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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-8-16
pubmed:abstractText
Melanoma remains notoriously resistant to current chemotherapeutics, leaving an acute need for novel therapeutic approaches. The aim of this study was to determine the prognostic and therapeutic significance of X-linked inhibitor of apoptosis protein (XIAP) in melanoma through correlation of XIAP expression with disease stage, RAS/RAF mutational status, clinical outcome, and susceptibility to endoplasmic reticulum (ER) stress-induced cell death. XIAP expression and N-RAS/B-RAF mutational status were retrospectively determined in a cohort of 55 primary cutaneous melanocytic lesions selected and grouped according to the American Joint Committee on Cancer staging system. Short hairpin RNA interference of XIAP was used to analyze the effect of XIAP expression on ER stress-induced apoptosis in response to fenretinide or bortezomib in vitro. The results showed that XIAP positivity increased with progressive disease stage, although there was no significant correlation between XIAP positivity and combined N-RAS/B-RAF mutational status or clinical outcome. However, XIAP knockdown significantly increased ER stress-induced apoptosis of melanoma cells in a caspase-dependant manner. The correlation of XIAP expression with disease stage, as well as data showing that XIAP knockdown significantly increases fenretinide and bortezomib-induced apoptosis of metastatic melanoma cells, suggests that XIAP may prove to be an effective therapeutic target for melanoma therapy.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2250-8
pubmed:dateRevised
2011-3-14
pubmed:meshHeading
pubmed-meshheading:20520630-Antineoplastic Agents, pubmed-meshheading:20520630-Apoptosis, pubmed-meshheading:20520630-Boronic Acids, pubmed-meshheading:20520630-Drug Resistance, Neoplasm, pubmed-meshheading:20520630-Endoplasmic Reticulum, pubmed-meshheading:20520630-Female, pubmed-meshheading:20520630-Fenretinide, pubmed-meshheading:20520630-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20520630-Genes, ras, pubmed-meshheading:20520630-Humans, pubmed-meshheading:20520630-Male, pubmed-meshheading:20520630-Melanoma, pubmed-meshheading:20520630-Middle Aged, pubmed-meshheading:20520630-Mutation, pubmed-meshheading:20520630-Nevus, Pigmented, pubmed-meshheading:20520630-Proto-Oncogene Proteins B-raf, pubmed-meshheading:20520630-Pyrazines, pubmed-meshheading:20520630-RNA, Small Interfering, pubmed-meshheading:20520630-Skin Neoplasms, pubmed-meshheading:20520630-Stress, Physiological, pubmed-meshheading:20520630-X-Linked Inhibitor of Apoptosis Protein
pubmed:year
2010
pubmed:articleTitle
Targeting X-linked inhibitor of apoptosis protein to increase the efficacy of endoplasmic reticulum stress-induced apoptosis for melanoma therapy.
pubmed:affiliation
Dermatological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't