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

Prostate-specific membrane antigen is a type II membrane protein with folate hydrolase activity produced by prostatic epithelium. The expression of this molecule has also been documented in extraprostatic tissues, including small bowel and brain. In the present study, an extensive immunohistochemical analysis was performed on a panel of well-characterized normal and malignant human tissues to further define the pattern of prostate-specific membrane antigen (PSMA) expression. Detectable PSMA levels were identified in prostatic epithelium, duodenal mucosa, and a subset of proximal renal tubules. A subpopulation of neuroendocrine cells in the colonic crypts also exhibited PSMA immunoreactivity. All other normal tissues, including cerebral cortex and cerebellum, had undetectable levels of PSMA. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases displayed tumor cell PSMA immunostaining. Eight of 18 prostate tumors metastatic to bone expressed PSMA. All of the other nonprostatic primary tumors studied had undetectable PSMA levels. However, intense staining was observed in endothelial cells of capillary vessels in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas, and 3 of 19 colon carcinomas. Extraprostatic PSMA expression appears to be highly restricted. Nevertheless, its diverse anatomical distribution implies a broader functional significance than previously suspected. The decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation. The neoexpression of PSMA in endothelial cells of capillary beds in certain tumors may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.
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PMID:Prostate-specific membrane antigen expression in normal and malignant human tissues. 981 41

Accurate staging is an important issue in managing patients with prostate cancer. Current staging modalities are poor predictors for locally advanced disease. In the present study, we investigated the role of a peripheral blood-based, nested reverse transcription-PCR (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) in prostate cancer staging. Our nested RT-PCR could detect both PSA and PSM mRNA in one LNCaP cell diluted in 10(6) mononuclear cells. None of the controls, including patients with benign prostate hyperplasia, normal male subjects, and female subjects, were positive for either marker, confirming the assay's specificity for prostate cancer. In patients with bony metastases, 100% were positive by combined PSA/PSM assays (64% by PSA and 91% by PSM). In patients with clinically localized prostate cancer, 29% were positive by combined PSA/PSM assays (13% by PSA and 23% by PSM). The combined PSA/PSM assay is more sensitive than the PSA assay alone in detecting circulating prostatic cells (P = 0.0071). PSM is a more sensitive marker than PSA (P = 0.042). We also correlated preoperative nested RT-PCR results with pathological findings in prostatectomy patients. Nested RT-PCR for PSA/PSM has an odds ratio of 20 in predicting tumor extracapsular penetration (P = 0.017). These results indicate that a nested RT-PCR result may provide the staging information unavailable from other modalities, including the clinical stage, initial serum PSA, and Gleason score. Additional investigation is needed to determine the ultimate role of this assay in the management of patients with prostate cancer.
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PMID:Combined nested reverse transcription-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in detecting circulating prostatic cells. 981 2

It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.
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PMID:Recognition of prostate-specific antigenic peptide determinants by human CD4 and CD8 T cells. 982 72

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.
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PMID:Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. 983 72

Detection of prostate-specific membrane antigen (PSM)-mRNA expression in blood samples using reverse transcription polymerase chain reaction (RT-PCR) is discussed as a new diagnostic marker of circulating micrometastases in prostate cancer patients. We applied the RT-PCR technique to different human tissues and obtained positive signals for PSM transcripts in human genital and multiple extra-genital tissue sites. The cDNAs were prepared from different human tissues and prostatic cell lines. RT-PCR and nested RT-PCR for PSM was performed with primers derived from the published PSM cDNA. The RT-PCR fragments obtained were cloned and showed 100% sequence homology to PSM. Southern blot hybridization with labeled probes was used to confirm the specificity of the amplicons. In addition to the known PSM expression in the human brain, PSM-mRNA was detected in cDNA isolated from human testis, epididymis and seminal vesicles and in the PC-3 prostatic cancer cell line. Furthermore, we found PSM-mRNA in heart, liver, lung, kidney, spleen, and thyroid gland. The results indicate that PSM expression is not restricted to the prostate gland, but represents a more general component of genital and extra-genital human tissues. This must be considered when RT-PCR and nested RT-PCR screening for PSM expression is performed as a diagnostic measure in blood from prostate cancer patients.
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PMID:Prostate specific membrane antigen (PSM) is expressed in various human tissues: implication for the use of PSM reverse transcription polymerase chain reaction to detect hematogenous prostate cancer spread. 1009 50

