摘要:

Although flavonoids seem to be capable of acting at all stages of the carcinogenic process, little information is available on their action in melanoma cell lines. The aim of this study was to assess the response of B16F10 and SK-MEL-1 melanoma cell lines to treatment with six different flavonoids after 24 and 72 h of exposure and to relate the response to their structure. We then compared the findings with those for melphalan treatment. When cultures were treated for 24 h, only slight inhibition at the highest concentrations (25 and 50 μM) of tangeretin and luteolin were observed, whereas melphalan caused a dose-related inhibition of growth at all concentrations. Quercetin, hesperetin, 7,3′-dimethylhesperetin and eriodictyol did not produce any effect at 24 h on B16F10 or SK-MEL-1 cells, results which point to the low toxicity of flavonoids. After 72 h of exposure culture growth was inhibited by 7,3′-dimethylhesperetin at 50 μM, but lower concentrations had no effect. Tangeretin was the most effective of the flavonoids in inhibiting B16F10 and SK-MEL-1 cell growth, showing a clear dose–response curve after 72 h. These results suggest that the absence of the C2–C3double bond on hydroxylated flavonoids results in a loss of effect on both the cell lines, while the higher activity of tangeretin compared with 7,3′-dimethylhesperetin suggests that the presence of at least three adjacent methoxyl groups confers a more potent antiproliferative effect.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A number of studies have reported that increased P-glycoprotein expression in drug-resistant tumour cells may be associated with decreased expression of a family of surface glycoproteins. However, despite its potential biological and clinical relevance, this phenomenon has not been extensively studied. In this study the phenotypic alterations that are associated with the acquisition of the multidrug-resistant phenotype in tumour cells, together with drug transporter overexpression, were investigated in human melanoma cells. The expression of cell adhesion molecules was analysed in a panel of multidrug-resistant melanoma cell lines (M14Dx) showing different degrees of resistance to doxorubicin and different levels of the expression of the drug transporter P-glycoprotein. In particular, expression of intercellular adhesion molecule-1 (ICAM-1), CD44, very late activation antigen (VLA)-5 and VLA-2 was determined by flow cytometry in the different resistant cell lines. A progressive downregulation of all the adhesion molecules examined was revealed in M14Dx cells, in parallel with an increasing level of expression of the drug transporter P-glycoprotein. The results obtained raise the question of the role of P-glycoprotein in the invasive and metastatic behaviour of tumour cells.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The cellular uptake and incorporation in macromolecules of iodine-125 labelledN-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), a melanoma imaging agent, was studied using human melanoma cells M3Dau (amelanotic) and M4Beu (melanotic). The interaction between [125I]BZA and synthetic melanin was examined in various conditions of incubation. The results showed that uptake was high only for M4Beu, whereas the incorporation in trichloroacetic acid-precipitable proteins was very low for both model cell lines, with no correlation with melanin content. Experiments with synthetic melanin showed that BZA binding to melanin was saturable and reversible, and involved several types of interaction. The influence of the ionic environment indicated that electrostatic forces play a role in the affinity, and the decrease in binding produced by the presence of an alcohol in the medium suggested that hydrophobic interactions may be involved in the binding mechanism. This was supported by the Scatchard analysis, which revealed two classes of binding sites, and the determination of two association constants (K1= 3.9 ± 1.9 × 106/M andK2= 2.9 ± 0.9 × 104/M). The affinity of BZA for melanin might explain the good results obtained in a phase II clinical trial for the diagnosis of malignant melanoma metastases, in which the specificity was 100%.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Identifying and evaluating the priming agents for cytokine release by neutrophils might be helpful in controlling the innate immune response of the host. In the present study we examined the role of granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) as priming agents for interleukin (IL)-1β, IL-6 and TNF-α production by stimulated neutrophils from control subjects and malignant melanoma patients. When the cells from controls and patients were preincubated with primer agents, opsonized zymosan-stimulated inflammatory cytokine production was enhanced. The major neutrophil-priming factor for IL-6 secretion by polymorphonuclear leukocytes (PMNs) in the control and patient groups was TNF-α. However, GM-CSF and IFN-γ are also significant primers. GM-CSF priming was critical for the release of TNF-α from PMNs in control and melanoma patients. The ability of GM-CSF, IFN-γ and TNF-α to serve as effective priming agents for inflammatory mediator production by PMNs revealed a new role for these cytokines in the innate immune response of the melanoma-bearing host.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Although the transfection of the T-cell costimulatory molecule CD80 cDNA into human tumours can augment their immunogenicityin vitro, its expression alone is ineffective in many tumour systems. We evaluated the influence of CD80 expression on the immunostimulatory activity of ocular melanoma cell lines and determined whether IFN-γ could enhance the effect. Two ocular melanoma cell lines were transfected with CD80 cDNA. The immunostimulatory capacity of the CD80+transfectants was determined by their ability to stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMC). The influence of additional accessory molecules on PBMC proliferation was assessed by pre-treating the CD80 transfectants with IFN-γ. The CD80+transfectants induced proliferation of allogeneic PBMC. IFN-γ treatment of the tumour cells induced upregulated expression of MHC class I,de novoexpression of MHC class II and CD54, and enhanced the ability of the CD80+transfectants to stimulate PBMC proliferation. CD4+T cells were not required for the proliferative response against untreated CD80+tumour cells but were necessary for the augmentation of proliferation observed following IFN-γ treatment. CD80+ocular melanoma cells possess immunostimulatory potential which is augmented by IFN-γ induced upregulation of cell surface molecules. Further studies on the role of costimulatory molecules in inducing anti-tumour immunity in ocular melanoma may help to define new strategies for application of immunotherapeutic approaches to treat this aggressive disease.