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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines. Some of these in vitro cell lines (i.e., G, AT-1, AT-2) retain a low metastatic ability when inoculated back into syngeneic Copenhagen male rats, while others (i.e., AT-3, MAT-LyLu, MAT-Lu) retain a very high metastatic ability. A series of genetic (i.e., DNA content per cell, modal chromosomal number), as well as phenotypic parameters (i.e., morphology, 5 alpha-reductase, androgen receptor, estrogen receptor) were used to validate that the in vitro cell lines retained the major characteristics of the parental in vivo tumor sublines used for their respective establishment. A series of additional characteristics (i.e., morphology, growth rate, saturation density in surface culture, anchorage-dependent and -independent clonogenic potential) were compared between the high vs. the low metastatic in vitro cell lines to determine if a discriminatory parameter could be identified which reproducibly predicted the metastatic abilities of the particular prostatic cancer cell line. While the combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, no single parameter yet measured is entirely successful in making this important distinction.
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PMID:Establishment and characterization of seven Dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers. 377 32

The authors investigated the ability of androgen receptor binding in prostate cancer tissue to predict the response of prostate cancer patients to endocrine therapy. The clinical response of 37 previously untreated patients with various grades and stages of prostate cancer was correlated with androgen receptor binding and detailed histologic data obtained before treatment. All patients underwent cold-punch transurethral resection of the prostate and received endocrine therapy. The association between time to progression and cytosolic androgen binding was not significant. However, the associations of time to progression to nuclear binding and to total androgen binding were significant (P = 0.029 and 0.038, respectively). The authors found no association between clinical stage and time to progression, but did find an association between time to progression and pathologic grade (P = 0.003); grade 4 lesions were the least responsive to hormone therapy. When grade 4 lesions were excluded (N = 3), binding levels were still predictive of progression independently of grade and stage. The authors conclude that nuclear receptor binding activity in localized and metastatic prostate cancer tissue is predictive of response to hormonal manipulation.
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PMID:Relationship between androgen receptor binding activity in human prostate cancer and clinical response to endocrine therapy. 382 60

Fluorescent androgen ligands were employed to study putative androgen-binding (AB) sites in a number of men with prostatic adenocarcinoma. Results were compared with biochemical androgen receptor determinations in over 150 patients with agreement in 86% (p less than 0.001). AB by histochemistry correlated significantly with the outcome of hormonal manipulation (p less than 0.001) but not with response to radiation therapy (p = 0.55) or to 125I implantation (p = 0.54). There was a degree of positive interaction between histochemically and biochemically determined AB sites which produced a significant improvement in assay specificity (p less than 0.05). These findings indicate that the best method for prediction of hormone response in prostate cancer is provided by a combination of assay techniques.
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PMID:Androgen binding in prostatic carcinoma by histochemistry: update 1985. 384 64

It has been proposed that concentrations of nuclear androgen receptor may be predictive of tumor hormone dependence in cases of advanced human prostatic cancer. We have investigated the ability of this receptor population to reflect patient prognosis during endocrine therapy in 12 cases of stage D disease. KCl-extractable, nuclear matrix-bound and total nuclear androgen receptor concentrations showed a significant positive correlation with duration of patient survival (p less than 0.05) while cytosolic and total cellular androgen receptor concentrations were not significantly correlated with survival. However, use of selected threshold concentrations of receptors revealed that only cytosolic, nuclear KCl-extractable and total cellular receptors could significantly differentiate long-term and short-term survivors. Even given the small number of patients studied, the potential use of this androgen receptor assay as an index of both tumor hormone-dependence and patient prognosis was evident. Therefore, in order to make these androgen receptor assays more applicable, we attempted to simplify the methods for use on readily available tissues. Similar amounts of nuclear androgen binding were observed in crude and purified nuclear pellets, in nuclei treated with DNase and KCl in differing orders or in nuclei from tissue homogenized using glass or Polytron homogenization procedures. More importantly, nuclear androgen receptor concentrations in specimens of prostatic cancer or benign hyperplasia taken by needle biopsy or transurethral resection involving electrocautery did not differ from those of parallel specimens taken by Thompson cold punch. Simplified nuclear androgen receptor assays of needle biopsy or electrocautery specimens are accurate and should prove clinically applicable.
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PMID:Applicability of nuclear androgen receptor quantification to human prostatic adenocarcinoma. 394 59

