Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic chemotherapy with currently available agents has not improved survival for patients with hormone refractory prostate cancer (HRPC), consequently, the evaluation of new agents is warranted. Topotecan is a specific inhibitor of topoisomerase I with broad antitumor activity in preclinical studies. The purpose of this phase II trial was to determine the objective response rate of topotecan administered as a 30 minute infusion for five consecutive days in men with metastatic HRPC. Thirty-four evaluable patients were treated with topotecan 1.1-1.5 mg/m2 as a 30 minute infusion daily for five days, repeated every three weeks until disease progression or unacceptable toxicity. Response was assessed with a combination of standard solid tumor response criteria and the serum prostate specific antigen (PSA) for patients with bidimensionally measurable disease, and by serial measurements of the PSA in patients with bone only (evaluable) disease. One of 13 patients (7.6%) with measurable soft tissue disease had a PR in nodal sites. Of 21 patients with only osseous metastases, 1 (4.7%) had improvement in bone scan. Six of the 34 evaluable patients (17.6%) had the serum PSA decrease by > or = 50% and 2 (5.8%) had PSA decreases of > or = 75%. Toxicity was chiefly hematologic with 66% of patients experiencing Grade 3 or 4 granulocytopenia. Thirty-nine percent of cycles required a delay to allow for hematologic recovery and ten patients required red cell transfusions. Non-hematologic toxicity, mainly nausea and alopecia, was mild. Topotecan administered at this dose and schedule has limited activity in patients with HRPC. Further trials of topo I inhibition in HRPC should utilize alternative schedules of topotecan (e.g., prolonged infusion) or other camptothecin analogs with more potent topo I inhibitory activity.
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PMID:Phase II study of topotecan in metastatic hormone-refractory prostate cancer. 872 52

Immunohistochemical detection of prostate specific antigen (PSA) in metastases of adenocarcinomas is widely used as an aid to identify the prostatic origin of metastatic cells. However, on the one hand, PSA may not be expressed in some poorly differentiated prostatic carcinomas, while on the other, PSA immunoreactivity has been found in small amounts in non-prostatic tissues. The aim of the current study was to evaluate the prevalence of PSA immunoreactivity in normal non-prostatic tissues and in breast carcinoma. PSA was localized by immunohistochemistry with four commercial antibodies in 34 different normal human tissues, and in 15 ductal and seven apocrine breast carcinomas. Concentrations of PSA in tissue homogenates of prostate and nine non-prostatic tissues from autopsied subjects were measured by a two-site immunoradiometric assay. Weak PSA immunoreactivity was found by immunohistochemistry in kidney, parotid gland and pancreatic tissues. Variable PSA immunoreactivity was seen in three cases of ductal (20%) and two cases of apocrine breast carcinoma (28%). No consistent PSA immunoreactivity was found in homogenates of non-prostatic tissues by the immunoradiometric assay. We conclude that PSA is a quite specific marker of prostatic tissue. However, there are some non-prostatic neoplastic and normal tissues that express PSA. Therefore, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of immunolabelling for PSA alone.
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PMID:Immunohistochemical labelling for prostate specific antigen in non-prostatic tissues. 873 70

Casodex (bicalutamide, Zeneca Ltd), has been developed for prostate cancer therapy. Its preclinical, pharmacokinetic, pharmacodynamic, clinical efficacy and tolerability data are described. Casodex is a potent and specific non-steroidal antiandrogen. Clinical studies indicated that Casodex is orally bioavailable and well absorbed, with a plasma half-life of around 1 week. A Casodex dose of 50 mg daily decreased prostatic acid phosphatase comparable with castration. This dose was, therefore, evaluated initially as monotherapy and later as a component of maximal androgen blockade. Using prostate specific antigen as an end point, Casodex 150 mg daily was well-tolerated with demonstrable evidence of activity. Casodex 150 mg monotherapy was less effective than castration in terms of efficacy in patients with metastatic disease at entry. However, in patients non-metastatic at entry, Casodex 150 mg monotherapy appeared to be equivalent to castration in terms of time to death (data immature). Casodex was well-tolerated. In combination treatment, Casodex at 50 mg daily was at least as effective as 750 mg flutamide (Eulexin, Schering-Plough International) with respect to time to treatment failure, equivalent in terms of survival, and better tolerated with respect to diarrhoea. In conclusion, Casodex is a good option for the antiandrogen component of maximal androgen blockade.
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PMID:Casodex (bicalutamide): overview of a new antiandrogen developed for the treatment of prostate cancer. 907 8

The contrasting radiological appearances of metastatic deposits in the mandible of prostatic adenocarcinoma in two patients are described. The clinical presentation was similar in that both presented with altered sensation of the lower lip. Radiologically, they differed in that one patient suffered from a large predominantly osteoblastic mass, while the other, who gave a history of previously treated prostatic adenocarcinoma, presented with a rather small osteolytic deposit. Investigations for bony metastatic disease usually include a bone scan which is a highly sensitive technique although non-specific. A skeletal survey can be useful although less sensitive than a bone scan. Blood investigations such as acid phosphatase and prostate specific antigen levels are also indicated in male patients where prostatic disease is suspected. Reasonable long term survival using relatively simple drug therapy without significant local surgery, highlights the need for accurate recognition and tissue diagnosis to differentiate this condition from osseous malignancy of the jaws, other metastatic disease or osteomyelitis.
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PMID:Case report. Two contrasting radiological presentations of prostatic adenocarcinoma in the jaws. 916 Nov 83

