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Biomedical subjects

F H Schroeder

Publications and source records attributed to F H Schroeder.

At least 37 records · Page 2Linked to original sources
PubMed1989

Treatment of benign prostatic hyperplasia by androgen deprivation: effects on prostate size and urodynamic parameters.

The possible effect of medical androgen deprivation in the treatment of benign prostatic hyperplasia has been studied in 12 patients. Six patients received the luteinizing hormone-releasing hormone agonist buserelin and 6 others received the antiandrogen cyproterone acetate. The treatment resulted in an average decrease in prostatic size of 29 per cent after 12 weeks as measured by ultrasonography. This decrease led to an increase in peak urinary flow rate, a reduction in residual urine volume and a decrease in daytime voiding frequency. However, it caused no decrease in urethral resistance but only an increase in the bladder contraction strength. After discontinuation of the treatment the prostates showed regrowth to the initial sizes within 6 to 36 weeks. The urodynamic changes were reversed as well. Although statistically significant, the urodynamic changes were minimal from a clinical viewpoint and did not lead to an unobstructed state after 12 weeks of treatment. For this reason the clinical indication for use of medical androgen deprivation in benign prostatic hyperplasia patients will remain limited for the time being.

Androgen Antagonists↗
PubMed1989

Treatment of localised prostatic carcinoma.

Treating stage T3 prostatic carcinoma by surgery alone without adjuvant treatment, offers a potential 30% chance of curing these patients. In addition, the surgical approach offers an effective means of identifying patients not amenable to cure by local measures.

Humans↗
PubMed1989

In vivo administration of a GnRH antagonist to male mice: effects on pituitary gonadotropin secretion in vitro.

The potent luteinizing hormone-releasing hormone antagonist [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]GnRH (4 mg/kg) was administered sc once or daily for 21 days to immune-deficient (nude) and normal immune-competent (NIC) male mice derived from the same genetic background. Effects of in vivo pretreatment with the antagonist on gonadotropin secretion from hemipituitary glands from both types of mice were studied in vitro in the presence or absence of synthetic GnRH. Treatment with the GnRH antagonist caused differential effects on release of FSH and LH from and amounts of FSH and LH in hemipituitary glands. Pituitary FSH secretion was effectively inhibited, whereas effects on pituitary LH were less evident or nonsignificant under these experimental conditions. Long-term treatment with the antagonist caused larger effects on pituitary secretion and content of FSH, when compared with short-term treatment. No significant effects of duration of treatment on secretion or pituitary content of LH were detected. Addition of synthetic GnRH to the incubation medium caused stimulation of gonadotropin release. Therefore, it was concluded that the high doses of this GnRH antagonist were not able to block GnRH receptors effectively in the pituitary glands of nude and NIC male mice. The incomplete suppression of LH secretion by this high dose of the GnRH antagonist may partly explain the inability of the antagonist to suppress plasma testosterone levels and the growth of androgen-dependent tumours in male mice.

Animals↗
PubMed1988

Serum retinol and prostate cancer.

Levels of retinol, beta carotene, and alpha tocopherol were assayed by high performance liquid chromatography (HPLC) in serum from subjects with clinical prostatic cancer (n = 94), focal prostatic cancer (n = 40), benign prostatic hyperplasia (n = 130), and from hospital controls (n = 130). Levels of beta carotene and alpha tocopherol varied for prostatic cancer patients by disease stage and by the period in the treatment sequence when blood was collected. This made any assessment of their association with prostatic cancer risk difficult. The mean level of serum retinol was significantly lower (P less than 0.05) in prostatic cancer patients than in the controls. For serum retinol this difference did not appear to be attributable to age, stage of disease, period in which the blood was collected, or to several other potentially confounding factors. When the serum retinol level was considered in quintile classes, there was a statistically significant (P less than 0.05) trend of increased prostatic cancer risk associated with decreasing serum retinol levels.

Age Factors↗
PubMed1988

Quantitation of polyamines in cultured cells and tissue homogenates by reversed-phase high-performance liquid chromatography of their benzoyl derivatives.

A rapid and simple method, originally described by Redmond and Tseng [J. Chromatogr., 170 (1979) 479] was applied to the analysis of di- and polyamines in cultured human tumour cells and human tumour xenografts. Optimization of the procedures and evaluation of the characteristic features of the assay are described. The (modified) procedure employs precolumn derivatization with benzoyl chloride, extraction of the derivatives by chloroform, separation by reversed-phase high-performance liquid chromatography under isocratic conditions and detection by ultraviolet absorbance measurement at 229 nm. The complete analysis was accomplished within 10 min per sample. The detection limit was ca. 1 pmol. The intra- and inter-assay coefficients of variation were 2.5-4.4% and 3.4-13.1%, respectively. The presence of well known inhibitors of polyamine biosynthesis, such as DL-alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone), did not interfere with the assay, and disturbance by cyclohexylamine could be avoided by changing the polarity of the mobile phase. The method proved to be very suitable because it is rapid, simple, requires a minimum of sample pretreatment, and still provides sufficient sensitivity to quantitate polyamines in relatively small amounts of cells (10(5) cells) or tumour tissues (less than 1 mg), even after treatment with inhibitors of polyamine biosynthesis.

