摘要:

A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6–2.1), increasing Clark level (OR 1.8, 95% CI 1.6–2.0), ulceration (OR 1.8, 95% CI 1.6–2.0), nodular melanoma (OR 1.5, 95% CI 1.3–1.6) and increasing age (continuous variable,P< 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7–0.9), inflammation (OR 0.8, 95% CI 0.7–0.9) and female gender (OR 0.8, 95% CI 0.8–0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2–1.7) and ulceration (OR 1.4, 95% CI 1.2–1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7–0.9), inflammation (OR 0.8, 95% CI 0.7–0.9) and female gender (OR 0.8, 95% CI 0.8–1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P= 0.01) and 1989 (P= 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P= 0.04), as did age at diagnosis (P= 0.005).

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

CDKN2Ais thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in theCDKN2Agene may produce an imbalance between functional p16 and cyclin D, causing abnormal cell growth. We here describe a novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon 67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a female subject from a melanoma-prone family, presented at the age of 47 years with a superficial spreading melanoma of the trunk. Her father had colon cancer at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric cancer, and her grandfather had laryngeal cancer.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Vaccination-based therapy of melanoma has so far mainly focused on monovalent approaches using either melanoma differentiation antigens or cancer/testis antigens. To study the complementarity of expression from these two families of antigens recognized by T-cells, we screened 47 metastatic lesions of cutaneous melanoma for the expression of three melanoma differentiation antigens and eight cancer/testis antigens using reverse transcription-polymerase chain reaction (RT-PCR). The melanoma differentiation antigens were expressed in a somewhat higher percentage of lesions (94% positive for at least one marker) than the cancer/testis antigens (91% positive for at least one marker). Nearly all the melanoma metastases (98%) expressed at least one of the markers tested. One melanoma metastasis was negative for all the markers. Two out of 47 lesions did not express any of the three differentiation markers but expressed one or more of the cancer/testis antigens, indicating some additional potential for these antigens compared with the melanoma differentiation antigens. Therefore, we conclude that polyvalent immunotherapy using multiple epitopes from both families of antigens might increase the eligibility of melanoma patients and the efficacy of the treatment.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A selection of natural and synthetic coumarin compounds, including the hydroxylated and nitrated derivatives, were assessed for their cytotoxic potential using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cellular viability. For the first time this study utilized both human skin malignant melanocytes (SK-MEL-31) and normal human skin fibroblastic cells (HS613.SK), allowing identification of those coumarin derivatives that are selectively toxic. Coumarin was found to exhibit comparatively low toxicity in both cell types, while 7-hydroxycoumarin (7-OHC) and coumarin had similar activity in SK-MEL-31 cells. The entire series of hydroxylated coumarins were considerably more toxic in HS613.SK than in SK-MEL-31 cells. Novel synthetic nitrated coumarins, 6-nitro-7-hydroxycoumarin (6-NO2-7-OHC) and 3,6,8-nitro-7-hydroxycoumarin (3,6,8-NO2-7-OHC), were shown to be significantly more toxic to SK-MEL-31 than HS613.SK cells. In the malignant melanocyte skin cell line (SK-MEL-31) the cytotoxic effects of these nitro-derivatives were shown to be dose and time dependent. Therefore, the cytotoxic potential of coumarins appears to be highly dependent on the nature and position of the functional group. In addition, nitration of 7-OHC produced compounds that were cytotoxic to malignant melanocytes, suggesting that these nitro-derivatives may have a chemotherapeutic role in the future.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Hyperthermia produces regression of human cancer. Because hyperthermia has produced only limited results, attention has focused on searching for substances able to sensitize tumour cells to the effects of hyperthermia. The flavonoid quercetin has been reported to be a hyperthermic sensitizer in ovarian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin and tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed that both quercetin and tamoxifen synergize with hyperthermia (42.5°C) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed by flow cytometric and Northern blot analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at both protein and mRNA levels. Our results suggest that quercetin and tamoxifen can be usefully combined with hyperthermia in the therapy of recurrent and/or metastatic melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Tumour-induced hypercalcaemia (TIH) is a frequent complication of advanced cancer but has been rarely reported in patients with malignant melanoma, and its pathogenesis remains unexplored. We studied eight patients with TIH and melanoma. We determined the incidence and pathogenesis of this complication and the effects of bisphosphonate therapy. The incidence of TIH in 751 patients with melanoma was 1.1%. All patients had liver and bone metastases at the time of hypercalcaemia. All patients had osteolytic lesions, most often multiple. The median survival was 30 days (range 4–136 days). After rehydration, the mean (± SEM) corrected calcium was 3.42 ± 0.17 mmol/l. Parathyroid hormone levels were adequately suppressed and vitamin D concentrations were normal. Serum osteocalcin, a marker of bone formation, was low, except in the two patients with renal insufficiency, whereas fasting urinary calcium and hydroxyproline were increased, indicating inhibition of bone formation and stimulation of bone resorption. Increased parathyroid hormone-related protein secretion was noted in only one patient. Three of four patients became normocalcaemic after bisphosphonate therapy for a median duration of 2 weeks. In conclusion, hypercalcaemia is a rare complication of melanoma. It occurs in the context of far advanced disease and is essentially due to aggressive lytic bone metastases with an uncoupling in bone turnover. Bisphosphonates can offer short-term palliation.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

