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Biomedical subjects

G R Prout

Publications and source records attributed to G R Prout.

At least 127 records · Page 7Linked to original sources
PubMed1979

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Chlorambucil↗
PubMed1979

Intravesical thio-tepa: a study of 3H-thymidine uptake in normal urothelium and FANFT-induced tumors in rats.

Treatment of superficial low-grade bladder cancer often incorporates intravesical instillations of the alkylating agent thio-TEPA. Current dosages and administration schedules are empiric inasmuch as cytokinetic data are sparse. The FANFT-induced bladder rat tumor model closely approximates human bladder cancer. This study measuring 3H-thymidine uptake identified peaks of maximal synthetic activity at 3 and 9 days after thio-TEPA exposure in both normal and neoplastic urothelium. Thus, repeat instillation at these intervals may improve cytotoxicity and overall response rate.

Animals↗
PubMed1979

Galactosyl transferase activity in human transitional cell carcinoma lines and in benign and neoplastic human bladder epithelium.

Cultured cells of human transitional cell carcinoma line MGH-U1, in suspension, were assayed for galactosyl transferase by measurement of the transfer of [3H]galactose from uridine diphosphate:[3H]galactose to desialylated ovine submaxillary mucin. The assay was optimized with respect to time and to protein, uridine disphosphate:galactose, desialyated ovine submaxillary mucin, and Triton X-100 concentrations. This assay was then applied to fresh specimens of benign, inflamed, and neoplastic bladder epithelium from 33 patients who under went cold-cup biopsies at cytoscopy. Transitional cell carcinoma specimens gave values in the range of 24.7 to 184.8 cpm [3H]galactose transferred per microgram protein per hr [72.0 +/- 44.7 (S.D.); n = 25]; normal and inflamed specimens ranged from 0.8 to 46.1 cpm/microgram protein per hr [8.3 +/- 8.4 (S.D.); n = 35]. By using a known method of cell rupture, cell ghosts, representing cell-surface membranes, were isolated both from the cultured cell line and from two biopsy specimens of transitional cell carcinoma. Although a complete enzymatic and electron microscopic analysis was not undertaken, the coincidence of an enzyme marker with the cell ghost fraction containing the elevated galactosyl transferase made it appear probable that this enzyme is located in the cell surface.

Carcinoma, Transitional Cell↗
PubMed1978

Biopsy of apparently normal urothelium in patients with bladder carcinoma.

We obtained 246 cold cup biopsies from pre-selected sites of apparently non-tumor-bearing bladder urothelium from 82 patients who presented with bladder cancer for the first time. Of 75 patients with transitional cell carcinoma 32 (43 per cent) suffered coincidental urothelial abnormalities, the most common being atypia. Significant abnormalities occurred more commonly (77 per cent) in association with high grade tumors than with low grade tumors (15 per cent).

Adenocarcinoma↗
PubMed1978

The effect of intravesical thio-tepa on normal and tumor urothelium.

Intravesical thio-tepa instillations for 55 patients with superficial transitional cell carcinoma were evaluated prospectively in the treatment of residual disease (therapeutic) and the prevention of recurrence (prophylactic). The over-all response rate to therapeutic thio-tepa was 56 per cent, with toxicity observed in 26 per cent of the cases. Patients with microscopic residual tumor showed better response and less toxicity than those with gross residual tumor. Prophylactic thio-tepa had no effect in lowering recurrence rates. Examination of pre-treatment and post-treatment biopsies showed no worsening of atypia and no correlation between improvement in atypia and gross tumor response. A charcteristic post-treatment thio-tepa effect was observed in non-tumorous urothelium but not in tumor biopsies. The differentiation of such thio-tepa effect cells from pre-malignant atypical cells is discussed.

Carcinoma, Transitional Cell↗
PubMed1978

Clinical significance of serum alkaline phosphatase isoenzyme levels in advanced prostatic carcinoma.

The alkaline phosphatase isoenzymes in 105 patients with stage D carcinoma of the prostate who entered the National Prostatic Cancer Study were analyzed and these values were correlated to clinical response. Only patients with at least 3 measurements of alkaline phosphatase were evaluated. In 91% of patients with metastatic bone disease, bone alkaline phosphatase was elevated. Those patients with higher pre-treatment levels of alkaline phosphatase generally showed a poorer response to therapy. The results of alkaline phosphatase isoenzyme estimation indicate that these biological markers may be used in the evaluation of patients with metastatic prostatic cancer to predict and monitor their response to chemotherapy. The evaluation of bone and liver alkaline phosphatase isoenzymes in earlier stages also may be valuable.

