Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of chemotherapy for prostatic cancer is difficult to evaluate owing to the low incidence of measurable indicator lesions and the resulting need for indirect response criteria. Although complete regressions remain exceptional, a number of agents, eg, doxorubicin and cisplatin have been shown to be effective in the treatment of this disease. So far, combinations of effective agents with or without concomitant hormone therapy have not proven to be more effective than single agents. Androgen priming has considerable theoretical appeal and deserves further consideration. A higher effectiveness of chemotherapeutic agents might be obtained by linkage to various carriers. Estramustine phosphate is an example of such a complex that has a cytotoxic effect in test systems in which estrogen has no effect and in patients with hormone-refractory prostatic cancer. The use of hormonal and other carriers that could increase the specificity of chemotherapeutic agents deserves extensive exploration.
 ...
PMID:Chemotherapy principles in the treatment of prostatic cancer. 636 76

Androgen-binding protein (ABP) appears to originate in the Sertoli cells, which are stimulated by FSH and androgens, and serves to transport androgen into the lumen of the seminiferous tubules. Androgen may be more readily available for the process of spermatogenesis and sperm maturation. ABP was measured in rabbit and human testes using the method of polyacrylamide gel electrophoresis described by Ritzen et al. (1974). The values of ABP were as follows: rabbit testes (n=6) 0.44 +/- 0.05 pmoles/mg protein, rabbit caput epididymides (n=5) 5.52 +/- 1.4 pmoles/mg protein, rabbit corpus epididymides (n=5) 1.35 +/- 0.43 pmoles/mg protein, rabbit cauda epididymides (n=5) 0.39 +/- 0.12 pmoles/mg protein, rabbit efferent duct fluid (n=2) 62.4 +/- 24.6 pmoles/mg protein and human testes (obtained from untreated patients with prostatic cancer)(n=3) 0.30 +/- 0.22 pmoles/mg protein. Since we could not distinguish ABP from testosterone-estrogen binding globulin (TeBG) with the assay, the values were corrected at first by Hb concentration, but it was not satisfactory, and other methods are now being studied.
 ...
PMID:[Studies of androgen binding protein. 1st report: Androgen binding protein in testis and epididymis of rabbit and human (author's transl)]. 719 99

Androgen suppression is the routine approach to the treatment of advanced prostate cancer. Using intermittent androgen suppression by taking the advantage of the reversible action of medical castration results in the maintenance of apoptotic potential. The experiments in the androgen-dependent androgen-dependent Shionogi carcinoma tumor model as well as clinical experience in a group of men with prostate malignancy are presented in this report. These consecutive cycles of androgen withdrawal and replacement afford an improved quality of life when the patient is off therapy. It is possible to reduce toxicity, cost of treatment and to delay tumor progression. Whether survival is affected in a beneficial or adverse way still remains to be studied.
 ...
PMID:[Theoretical considerations and initial clinical results of intermittent hormone treatment of patients with advanced prostatic carcinoma]. 748 55

The presence of specific steroid hormone-binding receptors has been correlated with the clinical response to hormonal therapy in a number of different neoplasias, including breast and prostate cancer. In this article, we investigated the expression of the androgen, estrogen, glucocorticoid, and progesterone receptor messenger ribonucleic acid (mRNA) and protein in a number of astrocytic neoplasms of various histological grades. Androgen and glucocorticoid receptor mRNA were detected in all astrocytic neoplasms examined, regardless of histological subtype. In contrast, progesterone receptor mRNA was observed more frequently in high-grade tumors than in low-grade tumors. Estrogen receptor mRNA was undetectable in all astrocytic tumors examined. These studies suggest a possible adjunct clinical use of hormonal therapy for the treatment of astrocytomas. Specific antagonists and agonists may allow the modulation of the growth of these tumors. Development of this body of knowledge may lead to the development of better treatment for these aggressive tumors.
 ...
PMID:Steroid hormone receptors in astrocytic neoplasms. 750 Nov 16

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.
 ...
PMID:Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the prostate. 750 21

A total of 37 selected patients with clinical stage T2b or T3 prostate cancer received androgen deprivation prior to radical retropubic prostatectomy. A luteinizing hormone-releasing hormone (LHRH) analog alone was given to 15 individuals; 19 received an LHRH analog with flutamide. Three underwent bilateral orchiectomy instead of chemical castration. The duration of androgen deprivation prior to radical prostatectomy varied from 3 to 16 months, with 31 individuals undergoing induction therapy for 3-6 months. Three received androgen deprivation for more than 1 year. In all, 15 patients had clinical stage T2b disease and 22, stage T3 prostate cancer. The prostate size decreased approximately 30%-50% following induction therapy. Prostate-specific antigen (PSA) values decreased in all 19 instances where this was obtained. In all, 6 of 15 (40%) patients with clinical T2b lesions and 9 of 22 (41%) with clinical T3 tumors had a positive surgical margin; 5 (13%) had 1 or more positive lymph nodes. Androgen deprivation was continued following surgery in 13 cases. Only one patient received postoperative radiation therapy. After a mean follow-up period of 33 months, 35 (95%) patients are alive. Two patients died, one of poorly differentiated prostate cancer with subsequent metastasis and one of a myocardial infarction 33 months after surgery without showing any evidence of disease. Of 23 patients without postoperative adjuvant therapy, 6 (26.1%) progressed (PSA level, > 0.4 ng/ml). None of the patients who underwent adjuvant therapy progressed over a follow-up period of 6-75 months (mean, 38 months).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Significance of androgen deprivation prior to radical prostatectomy, with special reference to prostate-specific antigen. 750 88

