ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Camptothecin (CPT) and some of its derivatives are currently used in several clinical studies with patients bearing leukaemias, lymphomas, and malignancies of various solid tissues. Therefore, it is important to establish parameters and conditions that will allow the drugs to exhibit maximal anticancer effectiveness with minimal toxic effects. We tested several water-insoluble CPT derivatives for their ability to inhibit growth of human melanoma tumours xenografted in nude mice. We found that anti-tumour effectiveness and drug-induced toxicity depended on (a) the CPT derivative; (b) the drug dose administered; (c) the mode of administration; and (d) the scheduling of drug administration. For all practical purposes, oral administration of the CPT derivative, 9-nitrocamptothecin, has produced the best overall results.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Arg substitution at codon 61 of NRAS (N-RAS/61+), were also examined. Melanoma cells and clones were used as targets of allogeneic LAK in a 4-h51Crrelease assay. LAK showed a higher lysis on melanoma lines and clones harbouring a mutated RAS compared with counterparts bearing no RAS mutations. In addition, LAK-mediated lysis drastically decreased on Me665/2 sublines progressively selected by exposure to LAK. This loss was paralleled by a reduction or even disappearance of N-RAS/61+mRNA signal in Me665/2 sublines. To evaluate whether N-RAS could directly modulate LAK susceptibility to lysis, N-RAS/61+gene was transfected in two N-RAS wild type (N-RAS/61-) 665/2 melanoma clones by a cosmid vector. In contrast to the high lysability of melanoma cells constitutively expressing the mutationally active N-RAS oncogene, N-RAS/61+transfectants did not show a consistent high lysability by LAK, compared with some control pSV2neo transfectants. Taken together, these results indicate that expression of a mutated RAS gene can be considered as a factor, although not the only one, that characterizes human melanoma cells with high susceptibility to lysis and may thus affect their response to therapeutic lymphocytes.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

An autocrine multitherapy resistance factor (MTRF) produced by a radioresistant subclone of S91 mouse melanoma (S91/I3) causes an increase in radioresistance of a radiosensitive subclone (S91/amel). MTRF has no effect on the survival of S91/I3, which is already relatively resistant to ^-irradiation. In this study, we examined the effect of MTRF in the form of S91/ 13 conditioned medium or as S91/I3 heavily-irradiated cells (13- HRCells) on cellular responses of S91/amel cells after exposure to yrays. Target S91/amel cells retained more than half of their ability to respond to rescue by MTRF on day 4 after exposure to 3 Gy. Continuous presence of MTRF during colony formation was necessary for maximum plating efficiency. Although the extent of double strand DNA breakage and repair was the same in S91/amel and S91/I3, split-dose recovery experiments with MTRF revealed previously undetected repair of sublethal damage in S91/amel cells. MTRF did not alter the extent of potentially lethal damage repair (PLDR) in S91/I3 or S91/amel. S91/amel cells were more responsive to MTRF if they had been harvested from confluent dishes, while S91/I3 cells produced a more effective factor if they had been harvested in exponential phase. These findings demonstrate that MTRF has unique properties. It does not appear to be involved in genome repair since it does not alter the extent of PLDR and it is effective when added to cells after complete split-dose recovery has occurred.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A gene for familial melanoma (MLM) has been mapped to 9p22-p13 by linkage analysis using simple tandem repeat polymorphisms (STRPs) at the IFNA and D9S126 loci. This localization is consistent with the finding of homozygous deletions of these markers in DNA from two melanoma cell lines, which suggest that the locus has the properties of a tumour suppressor gene. In an attempt to further define the position of the MLM locus we have typed 10 STRPs from the short arm of chromosome 9 in 15 Australian malanoma kindreds. Extended haplotype analysis of these markers and identification of recombinants in our pedigrees indicate that the MLM gene is flanked on the centromeric side by D9S169 and on the telomeric side by D9S156. These results limit the location of the MLM locus to an interval of about 16 centimorgans.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Derangement of thep53tumor suppressor gene has been implicated in the aetiology of a wide range of human neoplasias. We have previously determined that overexpression and mutation of thep53gene in cultured metastatic melanomas is low (11%). However, two recent immunohistochemical studies have reported that >85% of malignant melanoma specimens overexpress mutated p53 protein. In an effort to resolve this contradiction in the published literature, we have re-evaluated a range of cultured and non-cultured melanocytic lesions for the occurrence of point mutations in thep53gene using DNA- and RNA-dependent single strand conformation polymorphism (RNA-SSCP) and direct DNA sequencing of polymerase chain reaction (PCR) amplified DNA, and overexpression of the p53 protein using immunohistochemistry. We found point mutations in 25% (9 of 36) of cultured melanomas and 0% in 34 fresh melanoma biopsies; however, increased p53 expression was found in 42% of paraffin-embedded melanoma specimens and 7% of benign lesions. The low frequency ofp53point mutations and high frequency of p53 expression suggests that derangement of thep53gene by point mutations is not a common perturbation in the majority of melanoma cells, and that overexpression of p53 in this tumour type is due to a mechanism other than point mutation.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Flow cytometric analysis of DNA ploidy and S-phase fraction was performed on the primary melanomas and the first metastases from 55 melanoma patients with regional lymph node metastases or in transit metastases. The frequency of aneuploidy was significantly higher in metastases than in the primary tumour (p= 0.009), suggesting a higher growth potential in melanoma metastases than in the primary tumours. In 18 patients with reliable S-phase determinations from both primary tumour and metastasis there was no significant difference in mean S-phase fraction between primary melanomas and metastases. Skin metastases localized in dermis and subcutis had a significantly (p=0.012) higher mean S-phase fraction than lymph node metastases.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The analysis of fine-needle aspirates and effusions has proved to be a valuable tool for the cytological identification of metastatic melanoma. Nevertheless, while malignant pigmented cells can be easily detected on cytological specimens, their identification may be very difficult in patients bearing amelanotic lesions. In the present study we have evaluated whether this limitation can be overcome using two monoclonal antibodies (mAbs) HMB45 and Ep1-3, which are highly specific for the melanocyte lineage. These reagents were assayed in immunocytochemical tests performed on cytological material obtained from 50 patients with a past history of melanoma and 463 bearing metastases from a cryptic primary tumour. These mAbs, employed in combination with a panel of monoclonal reagents with well-defined tumour specificity, may improve the accuracy of the conventional cytopathological diagnosis of melanoma metastases in the two groups of patients.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The goal of this study was to determine the effect of oral melatonin in divided doses on plasma melatonin levels in patients with metastatic melanoma. Hourly blood samples were obtained from five patients for 24 h prior to melatonin administration and for 24 h during oral administration of melatonin, 50 mg every 4 h. In two of the five patients, the expected nocturnal plasma melatonin peak was observed. Oral melatonin was well absorbed. Plasma melatonin levels exhibited six peaks and troughs, were two to four-fold higher during peaks than troughs, and remained more than 25 times higher than peak pretreatment melatonin levels, even during troughs. Divided oral doses of melatonin were well tolerated and maintained plasma melatonin levels 25-80 times higher than endogenous peak values.

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0960-8931    

出版商:OVID    

年代:1994

数据来源: OVID