Abstract:
:The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Sarojini S,Pecora A,Milinovikj N,Barbiere J,Gupta S,Hussain ZM,Tuna M,Jiang J,Adrianzen L,Jun J,Catello L,Sanchez D,Agarwal N,Jeong S,Jin Y,Remache Y,Goy A,Ndlovu A,Ingenito A,Suh KSdoi
10.1097/CMR.0000000000000174subject
Has Abstractpub_date
2015-10-01 00:00:00pages
376-89issue
5eissn
0960-8931issn
1473-5636journal_volume
25pub_type
杂志文章abstract::Many melanoma epitopes are presented to cytotoxic T-lymphocytes (CTLs) by major histocompatibility complex (MHC) class I molecules, and it is reasonable to expect that the epitopes would be good substrates for the transporter associated with antigen processing (TAP), as TAP plays a major role in the transport of pepti...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199808000-00008
更新日期:1998-08-01 00:00:00
abstract::Anecdotal cases of partial or complete responses have been reported after ipilimumab therapy for stage IV melanoma with brain metastasis treated earlier by surgery or radiosurgery. We report the first case of ipilimumab monotherapy resulting in durable complete remission of untreated, progressive brain metastases in a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283364a37
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::We describe a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the second pregnancy of a 28-year-old woman. She was aware of a greyish-brown nodular lesion on the right gluteus during her first pregnancy. On histological examination, this lesion resulted to be an amelanocitic...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/CMR.0b013e32833faf6a
更新日期:2010-12-01 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::We have observed that an early increase in the CD4+/CD8+ ratio of metastatic melanoma patients during chemoimmunotherapy is the most favourable independent prognostic factor. In this study, 87 patients with metastatic melanoma were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) before and during che...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200412000-00009
更新日期:2004-12-01 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::Between 1983 and 1992, 21 patients with extremity stage IIIA or IIIAB melanoma underwent hyperthermic isolation limb perfusion (HILP) with cisplatin in dosages varying from 26 to 237 mg/m2 as part of a pharmacokinetics and maximum-tolerated dose study. Extremity temperatures were up to 40 degrees C and the pH was cont...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-03-01 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
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journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/00008390-200010000-00001
更新日期:2000-10-01 00:00:00
abstract::Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. We ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000668
更新日期:2020-10-01 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::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::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::Melanoma cells are unusual because, unlike most epithelial tumours, constitutive expression of HLA class II antigens is common. We have previously demonstrated that a peptide-specific CD4+ T-cell clone proliferates briskly in response to peptide and HLA class II expressing melanoma cell lines derived from metastases. ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199904000-00010
更新日期:1999-04-01 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::Immune checkpoint inhibitors targeting the programmed cell death (PD)-1 receptor have dramatically changed the landscape of metastatic melanoma treatment. Nevertheless, these immuno-modulatory agents have associated side effects, including dermatologic manifestations. To this end, we report a patient with metastatic m...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000477
更新日期:2018-10-01 00:00:00
abstract::Melanomas are promising targets for immunotherapy, as they express a number of tissue-specific antigens against which immune responses can be elicited. We have previously described transgenic mice in which malignant cutaneous melanomas are produced. The 1042 melanoma cell line, derived from a primary melanoma in one o...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200412000-00019
更新日期:2004-12-01 00:00:00
abstract::Superficial spreading melanoma (SSM) is the most common type of melanoma. Large, population-based studies analyzing the incidence and survival of SSM are limited. This retrospective study was designed to evaluate demographic factors influencing the incidence and survival of SSM using a national population-based databa...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000245
更新日期:2016-08-01 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::When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enha...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200012000-00010
更新日期:2000-12-01 00:00:00
abstract::The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282f1d2ec
更新日期:2007-12-01 00:00:00
abstract::The aim of this study was to present the epidemiological, clinicopathological, and treatment characteristics of patients diagnosed and treated in a tertiary referral center and to analyze independent factors associated with these characteristics. In this cohort study, epidemiological, clinicopathological, and treatmen...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000456
更新日期:2018-08-01 00:00:00
abstract::One of the principal applications of tumour markers is the early detection of recurrent disease in the follow-up of patients. In the study described here, we compared the usefulness of two serum markers for melanoma, 5-S-cysteinyldopa (5-S-CD) and melanoma inhibitory activity (MIA), in the monitoring of postsurgical m...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200208000-00003
更新日期:2002-08-01 00:00:00
abstract::The aim of this study was to evaluate S100B in bone marrow (BM) plasma from malignant melanoma patients. BM aspirates and peripheral blood (PB) plasma from 56 patients and BM aspirates from 29 healthy volunteers were collected. S100B was measured using an immune radiometric assay, which is a two-site sandwich assay ba...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282f623d9
更新日期:2008-04-01 00:00:00
abstract::This study examines whether 6-thioguanine resistant T cells (mutant) from metastatic melanoma patients are enriched for melanoma-associated T cells compared to T cells obtained analogously without thioguanine selection (wild-type). Melanoma-associated antigen pentamer staining was performed on 5 tumour and 9 periphera...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000625
更新日期:2020-02-01 00:00:00
abstract::Electrochemotherapy (ECT), chemotherapy administered in combination with electric fields, has the potential to be an effective localized treatment for cutaneous malignancies. Bleomycin's cytotoxicity was enhanced by exposing tumour cells to electrical fields following intravenous injection of the chemotherapeutic agen...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199702000-00003
更新日期:1997-02-01 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::Several hypotheses have explicitly implicated the role of an altered redox status of melanin in the aetiology of melanoma and macular degeneration. The balance between the intrinsic anti-oxidant and pro-oxidant properties of melanin is lost, resulting in an altered redox phenotype. We propose that such an alteration o...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/01.cmr.0000195699.35143.df
更新日期:2006-02-01 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