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LNCaP is an androgen-responsive prostatic carcinoma cell line that exhibits a bell-shaped growth response curve to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this unique growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In an early study, we demonstrated that LNCaP proliferation was stimulated by interleukin (IL)-6 in a paracrine manner, because these cells did not express a significant amount of IL-6. In the present study, the role of IL-6 in mediating androgen regulated proliferation in LNCaP cells was investigated. DHT, at increasing doses up to 10(-8) M, resulted in a release of IL-6 from LNCaP cells. This dose-dependent effect of DHT on LNCaP proliferation could be partially inhibited by the addition of antibody against IL-6 into the culture medium. These results indicate that the DHT-induced expression of IL-6 stimulates proliferation of LNCaP cells in culture in an autocrine manner.

Multilocular cystic renal cell carcinoma (MCRCC) appears to be a distinct subtype of renal cell carcinoma with characteristic gross and microscopic features. The authors' ten-year experience (1977-1987) included six cases of MCRCC that were followed for a minimum of two years, with neither recurrence nor metastasis observed in any of the cases. During this period, there were 855 urologic procedures for the upper urinary tract, with 256 neoplasms or cysts identified. These included 32 simple cysts, 41 transitional cell carcinomas, 133 renal cell carcinomas, 17 papillary renal cell carcinomas, and 33 miscellaneous tumors. Histologically, the MCRCCs were well-demarcated multicystic lesions containing variably sized aggregates of neoplastic clear cells showing grade 1 nuclear features and little or no mitotic activity. The cyst walls were densely fibrotic, and the lining was often devoid of epithelium. Flow-cytometric analysis performed in five of the six cases with the use of paraffin-embedded tissue showed the tumors to be diploid in all instances, with low proliferative activity. The authors believe that this tumor is a low-grade variant of renal cell carcinoma and should be studied further to determine appropriate therapy.

A 34-year-old woman presented with a renal pelvic mass. A nephroureterectomy including a cuff of bladder, was performed and pathologic examination revealed a hamartoma involving the renal parenchyma and pelvis. The pelvic portion of the tumor was composed of papillae lined by urothelium; the parenchymal portion of the tumor was composed of tubules within a fibromuscular stroma. The authors propose that this is a distinct entity not previously described in the literature.

To assess the reactivity of a bladder carcinogen, the absorption by the rabbit (male New Zealand White) bladder mucosa of N-2-acetylaminofluorene (AAF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF), and the N-O-glucuronide of AAF (N-OGI-AAF), as well as binding to the protein and RNA of bladder mucosa, was measured in vivo and in vitro. Mucosal pieces incubated for 3 hours in medium containing a carcinogen demonstrated that the fluorene nucleus of both AAF and N-CH-AAF bound equally with cellular proteins, while N-OGI-AAF binding was lower. In the presence of an excess of beta-glucuronidase, however, N-OGI-AAF showed binding equivalent to its metabolic precursor. After a 3-hour instillation into the bladder lumen of radioactive carcinogens suspended in urine in vivo, transmural absorption of AAF and N-OH-AAF (90%) was substantial, while N-OGI-AAF was absorbed less (55%). The renal excretion during this period varied from 18 to 52% of the instilled radioactivity. There was little reactivity of these carcinogens with the mucosal RNA, both in vivo and in vitro. The metabolism of N-OH-AAF and N-OGI-AAF was such, both in vitro and in vivo, that the acetyl group was not included in the final protein-carcinogen complex in what appeared to be an enzyme reaction.

Awareness of the existence of a tunica muscularis mucosae in the urinary bladder complicates the assessment of muscle invasive carcinomas on bladder biopsy. Sixty cystectomy specimens and select bladder biopsies were reviewed to analyze this problem. The patterns of development of the tunica muscularis mucosae were categorized as continuous, interrupted, scattered, or absent. Most bladders demonstrated several patterns of development rather than a uniform appearance. The most frequently observed pattern was that of scattered smooth muscle fibers seen in 33 of 40 (82.5%) cases. The rarity of carcinomatous invasion limited to the tunica muscularis mucosae is emphasized. The authors conclude that the potential for overstaging bladder carcinomas because of misinterpretation of this structure is small.

A human colon epithelial tumor cell line (LS174T) recultured in vitro following passage through hamsters displayed differences in its cell doubling time and synthesis of carcinoembryonic antigen when compared with the cells grown solely in vitro. These animal-passaged cells more closely resembled the parent tumor cell line (LS180) derived from the primary tumor than LS174T, the trypsinized variant of LS180. Analysis of lactate dehydrogenase isoenzymes indicated that the tumor cells recovered from the hamsters were free of xenogeneic host tissue. Furthermore, LS174T grafted to athymic (nude) mice grew as a mucinous adenocarcinoma microscopically resembling the original tumor. The altered growth potential of LS174T was also demonstrated on confluent feeder monolayers of normal cells and by uninhibited multiplication in vitro. These results suggest that, at least in this one case, short-term passage of long-term cultured cells into xenogeneic hosts may effect a phenotypic reversion such that the cells regain properties observed in the primary tumor and the initial in vitro explant.

Mammary tumors induced in outbred Sprague-Dawley rats by 7,12-dimethylbenz]a]anthracene were excised, cut into 1- to 2-mm3 pieces, and then autotransplanted sc along the mammary line at six sites. Following an average period of 20--30 days, these autografts grew to approximately 2 cm in diameter in 32 of 48 rats (67%). Autografts in the other 33% of the rats remained dormant. Mammary tumors transplanted into allogeneic hosts failed to grow. Tumors derived from autotransplantation were indistinguishable from their primary tumors with respect to their histologic features, the nature of hormone dependency, the content of estrogen receptors, and their ability to incorporate [3H]leucine. Furthermore, autotransplanted tumors derived from a single primary tumor varied little with regard to the preceding parameters; thus they provided an opportunity for serial sampling of individual tumors for repeated morphologic and biochemical evaluations.

Effect of dietary indole on the urinary bladder tumorigenesis by chronic dibutylnitrosamine (DBN) treatment was evaluated in hamsters. In the first experiment, in which DBN-water and diet were given ad libitum, dietary indole significantly suppressed bladder tumor incidence. The inhibitory effect was more pronounced in males. In the second experiment, in which consumption of both diet and DBN-water was rigidly controlled by pair-feeding, dietary indole again significantly suppressed bladder tumor incidence; its effect was similar in both males and females. This suppressive effect of indole on bladder tumorigenesis contrasted markedly with its failure to suppress tumors at other sites such as nasal sinuses, trachea, esophagus, and fore-stomach.

Tested in hamsters was the effect of neonatal treatment with 2-acetylaminofluorene (AAF) followed by prolonged feeding in combination with indole on the development of bladder tumors. Neonatal males and females were given intraperitoneal injections of AAF, 5 mg/100 g body weight, 3 times weekly until weaning. They were then fed a synthetic diet containing 0.06% AAF and 1.6% indole. The 26 hamsters surviving 10-12 months developed transitional cell carcinomas of the bladder, all but 2 of which were invasive. No hamsters had malignant tumors in the liver. Seven hamsters developed peliosis of the spleen.