UMLS:C0376358 - FACTA Search

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

With the completion of the Human Genome Project and high-throughput screening methods using cDNA array and tissue microarray (TMA) technology, there is a pressing need to manage the voluminous data sets generated from these types of investigations. Herein is described a database model to handle 1) clinical and pathology data, 2) TMA location information, and 3) web-based histology results. The model is useful for managing clinical, pathology, and molecular data on >1300 prostate cancer patients dating back to 1995 from the University of Michigan Specialized Program of Research Excellence for prostate cancer. The key components in this multidatabase model are 1) the TMA database, 2) the TMA-image database (TMA-I DB), and 3) the prostate pathology and clinical information databases. All databases were created in Microsoft Access (Microsoft, Redmond, WA). Desired patient, tissue, block, diagnosis, array location, and respective clinical and pathology information is obtained by linking the unique identifier fields among database tables. The TMA database is comprised of interrelated data from 336 prostate cancer patients transferred into 19 TMA blocks with 5451 TMA biopsy cores. Tissue samples include 1695 normal prostate, 3171 prostate cancer, 464 prostatic intraepithelial neoplasia, and 121 atrophy. All 19 TMA blocks have been analyzed over the Internet for several immunohistochemical biomarkers including E-cadherin, prostate-specific antigen, p27(Kip1), and Ki-67 labeling index. This system facilitates the statistical analysis of high-density TMA data with clinical and pathology information in an efficient and cost-effective manner. Because the review is performed over the Internet, this system is ideal for collaborative multi-institutional studies.
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PMID:Relational database structure to manage high-density tissue microarray data and images for pathology studies focusing on clinical outcome: the prostate specialized program of research excellence model. 1154 76

Prostate-specific antigen (PSA) is the most widely used marker for the diagnosis of prostate cancer and is an independent predictor of prostatic capsular invasion. A number of studies have identified E-cadherin, a cell adhesion protein, as a potential invasion suppressor which is decreased in prostate adenocarcinoma. Our goal in the present study was to evaluate E-cadherin expression in primary cultures and determine the relationship between E-cadherin expression and PSA secretion in both primary cultures and the prostate tumor cell line, LNCaP. Immunohistochemical studies and Western blot analysis confirmed greater expression of E-cadherin in normal epithelial cells than tumor-derived prostate cells. This is the first report that the incubation of normal prostate epithelial cells with E-cadherin antibody increases the amount of PSA detected in the media of normal cells as well as in LNCaP. Since E-cadherin may function as an invasion suppressor, an understanding of the decreased expression of this adhesion factor and the impact on PSA secretion may aid in understanding epithelial tumorigenesis.
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PMID:E-cadherin expression and PSA secretion in human prostate epithelial cells. 1158 86

Hypermethylation of CpG island is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed 13 genitourinary cancer cell lines for aberrant DNA methylation of 5 tumor-related genes using methylation- specific polymerase chain reaction (MSP). GSTP1 was methylated in 5 (38.5%), E-cadherin in 1 (8%), VHL in 1 (8%), and MGMT and hMLH1 in none (0%). Six out of thirteen genitourinary cancer cell lines had methylation of at least one of five genes; 5 had one gene methylated, and, 1 had two genes methylated. Methylation of these 5 genes was not detected in any of the bladder cancer cell lines. GSTP1 was methylated in all of the 3 prostate cancer cell lines. We conclude that aberrant hypermethylation may be an important mechanism for the inactivation of cancer-related genes in kidney and prostate cancer cell lines.
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PMID:Hypermethylation of tumor-related genes in genitourinary cancer cell lines. 1174 58

The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. beta-Catenin plays a critical role in embryonic development and tumorigenesis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Here, we demonstrate that a specific protein-protein interaction occurs between beta-catenin and AR. Unlike the steroid hormone receptor coactivator 1 (SRC1), beta-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor alpha, progesterone receptor beta, and glucocorticoid receptor. The ligand binding domain of AR and the NH(2) terminus combined with the first six armadillo repeats of beta-catenin were shown to be necessary for the interaction. Through this specific interaction, beta-catenin augments the ligand-dependent activity of AR in prostate cancer cells. Moreover, expression of E-cadherin in E-cadherin-negative prostate cancer cells results in redistribution of the cytoplasmic beta-catenin to the cell membrane and reduction of AR-mediated transcription. These data suggest that loss of E-cadherin can elevate the cellular levels of beta-catenin in prostate cancer cells, which may directly contribute to invasiveness and a more malignant tumor phenotype by augmenting AR activity during prostate cancer progression.
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PMID:Linking beta-catenin to androgen-signaling pathway. 1179 9

