ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The response of B16F10 melanoma and Melan-a melanocyte cell lines to treatment with five polyhydroxylated flavonoids and gallic acid, after 24 and 72 h of exposure, was determined, and the relationship between any antiproliferative effects observed and the chemical structure is discussed. After 24 h, none of the studied compounds showed significant cytotoxic activity in the B16F10 cell line, whereas compounds with an adjacent trihydroxylated substitution pattern did affect the viability of the Melan-a cell line. After 72 h of exposure, myricetin, baicalein and gallic acid significantly inhibited both B16F10 and Melan-a cell cultures, whereas luteolin and quercetin had only a moderate effect. Eriodictyol only had an effect on Melan-a cell viability, which was reduced slightly. These results suggest that the presence of a C2–C3double bond and three adjacent hydroxyl groups in the flavonoid A- or B-rings confers greater antiproliferative activity to the flavonoid.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Dissemination of a malignant tumour is the result of a cascade of events beginning with detachment of cells from primary tumour followed by extravasation and growth at secondary sites. The differences in metastatic ability could be attributed to properties intrinsic to the various tumour types. Thus the clonal selection of tumour cells from successive metastases apparently results in cells better equipped for survival and formation of colonies in secondary sites, indicating that survival is not a random phenomenon. Many studies of malignant cells have correlated the overexpression of adhesion receptors such as integrins and the production of cysteine proteases and glycosidases with the progression of malignancy. The interaction of cysteine proteases with basement membrane components has been implicated in tumour invasion, activation of hormones and growth factors. On the other hand, the expression of the heparanase gene and its protein has been associated with the metastatic potential of several human and mouse tumour cell lines. This study aimed to investigate the correlations between the metastatic properties of clones with high and low metastatic potential and their ability to adhere to the extracellular matrix and to degrade proteins and sulphated glycosaminoglycans present there. Clonal selection of the B16F10 cell line was performed, and the clones were examined for the expression of an integrin-type laminin receptor. A significantly higher level was detected in a high metastatic clone. Enzymatic assays showed higher activity for α-d-N-acetylglucosaminidase, β-d-N-acetylgalactosaminidase and β-d-glucuronidase in conditioned medium from low metastatic clones compared with that from high metastatic clones. However, higher endopeptidase activity was observed in conditioned medium from high metastatic clones. In summary, these results showed a positive correlation between high metastatic potential and endopeptidase secretion. Similarly, a positive correlation was observed between low metastatic cells and the secretion of glycosaminoglycan-degrading glycosidases.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

