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Biomedical subjects

Tsuguru Usui

Publications and source records attributed to Tsuguru Usui.

28 records · Page 2Linked to original sources

Interaction of ligand-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer: a possible predictor of metastasis.

Interaction of ligand-receptor systems between stromal-cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) is closely involved in the organ specificity of cancer metastasis. We hypothesized that SDF-1-CXCR4 ligand-receptor system plays an important role in prostate cancer metastasis. To test this hypothesis, expression level of SDF-1 and CXCR4 was analyzed in prostate cancer (PC) cell lines (LNCaP, PC3, and DU145) and normal prostate epithelial cell line (PrEC). We also performed migration assay and MTT assay to investigate the chemotactic effect and growth-promoting effect of SDF-1 on DU145 and PC3 cells, respectively. Furthermore, we performed immunohistochemical analysis of CXCR4 expression in tissues from 35 cases of human prostate cancer. CXCR4 expression was detected in all three prostate cancer cell lines, but not in PrECs. SDF-1 significantly enhanced the migration of PC3 and DU145 cells in a dose-dependent manner, and anti-CXCR4 antibody inhibited this chemotactic effect. However, SDF-1 itself did not significantly stimulate the cell growth rate of prostate cancer cell lines. Positive CXCR4 protein was found in 20 out of 35 clinical PC samples (57.1%). Three patients with lung metastasis showed definitely positive CXCR4 immunostaining. Logistic regression analysis revealed that positive expression of CXCR4 protein was an independent and superior predictor for bone metastasis to Gleason sum (P < 0.05). Furthermore, among PC patients with PSA greater than 20 ng/mL, the positive rate of CXCR4 protein was significantly higher in patients with bone metastasis than in those with no bone metastasis (P = 0.017). These findings suggest that the interaction between SDF-1 and CXCR4 ligand-receptor system is involved in the process of PC metastasis by the activation of cancer cell migration. This is the first report to investigate the role of interaction of ligand-receptor systems between SDF-1 and CXCR4 in prostate cancer metastasis.

Biomarkers, Tumor↗

Lack of the complete circular rhabdosphincter and a distinct circular smooth muscle layer around the proximal urethra in elderly Japanese women: an anatomical study.

Histological observations of semiserial sections obtained from the cadavers of 30 elderly Japanese women (aged 61-93 years) found that the urethral rhabdosphincter (URS) usually occurred as a ventrally localized structure instead of exhibiting the normal completely circular configuration. The superoinferior length, thickness and muscle fiber density of the URS area showed significant interindividual variation. A thick fascicle, extending posterolaterally from the URS and radiating to the lateral vaginal wall and other perineal tissues, was usually observed. A circular smooth muscle layer, which immediately surrounded the longitudinal smooth muscle layer, was consistently present in the proximal urethral but not in the bladder neck. These findings suggest that voluntary sphincteric action is weak or incomplete in elderly Japanese women. We therefore hypothesize that upward retraction of the midurethra by the URS, compression of the distal urethra by its posterolateral extensions, and tonus provided by the outer circular smooth muscle layer all contribute to maintaining continence in these women.

Aged↗

The micturition habits and prevalence of daytime urinary incontinence in Japanese primary school children.

PURPOSE: We assessed the prevalence of daytime urinary incontinence (DUI) and the daytime frequency of voiding by age and sex in neurologically normal children in primary school. We also investigated the association of DUI with background factors. MATERIALS AND METHODS: We performed an anonymous questionnaire survey of DUI in primary school children. A total of 11 primary schools in Hiroshima City were randomly selected and 6,917 school children 7 to 12 years old were enrolled. DUI was defined as any involuntary leakage of urine during the daytime occurring more frequently than once monthly in the 6 months before the survey. Slight dampness of the child underwear was also regarded as DUI. RESULTS: The overall response rate was 76.4% of 6,917 school children. The prevalence of DUI was 6.3% and it was inversely related to age, decreasing from about 9% at age 7 to 2% at age 12 years. Children urinated about 5 or 6 times daily and increased daytime frequency occurred in 14.6% of all children. Daytime frequency of voids, history of cystitis and infrequent bowel habits had a statistically significant positive correlation with DUI. CONCLUSIONS: We found that the overall prevalence of DUI in primary school children was 6.3%, gradually decreasing with age. Increased daytime frequency, history of cystitis and infrequent bowel habits were significantly related to DUI. The link between DUI and daytime frequency, urinary tract infections and constipation deserves more attention.