A case of prostatic signet-ring adenocarcinoma is described in a man with a history of open prostatectomy for prostate carcinoma (18 years previously). Immunostaining confirmed the prostatic origin of the signet-ring tumor which stained for prostatic acid phosphatase (PSAP) and prostate specific antigen (PSA). Cytokeratin immunostaining showed the vacuoles to be true lamina with clear and distinct outlines, the feature confirmed by ultrastructural examination. This aggressive tumor is an uncommon but distinct variant of primary prostatic carcinoma which should be distinguished from artefactual vacuolation of tumor, inflammatory and stromal cells, and metastatic disease.
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PMID:Signet-ring carcinoma of the prostate. 918 94

Laparoscopic pelvic lymph node dissection (LPLND) is a low-morbidity procedure used to stage prostate cancer accurately prior to definitive local therapy. To better select patients for LPLND, we reviewed the clinical features of 120 patients with clinically localized prostate cancer who underwent LPLND to define significant risk factors for nodal metastases. The age ranged from 43 to 79 years (mean 68). Serum prostate specific antigen (PSA) concentration ranged from 1.3 to 329 ng/mL, Gleason score ranged from 2 to 9, and clinical stage ranged from T1b to T3c. Nodal metastases were discovered in 15 patients (13%). Among men with a Gleason score > or = 7, 21% had nodal metastases (P = 0.004). A serum PSA > 20 ng/mL and clinical stage T1b, T2b, or greater also were statistically significant predictors of lymph node metastases (20% and 19%, respectively). In multivariate analysis, Gleason score significantly predicted nodal metastases when controlling for all other clinical measures. Therefore, LPLND is indicated for any patient with a Gleason score > or = 7, PSA > 20 ng/mL, and advanced clinical T stage, independently or in combination.
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PMID:Risk of nodal metastases at laparoscopic pelvic lymphadenectomy using PSA, Gleason score, and clinical stage in men with localized prostate cancer. 937 45

Recently published protocols using Reverse Transcriptase Polymerase Chain reaction (RT-PCR) for prostate specific antigen (PSA) provide a sensitive means for detecting circulating prostate cancer cells. Attempts to use these assays for staging of prostate cancer have produced conflicting results. As a first step towards rectifying these discrepancies, a modified immunobead-RT-PCR assay capable of detecting as few as 10 prostate cancer cells in 8cc of blood was developed. This 10 fold increase in sensitivity was achieved in part by introducing two target cell enrichment steps. As a model system to assess sensitivity of the modified assay, template RNA was extracted from PSA positive human carcinoma cells suspended in human blood and isolated with immunomagnetic beads following incubation with an epithelium specific antibody. After 45 cycles of PCR, product from as few as 10 target cells could be readily detected when displayed on a 2% agarose gel stained with SYBR Green fluorescent dye. The identity of amplified DNA fragments was confirmed by Southern blot hybridization. When applied to blood samples from patients with proven metastatic disease, the immuno-bead RT-PCR assay was successful in detecting circulating PSA positive epithelial cells, suggesting this assay may be useful for assessment of disease progression or recurrence.
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PMID:Application of immunomagnetic beads in combination with RT-PCR for the detection of circulating prostate cancer cells. 940 55

The authors evaluate the role of prostate specific antigen (PSA) and bone scintigraphy in the follow-up of radical prostatectomy-treated and radiotherapy-treated patients. 784 patients were evaluated by simultaneous PSA assay and bone scans. The correlation between PSA levels and extension of bone metastases was good. The frequency of extraskeletal metastases was low: only 13 patients had soft tissue metastases without bone involvement and 33/138 patients with bone metastases had also extraskeletal metastases. The results underline the importance of PSA and the possibility to omit bone scan when the PSA level is below 8 ng/ml in patients who did not undergo anti-androgenic treatments.
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PMID:PSA and bone scintigraphy. 958 5

The case of a 46-year-old women with well-differentiated adenocarcinoma of the female prostate (Skene's paraurethral glands and ducts) with inguinal metastases is reported. Besides adenocarcinomatous structures, also more solid parts of the tumor and anaplastic regions with dark cells were found on histological examination. Clear cancerous cells were typical for glandular and solid tumor parts. The cancerous cells showed distinct immunohistochemical positivity of prostate specific antigen (PSA) and prostate (specific) acid phosphatase [P(S)AcP]. These are the first published results of electron microscopic examination of formalin fixed tissue showing the ultrastructure of female prostate carcinoma, comparable to that of the male prostate carcinoma. In the female, similar to the male, the prostate carcinoma probably originates from the secretory (luminal) cells of the female prostatic glands.
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PMID:Metastasizing adenocarcinoma of the female prostate (Skene's paraurethral glands). Histological and immunohistochemical prostate markers studies and first ultrastructural observation. 958 26

The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio was compared with that of the total prostate specific antigen (tPSA) value for the prediction of clinical stage in patients with prostate cancer. The f/t PSA ratio was obtained from the frozen sera of 56 untreated patients with histologically proven BPH and 78 patients with prostate cancer. The clinical stage was organ-confined in 36, locally advanced in 20 and metastatic in 22 patients. Serum levels of free PSA (fPSA) and tPSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the tPSA value and was compared with tPSA and fPSA in the correlation with clinical stage via the Spearman rank correlation test. Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The f/t PSA ratio did not differ between patients with clinically localized and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent of bone metastasis more accurately than the f/t PSA ratio. The extent of bone metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional value in clinical staging compared to tPSA. Our study suggests that the f/t PSA ratio does not reflect tumor load.
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PMID:Free-to-total prostate specific antigen ratio in clinical staging of prostate cancer. 965


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