Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

National screening programs resulting in an increased detection rate of prostatic adenocarcinoma have prompted the search for new methods of predicting disease outcome that can be applied to the initial narrow bore needle biopsy specimens. Cathepsin D, a lysosomal aspartyl protease and autocrine mitogen, has been studied in a wide variety of human neoplasms as an invasion and metastasis marker. Prostatic carcinoma needle biopsy tumor cell cathepsin D content was measured in 61 men using a semiquantitative image analysis assisted immunohistochemical procedure. Results were compared with preoperative serum prostatic specific antigen levels, tumor grade, DNA ploidy status, pathologic stage after radical prostatectomy and disease recurrence during a median 2.6 year follow-up. Biopsy cathepsin D levels significantly correlated with tumor grade (P = .022) and DNA ploidy status (P = .028) by logistic regression analysis. Post-prostatectomy pathologic stage and disease recurrence did not correlate with tumor cathepsin D levels. Final prostatectomy grade and DNA ploidy status independently predicted metastasis and post-operative disease recurrence (P < .001). Although this study did not find independent prognostic status for cathepsin D in prostate cancer, the correlation with tumor grade and DNA ploidy status is noteworthy and the inter-relationship of outcome variables may prove of interest and warrant further evaluation of this potential predictor or CO-predictor of disease outcome.
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PMID:Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies. Correlation with tumor grade, stage, PSA level, and DNA ploidy status. 754 34

We made an effort to identify a reliable source for obtaining large quantities of both free (PSA) and PSA-ACT complex for the preparation of the calibrator for the PSA assay. Using size exclusion chromatography, we found both free PSA and PSA-ACT complex in the conditioned cell medium of the LNCaP cell line, which was derived from a human metastatic adenocarcinoma of the prostate. An assay specific for PSA-ACT reacted only with the PSA-ACT complex from cells grown in serum-free medium, and not with the complex from the cell medium grown in 10% calf serum. We also found both free PSA and PSA-ACT complex in 15% of cytosols prepared from breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110 ng/ml. No correlation was found between cytosol PSA and concentrations of estrogen receptor, progestin receptor, epidermal growth factor receptor, cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic characterizations and the slope of their dose-response curves, it appears that both free PSA and PSA-ACT complex found in the cytosols are similar to PSA complex from the cell medium and the serum of prostate cancer patients. Ectopic PSA was also detected in pooled sera from patients with breast, ovarian, pancreatic, and colon carcinoma. The PSA concentrations in these serum pools increased with the level of their dominant tumor marker. In any event, the LNCaP cell medium appears to be a reliable source for obtaining both free and ACT-complexed PSA of human tumor origin for the preparation of PSA assay calibrators.
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PMID:PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and female serum. 756 42

Cathepsin D is a carboxyl protease that has been implicated as an important factor in tumor cell invasion. Sixty-nine cases of primary adenocarcinoma of the prostate were studied by the indirect immunoperoxidase method using a primary monoclonal anti-cathepsin D antibody. Immunoreactivity was graded from 0 (negative) to 4+ (intense reaction). The normal tubuloalveolar glands were, in general, negative. However, nine cases revealed focal staining of nonneoplastic luminal cells. Basal cells were negative except in areas of basal-cell hyperplasia, which were intensely positive. Thirty-nine of 78 carcinoma samples revealed 2+ or greater positive punctate lysosomal staining. In the 39 positive-stained cases, the reactivity was diffuse in three and focal in the remainder. The percentage of carcinoma cases whose worst lesions stained 2+ or greater showed a nonsignificant (P = 0.055) relation to Gleason grade but a significant (P = 0.031) relationship to pathologic stage. Thus, cathepsin D may prove to be a useful marker of prostate cancer progression.
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PMID:Immunohistochemical analysis of cathepsin D in prostate carcinoma. 782 8

Six men who had undergone hip replacements for degenerative joint disease or trauma subsequently had radical prostatectomies or cystoprostatectomies with bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or transitional cell carcinoma of the urinary bladder. The hip prostheses implanted in three patients were known to contain cobalt-chromium alloy and titanium. The pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark brown or black cut surfaces. These lymph nodes did not contain carcinoma but showed florid sinus histiocytosis characterized by large polygonal histiocytes filling and expanding sinuses and interfollicular regions. The foamy histiocytes contained cobalt-chromium and titanium microparticles by light microscopy, ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes uninvolved by the histiocytic reaction lacked the heavy metal microparticles. Four cases were found to have a small number of polyethylene particles, which might have contributed to the histiocytic response. By immunohistochemistry, the foamy cells displayed immunoreactivity for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and cathepsin D, providing additional support for their histiocytic derivation. To our knowledge, this is the first time that microparticles of cobalt-chromium and titanium that migrate from hip prostheses to pelvic lymph nodes have been shown to elicit a distinctive type of florid sinus histiocytosis. Pathologists should be aware of this characteristic foreign-body tissue response to avoid confusion with other types of sinus histiocytosis or with metastatic carcinoma.
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PMID:Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium. 827 30

Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.
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PMID:Lipofuscin pigment can be used as a prognostic marker in prostatic adenocarcinoma. 1697 16