The effect of rhodamine-123 on 3 prostate tumors from the rat.

PURPOSE: Rhodamine-123 (Rh-123) was found to have a specific attraction to the mitochondria of tumor cells. The destruction of rat prostate tumor cells by Rh-123 is described. MATERIALS AND METHODS: Tissue was used from rat prostate studies of Rh-123 treatment of R3327-H, PA III prostate tumor of Pollard and the autochthonous tumor in Lobund-Wistar rats. All tissues were fixed in 10% buffered formalin, paraffin embedded and sectioned at 1 to 3 micron. for good cellular detail. RESULTS: Destructive processes were seen in all 3 rat prostate tumor models evaluated. The changes included acinar cell clumping, acinar destruction with scarring, cyst formation within acinar cells and increased stromal cells. CONCLUSIONS: Since all tumor models were found to respond to Rh-123 in a similar manner, any of them could be used for the evaluation of anticancer agents. These studies demonstrated that Rh-123 was effective in suppressing the growth of hormone sensitive and insensitive rat prostate tumor cells.

Extracellular matrix in prostate adenocarcinoma: Changes in the glycoprotein component of the basement membrane.

This study was designed to assess the condition of the basement membrane of archival prostate carcinoma tissue when adjacent to tumor cells of varying degrees of malignancy, using a simple staining technique. Tissue was obtained from 87 patients with untreated prostate cancer. Tissue was randomly selected from four patients from each of four Gleason grades of 2, 3, 4, and 5. Tissue was fixed in 10% formalin and routinely processed. Sections were freshly cut from paraffin blocks and slides were subjected to the periodic acid-Schiff (PAS) reaction. Gleason grades 2, 3, 4, and 5 were visualized. As the Gleason grade increased, the intensity of staining, density, and thickness of the gel-like basement membrane decreased. With the increasing Gleason grade, as seen by the PAS stain, the basement membrane glycoprotein decreased in its density and thickness with increased fragmentation, which suggested that the basement membrane would be so modified by the tumor cells to allow the tumor to spread locally. The breakdown of the basement membrane is probably a consequence of increased intratumor pressure, certain proteolytic enzymes, and increased cell motility associated with increased degree of malignancy.

Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro.

The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L-W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60-95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines.

Transscrotal approach to testicular tumors: an anatomical approach.

Performing a conventional radical inguinal orchiectomy for suspected testicular cancer has three important deficiencies: 1) A benign lesion can unnecessarily and unknowingly be treated by orchiectomy. 2) Alternate routes of tumor dissemination (superficial external pudendal veins) are not clamped or destroyed before the tumor-bearing testis is brought up through the external inguinal ring. 3) The act of squeezing the testis through the external inguinal ring may be an important cause of tumor spread. Presented in this paper is a transscrotal approach that eliminates these three deficiencies. It is advocated for critical clinical evaluation.

Rapid drop in serum testosterone after bilateral subcapsular orchiectomy.

Bilateral subcapsular orchiectomy was performed in six patients with metastatic prostatic carcinoma. In these patients the serum levels of testosterone were determined serially up to twenty-four hours. Castrate levels of testosterone were achieved in about two and one-half hours. This is the first published report of such a rapid decrease in serum testosterone. Castrate levels of serum testosterone using the luteinizing hormone releasing hormone (LH-RH) agonists are achieved in fourteen to twenty-one days. The relative cost of orchiectomy and LH-RH agonists, for thirty-six months, was $2,042.00 and $12,780.00, respectively. LH-RH agonists may be effective for only a year. Urologists are urged to continue using bilateral subcapsular orchiectomy and not use LH-RH agonists in the management of metastatic prostatic carcinoma.

Use of rhodamine 123 in the treatment of the Pollard III rat prostate adenocarcinoma.

Significant destruction of the Pollard III rat prostate adenocarcinoma was achieved by treatment with rhodamine 123 at a dosage of 15 mg/kg every other day for 33 to 38 days. Injection of tumor remnants into untreated animals produced no tumor regrowth. Our data have demonstrated rhodamine 123 to be a significant drug for the management of the very aggressive Pollard III tumor.

Metachromasia in the human prostate: a histochemical difference between benign prostatic hyperplasia and prostatic carcinoma.

Metachromasia is a histological staining reaction in which a dye is changed by the tissue from its original to a contrasting color. With toluidine blue at a pH of 8.3 or 3.8 metachromatic staining is seen in the tissue of benign prostatic hyperplasia. When adenocarcinoma is adjacent to or even within the prostate containing benign hyperplasia, no metachromasia is seen around the benign acini. No such staining was seen in glands examined that contained either well differentiated or moderately well differentiated adenocarcinoma. No metachromatic periacinar staining was noted in the normal prostate. This observation may provide information as to the morphogenesis of prostatic hyperplasia.

Adenomatoid tumors in the tunica albuginea of the testis.

Adenomatoid tumors of the tunica albuginea of the testis is rarely seen. Only 15 such cases have been described. A patient is presented in whom such a tumor was found and excised through a scrotal incision. He is alive and well 27 years later. The author presents reasons for the type of scrotal exploration done. The pathological histology is discussed. An adenomatoid tumor can easily be confused with a prostatic adenocarcinoma on frozen section.

Rhodamine-123 as effective agent in rat prostate tumor R3327-H. Preliminary report.

Rhodamine-123 is a fluorescent dye that preferentially stains mitochondria and causes damage to mitochondria of malignant cells. The effect of this mitochondriacide on the transplantable rat prostate tumor R3327-H was determined in this study. Rhodamine was administered subcutaneously every other day at a dosage of 15 mg/Kg body weight for fifty-two days. There was significant alteration of the acinar cells with disruption of the cells from the basement membrane, as well as vacuolization and change in fibroblast shape and density. Rhodamine-123 may have a role in the treatment of prostatic cancer.

Cytochemical localization of lipid, peroxidase, and carbohydrate substances in the Dunning prostatic adenocarcinoma R3327H: an ultrastructural analysis.

The ultrastructural organization of the cells of the transplantable prostatic adenocarcinoma of the rat, R3327H, has been studied on a cytochemical level. The techniques used were those to localize lipids, peroxidase, and carbohydrate-like substances. This study has clearly shown that there are, in the tumor cells and not in normal prostatic epithelial cells, both lipid compartments with an intense peroxidase membrane. Within the lipid "droplet" we find it to be compartmentalized by conconavalan A-positive material. These observations suggest that this tumor cell may be a "degenerating" or old cell. It may well be that this cancer is a disease of dying cells--the degrading consequence of cell growth.

Apparent resistance of the integument of the inverterbrate Lehmannia poireri to production of papillary tumors by a known chemical carcinogen.

Papillary tumors of the skin of the land invertebrate Lehmannia poireri (a gastropod) could not be induced by using a potent vertebrate carcinogen. With the same agent 7,12-dimethylbenz (a) anthracene papillary tumors can readily be induced in mice. The resistance of this invertebrate to a known vertebrate carcinogen is discussed and the ramifications are conjectured.

Use of parenteral human globulin in acute, chronic, and recurrent urinary tract infections.

Sixty-four patients with recurrent or chronic urinary tract infections without evidence of disease demonstrated by conventional diagnostic methods underwent serum immunoglobulin studies. Only 23 were shown to have a deficiency of immune globulins, IgA, IgM, or IgG. Treatment with parenteral globulins resulted in sterile urine for the three-year follow-up period. Other urologists are urged to try this treatment under the conditions outlined.