Abstract:
:Glutathione (GSH) is the major non-protein thiol in cells that plays a critical role against damage from electrophilic agents such as alkylating drugs. Selective therapeutic GSH elevation in normal but not in tumour cells has been suggested as a means of protecting host tissues against more intense doses of chemotherapy. The present study investigated the response of B16 melanoma to treatment with the cysteine pro-drug L-2-oxothiazolidine-4-carboxylate (OTZ), alone and in combination with cyclophosphamide (CY). We found that OTZ decreased the GSH levels and proliferation rate of B16 melanoma cells in vitro, sensitizing them to the cytotoxic action of the activated metabolite of CY, acrolein (AC). In contrast to OTZ, the cysteine deliverer N-acetylcysteine (NAC) enhanced B16 melanoma cell proliferation by increasing GSH levels, and markedly decreased the sensitivity of these tumour cells to AC. In vivo studies showed the antitumoral activity of OTZ in B16 melanoma liver metastasis-induced mice, increasing their life span. We also observed that, whereas with CY treatment the GSH levels in peripheral blood mononuclear cells (PBMCs) were reduced and a dose-dependent leukopenia was produced, OTZ significantly increased PBMC GSH content, reducing toxicity and enhancing the survival of mice bearing established melanoma liver metastases treated with lethal dose CY. These results suggest a critical role for OTZ in protecting against alkylator agent-induced immunosuppression, which may allow the dose escalation of these cytostatic drugs to improve their therapeutic benefit in the treatment of malignant melanoma.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
del Olmo M,Alonso-Varona A,Castro B,Calle Y,Bilbao P,Palomares Tsubject
Has Abstractpub_date
2000-04-01 00:00:00pages
103-12issue
2eissn
0960-8931issn
1473-5636journal_volume
10pub_type
杂志文章abstract::Cerebral metastases from melanoma are correlated with a poor prognosis. Temozolomide is an oral alkylating agent that can cross the blood-brain barrier and in phase II and III trials, patients with advanced metastatic melanoma achieved overall response rates of 13 to 21%. The present study evaluated the efficacy and t...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.cmr.0000136707.60108.ab
更新日期:2004-08-01 00:00:00
abstract::Conjunctival melanoma is a rare disease, and little is known about its molecular background. Here, we present the case of a 48-year-old patient with conjunctival melanoma and metachronic lymph node and skin metastasis with KRAS p.K117Y mutation in exon 4 in all the lesions. The cancer genome interpreter predicted this...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/CMR.0000000000000423
更新日期:2018-04-01 00:00:00
abstract::Malignant melanoma is a cancer whose incidence is rising rapidly. Extensive studies of primary tumors and tumor-derived cell lines revealed that inappropriate activation of signal transducer and activator of transcription (STAT) proteins, particularly of STAT3 and 5, occurs with high frequency in various human cancers...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32830ce7d7
更新日期:2008-12-01 00:00:00
abstract::To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was e...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200010000-00011
更新日期:2000-10-01 00:00:00
abstract::In metastatic melanoma (MM) immunomodulating agents, such as interleukin-2 (IL-2) and interferon-α (IFN-α), have shown therapeutic benefit as they enhance antitumor immune response. Considering tumor-induced suppression of natural killer (NK) cell activity, it is of interest to study the affect of these cytokines on t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32833e3286
更新日期:2010-12-01 00:00:00
abstract::The treatment of cancer during pregnancy presents a unique challenge. Optimal treatments are often altered or even delayed to protect fetal growth and organogenesis. The landscape of cancer treatment has shifted dramatically over the past several years and treatment with checkpoint inhibitors, including anti-PD1 and a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000657
更新日期:2020-08-01 00:00:00
abstract::During the initiation and progression of malignant melanoma a series of genetic events accumulate, including alterations of chromosome 11q. Recently, an important tumour suppressor gene, the multiple endocrine neoplasia type 1 (MEN1) gene, has been mapped on 11q13 and has been cloned. To assess whether the MEN1 region...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199906000-00006
更新日期:1999-06-01 00:00:00
abstract::Uveal melanoma is a rare form of melanoma and the most frequent primary eye malignancy in adults. The major molecular alterations underlying uveal melanoma pathogenesis affect mainly the GNAQ, GNA11, SF3B1, and BAP1 genes. In this study, we somatically genotyped 31 Brazilian uveal melanomas for BRAF, GNA11, GNAQ, SF3B...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000523
更新日期:2019-06-01 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::The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vac...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200106000-00003
更新日期:2001-06-01 00:00:00
abstract::Treatment strategies for metastatic melanoma have changed markedly in recent times due to the advent of targeted systemic therapies. In addition to these developments, surgery remains a useful adjunct that can confer survival benefits in selected patients. In this review, we examine the current literature to highlight...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/CMR.0000000000000128
更新日期:2015-02-01 00:00:00