This study addressed the independent association of past and recent sun exposure indicators and other host factors with the prevalence of major digital epiluminescence microscopy (D-ELM) features such as the pigment network (PN), brown globules (BGs), and pigment dots (PDs) in acquired melanocytic naevi. In a consecutive series of 189 patients (median age 28 years; range 10–73 years) with one or more naevi as diagnosed on D-ELM, we evaluated 35 solitary lesions and one naevus randomly selected from each of the 154 patients with multiple lesions. D-ELM images were classified for the presence or absence of PN, BGs and PDs on two blind readings. Data analysis was based on multiple logistic regression. Patient age was positively associated with PN and inversely associated with BGs. The probability of PN increased with more than 110 days since last exposure to the sun, whereas a rapid decrease for BGs and PDs was observed after approximately 1 month. PDs were significantly more likely among lesions with 6–10 h/day of recent exposure. Sex, total lifetime hours of exposure, sunbed use, skin type and colour of hair exerted no effect. In conclusion, major D-ELM features appeared to differ in their relationship with sun exposure indicators.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Amelanotic cutaneous melanoma (ACM) often defies clinical diagnosis because of the lack of pigmentation. In an attempt to find diagnostic clues, we retrospectively studied the clinical features of 15 thin (< 1 mm thick or Clark level I) ACM lesions. The clinical features of early ACMs are identified and illustrated to enable early diagnosis and cure of these lesions. The typical early lesion presents as an asymmetric macula, which may be uniformly pinkish or reddish or, more often, has faint light pigmentation (tan, brown or grey) at the periphery; it has borders that may be well- or ill-defined. In our study, these features suggested the correct clinical diagnosis in only a minority (40%) of cases. Nine cases in this series were also subjected to dermatoscopy. By this technique we identified, as constant feature, the presence of small red dots, evenly distributed or grouped on a whitish or pink-red background. Our results show the importance of dermatoscopy in the evaluation of equivocal pink or reddish lesions. Red dots seen with this technique can be an important sign for the diagnosis of thin ACM. Since this sign does not appear to be pathognomonic, the presence of an associated pigmentary network can be decisive in the differential diagnosis.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other algorithms. However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed objectively and no golden standard of asymmetry diagnosis exists. The aim of this study was to assess the sensitivity of axis (a-) symmetry using latent class analysis. We analysed ratings from four experts in dermatoscopy of 232 pigmented lesions by latent class analysis (LCA). Possible ratings were ‘no asymmetry', ‘asymmetry in one axis’ and ‘asymmetry in two axes'. A subset of melanocytic lesions (blue naevi excluded) was analysed. Based on LCA, the asymmetry of the singular lesion was determined. The sensitivity of ‘no asymmetry’ was 40–77%, 40–70% for one-axis asymmetry, and 77–92% for two-axes asymmetry. Overestimation of asymmetry was more common than underestimation. Melanomas were significantly more asymmetric than pigmented naevi, atypical naevi and papillomas, but not basal cell cancers. Analysis of the melanocytic subset gave similar results. The median asymmetry of malignant melanomas (1.67, interquartile range 1.81–1.99) was higher than for melanocytic naevi. In conclusion, asymmetry and symmetry are important criteria for diagnosing or excluding malignant melanoma using the dermatoscopic ABCD rule, risk stratification and other diagnostic rules. Using LCA, we minimized observer dependence in the assessment of axis (a-) symmetry. LCA, besides conceptualizing the diagnostic process, enables the assignment of lesions to their true diagnostic class.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The feasibility of using transscleral thermotherapy (TSTT) to induce necrosis of choroidal melanoma without causing damage to the sclera was investigated. Fifty-two subcutaneously implanted hamster melanomas covered by human donor sclera were irradiated for 1 min with an 810 nm laser using a 3 mm spot diameter, with and without cooling of the scleral surface. Immediately after irradiation the temperature of the scleral surface was measured with an infrared camera. Irradiation at 2000 mW, without cooling of the sclera, resulted in tumour necrosis to a mean depth of 4.4 mm and a mean diameter of 5.5 mm, without causing damage to the scleral collagen; the surface temperature of the sclera was 44.5°C, and the estimated temperature at the sclera–tumour interface was 60.1°C. There was a sharp demarcation between the viable and the necrotic part of the tumour. TSTT at 2500 mW, without cooling of the sclera, caused maximal tumour necrosis to a mean depth of 5.2 mm and a mean diameter of 5.9 mm; the scleral layers adjacent to the tumour had an estimated temperature of 67.6°C and showed signs of damage in 14% of the experiments. Cooling of the sclera resulted in less thermal damage to the sclera but also less tumour necrosis. Results indicate that TSTT has potential in the treatment of choroidal melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2001

数据来源: OVID