Animals↗
PubMed1988

Dietary beta-carotene and cancer of the prostate: a case-control study in Kyoto, Japan.

One hundred patients with prostate cancer and two different control series [100 benign prostatic hyperplasia (BPH) patients and 100 general hospital patients] were matched to each other upon hospital admittance, age (+/- 3 years) and date of admission (+/- 3 months), and directly interviewed during admission from 1981 to 1984 in Kyoto, Japan. Major dietary findings derived from a quantitative food frequency technique for estimating usual diet are as follows. (a) The smaller the dietary intake of beta-carotene and vitamin A as well, the higher the risk, with a highly significant linear trend. From the beta-carotene analyses, the relative risk (95% confidence interval) for the lowest intake quartile relative to the highest was 2.10 (0.98-4.47) for the uncorrected intake, 2.35 (1.08-5.12) for the intake per kg, and 2.94 (1.34-6.44) for the intake per kcal in the comparison with BPH patients; 2.88 (1.31-6.32), 2.56 (1.14-5.76), and 3.50 (1.52-8.06), respectively, in the comparison with hospital controls. The corresponding relative risk obtained from the vitamin A analyses was 2.82 (1.30-6.14), 2.64 (1.24-5.60), and 3.29 (1.47-7.35) in due order in the comparison with BPH patients; 2.69 (1.22-5.94), 4.78 (1.98-11.52), and 3.50 (1.52-8.06) in the comparison with hospital controls. (b) beta-Carotene as well as vitamin A contained in green/yellow vegetables were significantly protective, and those in seaweeds and kelp suggestively protective. But those in fruits appeared to enhance the risk. (c) The risk reduction by dietary beta-carotene and vitamin A was significant in the older men (70-79 years), but not in the younger men (50-69 years). (d) Total energy intake and the dietary intake of fat, protein, carbohydrate, water, fiber, ash, such vitamins as retinol, B1, B2, C, and niacin, and such minerals as calcium, potassium, sodium, phosphorus, and iron were not linked with prostate cancer risk. (e) A protective effect of dietary beta-carotene and vitamin A against prostate cancer could be related to the low overall fat intake in Japan.

Age Factors↗
PubMed1988

Application of the MTT assay to human prostate cancer cell lines in vitro: establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects.

In this study the usefulness of the MTT assay for the quantitation of growth modulating effects on cultured prostate cancer lines (PC-3, PC-93, and LNCaP) was investigated. The MTT test is based on the enzymatic reduction of the tetrazolium salt MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide++ +] in living, metabolically active cells but not in dead cells. The reaction is carried out in situ in multiwell plates, and the reaction product, a purple-colored formazan soluble in dimethylsulfoxide, is measured colorimetrically, using a multiwell plate reader. Optimal test conditions were established for each of the cell lines used. With the hormone-sensitive cell line LNCaP, and stimulatory effect of the synthetic androgen R1881 was demonstrable by the MTT test. A sharp optimum occurred at a concentration of 10(-10) M R1881. Treatment of cells of either cell line with antineoplastic agents resulted in a dose-dependent reduction of MTT converting activity, reflecting the impaired survival of the drug-treated cells. Good correlations of the results obtained with the MTT-test, as compared with a thymidine incorporation assay or with direct DNA measurements, were observed. As the MTT test offers a high degree of precision and is easy to do, it is suitable for the purpose of (large-scale) chemosensitivity testing. Moreover, serial measurements might easily be performed in order to provide additional information on the mode of action of the drugs tested, i.e., to discriminate between cytostatic and cytotoxic drug effects.

Androgens↗
PubMed1988

A case-control study of prostatic cancer with reference to dietary habits.

