Gemcitabine combined with oxaliplatin is safe and effective in patients with previously untreated advanced pancreatic adenocarcinoma

AIM: The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1% with a 12.5% complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. CONCLUSION: These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patients with locally-advanced disease.     

Histone deacetylase 6 inhibition enhances oncolytic viral replication in glioma

Oncolytic viral (OV) therapy, which uses genetically engineered tumor-targeting viruses, is being increasingly used in cancer clinical trials due to the direct cytolytic effects of this treatment that appear to provoke a robust immune response against the tumor. As OVs enter tumor cells, intrinsic host defenses have the potential to hinder viral replication and spread within the tumor mass. In this report, we show that histone deacetylase 6 (HDAC6) in tumor cells appears to alter the trafficking of post-entry OVs from the nucleus toward lysosomes. In glioma cell lines and glioma-stem–like cells, HDAC6 inhibition (HDAC6i) by either pharmacologic or genetic means substantially increased replication of oncolytic herpes simplex virus type 1 (oHSV). Moreover, HDAC6i increased shuttling of post-entry oHSV to the nucleus. In addition, electron microscopic analysis revealed that post-entry oHSVs are preferentially taken up into glioma cells through the endosomal pathway rather than via fusion at the cell surface. Together, these findings illustrate a mechanism of glioma cell defense against an incoming infection by oHSV and identify possible approaches to enhance oHSV replication and subsequent lysis of tumor cells.     

Rapid rule out of myocardial infarction with the use of copeptin as a biomarker for cardiac injury

Copeptin is a non‐specific marker of an endogenous stress response. A dual biomarker marker approach involving the simultaneous use of troponin and copeptin assays may assist early exclusion of acute coronary syndrome in Australian emergency departments. The utility and limitations of this approach are discussed.     

Novel quasi-subgenotype D2 of hepatitis B virus identified in Taiwanese aborigines

The hepatitis B virus (HBV) genomes in Taiwanese aborigines, whose ancestors have lived in Taiwan for over 10,000 years, have not been characterized. In order to characterize of HBV in this special population, serum samples were obtained from serologically HBsAg-positive 27 Taiwanese aborigines. The pre-S1/S2 region and the full-length 3.2 kb of the HBV genome were amplified by PCR. Obtained amplicons were sequenced and confirmed the HBV genotypes by phylogenetic analysis. By phylogenetic analysis of the sequence of pre-S1/pre-S2 region, HBV/B2 (21/27: 78 %) was the most prevalent followed by genotype D (6/27: 22 %). Two strains of HBV/B2, each having 3,215 bp genomes, had recombination with genotype C in the pre-C/C gene which is characteristic of subgenotype B2 circulating in Southeast Asia. Interestingly, six strains of genotype D formed a distinct cluster between subgenotypes D1 and D2 suggesting a novel group of HBV. A similar finding could also be confirmed based on the entire 3,182 bp genome from four strains of HBV/D. This new cluster was supported by a branch with 99 % bootstrap value and 3.4–5.8 % nucleotide divergence over the entire genome from other known subgenotypes D1 to D9. Four strains of the new D subgenotype showed serotype ayw2, but had unique amino acid sequences consisting of N115 in the preS/S gene; P41 in the X gene; S239, K/E295, V567, and P708 in the P gene, respectively. From the above results, we provisionally proposed to designate it as novel quasi-subgenotype D2 identified in Taiwanese aborigines.