Microsurgical technique is safe and may improve SRR for TESE in a variety of patients with NOA, especially patients with heterogeneous testicular tubules.

BACKGROUND In prostate cancer, several growth factors derived from stromal cells regulate tumor cell growth. Hepatocyte growth factor (HGF) possesses biological activities that promote cancer proliferation and invasion through tumor‐stromal interaction. We examined how prostate stromal cell‐derived HGF affects invasion of prostate cancer cells through this interaction. METHODS The effects of HGF, various growth factors (transforming growth factor (TGF)‐α, TGF‐β1, basic fibroblast growth factor, keratinocyte growth factor, and platelet‐derived growth factor), and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC‐3, and DU145) were determined by collagen gel invasion assay. DU145 cells and PrSC were cocultured for Matrigel invasion chamber assay. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by the ELISA method and Western blotting. RESULTS LNCaP and PC‐3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF‐β1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or cocultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF‐β1. Native‐type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells. CONCLUSIONS PrSC‐derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor‐stromal interaction, wherein DU145 cells secreted some HGF‐inducer(s) for PrSC. Prostate 41:145–153, 1999. © 1999 Wiley‐Liss, Inc.

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The technical developments and expanded indications for testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) provide great advantages for patients with non-obstructive azoospermia. Such success, however, also means that genetic abnormalities in non-obstructive azoospermia can be transmitted to the next generation, demonstrating the importance of being able to understand the genetic background of non-obstructive azoospermia. We have previously reported that human leukocyte antigens (HLA)-A33 and -B44 in the HLA class I region and the HLA-DRB1*1302 allele in the HLA class II region are linked to susceptibility to non-obstructive azoospermia in Japanese men. However, strong linkage of HLA-DRB1*1302 with HLA-A33 and -B44 is also evident in the Japanese population. Thus, uncertainty prevails as to whether the HLA class I or class II molecule is more directly associated with non-obstructive azoospermia. In the present study, we performed association analysis with 21 polymorphic microsatellite markers identified near the HLA genes to map the gene involved in the development of non-obstructive azoospermia more precisely. Microsatellite markers located in the HLA class I region or the class III region showed no statistically significant association with this disorder, although once again the HLA-A33 and -B44 alleles showed a significant association. In contrast, some of the microsatellite markers in the HLA class II region and at the HLA-DRB1 and -DQB1 loci displayed strong associations with non-obstructive azoospermia. Taken together, our previous and present data suggest that the critical region for development of non-obstructive azoospermia is near the HLA-DRB1 and -DQB1 segments in the HLA class II region.

Urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are involved in a proteolytic cascade resulting of extracellular matrix degradation. Upstream, uPA and uPAR are regulated by various factors including hepatocyte growth factor (HGF), which stimulates the uPA/uPAR proteolytic system and increases invasion of cancers. We recently demonstrated that HGF induces invasion of DU145 prostate cancer cells into collagen gel matrix. We therefore examined effects of HGF on uPA and uPAR expression in DU145 cells. Effects of HGF on uPA expression in culture medium were determined by Western blotting and fibrin zymography, effects on uPAR expression in cell-associated protein were examined by Western blotting. HGF increased uPA and uPAR production in a dose-dependent manner up to 10 ng/mL, while effects of 20 ng/mL were approximately equal to those of 10 ng/mL. HGF stimulated uPA production beyond that in control cultures from 8 h until 48 h after HGF addition. HGF stimulated a uPA/uPAR proteolytic network in DU145 cells, which may be important for acquisition invasive potential by prostate cancer.