Middleburg, VA, United States
Middleburg, VA, United States
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Wang G.,University of Jinan | Wang G.,Chinese National Institute for Viral Disease Control and Prevention | Dong X.,Five Plus | Tian W.,Chinese National Institute for Viral Disease Control and Prevention | And 5 more authors.
Shengwu Gongcheng Xuebao/Chinese Journal of Biotechnology | Year: 2013

We evaluated the anti-HBV effects of nucleotide analogues, Entecavir (ETV) and Lamivudine (LAM) targeting mouse model of HBV persistent infection with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV). Ninety percent (27 of 30 mice) of rAAV8-treated mice were chosen as mouse model. Four groups were orally administrated with different doses of ETV (1 mg/(kg·d) or 0.1 mg/(kg·d)) and LAM (500 mg/(kg·d) or 100 mg/(kg·d) once a day for 10 days. The other two groups were set as normal saline treated and untreated control. We detected the levels of HBV DNA, HBeAg and HBsAg in sera at different time. Results indicate that HBV DNA level decreased significantly (P lt; 0.05) in drug-treated groups compared with normal saline group after drug administration. Fifteen days after the drug withdrawal, HBV DNA level rebounded back obviously (P lt; 0.05) in groups with low doses of ETV and LAM. However, there was no apparent change of HBeAg and HBsAg in the whole process among all groups. These results showed that our model could reflect the anti-viral effect of nucleotide analogues. This model can be a useful and convenient tool for anti-HBV drug discovery. © 2013 by the institute of Microbiology.

Oeffinger K.C.,Sloan Kettering Cancer Center | Hudson M.M.,St Jude Childrens Research Hospital | Mertens A.C.,Emory University | Smith S.M.,Stanford University | And 6 more authors.
Pediatric Blood and Cancer | Year: 2011

Background: Hodgkin lymphoma (HL) survivors face substantially elevated risks of breast cancer and cardiovascular disease. They and their physicians are often unaware of these risks and surveillance recommendations. +Procedure: A prospective one-arm study was conducted among a random sample of 72 HL survivors, ages 27-55 years, participating in the Childhood Cancer Survivor Study (CCSS) who were at increased risk for breast cancer and/or cardiomyopathy and had not had a screening mammogram or echocardiogram, respectively, within the prior 2 years. A one-page survivorship care plan with recommendations for surveillance was mailed to participants. In addition, survivors' primary physicians were contacted and provided patient-specific information and a web-based Virtual Information Center was made available for both survivors and physicians. Outcomes were assessed by telephone 6 months after the intervention. +Results: The survivor participation (62/72; 86%) and 6-month retention (56/61; 92%) rates were high. Tension and anxiety, measured by the Profile of Mood States, did not increase following risk notification; 91% of survivors described their reactions to receiving the information in positive terms. At 6 months, 41% of survivors reported having completed the recommended mammogram; 20% reported having an echocardiogram (females 30%, males 10%). Only 29% of survivors visited the website. Nine physicians enrolled, and none used the study resources. +Conclusion: A mailed, personalized survivorship care plan was effective in communicating risk and increasing compliance with recommended medical surveillance. Internet- and telephone-based strategies to communicate risk were not utilized by survivors or physicians. © 2011 Wiley-Liss, Inc.

PubMed | Fudan University and Five Plus
Type: Journal Article | Journal: Frontiers of medicine | Year: 2016

Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5 10(11) and 1 10(11) virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.

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