ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Estimates have been made of the proportion of cutaneous malignant melanomas caused by sun exposure by comparing the observed incidence of melanoma with estimates of the incidence in the absence of sun exposure. The estimated proportions varied from 0.97 in males and 0.96 in females in Queensland, Australia, when the Incidence on the whole body was compared with that on unexposed sites, to 0.68 when Incidence In people born in Australia was compared with that in migrants to Australia from areas of lower sun exposure. A comparison of US Whites and US Blacks, in which the Incidence In Blacks was taken as the Incidence In unexposed Whites, gave estimates of 0.96 in males and 0.92 In females. It was estimated that some 59 000 (65%) of about 92000 melanomas that occurred worldwide in 1985 were caused by sun exposure. This is probably a minimum estimate. That 20% of the world's melanomas are estimated to occur in Black African and Asian populations and are of unknown cause would justify studies of the causes of melanoma In these populations.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Both In vitro and In vivo observations have suggested that melatonin modulates malignant cell growth. The present studies aimed to characterize the interactions of melatonin with cultured murine B16 melanoma cells. Time- and temperature-dependent specific melatonin accumulation by B16 murine melanoma cells was observed. B16 cells possessed a high affinity binding site (KD= 1.4 nM) which exhibited structural specificity in its affinity for analogues of melatonin (melatonin > 6-hydroxymelatonin = N-acetyl-5-hydroxytryptamine > 5-methoxytryptamlne > 5-hydroxytryptamine). Evidence for a lower affinity uptake system without structural specificity was also observed. Ninety-five per cent of the specific cell-associated melatonin in B16 cells was present In the soluble subcellular fraction of lysed cells; more than 97% of the cell-associated radioactivity was authentic melatonin. When the solubilized cell extracts from the binding assay were analysed by gel filtration immediately, all of the bound counts eluted at the void volume. Continuous exposure to melatonin for 48–120 h did not affect B16 cell proliferation as determined by cell counts, 3-[4,5-dlmethylthlazol-2-yl]-2,5-diphenyltetrazoll-um bromide assay or [3H]thymldine incorporation. After 8-h pulse exposures to melatonin daily for 3 days, a 15% stimulation of B16 cell proliferation (p < 0.02) was observed at melatonin concentrations of 0.1 and 1 nM. The anti-oestrogen, tamoxifen, Inhibited B16 cell growth and Increased specific melatonin accumulation by B16 cells at 1 ± 10−6M (p < 0.02). Cultured B16 murine melanoma cells possessed a specific, high affinity uptake system for melatonin which appeared to be altered by anti-oestrogen exposure.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

