Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity of lysosomal proteinases cathepsin B, L and D was studied in tissues of malignant tumors, cancer and normal lymph nodes and mucosal membrane obtained from 18 patients with gastric cancer. The enzymatic activity was distinctly higher in cancer tissues as compared with controls. Activity of cathepsin D was increased in tissues with diminished rate of the tumor differentiation, with pronounced cancer invasion and metastases to regional lymph nodes--the group of highly negative prognosis. At the same time, activity of cathepsin B was increased in tissues of patients with positive prognosis of gastric cancer; negative correlation of cathepsin B activity was observed in both groups of patients. This correlation may be considered as an additional prognostic factor.
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PMID:[Proteolytic enzyme activity in stomach cancer patients with various prognoses]. 807 38

Malignant tumors derived from 60 patients with primary ovarian cancer were assayed for lysosomal cysteine proteinases--cathepsins B and L (Cat B, Cat L) and lysosomal aspartyl proteinase--cathepsin D (Cat D) as compared with benign ovarian tumors in controls. Malignant ovarian tumors exhibited significantly increased Cat B and Cat L activity (18.5- and 9-fold, respectively, p < 0.001) and moderately increased Cat D activity (1.5-fold, p < 0.01) as compared with those of benign tumors. The data obtained indicate that malignant ovarian tumors with a high Cat B activity (higher than the critical level of 723.5 +/- 100.0 Opmol/min. mg protein) proved to be more malignant in nature (low cell differentiated tumors predominated with early metastases spreading and relapses). Retrospective analysis of the disease development in 38 patients with ovarian tumors revealed that patients with early relapses (within the first year after surgery) demonstrated higher Cat B activity in tumors as compared with both the critical level and with that of patients without relapses; in the latter group the increase was found to be 2.4-fold (p < 0.01). The rate of CatB activity increases proved to be 56% and 8% in patients with and without relapses, respectively. Therefore, evaluation of the critical level of CatB activity in patients with primary ovarian cancer may be employed for prognostic purposes.
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PMID:[Prognostic significance of determining cathepsin B activity in malignant ovarian tumors]. 812 4

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.
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PMID:The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group. 826 79

Acetone-fixed, cryostat sections of 81 snap-frozen invasive breast carcinomas were immunostained with monoclonal antibodies to Cathepsin D (CD), a protease believed to mediate extracellular matrix dissolution, and Type IV collagen, a constituent of basal lamina (BL). Most cases (48/81, 53%) exhibited focal, patchy BL distribution (1+) around tumor cell nests, although subsets with diffuse continuous (2+) peritumoral sheets (15/81, 19%) or near complete absence (0+, 23/81, 28%) were also observed. Elaboration of BL was correlated with favorable morphologic differentiation (0+ BL-57% poorly differentiated vs. 2+ BL-13% poorly differentiated, p = .01), absence of nodal or systemic metastases (0+ BL-78% metastatic vs. 2+ BL-40% metastatic, p = .02), and improved disease-free survival (0+ BL-63% recurred vs. 2+ BL-20% recurred, p = .05). In addition, neoplastic cells expressed CD more frequently in tumors which lacked detectable BL synthesis (0+ BL-91% CD+ vs. 2+ BL-57% CD+, p = .03). The observed relationships between morphologic growth pattern, BL synthesis and CD expression imply conventional grading in large parts reflects activity or extent of host tissue invasion by a given neoplasm. Widespread but heterogeneous distribution of BL in breast tumors also suggests partial equilibrium between neoplastic and host tissues in most cases.
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PMID:Immunohistologic analysis of invasive phenotype in breast carcinoma. A clinicopathologic study. 830 8

Immunostaining of two invasion-associated proteolytic enzymes, cathepsin D (CD) and urokinase-type plasminogen activator (uPA), was assessed in cryostat sections of 86 stage-heterogeneous breast carcinomas using monoclonal antibodies. Most tumors displayed a focal and/or heterogeneous staining pattern. Overall, staining was more frequent in host-derived stromal and inflammatory cells (uPA 54%, CD 89%) than neoplastic epithelium per se (uPA 24%, CD 70%). Intense (i.e., 2+) stromal, but not neoplastic, CD was significantly correlated with nodal or systematic metastases (node negative--10% versus node positive/systemic--33%, p = 0.04). Further, cumulative staining of more than one enzyme (CD + uPA) or more than one tumor component (stroma + epithelium) correlated with metastatic disease (no metastases--35% versus metastatic--72%, p = 0.005). Neither stromal nor epithelial CD alone was significantly correlated with short-term recurrence free survival, however additive CD staining (i.e., stromal + epithelial) was strongly predictive, overall (both + -75% recurred versus both weak/negative--16% recurred, p = 0.0004) and in node positive patients (p = 0.02). We conclude that (a) enzymes putatively mediating extracellular matrix dissolution may be derived from multiple sources and (b) the metastatic capacity and/or clinical aggressiveness of breast carcinomas may reflect overall proteolytic enzyme expression, suggesting that cooperative enzyme interaction may be required for invasive growth and/or metastasis.
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PMID:Immunohistologic evaluation of invasion-associated proteases in breast carcinoma. 834 78