The detection of prostate-specific membrane antigen (PSM) mRNA in the peripheral blood of prostate cancer patients by a nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay is a useful and sensitive method for the identification of small foci of metastatic lesions. In this study, a nested RT-PCR assay was performed using the two different PSM-derived oligonucleotide primer sets reported by Israeli et al. and Loric et al. (termed PSM primers-1 and primers-2, respectively, in this report), and the differences in the specificity and sensitivity of these primer sets for detecting prostate cancer cells in the blood are discussed. The PCR assay using PSM primers-1 showed DNA bands for 4 of 7 cases of metastatic prostate cancer and amplified the untreated genomic DNA, while that using PSM primers-2 showed 6 bands without the amplification of the genomic DNA. In conclusion, PSM primers-2 is superior to PSM primers-1 for the detection of PSM mRNA in the peripheral blood of prostate cancer patients.
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PMID:Prostate-specific membrane antigen-derived primers in a nested reverse transcription polymerase chain reaction for detecting prostatic cancer cells. 1018 95

A better understanding of the molecular changes associated with the onset and progression of prostate cancer may provide us with a rational basis for the development of new diagnostic and therapeutic tools. Likewise, the recent identification of critical biochemical pathways, including angiogenesis, programmed cell death, cell adhesion and signal transduction, provide us with promising targets for therapeutic approaches. Furthermore, the identification and characterization of new tumor-specific antigens or prostate-cancer-specific gene promoters could be instrumental for the development of new treatment modalities. Many research groups are trying to identify genes that are involved in prostate cancer development and which may serve as new tumor markers and potential targets for therapy. In addition to prostate-specific antigen, prostate-specific membrane antigen and human kallikrein-2, the recently identified prostate stem cell antigen may also provide us with a new tool for the diagnosis and treatment of prostate cancer. Our own studies led to the identification of DD3, a gene that is strongly overexpressed in human prostatic cancers and the expression of which appears to be restricted to the prostate. Further studies are necessary to establish the clinical usefulness of these new prostate-cancer-specific genes for the management of prostate cancer patients.
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PMID:Changes in gene expression and targets for therapy. 1032 97

Vaccine therapy may provide an alternative for prostate cancer patients whose disease no longer responds to hormone therapy. Administration of dendritic cells pulsed with prostate-specific membrane antigen (PSMA) induces cellular immune responses against the tumor with virtually no adverse effects. About 30% of the evaluable patients were identified as partial responders, based on the National Prostate Cancer Project (NPCP) criteria. In addition, there was a 50% decrease of serum prostate-specific antigen or resolution of previously measurable lesions on imaging. Dendritic cell vaccine therapy may have a synergistic effect, when combined with other therapies.
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PMID:Vaccine therapy for prostate cancer. 1036 59