abstract::In an attempt to define the role of plasminogen activator in invasiveness and differentiation of human melanoma cells, the modulation of these parameters was studied in two melanoma clones characterized by marked differences in their basal features, using 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and retinoic acid, ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199408000-00007
更新日期:1994-08-01 00:00:00
abstract::Loss of expression of E-cadherin, the major cell-cell adhesion receptor on keratinocytes, has been linked to tumour progression in various carcinomas. As E-cadherin has been reported to be expressed in cultured human melanocytes, we questioned whether loss of E-cadherin expression may also be related to melanocytic tu...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199604000-00007
更新日期:1996-04-01 00:00:00
abstract::The liver is the predominant site of metastases in the majority of patients with uveal melanoma, suggesting the evaluation of regional treatment approaches. Here we report our experience with transarterial chemoembolization (TACE) in uveal melanoma patients with pretreated liver metastases. Twenty-five patients were t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328334c36e
更新日期:2010-06-01 00:00:00
abstract::Violacein is the main pigment produced by Chromobacterium violaceum, a saprophytic gram-negative bacillus. Violacein is formed by the condensation of two modified tryptophan molecules and has potential anti-neoplastic effects. The purpose of this pilot study was to investigate the in vitro activity of violacein in hum...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200410000-00014
更新日期:2004-10-01 00:00:00
abstract::In the present study, we constructed a pEgr-tumour necrosis factor-alpha (TNFalpha) plasmid and investigated its expression properties in B16 cells on exposure to ionizing irradiation and, furthermore, the effect of gene radiotherapy on a melanoma model. Firstly, the recombinant pEgr-TNFalpha plasmid was constructed a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200506000-00007
更新日期:2005-06-01 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 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::Pelvic sentinel lymph nodes (SLNs) are commonly identified during inguinal SLN biopsy for melanoma, but retrieval is not uniform among surgeons/centers. Few studies have assessed rates of micrometastases in pelvic versus superficial inguinal SLNs. Previous studies suggested that presence of pelvic SLNs was predicted b...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000498
更新日期:2019-02-01 00:00:00
abstract::The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 p...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000063
更新日期:2014-06-01 00:00:00
abstract::There is no general consensus regarding the optimal follow-up strategy for patients with melanoma. We sought to determine the utility and cost effectiveness of radiological restaging of patients with stage IIB-IIIC melanoma at the 3-year follow-up time point. A retrospective review of 210 patients diagnosed with stage...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283471086
更新日期:2011-08-01 00:00:00
abstract::Levels of eumelanin (EM) and pheomelanin (PM) of uveal melanoma cells have not been measured and compared with those of normal uveal melanocytes. EM and PM amounts in four immortal human uveal melanoma cell lines were measured by chemical degradation and microanalytical high-performance liquid chromatography and compa...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328329ae49
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Melanoma is the leading cause of death from skin cancers and its etiology is complex. Recent discoveries related to genetic risk factors are helping us to understand melanoma pathogenesis better. Nuclear factor-κB (NF-κB) has a critical role in immunity, inflammation, and tumor growth. The 94ins/del ATTG (rs...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000267
更新日期:2016-08-01 00:00:00
abstract::This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BC...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00008390-200104000-00015
更新日期:2001-04-01 00:00:00
abstract::Hyperthermic isolated limb perfusion (ILP) with melphalan is well established as an effective form of treatment for recurrent melanoma confined to an extremity. High drug concentrations in the limb are readily achieved, without systemic side-effects. However, regional toxicity can lead to considerable morbidity and fu...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
doi:10.1097/00008390-199606000-00010
更新日期:1996-06-01 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::The objective of this study is to assess the expression of heat shock protein 105 (HSP105) in melanoma and benign melanocytic lesions. The expression of HSP105 in 62 human melanoma samples--46 primary and 16 metastatic lesions--and 42 melanocytic naevi samples, was assessed by immunohistochemistry. Western blotting wa...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282fe9a16
更新日期:2008-06-01 00:00:00
abstract::Patients with melanoma may experience a variety of different vision symptoms, in part associated with melanoma-associated retinopathy. For several melanoma patients with or without melanoma-associated retinopathy, colour vision deficiencies, especially involving the tritan system, have been reported. The frequency of ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000222599.35062.84
更新日期:2006-10-01 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::Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283350554
更新日期:2010-04-01 00:00:00