ArticleJournal of translational medicine2007
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization.
Article in Journal of translational medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 103 citations in OpenAlex.
- Expression of drug targets in patients treated with sorafenib, carboplatin and paclitaxel.PloS one · 2013Trial
- Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer.BMC clinical pharmacology · 2011Trial
- Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Trial
- ZNF468 stabilization by RNF4 enhances apoptosis resistance and carboplatin resistance in breast cancer via transcription activation of XIAP.Genes & genomics · 2026Article
- Reduced expression of BIRC2 and BIRC3 associated with longer survival in pediatric high-grade gliomas.Scientific reports · 2026Article
- Recent advances on Hippo-YAP pathway in skin diseases.Frontiers in immunology · 2025Review
- Ecto-NOX Disulfide-Thiol Exchanger 2 (ENOX2/tNOX) Is a Potential Prognostic Marker in Primary Malignant Melanoma and May Serve as a Therapeutic Target.International journal of molecular sciences · 2024Article
- Review
- Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis.Molecules (Basel, Switzerland) · 2022Article
- The role of isoflavones in augmenting the effects of radiotherapy.Frontiers in oncology · 2022Review
- β-Thujaplicin Enhances TRAIL-Induced Apoptosis via the Dual Effects of XIAP Inhibition and Degradation in NCI-H460 Human Lung Cancer Cells.Medicines (Basel, Switzerland) · 2021Article
- circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway.Oxidative medicine and cellular longevity · 2021Article
- Phenoxodiol sensitizes metastatic colorectal cancer cells to 5-fluorouracil- and oxaliplatin-induced apoptosis through intrinsic pathway.EXCLI journal · 2020Article
- XIAP Interaction with E2F1 and Sp1 via its BIR2 and BIR3 domains specific activated MMP2 to promote bladder cancer invasion.Oncogenesis · 2019Article
- Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer.Cell adhesion & migration · 2019Article
- Triggering of eryptosis, the suicidal erythrocyte death, by phenoxodiol.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade.Cancer immunology, immunotherapy : CII · 2019Article
- Synthesis of Dextran-Phenoxodiol and Evaluation of Its Physical Stability and Biological Activity.Frontiers in bioengineering and biotechnology · 2019Article
- Comparative proteomic study of dog and human saliva.PloS one · 2018Article
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
XIAP up-regulation is associated with chemotherapy resistance. Phenoxodiol causes XIAP degradation and chemotherapy sensitization in ovarian cancer. Here we assessed XIAP expression in melanomas, using tissue microarrays containing 436 melanomas and 336 nevi by a novel method of automated, quantitative analysis (AQUA). We used S100 to define pixels as melanoma (tumor mask) within the array spot, and measured XIAP expression using Cy5-conjugated antibodies within the mask. XIAP expression was significantly higher in melanomas than nevi (P < 0.0001), and higher in metastatic than primary lesions (P < 0.0001). We then assessed a panel of melanoma cell lines for XIAP expression, and found high expression in all cell lines. Three of the cell lines were assessed for Phenoxodiol and Carboplatin sensitivity; all were resistant to Carboplatin and showed variable sensitivity to Phenoxodiol. Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization. We conclude that XIAP levels in clinical specimens are significantly higher in melanomas than their benign counterparts, and higher in metastatic than in primary specimens, suggesting an association with malignant progression and disease aggression. Melanoma resistance to Carboplatin is possibly due to XIAP over-expression. Phenoxodiol can sensitize melanoma cells to Carboplatin in vitro with corresponding XIAP degradation, although the precise target and mechanism of action of Phenoxodiol are subject to further assessment. Targeting XIAP warrants additional investigation as a therapeutic approach for metastatic melanoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.