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Search Results: 1 - 10 of 194152 matches for " Lawrence D True "
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Differences in Upgrading of Prostate Cancer in Prostatectomies between Community and Academic Practices
Franklin Lee,Henry Gottsch,William J. Ellis,Lawrence D. True,Daniel W. Lin,Jonathan L. Wright
Advances in Urology , 2013, DOI: 10.1155/2013/471234
Abstract: Objective. To determine whether initial biopsy performed by community or academic urologists affected rates of Gleason upgrading at a tertiary referral center. Gleason upgrading from biopsy to radical prostatectomy (RP) is an important event as treatment decisions are made based on the biopsy score. Materials and Methods. We identified men undergoing RP for Gleason or disease at a tertiary care academic center. Biopsy performed in the community was centrally reviewed at the academic center. Multivariate logistic regression was used to determine factors associated with Gleason upgrading. Results. We reviewed 1,348 men. There was no difference in upgrading whether the biopsy was performed at academic or community sites (OR 0.9, 95% CI 0.7–1.2). Increased risk of upgrading was seen in those with >1 positive core, older men, and those with higher PSAs. Secondary pattern 4 and larger prostate size were associated with a reduction in risk of upgrading. Compared to the smallest quartile of prostate size (<35?g), those in the highest quartile (>56?g) had a 49% reduction in risk of upgrading (OR 0.51, 95% CI 0.3–0.7). Conclusion. There was no difference in upgrading between where the biopsy was performed and community and academic urologists. 1. Introduction Prostate cancer risk stratification prior to definitive treatment is crucial as treatment selection relies on these factors. Whereas the PSA and clinical stage can be easily repeated with minimal patient risk, repeating the prostate needle biopsy to confirm accurate Gleason grading is much more invasive. Thus, adequate sampling of the prostate during biopsy is paramount. Despite improvements in sampling techniques at prostate needle biopsy, discordance between the diagnostic biopsy Gleason score and radical prostatectomy (RP) Gleason score occurs in up to 40% of the cases [1]. Several factors are associated with an increased risk of pathologic upgrading. These include smaller prostates [2, 3], higher PSAs [3, 4], and higher volume cancer at biopsy [5]. In addition, interobserver variability in pathologic interpretation of PCa specimens plays a role in this discordance [6–8]. Central pathologic review by dedicated genitourinary pathologists has been shown to lead to more accurate grading of the biopsy Gleason score and subsequent higher concordance with RP Gleason score [9]. It is now common for tertiary centers to require internal review of all outside biopsies prior to treatment. Several technical aspects to improve prostate sampling have been instituted including laterally directed biopsies [10], increased
Differential expression of CD10 in prostate cancer and its clinical implication
Marc A Dall'Era, Lawrence D True, Andrew F Siegel, Michael P Porter, Tracy M Sherertz, Alvin Y Liu
BMC Urology , 2007, DOI: 10.1186/1471-2490-7-3
Abstract: Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions.CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08–10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters.These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical utility for stratifying prostate cancer to predict biological behavior of the tumor.The cluster designation (CD) antigens are cell surface molecules first defined on human leukocytes and later found to be expressed by a variety of human cell types in both normal and pathologic states. The human prostate has been CD immunophenotyped and differences in the expression of several CD molecules were seen between cancer and normal prostate tissue [1]. Among these is
Molecular and cellular characterization of ABCG2 in the prostate
Laura E Pascal, Asa J Oudes, Timothy W Petersen, Young Goo, Laura S Walashek, Lawrence D True, Alvin Y Liu
BMC Urology , 2007, DOI: 10.1186/1471-2490-7-6
Abstract: Immunolocalization of ABCG2 was performed on normal prostate tissue obtained from radical prostatectomies. Normal human prostate SP cells and ABCG2+ cells were isolated and gene expression was determined with DNA array analysis and RT-PCR. Endothelial cells were removed by pre-sorting with CD31.ABCG2 positive cells were localized to the prostate basal epithelium and endothelium. ABCG2+ cells in the basal epithelium constituted less than 1% of the total basal cell population. SP cells constituted 0.5–3% of the total epithelial fraction. The SP transcriptome was essentially the same as ABCG2+ and both populations expressed genes indicative of a stem cell phenotype, however, the cells also expressed many genes in common with endothelial cells.These results provide gene expression profiles for the prostate SP and ABCG2+ cells that will be critical for studying normal development and carcinogenesis, in particular as related to the cancer stem cell concept.Experimental