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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasculature plays an important role in the normal and malignant prostate. Under basal conditions both glandular epithelial and stromal prostate cells produce an abundance of blood flow and angiogenesis regulating substances and the expression of these is generally increased in prostate tumors. The proportion of proliferating endothelial cells is high in the normal prostate compared to other tissues in the body. After castration effects on the vasculature, such as decreased blood flow and vascular regression, precede effects on the glandular compartment. Correspondingly, hormone induced prostate growth is characterized by early effects on the vasculature such as increased blood flow and endothelial cell proliferation, thus indicating that the vasculature may be involved in the androgenic regulation of the prostate. Prostatic intraepithelial neoplasia (PIN) and prostate cancer are associated with increased vascular density and in experimental models prostate cancer growth is apparently angiogenesis-dependent since tumor growth and progression can be inhibited by antiangiogenic treatment. Moreover, vascular density has been related to prognosis in prostate cancer patients. A better understanding of the pathways regulating angiogenesis in the normal prostate and how these pathways change during malignant transformation can hopefully lead to better prognostic markers and therapies for the large group of patients with prostate cancer. The purpose of this review is therefore to summarize the current knowledge on the role and regulation of the vasculature in the prostate and its potential clinical applications.
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PMID:Blood vessels are regulators of growth, diagnostic markers and therapeutic targets in prostate cancer. 1184 22

PSA is emerging as the best marker in oncology and had a profound impact on all aspects of prostate cancer care. From clinically suspected prostate tumor, 395 serum samples were taken out and estimated for serum PSA. Among elevated serum PSA, 98 were correlated with histologic findings. 42(42.8%) cases were BHP among 98 cases and 78.7% had serum PSA level within 10 ng/ml. 5 patients (5.1%) had PIN histologically, 3(60%) of which had PSA level upto 10 ng/ml and 2(40%) had serum PSA upto 20 ng/ml. 51(52%) were adenocarcinoma prostate of different grades and PSA level varies from less than 10 ng/ml to more than 50 ng/ml which almost correlates with the tumor grades.
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PMID:Prostate specific antigen as tumor marker: relationship with histologic grading. 1202 9

The important progress achieved in the treatment of prostate cancer comes by exacting significant costs [11, 16-18, 20, 23, 25]. Currently, there is incomplete evidence that the radical interventions at hand significantly reduce the human costs of the disease. Surgery and radiotherapy induce substantial risks of incontinence and impotence. The PSA test has probably decreased the stage at which prostate cancer is diagnosed [15]. Nonetheless, the PSA is a means of earlier detection; it does not elucidate quantitatively distinct modes of treatment. The PSA test is not a means of prostate cancer prevention. The continuing incidence, morbidity, and mortality imposed by this disease strongly indicate that preventive strategies for its control are necessary. Chemoprevention with selenium and other agents offers a promising approach that is undergoing intensive investigation. Randomized trials underway at the authors' center are building on the important clinical trial results reported by Dr. Larry C. Clark. These studies will evaluate the activity of selenium at several points along a continuum ranging from cancerous prostatic tissue in men with diagnosed cancer to premalignant tissue in men with high-grade PIN to healthy tissue in high-risk men with negative biopsy to long-term effects on cancerous tissue in men with frank cancer. These trials will also offer an opportunity for preliminary evaluation of the mechanisms by which selenium treatment could result in the slower development or progression of prostate cancer.
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PMID:Prostate cancer and selenium. 1210 57

