Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexamethasone may selectively inhibit the expression of PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.
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PMID:Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas. 136 Aug 48

Features of 111 mammary carcinomas derived from breast cancer screening were compared with those of 69 carcinomas presenting 'clinically'. Screen detected cancers were smaller, had less likelihood of nodal metastases, included a higher proportion of in situ tumours and if invasive, tended to be of lower grade. Using immunohistochemical methods, the expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGFR) and cathepsin D were compared in the two groups. A similar proportion of screened and unscreened tumours expressed c-erbB-2 oncoprotein and EGFR but expression of the oestrogen regulated protein cathepsin D was significantly more frequent in the screened group (P less than 0.05). Although a relatively small series, the results suggest a biological difference between 'screened' and 'clinical' tumours.
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PMID:Immunohistochemical and other features of breast carcinomas presenting clinically compared with those detected by cancer screening. 168 Mar 69

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

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.
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PMID:Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors. 766 16

Differential reactivity for cathepsin D (cath-D) and epidermal growth factor receptor (EGFR) was compared in 102 archival cases of human primary prostatic carcinoma and nine prostate carcinoma metastases by immunohistochemical techniques using commercially available antibodies (Ciba-Corning, Triton Diagnostics Division, Alameda, CA). Western immunoblotting confirmed that the anti-cath-D and anti-EGFR antibodies recognized the appropriate-sized proteins in extracts of human prostatic carcinoma cell lines. For immunohistochemical analysis, the primary prostate carcinomas ranged from Gleason's combined scores of 2 to 9. High-grade prostatic intraepithelial neoplasia was coexistent in 79 of the cases. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). Heterogenous moderate to strong reactivity with anti-cath-D was detected in 96 of 102 cases of primary prostate carcinoma (94%), with a mean H score of 176.5. EGFR reactivity was much less common and less strong, with 41 of 102 primary prostate carcinomas staining (40%) at a mean H score intensity of 29.2. The immunohistochemical (H) scores of cath-D and EGFR reactivity both significantly correlated with the Gleason's combined score of the tumors. There was no significant correlation between the cath-D and EGFR scores. Ninety-nine percent of the examples of prostatic intraepithelial neoplasia were reactive with anti-cath-D, with no clear correlation between the intensity of staining of prostatic intraepithelial neoplasia and the adjacent carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of cathepsin D and epidermal growth factor receptor in prostate carcinoma. 789 62

Cathepsin D and the epidermal growth factor receptor (EGFr) have both been proposed as poor prognostic markers in breast cancer. We have compared the tumour cytosolic cathepsin D level with EGFr and oestrogen receptor (ER) levels and the axillary node status of 131 patients with operable breast cancer, to see if EGFr and cathepsin D are co-regulated. Cathepsin D level was measured using a two-site immunoradiometric assay kit. No correlation was found between the level of cathepsin D and EGFr, ER or nodal status. Since the raised level of cytosolic cathepsin D was not related to EGFr, it may be that measuring the level of both of these markers in the same sample will give additional prognostic information.
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PMID:Cathepsin D levels in primary breast cancers: relationship with epidermal growth factor receptor, oestrogen receptor and axillary nodal status. 839 46

Biopsy specimens from 177 bladder tumours were analysed by immunohistochemical methods for the expression of cathepsin D. Strong expression of cathepsin D was detected in transitional carcinoma cells in 40 per cent of cases. Umbrella cells were positive in 29 per cent of cases and a cathepsin D-positive cell zone composed of tissue macrophages was detected at the invasion front in 34 per cent of tumours. Strong expression of cathepsin D was related to muscle invasive growth phase (T > or = 2) (P = 0.019), grade 2-3 histology (P = 0.008), S-phase fraction over 10 per cent (P = 0.032), and overexpression of epidermal growth factor receptor (EGFR) (P < 0.001). Umbrella cells were positive in low-grade (P = 0.03) papillary tumours (P = 0.02) with an S-phase fraction < or = 10 per cent (P = 0.02). Cathepsin D was expressed in macrophage-like cells in the invasion front in tumours which were densely infiltrated by inflammatory cells (P = 0.017) and in tumours overexpressing EGFR (P = 0.017) or p53 protein (P = 0.007). Progression in N- (P = 0.04) and M-categories (P = 0.01) was related to strong expression of cathepsin D in cancer cells and in univariate survival analysis; this was weakly related to poor outcome (P = 0.09). In multivariate analysis, papillary status (P = 0.055) and S-phase fraction (P = 0.079) predicted prognosis in Ta-1 tumours. In T2-4 tumours, T-category (P < 0.001), papillary status (P < 0.001), S-phase fraction (P = 0.028), and the presence of cathepsin D-positive tissue macrophages (P = 0.017) were independent prognostic factors.
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PMID:Expression of cathepsin D in transitional cell bladder tumours. 877 18

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

In 215 patients with operable breast cancer (T1-T3, N0-1, M0) and no other or previous cancer, presenting to a single breast unit, sufficient tumour was available for the prospective determination of four putative biochemical markers of prognosis: oestrogen receptor (ER) activity, cathepsin D (cath D), epidermal growth factor receptor (EGFR) activity and cyclic AMP-binding proteins (c-AMP-b). There were significant inter-relationships between ER and EGFR (r = -0.26), c-AMP-b and cath D (r = +0.32) and ER and c-AMP-b (r = +0.14). After follow-up (median 36.2 months), a total of 55 recurrences (18 locoregional only) and 35 deaths were recorded. By univariate analysis, up to 10 of 18 biochemical, clinical and histopathological variables of potential prognostic value were significantly related to disease-free interval or death, but by multivariate analysis only oestrogen receptor concentration and node status contributed significantly to risk of both distant recurrence/death; in addition, tumour size made a small contribution to the risk for a distant recurrence only. Only two parameters, tumour grade and ER concentration, were significantly related to risk of locoregional recurrence by univariate analysis, but by multivariate analysis, only tumour grade was important. It is concluded that tumour ER concentration, axillary nodal status and tumour grade remain as the most important prognostic factors in the early years after presentation of operable breast cancer, with a minor influence of tumour size. At this time, the prognostic significance of quantitative measurements of ER concentration, carefully controlled for the quality of both assay and tumour specimen, is probably greater than is generally appreciated. We have yet to identify other factors, which add significantly to the short-term prognostic value of these key features.
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PMID:Prospective evaluation of prognostic factors in operable breast cancer. 891 47

The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
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PMID:Specific oncological contribution of cathepsin D and pS2 in human breast cancer: their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification. 892 Feb 30


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