Child↗

Restoration of insulin-like growth factor binding protein-related protein 1 has a tumor-suppressive activity through induction of apoptosis in human prostate cancer.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), a member of the IGFBP super family, is down-regulated at the mRNA level in several solid cancers. We hypothesize that IGFBP-rP1 has a tumor-suppressive effect on prostate cancer growth and its inactivation is through CpG hypermethylation. We tested this hypothesis through expression analysis of IGFBP-rP1, transfection studies, growth analysis, and CpG methylation in prostate cancer cells and tissues. In situ hybridization revealed IGFBP-rP1 mRNA expression was detected in the stroma and epithelium of benign prostatic hyperplasia tissues but was either weak or lost in prostate cancer tissues. The mRNA expression for IGFBP-rP1 was lacking in DU145, LNCaP, ND-1, and PC-3 prostate cancer cell lines, and after demethylation (5-aza-dC treatment), the expression was restored suggesting that methylation inactivated IGFBP-rP1 expression in prostate cancer cells. We further tested whether transfection of IGFBP-rP1 can modulate prostate cancer cells growth. We transfected PC-3 cell lines with IGFBP-rP1 cDNA (PC-3-rP1) and Northern blotting confirmed mRNA transcript of IGFBP-rP1 in these PC-3-rP1 clones. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed growth rate was significantly lower in PC-3-rP1 cells than in the nontransfected control. In addition, the medium obtained from PC-3-rP1 cells reduced the growth rate in both PC-3-rP1 and control PC-3 cells. A soft agar colony-forming assay revealed that colony formation was markedly decreased in PC-3-rP1 cells. The number of apoptotic cells and caspase-3 expression were increased in the PC-3-rP1 cells as compared with control PC-3 cells. This is the first study that suggests inactivation of IGFBP-rP1 is through CpG methylation, and tumor-suppressive activity of IGFBP-rP1 is through induction of apoptosis in an IGF-I independent manner in prostate cancer.

Antimetabolites, Antineoplastic↗

Topographic anatomy of the male perineal structures with special reference to perineal approaches for radical prostatectomy.

AIM: Although perineal approaches for radical prostatectomy have recently gained renewed attention as excellent methods for minimally invasive surgery, the most commonly used techniques, Belt's and Young's approaches, have inadequacies regarding the topographical relationship between the rectourethral and levator ani muscles. METHODS: Using macroscopic observations of sagittal slices of 27 male pelvises and smooth muscle immunohistochemical staining of semiserial sections of another eight pelvises, we investigated the topographical anatomy of the perineal structures and their interindividual variations in elderly Japanese men. RESULTS: The inferomedial edge of the levator ani was located 5-15 mm lateral to the midsagittal plane in an area between the urethra and the rectum. The rectourethral smooth muscle had a superoinferior thickness of 5-10 mm and occupied a space between the right and left levator slings. The levator was adjacent to, or continuous with, the striated anal sphincters. A thick connective tissue septum, composed of smooth muscle, was evident between the rectal smooth muscle and the anal sphincter-levator ani complex. CONCLUSION: Because the connective tissue septum guides the surgeon's finger upwards towards the rectoprostatic space, Belt's approach appears relatively easy; however, rectal injury can sometimes occur if the surgeon loses this guidance. In contrast, if the levator edge is identified as the first step in Young's approach, the rectourethral muscle can be precisely divided, leaving a 3-5-mm margin from the rectum and sphincter-levator complex. Clinical investigations are now required to modify Young's approach based on the present results.