The use of ATP content as a measurement for cell growth was evaluated in the LNCaP prostatic cancer cell line. ATP content was found to correlate well with cell counts and was an easy and reliable method for following the effect of substances on cell growth. During cultivation for 9 days no effect on cell counts or ATP content could be seen when testosterone (10(-10) to 10(-6) M), estradiol-17 beta (10(-10) to 10(-5) M), 5 alpha-DHT (10(-9) to 10(-6) M), prolactin, vitamin A, or antiandrogen was added to the cell medium in different combinations. However, a weak positive effect was seen on the mitotic index when 10 or 100 nM 5 alpha-DHT was added to the cells, whereas 1 microM 5 alpha-DHT inhibited cell growth. Thus despite the fact that this LNCaP line contained 16 fmol androgen receptor/mg protein (Kd 0.6 nM), it is unresponsive to hormones and should be designated LNCaP-r (resistant). Chromosome analysis revealed that a shift in the modal chromosome number had occurred from the original LNCaP line, which could account for the lack of hormonal sensitivity.
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PMID:Effect of hormones on growth and ATP content of a human prostatic carcinoma cell line, LNCaP-r. 404 15

Two populations of nuclear androgen receptors have been characterized in human prostatic tissue, and the levels and proportions of each were found to differ in normal prostates, benign hyperplastic prostates (BPH), and malignant prostates. A significant percentage (35 to 50%) of total nuclear androgen receptors was associated with the salt-resistant nuclear matrix fraction. The remainder were easily extracted from nuclei by 0.6 M KCl. Optimal conditions for measuring receptors in both compartments involved the use of an inhibitor of proteolysis (phenylmethylsulfonyl fluoride) and the omission of dithiothreitol from buffers. In the presence of dithiothreitol, most of the nuclear salt-resistant receptors were rendered salt extractable. Cytosol androgen receptor levels were not significantly different in normal, BPH, or malignant prostatic tissues. In contrast, the levels and distribution of nuclear salt-extractable and salt-resistant androgen receptors exhibited characteristic patterns. Compared to normal prostatic tissue, nuclear salt-extractable receptors were significantly elevated in both BPH and cancer, whereas nuclear salt-resistant receptors were elevated in BPH but not in cancer. The ratio of salt-extractable to salt-resistant receptors was approximately 1:1 in both normal and BPH tissues and 2:1 in cancer. In addition, a microassay has been developed for the measurement of androgen receptors in the three subcellular compartments of needle biopsy specimens of prostatic cancer. Studies are in progress to determine whether the measurement of both nuclear salt-extractable and salt-resistant receptors may improve the usefulness of receptor levels to predict the hormonal responsiveness of prostatic cancer.
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PMID:Subcellular distribution of androgen receptors in human normal, benign hyperplastic, and malignant prostatic tissues: characterization of nuclear salt-resistant receptors. 618 70

Estrogens have been proposed as a major etiological factor in the pathogenesis of benign prostatic hyperplasia in man. The presence of estrogen receptor in benign prostatic hyperplasia would support this concept. Using the receptor stabilizer, sodium molybdate, and a hydroxylapatite assay we assayed human benign prostatic hyperplasia for the presence of cytosolic estrogen receptor. For comparison, we assayed estrogen receptor in cytosols of prostatic cancer and normal tissue, and we also measured androgen receptor and progesterone receptor concentrations in the 3 tissue types. Estrogen receptor was present in 8 of 15 benign prostatic hyperplasia specimens at a mean concentration of 9.2 fmol./mg. protein for the estrogen-receptor-positive samples. Sucrose gradient analysis of the estrogen receptor of benign prostatic hyperplasia revealed that it sedimented in the region of 8S, and steroid specificity studies confirmed that the binding to estrogen receptor was estrogen-specific. Estrogen receptor was also found in normal (3 of 3) and malignant (4 of 6) tissues, and all tissues were positive for androgen receptor. The presence of estrogen receptor in human benign prostatic hyperplasia supports the proposal that circulating estrogens may have a role in the pathogenesis of this disorder.
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PMID:Estrogen receptor in human benign prostatic hyperplasia. 619 Oct 47