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that, for all practical purposes, is specific for prostatic tissue. PSA is usually detected at low concentrations (0.0-4.0 ng/ml) in the serum and is the most important tumor marker for detecting otherwise unsuspected prostate cancer; it also useful for monitoring the response of prostate cancer to various types of therapy. Androgen deprivation therapy (ADT) includes bilateral orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, and 5-alpha-reductase inhibitors. Treatment of benign prostatic hypertrophy (BPH) or prostate cancer with ADT usually decreases the serum PSA concentration. Recent basic science research has demonstrated that the expression of the PSA gene is controlled by androgens acting via the androgen receptor. Therefore, in some patients a low serum PSA concentration will be the result of hormonal down-regulation of the genetic expression of PSA and not the result of the antitumorigenic activity of the therapy. Nevertheless, in spite of the direct effect of ADT on PSA expression, PSA remains a valuable prostate cancer tumor marker for prognosticating the response to ADT and portending clinical progression after this type of treatment for most patients.
 ...
PMID:Prostate-specific antigen and androgen deprivation therapy. 750 89

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogeneous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2 patients, with a small number of bone lesions (> or = 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (> 3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors.
 ...
PMID:A more objective staging of advanced prostate cancer--routine recognition of malignant endocrine structures: the assessment of serum TPS, PSA, and NSE values. 750 85

Proliferation of LNCaP 104-S cells, a clonal subline of the human prostate cancer cell line, was very slow in androgen-depleted medium but increased 10-13-fold in the presence of 0.1 nM of a synthetic androgen, R1881. This induction of proliferation was diminished at higher concentrations of R1881, indicating the biphasic nature of the androgen effect. After 20-30 passages in androgen-depleted medium, these cells progressed to 104-I cells, which exhibited much lower proliferative sensitivity to 0.1 nM R1881. After another 20-30 passages, LNCaP 104-I cells gave rise to 104-R cells, which proliferated rapidly without additional androgen. Proliferation of 104-R cells was induced 2-fold by 0.01 nM R1881 but was repressed by 0.1 nM R1881 and above. Thus, androgen induction and repression of proliferation could be seen at lower concentrations of androgen as the cells progressed. During the transition of 104-S cells to 104-R cells, the androgen receptor mRNA level increased 2.5-fold whereas the androgen receptor protein level increased 15-fold in the absence of androgen. Androgen receptor transcriptional activity, measured by androgen induction of prostate-specific antigen mRNA and chloramphenicol acetyltransferase activity in transfected cells, increased up to 20-fold during the progression. LNCaP cells, therefore, appear to be able to adapt to reduced androgen availability by increasing their sensitivity to androgen, raising questions concerning the therapeutic strategies used against prostate cancer. Androgen induction of c-myc expression in 104-R cells occurred at a 10-fold lower concentration (0.01 nM) than in 104-S cells (0.1 nM). In all stages, cell proliferation and c-myc expression were repressed by androgen at a high concentration (20 nM), but the repression of cell proliferation was blocked by retroviral overexpression of c-myc.
 ...
PMID:Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. 751 Oct 45

The therapeutic benefit of chemotherapy in androgen independent prostate cancer is limited. 5-Fluorouracil has been reported to have modest antitumor activity in androgen independent prostate cancer. Although alpha-interferon is inactive as a single agent in prostate cancer, preclinical data indicate that it increases the in vitro cytotoxicity of 5-fluorouracil against a variety of malignant cells. We evaluated the relative antitumor activity and tolerance of 5-fluorouracil versus 5-fluorouracil plus alpha-interferon in 50 patients with histologically confirmed metastatic adenocarcinoma of the prostate. These patients had progressive disease in the presence of castrate levels of testosterone. A prospective randomized phase II open labeled trial was performed because of the difficulty in measuring responses in patients with metastatic prostate cancer. Of 23 patients treated with 5-fluorouracil alone and 28 treated with 5-fluorouracil plus alpha-interferon 17 and 23, respectively, were evaluable for response and toxicity, and 5 and 5, respectively, were evaluable for toxicity only. Only 2 of 17 (11.7%) and 4 of 23 (17%) patients, respectively, showed a greater than 50% decrease in serum prostate specific antigen (no significant difference). There was no difference in duration of response or duration of survival between the 2 groups (mean duration of response 8.64 and 6.17 weeks, respectively, and mean duration of survival 33.70 and 38.65 weeks, respectively). Both regimens caused significant morbidity (mucositis and neurotoxicity) and 3 treatment related deaths at the high 5-fluorouracil doses. 5-Fluorouracil alone and with alpha-interferon at the doses used have minimal antitumor activity against androgen independent prostate cancer and, therefore, should not be tested further in these patients. Androgen independent prostate cancer selected using our criteria is a rapidly progressive disease, and these patients are an ideal target population for phase II studies.
 ...
PMID:The results of a phase II randomized trial comparing 5-fluorouracil and 5-fluorouracil plus alpha-interferon: observations on the design of clinical trials for androgen-independent prostate cancer. 771 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>