Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five randomized pilot studies of screening for prostate cancer (PC) have been conducted in the area of Rotterdam from 1991 to 1994. The purpose of these studies was to establish the feasibility of a randomized screening protocol with PC mortality as the major end point in The Netherlands and at a European level. All procedures related to recruitment of participants, to application of the screening tests and to data collection were evaluated. Men (7,200) aged 55-74 years were invited through the Rotterdam Population Registry. The recruitment rate over the 5 pilot studies averaged 38.2% (2,747 men). Recruitment procedures proved to be relevant for establishing higher participation rates (invitation and consent by mail). The screening tests were well accepted and tolerated. The general population-based character of the sample was confirmed by studying symptoms of prostatic disease in participants and in men who refused participation. Data based on one PSA serum determination, rectal examination and transrectal ultrasonography are presented; 204/1,403 men (14.5%) had a positive screening result by either test combination and underwent biopsy. Forty-nine cancers were found in 1,403 men (3.5%); 65% of prostate cancers (17/26) identified in men who eventually underwent radical prostatectomy proved to be locally confined. From the pilot studies, we conclude that a large contribution to a European Randomized Study of Screening for Prostate Cancer (ERSPC) can be made by recruiting about 40,000 men in the area of Rotterdam. The preliminary data suggest that after confirmation of the present data during the first years in the European study, DRE and TRUS can be withheld depending on the PSA result in a large proportion of the screening population.
Int J Cancer 1996 Jan 17
PMID:European randomized study of screening for prostate cancer--the Rotterdam pilot studies. 856 9

Prostate cancer is a common cancer and a leading cause of cancer death in men. It is potentially detectable at early, possibly curative stages through various combinations of testing, including DRE, PSA, and TRUS of the prostate. Still unproven is the effectiveness of prostate cancer treatment, and because of that lack of proof, the optimal screening strategies are also elusive. It is possible that what is known as prostate cancer today may be, in fact, multiple entities with different natural histories, different treatment needs, and, consequently, different screening strategies. The role of informed consent has been suggested as a means to involve patients in the decision process, especially because the literature presents an environment of intense controversy. It is hoped that the PIVOT trial or similar efforts and further research into the basic mechanisms of the disease will provide clearer answers in the future.
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PMID:Prostate cancer screening. 856 2

Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.
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PMID:Collagen derived serum markers in carcinoma of the prostate. 857 75

Large numbers of men have an undetected prostate tumor, but in only a small proportion of cases do these lesions ever become clinically significant. That being so, it will take time to demonstrate the PSA screening or any given treatment strategy has benefit. Meanwhile, patients need help deciding whether to undergo screening and, if cancer is found whether to opt for aggressive treatment.
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PMID:Management dilemmas in prostate cancer. 859 92

Metastatic prostate adenocarcinoma is a leading cause of cancer-related deaths among men. First line treatment is primarily aimed at blocking the synthesis and action of androgens. As primary endocrine treatment, androgen deprivation is usually achieved by orchidectomy or LHRH analogues, frequently combined with androgen receptor antagonists in order to block the residual adrenal androgens. However, nearly all the patients will eventually relapse. Available or potential second line therapies include, among others, alternative endocrine manipulations and chemotherapy. Cytochrome P450-dependent enzymes are involved in the synthesis and/or degradation of many endogenous compounds, such as steroids and retinoic acid. Some of these enzymes represent suitable targets for the treatment of prostate cancer. In first line therapy, inhibitors of the P450-dependent 17,20-lyase may achieve a maximal androgen ablation with a single drug treatment. Ketoconazole at high dose blocks both testicular and adrenal androgen biosynthesis but its side-effects, mainly gastric discomfort, limit its widespread use. A series of newly synthesized, more selective, steroidal 17,20-lyase inhibitors related to 17-(3-pyridyl)androsta-5,16-dien-3beta-ol, may open new perspectives in this field. In prostate cancer patients who relapse after surgical or medical castration, therapies aiming at suppressing the remaining adrenal androgen biosynthesis (ketoconazole) or producing a medical adrenalectomy (aminoglutethimide+hydrocortisone) have been used, but are becoming obsolete with the generalization of maximal androgen blockade in first line treatment. The role of inhibition of aromatase in prostate cancer therapy, which was postulated for aminoglutethimide, could not be confirmed by the use of more selective aromatase inhibitors, such as formestane. An alternative approach is represented by liarozole fumarate (LIA), a compound that blocks the P450-dependent catabolism of retinoic acid (RA). In vitro, it enhances the antiproliferative and differentiation effects of RA in cell lines that express RA metabolism, such as F9 teratocarcinoma and MCF-7 breast carcinoma cells. In vivo, monotherapy with LIA increases RA plasma levels and, to a greater extent, endogenous tissue RA levels leading to retinoid-mimetic effects. In the rat Dunning prostate cancer models, it inhibits the growth of androgen-independent as well as androgen-dependent carcinomas relapsing after castration. Concurrently, changes in the pattern of cytokeratins characteristic of increased differentiation were observed. Early clinical trials show that LIA, in second or third line therapy in metastatic prostate cancer, induces PSA responses in about 30% of unselected patients. In some patients regression of soft tissue metastasis ha been observed. In a subgroup of patients, an important relief of metastatic bone pain was also noted.
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PMID:P450-dependent enzymes as targets for prostate cancer therapy. 860 34

