Mesothelioma is an uncommon malignancy whose global incidence continues to rise. The therapeutic standard for advanced disease is intravenous pemetrexed and cisplatin. The antifolate capecitabine is significantly less effective than pemetrexed. The balance between thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and Thymidine Phosphorylase (TP) is critical to the efficacy of capecitabine. DNA from mesothelioma cell lines was bisulfite treated and examined by MS-PCR, RNA was obtained for real time PCR analysis, and protein lysates were obtained for Western immunoblot analysis. Cytotoxicity was assessed by MTT assay, comparing 5-aza-CdR pretreated or untreated cells with 5′-Deoxy-5-fluorouridine (DFUR), 5-FU, and pemetrexed. Finally bisulfite sequencing of the extracellular growth factor-1 (ECGF-1) gene was performed on 4 mesothelioma samples and pericardial tissue. One of the four cell lines tested (H290) was methylated for ECGF-1. This corresponded to a lack of TP expression by real time PCR and Western immunoblot. Treatment with 1 μM 5-aza-CdR increased TP mRNA and protein expression in H290. DFUR, the substrate for TP, showed increased cytotoxicity when delivered after 5-aza-CdR exposure in the methylated cell line. There was no difference in any of the unmethylated cell lines when cells were exposed to 5-FU or pemetrexed with or without 5-aza-CdR. Patient tumor samples revealed an increased number of methylated CpG sites in ECGF-1 compared to normal pericardium. Methylation of ECGF-1, leads to transcriptional silencing of TP and may explain the lack of any effect of capecitabine, especially when compared to pemetrexed.

Vpx is a virion-associated protein of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency viruses. The yeast two-hybrid system was used to identify invariant chain (Ii) as a cellular protein that interacts with HIV-2 Vpx. Vpx-Ii interaction was confirmed in cell-free reactions using bacterially expressed glutathione S-transferase fusion proteins and by coimmunoprecipitation in transfected and infected cells. In chronically infected cells expressing Vpx, Ii levels were markedly decreased, presumably due to enhanced degradation. These findings suggest that Vpx may disrupt major histocompatibility complex class II antigen presentation.

Age and preoperative jaundice are more predictive of malignancy than CA19-9 alone unless levels are greater than 150 U/mL. Preoperative CA19-9 levels should be interpreted within the context of these other clinical factors.

Objectives: There is a paucity of data exploring treatment options for refractory pancreatic cancer. Oxaliplatin has interesting activity in second-line therapy. Fixed-dose-rate gemcitabine (GFDR, 10 mg/m²/min) has shown promising results in patients with advanced pancreatic cancer over standard-dose-rate (30 min) gemcitabine (GSDR). Methods: We conducted a retrospective analysis of the experience of our cancer center with GFDR and oxaliplatin (GEMOX) in patients who failed GSDR. GEMOX consisted of gemcitabine 1,000 mg/m² over 100 min on day 1 and oxaliplatin 100 mg/m² over 2 h on day 2 every 2 weeks. Eligible patients were required to have measurable metastatic adenocarcinoma of the pancreas and to have failed prior GSDR. Results: Seventeen patients (median age 62 years) who were treated at the Ohio State University with GEMOX following GSDR failure between November 2003 and January 2008 were included in this study. Twenty-four percent of all patients had a partial response, 29% had stable disease and 47% had progressive disease. The median progression-free survival was 2.6 months and the median overall survival was 6.4 months. There were no unexpected toxicities. Conclusion: GEMOX shows interesting activity and acceptable tolerability in patients with metastatic pancreatic cancer who failed prior GSDR. Our results are consistent with previously published results.