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)

The incidence of prostate cancer in the UK is increasing, and the disease is being detected more often in younger patients (e.g. from routine PSA measurement during health-care screening). Left untreated, a significant proportion of patients will undergo progression of their disease locally and/or develop metastases. Modern imaging techniques have greatly aided the assessment of early prostatic cancer, enabling both accurate assessment of the primary tumour and giving valuable information regarding lymph node metastases. PSA measurements are also extremely helpful, and this has replaced acid phosphatase as a marker for prostatic malignancy. Controversy still remains, however, over the best form of management. Radical prostatectomy undoubtedly produces the best results in the literature, but the patients are highly selected (e.g. those with nodal metastases are excluded) and some patients with well differentiated tumours may have been over-treated, as they may have been expected to do well with surveillance alone. Full clinical trials are required in identically staged patients to assess the relative merits of surveillance, radiotherapy and surgery, and this should now be possible with recent advances in imaging techniques.
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PMID:Current trends in the management of localised prostate cancer. 130 88

The role of glycochains of cell surface glycoproteins in the cell to collagen interaction was examined by studying the effect of lectins on the fibroblast-mediated collagen gel contraction. Lectins of Phaseolus vulgaris agglutinin (PHA), concanavalin A (ConA), lentil seed agglutinin (LCA), pea agglutinin (PSA), Ricinus communis agglutinin-60 (RCA), and wheat germ agglutinin (WGA) dose-dependently inhibited gel contraction, while lectins of mushroom agglutinin (ABA), peanut agglutinin (PNA), pokeweed mitogen (PWM), and soybean agglutinin (SBA) did not. Of these lectins, PHA seemed to be worthy of further analysis, because PHA, but not other lectins, inhibited spreading of fibroblasts on collagen fibrils but not on plastic or gelatin, suggesting that cell-surface glycoproteins responsive to the lectin are involved in the specific binding of fibroblasts to native collagen fibrils. The inhibitory effect of PHA-E4, an isolectin of PHA, was more intense than that of PHA-L4, another isolectin of PHA. The collagen gel contraction was also inhibited by tunicamycin and monensin in a concentration-dependent and reversible manner. These results strongly suggest that PHA-E4-reactive glycoproteins of the fibroblast surface play an important role in cell to collagen binding during the gel contraction. Five membrane proteins including beta 1 subunits of the integrin family were obtained by affinity chromatography with PHA-E4.
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PMID:Recognition of collagen by fibroblasts through cell surface glycoproteins reactive with Phaseolus vulgaris agglutinin. 132 83

The prevalence of neural elements in prostatic carcinoma and their effects on the behavior of the lesion have recently been recognized. Recent reports suggest that chromogranin-A- and neuron-specific enolase-expressing tumors have an earlier progression and a lower response rate to hormonal therapy. The extreme presentation of this tumor is presumed to be small cell carcinoma of the prostate. This bombesin-secreting tumor, which has a characteristic clinical picture of early visceral involvement, wide-ranging metastases, and a relatively low rate of expression of PSA and PAP, is highly responsive to chemotherapy. The relatively high rate of expression of neural elements in primary prostatic carcinoma is discordant with the low frequency of clinical small cell carcinoma of the prostate. In order to account for these differences, one can assume that neural elements may play a role in the progression of this disease by either developing their own neoplastic process (small cell carcinoma of the prostate) or, in the majority of cases, causing paracrine progression of the tumor. Bombesin is typically secreted by small cell carcinoma of the lung and possibly by the prostate. It has been shown to be a growth factor mediating the progression of this disease in a number of experiments. Preclinical data demonstrate increased invasiveness and increased proliferation associated with bombesin in the treatment of prostatic carcinoma. Based on the hypothesis that neural peptides may be important mediators of androgen-independent growth of prostatic carcinoma as well as predicting poor prognosis, inhibition of these factors may represent a therapeutic strategy of relevance for the treatment of patients with prostatic carcinoma.
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PMID:The inhibition of the paracrine progression of prostate cancer as an approach to early therapy of prostatic carcinoma. 133 63