During the process of melanogenesis free radicals are generated. The aim of this study was to investigate the effects of melanogenesis in B16 melanoma on lipid peroxidation and antioxidant capacity in selected tissues of black C57BL/6J mice. The study was conducted on 24 mice: 12 healthy controls and 12 with a transplanted B16 melanoma. Two weeks after the melanoma transplant, when the average weight of the tumours was approximately 2.0 g, blood samples were taken from the orbital venous plexus. The mice were killed by dislocation of the spinal cord, and the brain, liver and lungs were removed for analysis. The level of thiobarbituric acid-reactive substances (TBARS) and of 1,1-diphenyl-2-picrylhydrazyl (DPPH) reactive substances were determined in full liver, lung and brain homogenates and in serum. The activity of superoxide dismutase (SOD) was determined only in homogenized tissue. The concentration of TBARS and the SOD activity were statistically significantly higher in all the studied tissues from mice with B16 melanoma than in tissues from healthy mice. The antioxidant capacity, however, was lower in the tissues of melanoma-bearing mice. The results obtained demonstrate an increase in oxidative stress in the tissues of mice bearing a transplanted B16 melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The aim of this study was to investigate whether there is an inverse relationship between the density of cutaneous hair and the number of pigmented lesions in patients with malignant melanoma, and to review the clinical and experimental findings with regard to this relationship. Cutaneous hair density and pigmented lesion counts were determined at nine sites by two physicians using specified criteria in 10 patients with a history of malignant melanoma and 22 control subjects. Study participants were Caucasian males of similar age, height and weight, and had similar occupational, ethnic, socioeconomic and sun exposure backgrounds. Statistical analysis was performed using combined data from all the sites and individual site data to determine whether an inverse relationship between cutaneous hair density and pigmented lesion counts exists. The results demonstrated statistically significant inverse relationships for the chest, upper back, upper arm and forearm in the melanoma patients, but not in the controls. For all the sites combined, both groups demonstrated statistically significant inverse relationships. The study findings are consistent with the hypothesis that some pigmented lesions may arise from the melanocytes of the hair follicle. This hypothesis may lead to new approaches to studying and treating melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Deletions in 1p36 in malignant melanoma have been found in high percentages in nodular melanomas and melanoma metastases. Despite many efforts, no candidate tumour suppressor gene associated with malignant melanoma has so far been found in this region. To further determine a possible tumour suppressor gene locus, we carried out a deletion mapping of chromosome 1p36 at nine microsatellite loci in 74 malignant melanomas. Loss of heterozygosity (LOH) in this region was found in 77% of nodular melanomas (NMs), 86% of metastatic melanomas, but only 20% of superficial spreading melanomas (SSMs). Regarding the allelic losses, the nodular and metastatic melanoma samples could be divided into three groups: one showing LOH at the more telomeric loci D1S243 and D1S468 (1p36.33), one displaying allelic loss at the more centromeric loci D1S214 and D1S253 (1p36.32–31) and one with LOH over all informative loci between D1S243 and D1S160. We did not find any significant correlation between a deletion in any of the investigated loci and the survival data of the patients. However, our results confine the deleted region in malignant melanoma to a very small area around 1p36.32, thus facilitating the search for the tumour suppressor gene with importance in malignant melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The purpose of this prospective study of sentinel lymph node (SLN) biopsy in a large series of melanoma patients with clinically negative regional lymph nodes from one cancer centre was to analyse the reliability of the procedure, the pattern of failures during follow-up and the factors affecting the clinical outcome of patients. Between April 1995 and November 2001, 726 consecutive patients with primary cutaneous malignant melanoma underwent SLN biopsy with preoperative lymphoscintigraphy. The vital blue dye technique was used in 170 patients, and the blue dye technique combined with intraoperative lymphoscintigraphy in 556 patients. The primary melanoma sites were head and neck in nine patients, the extremities in 419 patients, and the trunk in 298 patients. The median Breslow thickness was 3.0 mm. All patients were followed closely, the median follow-up time being 34 months. The sentinel node(s) were successfully identified in 96% of patients. Intraoperative lymphoscintigraphy combined with the blue dye technique improved the SLN identification rate (technical success in 97.3% of cases) compared with the blue dye technique alone (technical success in 91.6%). The rate of failed SLN procedures was significantly (P= 0.007) lower in inguinal basins (3.1%) compared with axillary basins (7.9%). SLN metastases were detected in 147 patients (20.2%). The presence of SLN metastases correlated significantly with primary tumour thickness and ulceration (P<0.001). The false-negative SLN biopsy rate was 4.66% (27 out of 579 SLN-negative patients). All but two node-positive patients underwent complete lymphadenectomy. Lymph nodes other than SLNs were found to contain metastases in 26.9% of patients (39 out of 145). The 5 year overall survival (OS) rate was 84% for SLN-negative patients and 40% for SLN-positive patients. Five variables showed a strong, statistically significant negative independent prognostic association with OS: positive SLN status (P= 0.000001), primary melanoma thickness>4 mm (P= 0.0009), male gender (P= 0.001), more than one lymph node involvement (P= 0.02) and lymph node extracapsular extension (P= 0.03). SLN biopsy is currently a valuable and effective diagnostic procedure for the precise staging of patients with clinically N0 cutaneous melanoma. So far SLN biopsy seems to be the only accessible method for consciously oriented detection of nodal micrometastases in melanoma that would otherwise go undetected. SLN status is the most important factor proven to distinguish high and low risk melanoma patients.