Transformed fibroblasts coinoculated with epithelial cells accelerated the growth and shortened the latency period of human epithelial tumors in athymic mice. Addition of NbF-1 fibroblasts caused epithelial tumors to grow from five marginally tumorigenic or "nontumorigenic" (nontumorforming) human tumor cell lines or strains: PC-i (prostate), WH (bladder), , and cells derived from the ascites fluids of patients with metastatic renal pelvic or prostate cancers. Evidence for the human and epithelial nature of these experimental tumors was provided by histologic, immunohistochemical, Southern and dot-blot hybridization, and cytogenetic analyses. Transformed fibroblasts induced predominantly carcinosarcomas, whereas nontumorigenic fibroblasts (NIH 3T3) and lethally irradiated transformed fibroblasts induced exclusively carcinomas. The fibroblast-epithelial interaction appears to occur bidirectionally and does not result from cell fusion. Because coculture experiments in vitro did not demonstrate an increased cell proliferation, it appears that undefined host factors can influence tumor growth. This tumor model may be useful in drug-screening programs and in mechanistic studies of factors regulating human tumor growth and progression.Interactions between epithelium and mesenchyme mediate crucial aspects of normal development and are also believed to be important in neoplasia (1)(2)(3)(4). By employing tissuerecombination techniques, it has been demonstrated that the growth and differentiation of normal epithelium is regulated either inductively or permissively by neighboring mesenchymal components (5, 6). Studies of stromal-epithelial interaction in the prostate gland revealed that mesenchyme isolated from the fetal urogenital sinus (7, 8) but not from the prostate of newborns (9) or adults (10) can stimulate proliferation of well-differentiated adult epithelium. Mesenchymal mediation of sex steroid action on glandular epithelium has also been demonstrated. The growth of the prostate (7, 8), the regression of the mammary gland by androgen stimulation (11,12), and the growth (13) and the expression of progesterone receptors (14) by the mammary epithelium in response to estrogen have been shown to be mediated by the indirect action of sex steroids on the fibromuscular stroma.Stromal influences on epithelial neoplasia have also been documented in the salivary gland (15), the mammary gland (16), the urinary bladder (17), and the skin (18 Tumorigenicity Determinations. The athymic nude BALB/c mouse strain (20-25 g, Charles River Breeding Laboratories) was used in all experiments. Tumor volumes were calculated by the formula weight x length x height x 0.5236 (24). With the exception of the PC-3 cell line (25), our definition of "tumorigenicity" conformed to the published data. Dot Blot and Southern Hybridization. DNA was prepared from tissues and tumors according to the method described by Davis et al. (26), with slight modification to include treatment steps with proteinase K (0.2 mg/ml, Sigma) and RNase A (20 ,g/...

Improved erectile dysfunction and lower urinary tract symptoms with sildenafil in men with the 2 conditions were associated with improved quality of life and treatment satisfaction. Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic pathophysiology paradigm is needed to explain the etiology of lower urinary tract symptoms.

The time course of uptake, retention and clearance of the cationic lipophilic dye, rhodamine 123 (Rh123), within the central nervous system was qualitatively evaluated in rats. Weanling rats were injected intracerebrally with avian sarcoma virus, which induced malignant gliomas in situ before injection of Rh123. Comparison was made of the amount of fluorescence of Rh123 within the normal cerebral cortex, myelinated tracts of the brain, meninges, choroid plexus, and neoplastic foci at 1, 4, 8, 12 and 24 hours after intravenous injection. Fluorescence microscopy was utilized to identify tissues containing the dye. Normal neuropil did not contain Rh123 at any of the time periods studied. Gliomas retained the dye at 1, 4, 8 and 12 hours, with increasing uniformity of distribution and decreasing intensity of fluorescence over this time period. Fluorescence was not detected at 24 hours within the neoplastic tissues, but was evident at all time periods studied within the choroid plexus. The specific retention of Rh123 by malignant glioma and by the choroid plexus in vivo suggests that Rh123 may be useful for photochemotherapeutic treatment of brain neoplasms and disorders of the choroid plexus.

The photo-induced toxicity of hematoporphyrin derivative on Dunning R3327 rat prostate cancer cells was studied. Dunning R3327 cells in culture were incubated for two hours in hematoporphyrin derivative and then exposed to red light at 630 nanometers wavelength from an argon pumped dye laser. Cell survival was measured for varying laser power densities, variable concentrations of hematoporphyrin derivative and variable light exposure times. AT1 cells not incubated with hematoporphyrin derivative were directly killed by laser light exposure at power densities greater than 500 mw./cm.2, probably due to hyperthermia. Cells that retained hematoporphyrin derivative were effectively killed using non-thermal levels of red light exposure due to a photochemical effect. Decreasing cell survival of cells that retained hematoporphyrin was related to increasing time of exposure to red light. This form of therapy may be applicable to the treatment of locally invasive prostatic carcinoma in man.

The authors evaluated 440 men with clinically staged and untreated prostate cancer with a monoclonal prostate-specific antigen (PSA) assay. The serum PSA value correlated significantly with both the stage and grade of disease (P < 0.00005). The relationships between PSA and consecutive Stages A, B, C, and D, (a = 0.15) and between progressive Gleason's scores 2 to 4, 5 to 7, and 8 to 10 (a = 0.15) were statistically significant. Also statistically significant was the correlation between serum PSA level and intracapsular versus extracapsular disease (P < 0.00005), although no one value can be used to differentiate reliably between patients in these two categories. The probability of clinically detectable metastasis (Stage DZ) is 85% if the serum PSA level is greater than 30; however, 12% of patients without clinical evidence of metastases (Stages A, B, and C) have such a serum PSA value. Despite the statistically significant association between PSA and tumor differentiation and volume as reflected by tumor grade and clinical stage, this marker cannot be used to determine either for an individual patient. Cancer 67:2200-2206,1991. ROSTATE-SPECIFIC ANTIGEN (PSA) Was identified inP 1979 by Wang and associates,' who localized its production to the prostatic epithelial cells. Since then, its biologic characterization and amino acid sequence have been determined.2,3 It was first used immunohistochemically to confirm the prostatic origin of metastatic malignant turn or^.^-^ Only recently has the potential clinical value of serum PSA been appreciated. As a tumor marker, it is useful to monitor the status of patients who have undergone radical p r o s t a t e c t~m y ,~~~ irradiation, or hormonal therapy. 'O," Comparative studies have shown that PSA is more sensitive than prostatic acid phosphatase (PAP) as a prostate cancer tumor marker.'2,13From the