Variation in the expression of p53, c-myc, and bcl-2 oncoproteins in individual patient cultures of normal urothelium exposed to cobalt 60 gamma-rays and N-nitrosodiethanolamine.

The controls determining the initial response of cells to DNA damage probably determine whether a cancer will ultimately occur. Efficient repair or apoptosis represents extremes of control mechanisms. Misrepair can lead to fixation of damage. The changes in oncoprotein expression of three genes involved in the regulation of repair of DNA damage and postdamage proliferation of cells were measured in cultures of normal urothelium from 55 patients without any malignancy. The aim was to obtain information on interperson variation in response to carcinogens in the human population. The group included 10 pediatric patients < 2 years old. Two different carcinogenic agents, ionizing radiation and N-nitrosodiethanolamine, which represent widely different DNA-damaging pathways, were used. Both of these cause bladder cancer in humans. Cells from explanted tissue were examined after carcinogen exposure for levels of p53, c-myc, and bcl-2 proteins. Both carcinogens led to increased levels of cytoplasmic p53 protein expression, although there was significant interpatient variation. bcl-2 showed a very significant increase in expression after radiation exposure. c-myc was high and variable pre- and postexposure. Individual patient culture changes in the expression of the three oncoproteins did not correlate significantly with each other or with cell growth, suggesting that the controls are complex. Pediatric samples had lower mean control values of p53 and bcl-2 than did adult samples. This was due to the absence in this group of high controls seen in some adult cultures. The result suggest that an early breakdown in control mechanisms of growth arrest and apoptosis may occur in urothelium after carcinogen exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

'Congenital' hydronephrosis: limitations of diagnosis by fetal ultrasonography.

OBJECTIVE: To determine whether children presenting clinically with pelvi-ureteric junction obstruction had fetal hydronephrosis. PATIENTS AND METHODS: Forty-three children, born during or after 1985, presented clinically with pelvi-ureteric junction obstruction. Records of the maternal pregnancies were reviewed with reference to the findings of any fetal ultrasonography. RESULTS: In 25 patients fetal ultrasonography was performed at or beyond 30 weeks' gestation (mean 33.2). None had significant fetal hydronephrosis. CONCLUSION: Hydronephrosis due to pelvi-ureteric obstruction is not necessarily congenital and patients presenting clinically may differ inherently from those detected fetally.

The expression of epidermal growth factor receptor on human bladder cancer: potential use in radioimmunoscintigraphy.

Monoclonal antibody 425, which binds to an extracellular domain of the epidermal growth factor receptor, was used to evaluate the expression of this antigen on bladder cancer cells. Epidermal growth factor receptor was found on all bladder cancer cell lines tested. Immunoperoxidase staining of fourteen invasive human bladder cancers with monoclonal antibody 425 demonstrated that ten showed strong staining, one showed weak staining and three were negative. Five noninvasive tumors were similarly examined. Four of these were negative and one showed weak staining. Biodistribution experiments with human bladder tumor xenografts in athymic nude mice using radiolabeled monoclonal antibody 425 and an isotype matched control antibody demonstrated specific tumor localization at five and seven days following antibody injection. Successful imaging of a human bladder tumor xenograft was achieved five days post antibody injection. These data confirm that epidermal growth factor receptor expression correlates with bladder cancer stage and suggests that epidermal growth factor receptor may serve as a target antigen for radioimmunoscintigraphy.

Uptake of 2-deoxy, 2-(18F) fluoro-D-glucose in bladder cancer: animal localization and initial patient positron emission tomography.

An orthotopically transplanted, locally metastasizing rat bladder tumor model was developed to evaluate the extent of uptake of fluoro-deoxy-glucose (FDG) in bladder cancer. Significant uptake of FDG in localized bladder tumors in rats was shown, with an average tumor-to-blood ratio of 39 at 2 hours after intravenous FDG administration. Metastases (3 nodal and 1 peritoneal) also showed significant uptake of FDG, with an average metastasis-to-blood ratio of 21.7, and tumor involved-to-normal lymph node ratio of 5.3. Because FDG is excreted in the urine, urinary FDG potentially could prevent the use of FDG/positron emission tomography (FDG/PET) scanning for localized bladder cancer. Bladder lavage successfully reduced the retention of FDG in the normal rat bladder, with an estimated uptake ratio of tumor-to-normal bladder of 13.1 after 5 ml. saline irrigation. Based on these data, we performed an FDG/PET scan of a patient with biopsy proved recurrent intravesical bladder cancer after radiation therapy. Computerized tomography (CT) of the pelvis showed abnormalities consistent with radiation scarring and extravesical tumor. Due to the scarring, the extent of tumor growth could not be determined. The patient also had pulmonary opacities seen on chest radiography. The FDG/PET scan of this patient showed significant extravesical uptake in the pelvis, confirming the abnormality noted on CT. Good images of the clinically apparent metastases in the chest also were obtained. These preliminary data indicate that FDG/PET imaging of bladder cancer is feasible and it may provide new information for the diagnosis and staging of patients with bladder cancer.