The bioassay using the polythemic mice demonstrated persistent erythropoietin (Ep) activity in 24 renal carcinoma patients. Eight patients without clinical evidence of renal carcinoma had Ep levels that were slightly higher than those of controls, suggesting the possibility of occult disease. Increased levels of Ep were noted in 5 patients with other genitourinary carcinomas. This selective study reaffirms the value of Ep as a biologic marker in some renal cell cancers, and occasionally in other genitourinary tumors.

In the Wistar/Furth rat, twenty-four hours after unilateral nephrectomy, the remaining contralateral kidney produces maximum amounts of renotropic growth factors. These factors stimulate tumor growth in recipient rats with s.c. Wilms tumor, but have no effect on kidney weight. In tumor-free recipients, kidney hypotrophy results when the factors are administered.

Contralateral kidneys; removed forty-eight hours after unilateral nephrectomy, contain renotropic growth factors with different effects on normal kidney and Wistar/Furth rat Wilms tumor. Receptors on tumor cells bind factors which, when eluted followed by in vivo bioassay, stimulate the growth of Wilms tumor. Receptors on normal kidney cortex cells bind factrs which, when eluted, produce kidney hypotrophy in nontumor-bearing rats.

Wistar/Furth rats received chemotherapy with vincristine, actinomycin D and adriamycin alone and in combination following renal subcapsular implantation of a transplantable murine Wilms' tumor and nephrectomy. Each agent prolonged survival significantly compared to control, and both two-drug regimens were superior to single agent therapy. The two-drug programs were equally effective. No drug regimen was effective in preventing abdominal recurrence.

A retrospective study of all cases of seminoma treated at Roswell Park Memorial Institute from 1970 through 1979 was conducted. Fifty-six evaluable patients treated initially with radiation therapy were seen during this period, and the overall survival rate at an average follow-up period of 52 months was 82%. The survival rate in patients with bulky abdominal or supradiaphragmatic metastases was only 33% (4 of 12 patients). Treatment failures were analyzed to determine their apparent causes and the implication of such failures to the future management of seminoma. The use of combination chemotherapy as the initial treatment modality in advanced seminoma is discussed in light of these results.

Growth characteristics, survival time, and various other parameters such as chromosome studies and DNA synthesis were evaluated in a transplantable transitional cell mouse bladder tumor induced by N-[4-5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT). When the tumor was implanted subcutaneously, the mice were observed to survive mean 43 + 7 days (mean +/- SEM) with an average tumor burden of mean 8.45 +/- 0.60 gm (mean +/- SEM) of solid tumor tissue. In the tumor control animals, lung metastasis was noted in 3 animals at 42-49 days post implantation. The histological appearance of the primary tumor and the lung metastasis presented an undifferentiated anaplastic tumor with many spindle cells. The modal number of chromosome is 65 with several markers identifiable as abnormal in morphology. A significant decrease (p less than 0.001) in DNA synthesis was noted between 13 days and 20 days post implantation. In the evaluation of chemotherapy drugs, Cis-dichloro-trans-dihydroxy-bis-iso propylamine platinum IV (CHIP), Cis-diaminedichloroplatinum II (DDP), Cyclophosphamide (CTX) and Methotrexate (MTX) tumor growth was significantly retarded (p less than 0.005) in the DDP treated groups, however survival was not improved. Survival was significantly improved in the CTX treated group (p less than 0.001), although no significant decrease was noted in tumor growth. Lung metastasis was noted in all groups. This model has certain characteristics which make it a good model to study locally invasive bladder cancer.

The ability of choline (C) to prevent hepatic toxicity due to chronic administration of 6-mercaptopurine (6-MP) was evaluated in male Wistar rats. Two dose levels of 6-MP and two dose levels of C were used. Choline did not prevent or diminish the hepatic accumulation of triglyceride when administered in combination with 6-MP. The 6-MP did impair the growth of the experimental animals, and this effect was antagonized by C administration. The data provided experimental support for the clinical observation of growth impairment in children treated with chronic antimetabolite therapy for acute lymphoblastic leukemia.

