Isolated Hepatic Perfusion with High-Dose Melphalan Results in Immediate Alterations in Tumor Gene Expression in Patients with Metastatic Ocular Melanoma
| Autor: | Marybeth Hughes, Hui Xu, David L. Bartlett, James F. Pingpank, Sheelu Varghese, Tatiana Beresnev, H. Richard Alexander |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Melphalan RFC5 Isolation perfusion Isolated hepatic perfusion Ocular Melanoma Cohort Studies Surgical oncology Gene expression Biomarkers Tumor medicine Humans RNA Messenger Antineoplastic Agents Alkylating Melanoma Aged Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Microarray analysis techniques business.industry Eye Neoplasms Gene Expression Profiling Liver Neoplasms Hyperthermia Induced Middle Aged Survival Rate Treatment Outcome Oncology Chemotherapy Cancer Regional Perfusion Cancer research Female Surgery business medicine.drug |
| Zdroj: | Annals of Surgical Oncology. 17:1870-1877 |
| ISSN: | 1534-4681 1068-9265 |
| Popis: | Patients with ocular melanoma liver metastases have a poor prognosis, treatment options are limited, and median survival is less than 1 year. In this study, we characterized the early molecular changes that occur in tumors immediately after vascular isolation perfusion with melphalan with hyperthermia in patients with hepatic metastases from ocular melanoma. Patients underwent treatment on a clinical trial using a 60-min hyperthermic isolated hepatic perfusion (IHP) with melphalan. Microarray analysis was performed in 28 tumor samples obtained intraoperatively of which 12 were pre- and 16 were post-IHP. Various statistical analyses were performed to identify differentially expressed genes and gene categories between the groups. Median survival of 17 treated patients was 11.9 months. Unsupervised hierarchical clustering of all tumors resulted in separation of pre and post-IHP samples into two distinct groups. Analysis of genes showed that the Ras GTPase activator, ecotropic viral integration site 5 (EVI5), and several other melanoma-associated genes were overexpressed in pre-IHP tumors. In post-IHP samples the overexpression of a DNA replication associated gene, replication factor C (RFC5), was significantly associated with shortened survival (P |
| Databáze: | OpenAIRE |
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