evidence suggests that prostatic epithelial stem cells exist and are likely localized to the basal epithelium [1]. Basal, luminal secretory and a small population of neuroendocrine cells constitute the epithelial component of prostatic acini. Basal and luminal cells may belong to two functional cell types descended from a common stem cell type. We are interested in identifying and isolating this prostatic stem cell. Studies to date suggest that stem cells from diverse tissue sources may contain a common set of gene transcripts, which are required for maintenance of the stem cell phenotype [2]. Considerable research efforts have been directed towards discovery of markers associated with the putative prostate stem cell, including the side population (SP) phenotype [3], integrin α2β1 (CD49b/CD29) [4,5] and PROM1 (CD133) [6]. Identification and characterization of a stem/progenitor cell population is important to our understanding of not only normal prostate development but also the cancer process, particularly
The urologic epithelial stem cell database (UESC) – a web tool for cell type-specific gene expression and immunohistochemistry images of the prostate and bladder
Laura E Pascal, Eric W Deutsch, David S Campbell, Martin Korb, Lawrence D True, Alvin Y Liu
BMC Urology , 2007, DOI: 10.1186/1471-2490-7-19
Abstract: Two major data types were archived in the database, protein abundance localization data from immunohistochemistry images, and transcript abundance data principally from DNA microarray analysis. Data results were organized in modules that were made to operate independently but built upon a core functionality. Gene array data and immunostaining images for human and mouse prostate and bladder were made available for interrogation. Data analysis capabilities include: (1) CD (cluster designation) cell surface protein data. For each cluster designation molecule, a data summary allows easy retrieval of images (at multiple magnifications). (2) Microarray data. Single gene or batch search can be initiated with Affymetrix Probeset ID, Gene Name, or Accession Number together with options of coalescing probesets and/or replicates.Databases are invaluable for biomedical research, and their utility depends on data quality and user friendliness. UESC provides for database queries and tools to examine cell type-specific gene expression (normal vs. cancer), whereas most other databases contain only whole tissue expression datasets. The UESC database provides a valuable tool in the analysis of differential gene expression in prostate cancer genes in cancer progression.Public databases for the storage and retrieval of genomic and proteomic data have become an integral component of biomedical research. These databases can aid in the identification of genes and proteins responsible for disease and health and defining their function by enabling investigators in diverse research areas and interests with a range of computer expertise to have ready access to the stored information through one user interface. Previously, the Prostate Expression Database (PEDB) established a centralized archive of gene expression information for human prostate [1]. This database contains a large cDNA library of gene sequences obtained for normal/benign, benign prostatic hyperplasia (BPH), prostatic intraepith
Transcriptomes of human prostate cells
Asa J Oudes, Dave S Campbell, Carrie M Sorensen, Laura S Walashek, Lawrence D True, Alvin Y Liu
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-92
Abstract: Using monoclonal antibodies specific for basal (integrin β4), luminal secretory (dipeptidyl peptidase IV), stromal fibromuscular (integrin α 1), and endothelial (PECAM-1) cells, respectively, we separated the cell types of the prostate with magnetic cell sorting (MACS). Gene expression of MACS-sorted cell populations was assessed with Affymetrix GeneChips. Analysis of the data provided insight into gene expression patterns at the level of individual cell populations in the prostate.In this study, we have determined the transcriptome profile of a solid tissue at the level of individual cell types. Our data will be useful for studying prostate development and cancer progression in the context of single cell populations within the organ.Prostate cancer is the second leading cause of cancer death among American men [1,2]. Due to the high incidence of prostate cancer the biology of the organ has been extensively studied. Crucial to our understanding of the cancer process is the biology of prostate development, in particular, the gene expression changes that accompany epithelial cell differentiation. DNA microarray technology has revolutionized the field of gene expression profiling and has seen wide application in the study of prostate cancer [3-5] as well as other types of cancer [6]. A byproduct of these studies is the gene expression profiles of most tissues of the human body have been assessed (e.g., the Novartis GeneAtlas). The next step in understanding how a tissue functions at a molecular level is to determine the transcriptome profile of individual cell types that constitute the tissue. Cell-type specific transcriptomes will allow us to more precisely define prostate cell lineages, cell-cell interactions, autocrine or paracrine signaling pathways, and would be useful to identify biomarkers for diseases such as cancer.The main problem encountered in studies of cells from solid tissue has always been determining a method to separate the cells of interest from the
