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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Markers of human prostatic cancer are important diagnostic aids in the management of this most common tumor among US men. A rapidly expanding body of basic and clinical knowledge about the properties and behavior of these unique organ-specific macromolecules bridges the gap between sophisticated immunochemistry and everyday practice. As a consequence, the patient benefits, because greater opportunities for early detection of prostatic cancer provide more freedom in selecting the most effective treatment modalities. Parallel improvement in quantitative assessment of an existing tumor mass allows earlier and more precise monitoring of the positive therapeutic responses and/or disease progression, as well as better overall prognosis. In addition, marker molecules can provide specific targets for antibody-directed therapeutic compounds active against prostatic cancer. This study focused on three such markers: prostatic acid phosphatase, prostate-specific antigen, and a new membrane-associated marker defined by a monoclonal antibody called 7E11-C5. A critical evaluation of clinical usefulness and prospects for future developments are presented.
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PMID:Lucy Wortham James Basic Research Award. Markers of prostatic carcinoma. 172 Sep 51

Expression of prostate-specific antigen (PA) mRNA was tested at various time periods after incubation of the human prostate tumor cell line LNCaP with the synthetic androgen R1881. Androgen-stimulated expression was observed within 6 h after addition of R1881 to the cells. Run-on experiments with nuclei isolated from LNCaP cells showed that expression of the PA gene could be regulated by R1881 on the level of transcription. DNase I footprints of the promoter region of the PA gene (-320 to +12) with nuclear protein extracts from LNCaP cells showed at least four protected regions. The protected areas include the TATA-box, a GC-box sequence, and a sequence AGAACAgcaAGTGCT at position -170 to -156, which closely resembles the reverse complement of the consensus sequence GGTACAnnnTGTTCT for binding of the glucocorticoid receptor and the progesterone receptor. Fragments of the PA promoter region were cloned in front of the chloramphenicol acetyltransferase (CAT) reporter gene and cotransfected with an androgen receptor expression plasmid into COS cells in a transient expression assay. CAT activity of COS cells grown in the presence of 1 nM R1881 was compared to untreated controls. A 110-fold induction of CAT activity was found if a -1600 to +12 PA promoter fragment was used in the construct. By further deletion mapping of the PA promoter a minimal region (-320 to -155) was identified as being essential for androgen-regulated gene expression. Mutation of the sequence AGAACAgcaAGTGCT (at -170 to -156) to AAAAAAgcaAGTGCT almost completely abolished androgen inducibility of the reporter gene constructs. One or more copies of the sequence AGAACAgcaAGTGCT cloned in front of a thymidine kinase promoter-CAT reporter gene confers androgen regulation to the reporter gene. These findings provide strong evidence for transcription regulation of the PA gene by androgens via the sequence AGAACAgcaAGTGCT. Interestingly, in addition to the AGAACAgcaAGTGCT element, an upstream region (-539 to -320) is needed for optimal androgen inducibility of the PA promoter.
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PMID:The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. 172 87

Prostate-specific antigen (PSA) is increasingly used in the diagnosis of prostatic pathology. Its usefulness in the early diagnosis of prostatic cancer is controversial. The aim of the study is to evaluate the sensitivity and specificity of PSA in a population with prostate diseases. Moreover, we wanted to know if the measure of the prostate volume may increase the sensitivity of the test. In benign prostatic hypertrophy (88 patients), a good correlation exists between circulating PSA and the prostatic volume or the volume of the adenoma. This correlation disappears in the presence of an adenocarcinoma at the profit of the tumor volume (46 patients). Used as a means of screening for cancer, the serum level of PSA with a threshold value of 2.5 ng/ml has a sensitivity of 91% and a specificity of 32%. The sensitivity is 50% and the specificity is 85% at a level of 15 ng/ml. Taken alone, the level of PSA is inadequate for diagnosis: If the lower level is chosen (2.5 ng/ml), the majority of benign prostatic hypertrophies will be the object of a biopsy. If the higher level is chosen (15-23 ng/ml), 50% of localized cancers of the prostate will escape detection. Nevertheless, a level of PSA < 15 ng/ml is an argument for a strong suspicion in favor of an adenocarcinoma of the prostate. The capacity of BPH to "secrete" serum PSA is five times greater than that of the normal peripheral prostate, and the capacity of cancer is 20 times greater than that of an adenoma. The individual variability of serum PSA per cubic centimeter of prostatic tissue is too great to allow a precise interpretation as a function of volume.
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PMID:[Circulating prostatic-specific antigen in benign hypertrophy and localized prostate cancer: can PSA be considered a screening examination for localized cancer?]. 172 43

