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Biomedical subjects

D Kadmon

Publications and source records attributed to D Kadmon.

67 records · Page 4Linked to original sources

Inhibition of mouse bladder tumor proliferation by murine interferon-gamma and its synergism with interferon-beta.

We studied the effect of interferon-gamma (IFN-gamma) and mouse L-cell interferon (IFN-beta) on the proliferation of a mouse bladder tumor, MBT-2. A liquid culture clonogenic assay was used, and a linear relationship was obtained between the number of cells plated and the number of colonies formed. When the cells were assayed in the presence of various doses of murine IFN-gamma or IFN-beta, colony formation was inhibited in a dose-dependent manner. Partially purified IFN-gamma was more effective than IFN-beta in inhibiting MBT-2 colony formation in that IFN-beta exhibited a 50% inhibition dose of approximately 1000 units/ml, while the 50% inhibition dose for the partially purified IFN-gamma was approximately 70 units/ml. The 50% inhibition dose for recombinant IFN-gamma was 700 units/ml, suggesting that multiple lymphokines were active in the partially purified preparation. Further studies with partially purified IFN-gamma showed that the inhibitory effect was time dependent with the maximal effect observed after 48 hr of exposure in a 5-day assay. Treatment of partially purified IFN-gamma for 24 hr at pH 2.0 resulted in the abrogation of the antiproliferative effect. Studies in which partially purified IFN-gamma preparations were treated with a monoclonal antibody against IFN-gamma also resulted in abrogation of antiproliferative activity, confirming the nature of the antiproliferative agent to be IFN-gamma. Further studies showed that murine recombinant IFN-gamma also inhibited MBT-2 proliferation in a dose-dependent manner, confirming that IFN-gamma alone mediates antiproliferative activity. Combinations of IFN-beta and recombinant IFN-gamma acted synergistically in the inhibition of MBT-2 proliferation.

Animals↗

Copenhagen rat prostatic tumor ornithine decarboxylase activity (ODC) and the effect of the ODC inhibitor alpha-difluoromethylornithine.

The R3327MAT-Lu tumor is a rapidly growing anaplastic derivative of the Dunning R3327 prostatic adenocarcinoma. We have found the ornithine decarboxylase (ODC) activity of this tumor to be as sensitive to inhibition by alpha-difluoromethylornithine (DFMO) as normal rat prostate. The same was true for all the other R3327 tumor derivatives we studied. The in vivo inhibition of ODC by DFMO allowed increased uptake of exogenously administered putrescine by the R3327AT tumor. Further, DFMO was inhibitory to the growth of the R3327MAT-Lu both in vitro and in vivo.

Animals↗

Prostatic cancer, acid phosphatase, creatine kinase-BB and race: a prospective study.

To examine the effectiveness of prostatic acid phosphatase and creatine kinase-BB determinations in detecting prostatic cancer serum from 594 men more than 40 years was assayed for prostatic acid phosphatase with the thymolphthalein monophosphate substrate and a radioimmunoassay kit. Creatine kinase-BB levels also were measured with a radioimmunoassay kit. Patients with benign prostatic hyperplasia had higher prostatic acid phosphatase levels than normal controls. Accordingly, to avoid a high incidence of false positives in patients with benign prostatic hyperplasia the 92.5 percentile level of the patients with benign prostatic hyperplasia (3.9 ng./ml.) was chosen as the upper limit of normal. With this critical value elevated prostatic acid phosphatase levels were observed in 6 per cent of the patients with clinical stage A disease, 8 per cent with stage B, 35 pr cent with stage C and 68 per cent with stage D. The radioimmunoassay was no more effective than the enzymatic assay in detecting prostatic cancer. A correlation between prostatic acid phosphatase levels and patient race was observed, with 80 per cent of the black patients with extracapsular prostatic cancer having elevated prostatic acid phosphatase levels compared to 34 per cent of the white patients with similar stage disease. Creatine kinase-BB was elevated only in patients with advanced disease and was of little value in the diagnosis of prostatic cancer.

Acid Phosphatase↗

Treatment of a metastatic prostate derived tumor with surgery and chemotherapy.

The R3327/MAT-Lu tumor is a metastasizing variant of the Dunning R3327 Copenhagen rat prostatic carcinoma which, when implanted subcutaneously in the flank or intramuscularly in the hind leg, invariably metastasizes to the lungs. We examined treatment with either single dose chemotherapy, surgical excision of the primary tumor, or a combination of tumor excision and postoperative single dose chemotherapy. All 3 regimens significantly reduced the number of lung metastases; however, only the combination of tumor excision, followed by postoperative chemotherapy substantially prolonged survival and produced cures.

