Kyoko Arai

Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour

Objective To clarify the role of Rho small GTP‐binding protein (Rho) in the progression of testicular germ cell tumour (GCT), by examining the expression levels of mRNAs of Rho genes in testicular GCT.

Serial lectin affinity chromatography demonstrates altered asparagine-linked sugar-chain structures of prostate-specific antigen in human prostate carcinoma.

Differences between prostate carcinoma (PCA) and benign prostatic hyperplasia (BPH) in asparagine (N)-linked sugar-chain structures of prostate-specific antigen (PSA) were investigated using serial lectin affinity chromatography. The amounts of PSA passing through columns of concanavalin A (Con A), phytohaemagglutinin E4 (PHA-E4) and PHA-L4 were significantly greater for PCA-derived PSA than BPH. We propose that the sugar moiety structure of PSA which is increased in PCA is a multiantennary complex type with branched N-acetylglucosamine beta(1->4) mannose. We suggest that N-linked sugar chains in PSA are altered during oncogenesis in the human prostate and may serve as diagnostic tools for PCA.

RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer

To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA.

Prognostic significance of p27Kip1 and Ki-67 expression in carcinoma of the renal pelvis and ureter

Objective To determine the significance of p27Kip1 (p27) for tumour behaviour and prognosis of patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter.

Serum concentration of type I collagen metabolites as a quantitative marker of bone metastases in patients with prostate carcinoma

Bone scans, widely used for the detection of bone metastases from prostate carcinoma, can neither quantitate metastatic lesions nor detect osteolytic lesions.

Serial lectin affinity chromatography with concanavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

Preliminary report of the clinical performance of a new urinary bladder cancer antigen test: comparison to voided urine cytology in the detection of transitional cell carcinoma of the bladder

We compared the ability of a new urinary bladder cancer antigen (UBC) test with conventional cytology for the detection of transitional cell carcinoma of the bladder using voided urine samples. The UBC was measured and corrected for the creatinine concentration in the urine of 61 patients with transitional cell carcinoma of the bladder (group 1), 23 patients without recurrent bladder tumors during follow-up (group 2), 28 patients with benign prostatic hyperplasia (group 3), nine patients with prostate cancer (group 4), and 90 healthy volunteers free of urological diseases (group 5). The UBC concentrations were 408.8+/-578.5, 18.8+/-26.6, 23.9+/-32.7, 17.5+/-18.6 and 4.6+/-6.7 ngmg(-1) creatinine (mean+/-S. D.) for groups 1-5, respectively. The level for group 1 was significantly higher than for any other group. The sensitivity and specificity, which were optimized using receiver-operating characteristic curves for groups 1 and 2 were 82.0% and 82.6%, respectively, at a threshold value of 39 ngmg(-1) creatinine. The sensitivity and specificity of cytology for these same groups were 60.7% and 86.9%, respectively. The sensitivity of the UBC was significantly higher than that of cytology, not only for total bladder tumors (82.0% vs. 60.7%, P<0.02) but also for grade I transitional cell carcinoma of the bladder (76.5% vs. 11.8%, P<0. 001). While offering a similarly high specificity, the UBC test might have an advantage over cytology in terms of superior sensitivity, particularly for low-grade tumors.

Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer.

The relationship between clinical response to DNA‐damaging drugs and p53 and p21 status in patients with locally advanced transitional cell carcinoma (TCC) of the bladder was assessed. The response to intraarterial chemotherapy (IAC) comprising 100 mg/m2 of cisplatin (CDDP) and 40 mg/m2 of pirarubicin (THP) and the prognosis were assessed in 23 patients (the mean follow‐up period was 19 months). The p53 gene status of tumors was analyzed at exons 5–8 using polymerase chain reaction‐single strand conformation polymorphism analysis in 19 patients, and paraffinembedded tumor sections were immunostained for p53 and p21 in 23 patients. The overall objective response rate (incidence of good responders) was 70%. The negative p53 group (n=17) showed a significantly higher objective response rate than the positive p53 group (n=6) (82% vs. 33%; P=0.045). The p53 gene status or p21 staining status was not significantly associated with responsiveness. When the p53 and p21 immunostaining results were combined, good responders were more accurately predicted than by p53 staining status alone; the negative p53/positive p21 group (n=12) showed an objective response rate of 92%, which was significantly higher than that of the positive p53 and/or negative p21 group (45%, n=11) (P=0.027). Cause‐specific survival of the negative p53 group was significantly superior to that of the positive p53 group (P=0.015). Negative p53/positive p21 immunostaining is a possible predictor of favorable chemotherapeutic response in patients with TCC of the bladder.

Separation methods applicable to prostate cancer diagnosis and monitoring therapy.

During the last decade, significant research has been conducted using prostate-specific antigen (PSA) in the basic and clinical sciences and many advances have occurred in the clinical use of PSA for detecting and monitoring prostate cancer (PCa). Separation methods including gel-permeation chromatography, isoelectric focusing, lectin-affinity chromatography, polyacrylamide gel electrophoresis and high-performance liquid chromatography have made significant contributions to the discovery and identification of different molecular forms of PSA. Furthermore, the measurement of free and total PSA has improved the ability of PSA to detect early PCa. However, unnecessary biopsies are still needed for men with slightly elevated PSA values. On the other hand, PSA is not adequate for staging newly diagnosed PCa and prognosticating the course in individual cases. The possible application of separation methods in the basic science of prostate cancer may be associated with identification of more cancer-specific forms of PSA and discoveries of other serum proteins useful not only for detecting, but also for staging and prognosticating PCa. Such novel markers might lead to a better understanding of PCa aggressiveness and to developments in the clinical field of treatment.

Serial lectin affinity chromatography demonstrates altered asparagine-linked sugar chain structures of γ-glutamyltransferase in humaa renal cell carcinoma

Differences between human renal cortex and human renal cell carcinoma (RCC) in asparagine (Asn)-linked sugar chain structures of gamma-glutamyltransferase (GGT) were investigated by using a serial lectin affinity chromatographic technique. The relative amounts of GGT which passed through the concanavalin A (Con A) column but bound to the phytohaemagglutinin E column, were significantly decreased in RCC, but there were significant increases in the relative amounts of GGT which bound weakly to the Con A column and passed through the pea lectin (PSA) column, and bound strongly to the Con A column and bound to the wheat germ agglutinin column in RCC compared with those of the normal renal cortex. A significant correlation was observed in RCC between nuclear grade and relative amount of GGT which bound weakly to the Con A column and passed through the PSA column. The findings indicate that Asn-linked sugar chain structures are altered in RCC and suggest that studies of qualitative differences of sugar chain structures of GGT might lead to a useful diagnostic tool for human RCC.