Aged↗

Regulation of estrogen receptor alpha and beta expression by testosterone in the rat prostate gland.

Although ER beta is known to be expressed at high levels in the rat prostate gland, its regulation is not well understood. Here we examined ER mRNA expression and the effects of testosterone administration in male rats at 1, 4 and 9 weeks of age who were castrated and/or treated with testosterone for a week, and then sacrificed. ER alpha was the major type of ER expressed in 2 week-old animals while dominant expression of ER beta mRNA was apparent in older age groups. Interestingly while ER beta expression was diminished and ER alpha mRNA increased in the castrated group, testosterone administration reversed this effect. A time-course study indicated that induction of ER beta mRNA increased within 9 hr and ER alpha decreased in 2 days after an injection (i.p.) of testosterone. Our results suggested that 1) testosterone up-regulates ER beta mRNA expression while ER alpha is down-regulated; and that 2) great changes in ER alpha and beta expression in the prostate gland during development from the newborn to adult may be due to the influence of testosterone.

Animals↗

Localization and expression of tissue inhibitor of metalloproteinase-1 in human urothelial cancer.

PURPOSE: We evaluated the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the invasion and metastasis of human urothelial cancer. MATERIALS AND METHODS: The expression level of TIMP-1 messenger (m)RNA was determined in 33 urothelial carcinomas, including upper urothelial cancer in 15 cases and bladder cancer in 18, by Northern blot analysis. Localization of TIMP-1 mRNA was analyzed by in situ hybridization. These data were compared with clinicopathological features. We also determined the growth activity of tumor cells using immunohistochemical staining for Ki-67 and compared it with the expression levels of TIMP-1 mRNA. These data were also compared with clinicopathological features. RESULTS: The expression level of TIMP-1 mRNA significantly correlated with pathological stage and histological differentiation. In situ hybridization showed that TIMP-1 mRNA was expressed in the cytoplasm of urothelial cancer cells. The Ki-67 labeling index significantly correlated with the expression level of TIMP-1 mRNA in urothelial cancer. Patients with high expression of TIMP-1 mRNA had a poorer prognosis than those with low expression. CONCLUSIONS: TIMP-1 mRNA is expressed in the cytoplasm of cancer cells and high expression indicates more malignant potential in cases of urothelial cancer.

Aged↗

Three-dimensional navigator for retroperitoneal laparoscopic nephrectomy using multidetector row computerized tomography.

PURPOSE: We evaluated the efficacy of a 3-dimensional (D) navigator for retroperitoneal laparoscopic nephrectomy. MATERIALS AND METHODS: A total of 21 patients with malignant localized renal (16) or ureteral (5) neoplasms underwent multi-detector row computerized tomography. The 3-D navigator was created using volume rendering technique. These findings were compared with videos obtained during laparoscopy. RESULTS: The 3-D navigator depicted all renal arteries (100% sensitivity) and 24 of the 25 renal veins (96% sensitivity). Hilar anatomy, including the tumor, major vessels and adrenal gland, and their relationships were visualized as in laparoscopic views. CONCLUSIONS: The 3-D navigator has a potentially important role in retroperitoneal laparoscopic nephrectomy. It is able to guide surgeons and aid in avoiding operative risks and possible complications.

Adult↗

[Ductal carcinoma of the prostate with multilocular cystic formation].

A 72-year-old man was admitted to our department with the complaint of nocturia. PSA was elevated to 18.2 ng/ml. Transrectal ultrasonography, CT scan and MRI showed multilocular cystic lesions at the posterior site of the prostate, with rectal and bladder invasion and lymph node metastasis. Transrectal needle biopsy of the prostate and fluid aspiration of the prostatic cyst were performed. The aspirated fluid was bloody, but the result of cytology was negative. Histopathological examination of the needle biopsy specimen revealed ductal carcinoma of the prostate. We diagnosed this case as a T4N1M0 prostatic cancer, and started endocrine therapy. Thirty-nine cases of adenocarcinoma of the prostate with cystic formation in the Japanese literature are reviewed.

Aged↗