[Retrospective evaluation of PSA density for selection of biopsy candidates with prostate specific antigen in the gray zone].

PURPOSE: We examined the usefulness of prostate specific antigen density (PSAD) for selection of biopsy candidate with prostate specific antigen levels between 4.1 and 10.0 ng./ml. in prostate cancer screening retrospectively. MATERIALS AND METHODS: The screening was conducted on male candidates in Natori city, aged 55 years or older, for 6 years from 1994 through 1999. We could analyze serum PSA levels and PSA density in 118 men with PSA levels between 4.1 and 10.0 ng./ml. All of 118 men underwent ultrasound guided systematic prostate biopsy regardless of findings of digital rectal examination and transrectal ultrasound. Prostate volume was estimated by transrectal ultrasound measurements using the prolate ellipse formula (pi/6 x length x width x height). PSAD was calculated by dividing serum PSA level by prostate volume. Serum PSA levels were determined by Tandem-R assay. RESULTS: In 118 men, twenty-five men had prostate cancer. There was no significant difference in mean PSA between those with prostate cancer and those without prostate cancer, but the difference was significant in the mean PSA density (mean 0.26 and 0.16, respectively, p < 0.0001). Receiver operating characteristic curves for PSA and PSAD demonstrated superior benefit for PSAD in 118 men. A sensitivity, a specificity, a positive predictive value and a negative predictive value of PSAD cut-off of 0.15 were 88%, 52.7%, 33.3% and 94.2%. PSAD cut-off of 0.18 showed the highest sum of sensitivity and specificity, which gave a sensitivity of 80%, a specificity of 72%, a positive predictive value of 43.5% and a negative predictive value of 93.1%. PSAD cut-off of 0.15 would seem to be preferable to cut-off of 0.18 because of less cancer missing. CONCLUSIONS: Although further studies are needed to determine optimal cut-off value to be used in clinical practice, PASD seems to be useful for the selection of biopsy candidates with PSA levels of 4.1 to 10.0 ng./ml. in the prostate cancer screening.

Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.

We reported previously that non-invasive bladder cancer expresses high level of GM3 ganglioside, whereas invasive tumors have low levels. Since glycosphingolipid synthesis in Golgi is modified greatly by a macrocyclic lactone isolated from fungi, brefeldin A (BFA), we studied effects of BFA on expression of glycosphingolipids and on invasiveness of bladder cancer cell lines. Only GM3 synthesis in invasive tumors was greatly enhanced upon treatment with BFA; synthesis of other glycosphingolipids with lacto-series type 2 or globo-series structure in both invasive and non-invasive tumors was not changed. Invasiveness of bladder cancer cells was greatly decreased in association with the great increase of GM3 synthesis induced by BFA treatment. Level of sialyl-Lex expressed in invasive cell line YTS1, which provides the adhesive property of the cells to E-selectin, was unchanged upon BFA treatment. All the bladder cancer cell lines, regardless of invasiveness, highly express tetraspanin CD9. GM3 has been implicated as a co-factor of CD9 in control of tumor cell motility. Down-regulation of CD9 is associated with metastatic properties of tumor cells and survival of patients with colonic cancer. Therefore, enhanced synthesis of GM3 induced by BFA, causing decrease of invasiveness in bladder cancer, is ascribable to the capability of GM3 to interconnect integrin with CD9, in analogy to colonic cancer and perhaps many other types of cancer.

Telomerase activity Simplification of assay and detection in bladder tumor and urinary exfoliated cells.

Detection of telomerase activity can differentiate malignant from benign cells. However, the original telomeric repeat amplification protocol (TRAP) methods had a number of limitations including a radioisotope labeling [α(32)P] dCTP [α(32)P] dGTP system. We developed digoxigenin labeled CX primer to detect telomerase activity without using radioisotope and attempted to detect telomerase activity of bladder tumor and exfoliated cells in bladder cancer patients. Telomerase activity was detected in 5 (71%) of 7 patients diagnosed with grade 1, 31 (97%) of 32 grade 2, and 11 (100%) of 11 grade 3 bladder tumors. In urinary exfoliated cells, 32 (82%) of 39 grades 1 or 2 bladder tumors were positive for telomerase activity but 20 (51%) of 39 were positive for urinary cytology (P < 0.01). Ten (91%) of 11 of grade 3 tumors were positive for telomerase activity and 11 (100%) of 11 were positive urinary cytology. Three of 100 noncancerous patients were positive for telomerase activity. Sensitivity, specificity, and positive predictive value of telomerase activity assay in urinary exfoliated cells were 84%, 97%, and 93%, respectively. Telomerase activity may be a useful diagnostic marker to detect the existence of immortal cancer cells in the urine.

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors.

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.

Lack of selectin-dependent adhesion in prostate cancer cells expressing sialyl Le(x).

BACKGROUND: Recently, it has been reported that upregulation of the oligosaccharide sialyl Le(x) (SLe[x]) in prostate cancer is associated with hormone-resistant, aggressive disease. However, it is not clear that SLe(x) expressed on prostate cancer cells has a biological function related to metastatic potential. METHODS: The expression levels of SLe(x), sialyl Le(a) (SLe[a]), disialosyl galactosylgloboside (DSGG), monosialosyl galactosylgloboside (MSGG) and variousfucosyltransferases in 3 prostate cancer cell lines were determined. The function of SLe(x) expressed on prostate cancer cell lines was determined by a selectin-dependent adhesion assay. RESULTS: No prostate cancer cell lines expressed SLe(a), DSGG, or MSGG, but all prostate cancer cells moderately expressed SLe(x). Fucosyltransferase expression did not correlate with the expression of SLe(x), and all prostate cancer cells failed to bind immobilized selectin. CONCLUSION: The expression of SLe(x) on these prostate cancer cells does not correlate with selectin-dependent adhesion.

[The concentration of Tamsulosin hydrochloride in the blood and prostatic tissue of the patients in benign prostatic hyperplasia].

BACKGROUND: The penetration of Tamsulosin hydrochloride into the blood and the prostatic tissue was examined. METHODS: Fifty-two patients with benign prostatic hyperplasia treated with transurethral resection of the prostate were entered in this study. This drug was administered orally in a dose of 2.0 mg once a day for 7 to 179 days preoperatively. The blood samples were taken simultaneously at the time of the prostatic tissue sampling. RESULTS: 1. The correlation coefficient was hardly significant between aging and concentration of the drug in the blood or in the prostatic tissue. 2. The correlation coefficient was hardly significant between the duration of the drug administration and concentration of the drug in the blood or the prostatic tissue. 3. The correlation coefficient was significant between the concentration of the drug in the blood and the prostatic tissue. 4. The fifty-two patients showed no significant adverse reactions during administration of the drug. CONCLUSION: These results suggest that the drug can be administered safely to the aged even in a long-term and can be penetrated into the blood and the prostatic tissue with a positive correlation.

G(M3) inhibits murine MET-2 tumor invasion and growth.

G(M3) has some important roles in cell-to-cell interaction and has proved to have an optimal concentration for fibronectin mediated cell adhesion. G(M3) content in murine bladder tumor (MBT-2) assessed by thin-layer chromatography was similar to human invasive bladder tumor. From glycolipid composition also, MBT-2 is considered as an appropriate model for human invasive bladder tumor. Anti-tumor effect of locally administered G(M3) On MBT-2 tumor was investigated. MBT-2 cells were injected subcutaneously into the right hind limb of CH3/HeSlc female mice on day 1. Tumor bearing mice were randomly placed on day 8 into G(M3) treatment, G(D3) treament, sialic acid treament and control groups. G(M3) was administered between tumor and fascia at 10 mu g in 0.1 ml, 1 mu g in 0.1 ml from day 8 to day 20 every other day, 7 times in total. Control group was given 0.1 mi of saline. G(D3) group was given 12.5 mu g of G(D3), and sialic acid group 2.5 mu g of sialic acid. The relative growth rates of control group, G(M3) 1 mu g group, G(M3) 10 mu g group on day 22 were 139+/-74, 56+/-39, 22+/-14, respectively, and statistically significant among these three groups (Mann-Whitney's U test p<0.01). There were no significant difference between control and G(D3) or sialic acid group. All of the 15 control mice had muscle invasion, however, of the 19 G(M3) 10 mu g administered mice, only 4 had muscle invasion. The incidence of muscle invasion between these 2 groups was statistically significant in chi(2) test (p<0.001). Locally administered G(M3) inhibited both invasion and growth of MBT-2 tumor. This mechanism could be explained by an important role of G(M3) in cell adhesion mediated by integrin and fibronectin interaction. These results may be applied to antiadhesion therapy of human invasive bladder tumor.