The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer.

PURPOSE: Epithelial ovarian cancer is one of the most lethal female genital tract cancers. Early diagnosis of EOC would benefit the patients a lot. Human epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the role of HE4 in diagnosis of epithelial ovarian cancer (EOC). METHODS: We searched Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for articles that included HE4's origin, characteristics, detection methods, clinical efficacy alone or combined with CA125, the risk of malignancy index, and the risk of ovarian malignancy algorithm. The diagnostic performance for the EOC and the role in the recurrence and procession in EOC were also discussed. RESULTS: We got 83 most related articles and found that there were significantly difference existing among the studies, such as the clinical characteristics of patients, the methodology for measuring HE4, the different cut-offs for HE4 and so on. CONCLUSION: HE4 is a promising biomarker for the early diagnosis of EOC. However, each lab should establish its own reference internal of HE4.

Association of 14 bp insertion/deletion polymorphism of the HLA-G gene in father with severe preeclampsia in Chinese.

Preeclampsia (PE), especially severe PE including early (before 34 weeks' gestation) and late (after 34 weeks' gestation) onset PE, is one of the leading causes of maternal and fetal mortality and morbidity. It is well known that abnormal human leukocyte antigen subtype G (HLA-G) expression may contribute to PE. In this study, we investigated allelic and genotypic frequencies of the 14 bp deletion/insert polymorphism in the 3(')-untranslated region (3(')-UTR) of the HLA-G gene in cases (120 pairs of mother-offspring, 82 couples, and 67 pairs of father-offspring with severe PE) and controls (158 pairs of mother-offspring, 87 couples, and 75 pairs of father-offspring with normal pregnancy). We found that the frequencies of the +14 bp/+14 bp HLA-G genotype of the offspring were significantly higher in the severe and early onset severe PE cases compared with controls, and the frequencies of the -14 bp/-14 bp HLA-G genotype of the offspring were significantly lower in the early onset severe PE cases compared with controls. The frequency of combined -14 bp/+14 bp mother/+14 bp/+14 bp offspring genotypes was significantly higher in the severe and early onset severe PE cases compared with controls, and the frequency of combined -14 bp/+14 bp mother/-14 bp/-14 bp offspring genotypes was significantly lower in the early onset severe PE cases compared with late onset severe PE cases. The frequency of combined -14 bp/-14 bp father/-14 bp/-14 bp offspring genotypes was significantly lower in the early onset severe PE cases compared with late onset severe PE cases and controls. In overview, the HLA-G 14 bp deletion/insert polymorphism is associated with severe PE in father-offspring, and its distribution is different between the early and late onset severe PE.

An hepatitis B virus surface antigen specific single chain of variable fragment derived from a natural immune antigen binding fragment phage display library is specifically internalized by HepG2.2.15 cells.

Hepatitis B virus surface antigen (HBsAg), a specific antigen on the membrane of hepatitis B virus (HBV)-infected cells, provides a perfect target for therapeutic drugs. In order to mediate successful targeted delivery of these therapies, it is essential to have antibodies that recognize HBsAg with high specificity and affinity. In this report, we constructed a natural immune antigen binding fragments (Fab) antibody phage display library against HBsAg and after three rounds of panning, five Fab fragments with significant HBsAg binding ability were selected and analysed. DNA sequencing revealed that all the light chains had the same sequence, while all the Fd genes exhibited different sequences. For further application, all of the Fab antibodies were reconstructed into single chain antibodies (scFvs) and expressed in Escherichia coli BL21 cells. Indirect enzyme-linked immunosorbent assay analysis demonstrated that all five scFvs maintained a high affinity for HBsAg and could bind HBsAg on the membrane of HBV-infected cells. Indirect fluorescent staining analysis revealed that one of the scFvs (scFv15) could be internalized into HBsAg-positive HepG2.2.15 cells through clathrin-mediated endocytosis pathway. The internalizing scFv15 antibody would have great potential for the targeted delivery of therapeutics to HBV-infected cells.

Selective proapoptotic activity of a secreted recombinant antibody/AIF fusion protein in carcinomas overexpressing HER2.

Apoptosis-inducing factor (AIF) represents a caspase-independent apoptotic pathway in the cell, and a mitochondrial localization sequence-truncated AIF (AIFDelta1-120) can be relocated from the cytoplasm to the nucleus and exhibit a constitutive proapoptotic activity. Here, we generated a chimeric immuno-AIF protein, which comprised an HER2 antibody, a Pseudomonas exotoxin translocation domain and AIFDelta1-120. Human Jurkat cells transfected with the immuno-AIF gene could express and secrete the chimeric protein, which selectively recognized HER2-overexpressing tumor cells and was endocytosed. Subsequent cleavage of truncated AIF from immuno-AIF and its release from the internalized vesicles resulted in apoptosis of tumor cells. Intramuscular injection of the immuno-AIF gene caused significant suppression of tumors and substantially prolonged mice survival in an HER2-overexpressing xenograft tumor model. Our study demonstrates the feasibility of the immuno-AIF gene as a novel approach to treating cancers that overexpress HER2.