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In this study we evaluated the overexpression status of HER-2 and its prognostic significance on survival in patients with thick cutaneous malignant melanoma. The immuno-alkaline phosphatase antigen detection technique was applied to archival diagnostic material from 51 patients with primary lesions measuring⩾10 mm in Breslow thickness. Eleven additional patients with primary lesions measuring⩽1 mm were also studied. HER-2 overexpression was evaluated using conventional light microscopy and an automated cellular imaging system (Chromavision Medical System). Fifteen (29.4%) out of 51 patients with thick lesions showed HER-2 overexpression. In contrast, no overexpression was seen in any of the thin lesions. Overexpression of HER-2 in this group of patients was of no prognostic significance for freedom from recurrence or survival when studied using univariate and multivariate analyses. Whilst the incidence of HER-2 overexpression in patients with thick cutaneous primary melanoma is similar to that reported in breast cancer, it was of no prognostic significance for survival in this study. However, further evaluation in larger numbers of patients with the full spectrum of Breslow thickness is clearly indicated.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Sentinel node (SN) mapping and biopsy seems at present the best way to assess the nodal status in cutaneous melanoma without removing the lymphatic chain. The procedure is minimally invasive, safe and low cost, and allows selection of patients who can benefit from elective node dissection. From March 1997 up to July 1999 we examined 112 SNs excised after lymphatic mapping from 95 patients (48 males and 47 females) with stage I cutaneous melanoma affecting the trunk or limbs. Of these, 88 SNs from 74 patients were submitted to polymerase chain reaction (PCR) in order to detect tyrosinase mRNA. A new antibody (anti-tyrosinase, Clone T311, IgG2a type, Lab Vision Corporation) was used to detect nodal micrometastases. The search for micrometastases was histologically positive in 15 SNs and negative in 97. The 88 SNs examined using molecular biology were positive in 40 cases and negative in 48. In 28 only the PCR was positive. The new antibody used to detect micrometastases was shown to be very useful. Cases positive on both conventional histology and PCR were Clark level II or more and were thicker than 0.6 mm. No difference with regard to site or sex was observed. Lymphoedema and hypersensitivity reactions, nor the inability to work, did not occur. Only patients with histologically proven micrometastases underwent elective node dissection. Cases positive only on molecular biology were submitted to close follow-up.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The resolving power of imaging systems used in the diagnosis of cutaneous malignant melanoma is usually presented in the literature in terms of numerical values, yet it is often difficult for the reader to ascertain what tangible information these systems are extracting. This paper presents a classification system of two aspects of imaging systems that allows rapid appraisal of the resolution of the different imaging systems used in the diagnosis of melanoma and the additional clinical information they reveal.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Medical photography is often used in dermatology to aid in the clinical surveillance of patients with pigmented lesions. This study aimed to assess the utilization, logistics, rationale and beliefs about the usefulness of baseline photography in patients with pigmented lesions by physicians in dermatology residency programmes, and to compare current utilization to that reported in the last decade. Questionnaires were mailed to directors of all accredited dermatology residency programmes in the United States (n= 105). Eighty-three physicians responded to the questionnaire (79%). Utilization of total body and individual lesion photography was reported by 63% and 75% of the respondents, respectively; 16% of the respondents did not use any method of photography. Reasons for using photography included the following beliefs: that it helps detect early melanoma, it results in fewer biopsies, and it reduces patient anxiety. Financial and logistical constraints were reasons why some programmes were not utilizing photography. Thus baseline photography is currently used in a majority of academic dermatology programmes as an aid in the early detection of melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A retrospective study of 385 melanoma patients was performed, with the goal of evaluating the clinical characteristics, the role of imaging and the impact of treatment on patients with gastrointestinal (GI) metastases. Eighteen patients (4.7%) had GI tract metastases. In 50% the primary lesion was on the lower extremities (P< 0.01), while 61.1% had nodular melanomas (P< 0.01). Imaging and/or endoscopy were undertaken in 72.2% of the patients, yielding positive results in all. Eight patients underwent curative surgery, two received no treatment, while the remaining eight patients had chemotherapy or immunochemotherapy. Long-term palliation was offered to 87.5% of the surgical patients compared with 50% of the patients treated medically. Median survival in the patients treated with surgery was 47.5 months compared with 5.8 months in the medical group (P< 0.01). GI tract metastases were more common in patients with nodular melanoma of the lower extremities. To our knowledge, this is the first study correlating the primary lesion's characteristics with the development of GI tract metastases. Imaging is effective in the diagnosis of GI tract involvement. Melanoma patients with GI tract metastases can benefit from palliation by surgical resection. Survival is improved when such patients are treated with curative surgery.

ISSN:0960-8931    

出版商:OVID    

年代:2002

数据来源: OVID