We have previously isolated a series of MCF-7 human breast cancer cell variants which no longer require estrogen-supplementation for tumor growth in nude mice (Clarke et al. Proc Natl Acad Sci USA 86: 3649-3653, 1989). We now report that these hormone-independent and hormone-responsive variants (MIII, MCF7/LCC1) can invade locally from solid mammary fat pad tumors, and produce primary extensions on the surface of intraperitoneal structures including liver, pancreas, and diaphragm. Both lymphatic and hematogenous dissemination are observed, resulting in the establishing of pulmonary, bone, and renal metastases. The pattern of metastasis by MIII and MCF7/LCC1 cells closely resembles that frequently observed in breast cancer patients, and provides the first evidence of metastasis from MCF-7 cells growing in vivo without supplementary estrogen. The interexperimental incidence of metastases, and the time from cell inoculation to the appearance of metastatic disease are variable. The increased metastatic potential is not associated with an increase in either the level of laminin attachment, laminin receptor mRNA expression, or secreted type IV collagenolytic activity. We also did not detect a significant decrease in the steady-state mRNA levels of the metastasis inhibitor nm23 gene. However, when growing without estrogen in vitro, MCF7/LCC1 cells produce elevated levels of the estrogen-inducible cathepsin D enzyme.
Clin Exp Metastasis 1993 Jan
PMID:The invasive and metastatic properties of hormone-independent but hormone-responsive variants of MCF-7 human breast cancer cells. 838 Jul 60

The study of several human breast cancer cell lines containing oestrogen receptors has allowed characterization of a number of oestrogen-induced proteins (e.g. progesterone receptor, cathepsin D, pS2, Hsp27, c-Myc). In primary tumours these markers have different prognostic significance for predicting whether the tumour will be hormone responsive (e.g. pS2, progesterone receptor) and whether it will metastasize (e.g. cathepsin D). The mechanism of regulation of gene expression by oestrogens and anti-oestrogens in breast cancer is complex and varies according to the nature of both the gene and the cell in which it is transcribed. Our laboratory has identified the sequences mediating oestrogen activity in the proximal region of cathepsin D, including a non-consensus oestrogen-responsive element located at -260 which acts in synergy with other regulatory elements. In addition to the classical effect of oestrogen receptor in stimulating transcription of genes controlled by the oestrogen-responsive element, we found that estrogen receptor is able to modulate transcription of AP-1-responsive genes without interacting directly with DNA. Cross-talk between oestrogen receptor and members of the Fos/Jun family via protein-protein interactions may explain how anti-oestrogens inhibit the mitogenic effect of growth factors in the apparent absence of oestrogens and why tamoxifen is able to stimulate cathepsin D gene expression and induce apoptosis in certain oestrogen receptor-positive breast cancer cells. The nature and degree of this cross-talk appears to vary according to the gene, the cell type and the type of oestrogen receptor ligand involved. Studies of oestrogen-regulated genes are not only useful for classifying breast cancers according to their ability to metastasize and respond to therapies, but also should lead to new therapeutic approaches for hormone-dependent and hormone-resistant cancers.
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PMID:Oestrogen- and anti-oestrogen-regulated genes in human breast cancer. 858 2

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.
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PMID:Cathepsin D concentration in primary laryngeal cancer: correlation with clinico-pathological parameters, EGFR status and prognosis. 860 76

In order to determine possible overexpression of cathepsin D and PAI-1 (plasminogen activator inhibitor) in head and neck tumours, cytosols from 92 primary squamous cell carcinomas (SCC), 19 lymph node metastases and 24 adjacent normal tissue samples were examined. For both cathepsin D and PAI-1, significantly elevated concentrations in SCC compared to normal tissue were found, even in pairwise comparison. Moreover, significantly higher cathepsin D and PAI-1 concentration in lymph node metastases than in corresponding normal tissue were also present. The conclusion was drawn that cathepsin D and PAI-1 may play a specific role in the biology of head and neck SCC.
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PMID:Cathepsin D and PAI-1 expression in human head and neck cancer. 861 52

It has been suggested that cathepsin D expression in stromal cells affects the prognosis of breast cancer. With reference to colon and breast cancer, this study verified cathepsin D immunostaining in epithelial and stromal cells of primary tumours and lymph-node metastases from 46 colorectal carcinomas. Eight of 46 cases (17%) were cathepsin D+ both in cancer and stromal cells. No staining was found either in cancer or stromal cells of the remaining cases. The results presented here suggest the possible paracrine influence of another diffusible factor produced by cancer cells which stimulates cathepsin D production in stromal and cancer cells.
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PMID:The immunohistochemical expression of cathepsin D in colorectal cancer. 861 73


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