Animals↗

Difluoromethylornithine enhancement of putrescine uptake into the prostate: concise communication.

We studied the effect of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, on putrescine uptake by the rat prostate. Using C-14 putrescine, we found a several-fold increase in uptake by both the dorsal and ventral prostates of DFMO-pretreated intact animals, compared with untreated controls. When previously castrated animals were treated with a combination of testosterone and DFMO, the prostatic uptake of exogenously administered C-14 putrescine increased more than tenfold. Under these conditions, DFMO enhanced the uptake by the prostate to a greater extent than by any other tissue studies.

Animals↗

Inhibition of the R3327MAT-Lu prostatic tumor by diethylstilbestrol and 1,2-bis(3,5-dioxopiperazin-1-yl)propane.

We have previously described the inhibitory effects of diethylstilbestrol on the growth of the androgen-independent, anaplastic Copenhagen rat prostatic tumor, R3327AT, which has a low metastatic potential. We have now selected a variant of the R3327AT tumor that metastasizes exclusively to the lungs, and we have designated it the R3327MAT-Lu. In a dose-response protocol, diethylstilbestrol was inhibitory to the primary R3327MAT-Lu tumor, thereby also inhibiting the formation of lung metastases. Inhibition was also observed in this model tumor by the chemotherapeutic agent 1,2-bis(3,5-dioxopiperazin-1-yl)propane.

Animals↗

Effect of surgery and adjuvant chemotherapy on the R3327 MAT-Ly Lu tumor.

The R3327 MAT-Ly Lu is a prostate derived, anaplastic, hormone independent carcinoma. It spreads primarily to regional lymph nodes, followed by lung metastases. Combination therapy with surgery (tumor removal with or without regional lymphadenectomy) and chemotherapy (ICRF-159) was more effective treatment than either one alone. Primary tumor excision plus lymphadenectomy appeared to reduce the number of pulmonary metastases.

Animals↗

Effect of mini-dose heparin on lymphocele formation following extraperitoneal pelvic lymphadenectomy.

To evaluate the effect of mini-dose heparin therapy on lymphocele formation after extraperitoneal pelvic lymphadenectomy we reviewed the records of 38 patients undergoing this procedure for prostatic cancer during a 24-month period. All patients had a minimum of 6 months of followup. Lymphoceles occurred in 3 of 8 patients (38 per cent) receiving mini-dose heparin and prolonged lymph drainage occurred in 1 other patient (12 per cent). In contrast, only 1 of 30 patients (3 per cent) not receiving mini-dose heparin had a lymphocele and 1 (3 per cent) had prolonged lymph drainage. The results suggest that mini-dose heparin may delay clotting of lymph and, thus, may be associated with an increased incidence of lymphocele formation after extraperitoneal lymphadenectomy.

Heparin↗

Surgical considerations in treatment of intraductal carcinoma of the prostate.

Intraductal carcinomas of the prostate comprise about 3 per cent of all prostatic carcinomas and constitute a heterogeneous group of tumors that include 1) transitional or squamous cell carcinoma, 2) intraductal adenocarcinoma, 3) endometrioid carcinoma and 4) mixed ductal carcinoma. Generally, these tumors are poorly responsive to endocrine and radiation therapy, and complete surgical excision offers the best chance for long-term survival. A case of intraductal adenocarcinoma is presented that illustrates many of the features of these tumors.

Carcinoma, Intraductal, Noninfiltrating↗

Growth inhibition of a prostate tumor by alpha-difluoromethylornithine and by cyclophosphamide.

The effects of the ornithine decarboxylase suicide substrate, difluoromethylornithine (DFMO), and of cyclophosphamide, individually and in combination, on the growth of the R3327MAT-Lu prostate derived tumor were determined. DFMO decreased the growth rate and resulted in a 75% reduction in DNA content compared to the control group. Cyclophosphamide produced a greater inhibition of growth and resulted in a 96% reduction in DNA content relative to the control. DFMO in combination with cyclophosphamide provided no greater inhibition of tumor growth than that of cyclophosphamide as a single agent. Further, in the schedule used in this experimental protocol the toxicity to the host of the drug combination was additive.

Animals↗