AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Balancing Narrow and Broad Perspectives in Radiology.

OBJECTIVE. The purpose of this article is to help radiologists achieve a balance between narrow and broad perspectives in their work. CONCLUSION. There are two fundamentally different perspectives from which radiologists can work: narrow and broad. Both have important roles, yet if the balance between these perspectives shifts excessively in one direction or the other, problems can arise. By understanding the respective strengths and weaknesses of each perspective, radiologists can achieve a more appropriate balance between them.

Experimental Evaluation of (L)Au Electron-Donor Ability in Cationic Gold Carbene Complexes.

29 Si NMR spectroscopy was employed to evaluate the electron donor properties of the (L)Au fragments in the cationic gold (ß,ß-disilyl)vinylidene complexes [(L)Au=C=CSi(Me)2 CH2 CH2 Si(Me)2 ]+ B(C6 F5 )4- [L=P(tBu)2 o-biphenyl or NHC] relative to the p-substituted aryl group in the α-aryl-(ß,ß-disilyl)vinyl cations [(p-C6 H4 X)-C= CSi(Me)2 CH2 CH2 Si(Me)2 ]+ B(C6 F5 )4- . Similarly, 19 F NMR was employed to evaluate the σ- and π-electron donor properties of the (L)Au fragments in the neutral gold fluorophenyl complexes (L)Au(C6 H4 F) and in the cationic (fluorophenyl)methoxycarbene complexes [(L)AuC(OMe)(C6 H4 F)]+ SbF6- [L=P(tBu)2 o-biphenyl or IPr] relative to the p-substituted aryl group of the protonated monofluorobenzophenones [(p-C6 H4 X)(C6 H4 F)COH]+ OTf- . The results of these studies indicate that relative to p-substituted aryl groups, the gold (L)Au fragments [L=P(tBu)2 o-biphenyl or NHC] are significantly more inductively electron donating and are comparable π-donors and for this reason, the extent of (L)Au→C1 electron donation in gold carbene complexes appears to exceed that provided by a p-(dimethyamino)phenyl group. Furthermore, the [L=P(tBu)2 o-biphenyl]Au fragment is a nominally stronger electron donor than the (IPr)Au fragment, and both are significantly more inductively electron donating than the (PPh3 )Au and [P(OMe)3 ]Au fragments.

An efficient virtual dissection tool to create generic models for anatomical atlases.

We have developed an efficient virtual dissection tool to create generic 3D models for anatomical atlases without the need for artistic drawings. Our custom-developed tool can be used to extract 3D models from 2D medical image stacks, cut the models and align the sub-models. Corresponding 2D medical image portions of the sub-models can then be registered and averaged. In the end, a generic model can be obtained from the averaged 2D images of several subjects. The technique optimizes the functionalities of existing toolkits and the resulting software package will allow biologists to build their atlases more quickly and accurately.