To determine whether long-term oral administration of UFT, a combination of 5-fluorouracil and uracil, in addition to conventional estrogen therapy improved the response and survival of the patients with advanced stage D2 prostate adenocarcinoma, a randomized prospective study was performed with either estrogen alone (Honvan 200 mg/day or presexol 1 mg/day: group A) or estrogen plus UFT (400 mg/day:group B). This study comprises 34 newly diagnosed patients with poorly differentiated prostatic adenocarcinoma (18 patients in group A and 16 in group B). Survival from all causes of death or cancer-specific death were compared using Kaplan-Meier actual methods among the patients separated by histological composition of tumors analyzed WHO histologic patterns, score of extent of disease (EOD), and with or without normalization of serum PSA or PAP levels after treatment. Although combination therapy with UFT against overall survival was effective without statistical significance, better survival in this group than the patients treatment with estrogen alone assessed among the patients whose tumor contained more than 70% of medullary and/or column-cord histological components. The survivals among the patients with EOD score 3 and whose serum PSA or PAP levels did not lead to decrease within normal levels after treatment were also better in group B than in group A. These findings suggest the validity of the combination therapy with UFT in addition to estrogen against highly advanced prostatic cancer patients whose tumor composed of abundant non-hormone-refractor histological components.
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PMID:[Combination therapy with estrogen and UFT in newly diagnosed prostatic cancer (poorly differentiated, stage D2)]. 861 89

Recently, the concept of PSA density has been introduced in order to increase the diagnosis sensitivity obtained with serum PSA dosing. The usefulness of this parameter has been assessed in 47 patients with benign prostate hyperplasia (BHP) and 26 patient with non-disseminated prostate adenocarcinoma. Using 0.15 as cut-off value, below which were 97% of patients with uncomplicated BHP, we obtained a 73% overall sensitivity. This sensitivity was stage related, reaching 100% in stage C patients. On the contrary, the test specificity was relatively low, since it considered patients with complicated HPB with urinary infection or with in-dwelling vesical catheter, obtaining 41% false positives. These results suggest a special usefulness of this test for the correct diagnosis of those prostate cases with mild suspicion of cancer.
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PMID:[The diagnostic utility of PSA density]. 865 75

Prostatic intraepithelial neoplasia (PIN) fulfils the majority of requirements for a premalignant change in the human prostate. Forty-eight patients were diagnosed to have high grade PIN on prostatic needle biopsy. During a follow-up period, 23 (47.9%) were found to have adenocarcinoma on subsequent biopsies. We compared the patients age, the digital examination, the transrectal ultrasound appearance (TRUS) and the serum PSA level between those in whom cancer was detected subsequently and those with PIN alone. There was a statistically significant difference in the transrectal ultrasound appearance (TRUS) and the serum PSA level between the two groups (p < 0.001, p < 0.016 respectively). In conclusion, patients with high grade PIN, elevated serum PSA with hypoechoic zone on TRUS should be rebiopsied 3 months after the initial diagnosis. If the results are negative, close follow-up is mandatory.
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PMID:[High-grade intraepithelial prostatic neoplasms: diagnosis and association with prostate cancer]. 865 30

The state of the art concerning major biological phenomenons of importance for current research on urological cancers is first briefly presented, followed by notes on the more outstanding presentations in this field. These notes are organized in a synthetic fashion, in order to point to the meaning of the hypotheses and findings presented, when taken together, as they pertain to the understanding of the mechanisms at play in urological cancers, as we see them in 1995. Some concepts seem to have now reached a point where we can expect to see some applications in a not so distant future: in prostate cancer, it is confirmed that the machinery of apoptosis is functional even in the hormone-insensitive cells, suggesting that its enhancement might be useful in these often difficult situations; techniques to detect circulating malignant cells, which have been greatly refined (RT-PCR of PSA and PSM), are now extremely sensitive and may prove unvaluable in providing intermediate end points to compare the relative efficacy of treatment regimens in clinical trials; the symposium on prostate cancer screening by PSA dosage was an excellent opportunity to review extensively the data available on this topic, but -as expected- it could not decide on some essential issues; in bladder tumors, data on the expression of adhesion molecules (CD44 variant) are still preliminary, but some provocative observations have been reported (presence on mature ARN, only in bladder cancer cells, of intronic sequences that have not been excised); in renal cell cancer, a considerable amount of knowledge has accumulated on the von Hippel-Lindau gene, a putative anti-oncogene, and work is in progress to define the function of its protein; finally, pathways essential to understanding and treating cancer have been dissected, particularly the apoptosis-proliferation network, and the involvement in it of p53, Waf-1 and the bcl-2 gene family cascade.
Bull Cancer 1996 Jan
PMID:[The annual meeting of the American Association for Cancer Research (AACR), Toronto (Ontario), 18-22 May 1995]. 867 62

In Japan, the proportion of patients with localized prostate cancer treated by radical prostatectomy is increasing rapidly. The recent improvements and treatment results of radical prostatectomy were reviewed. As for the qualifications of patient candidates for radical surgery, including patient age, various clinical and pathological findings to predict tumor extent and disease-free outcome (clinical stage, serum prostate specific antigen, PSA density, number of positive biopsies, histological grade, etc) must be kept somewhat tidy. Recently, there has been increased interest in the application of preoperative hormone treatment for localized tumor group in order to improve radicality and survival. Several studies reported the results of neoadjuvant endocrine therapy. As for stage C tumors, the proportion of patients with capsular invasion, positive surgical margin, invasion of seminal vesicle and positive node metastasis are 67-86%, 39-64%, 32-47% and 38-50%, respectively. Prospective randomized studies should provide conclusive information on the potential benefits of this treatment modality. The new anatomical approach to radical retropubic prostatectomy with its nerve-sparing option assures preservation of erection. This procedure achieves excellent cancer control for patients with a definite organ-confined tumor, but it is difficult to diagnose a specimen-confined tumor preoperatively. There is limited information on cancer control with the nerve-sparing option. More time is needed to obtain information on the long-term outcome after radical prostatectomy.
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PMID:[Recent improvements and results of radical prostatectomy]. 867 90


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