Carcinoma is found unexpectedly in approximately 10% or more of the 400,000 prostatectomies performed annually in the United States. Patients with Stage A2 carcinoma die of their disease in only 35% of the cases. To alter the course of disease in these patients, 65% of Stage A2 patients may be treated unnecessarily by radical prostatectomy, radiation therapy, or hormonal therapy. An accurate method to predict the outcome of patients with Stage A2 carcinoma is needed. Histologic sections from 18 patients with Stage A2 prostatic carcinoma followed without further treatment until progression, or followed without progression, were evaluated by several investigators who did not have knowledge of patient outcomes and who employed standard pathologic grading systems as well as morphometric, cytophotometric, flow cytometric, and immunohistochemical techniques. Outcome was predicted correctly by random sampled absolute (17 of 18 cases) and relative (16 of 18) nuclear roundness factor (NRF), tumor volume expressed as percent of specimen (13 of 16), primary (13 of 18), secondary (14 of 18), sum (15 of 18), and worse (14 of 18) Gleason grades and prostate-specific antigen immunohistochemical findings (13 of 18) that produced statistically significant separation of the two groups. Significant separation was not obtained with Mostofi's pattern, nuclear, sum, and worse grades, Johns Hopkins' grade, absolute tumor volume, nuclear DNA content measured by image cytophotometric study of Feulgen-stained histologic sections and flow cytometric study of propidium iodide-labeled suspensions of nuclei obtained from paraffin blocks, nonrandom sampled NRF of worse and most prevalent neoplastic areas, and prostatic acid phosphatase and peanut agglutinin immunohistochemical study. NRF measured by a random technique best predicted outcome in these patients with A2 prostatic carcinoma and should be evaluated prospectively as a means for selecting patients who require therapy.
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PMID:Prediction of prognosis in untreated stage A2 prostatic carcinoma. 172 82

Between 1976 and 1989, 115 patients at UCLA had radical retropubic prostatectomy for clinically localized prostate cancer with positive surgical margins, penetration of tumor into or through the capsule, or positive seminal vesicles. Twenty-four of those received adjuvant radiotherapy after having recovered from surgery. Complications of adjuvant treatment were uncommon and included urethral strictures in 3 patients and transient leg edema in 1. No patient in this group has had proved clinical disease progression though 6 have isolated detectable serum prostate-specific antigen (PSA) values. Clinical disease-free survival at five and seven years was 92 percent. If detectable PSA is also considered as evidence of tumor recurrence, the corresponding disease-free survival rates were 75 percent at five years and 54 percent at seven years. The 91 patients who received no postoperative radiotherapy had a clinical disease-free survival of 67 percent at five years and 56 percent at seven years. Disease-free survival drops to 43 percent and 24 percent, respectively, if detectable follow-up PSA is considered an indicator of disease progression. The comparisons of the survivorship curves in this retrospective study for the two treatment groups are statistically significant both for disease-free survival (p = 0.041), and disease-free survival with undetectable PSA (p = 0.043). Adjuvant radiotherapy has a beneficial effect after radical prostatectomy in patients with local tumor extension.
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PMID:Adjuvant radiotherapy in patients post-radical prostatectomy with tumor extending through capsule or positive seminal vesicles. 172 97

Prostate glands exposed to androgen deprivation with leuprolide +/- flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment-related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment-related histologic effects and initial tumor grade and clinical stage as well as expression of prostate-specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide-treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug-related variations in tumor morphologic features are appreciated.
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PMID:Pathologic changes associated with androgen deprivation therapy for prostate cancer. 190 75