Stromal mesenchyme cell genes of the human prostate and bladder
Young Ah Goo, David R Goodlett, Laura E Pascal, Kelsey D Worthington, Robert L Vessella, Lawrence D True, Alvin Y Liu
BMC Urology , 2005, DOI: 10.1186/1471-2490-5-17
Abstract: Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR.The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13+ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer.Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development.The functional development of the prostate is governed by stromal mesenchyme induction and epithelial response. This stromal/epithelial interaction was demonstrated by heterotypic tissue recombinants engrafted in animal hosts in which the stromal element dictated the organogenesis of the implanted epithelial component [1]. For example, adult human bl
Androgen Receptor Variants Occur Frequently in Castration Resistant Prostate Cancer Metastases
Xiaotun Zhang, Colm Morrissey, Shihua Sun, Melanie Ketchandji, Peter S. Nelson, Lawrence D. True, Funda Vakar-Lopez, Robert L. Vessella, Stephen R. Plymate
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027970
Abstract: Background Although androgens are depleted in castration resistant prostate cancer (CRPC), metastases still express nuclear androgen receptor (AR) and androgen regulated genes. We recently reported that C-terminal truncated constitutively active AR splice variants contribute to CRPC development. Since specific antibodies detecting all C-terminal truncated AR variants are not available, our aim was to develop an approach to assess the prevalence and function of AR variants in prostate cancer (PCa). Methodology/Principal Findings Using 2 antibodies against different regions of AR protein (N- or C-terminus), we successfully showed the existence of AR variant in the LuCaP 86.2 xenograft. To evaluate the prevalence of AR variants in human PCa tissue, we used this method on tissue microarrays including 50 primary PCa and 162 metastatic CRPC tissues. RT-PCR was used to confirm AR variants. We observed a significant decrease in nuclear C-terminal AR staining in CRPC but no difference between N- and C-terminal AR nuclear staining in primary PCa. The expression of the AR regulated proteins PSA and PSMA were marginally affected by the decrease in C-terminal staining in CRPC samples. These data suggest that there is an increase in the prevalence of AR variants in CRPC based on our ability to differentiate nuclear AR expression using N- and C-terminal AR antibodies. These findings were validated using RT-PCR. Importantly, the loss of C-terminal immunoreactivity and the identification of AR variants were different depending on the site of metastasis in the same patient. Conclusions We successfully developed a novel immunohistochemical approach which was used to ascertain the prevalence of AR variants in a large number of primary PCa and metastatic CRPC. Our results showed a snapshot of overall high frequency of C-terminal truncated AR splice variants and site specific AR loss in CRPC, which could have utility in stratifying patients for AR targeted therapeutics.
Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes
Laura E Pascal, Young Goo, Ricardo ZN Vêncio, Laura S Page, Amber A Chambers, Emily S Liebeskind, Thomas K Takayama, Lawrence D True, Alvin Y Liu
BMC Cancer , 2009, DOI: 10.1186/1471-2407-9-317
Abstract: Prostate CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between histologically normal and tumor-associated stromal cells. For comparison, stromal cells were also isolated and analyzed from the urinary bladder.The tumor-associated stromal cells were found to have decreased expression of genes involved in smooth muscle differentiation, and those detected in prostate but not bladder. Other differential expression between the stromal cell types included that of the CXC-chemokine genes.CD90+ prostate tumor-associated stromal cells differed from their normal counterpart in expression of multiple genes, some of which are potentially involved in organ development.Prostate stromal mesenchyme fibromuscular cells provide a regulatory extracellular matrix and direct epithelial differentiation and development through growth factors and androgen stimulation [1]. The critical role stromal cells play in prostate development has been demonstrated by co-implantation in animals of stem cells and stromal cells to achieve functional glandular development [2-7]. Although prostate cancer is epithelial in origin, there is a growing body of evidence suggesting that the stromal microenvironment plays a significant role in the cancer process [8-12]. Prostate tumor-associated or 'reactive' stroma is characterized by a decrease in smooth muscle cell differentiation and an increase in myofibroblasts and fibroblasts, with characteristics of a wound repair stroma [13]. Defining the gene expression changes in the stroma of prostate cancer has been the focus of several recent studies and is an important step in defining the underlying mechanisms of stromal-epithelial interaction in cancer. Previous studies have characterized gene expression profiles of tumor-associated stromal cells isolated by laser-capture microdissection (LCM) [14,15] and cultures established from histologica
