Masahito Tsuji

A case of renal metanephric adenoma: histologic, immunohistochemical and cytogenetic analyses.

Background: A unique case of metanephric adenoma of the left kidney is reported in a 61‐year‐old woman presenting with an incidental renal mass on ultrasonography.

Role of the Matrix Metalloproteinase and Tissue Inhibitors of Metalloproteinase Families in Noninvasive and Invasive Tumors Transplanted in Mice With Severe Combined Immunodeficiency

OBJECTIVES To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.

Adenocarcinoma arising from a mature cystic teratoma of the testis

Abstract A 52‐year‐old male diagnosed pathologically with metastatic adenocarcinoma of the skin was referred to our department. Physical examination revealed a right scrotal mass the size of childs head and several skin tumors. Right high orchiectomy and resection of skin tumors were performed. Histopathological examination revealed a well‐differentiated, mucinous adenocarcinoma originating from the gastrointestinal epithelium in a mature cystic teratoma (dermoid cyst) of the testis and metastatic mucinous adenocarcinoma of the skin. We made a diagnosis of teratoma with malignant transformation (TMT) of the testis. Combination chemotherapy with low‐dose cisplatin/5′‐deoxy‐5‐fluorouridine (CDDP/5′‐DFUR) was initiated, but the patient died 8 months after orchiectomy. At autopsy, similar mucinous adenocarcinoma of the testis and the skin were observed at the metastatic sites.

Impact of Aging and Diabetes Mellitus on the Expression of the Proliferating Cell Nuclear Antigen in Rat Testicular Tissue

This study evaluated the expression of proliferating cell nuclear antigen (PCNA), which is one of the important markers of cell proliferation, in testicular tissue with aging and progress of diabetes mellitus (DM). OLETF rats were used as animal models for non-insulin-dependent DM. They were 12, 30, 50, and 70 weeks old. The controls were age-matched nondiabetic LEIO rats. Testes were taken from all the rats and paraffin-embedded sections were cut and stained with PC 10 monoclonal AB (x50). Labeled cells were assessed in randomly selected fields. Labeling index (LI) for each stage of spermatogenesis was estimated and total LI for each specimen was calculated. In control rats, the 12-week-old animals showed the highest PCNA-LI. The indexes started to decrease in other older animals, with an increase in the number of suppressed stages as the animals aged, leading to significant differences among groups except between the 12- and 30-week-old groups. The same features were also seen in DM animals as the disease progressed. The total LI of controls were significantly higher and the number of suppressed stages was lower than those of DM animals, except among the 12-week-old group. Both aging and DM have depressing effects on the expression of PCNA in testicular tissue. The decline in PCNA expression is parallel with advancement of age and progress of DM. However, DM has a more suppressing effect than aging on that expression. This suppression could explain the decrease in male fertility potential that may be associated with both conditions.

The proliferation index of MIB-1 as a prognostic factor for patients with transitional cell carcinoma of the upper urinary tract

Recently, several reports have shown that immunohistochemical analysis using MIB‐1 antibody, which recognizes Ki‐67 (a human nuclear antigen expressed of proliferating cells), is a useful method for determining the proliferative activity of various cancers. In this study, the authors evaluated the prognostic usefulness of the proliferation index using MIB‐1 antibody in transitional cell carcinoma of the upper urinary tract.

Analysis of CD44 isoform v10 expression and its prognostic value in renal cell carcinoma

Objective To examine the expression of CD44 isoform v10 (CD44v10) in patients with renal cell carcinoma (RCC), analyse its role in RCC and its relationship with conventional clinical‐histopathological experience.

Immediate Effects of Extracorporeal Shock Waves on the Male Genital System of Rabbit: Preliminary Report

Hemospermia was reported to occur following extracorporeal shock wave lithotripsy of lower ureteric stones. Because no studies showed clearly the possible effect of extracorporeal shock waves (ESW) on the male genital system, we were prompted to study this effect. Eighteen male white New Zealand rabbits were divided into three groups (six in each) and subjected to different doses of ESW (2000, 3000 and 4000) using a Dornier MFL 5000. Shocks were focused on the lower parts of the bladder. Four animals were used as controls. Two hours later, the animals were dissected. Gross examination of the genital systems showed bleeding in the testicles and prostates of only some animals, whereas microscopic examination revealed bloody spots in the genital structures of all animals. The amount of bleeding was ESW dose-independent. In conclusion, ESW showed evident immediate effects on the male genital system. Application of shock waves in treating lower ureteric or vesical stones in doses between 2000 and 4000 may cause bleeding in the structures of this system, which can lead to hemospermia. More studies will be needed to show the long-term sequelae of these changes on the male genital system.

Serological evaluation of soluble CD44 in renal cancer

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme‐linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico‐pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745±170 ng/ml vs. 563±159 ng/ml, P=0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287±121 vs. 220±59, P=0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico‐pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth‐type cancers than in the slow growth‐type cancers (3.95±2.12 vs. 2.63±0.82, P=0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth‐type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth‐type cancers.

Proliferating cell nuclear antigen in testes of infertile men with varicocele--preliminary results of interrelationship with sperm count before and after varicocelectomy.

Objective: This study was conducted to assess germ cell kinetics and correlate them with sperm counts before and after varicocelectomy. Material and Methods: Forty-three testicular biopsy specimens were obtained from 47 patients with varicocele during varicocelectomy. Similar specimens were obtained from 8 fertile volunteers. All specimens were immunostained using anti-proliferating cell nuclear antigen (anti-PCNA) antibody. PCNA expression was evaluated by assessing its staining intensity (SI) and labeling index (LI). Results: The varicocele specimens revealed significantly lower SI and LI than the controls. There was a significant correlation between initial sperm concentration and LI but not SI. Coexistence of LI S 31 and preoperative sperm count >1 million/ml correlated with a significant rise in the postoperative sperm count. Conclusions: PCNA is a useful molecular marker for assessing germ cell kinetics in varicocele patients. The decline in DNA synthesis, as suggested by the lower PCNA SI and LI in varicocele specimens, could be a reason for the disordered spermatogenesis in these patients. PCNA LI may also be considered as a beneficial clinical marker and may help to predict the surgical outcome after varicocele repair.

TRANSFORMING GROWTH FACTOR (β1) IN TESTES OF AGED AND DIABETIC RATS: CORRELATION WITH TESTICULAR FUNCTION

This study was conducted to evaluate the expression of transforming growth factor- g 1 (TGF- g 1) in testis with aging and progress of diabetes mellitus (DM) and correlated this with testicular function. Zucker diabetic fatty rats (15, 40, and 75 weeks old) were used as models for non-insulin-dependent DM. The controls were age-matched nondiabetic Zucker fatty rats. Serum testosterone levels and daily sperm production were evaluated. Testicular tissue was immunostained with anti-TGF- g 1. Labeled cells were assessed and the staining intensity was estimated. The 15-week control and diabetic animals showed the lowest levels of staining intensity but this started to increase significantly in the older animals of both categories. However, the diabetic animals had significantly deeper intensities relative to controls at the different age groups. These changes in TGF- g 1 expression were negatively correlated with both testosterone and sperm production. Therefore, aging and DM enhanced the expression of TGF- g 1 in testis, and this was parallel with progress of both conditions, although DM seems to be predominant. These alterations in TGF- g 1 expression may be related to changes in testicular function associated with both conditions.