Rhodamine-123, a lipophilic, cationic, rhodocyanine dye, has been reported to have carcinoma selective toxicity in vitro and in vivo. This phase I clinical trial established the safety and pharmacokinetics of Rhodamine-123 administered to men with hormone refractory prostate cancer. A single dose toxicity study of Rhodamine-123 determined the maximum tolerated dose. A multiple dose toxicity study assessed the safety of Rhodamine-123 at the maximum tolerated dose level. Transient and variable toxicities noted following Rhodamine-123 infusion resolved within 6 hours following infusion. Pharmacokinetic analyses of sera showed no accumulation of drug with repeated monthly administrations. Drug retention was confirmed in prostatic tissue following Rhodamine-123 administration. PSA doubling times lengthened variably suggesting drug efficacy but the data were not statistically significant. The maximum tolerated dose of Rhodamine-123 is 96 mg/m2. The drug can be safely administered at monthly intervals without detectable drug accumulation in serum. Rhodamine-123 is retained by prostatic tumor tissue.

The establishment, characterization, and tumorigenicity of a new epithelial cell line (PC-3) from a human prostatic adenocarcinoma metastatic to bone is reported. The cultured cells show anchorage-independent growth in both monolayers and in soft agar suspension and produce subcutaneous tumors in nude mice. Culture of the transplanted tumor yielded a human cell line with characteristics identical to those used initially to produce the tumor. PC-3 has a greatly reduced dependence upon serum for growth when compared to normal prostatic epithelial cells and does not respond to androgens, glucocorticoids, or epidermal or fibroblast gowth factors. Karyotypic analysis by quinacrine banding revealed the cells to be completely aneuploid with a modal chromosome number in the hypotriploid range. At least 10 distinctive marker chromosomes were identified. The overall karyotype as well as the marker chromosomes are distinct from those of the HeLa cell. Electron microscopic studies revealed many features common to neoplastic cells of epithelial origin including numerous microvilli, junctional complexes, abnormal nuclei and nucleoli, abnormal mitochondria, annulate lamellae, and lipoidal bodies. Overall, the functional and morphologic characteristics of PC-3 are those of a poorly-differentiated adenocarcinoma. These cells should be useful in investigating the biochemical changes in advanced prostatic cancer cells and in assessing their response to chemotherapeutic agents.

The successful isolation of a malignant human, prostatic epithelial cell line, PC-3, is reported. A partial characterization and ultrastructural analysis is included.

Epithelial cell cultures of the normal human prostate gland were established. The subculturing of these cultures was accomplished with a novel nonenzymatic technique. These cultures were defined as normal epithelial cells on the basis of ultrastructure, karyotype, and inability to grow in soft agar.

Six epithelial cell cultures established from adult Wistar rat liver were examined by electron microscopy for oncornavirus-like particles. Two heteroploid and tumorigenic cultures demonstrated many cells with virus-like particles of type-A and type-C morphology. The remaining four, composed of diploid nontumorigenic cells, demonstrated similar virus-like particles but in few cells and only after bromodeoxyuridine treatment. The virus-like particles in the tumorigenic cultures were identified as a rat type-C virus by serological assays.

Maintenance media incubated with biopsy specimens of human skin tissues contained minute (10-12 nm wide), ring-shaped particles (RSP) similar to those described previously in culture media of mammalian cell lines. In addition to the qualitative demonstration of the particles by electron microscopy, a quantitative method was applied to estimate in media the amount of DNA that could be attributed primarily to RSP content. The amounts of DNA, obtained with 146 test specimens, varied with the pathologic condition of the tissue in the following ascending order: normal skin, verruca vulgaris, seborrheic verruca, actinic keratosis, basal cell carcinoma, and squamous cell carcinoma.