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Serum S100B and lactate dehydrogenase (LDH) levels were evaluated for their ability to predict response in patients with metastatic malignant melanoma and to determine their usefulness in monitoring the results of chemoimmunotherapy. Levels were studied in 53 patients with metastatic malignant melanoma receiving chemoimmunotherapy and in 19 control patients with metastatic renal cell carcinoma receiving a similar immunotherapy regimen. The serum S100B level was elevated in 81% of the patients before treatment. Marker levels were significantly higher in patients who did not respond (n= 22). Patients with S100B levels⩾1.0 μg/l were less likely to obtain remission or stable disease than the group with normal or moderately elevated serum concentrations (P<0.01). After treatment, 17 of the 31 (55%) patients with stable or responsive disease had a S100B serum level below the cut-off point versus only one of the 22 (5%) patients in the group with progressive disease. For LDH the proportions of patients were 17 out of 31 (55%) and nine out of 22 (41%), respectively. In 15 melanoma patients there was a transient rise in the level of serum S100B at the beginning of systemic therapy. All 19 patients in the control group had an initial serum S100B level⩽0.16 μg/l, but nine showed a transient rise during immunotherapy. In conclusion, S100B levels are of value for predicting the response to and for monitoring patients during chemoimmunotherapy.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Hypoxic pelvic and limb perfusion by means of a balloon occlusion technique was evaluated in patients with recurrent melanoma of the lower limbs who were non-responders to isolated hyperthermic limb perfusion or who were not eligible for this procedure. A pilot study was performed in 17 patients, who underwent hypoxic pelvic and limb perfusion with 50 mg/m2of melphalan or 50 mg/m2of melphalan and 25 mg/m2of mitomycin C. Each procedure was followed by haemofiltration. A leakage monitoring study was performed in five of the 17 patients. The response rate and time to disease progression were the primary endpoints, with overall survival as the secondary endpoint. During the procedures there were no technical, haemodynamic or vascular complications, and no deaths occurred during surgery or in the postoperative period. Significant leakage (median 40%) was measured in the five patients studied. No severe systemic or regional toxicity was observed. After one course of treatment, the objective response rate was 47% (95% confidence interval 22.5–71.5%), the median time to disease progression was 10 months (range 2–40 months), and the 3 year overall survival was 20%. Hypoxic pelvic and limb perfusion seems to be a safe and effective treatment for patients with unresectable recurrent limb melanoma who are not eligible for isolated hyperthermic limb perfusion. Due to the non-homogeneity of the study, with some patients receiving a combination of melphalan and mitomycin C and others receiving only melphalan, it is not possible to make definite conclusions with regard to efficacy. Further studies are necessary to establish whether the response rates can be improved by using different drug regimens.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Local therapies have been highly effective in the treatment of melanoma. The objective of this study was to evaluate the use of a novel intralesional chemotherapy – cisplatin/adrenaline injectable gel – for the treatment of refractory or recurrent cutaneous and soft tissue melanoma metastases. The gel is injected directly into the lesion and delivers high concentrations of cisplatin at the injection site, where it is retained for extended periods, with little systemic exposure. A total of 28 patients with refractory or recurrent melanoma were enrolled in this open-label, multicentre study. Of these, 25 patients with 244 lesions were evaluable for efficacy. Lesions were injected with 0.5 ml (2 mg cisplatin + 0.05 mg adrenaline) of gel/cm3of tumour. Patients received up to six weekly treatments within an 8 week period. The objective response rate (complete responses [CRs] plus partial responses [PRs]) for all the tumours treated (1–72 per patient) was 53% (130 out of 244; 114 CRs, 16 PRs). The response rate for the target tumours (i.e. each patient's single, most symptomatic, largest or most threatening tumour) was 44%. The median response duration for all tumours was 347 days (range 30–783 days) and median number of treatments per tumour was five (range one to twelve). Systemic toxicity was negligible; local adverse reactions such as erythema, necrosis or pain occurred frequently, but were easily managed in most cases. In conclusion, cisplatin/adrenaline injectable gel was well tolerated, easy to administer, and effective in treating metastatic melanoma confined to the skin or soft tissues.

ISSN:0960-8931    

出版商:OVID    

年代:2003

数据来源: OVID