An IgM human monoclonal antibody (human MAb) was generated by fusing lymph node cells Isolated from a surgical specimen of malignant melanoma with the heteromyeloma cell line SHMD-33. The antibody, designated 7c11.e8, reacted with surface antigens on human melanoma cells as shown by live cell immunofluorescence and absorption assays. The MAb 7c11.e8 reacted with DSI, SPG, GM4, GM3 and GD3 In enzyme-linked Immunosorbent assays (ELISA), and did not react with GD2, GM1, GM2, GD1a, GD1b, GT1b and a number of neutral glycosphingollplds. The main binding epitope for the MAb was, therefore, the terminal N-acetylneuramlnlc acid 2–3 Gal linked by a β1–1 bond to the ceramlde, or a β-4 bond to glucose or glucosamine. As shown by immunohlstochemlcal assays, 7c11.e8 antigen was expressed on all melanoma tumour tissues, and on a few samples of colon carcinoma, normal colon, skin, spinal cord, kidney and liver. However, other normal organs such as breast, lung, small Intestine, stomach and lymph nodes did not react with the MAb. In the presence of human serum the antibody Initiated a strong lysis of melanoma tumour cells In complement-dependent cellular cytotoxicity (CDCC) assays. This study demonstrates that It Is possible to Isolate human monoclonal antibodies directed to cell surface antigens using viable cell assays In the screening protocol. The preferential binding of 7c11.e8 to melanoma tissues and the reactivity with two of the major melanoma gangliosides (GM3 and GD3) suggest that 7c11.e8 may provide a useful reagent for diagnosis and therapy of malignant melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Various cytokines are involved in growth regulation of human melanoma cells. Malignant melanoma cells express multiple growth factors, including basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-α, platelet-derived growth factor (PDGF)-α, and melanoma growth stimulatory activity (MGSA), substances which are not expressed in normal human melanocytes. The simultaneous synthesis of growth factors and expression of their receptors by melanoma cells, leading to permanent stimulation of cell proliferation, has been clearly shown for bFGF and MGSA. This phenomenon has been designated autocrine growth stimulation. Increased or altered expression of growth factor receptors has been described for nerve growth factor (NGF) receptor, for PDGF-β receptor and for a truncated form of epidermal growth factor (EGF) receptor encoded by the c-ero-B2 oncogene. Lymphoklnes are mainly Involved in growth control of melanoma cells. Interferons (IFN)-α,-α and-ν, Interleukins (IL)-1 and −6 as well as tumour necrosis factor (TNF)-α, Inhibited melanoma cell proliferation, with the strongest effects displayed by IFN. TGF-β which was found to inhibit proliferation of normal human melanocytes exhibited marginal effects on melanoma cells, or even stimulated their growth. In conclusion, a complex network of cytokines Is Involved In the regulation of melanoma cell growth. Further insight into these mechanisms may contribute to the finding of new strategies in melanoma therapy.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent findings Indicate that variable expression of β Integrins may play a role In differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their β1, α2, α3, and α6, Integrln subunlt expression and cell migration on type IV collagen (CN IV) or lamlnln (LN). The MM cell line expressed markedly Increased levels of the β1, α2and α3, but not α6subunlt compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly Inhibited by function-blocking antl-β1and anti-α3MAbs, but not by the antl-α6MAb tested. In contrast, the anti-α2MAb significantly Inhibited MM but not PM cell migration. These data show that the α3subunlt plays a significant role in melanoma cell motility on CN IV and LN and that. the α3subunlt has a significant contribution to the motility of the MM cell line.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Certain mono- and dlhydroxybenzene derivatives are selectively cytotoxic for melanocytes In vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxiclty/hair depigmentation in C57BI mice by injection of 0.032–1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihy-droxyphenylalanlne (DOPA) or 3,4-dlhydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective Isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57BI mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 μM bovine serum albumin (BSA) In vitro varies widely, with tBCQ ≫ MMEHQ = DOPACQ > DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyroslnase-generated 1,2-quinones. This mechanism evidently differs from that involved In In vitro hydroxybenzene melanocytotoxlclty of melanoma cells, in which active oxygen Intermediates generated by hydroxybenzene autoxldatlon play a significant role. The most reliable prognosticator of In vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reactina with orotein -SH.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Active specific Immunotherapy for cancer often requires the use of autologous or allogeneic tumour cells as Immunizing antigen. Tumours were obtained for such a protocol. However, estimation of viable cell yield from pre-processed fresh tumour mass was difficult, and Initially there did not appear to be a direct relationship between pre-processed tumour mass and viable cells obtained after processing. We therefore analysed all of 293 tumour specimens processed to attempt to discern such a relationship. Of these 137 were melanoma, 14 were sarcoma, 48 were adenocarcinoma, 59 were renal cell carcinoma and 35 were classified as other. A positive correlation was found between pre-processed tumour mass and viable cell yield, with Spearman correlation values varying from r = 0.49 (adenocarcinoma) to r = 0.84 (melanoma). For all tumours the Spearman correlation was r=0.70 (p = 0.0001). Not surprisingly, the most frequent site of removal associated with bacterial contamination was bowel. In conclusion, this study provides useful curves for predicting viable tumour cell yield from pre-processed tumour mass of given histology.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Cytogenetic Investigations of posterior uveal melanomas have Identified non-random changes of chromosomes 3, 6, and 8. Monosomy of chromosome 3 with additional copies of 8q occur principally in the subgroup of uveal melanomas arising from the ciliary body. To determine whether ciliary body and choroidal melanomas maintain submlcroscoplc differences in their genetic aetiology, studies of the loss of heterozygosity (LOH) of THRB (ERBA β) on 3p were undertaken. DNA from the blood and tumours of 19 patients with uveal melanoma were analysed for LOH of two restriction fragment length polymorphisms (RFLP). Approximately 60% of the uveal melanomas demonstrated allelic loss of THRB. Although the majority of tumours with allelic loss originated wholly, or In part, from the ciliary body, choroidal melanomas also demonstrated allelic loss of THRB. These results suggest that deletions of chromosome 3 occur in the absence of visible cytogenetic changes and may imply that alterations of chromosome 3 are integral to the tumourlgenesis of both sets of uveal melanomas.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This study reports our success in developing a murine monoclonal antibody (mAb) against phaeomelanin and its major precursor, 5-S-cysteinyldopa (5-S-CD). A competitive enzyme-linked Immunosorbent assay was developed and demonstrated that the new mAb, designated as 6D4 (lgG1, k), reacted with both 5-S-CD and phaeomelanin, but not with eumelanin. The concentrations required for 50% inhibition of 5-S-CD and phaeomelanin were 65 ng/ml and 95 ng/ml respectively. The minimal amount of 5-S-CD and phaeomelanin which could be detected by mAb 6D4 was approximately 5 and 6 ng/ml, respectively. The immunohistochemical assay indicated that the antigenic epitope(s) recognized by mAb 6D4 was localized In the cytoplasm of certain types of melanocytlc tumours, such as superficial spreading melanoma.

ISSN:0960-8931    

出版商:OVID    

年代:1993

数据来源: OVID