Alkaline Phosphatase↗
PubMed1978

Altered androgen metabolism in metastatic prostate cancer.

Admixture of androgen-sensitive elements from normal or hyperplastic prostatic tissue interferes with biochemical studies of prostate cancer in its primary site. Heterogeneity of cancer tissues, varying in stromal and epithelial elements, also complicates interpretation of data relating to androgen metabolism. Accordingly, we have compared metastatic deposits composed of epithelial cancer cells to the primary biopsies of 4 patients in respect to uptake of 3H-testosterone and its conversion to 5-alpha-dihydrotestosterone during in vitro incubation. 3H-testosterone uptake was similar for both tissue sites but 3H-dihydrotestosterone formation was reduced by 76% in the metastases compared to primary tissues. This group was not large enough to show statistical significance, whereas a total of 11 such primary studies compared to 6 metastatic specimens was significant. When either primary or secondary tissue results were compared to 12 cases of benign prostatic hyperplasia similarly studied the differences were highly significant. These results demonstrate a major impairment in the formation of dihydrotestosterone by metastatic prostatic cancer and a similar but less evident alteration in the primary site. This abnormality in testosterone metabolism is of major importance in the attempt to obtain effective hormonal control of human prostatic cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1978

[32P] diphosphonate dose determination in patients with bone metastases from prostatic carcinoma.

In an initial safety study, phosphorus-32 (as diphosphonate) was administered intravenously to five patients with painful bone metastases from prostatic carcinoma; two patients received 9 mCi and three were given 3 mCi. Hematological, biochemical, ECG, x-ray, bone-scan data, and clinical observation, were followed for 2 mo. At both dose levels, bone-marrow depression was noted. One of the patients, who received 9 mCi, had only a slight dip in the levels of circulating white blood cells and platelets. The other 9-mCi patient was the only one with discrete metastases by bone scan; he had bone-marrow depression, from which he recovered, and was the only one of the five who had relief of bone pain.

Adenocarcinoma↗
PubMed1978

In vivo growth of human bladder cancer cell lines.

Two human bladder cancer cell lines grew predictably in rats immunosuppressed with antilymphocyte serum. Intraperitoneal inoculation of tumor cell suspensions resulted in diffuse intraabdominal carcinomatosis with consequent host death after 10 to 20 days. Subcutaneous inoculation of tumor cell suspensions resulted in local tumors which grew exponentially for 20 to 30 days before eventual regression after 40 to 50 days; lung metastases developed in at least 13 per cent of the animals with subcutaneous tumors. The histologic appearance of the xenografted tumors closely resembled that of the original tumors. Subsequent in vitro culture of the xenografted tumors provided cell lines that were morphologically identical to the primary lines and that retained a human karyotype. It is proposed to employ this model of human bladder cancer to evaluate chemotherapeutic agents for possible use in the clinical disease.

Animals↗
PubMed1978

Immunochemical detection of serum prostatic acid phosphatase. Methodology and clinical evaluation.

An immunochemical method for detection of prostatic acid prosphatase is described. Purified acid phosphatase was isolated from cancerous human prostate. A specific antiserum to the purified enzyme was produced in rabbits. The antiserum to postatic acid phosphatase did not react with acid phosphatase originating from other tissues. A counter immunolectrophoresis, utilizing the specific antibodies and a chemical staining technique, has been developed and clinically evaluated. Sera from patients with prostatic carcinoma (6/20 of stage B, 27/49 of stage C, and 98/125 of stage D) gave positive results. Sera from 19 patients with benign prostatic hypertrophy, from 89 patients with other tumors, from 12 patients with Gaucher's disease, from 107 healthy volunteers, and from 50 normal age-matched men all gave negative results. The sensitivity of this method was 0.4 IU of enzyme activity or 20 ng per ml of prostatic acid phosphatase protein. Further clinical evaluation of patients in the early stage of prostatic cancer and of patients undergoing chemotherapy is in progress.

Acid Phosphatase↗
PubMed1978

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9 percent of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Drug Therapy, Combination↗