Six-Transmembrane Epithelial Antigen of the Prostate-1 (STEAP-1)-Targeted Ultrasound Imaging Microbubble Improves Detection of Prostate Cancer In Vivo.

PURPOSE: To investigate the feasibility of the 6-transmembrane epithelial antigen of the prostate-1 (STEAP-1)-targeted microbubbles for enhancing ultrasound imaging of prostate tumors in the nude mouse xenograft models. METHODS: Contrast agents were established by conjugating biotinylated STEAP-1 monoclonal antibodies with streptavidin coated SonoVue microbubbles. Then, ordinary SonoVue (Bracco, Milan, Italy) microbubble and STEAP-1-targeted SonoVue microbubble were used, respectively, for contrast-enhanced sonography to detect prostate tumors in the nude mouse xenograft models. The characteristics, including peak intensity, time to peak, area under the curve, and mean transit time, were measured. RESULTS: The biological characteristics of STEAP-1-targeted SonoVue microbubbles were stable. STEAP-1-targeted SonoVue microbubbles can successfully conjugate to prostate cancer cell lines in vitro. Enhancement of ultrasound signal intensity was determined after injection of STEAP-1-targeted SonoVue microbubble, compared with ordinary SonoVue microbubble. Higher intensities of ultrasound signals in xenograft tumor of prostate cancer were associated with increased levels of STEAP-1 expression. CONCLUSION: Our results suggest that SonoVue microbubble carrying STEAP-1 monoclonal antibody could improve the ultrasound visualization of prostate cancer and identify the tumor more effectively in vivo. A prospective study is required to validate our finding in patients with prostate cancer.

High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program.

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

Improved myocardial perfusion and cardiac function by controlled-release basic fibroblast growth factor using fibrin glue in a canine infarct model.

OBJECTIVE: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors. Fibrin glue (FG) provides a reservoir for controlled-release of growth factors. The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF) incorporating FG on angiogenesis and cardiac performance in a canine infarct model. METHODS: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD). Group I (n=6) underwent ligation of LAD alone. In Group II, transmural channels were created in the infarct area (n=6). In Group III, non-transmural channels were created to locate FG cylinders containing bFGF (n=6). Eight weeks after operation, myocardial perfusion was assessed by single photon emission computed tomography, cardiac function by echocardiography, and vascular development by immunohistochemical staining. RESULTS: Total vascular density and the number of large vessels (internal diameter ≥50 µm) were dramatically higher in Group III than in Groups I and II at eight weeks. Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score. Animals in Group III presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups. CONCLUSIONS: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels, thus enabling improvement in myocardial perfusion and cardiac function.