Somatic mutations in the E-cadherin (CDH1) gene have frequently been reported in cases with diffuse gastric and lobular breast cancers. Recently, germline mutations have been identified in families with diffuse gastric cancers. In families with hereditary prostate cancer (HPC), a significant association of prostate cancer, gastric and/or breast cancer has been observed in epidemiological studies. The aim of this study was to investigate if germline mutations in CDH1 could explain the risk for cancer in HPC families with an excess of gastric and breast cancer. In total, 17 members from 13 HPC families and 3 members from 3 families with hereditary gastric cancer (HGC) were screened for germline CDH1 sequence alterations using PCR/Denaturing HPLC for initial screening of nucleotide variants followed by confirmatory direct sequencing analysis. The frequency of identified novel germline mutations were tested for in 136 cases with hereditary prostate cancer and 215 cases of sporadic prostate cancer with 422 age matched controls in an allelic discrimination assay. In total, 8 sequence variants were detected in 20 samples tested. In the HPC families, we found 2 missense mutations, A592T in exon 12 and a novel D777N in exon 15 and a mutation in intron 5, 687+92T>A. A previously known polymorphism in exon 13 and 3 sequence variations in introns and untranslated regions were also found, of which the significance is unknown. In HGC-023 with early onset diffuse gastric cancer a truncating mutation, R335X, was identified in exon 7. None of the missense mutations or 687+92T>A were found in the extended HPC material or in the sporadic prostate cancer cases with age-matched controls in the allelic discrimination assay. We found several germline mutations of unknown clinical significance in the CDH1 gene that probably do not explain the association of prostate, gastric and/or breast cancers in the HPC-families. Two missense mutations and a mutation in intron 5 were identified that do not influence the risk of hereditary or sporadic prostate cancer in general and are considered to be pedigree specific. In a family with hereditary gastric cancer of the diffuse type, we identified the first truncating germline mutation in a Scandinavian family.
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PMID:Germline mutations in E-cadherin do not explain association of hereditary prostate cancer, gastric cancer and breast cancer. 1194 60

Many cancers have altered expression of various cell adhesion molecules. One of these is CEACAM1, which has been found to be downregulated in several carcinomas, including prostate cancer. We explored its immunohistochemical expression in a set of 64 total prostatectomy specimens and compared it with that of the epithelial cell adhesion molecule E-cadherin and occludin, a tight junction-associated molecule. The luminal surface of the epithelial cells of normal prostate glands and ducts showed a dense expression of CEACAM1. This pattern prevailed in prostate cancer of Gleason grades 1 to 3 as long as the cells maintained their polarity and formed individual glands. With "fusion" of glands (ie, in the transition to Gleason grade 4), the expression of CEACAM1 was lost in polygonal nonpolar cells and was lost or focally very weak in cells lining a lumen in the cribriform complexes. E-cadherin, which outlined the basolateral cell membranes of contacting neighboring epithelial cells was also downregulated in prostate carcinomas. However, the loss of E-cadherin expression in higher grades was gradual and not related to the Gleason 3 to >4 transition. Occludin was also lost in polygonal (ie, unpolarized) cells of Gleason grades 4 and 5, but remained expressed in all cells facing a lumen in all grades of cancer, which CEACAM1 was not. In conclusion, downregulation of CEACAM1 as well as that of occludin in prostate cancer is associated with loss of cell polarity. It coincides with the formation of the complex glandular architecture of Gleason grade 4 pattern or complete loss thereof in Gleason grade 5 patterns. The proliferative activity, measured as Ki67 labeling index, showed a fourfold increase in the carcinoma cells with lost CEACAM1 expression, supporting previous observations that CEACAM1 regulates cell proliferation. Immunohistochemical analysis of CEACAM1 expression patterns may be useful in assessment of the malignant potential of prostate carcinoma.
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PMID:Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition. 1197 69

The following studies were undertaken using specimens of submucosal invasive colorectal cancer surgically or endoscopically resected from 104 patients: 1) measurement of the depth of submucosal invasion; 2-a) histological reevaluation of colon sm cancer by scoring of the degree of histological differentiation using a modified Gleason's grading system proposed for prostatic cancer; and 2-b) immunohistological evaluation of E-cadherin, a cell adhesion factor. Lymphatic node metastasis occurred in no case with the depth of submucosal invasion of less than 1,000 microns. In the histological reevaluation, high incidence of lymphatic metastasis was noted in the high-score group, while lymphatic node metastasis was not seen in any patients in the low-score group. Immunohistological evaluation of E-cadherin showed that the destructive pattern is correlated with lymphatic metastasis, suggesting that weakening of the cell adhesive factor was related to a decline in the degree of differentiation of the tumor. Findings obtained in the present study suggest that endoscopic therapy is indicated for colon cancer measuring less than 1,000 microns and that its indication can be expanded to colorectal cancer with the depth of submucosal invasion of more than 1,000 microns by adding histological reevaluation.
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PMID:[Clinicopathological study for reevaluation of the depth of submucosal invasion and histological classification of early colorectal cancer]. 1217 Jul 5

