, non-metastasizing form of thin melanoma may also have contributed

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Murine B16 melanoma sublines showing enhanced metastasis to lymph nodes were selected in vivo. Successive selections of tumours metastasizing from the footpad to para-aortic nodes yielded variant tumour cell lines, including an amelanotic line, with moderately increased potential for lymph node metastasis. The phenotype of the variant cells was distinct from that of the parental cells. The lymph node-selected cells had extensive dendritic-like pseudopodial projections and were more motile than the parental cells. In addition, the variant cells were more efficient than the parental cells in attaching to and spreading on preparations of lymph node extracellular matrix. This matrix is composed of an array of reticular fibres containing a core of collagen type III decorated with a basement membrane-like material rich in laminin and type IV collagen. In adhesion assays, the melanoma cells attached best to laminin, collagen, and f ibronectin, and poorly to the interstitial matrix proteins collagen types I and III. This pattern of ligand preference was confirmed in adhesion assays to cryostat tissue sections of amnion, in which the tumour cells attached to the basement membrane aspect but not the interstitial stromal matrix. Experiments using specific antibodies established that cell attachment to lymph node reticular fibres was mediated by the β1class of integrin receptor complexes. These results indicate that highly motile variant B16 sublines can be selected for distant lymphatic dissemination, and that interaction between invasive tumour cells and nodal reticular fibres may facilitate this metastatic process.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Tumour-infiltrating lymphocytes (TIL) derived from several histotypes, including melanoma, can be expanded in vitro in the presence of recombinant interleukin-2 (rlL-2) and infused as part of experimental adoptive immunotherapy protocols. Several authors have described the isolation and the expansion of TIL, but little is known about the actual proportion of unselected melanoma biopsies that give rise to 'positive' TIL cultures. We evaluated the proliferative, phenotypic, functional and molecular characteristics of cultured TIL obtained from 26 patients with metastatic melanomas, eligible for inclusion in a protocol of adoptive immunotherapy. Sixteen proliferating cultures were obtained. All TIL belonged to the T cell lineage and were characterized by a wide range of cytolytic activity against autologous and, to a lesser extent, allogeneic melanoma cells. Molecular analysis of the constant region of T cell receptor-β (TCR-β) showed an oligoclonal population of TIL in the majority of expanded samples, indicating that a selected subset of lymphocytes present in the tumour site could be expanded in vitro. These features, together with the high number of proliferating samples, make these populations of TIL suitable for infusion into patients with advanced disease.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In the period 1978-1990, 49 patients with locally inoperable melanoma of the limbs were treated with regional isolated perfusion according to four different perfusion schedules. Perfusion resulted in a complete remission in 28 patients (57%), with a median duration of 10 (1-55+ months, and a partial remission in 10 (21%), with a median duration of 3 (1-9) months. In patients treated with a double (normothermic or sequential hyperthermic) perfusion schedule the complete remission rate was higher. Regional lymph node involvement reduced the chance of achieving complete remission. Twelve patients with complete remission (43%) showed a relapse in the perfused area. The corresponding 3-year limb recurrencefree interval was 46%. This interval was mainly influenced by the number of lesions at the moment of perfusion. Three of the patients who failed to respond eventually required amputation of the affected limb. The median follow-up of the surviving patients was 23 (5-142) months. At the time of analysis 23 patients were still alive, 12 of whom had no evidence of disease. Patients with complete remission had a slightly, though statistically not significant better 3-year survival rate than patients without complete remission (49% vs 33%). Regional isolated perfusion halted progression in all of these 49 patients and resulted in a complete remission for 57%. It is, therefore, an important modality in the management of patients with locally inoperable melanoma and provides a valuable alternative to amputation.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID