Lack of enhancing effect of two Kampo medicines, Sho-saiko-to (TJ-9) and Sairei-to (TJ-114), on rat urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The modifying potential of two Kampo medicines (Japanese traditional herbal medicines), Sho-saiko-to (TJ-9) and Sairei-to (TJ-114), on urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN) was evaluated. Groups of 20 animals were given 0.05% BBN in their drinking water for 4 weeks and then 0.7 or 2.8% TJ-9, 0.9 or 3.6% TJ-114, or 3.0% sodium bicarbonate (NaHCO(3)) as a positive control substance in their diet for 32 weeks. All rats were killed after 36 weeks and examined histopathologically. No adverse effects of the test compounds were found in terms of survival, clinical sign, and body weight. Administration of 0.7 and 2.8% TJ-9 and 0.9 and 3.6% TJ-114 in the diet did not affect the incidences or extent of PN hyperplasia in the BBN-treated rats. Incidences and multiplicities of papillomas were also not affected in rats fed 0.7 or 2.8% TJ-9 and 0.9% TJ-114, while they were significantly decreased in animals given 3.6% TJ-114 in the diet. The results thus demonstrated that neither of the test chemicals exerted any promotional activity on urinary bladder carcinogenesis, in clear contrast to NaHCO(3). In addition, bladder carcinogenesis was reduced by 3.6% TJ-114 in the diet, under the present experimental conditions.

Enhanced detection of bladder cancer in urine cytology with Lewis X, M344 and 19A211 antigens.

Lewis X, M344 and 19A211, all glycoprotein antigens associated with bladder tumors, were evaluated in urine cytologic specimens from 52 patients with transitional cell bladder neoplasms and from 12 controls. Forty-three of 52 patients had a tumor on a concurrent bladder biopsy, while 9 of 52 patients had a negative biopsy. Of the 43, 27 (62.8%) had positive or suspicious cytology, 35 (81.4%) had positive immunocytochemical reactions with at least one antibody, and 36 (83.7%) had either cytologic or immunocytochemical abnormalities. Of the 15 patients with a low grade tumor (papilloma or grade 1 transitional cell carcinoma), 14 (93.3%) had positive immunohistochemical findings, while 6 (40%) had recognizable abnormal cells on routine cytology. Of 28 patients with a high grade tumor, 21 (75%) had positive immunohistochemical findings, while 21 (75%) had abnormal cytology. Staining of rare epithelial cells was seen in 2 of 12 control cases (specificity, 83.3%). Immunocytochemistry with antibodies to tumor-associated antigens can enhance the cytologic detection of exfoliated low grade bladder epithelial tumor cells.

Urinary type IV collagenase: elevated levels are associated with bladder transitional cell carcinoma.

Accumulating experimental evidence has linked the overproduction of extracellular matrix-degrading metalloproteinases with tumor cell invasion. In the present study one member of the metalloproteinase family, type IV collagenase (M(r) 72,000 gelatinase), is shown to be elevated in the urine of patients with transitional cell carcinoma of the bladder. The form of the enzyme in the urine was studied by three independent methods: enzyme-linked immunosorbent assay, Western immunoblotting; and gelatin zymography. Immunoblotting revealed that the enzyme was present as a series of fragments, each retaining the amino terminus of the mature proenzyme. A prominent M(r) 43,000 fragment was associated with the transitional cell carcinoma cases. Zymography demonstrated that multiple enzyme species with gelatinase activity were present in urine and that high-molecular-weight bands of substrate lysis corresponded to complexes between type IV collagenase and tissue inhibitor of metalloproteinases 2. The total amount of type IV collagenase antigen was significantly elevated in the urine of 37 transitional cell carcinoma patients (range, 0-1081 ng/ml; mean, 318.4 +/- 147.3) compared to 19 normal controls (P < or = 0.004) and 17 inflammatory disease controls (P < or = 0.011). Immunohistochemical staining of bladder tumor biopsies verified that the transitional cell carcinoma cells were producing the M(r) 72,000 enzyme. Thus, M(r) 72,000 type IV collagenase, which is present in the urine in many forms including fragments and complexes with inhibitors, may be a useful marker for bladder cancer diagnosis or prognosis.

[Endogenous risk factors for bladder neoplasms in women]. / Endogennye faktory riska novoobrazovanii mochevogo puzyria u zhenshchin.

A case-control study was performed to evaluate hormonal status in 154 female patients with bladder cancer and 213 healthy women. Cancer patients were characterized by shorter reproductive period and miscarriage, absence of gestation, endometrial and breast cancer and ovarian cysts in the past history. Evaluation of tryptophan metabolism in 131 male and 111 female patients with bladder cancer showed the occurrence of a carcinogenic metabolite--3-oxyanthranilic acid--in the urine to be higher in women. Blood hormone levels were measured in 55 female patients and 49 healthy women by radioimmunoassay. Decreased levels of progesterone and estradiol as well as of hormones potentiating their production (folitropin and lutropin) were the most frequent hormonal disorders encountered.

Various urinary properties in bladder tumor patients.

Urinary electrolytes, pH, urea nitrogen, creatinine, uric acid and osmolarity were measured in patients with bladder tumors and compared with those of a control group. There were 41 bladder tumor patients ranging in age from 29 to 87 (average 64) years with a male:female ratio of 32:9. According to histopathological classification of the bladder tumors, there were 34 transitional cell carcinomas (TCC) (21 G1, 10 G2, 3 G3), four squamous cell carcinomas, two adenocarcinomas and one inverted papilloma. The control group comprised 29 patients ranging in age from 35 to 80 (average 63) years with a male:female ratio of 26:3. Four urine samples were collected from each patient: early morning on the day of admission, just after admission, early morning on the day of return to hospital after temporary discharge, immediately after return to hospital after temporary discharge. The results indicated that the urinary Ca2+ and uric acid values were significantly lower in the bladder tumor group than in the control group. The urinary pH tended to be somewhat higher than in the control group, and the pH values tended to be especially high in the TCC G3 patients. There were differences in the various urinary properties between the TCC G1 and G2 and the TCC G3 patients.

Bladder cancer diagnosis by computer image analysis of cells in the sediment of voided urine using a video scanning system.

A video-based computerized semiautomated image analysis system was applied to the diagnostic evaluation of 119 sediments of voided urine: 103 from patients with a broad variety of neoplastic and nonneoplastic disorders of the lower urinary tract and 16 normal controls. Each specimen was presented to the machine as a single cytocentrifuge preparation, preserved in 2% Carbowax in 50% ethanol and stained-by the Papanicolaou method. Five hundred sequential "objects" were scanned within an area of 9 sq mm on each slide. "Objects" of no diagnostic value, such as dirt, debris, inflammatory cells, cell clusters, poorly preserved cells, etc., were eliminated from the final diagnostic analysis by a computer-based hierarchic triage system. The final specimen classifier was based on the cell images identified by the computer as well-preserved normal (NEG), atypical (ATY I), suspicious (ATY II) and malignant (POS) cells. For specimen classification by computer, the four categories of "abnormal," "inadequate," "acellular" and "negative" were defined. For high-grade tumors, the performance of the specimen classifier was generally comparable to the visual diagnosis. The specimen classifier unexpectedly identified twice as many low-grade papillary urothelial tumors as abnormal than did the visual analysis. Several false "alarms" were recorded by computer in patients with benign prostatic hypertrophy and prostatic carcinoma, some of whom had atypical urothelium. One of the 16 negative controls was misdiagnosed by the computer as abnormal. The possibility that the video system recognizes nuclear abnormalities not perceived by the human eye is being investigated further. The details of the computer analysis are reported, and the value of the system is discussed. The system appears to be promising as a future laboratory instrument, although it requires further extensive testing.

[The place of urinary cytology in the diagnosis of urothelial tumors]. / Place de la cytologie urinaire dans le diagnostic des tumeurs urothéliales.

A cytologic study was done in three groups of patients, either for screening purposes or for the follow up of vesical tumors already treated by transurethral resection or cystectomy. The reliability of urinary cytology is closely related to the degree of tumor anaplasia (81,8% positive cytology in grade III tumors). When a cytologic and cystoscopic follow-up is done, the results of these two methods are in agreement in 60% of the cases. In the follow up of patients already treated for vesical tumors, the association of cystoscopy and cytology increases the discovery of recurrences by 40%. The persistence of isolated positive cytologies is indicative of highly malignant lesions (grade III). In cystectomized patients, a close correlation exists between the histologic grade and the positivity of the cytologic survey. A cytologic follow up after cystectomy helps to discover a greater number of urethral recurrences.

Studies on the clinical significance of nonesterified and total cholesterol in urine.

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean +/- 2 SD) of 0.2-2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3-3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasizing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers.

[3-hydroxyanthranilic acid content in the urine of bladder cancer patients]. / Soderzhanie 3-oksiantranilovoi kisloty v moche bol'nykh rakom mochevogo puzyria.

The work has shown the possibility to determine immunologically 3-OAA-antigen in the urine of bladder cancer patients, which is absent in the urine of healthy individuals. By the identity reaction the authors proved the supposed structure of the detected antigen, i. e. the presence of 3-oxianthranilic acid in it. The data obtained may lie in the basis of the immunodiagnostic test to bladder cancer.

Use of heterogenous and monospecific antisera for the diagnosis of bladder cancer.

A rabbit antibody to antigens present in urine from bladder cancer patients was prepared and used in conjunction with various monospecific antisera to detect urine components related to bladder cancer. All urine samples were centrifuged routinely, dialyzed and concentrated 10 times before assay by gel diffusion versus the various antisera. Urine was considered positive when it showed reactivity with 2 or more antibodies. This method of analysis resulted in the diagnosis of 64% of the bladder papillomas and 77% of the bladder cancers tested, compared to only a 7% falsely positive rate with normal urine. These data support the potential usefulness of an antiserum panel in the immunological diagnosis of bladder cancer in the general population and in high risk individuals.