A search for novel and biologically relevant androgen-regulated genes and processes in the human prostate led to the intriguing observation that androgens provoke a remarkable and coordinated increase in the expression of several genes involved in triglyceride and cholesterol synthesis in various prostatic adenocarcinoma cell lines. This coordinated activation was shown to be the result of a novel and indirect pathway in which androgens cause activation of a secondary transcription regulator, Sterol Regulatory Element Binding Protein (SREBP), a pivotal factor in the control of intracellular lipid homeostasis. The biological relevance of increased lipogenesis in the biology of prostate cancer is underlined by recent immunocytochemical investigations on needle biopsies showing an increase in the expression of Fatty Acid Synthase (FAS) in 94% of the tumor-lesions examined. This increase is already evident in the earliest recognizable lesions (Prostatic Intra-epithelial Neoplasia; PIN) and is more pronounced in tumors with a higher Gleason score, suggesting that increased FAS expression may serve both as an early tumor marker and as a marker of tumor progression. As in tumor cell-lines, increased FAS expression in prostate tumors seems to be only part of a more general and coordinated activation of lipogenic pathways. Further studies revealed that lipogenesis in prostate tumor cells can be enhanced not only by androgens but also by growth factors and by tumor-associated disturbances in signal transduction pathways. EGF, for instance, is also able to activate lipogenesis via the SREBP pathway and activation of the P13 kinase system by inactivation of PTEN (a phenomenon observed in some 50% of the prostate cancers) also causes increased lipogenesis. The early and nearly universal activation of lipogenesis in prostate cancers (and also in various other tumors) suggests that this may be a fundamental event in the development of the tumoral phenotype, an element that certainly merits further investigation. In addition, there are serious indications that interference with enhanced lipogenic activity in tumor cells may cause tumor cell death and delayed tumor development, suggesting that increased lipogenic activity in tumor cells may open a novel avenue for therapeutic intervention.
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PMID:[Androgens and increased lipogenesis in prostate cancer. Cell biologic and clinical perspectives]. 1223 42

Because prostate cancer has a long latency and high incidence, it is a good target for chemoprevention by agents such as retinoids, antiandrogens, antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are frequently conducted on cohorts of patients with previous cancers or premalignant lesions who are scheduled for prostate cancer surgery; such trials are currently in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of men with high-grade PIN (HGPIN) are particularly useful in that they require a much smaller cohort of 200-400 patients instead of the 18 000 patients required for typical Phase III trials. Even with a smaller sample size, statistically significant evidence of cancer prevention is achieved due to the high probability of HGPIN progressing to cancer (35-55%). A Bayesian sequential monitoring system allows interim analysis of biomarker modulation as early as the completion of 30 patients. Putting all these strategies together will help inhibit, delay, or modulate the natural history of prostate carcinogenesis.
Prostate Cancer Prostatic Dis 1999 Jan
PMID:Strategies for chemoprevention of prostate cancer. 1249 54

There is increasing evidence that neuropeptides, including bombesin, may influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer. One of the molecules tightly involved in the regulation of neuropeptide activity is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The pattern of CD10 expression in hyperplastic and neoplastic conditions of the prostate gland has not been previously described. Immunohistochemical staining for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy specimens. Normal and hyperplastic acini showed strong and distinct membrane (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory cells. In contrast, no intercellular membrane or cytoplasmic staining of secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2 or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed CD10 expression in the secretory cells; those cases shared a distinct morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed consistent absence of intercellular membrane and cytoplasmic CD10 expression in the secretory cells, with preserved expression in basal cells. Interestingly, the basal cells in basal cell hyperplasia lacked CD10 expression, and no expression was noted in the secretory cells in all cases examined. Atrophic acini and those associated with acute and chronic inflammation retained CD10 expression. In conclusion, a consistent differential pattern of CD10 expression was seen in basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in the pathobiology of the prostate gland.
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PMID:The pattern of CD10 expression in selected pathologic entities of the prostate gland. 1279 18

Somatic inactivation of the glutathione S-transferase-pi gene (GSTP1) via CpG island hypermethylation occurs early during prostate carcinogenesis, present in approximately 70% of high-grade prostatic intraepithelial neoplasia (high-grade PIN) lesions and more than 90% of adenocarcinomas. Recently, there has been a resurgence of the concept that foci of prostatic atrophy (referred to as proliferative inflammatory atrophy or PIA) may be precursor lesions for the development of prostate cancer and/or high-grade PIN. Many of the cells within PIA lesions contain elevated levels of GSTP1, glutathione S-transferase-alpha (GSTA1), and cyclooxygenase-II proteins, suggesting a stress response. Because not all PIA cells are positive for GSTP1 protein, we hypothesized that some of the cells within these regions acquire GSTP1 CpG island hypermethylation, increasing the chance of progression to high-grade PIN and/or adenocarcinoma. Separate regions (n =199) from 27 formalin-fixed paraffin-embedded prostates were microdissected by laser-capture microdissection (Arcturus PixCell II). These regions included normal epithelium (n = 48), hyperplasticepithelium from benign prostatic hyperplasia nodules (n = 22), PIA (n = 64), high-grade PIN (n = 32), and adenocarcinoma (n = 33). Genomic DNA was isolated and assessed for GSTP1 CpG island hypermethylation by methylation-specific polymerase chain reaction. GSTP1 CpG island hypermethylation was not detected in normal epithelium (0 of 48) or in hyperplastic epithelium (0 of 22), but was found in 4 of 64 (6.3%) PIA lesions. The difference in the frequency of GSTP1 CpG island hypermethylation between normal or hyperplastic epithelium and PIA was statistically significant (P = 0.049). Similar to studies using nonmicrodissected cases, hypermethylation was found in 22 of 32 (68.8%) high-grade PIN lesions and in 30 of 33 (90.9%) adenocarcinoma lesions. Unlike normal or hyperplastic epithelium, GSTP1 CpG island hypermethylation can be detected in some PIA lesions. These data support the hypothesis that atrophic epithelium in a subset of PIA lesions may lead to high-grade PIN and/or adenocarcinoma. Because these atrophic lesions are so prevalent and extensive, even though only a small subset contains this somatic DNA alteration, the clinical impact may be substantial.
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PMID:Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. 1293 33

