Seiichi Naruo

SERUM LEVELS OF A TISSUE INHIBITOR OF METALLOPROTEINASES-1 (TIMP-1) IN BLADDER CANCER PATIENTS

Tissue inhibitors of metalloproteinases (TIMP‐1 and ‐2) are common inhibitors of matrix metallo‐proteinases (MMPs), thereby blocking degradation of extracellular matrix components. TIMP‐1 and ‐2 have been reported to exhibit inhibitory activities against tumor invasion and metastasis. We measured the serum TIMP‐1 levels in 16 healthy volunteers and in 69 patients with bladder cancer using a sandwich enzyme immunoassay, and evaluated the correlation between serum TIMP‐1 levels and clinicopathological features. Patients with bladder cancer showed significantly higher serum TIMP‐1 levels (251.1 96.0 ng/ml; p<0.01) than those of healthy volunteers (168.5 33.2ng/ml), and a positive correlation between the TIMP‐1 level and invasion and metastasis was observed. This is considered to be the result of the reactive production of TIMP‐1 in cancerous tissues. Thus, serum TIMP‐1 levels may become a reliable clinical marker of the progression of bladder cancer.

High-level Expression of the CD44 Variant Sharing Exon v10 in Renal Cancer

To examine whether renal cell carcinoma displays altered CD44 expression we performed reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of CD44 in 38 specimens from renal cancer, normal kidney and metastases of 19 patients and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT‐PCR Southern blot method. One out of 19 (5.3%) renal cancer specimens expressed a larger molecular weight band than 1 kb by RT‐PCR analysis, in contrast to previous findings in colon and breast cancer. The band patterns in RT‐PCR were different in 14/17 (82.4%) cases between normal kidney and tumors, and a band of about 700 bp was especially marked in 12/17 (70.6%) tumor specimens and 4/6 (66.7%) cell lines. By cloning and sequencing of the 700 bp band, we found that this variant is identical to the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 mRNA than paired normal kidneys. These findings suggested that the CD44 variants sharing exon v10 play some role in renal cancer.

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.

A case of renal cell carcinoma producing granulocyte-macrophage colony-stimulating factor.

Renal cell carcinomas frequently secrete hormones and cytokines (parathormone, prostaglandins. renin, gonadotropins and glucocorticoids). The underlying cause of the leukemoid reaction sometime seen in renal cell carcinoma is unknown. We report a case of renal cell carcinoma with leukemoid reaction and demonstrate that the autonomous production of granulocytemacrophage colony-stimulating factor in cancer tissue was the underlying mechanism.

The Camey-Le Duc antireflux technique for the Koch pouch: evaluation of the upper urinary tract.

Between November 1989 and June 1993, 41 patients (78 renal units) underwent Camey-Le Duc technique for prevention of reflux of a Kock pouch. In 30 patients the ileal reservoir was connected to the skin for cutaneous urinary diversion, and in 11 it was connected to the urethra for lower urinary reconstruction. The mean postoperative follow-up period was 23 months, with a range of 6-47 months. Postoperative excretory urography (IVP) was performed at least once a year to evaluate the upper urinary tract configuration, and ascending cystography was performed to evaluate the reflux. No urinary tract dilatation was observed in 73 renal units (93.6%), while slight dilatation was noted in 3 (3.8%), moderate dilatation in 1 (1.3%), and marked dilatation in 1 (1.3%). Reflux was not found in any patient. Of 23 renal units in 12 patients in whom the last IVP examination was performed 6 months postoperatively, dilatation was noted in 4 (17.4%). In contrast, of 55 renal units in 29 patients in whom the last IVP examination was performed 12 months or more after the Kock pouch operation, dilatation was noted in only 1 (1.8%). We conclude that the Camey-Le Duc antireflux technique is effective in terms of simplicity and reliability.