Application of affymetrix array and massively parallel signature sequencing for identification of genes involved in prostate cancer progression
Asa J Oudes, Jared C Roach, Laura S Walashek, Lillian J Eichner, Lawrence D True, Robert L Vessella, Alvin Y Liu
BMC Cancer , 2005, DOI: 10.1186/1471-2407-5-86
Abstract: Affymetrix GeneChip array and MPSS analyses were performed. Data was analyzed with GeneSpring 6.2 and in-house perl scripts. Expression array results were verified with RT-PCR.Comparison of the data revealed that both technologies detected genes the other did not. In LNCaP, 3,180 genes were only detected by Affymetrix and 1,169 genes were only detected by MPSS. Similarly, in C4-2, 4,121 genes were only detected by Affymetrix and 1,014 genes were only detected by MPSS. Analysis of the combined transcriptomes identified 66 genes unique to LNCaP cells and 33 genes unique to C4-2 cells. Expression analysis of these genes in prostate cancer specimens showed CA1 to be highly expressed in bone metastasis but not expressed in primary tumor and EPHA7 to be expressed in normal prostate and primary tumor but not bone metastasis.Our data indicates that transcriptome profiling with a single methodology will not fully assess the expression of all genes in a cell line. A combination of transcription profiling technologies such as DNA array and MPSS provides a more robust means to assess the expression profile of an RNA sample. Finally, genes that were differentially expressed in cell lines were also differentially expressed in primary prostate cancer and its metastases.Profiling the expression pattern of genes in a tissue or cultured cells is often a starting point for exploratory genomic studies. Serial analysis of gene expression (SAGE) [1] is a technology for gene expression studies that can provide whole transcriptome coverage; however, it is slow and relatively labor intensive because each clone that is generated during library construction must be sequenced. The invention of DNA microarray technology [2,3], in combination with sequence information for the human genome [4,5] has provided the ability to rapidly assess the transcriptome profile of an RNA sample. A recently developed technology called massively parallel signature sequencing (MPSS) [6] allows the transcriptome of
Correlation of mRNA and protein levels: Cell type-specific gene expression of cluster designation antigens in the prostate
Laura E Pascal, Lawrence D True, David S Campbell, Eric W Deutsch, Michael Risk, Ilsa M Coleman, Lillian J Eichner, Peter S Nelson, Alvin Y Liu
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-246
Abstract: Concordance between gene and protein expression findings based on 'present' vs. 'absent' calls ranged from 46 to 68%. Correlation of expression levels was poor to moderate (Pearson correlations ranged from 0 to 0.63). Divergence between the two data types was most frequently seen for genes whose array signals exceeded background (> 50) but lacked immunoreactivity by immunostaining. This could be due to multiple factors, e.g. low levels of protein expression, technological sensitivities, sample processing, probe set definition or anatomical origin of tissue and actual biological differences between transcript and protein abundance.Agreement between these two very different methodologies has great implications for their respective use in both molecular studies and clinical trials employing molecular biomarkers.Immunostaining and microarray analysis are techniques frequently used to characterize tissue phenotypes. Immunohistochemistry (IHC) is a method of assessing protein levels of gene expression that is based on the ability of antibodies to bind proteins expressed by cells in sections of frozen or formalin-fixed, paraffin-embedded tissues. IHC enables one to detect and localize a specific antigen to specific cell types. Gene arrays determine expression levels for thousands of genes simultaneously by detecting sequence segments or partial segments of mRNA in a sample. To fully understand the underlying mechanisms of biological processes, it is essential to determine whether observed changes in mRNA can also be seen in the translated protein, and to pinpoint what cell types are exhibiting these changes. Gene array analysis and immunostaining are powerful tools for determining gene and protein expression patterns in health and diseases. Establishing the extent of agreement between semi-quantitative immunostaining data and gene array data obtained from sorted cell populations and tissue specimens is important to account for possible discrepancies between these two very
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