A case-control study of prostatic cancer which consisted of 100 patients with prostatic cancer, matched for hospital, age (+/- 3 yr) and hospital admission date (+/- 3 months) to patients with benign prostatic hyperplasia (BPH) and hospital controls, was conducted from 1981 to 1984. Low daily intake of beta-carotene (RR = 2.13: 95% confidence interval, 1.20-3.77) and of vitamin A (RR = 1.94: 1.10-3.43), as compared to the intake of those substances by BPH controls, were factors significantly correlated with the development of prostatic cancer. Low daily intake of beta-carotene (RR = 2.13: 1.20-3.77), as compared with hospital controls, were significantly correlated with prostatic cancer development. Infrequent intake of bread (RR = 2.40: 1.31-4.38), intended to represent a westernized diet, and of spinach (RR = 1.96: 1.01-7.73), a typical green and yellow vegetable, as compared to BPH controls and infrequent intake of spinach (RR = 4.55: 1.82-11.11) as compared to by hospital controls, were significant risk factors for prostatic cancer. Intake of carbohydrates, protein, fat, total calories, fibers, vitamin B and vitamin C were not correlated with the development of prostatic cancer.

Aged↗
PubMed1987

Administration of an LHRH-antagonist to male mice: effects on in vivo secretion of hormones and on the growth of a transplantable human prostatic carcinoma.

The potent luteinizing hormone releasing hormone (LHRH) antagonist [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LHRH was chronically administered to male nude mice bearing the transplantable human hormone-dependent prostatic adenocarcinoma PC-82. Treatment of tumor-bearing male mice with a daily dose of 100 micrograms (4 mg/kg b w.) for 21 days did not significantly affect the growth of the PC-82 tumor tissue, or the weights of ventral prostate, seminal vesicles and testes. At 24 hours after the last dose of the antagonist the mean plasma-testosterone (T) value in these animals was not different from the control level. Administration of similar doses of the antagonist to intact normal immunocompetent male mice significantly reduced plasma LH concentrations and suppressed plasma-T to near-castrate levels, when blood was taken 2 hours after the last injection. At 24 hours after the last dose, however, plasma concentrations of LH and T had returned to control levels. This time-dependent pattern of T suppression by the antagonist was confirmed by a time-course experiment in animals receiving a single dose of the compound. These data demonstrate that a daily high dose of this antagonist cannot effectively suppress plasma-T in male mice. Therefore, the mouse may not be a suitable model for the investigation of the "castration-like" effect of LHRH-antagonists on androgen-dependent prostate xenografts.

Adenocarcinoma↗
PubMed1987

Transplantable human prostatic carcinoma (PC-82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue.

This paper is the first part of a series of three describing a number of observations made on the PC-82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen-dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1-90 nmol/liter) has been levelled out by the use of T-containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC-82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC-82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC-82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC-82 tumor tissue. Androgen withdrawal from T-implanted, tumor-bearing female mice caused a rapid reduction (90% within one day) of the tissue-T and a slower decline (up to 90% within seven to ten days) of tissue-DHT concentrations.

Adenocarcinoma↗
PubMed1987

Surgical treatment of locally advanced (T3) prostatic carcinoma: early results.

The fate of 48 patients with clinical stage T3 prostatic carcinoma after attempted curative surgical management was studied. In 23 of these patients positive frozen sections of the lymph nodes were found at pelvic lymphadenectomy and orchiectomy was performed. The median interval to progression was 61 months. Radical prostatectomy was performed in the remaining 25 patients. In 4 of these patients positive lymph nodes were found on paraffin sections but no additional treatment was given. Over-all, total tumor removal as defined by negative lymph nodes and negative margins of resection could be achieved in 14 of the 48 patients (29 per cent). During the same period 34 patients with clinical state T less than 3 prostatic carcinoma were treated in a similar manner. Orchiectomy was done in 4 patients because of positive frozen sections of the lymph nodes and radical prostatectomy was done in 30, including 1 in whom positive paraffin sections of the lymph nodes were found but no additional treatment was given. An attempt was made to study the impact of several prognostic factors by comparing the probability of progression between patients with stage pT3 disease with (T3pT3N0) or without (T less than 3pT3N0) extracapsular tumor growth as determined by preoperative rectal examination (36 versus 27 per cent progression at 3 years), with or without positive margins of resection (45 versus 20 per cent progression at 3 years) and with or without involvement of the seminal vesicles (47 versus 18 per cent progression at 3 years). Our results suggest that a certain proportion of patients with clinical stage T3 disease will benefit from radical prostatectomy. This is to be expected especially in patients with stage T3pT3N0 cancer and negative margins.

Aged↗
PubMed1987

Metastatic cancer of the prostate managed with buserelin versus buserelin plus cyproterone acetate.

