Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate tumor cell metastasis to the axial skeleton was induced in male Copenhagen rats using the intravenous injection of syngeneic metastatic R3327-MATLyLu tumor cells and concomitant caval vein clamping. The proliferation of tumor cells in the lumbar region was monitored by the progression, within 19 days post tumor cell injection, of hindleg paralysis which appeared in these animals. Histology confirmed the presence of tumor cells within the lumbar spine in 100% of cases displaying hindleg paralysis. Treatment with either of the bisphosphonate drugs, Cl2MDP or APD, suppressed and delayed the development of hind leg paralysis. Bisphosphonate treatment may be expected to delay the onset of axial skeletal metastasis effects in prostate cancer patients.
 ...
PMID:Progression delay of prostate tumor skeletal metastasis effects by bisphosphonates. 140 58

This review examines selected areas of contemporary prostate cancer research in terms of the impact of prostatic cellular and histopathological heterogeneity. Prostate tumor progression is accompanied by dysregulation of multiple growth factor networks as well as disruption of normal patterns of cell-cell interactions. Molecular and cytogenetic studies demonstrate that prostate cancer results from the accumulation of several different genetic defects. No single event predominates, but modifications in tumor suppressor genes or functional elimination of the suppressor gene product are more common than activation of known oncogenes. Intratumor heterogeneity is also detectable at the genetic level. This further complicates efforts to correlate modifications at specific loci with progression or outcome. The development of new in vitro and in vivo systems for the study of human prostate cancer should increase our understanding of this complex disease. In each approach, knowledge of the histopathology of the normal and neoplastic prostate is essential.
 ...
PMID:Prostate cancer progression. Implications of histopathology. 797 55

Prostate tumor initiation and progression to malignancy may involve upregulation of the androgen receptor known to stimulate prostate cell proliferation; other etiologic mechanisms may include dysfunction of the apoptotic pathway but also deregulation in signal transduction and control of the cell cycle in prostate tissue; such abnormalities could arise from overexpression or mutations in a number of oncogenes or down-regulation by inactivating mutations, allelic loss, or other epigenetic mechanisms in tumor suppressor genes. The advantages and drawbacks of various delivery systems (retroviral, adenoviral, liposomes) used for human gene therapy are being considered. Several ex vivo and in vivo as well as cell culture studies are suggested for the therapy of the human prostate cancer using transfer and expression of genes that might be implicated in prostate carcinogenesis especially of the tumor suppressor p53. Expression of suicidal genes in prostate cancer cells using prostate-specific promoter and enhancer elements as well as targeting of the androgen receptor or the insulin-like growth factor genes with triplex technology in prostate cancer cells and their metastases, is expected to be of therapeutic value.
 ...
PMID:Gene therapy of prostate cancer: p53, suicidal genes, and other targets. 917 86

Prostate cancer is the single most common malignancy among men in North America. Nevertheless, cytogenetic evaluation of bone marrow in patients with metastatic prostate neoplasm has been rare and, to date, only five such patients have been reported. We report an additional case where chromosomal abnormalities of a bizarre nature were found in the bone marrow. Though cytogenetic findings in prostate cancer are heterogeneously complex, the chromosome regions involved include 1p, 1q, 7q, 8p, 10q, 12p, and 17q and are considered hot spots. What is the significance of these so-called hot spots in metastasis of prostatic cancer to the bone marrow? At present, no meaningful conclusion can be drawn, as data are limited, but accumulation of such cases may provide valuable information concerning the role of chromosomal abnormalities in patients--specifically with metastatic stage--and may help urologists during therapeutic decision making, particularly if a genetic marker for aggressiveness can be determined.
 ...
PMID:Highly complex chromosomal aberrations in bone marrow of a patient with metastatic prostate neoplasm. 939 65

PSA is the most useful tumor marker for the diagnosis and treatment of prostate cancer. Its clinical use, however, still lacks the necessary sensitivity and specificity to be considered as ideal. In fact PSA is not specific for adenocarcinoma of the prostate: an elevated serum level of the marker does not necessarily mean malignant growth and normal levels too often hide an occult and potentially lethal cancer. With the discovery of different molecular PSA forms in the serum, an improved discrimination between benign prostate hyperplasia (BPH) and prostate cancer appears possible. This may be particularly useful in cases with equivocal PSA values and unpalpable prostate neoplasm to reduce the number of unnecessary prostate biopsies and increase the number of biopsies in cases without palpable or ultrasonic visible anomalies. The clinical use of PSA age-referenced levels is discussed. Their use is invaluable in screening programs where the routine adoption of age-specific values can help to pick-up younger patients with potentially curable prostate cancer and older patients with BPH where additional tests would be unnecessary. The role of PSA velocity (PASAV) s also discussed. An elevation rate of PSA of 0.75 ng/ml over 18 months on 3 serial samples appears to be the best cut-off to distinguish BPH from prostate cancer. However, the use of PSAV seems to be less useful in patients with elevated PSA levels and negative biopsy results. Free to total PSA ratio is probably the best parameter to reduce the number of unnecessary biopsies in men with a serum total PSA of 4 to 10 ng/ml. The advantages and limitations for different levels of cut-off are shown. A flow chart illustrating the role of various PSA "derivatives" in screening and subsequent evaluation of men over 50 years of age is also presented.
 ...
PMID:[The role of prostate specific antigen and its derivatives (age-specific PSA, PSA density, velocity, free/total PSA) in the diagnosis of prostate cancer]. 970 70