Little is known about the efficacy of flutamide monotherapy in previously untreated patients with prostatic carcinoma. In this study, 40 patients with advanced disease were treated with 250 mg flutamide, three times daily. The mean follow-up was 7 months. After 3 months, 35 patients were evaluable for efficacy; 17 showed a partial response and 18 showed no change. Tumor response after 6 months was evaluated in 22 patients; 10 had a partial response, nine had stable disease, and three had progression. The level of prostate-specific antigen was reduced markedly following 6 months' treatment with flutamide. Levels of testosterone increased slightly but significantly, and were still elevated not significant after a follow-up period of 1 year. Follicle-stimulating hormone did not change markedly, whereas luteinizing hormone rose significantly. Eighteen patients experienced mild gynecomastia and eight suffered diarrhea. In two patients, flutamide was discontinued for 2 weeks due to serious diarrhea. One patient was withdrawn after 6 weeks because of cholestatic hepatitis. Sexual potency was evaluated in 15 patients, 10 of whom remained sexually active during treatment. Flutamide monotherapy was concluded to be relatively safe and effective in patients with advanced prostatic cancer.
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PMID:Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. 194 17

Two examples of large, multiloculated, cystic tumors that arose within the pelvis in men of 28 and 37 years of age are described. The tumors were composed of glands and cysts lined by prostatic-type epithelium lying in a hypocellular fibrous stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen and prostatic acid phosphatase. Two apparently similar lesions were found in the literature; one tumor was attached to the prostate by a pedicle, and the other arose in the retrovesical space. These tumors, for which we propose the designation "giant multilocular prostatic cystadenoma," appear to be benign, although they may recur if incompletely excised. They may pose considerable diagnostic difficulty if the prostatic nature of the epithelium is not appreciated, an error that is likely if a relationship to the prostate is not recognized. This lesion should be included in the differential diagnosis of retroperitoneal cystic tumors in men.
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PMID:Giant multilocular prostatic cystadenoma: a distinctive lesion of the retroperitoneum in men. A report of two cases. 198 60

Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically. To develop criteria useful in resolving problem cases, the authors compared the reactivities of these conditions (nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme, antimacrophage M, and leukocyte common antigen (LCA). In granulomatous prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin; however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods.
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PMID:Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their distinction with the use of immunohistochemical methods. 199 42

Radical prostatectomy was performed in 14 patients following local failure of radiation therapy for adenocarcinoma of the prostate. Ten patients were treated with external beam and 4 with interstitial radiation. The interval from beginning radiation therapy to biopsy-proved residual or recurrent disease was twenty-four to one hundred fourteen months (mean 61 months). Ten patients had significant anterior and lateral fibrosis. Five patients had loss of tissue planes between the prostate and rectum, however, no rectal injuries occurred. Estimated blood loss was 300-8,000 cc (median 1,000 cc). Operative time was one hundred ten to three hundred seventy-five minutes (median 185 minutes). Significant late complications are impotence (100%) and incontinence (55%). Tumor volume was 1.1-27.2 cc (mean 11.1 cc). Seven patients had seminal vesicle involvement, 9 had level III capsule penetration, and 6 had positive surgical margins. Follow-up ranges from one to fifty-two months (median 18 months). Currently, 6 patients are clinically without disease and have serum prostate-specific antigen (PSA) of 0.0 ng/mL. Four patients have no clinical evidence of disease but do have detectable serum PSA, and 4 patients have evidence of metastatic bone disease on bone scan with elevated serum PSA levels. Radical prostatectomy following radiation therapy has no greater immediate morbidity or mortality compared with radical prostatectomy without prior irradiation and takes only slightly longer to perform. However, there is a marked increased risk of impotence and incontinence. More patients followed for a longer time are needed to assess the benefit of radical prostatectomy on survival of patients who fail radiation therapy.
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PMID:Radical prostatectomy after definitive radiation therapy for prostate cancer. 200 Jun 72


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