Juvenile nasopharyngeal angiofibromas (JNA) are rare. They have been frequently treated with estrogens, either solely or as an adjuvant therapy prior to surgery or irradiation. Clinical trials have proveded no evidence to explain the objective respose to estrogens observed in some tumors. Since the mechanism of steroid hormone action is mediated via specific receptors, we analyzed 8 JNA for tumor cytosol estrogen receptors. None were positive for estrogen receptors. Additionally, all were also negative for progesterone receptors. Nasopharyngeal angiofibromas occur predominantly in adolescent boys at a time when there is a gradual change in androgen availability. Therefore, three latter angiofibromas were also analyzed for the presence of cytosol androgen receptor. Specific testosterone and dihydrotestosterone binding components in the tumor cytosol were detected. This observation raises for the first time the possibility that JNA may be an androgen-dependent tumor. Estrogen may act as an antiandrogen on these tumors, an action similar to that on prostate cancer.
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PMID:Hormonal receptor determination in juvenile nasopharyngeal angiofibromas. 624 85

A x C rat prostate cancer cells were established in continuous culture. The polygonal epithelial cells had granular cytoplasm and well-defined cell margins, contained round to oval nuclei with prominent nucleoli, and were tumorigenic when inoculated into A x C male rats. The tumors produced by the injected prostate cancer cells grew as well-vascularized, solid, cribriform adenocarcinomas. The rat prostate cancer cells and derived tumors contained cytoplasmic and nuclear androgen receptors and prolactin receptors. Androgen regulation of prolactin receptor content and androgen receptor distribution in A x C rat prostate cancer cells were comparable to those of the normal ventral prostate gland. These studies suggest that the A x C rat prostate cancer cells and tumors may represent a unique model for studies of hormonal regulation of prostate cancer cell behavior.
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PMID:A x C rat prostate adenocarcinoma: initial characterization of testosterone regulation of hormone receptors of cultured cancer cells and derived tumors. 625 2

Elucidation of the mechanism whereby androgens are accumulated selectively by the prostate may help in the design of drugs for the treatment of prostatic cancer. The uptake and retention of [3H]testosterone, following intraperitoneal injection, by various tissues in the 24 hr castrate rat has been studied over an extended time course. The selectivity with which prostate, as compared with blood or other tissues, accumulated 3H was shown to be dose-dependent. At a low dose (0.15 microgram), selective prostatic accumulation was greater in 24 hr castrate and diethylstilboestrol-treated rats than in normal animals. Testosterone, 5 alpha-dihydrotestosterone and oestradiol, radioactively labelled, were each administered to 24 hr castrate rats by intraperitoneal injection. Specific prostatic accumulation of radioactivity was more dependent on steroid structure at a low dose than at a high dose (0.6 mg) and at the low dose (0.15 microgram) followed the order testosterone greater than 5 alpha-dihydrotestosterone greater than or equal to oestradiol. This order was surprising in view of the androgen receptor binding affinities of these steroids. It is concluded that small quantities of material could be directed with the greatest specificity to the prostate of castrate or diethylstilboestrol-treated animals if attached to testosterone. Androgens would be more useful for site-directed radiopharmaceuticals than cytotoxic agents.
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PMID:Uptake and retention of androgens by the rat ventral prostate and consideration of their use as site directing agents. 629 9


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