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 cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.
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PMID:Prostate-specific membrane antigen: current and future utility. 950 77

A 59-year-old man presented with a Gleason score of 4 + 4 = 8 prostate cancer and with multiple bilateral pelvic nodes involved at open pelvic lymph node dissection. On indium-111 capromab pendetide (ProstaScint) scan, there was increased tracer deposition in the prostate, the mesenteric nodes, the right pulmonary hilum, and the left supraclavicular fossa. The ProstaScint injection was repeated, and the gamma probe was used to localize tissue that accumulated radiotracer. Two nodes were excised, one that exhibited increased uptake and one that did not. The radioactive lymph node contained metastatic prostate cancer. No malignancy was found in the second node.
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PMID:Radioimmunoguided surgery using indium-111 capromab pendetide (PROSTASCINT) to diagnose supraclavicular metastasis from prostate cancer. 1101 34

Prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein highly restricted to prostatic epithelial cells. PSMA expression is increased in association with prostatic cancer, particularly in hormone refractory disease. Given its membrane-bound character, PSMA is an ideal sentinel molecule for use in targeting prostatic cancer cells. Monoclonal antibodies specific for PSMA are available, beginning with the antibody 7E11.C5 which originally defined PSMA and which has been developed for use in cancer detection via immunoscintiscanning in the ProstaScint test. Newer second generation antibodies specific for both linear amino acid sequence epitopes and protein conformational epitopes on the extracellular domain of PSMA have been reported. Although most of these are murine antibodies, both humanised and fully human examples have been developed. These antibodies are beginning to work their way into clinical applications for potential improved diagnostic and therapeutic uses. Results to date suggest that antibodies specific for extracellular epitopes are significantly better for clinical uses in vivo than the 7E11.C5 antibody that is specific for an intracellular epitope. Current knowledge relating to PSMA-specific antibodies and their clinical uses and potential is described and evaluated.
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PMID:PSMA specific antibodies and their diagnostic and therapeutic use. 1122 49

We describe our initial experience using ProstaScint scanning in addition to conventional imaging modalities for staging of high risk prostate cancer. Using our protocol, ProstaScint images detected abnormalities in pelvic lymph nodes not seen on CT scan or magnetic resonance imaging (MRI) in two patients. Subsequent surgical pelvic lymphadenectomy confirmed these abnormalities. Further patients will be accrued on this study to estimate the sensitivity and specificity of ProstaScint scanning.
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PMID:Surgical confirmation of ProstaScint abnormalities in two patients with high risk prostate cancer. 1126 8

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.
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PMID:The role of imaging studies and molecular markers for selecting candidates for radical prostatectomy. 1159 Aug 6

(111)In Capromab Pendetide (ProstaScintR) is a whole murine antibody that is reactive with prostate specific membrane antigen (PSMA), a glycoprotein on the surface of normal and abnormal prostate epithelium. It has proven to be of great value in assisting management decisions in prostate cancer patients who initially present with high risk for metastatic spread, or who develop a picture of recurrent disease after surgery or radiation therapy. Patterns of metastatic lymphatic spread have correlated well with autopsy reports in the literature. Unfortunately, other imaging study and/or histologic confirmation of scintigraphic findings has been difficult to obtain. Prostascint's role in predicting durable complete response (DCR) in postoperative patients having salvage radiotherapy to their prostate fossa is very promising. Further investigative work in larger patient populations is needed to confirm these early results.
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PMID:The role of (111)In Capromab Pendetide (Prosta-ScintR) immunoscintigraphy in the management of prostate cancer. 1211 76

Monoclonal antibodies (mAbs) to prostate-specific antigens, such as PSMA, have great potential as diagnostic and therapeutic tools in the management of advanced prostate cancer. PSMA is a very attractive target for mAb-based imaging. It is expressed by virtually all prostate cancers and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas. The ProstaScint scan (Cytogen, Princeton, NJ), based on the mAb 7E11-C5.3, is currently approved for the imaging of prostate cancer in soft tissue but is not approved for imaging bone metastases. It appears superior to conventional imaging studies for soft-tissue disease but has limitations attributed to its intracellular binding site on PSMA. Overcoming this limitation, new mAbs to the extracellular domain of PSMA have been developed. The radioisotopes, (111)Indium, (90)Yttrium, and (177)Lutetium have been conjugated to one such mAb, J591. Radioimmunoscintigraphy with this immunoconjugate has demonstrated excellent tumor targeting of prostate cancer sites not only in soft tissue but also in bone.
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PMID:The utility of monoclonal antibodies in the imaging of prostate cancer. 1221 74

A 77-year-old man with Gleason score 7 prostate cancer, after radical prostatectomy, in whom the prostate-specific antigen level increased to 5.0 ng/mL 8 years later, underwent a ProstaScint scan. Radiotracer deposition was noted in the prostatic "fossa," highly suspicious of recurrence. An additional focus in the mid abdomen was suspicious of adenopathy. Computed tomography disclosed an abdominal mass that, at biopsy, proved to be a malignant B-cell lymphoma. That lesion resolved after chemotherapy, and the prostate-specific antigen level substantially decreased with hormonal treatment. The possible association of prostate cancer and lymphoma is discussed.
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PMID:Detection of a non-Hodgkin's lymphoma by capromab pendetide scintigraphy (ProstaScint) in a patient with prostate carcinoma. 1235 May 3

Prostate cancer remains the most common cancer type in men in the United States. Efforts are increasing to evaluate and to discover diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), is a transmembrane protein highly expressed in all types of prostatic tissue, especially cancer. The radio-immunoconjugate form of the anti-PSMA monoclonal antibody (mAb) 7E11, known as the ProstaScint scan, is currently being used to diagnose prostate cancer metastasis and recurrence. Early promising results from various Phase I and II trials have utilized PSMA as a therapeutic target. Recently, PSMA expression in endothelial cells of tumor-associated neovasculature has been described. PSMA's possible role in malignant angiogenesis newly expands the realm of its possible beneficial uses, especially as new anti-PSMA mAbs continue to be developed and refined.
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PMID:The clinical role of prostate-specific membrane antigen (PSMA). 1247 35

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using (111)Indium Capromab Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint trade mark scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.
Prostate Cancer Prostatic Dis 2002
PMID:Evaluation of preoperative ProstaScint scans in the prediction of nodal disease. 1249 3


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