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)

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

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

Over the past two decades, monoclonal antibody technology has had an increasing impact on clinical diagnostic and therapeutic options, and this is true in the realm of managing prostate cancer. Several targets such as prostate-specific antigen and prostatic acid phosphatase as well as, more recently, angiogenic antigens such as vascular endothelial growth factor have been examined for therapy. Prostate-specific membrane antigen, a type II integral membrane glycoprotein initially characterized by the monoclonal antibody 7E11, has shown promise. Recent evidence suggests that prostate-specific membrane antigen is also expressed in tumor-associated neovasculature of a wide variety of malignant neoplasms. With its expression in prostate secretory-acinar epithelium and the prostate and in the neovasculature associated with tumors, prostate-specific membrane antigen represents an excellent antigenic target for monoclonal antibody diagnostic and therapeutic options. As research continues, the role of monoclonal antibody imaging and therapy will become increasingly important in the management of prostate cancer.
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PMID:Monoclonal antibodies: will they become an integral part of the evaluation and treatment of prostate cancer--focus on prostate-specific membrane antigen? 1057 76

We will review the evolution, benefits, and limitations of PSMA testing in the past, as well as its current and future value. Prostate cancer has been the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It has a wide spectrum of biological behavior between latent (indolent) and progressive (aggressive). Further identification of prostate-specific membrane antigen (PSMA) as a prognostic proliferation marker may enhance our understanding of the types of prostate cancer. A review of PSMA testing in the past as well as currently was conducted. Studies were reviewed that deal with detection of PSMA in serum and seminal fluid, reverse transcriptase-polymerase chain reaction (RT-PCR), immunoscintigraphy, and immunohistochemical assays. PSMA is expressed primarily in benign and cancerous prostatic epithelial cells. It is up-regulated in hormone resistant states, and in metastatic situations or other clinical situations where there is tumor recurrence or extension. Based on current results, PSMA detected in the serum by western blotting can assist in the identification, staging, and monitoring of metastatic prostate cancer. In addition, PSMA shows a promising role in directed imaging and therapy of recurrent or metastatic disease.
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PMID:Prostate-specific membrane antigen (PSMA): current benefits and future value. 1061 92

This article reviews the utility of reverse transcription-polymerase chain reaction (RT-PCR) in prostate cancer. RT-PCR aims to detect occult micrometastases in non-prostatic sites. Due to its exquisite analytical sensitivity, RT-PCR is able to amplify and detect even low-level, prostate-specific messages present at these extraprostatic sites. In recent years, a fair amount of data on the clinical utility of the technique had been reported. The target tissues under investigation are peripheral blood, bone marrow aspirate, and lymph nodes. Favorite markers of choice are prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and human glandular kallikrein-2 (hK2). False positives among negative controls are low. For the most part, RT-PCR is inadequate in detecting tumor cells in the peripheral blood from patients who are known to have metastatic prostate cancer. All studies showed that RT-PCR could detect PSA, PSMA or hK2 mRNAs in the circulation of patients who have organ-confined or extraprostatic disease. Most studies showed that RT-PCR utilizing current markers could not be used as a prospective test to diagnose prostate cancer. However, a few studies also showed that the detection rate could be predictive and sensitive enough to differentiate patients with organ-confined disease from those with extraprostatic disease. Data from PSA- or PSMA-RT-PCR using lymph nodes as the tissue source is more encouraging. RT-PCR was able to detect PSA and/or PSMA positive samples that have not been detected by conventional pathology.
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PMID:Detection of extraprostatic prostate cells utilizing reverse transcription-polymerase chain reaction. 1061 93

We assessed both non- and peptide-specific immune responses in prostate cancer patients before and after immunotherapy with dendritic cells exogenously pulsed with the prostate-specific membrane antigen-derived peptides, PSM-P1 and PSM-P2. For all subjects, we observed that clinical responses were strongly associated with two indicators of immunocompetence: skin test responses to recall antigens and cytokine secretion by T cells after nonspecific stimulation. In a subset of responders, we observed cytokine secretion or cytotoxicity against the immunizing peptides or an immunodominant epitope from an influenza recall antigen. The clinical results support the use of monitoring for overall immunocompetence to help determine why a patient has or has not responded to therapy. Moreover, it could be useful as an inclusion criterion to select those more likely to benefit from treatment.
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PMID:Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. 1070 88

BACKGROUND: Molecular techniques have been developed recently to assess for circulating tumor cells. This "molecular staging" of prostate cancer uses the reverse transcription-polymerase chain reaction (RT-PCR) to detect cells that contain PSA or PSMA in the bloodstream. Currently, the clinical application of this concept is controversial. METHODS: The authors discuss the current status of molecular biologic methods to detect circulating prostate cancer cells. They report on the limitations of the technology and the advances that will allow the quantification of these circulating cells. RESULTS: Studies generally indicate an increasing level of PSA RT-PCR positivity as disease advances. However, reports have been significantly diverse, and there is no clear explanation for this disparity. CONCLUSIONS: The determination of the "circulating prostate cancer cell load" by RT-PCR or other techniques may prove to be useful in the management of patients with prostate cancer, but questions remain to be answered before we can develop and assess new therapeutic strategies that will advance the treatment of prostate cancer before metastasis becomes evident. A better understanding of the biology of tumor cells present in the circulatory system is also needed.
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PMID:Circulating Prostate Cancer Cells Detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR): What Do They Mean? 1076 Oct 99

BACKGROUND: The incidence of bladder and prostate cancer continues to rise, with little accompanying improvement in management strategies. Opportunities exist for testing various types of chemopreventive interventions. METHODS: The authors review the biology of progression to invasive disease for cancers of the bladder and the prostate and identify intermediate disease and surrogate endpoint markers. Candidate interventions and initial clinical trial results are described. RESULTS: Markers of cellular proliferation and differentiation, as well as antigens such as Le(x), M344, DD23, and bladder tumor antigen, are promising for bladder cancer. Testing with prostate-specific antigen and prostate-specific membrane antigen is promising for prostate cancer. Several prevention intervention trials are in progress for both cancers. CONCLUSIONS: Vitamins, polyamine synthesis inhibitors, and oltipraz are undergoing clinical tests for chemopreventive effects in bladder cancer, and a large trial of finasteride to prevent prostate cancer is completing accrual. Results from these studies will direct future research.
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PMID:Chemoprevention of Bladder and Prostate Carcinoma. 1076 11


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