Abstract:
:Melanogenesis appears to be a unique target to develop anti-tumour agents specific for malignant melanoma. Among the anti-melanoma compounds that we have examined, 4-S-cysteaminylphenol (4-S-CAP), a phenolic amine, was found to have the most promising anti-melanoma effects. To further improve the efficacy as anti-melanoma agents, we have recently synthesized enantiomers of alpha-Me-4-S-CAP and alpha-Et-4-S-CAP. The enantiomers were found to be good substrates for tyrosinase. In vitro experiments showed that the enantiomers were highly cytotoxic to B16-F1 melanoma cells, and the cytotoxic effect was proved to be tyrosinase-dependent. In the present study, in vivo cytotoxicity experiments showed that i.p. administration of R-alpha-Me-4-S-CAP and S-alpha-Et-4-S-CAP (and 4-S-CAP) strongly inhibited the subcutaneous growth of B16 melanoma in mice, while the corresponding enantiomers were much less effective. Similarly, i.p. treatment with R-alpha-Me-4-S-CAP or S-alpha-Et-4-S-CAP, but not with 4-S-CAP, caused strong depigmentation of follicular melanocytes in C57BL black mice. Among 4-S-CAP and the enantiomers, only R-alpha-Et-4-S-CAP caused a moderate decrease in blood pressure in spontaneously hypertensive rats. These results confirm that the use of enantiomers increases the efficacy of tyrosinase-dependent cytotoxic phenolic amines.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Yukitake J,Otake H,Inoue S,Wakamatsu K,Ito Sdoi
10.1097/00008390-200404000-00006subject
Has Abstractpub_date
2004-04-01 00:00:00pages
115-20issue
2eissn
0960-8931issn
1473-5636pii
00008390-200404000-00006journal_volume
14pub_type
杂志文章abstract::A large body of evidence in the scientific literature suggests that the numbers of common and atypical nevi are strong, independent risk factors for the occurrence of cutaneous malignant melanoma. Furthermore, some studies recently found an association between high nevus counts and an improved melanoma prognosis. The ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000579
更新日期:2020-04-01 00:00:00
abstract::The management of metastatic melanoma is a difficult matter. Nevertheless, the advent of target therapy has significantly improved patient outcome, provided that tumor molecular characteristics become available: the detection of drug-resistant clones can contribute to understanding the reasons for resistance onset, in...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000510
更新日期:2019-02-01 00:00:00
abstract::Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-alpha (IFNalpha) as single drugs, or in combination, results in a response rate of approximately 15-20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFNalpha2b and verapamil (V...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200302000-00014
更新日期:2003-02-01 00:00:00
abstract::In a previous qualitative study it has been shown that the incorporation of pre-existing collagen bundles from the reticular dermis into the bulk of melanoma lesions metastatic to the skin indicates rapid systemic spread. In the present study the amount of pre-existing dermal collagen in the bulk of the melanoma lesio...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199804000-00010
更新日期:1998-04-01 00:00:00
abstract::Two human melanoma tumour cell lines, one radiation resistant and one radiation sensitive, were studied for their capacity for repair of sublethal radiation damage (SLDR) and for hyperthermia inhibition of radiation damage. The most resistant cell line demonstrated a survival curve with a large shoulder and a large SL...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199406000-00003
更新日期:1994-06-01 00:00:00
abstract::Ipilimumab, a fully human, recombinant, monoclonal antibody to cytotoxic T-lymphocyte antigen 4 improves overall survival (OS) in previously treated and untreated metastatic melanoma. This retrospective analysis reports data gathered by a questionnaire on the demographics, outcomes, and toxicity of ipilimumab administ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000108
更新日期:2014-12-01 00:00:00
abstract::Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200104000-00005
更新日期:2001-04-01 00:00:00
abstract::Significant advances have been made in the treatment of melanoma by targeting key cellular pathways, but additional targets are needed as many patients do not respond or relapse with resistant disease. MicroRNA-155 (MiR-155) has previously been shown to regulate melanoma cell growth and acts as a tumor suppressor. We ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000545
更新日期:2019-04-01 00:00:00
abstract::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 observe...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199311000-00003
更新日期:1993-12-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000445
更新日期:2018-08-01 00:00:00
abstract::Resistance to various antineoplastic agents is common in the clinical management of malignant melanoma. The biological mechanisms conferring these different drug-resistant phenotypes are still unclear. To identify potential factors mediating drug resistance to melanoma cells, the mRNA expression profiles of the parent...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000215037.23188.58
更新日期:2006-04-01 00:00:00
abstract::Cell free extracts from metastases of human melanoma contain a highly active ribonucleoside diphosphate reductase (RR) which uses guanosine diphosphate (GDP) as substrate and deoxythymidine triphosphate (dTTP) as effector. No activity could be detected in these extracts when cytidine diphosphate (CDP) was used as the ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199212000-00014
更新日期:1992-12-01 00:00:00
abstract::Melanoma is the most lethal skin tumor in large part because of a propensity for early metastasis. Good models of this most clinically relevant feature of melanoma are lacking. Here, we report the development of an in-vivo model of metastasis that relies on orthotopic injection of green fluorescent protein-tagged line...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328336ee17
更新日期:2010-10-01 00:00:00