Aggregation of attachment-dependent animal cells represents a series of motility, collision, and adhesion events applicable to such diverse fields as tissue engineering, bioseparations, and drug testing. Aggregation of human prostate cancer cells in liquid-overlay culture was modeled using Smoluchowski's collision theory. Using well (LNCaP) and poorly differentiated (DU 145 and PC 3) cell lines, the biological relevance of the model was assessed by comparing aggregation rates with diffusive and adhesive properties. Diffusion coefficients ranged from 5 to 90 microm(2)/min for single LNCaP and PC 3 cells, respectively. Similar diffusivities were predicted by the persistent random walk model and Einstein relation, indicating random motion. LNCaP cells were the most adhesive in our study with reduced cell shedding, 100% adhesion probability, and enhanced expression of E-cadherin. There was an increase in DU 145 cells staining positive for E-cadherin from nearly 20% of single cells to uniform staining across the surface of all aggregates; under 30% of PC 3 aggregates stained positive. Aggregation rates were more consistent with adhesive properties than with motilities, suggesting that aggregation in our study was reaction-controlled. Relative to other assays employed here, aggregation rates were more sensitive to phenotypic differences in cell lines and described size-dependent changes in aggregation at a finer resolution. In particular, model results suggest similar aggregation rates for two-dimensional DU 145 and PC 3 aggregates and upwards of 4-fold higher rates for larger three-dimensional DU 145 spheroids, consistent with expression of E-cadherin. The kinetic model has application to spheroid production, to cell flocculation and as an adhesion assay.
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PMID:Aggregation kinetics of well and poorly differentiated human prostate cancer cells. 1235 69

The E-cadherin protein mediates Ca(2+)-dependent interepithelial adhesion. Association of E-cadherin with the catenin family of proteins is critical for the maintenance of a functional adhesive complex. We have identified a novel truncated E-cadherin species of 100-kDa (E-cad(100)) in prostate and mammary epithelial cells. E-cad(100) was generated by treatment of cells with ionomycin or TPA. Cell-permeable calpain inhibitors prevented E-cad(100) induction by ionomycin. Immunoblotting for spectrin and mu-calpain confirmed calpain activation in response to ionomycin treatment. Both the mu- and m-isoforms of calpain efficiently generated E-cad(100) in vitro. The E-cad(100) fragment was unable to bind to beta-catenin, gamma-catenin, and p120, suggesting that this cleavage event would disrupt the E-cadherin adhesion complex. Mutational analysis localized the calpain cleavage site to the cytosolic domain upstream of the beta- and gamma-catenin binding motifs of E-cadherin. Because E-cadherin is inactivated in many adenocarcinomas we hypothesized that calpain may play a role in prostate tumorigenesis. A prostate cDNA microarray data base was analyzed for calpain expression in which it was found that m-calpain was up-regulated in localized prostate cancer, and to an even higher degree in metastatic prostate cancer compared with normal prostate tissue. Furthermore, we examined the cleavage of E-cadherin in prostate cancer specimens and found that E-cad(100) accumulated in both localized and metastatic prostate tumors, supporting the cDNA microarray data. These findings demonstrate a novel mechanism by which E-cadherin is functionally inactivated through calpain-mediated proteolysis and suggests that E-cadherin is targeted by calpain during the tumorigenic progression of prostate cancer.
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PMID:The role of calpain in the proteolytic cleavage of E-cadherin in prostate and mammary epithelial cells. 1239 69

Biochemical and genetic changes precede histologically identifiable changes accompanying cell transformation often by months or years. De-expression of the extracellular matrix adhesive glycoprotein tenascin and the cell-to-cell adherent protein E-cadherin have been suggested as markers of early neoplastic change in prostate epithelial cells. Previous studies have been inconclusive, probably due to epitope masking. This study examined 2,378 biopsy cores from 289 prostates using a heat antigen retrieval protocol at low pH to improve the accuracy of detection. Tenascin and E-cadherin de-expression was correlated with purinergic receptor and telomerase-associated protein labelling, as well as prostate-specific antigen (PSA) levels and Gleason scores. E-cadherin was a poor marker, as it was expressed in all lesions except carcinomas of the highest Gleason score. Tenascin was maximally expressed in the extracellular matrix and acinar basement membrane in normal and prostatic intraepithelial neoplasia tissue. In prostate cancer tissue, tenascin expression did not correlate with Gleason score but was significantly de-expressed as purinergic receptor and telomerase-associated protein expression increased. Marked changes in tenascin, telomerase-associated protein, and purinergic receptor expression were apparent before any histological abnormalities were visible by haematoxylin and eosin (H&E) stain, making these potential markers for early and developing prostate cancer. Moreover, the potential increased accuracy of diagnosis of underlying prostate cancer using purinergic receptor translocation (PRT) assessment suggests that PSA levels may be more accurate than has generally been supposed when apparent false negatives arising from H&E-based diagnoses are correctly categorized.
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PMID:Markers for the development of early prostate cancer. 1257 39

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