Rats were exposed to an acute dose of lead (Pb) to study the effect of Pb intoxication on different sialoglycoconjugates in serum, brain and liver. Serum levels of total sialic acid (TSA), perchloric acid (PCA)-soluble sialic acid (PSA), lipid-bound sialic acid (LBSA), free sialic acid (FSA) and alpha 1-acid glycoprotein (alpha 1-AG) were determined. They were also estimated in brain and liver tissues, except for LBSA and FSA. All these constituents were found to be significantly raised in the serum but not in the brain. In the case of the liver, only alpha 1-AG levels were found to be increased significantly, the rest were not altered. The levels of these sialoglycoconjugates in serum might be useful as biomarkers of heavy metal toxicity.
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PMID:Effect of lead on the blood serum, liver and brain sialoglycoconjugate levels in rats. 134 25

In a previous study we demonstrated that the homeobox peptide pAntp was able to penetrate into rat embryonic neurons in culture thus provoking their morphological differentiation [1]. In the present work we have started to analyse the process of penetration of the homeobox peptide. As illustrated in Figure 1 pAntp migrating as a homogeneous 7 kDa band could be recovered in the nuclear fraction 2 hrs. only after its addition to cultured embryonic neurons (lane 2). Penetration and nuclear targeting were quantitatively blocked by preincubating pAntp with its cognate recognition sequence present in the promoter of Hox-1.3 (lane 3) or by incubating the cells with an antibody directed against the NCAM-specific alpha 2-8 polysialic acid (lane 4). Similar inhibitions were observed when the peptide was incubated with double stranded DNA or added to cells deprived of alpha 2-8 polysialic acid by EndoN treatment (not shown). As illustrated in Figure 2, the strong pAntp-induced neurite growth was antagonized when pAntp internalization was prevented by the EndoN removal of PSA. This effect of EndoN was not due to the enzyme itself since morphological differentiation was not inhibited if EndoN was added after pAntp penetration (Fig. 2B). Polysialic acid is composed of long chains of neuraminic acids, each pyranose ring carrying a negatively charged carboxylic group linked to carbon in position 1. NMR studies of the molecule in solution have demonstrated that the alpha 2-8 link between each pyranose ring allows specific and stable helical conformation [2].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Are embryonic forms of NCAM homeobox receptors?]. 135 13

Biologic properties of breast cancer in men that might reflect alterations in pathogenesis from the disease in women were examined. We studied 22 tumors from males, 18 invasive carcinomas, three of which were papillary, and three in situ tumors of which one was papillary, and one papilloma. Our data support the previously reported high incidence of papillary carcinoma in men. Estrogen receptor status and the expression of cancer-associated antigens recognized by antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded sections using standard avidin-biotin techniques; anti-PSA was used to exclude the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were included as nonmalignant controls. The incidence of estrogen receptor positivity was higher in tumors from males (73%) than from females (54%), as has been reported previously. The range of expression of all breast cancer antigens tested in male tumors was similar to that observed in females, but some interesting differences were noted. With the exception of the anti-mucin DF3, all the antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c-erbB-2 was lower (17%) in males than in females (33%), despite the preponderance in men of the large-cell type carcinomas that have been associated with c-erbB-2 expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was expressed in 33% of tumors from males and, in contrast to females, was found in less differentiated tumors.
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PMID:Immunocytochemical characterization of male breast cancer. 136 97

