Abstract:
:Interleukin-24 (IL-24)/melanoma differentiation-associated gene-7 (mda-7) is a unique cytokine-tumor suppressor that displays ubiquitous antitumor properties and tumor-specific killing activity. Oncostatin M (OSM) is the most active IL-6-type cytokine and inhibits the proliferation of various solid tumor cell lines. Multigene-based combination therapy may be an effective practice in cancer gene therapy. The therapeutic potential of a combination of IL-24 and OSM in treating cancers is still elusive. In this study, we aimed to examine the enhanced antitumor activity of adenovirus-mediated IL-24/OSM tumor suppressor gene cotransfer in human melanoma cells. We constructed an IL-24/OSM bicistronic adenovirus and assessed its combined effect on A375 human melanoma cells in vitro and in vivo by detecting and comparing apoptosis in the bicistronic antioncogene group (Ad-IL-24-OSM) and in the IL-24 or OSM single antioncogene group. We also investigated the possible mechanism underlying this effect. The bicistronic adenovirus-mediated coexpression of IL-24 and OSM induced additive growth suppression and apoptosis and an overlapping effect on the upregulation of p21, p53, Bax, and cleaved caspase-3 in vitro and in vivo. Moreover, Ad-IL-24-OSM treatment additively reduced the expression of CDK4 and cyclin D1 in A375 melanoma cells and the expression of CD34 and Cox-2 in A375 xenograft tumors in athymic nude mice. The enhanced antitumor activity elicited by Ad-IL-24-OSM was closely associated with the activation of the apoptotic pathway and the additive inhibition of tumor angiogenesis. Therefore, our results indicate that cancer gene therapy combining two or more tumor suppressors, such as IL-24 and OSM, may constitute a novel and effective therapeutic strategy for treating malignant melanoma and other cancers.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Xu Y,Zhang F,Qin L,Miao J,Sheng W,Xie Y,Xu X,Yang J,Qian Hdoi
10.1097/CMR.0000000000000038subject
Has Abstractpub_date
2014-02-01 00:00:00pages
20-31issue
1eissn
0960-8931issn
1473-5636journal_volume
24pub_type
杂志文章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::The aim of this study was to evaluate metastatic latency and survival after the occurrence of metastases in patients with choroidal/ciliary body melanoma treated with proton therapy. This was a retrospective cohort study. All consecutive patients with choroidal/ciliary body melanoma treated with proton therapy between...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000519
更新日期:2020-06-01 00:00:00
abstract::Studies on cytogenetic abnormalities and cell lines have implicated chromosome 1p32 as being important in the pathogenesis of melanoma. Genetic linkage studies have also mapped a melanoma-susceptibility locus to chromosome 1p. The gene TAL1 is present on chromosome 1p32, and deletions within it are the commonest chrom...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199508000-00007
更新日期:1995-08-01 00:00:00
abstract::Prognostic groups defined by lactate dehydrogenase concentration and number of organ sites containing metastases have been reported for patients treated with dabrafenib and trametinib for advanced melanoma. We aimed to validate these prognostic groups for patients treated with vemurafenib and cobimetinib in the coBRIM...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000634
更新日期:2020-06-01 00:00:00
abstract::Tumor cell invasion through basement membranes and into stromal tissue are key steps for promoting growth and metastasis. Tumor cells express various extracellular-matrix-degrading enzymes such as matrix metalloproteinases (MMPs) to degrade extracellular matrix components to facilitate tumor migration and invasion. Hi...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282a660ad
更新日期:2007-08-01 00:00:00
abstract::We studied the levels of serum copper and zinc as possible diagnostic factors or markers for the early detection of patients with melanoma. Levels were determined in 35 melanoma patients at various clinical stages and in 39 healthy persons. Measurements were performed by atomic absorption spectroscopy using 5100-PC-Pe...