Differentiation-inducing agents, such as retinoids and short-chain fatty acids, have an inhibitory effect on tumor cell proliferation and tumor growth in preclinical studies. Clinical trials involving these compounds as single agents have been suboptimal in terms of clinical benefit. Our study evaluated the combination of phenylbutyrate (PB) and 13-cis retinoic acid (CRA) as a differentiation and antiangiogenesis strategy for prostate cancer. On the basis of previous evidence, common signal transduction pathways and possible modulation of retinoid receptors and retinoid response elements by PB could be responsible for such activities. We assessed the effect of the combination of PB and CRA on human and rodent prostate carcinoma cell lines. The combination of PB and CRA inhibited cell proliferation and increased apoptosis in vitro in an additive fashion as compared with single agents (P < 0.014). Prostate tumor cells treated with both PB and CRA revealed an increased expression of a subtype of retinoic acid receptor (retinoic acid receptor-beta), suggesting a molecular mechanism for the biological additive effect. The combination of PB and CRA also inhibited prostate tumor growth in vivo (up to 82-92%) as compared with single agents (P < 0.025). Histological examination of tumor xenografts revealed decreased in vivo tumor cell proliferation, an increased apoptosis rate, and a reduced microvessel density in the animals treated with combined drugs, suggesting an antiangiogenesis effect of this combination. Thus, endothelial cell treatment with both PB and CRA resulted in reduced in vitro cell proliferation. In vivo testing using the Matrigel angiogenesis assay showed an additive inhibitory effect in the animals treated with a combination of PB + CRA (P < 0.004 versus single agents). In summary, this study showed an additive inhibitory effect of combination of differentiation agents PB and CRA on prostate tumor growth through a direct effect on both tumor and endothelial cells.
 ...
PMID:Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis. 1124 54

Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.
 ...
PMID:Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. 1128 Jul 89

Familial predisposition together with several environmental factors may be involved in the pathogenesis of common prostate disease such as benign hypertrophy or prostate neoplasm. A higher incidence of both these conditions has been described in some insulin-resistant states such as obesity, but not much information is available on the effect of metabolic profile on gland morphology. The aim of this study was to evaluate the relation between glucose and lipid pattern and prostate diameters in two groups of non-diabetic individuals with benign prostate hypertrophy or cancer. 109 patients were recruited; plasma glucose, lipids and hormonal profile as well as an ultrasonographic evaluation of the gland volume and diameters were determined. Patients with prostate cancer had significantly higher levels of insulin and were more insulin resistant; in contrast, in subjects with prostate hypertrophy, fasting plasma glucose and--to a lesser extent--serum triglycerides emerged as the main determinants of gland volume. These observations may indicate that an improvement of insulin sensitivity and strategies to maintain a strict glucose and lipid control even in non-diabetic subjects are useful objectives in the prevention of prostate diseases.
 ...
PMID:Metabolic profile in patients with benign prostate hyperplasia or prostate cancer and normal glucose tolerance. 1291 99

Murine models have shown that IL-18 has antiangiogenic and antitumor effects, but little is known about IL-18 production in human tumors. We investigated IL-18 expression in clinically localized prostate cancers by immunohistochemistry and showed that 75% of the prostate cancers studied (27/36 cases) presented with tumor cells producing IL-18. Prostate tumor cell lines PC-3, DU 145 and LNCaP synthesized the immature form of IL-18 (p24). IFN-gamma produced in prostate cancers induced caspase-1 mRNA and IL-18 secretion of tumor cell lines, which was inhibited by the cell-permeable Tyr-Val-Ala-Asp-aldehyde caspase-1 inhibitor (YVAD-CHO). Interestingly, IFN-alpha also induced IL-18 secretion of the poorly differentiated cell line PC-3. PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18R alpha (IL-1Rrp) protein and transcripts for IL-18R beta (AcPL). Exogenous IL-18 increased mitochondrial activity of both cell lines evaluated by the tetrazolium (MTT) assay but did not influence their proliferation. This indicated that prostate tumor cells could secrete IL-18 in response to IFN-gamma in the tumor microenvironment and that IL-18 could act as a autocrine/paracrine factor for the tumor. In the cohort of patients studied, IL-18 expression in prostate cancers (with up to 10% of tumor cells stained) was associated with a favorable outcome and equally predictive as pathologic stage on multivariate analysis (log rank test, p = 0.02). Tumor IL-18 production is a novel physiopathologic feature of prostate cancer and appears to be a favorable event in the course of the disease. Modulation of IL-18 production by interferons could have a beneficial clinical effect, which deserves further investigation.
 ...
PMID:IL-18 is produced by prostate cancer cells and secreted in response to interferons. 1291 59

The incidence of secondary testicular tumors ranges from 0.02 to 2.5% among autopsies in general. With the exception of leukemias and lymphomas, prostate cancer is the most common primary site. It is diagnosed in autopsies or incidentally, following therapeutic orchiectomies in more advanced stages of the disease. In the present report, we show a case of testicular metastasis derived from prostate neoplasm whose clinical presentation as a single metastasis was similar to a primary testicular neoplasm. The diagnosis was evidenced after orchiectomy by histological examination and immunohistochemical tests.
 ...
PMID:Single testicular metastasis mimicking primary testicular neoplasm: a rare manifestation of prostate cancer. 1576 10


1 2 3 4 5 Next >>