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein that was initially characterized by the monoclonal antibody (mAb) 7E11. PSMA is highly expressed in prostate secretory-acinar epithelium and prostate cancer as well as in several extraprostatic tissues. Recent evidence suggests that PSMA is also expressed in tumor-associated neovasculature. We examined the immunohistochemical characteristics of 7E11 and those of four recently developed anti-PSMA mAbs (J591, J415, and Hybritech PEQ226.5 and PM2J004.5), each of which binds a distinct epitope of PSMA. Using the streptavidin-biotin method, we evaluated these mAbs in viable prostate cancer cell lines and various fresh-frozen benign and malignant tissue specimens. In the latter, we compared the localization of the anti-PSMA mAbs to that of the anti-endothelial cell mAb CD34. With rare exceptions, all five anti-PSMA mAbs reacted strongly with the neovasculature of a wide spectrum of malignant neoplasms: conventional (clear cell) renal carcinoma (11 of 11 cases), transitional cell carcinoma of the urinary bladder (6 of 6 cases), testicular embryonal carcinoma (1 of 1 case), colonic adenocarcinoma (5 of 5 cases), neuroendocrine carcinoma (5 of 5 cases), glioblastoma multiforme (1 of 1 cases), malignant melanoma (5 of 5 cases), pancreatic duct carcinoma (4 of 4 cases), non-small cell lung carcinoma (5 of 5 cases), soft tissue sarcoma (5 of 6 cases), breast carcinoma (5 of 6 cases), and prostatic adenocarcinoma (2 of 12 cases). Localization of the anti-PSMA mAbs to tumor-associated neovasculature was confirmed by CD34 immunohistochemistry in sequential tissue sections. Normal vascular endothelium in non-cancer-bearing tissue was consistently PSMA negative. The anti-PSMA mAbs reacted with the neoplastic cells of prostatic adenocarcinoma (12 of 12 cases) but not with the neoplastic cells of any other tumor type, including those of benign and malignant vascular tumors (0 of 3 hemangiomas, 0 of 1 hemangioendothelioma, and 0 of 1 angiosarcoma). The mAbs to the extracellular PSMA domain (J591, J415, and Hybritech PEQ226.5) bound viable prostate cancer cells (LNCaP and PC3-PIP), whereas the mAbs to the intracellular domain (7E11 and Hybritech PM2J004.5) did not. All five anti-PSMA mAbs reacted with fresh-frozen benign prostate secretory-acinar epithelium (28 of 28 cases), duodenal columnar (brush border) epithelium (11 of 11 cases), proximal renal tubular epithelium (5 of 5 cases), colonic ganglion cells (1 of 12 cases), and benign breast epithelium (8 of 8 cases). A subset of skeletal muscle cells was positive with 7E11 (7 of 7 cases) and negative with the other four anti-PSMA mAbs. PSMA was consistently expressed in the neovasculature of a wide variety of malignant neoplasms and may be an effective target for mAb-based antineovasculature therapy.
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PMID:Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. 1039 65

Cells from the prostate tumor cell line LNCaP have been grown as spheroids. The growth kinetics of the spheroids have been characterized by fitting a Gompertz equation to spheroid growth curves. The proliferation state of cells within spheroids of different diameters was assessed by bromodeoxyuridine staining. Scanning and electron transmission microscopy were performed to determine the ultrastructure of the spheroids. Prostate-specific antigen (PSA) secretion was monitored throughout spheroid growth. Consistent with Gompertzian kinetics, the volume of LNCaP spheroids initially increased exponentially and then reached a plateau. The doubling time during the exponential phase was 29 +/- 4 h. A core of nonproliferating cells was seen in spheroids with a diameter of 400 microm; at a diameter of 600 microm, a necrotic core had formed. In smaller, 200-microm diameter spheroids, a core of nonproliferating cells was not seen, but proliferating cells were concentrated at the spheroid periphery. Electron microscopy showed that the spheroids were enveloped by an extracellular matrix and that cell adhesion within the spheroids was due in part to desmosomes. PSA secretion by the spheroids could be modeled as originating from a spherical shell whose thickness was independent of overall spheroid diameter. The shell thickness obtained by fitting an appropriate equation to the data was consistent with that determined from the bromodeoxyuridine studies. LNCaP cells exhibit several important features of prostate cancer cells; in vivo, they are androgen responsive, and they express prostatic acid phosphatase, PSA, and prostate-specific membrane antigen. LNCaP spheroids provide a simple but relevant model for the study of drug delivery and response in prostate cancer.
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PMID:Growth and characterization of LNCaP prostate cancer cell spheroids. 1054 60


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