Li X.,Peking Union Medical College |
Kang J.,Institute for Viral Hepatitis |
Kang J.,Chongqing Medical University |
Pan Q.,Institute for Viral Hepatitis |
And 11 more authors.
Oncology Reports | Year: 2016
To identify rare mutations and retrospectively estimate the cancer risk of a 45-year old female patient diagnosed with Li-Fraumeni syndrome (LFS), who developed nine primary malignant neoplasms in a period of 38 years, we conducted next-generation sequencing in this patient. Whole-genome and whole-exome sequencing were performed in DNA of whole blood obtained a year prior to the diagnosis of acute myeloid leukemia (AML) and at the time of diagnosis of AML, respectively. We analyzed rare mutations in cancer susceptibility genes using a candidate strategy and estimated cancer risk using the Risk-O-Gram algorithm. We found rare mutations in cancer susceptibility genes associated with an increased hereditary cancer risk in the patient. Notably, the number of mutated genes in p53 signaling pathway was significantly higher than expected (p=0.02). However, the phenotype of multiple malignant neoplasms of the studied patient was unlikely to be caused by accumulation of common cancer risk alleles. In conclusion, we established the mutation profile in a rare case of Li-Fraumeni syndrome, illustrating that the rare mutations rather than the cumulative of common risk alleles leading to an increased cancer risk in the patient.
Yang J.,Institute for Viral Hepatitis |
Tang N.,Institute for Viral Hepatitis |
Sun H.,Institute for Viral Hepatitis |
Liu Q.,Institute for Viral Hepatitis |
Deng J.-C.,Chongqing Medical University
Medical Journal of Chinese People's Liberation Army | Year: 2016
Objective To construct recombinant adenovirus expressing augmenter of liver regeneration (ALR) gene and investigate its anti-apoptosis effect. Methods Recombinant shuttle vector pAdTrack-TO4-mALR and pAdTrack-TO4-hALR were constructed by recombinant DNA technology and recombinant adenovirus Ad-GFP-mALR and Ad-GFP-hALR were acquired by homologous recombination. After four cycles of amplification, high titers of the recombinant adenovirus Ad-GFP-mALR and Ad-GFP-hALR were obtained. The expression of green fluorescent protein was detected to evaluate the infection efficiency of Ad-GFPmALR and Ad-GFP-hALR, Western blotting was applied to assess the expression of ALR and Bcl-2/Bax protein, and CCK-8 assay was used to evaluate the proliferation activity of L02 cells when L02 cells were infected with either Ad-GFP-mALR or Ad-GFPhALR. Flow cytometry was utilized to detect the L02 cells' apoptosis rate induced by palmitic acid (PA). Results pAdTrack-TO4-mALR, pAdTrack-TO4-hALR, Ad-GFP-mALR and Ad-GFP-hALR were constructed successfully; the recombinant adenovirus Ad-GFP-mALR and Ad-GFP-hALR could infected L02 cells efficiently and expressed steadily in L02 cells. The L02 cells infected with either Ad-GFP-mALR or Ad-GFP-hALR had significantly increased proliferation activity compared with those uninfected and those infected with Ad-GFP. L02 cells with the infection of either Ad-GFP-mALR or Ad-GFP-hALR had significantly lower apoptosis rate, enhanced the Bcl-2 expression and decreased the Bax expression when L02 cells were treated with palmitic acid compared with those uninfected and those infected with Ad-GFP. Conclusion Recombinant adenovirus Ad-GFP-mALR and Ad-GFP-hALR here have been constructed successfully and the over expression of either mALR or hALR has the ability to promote the proliferation activity of L02 cells and the effect against L02 cell apoptosis induced by palmitic acid. © 2016, People’s Military Medical Press. All rights reserved.
Chen M.,Institute for Viral Hepatitis |
Hu P.,Institute for Viral Hepatitis |
Ling N.,Institute for Viral Hepatitis |
Peng H.,Chongqing Medical University |
And 4 more authors.
PLoS ONE | Year: 2015
Background γδ T cells play an important role in infectious, autoimmune, or neoplastic diseases. Here, a study was conducted to investigate the dynamic changes in phenotype and function of peripheral γδ T cells in patients with chronic hepatitis B (CHB) during pegylated-interferon (pegIFN)-α treatment, and to explore their roles in IFN- α therapy. Methods Total 15 CHB patients with pegIFN-α therapy and 6 healthy controls (HC) were enrolled in this study. Flow cytometry was used for the study of frequency of peripheral γδ T cells, subtypes, effector or memory γδ T cells, and also the IFN-γ+, TNF-α+, CD107a+ or Granzyme B+ γδ T cells in 10 patients at week 0, 4, 8, 12, 24, 36 and 48 of treatment. Another 5 CHB patients and 6 HC were recruited for the γδ T cell isolation, and gene expression in γδ T cells was evaluated before or after IFN-α treatment in vitro. Results Although γδT cells decreased in CHB patients during pegIFN-α therapy, their capacities to produce TNF-α and to express CD107a were enhanced. More effector γδT cells (CD27-CD45RA+) were found in the response group than in non-response group. Furthermore, IFN-α boosted the expression of Mx2 and cytokine genes in γδT cells from CHB patients in vitro. Conclusion IFN-α could enhance the cytokine production or cytotoxicity potential of γδT cells in vivo and in vitro. The enhanced function of γδT cells might contribute to the effect of IFN-α treatment. © 2015 Chen et al.
Qing Y.,Institute for Viral Hepatitis |
Chen M.,Institute for Viral Hepatitis |
Zhao J.,Institute for Viral Hepatitis |
Hu H.,Institute for Viral Hepatitis |
And 4 more authors.
Vaccine | Year: 2010
Background: The hepatitis B virus (HBV) DNA vaccine can generate both HBsAg-specific humoral and cellular immune responses. The immune response can be improved by inclusion of an adjuvant, such as the cytokine GM-CSF which is known to be a very good adjuvant. Methods: To investigate the ability of GM-CSF to enhance HBV-DNA vaccines, we constructed the plasmids by fusion of GM-CSF gene to the HBV-S gene. Normal and HBV-transgenic mice were then immunized with these plasmids. Results: Our results show that pCDNA3.1-GM-CSF-S induced the most powerful HBsAg-specific humoral and cellular immune response, and that it was able to overcome the non-response to HBsAg in HBV-transgenic mice. In contrast, pCDNA3.1-S-GM-CSF was able to induce only a very poor immune response. Conclusions: When the HBV-S gene is fused to the GM-CSF gene, the immune effects of the HBV DNA vaccine both in normal and HBV-transgenic mice can be strengthened and HBV-DNA plasmids fused with GM-CSF may be useful for both preventative and therapeutic purposes. © 2010 Elsevier Ltd. All rights reserved.