We recruited 71 previously untreated patients with metastatic prostatic carcinoma to 2 separate consecutive prospective phase 2 studies done by the same group of investigators according to the same protocols in which only the treatment regimens differed. Of the patients 58 were treated with the luteinizing hormone-releasing hormone analogue buserelin alone (0.4 mg. 3 times daily intranasally) and 13 were treated with buserelin combined with cyproterone acetate, a potent antiandrogen (50 mg. 3 times daily orally). The objective of the study was to investigate the efficacy, safety and tolerability of the medication used during at least 12 months by studying adequate endocrine parameters, the rate and duration of response, as well as the rate of progression and possible side effects. All endocrine parameters were studied in 1 laboratory. Modified response criteria of the National Prostatic Cancer Project were used. The endocrine studies showed an effective suppression of plasma testosterone to castration levels by buserelin after an initial increase during the first 2 weeks. Luteinizing hormone and follicle-stimulating hormones were lowered significantly and could not be re-stimulated by the intravenous application of luteinizing hormone-releasing hormone. There was no correlation of plasma testosterone with response and progression. However, a significant correlation existed between higher basal cortisol levels at entry, and after 3 and 6 months, and progression. Response is reported for all patients at the 12-month interval and did not seem to differ among treatment groups. The rate of progression after all patients had been treated for 1 year was 37.9 per cent in the buserelin group and 41 per cent in the buserelin plus cyproterone acetate group. Three early deaths occurred in the buserelin group. Except for impotence, only mild side effects were noted. Our study shows that treatment of metastatic prostatic cancer by means of the luteinizing-hormone-releasing hormone analogue buserelin is safe and effective. The results obtained are compatible with those obtained by castration. In our study a superiority of total androgen withdrawal over testicular suppression alone could not be shown.

Buserelin↗
PubMed1987

Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring.

The transplantable, hormone-dependent, human prostatic carcinoma PC-82 was used as an in vivo model for monitoring the proliferative fraction of tumor cells under the influence of androgen withdrawal and resubstitution. The number of cycling cells was assessed by means of an immunoperoxidase method and monoclonal antibody Ki-67. The number of Ki-67-positive tumor cells dropped from an average of 17% in androgen-supplemented, tumor-bearing female BALB/c mice to approximately 1.0% within 10 days after removal of the testosterone (T) implant. A similar effect was noted after castration of tumor-bearing male BALB/c mice. Androgen resubstitution after a 10-day period of T deprivation resulted in a rise in the tumor cell proliferation index to 20% within 4 days. The same pattern of response to androgen depletion and resubstitution also was found when the number of cycling cells in S phase was assessed by the 5-bromo-2'-deoxyuridine incorporation technique. Administration of supraphysiologic doses of T in intact male mice did not lead to an increase in the number of Ki-67-stained nuclei. Androgen manipulation did not influence the immunohistochemically assessed expression of prostatic acid phosphatase and prostate-specific antigen. The rapid effect of hormone deprivation and resubstitution in the tumor cell proliferation fraction suggests that monoclonal antibody Ki-67 can be used for monitoring the short-term effects of hormonal treatment of prostatic cancer.

Animals↗
PubMed1986

Measurement of the survival of human tumor cells after implantation in athymic nude mice.

A method has been developed to determine the survival of human tumor cells after implantation in athymic nude mice. The method involves the labelling of cells of the prostatic cancer cell line PC-3 with tritiated thymidine after attachment of the cells to Millipore filter disks. The amount of radioactive label incorporated in the cells remained constant for at least 48 hr during in vitro incubation. After s.c. implantation of the filter disks in nude mice, however, the fraction of surviving cells, reflected by the amount of radioactivity persisting on the filters, rapidly decreased with time. Only a relatively small fraction (approx. 10%) of the cells survived for more than 24 hrs under these conditions. Pretreatment of the mice with cyclophosphamide (100 mg/kg, 24 hr prior to implantation) resulted in a 2-fold increase of tumor-cell survival. Likewise, the frequency of tumor takes after injection of PC-3 cells was enhanced following cyclophosphamide pretreatment. These results indicate that immune defense mechanisms might be partly (but not completely) responsible for tumor-cell rejection in nude mice. The technique described here might be a valuable tool for the rapid evaluation of possible effects of various types of pretreatment of the host animal on tumor cell survival and, thereby, on tumor growth.

Animals↗
PubMed1986

Benign prostatic hyperplasia treated by castration or the LH-RH analogue buserelin: a report on 6 cases.

This article presents the clinical data of 5 patients treated by castration and 1 patient treated with an LH-RH analogue to relieve chronic urinary retention due to benign prostatic hyperplasia (BPH). Besides the clinical data related to prostatism, prostatic volume was studied in 4 of the 5 patients by means of transrectal ultrasonography. All 5 patients showed a marked decrease of prostatic volume, which averaged 31.4% (range 19-55%) after 2-3 months. This correlated well with a relief of urinary obstruction. In all 5 patients, the indwelling catheters could be removed, symptoms decreased or disappeared and all 5 patients became free of residual urine. LH-RH analogues, because of the reversibility of their effect, may be more acceptable for the treatment of BPH than castration. At this moment however, it remains unknown whether prostatic volume will increase again after cessation of androgen withdrawal.

Aged↗