Erythropoietin (ESF) levels were assayed in rats bearing the Wistar‐Furth Wilms' transplantable tumor. Sites of tumor inoculation varied from subcutaneous, intramuscular, intrarenal (subcapsular), to intra‐peritoneal. Two‐thirds of the animals exhibited ESF elevations without polycythemia, or severe anemia (HCT < 30.0 vol %). The elevations in ESF were not detectably related to the time of sacrifice (age of the animal), size of the primary tumor, or number of gross metastatic foci. The diminished ESF response noted to animals given intramuscular tumor implantations is believed to reflect differences in tumor blood and lymphatic supply at the various sites of inoculation. The pattern of ESF responses in the Wistar‐Furth Wilms' tumor model is thus quite similar to that which we have observed in man, and appears to represent an animal model for tumor‐related ectopic hormone release. The nature of the hormone is believed to differ from that seen in normal physiological states.

The development of animal bladder tumor models as a research tool for different modes of therapy has been widely evaluated. Recently these tumors have either spontaneously grown or have been propagated in inbred strains. Bladder tumors have also been chemically produced by N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) when orally administered over a long period of time. It has been further reported that these tumors have been inhibited by various chemotherapy regimens. The availability of an experimental bladder tumor model offers an opportunity to evaluate the effectiveness of a prescribed treatment. In our studies FANFT was noted to produce only from 33 to 40% bladder tumors in several experiments in an inbred strain of rats conducted over several years. Reproducible transplantability of these tumors was not demonstrable in the same inbred strain. In addition, treatment with mitomycin C an an effective chemotherapeutic agent was not detectable in part, since comparably the percentage of control bladder tumor growth was low. These findings of a three-year study should be carefully considered when evaluating recommendations for clinical adjuvant chemotherapy based on results obtained with FANFT.

The Wilms' tumor (Wistar-Furth, Columbia University) animal model kills the host in a predictable period of time, associated with widespread metastases (lungs, liver, spleen) regardless of the route of tumor transplantation. Actinomycin D in single or multiple doses has previously been shown to increase survival, reduce the primary tumor weight, as well as the number of metastases in this experimental model. The model thus has close similarity to man. The present report describes a remarkable effect of adriamycin in this animal system. The beneficial results are, however, limited by severe dose-related toxicity. Nevertheless, faced with recurrent or metastatic lesions following prior current conventional clinical therapy, based on the present experimental results, we believe adriamycin treatment should be given serious clinical consideration.

Fresh urine specimens in 34 selected renal allograft recipients were examined for the presence of pyronine-positive lymphocytes on 678 occasions during a two-year follow-up period. During the period of observation 15 clinical episodes of allograft rejection diagnosed by a variety of other tests and frequently confirmed by biopsy, correlated 100 per cent with the presence of a significant number of urinary pyronine-positive lymphocytes. No false positive or negative results were noted. These episodes occurred up to nine months after renal allotransplantation. In more than 80 per cent of instances in this carefully selected series, the pyronine-positive urinary lymphocytes were detected two to seven days prior to the clinical diagnosis of renal allograft rejection by other means. Thus this test is a valuable tool for follow-up monitoring of renal allograft recipients.

A murine renal adenocarcinoma was implanted unilaterally under the kidney capsule in more than 200 inbred Balb C mice and evaluated in nine groups: controls with and without tumor, and following left nephrectomy of tumorous kidney at seven, fourteen, and thirty-nine days after implant. Mean survival times for tumor-implanted, nephrectomized mice were 60.1, 56.4, 54.1, and 56 days, respectively. Pulmonary metastases were evident between fourteen and forty-five days, 100 per cent in the tumor control non-nephrectomized group, and 36 and 90 per cent in the respective nephrectomized groups. All tumor-implanted animals ultimately died of metastatic disease. Predictable and reproducible disease patterns were noted. This model lends itself to screening chemotherapeutic agents and other modes of therapy for the control of metastatic renal cancer following nephrectomy.