No abstract

Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (o7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/ Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.

Background and aims: A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects. Methods: From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years. Results: Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) −5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1-16; erosion 23.2% v 12.3%, 95% CI 1-21). Conclusion: A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.

Background: Fatty acid oxidation (FAO) disorders are a heterogeneous group of inborn errors in the transportation and oxidation of fatty acids. FAO disorders were thought to be very rare in the Chinese population.