The extracellular matrix (ECM) has been shown to play a major role in cell structure and function. Several studies have demonstrated that the ECM can alter cell morphology and effect DNA synthesis and gene expression. The ECM also interacts with growth hormones which have been shown to be located in or near the ECM where they are believed to effect cell structure and function. In the nontransformed cell, these ECM and hormone-mediated effects appear to be tightly regulated and this is believed to be accomplished through cell receptor-tissue matrix interactions. We, therefore, undertook a study to determine the effects of a variety of ECM components and the adrogenic hormone dihydrotestosterone (DHT) on the structure and function of the human prostate cancer cell line, LNCaP. The effects of individual matrix components in the presence and absence of 1 nM DHT on the static and dynamic morphology, growth rate, and PSA production of the LNCaP cell line were studied. We determine that the ECM and DHT interact in complex ways to effect cell structure and function. DHT produced alterations in cytoplasmic structure that increased cell size and decreased the nuclear area/cytoplasmic area ratio. Dynamic cell structure as measured by cell motility was very sensitive to the ECM components and the presence of DHT. PSA and growth could be regulated by substratum and DHT and there was an inverse relationship between PSA production and growth rate. These data exemplify the complex interactions which occur between prostate cancer cells, ECM components, and exogenous DHT that are reflected in cell structure and function.
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PMID:Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells. 137 Oct 8

Activity and side-effects of clodronate (Ostac), an inhibitor of osteoclastic bone resorption, were recorded in an open prospective uncontrolled study on 35 patients with metastatic prostatic cancer. All patients had progressive symptomatic bone metastases despite prior hormone therapy. Clodronate was initially administered i.v. for 8 days with 300 mg/day. This was followed by a daily oral administration of 1600 mg. The analgesic effect was evaluated by using a visual analogue scale and by recording the daily consumption of analgesic drugs. Karnofsky index and routine blood examinations, including PSA, were assessed. Repeated bone scans and radiological evaluations were performed. An improvement in pain was observed in 71% of the patients. The mean duration of improvement was 4 weeks. Average survival time was 12 weeks. There were no side-effects after i.v. administration. Slight gastrointestinal discomfort was observed in 3 patients after oral administration. No effect was observed on the extent or biology of the metastases. Clodronate is an effective drug for palliative treatment of symptomatic bone metastases of prostatic carcinoma. It causes fewer and less pronounced side effects than other palliative drug therapies.
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PMID:[Clodronate in the palliative therapy of bone-metastasized prostatic carcinoma]. 137 55

The currently available prognostic factors allow the identification of patients who are destined to do poorly with primary hormone therapy. Standardization of these factors is required so that they become incorporated into routine practice. For patients who relapse in osseous sites radiolabeled diphosphonates are one therapeutic alternative that can provide palliation. Future use will be directed to optimize treatment schedules, and use earlier in the course of the disease so that more durable palliation of bony metastases can be achieved. Evolving data on the use of PSA show that elevations antedate clinical relapse for most patients. In these cases, sequential changes can be used to assess therapeutic effects, which in turn can allow novel therapies to be screened more rapidly in the clinic. Criteria for the degree of change that is indicative of response must be standardized. Preliminary data suggest a 50% decline be the minimum that is used. The results with agents such as suramin, which interrupts autocrine and paracrine growth factor loops, are a therapeutic strategy that need further study. Future efforts will focus on defining which patients are best suited for specific therapeutic approaches.
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PMID:Therapeutic alternatives for hormone-refractory prostatic cancer. 137 15

Pre-operative serum prostate specific antigen (Tandem-R assay), T category, Gleason score and the metastatic (M1) status of a consecutive series of 60 patients with newly diagnosed carcinoma of the prostate were studied prospectively. The results revealed that, of these variables, pre-operative serum PSA (greater than 100 ng/ml) was the single most important indicator of metastatic disease, with 100% predictive value. With this alone, 83.3% of M1 disease could be correctly identified. For the remaining 17%, however, we advocate a high index of suspicion if the tumour is T3-T4 category on digital rectal examination (predictive value = 71.4%) and has a high grade with a Gleason score 8-10 (predictive value = 81%).
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PMID:Identification of metastatic disease by T category, gleason score and serum PSA level in patients with carcinoma of the prostate. 137 66


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