abstract::Melanomas contain subsets of cancer stem-like cells with tumor-initiating capacity. The frequency of these cells in the tumor is still a topic of debate. We investigated the phenotypic plasticity of cancer cells grown as melanospheres to elucidate the influence of the microenvironment on some features of melanoma stem...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283531317
更新日期:2012-06-01 00:00:00
abstract::Several comparative genomic hybridization studies provide evidence for overrepresentation of the long arm of chromosome 20 in malignant melanoma. These studies also suggest that chromosome 20q contains genes that may contribute to melanoma pathogenesis. To refine the region of 20q amplification and to identify potenti...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3280141617
更新日期:2007-02-01 00:00:00
abstract::The objective of this study was to identify novel tumor-suppressor genes in melanoma, using an integrative genomic approach. Data from: (i) earlier reports of DNA loss and gain in malignant melanoma accompanied by comparative genomic hybridization high-definition array data of the entire human genome; (ii) microarray ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328344a003
更新日期:2011-08-01 00:00:00
abstract::Little population-based data has been published about skin cancers in children and young adults. In this study, 200 cases of melanoma and non-melanoma skin cancers diagnosed under 25 years of age in the North of England from 1968-1995 were obtained from the Northern Region Young Persons' Malignant Disease Registry. Th...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000056259.56735.eb
更新日期:2003-08-01 00:00:00
abstract::Cutaneous melanoma is one of the most lethal cancers because of its increased rate of metastasis and resistance to available therapeutic options. Early studies indicate that metformin has beneficial effects on some types of cancer, including melanoma. To clarify knowledge of the mechanism of action of metformin on thi...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000391
更新日期:2017-12-01 00:00:00
abstract::We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow > or = 1 mm) did not decrease over time, ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199902000-00013
更新日期:1999-02-01 00:00:00
abstract::CDKN2A is thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in the CDKN2A gene 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) (CACGGc...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200110000-00002
更新日期:2001-10-01 00:00:00
abstract::Microsatellite instability (MSI) is caused by replication errors due to deficient DNA mismatch repair and has been associated with tumour progression in various types of cancer. Controversial results have been reported concerning the frequency and significance of MSI in malignant melanoma. In this study, the time of o...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200304000-00009
更新日期:2003-04-01 00:00:00
abstract::Melan-A is widely used in the diagnostics of human melanoma. The immunogenicity of this glycoprotein makes it a potential target in immunotherapy and several authors have suggested its potential as a prognostic factor. Up to now there has been no clear direct evidence of changes of Melan-A expression during the progre...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328303beac
更新日期:2008-08-01 00:00:00
abstract::In this study we investigated the antitumour effect and mechanism of action of cationic liposome-mediated murine interferon-beta (IFNbeta) gene therapy in mouse B16F1 melanoma cells in vitro and in vivo. Murine IFNbeta gene transfer by cationic liposome resulted in substantial growth inhibition of B16F1 melanoma cells...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200308000-00003
更新日期:2003-08-01 00:00:00
abstract::The mechanism of selective incorporation of thiourea into melanotic melanoma was investigated by model experiments in which the effect of the compound was examined at various stages of melanogenesis in vitro. Up to 50% inhibition of dopachrome formation was observed in the tyrosinase-dopa reaction in the presence of t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199712000-00006
更新日期:1997-12-01 00:00:00
abstract::Intercellular adhesion molecule (ICAM)-1 and mucin isotype MUC18 were originally identified as melanoma progression antigens by monoclonal antibodies (MAb) generated in a search for molecules expressed by melanomas but not detectable on benign naevi. As MAb detect single epitopes whose accessibility may be modulated, ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Single-agent anti-PD1 antibodies are usually very well tolerated, but serious toxicity can still occur. Despite the PD-1 pathway seems to be relevant in the pathogenesis of immune-related myositis, anti-PD1-related myositis is generally a rare side effect of the treatment and usually not serious. However, its frequenc...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000706
更新日期:2021-02-01 00:00:00
abstract::Cell clones derived from a human melanoma metastasis selected for different integrin profiles were examined in vitro for invasive potential and biological and biochemical features potentially related to this process. Clones which expressed high levels of integrins showed high invasive potential, extracellular matrix d...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199212000-00012
更新日期:1992-12-01 00:00:00
abstract::Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatmen...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200110000-00012
更新日期:2001-10-01 00:00:00
abstract::High-dose cisplatin regimens have been shown to be highly active in advanced melanoma patients but are associated with unacceptable side effects. In order to increase the platinum dose but avoid severe side effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma patients with a combination regimen of c...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200108000-00012
更新日期:2001-08-01 00:00:00
abstract::The presence or absence of melanoma cells in human peripheral blood has recently been shown to be associated with disease prognosis, including overall survival. The detection of tyrosinase mRNA-positive circulating melanoma cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited to dissemina...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200008000-00007
更新日期:2000-08-01 00:00:00