The aim of this work was to evaluate by immunohistochemistry (IHC) the expression of both LRP-1 and urokinase-type plasminogen activator receptor (uPAR) at different developmental stages of rat prostate disease by using a prostate cancer model previously developed in our laboratory. We found that LRP-1 was weakly expressed in normal prostates and in rats with hyperplastic glands. The expression of this receptor increased and correlated with the degree of premalignant lesions (PIN I, II, and III). The IHC for uPAR in normal prostates and in premalignant lesions showed a score of immunostaining that correlated with the expression of LRP-1. On the other hand, in prostates with adenocarcinomas and undifferentiated carcinomas, LRP-1 was undetectable or weakly detected, whereas uPAR showed a significantly higher level of expression. Based on the IHC results in rat prostates with premalignant and malignant lesions and considering that LRP-1, by mediating the internalization of uPAR, is involved in the regulation of extracellular matrix remodeling and cell migration, we conclude that a decreased expression of LRP-1 could be involved with the increasing activation of plasminogen activators shown in cancers.
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PMID:Decreased expression of the low-density lipoprotein receptor-related protein-1 (LRP-1) in rats with prostate cancer. 1462 25

Prostatic intraepithelial neoplasia (PIN) is considered the pre-malignant stage of prostate carcinoma, but little is known of its initiation and evolution. The identification of genes associated with these precursors of prostate cancer may elucidate the pathways of the early oncogenesis of this disease. Previously, we have reported that activin, a member of the TGFbeta superfamily, acted as an inhibitory growth factor in prostate cancer. We used laser capture microdissection, mRNA-library amplification (RNA-PCR), subtractive hybridization, and complementary DNA microarray to examine gene expression profiles in activin-positive PIN, compared with activin-negative PIN. Subtractive hybridization showed that 28 genes were differentially expressed (13 and 15 genes were up- and down-regulated, respectively). Microarray analysis identified 29 and 56 more genes (4 times) up- and down-regulated, respectively, suggesting that DNA microarray is a more effective method in screening gene profiles. We have validated the known genes identified by both subtractive hybridization and microarray technologies, using Northern blot analysis in the mRNA libraries generated from cells microdissected from pathological slides. We have successfully showed that at least 13 genes are involved in activin-associated PIN. The evaluation of candidate genes that emerge from these experiments provides a rational approach to investigate those genes significant in evolution from PIN to prostate carcinoma.
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PMID:Gene expression in precursor cells of prostate cancer associated with activin by combination of subtractive hybridization and microarray technologies. 1467 4

Although prostate cancer tends to be a slow-growing neoplasm affecting older men, there is clearly a subset of patients at high risk for developing early and possibly more aggressive disease. This group of high-risk patients includes men with a family history of prostate cancer and various histologic features such as PIN and ASAP identified on an initial biopsy. Black American men have a much higher risk of developing prostate cancer when compared with white men and especially Asian men. This finding may reflect both genetic and environmental factors. Screening men at increased risk of developing prostate cancer appears to be a logical strategy, especially in light of recent reports that suggest a benefit to aggressive treatment.
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PMID:Populations at high risk for prostate cancer. 1468 Mar 6


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