journal_title:Melanoma research
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::Interleukin-8 (IL-8) is a cytokine that is thought to promote melanoma tumour progression. We evaluated and adapted a non-radioactive, reverse transcriptase-polymerase chain reaction method for semiquantitative analysis of IL-8 mRNA expression. Using this technique we studied the regulation of IL-8 levels in the melan...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199608000-00005
更新日期:1996-08-01 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::Melanoma is one of the most common cancers worldwide and its incidence has been increasing over the past few decades. Gallic acid (GA) can inhibit the growth of human cancer cells in vitro and in vivo. However, there is no available information to address the effects of GA on migration and invasion of human skin cance...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283414444
更新日期:2011-08-01 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
abstract::Primary malignant melanoma of the esophagus is an extremely rare, but highly aggressive, tumor. The prognosis for primary malignant melanoma of the esophagus remains dismal in most literatures. We report here a case of primary malignant melanoma of the esophagus that was treated by surgical resection and, additionally...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283307c8a
更新日期:2010-02-01 00:00:00
abstract::We studied the efficacy, tolerability and clinical courses of dabrafenib in patients with metastatic melanoma who were ineligible for enrolment into a clinical trial. Between July 2011 and May 2013, patients with unresectable stage III or stage IV, V600-mutated metastatic melanoma who were not eligible for inclusion i...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000036
更新日期:2014-04-01 00:00:00
abstract::Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histologi...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200306000-00006
更新日期:2003-06-01 00:00:00
abstract::To our knowledge modulation of the expression of tumour necrosis factor-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. The specificity of the staining reaction ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199704000-00008
更新日期:1997-04-01 00:00:00
abstract::Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000214
更新日期:2016-02-01 00:00:00
abstract::The management of melanoma brain metastases (MBM) includes different therapeutic modalities, such as surgery, radiotherapy and chemotherapy. Despite the choice of treatments, survival remains poor, exceeding 1 year only in patients with solitary metastases and absence of extracranial disease. A total of 115 consecutiv...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000029
更新日期:2014-02-01 00:00:00
abstract::Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle control genes leading ultimately to DNA repair or apoptosis. The hypothesis examined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mutagenesis. Epstein-B...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200102000-00001
更新日期:2001-02-01 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::Between 6 and 14% of malignant melanomas have been reported to occur in a familial pattern. In this study 785 melanoma patients from the Victorian Melanoma Service and the private practice of a dermatologist were assessed for the total number of melanocytic naevi, the number of dysplastic naevi and other clinical char...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199810000-00011
更新日期:1998-10-01 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::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::In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with syste...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
doi:10.1097/00008390-199306000-00005
更新日期:1993-06-01 00:00:00
abstract::Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followe...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
doi:10.1097/00008390-200404000-00016
更新日期:2004-04-01 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::Recently, we reported on the associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma (CM). Considering the reported correlation between MMP1 expression and melanoma progression, we hypothesized that these promoter SNPs might affect CM p...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32834fc46b
更新日期:2012-04-01 00:00:00
abstract::An inactive cathepsin B-like enzyme with a molecular mass of 40 kD was found in a human melanoma culture medium. The inactive form of this enzyme was converted into an active form with a molecular mass of 28 kD by pepsin treatment. This activated cathepsin B-like enzyme had almost the same characteristics regarding mo...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199201000-00005
更新日期:1992-01-01 00:00:00
abstract::Malignant melanoma is not only one of the most aggressive and lethal types of neoplasm, but its incidence in the general population is currently increasing at an alarming pace. It is interesting that most melanomas retain many of their characteristics of differentiation, including a dendritic nature and the production...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:
更新日期:1991-11-01 00:00:00
abstract::Metabolic imaging with F-18 fluorodeoxy-D-glucose positron emission tomography is one of the most sensitive and non-invasive techniques, and has proved useful in melanoma. We designed, in 2004, at the Institute Gustave Roussy, a prospective study to determine the value of F-18 fluorodeoxy-D-glucose positron emission t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32815c10b0
更新日期:2007-06-01 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::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