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

Plasma and ascitic fluid of rats bearing the Yoshida ascites hepatoma AH-130 were shown to contain high levels of proteolytic enzymes belonging to different classes active at neutral and acidic pH. Relative to those measured in control rat plasma, in tumor-bearing animals, the activity levels of lysosomal cathepsins B and L, in their latent, acidic-activatable form, were approximately 5-fold higher in plasma and 9-fold higher in ascitic fluid, and cathepsin D activity was about 5-fold higher in both plasma and ascitic fluid. Plasma and ascitic fluid of tumor-bearing rats also contained novel neutral and acidic gelatinolytic activities. The latter, as revealed by zymographic analysis conducted at pH 6.0, in the presence of dithiothreitol and in the absence of divalent metal ions, was sensitive to iodoacetamide inhibition but not to EDTA, showed a molecular mass of approximately 90 kD on SDS-PAGE, and was lost upon limited proteolysis with pepsin. Therefore, this enzyme is not identifiable as cathepsin B or L or their related latent forms and may represent a novel, so far undescribed, gelatinase. Its presence exclusively in the body fluids of AH-130-bearing rats suggests its possible use as a tumor marker.
Invasion Metastasis 1995
PMID:High levels of proteolytic enzymes in the ascitic fluid and plasma of rats bearing the Yoshida AH-130 hepatoma. 862 Dec 67

The purpose of this study was to investigate a prognostic indicator that can differentiate node negative breast cancer patients (N = 39, T2N0M0) with high risk and low risk for the development of recurrence or metastases. Preoperative plasma prolactin (PRL) was estimated by radioimmunoassay. The expression of PRL, p53, nm23, and c-erbB2 was investigated by immunohistochemical (IHC) localization; cathepsin D (CD, Enzyme Linked Sorbant Assay) and estrogen- and progesterone-receptors (ER and PR, Dextran coated charcoal method) were estimated in the tumor cytosols. The follow-up period was 2-6 years. Statistical comparisons were made between each marker for relapse-free survival (RFS) and overall survival (OS). Of the 39 patients, 18 had hyperprolactinemia (PRL > 20.0 ng/ml plasma), whereas overexpression of p53 was observed in 55% (17/31) tumors. These were independently and in combination associated with a reduced RFS and OS. The rest of the investigated markers did not show promising results. Hyperprolactinemia and/or overexpression of p53 were associated with aggressiveness of the tumor, early disease relapse or metastases, and poor OS in patients with node negative breast cancer. These two markers may enhance our ability to identify node negative breast cancer patients with aggressive tumors, for whom the use of adjuvant chemo and/or endocrine therapy is unequivocally justified.
 ...
PMID:Node negative breast carcinoma: hyperprolactinemia and/or overexpression of p53 as an independent predictor of poor prognosis compared to newer and established prognosticators. 864 46

The FACS-analysis of diseases as different as cancer, autoimmune disorders and chronic (retro)viral infections, including HIV-infection, shows -at least temporarily- a common feature of lymphocyte hyperactivation, characterized by cellular activation markers (HLA-DR, CD26, CD38, CD69, CD2R and/or CD30), as well as by solubilized membrane structures, such as beta-2m, sICAM-I, sIL-2R/sCD25, sCD8, and by some oversecreted immunocyte products (e.g. neopterin, lysozyme and/or cathepsin D). We tested two potential approaches to down-regulate the pathologically elevated CD8+ and HLA-DR+ T cells: (a) In animal model, we tested the sensibility of these, disease inducing and maintaining T cell subsets to in vitro pretreated (cell death preprogrammed) semi-syngeneic and allogeneic donor T cells in tumor-bearing mice. (b) In the first clinical study, we used a novel combination of FDA-approved drugs which inhibits Ca(2+)-influx and concomitantly down-regulates cytosolic cAMP in patient's overstimulated immunocompetent cells. We could achieve a 94.6-100% long-term survival in tumor-bearing mice. In patients, large primary tumors and large metastases shrinked by 80-85% and small metastases disappeared completely. Since in HIV-infected persons, the increased number of HLA-DR+ CD38+T (T8) cells is associated with a fall in CD4-level and with development of AIDS, we are looking for the elimination of these HLA-DR+ targets by our novel technique in two AIDS-simulating (FIV/FeLV and SIV) animal models.
 ...
PMID:Treatment of solid tumors should obligatorily be combined with the in vivo codepletion of tumor-protecting, CD8+/HLA-DR(+)-suppressor T cells by alloreactive donor T cells whose preprogrammed cell death allows a high GvL-effect before GvHD can be established. Results of animal experiments, including more than 6000 mice. 873 48

We inoculated the KLE human endometrial cancer, MCF-7 and ZR-75 human breast cancer, and PC-3 human prostate cancer cells into three-dimensional type I collagen gel system that contained uniformy dispersed MG-63 osteoblast-like cells. Then, we analyzed the morphological evidence of osteoblasts reaction, local invasion around the inoculated cancer cells and expression of the cathepsin D and urokinase-type plasminogen activator (uPA) around the sites of inoculation using immunocytochemistry. The prostate cancer cells produced morphological evidence of blastic reaction presented as an increased number of MG-63 osteoblasts and increase density of type I collagen around the sites of inoculation with PC-3 cells. The inoculated MCF-7 and ZR-75 cells decreased the density of type I collagen and number of osteoblasts and invaded the collagen gel around the sites of inoculation. The KLE endometrial cancer cells and cell-free media produced no reaction at the inoculation sites suggestive of cancer cell-specific interactions with osteoblasts in this system. The expression of uPA was remarkably higher at the inoculation sites of PC-3 cells as compared with those of the other cancer cells. Cathepsin D expression was higher at the sites of inoculation with KLE, MCF-7 and PC-3 cancer cells. MG-63 osteoblasts contained relatively low expression of uPA and cathepsin D. We conclude that this collagen gel system is a useful model for studying the morphological evidence of local invasion and osteoblasts reaction produced in response to local growth of metastatic cancer cell in vitro.
 ...
PMID:Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells. 891 85

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.
 ...
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

Determination of cathepsin D has been proven to be prognostically relevant in breast cancer. Cathepsin D, a lysosomal proteinase, is suggested to be causally involved in tumor invasion. In this study we investigated cathepsin D expression immunohistochemically in 106 colorectal adenocarcinomas with the intention to evaluate its prognostic significance in this type of cancer. The majority of colorectal adenocarcinomas (93/106) stained positive for cathepsin D, while normal colon was almost completely negative. A trend toward stronger staining intensity was found in Dukes' stage C and D tumors (p < 0.1), but cathepsin D expression was found to have no influence on survival in this tumor type nor did it correlate with other known prognostic factors, e.g., histological differentiation, lymph vessel invasion, or rate of proliferation. Staining of lymph node metastases did not differ significantly from that of their primary tumors. Stronger staining intensity of tumor tissue in the neighborhood of inflammatory cells may be due to paracrine activation.
 ...
PMID:Immunohistochemical evaluation of cathepsin D expression in colorectal cancer. 909 5

The total cellular p185(HER-2/neu) protein (p185) content was measured by ELISA in 346 invasive primary breast cancers, and the results were compared with those of estrogen (ER) and progesterone (PR) receptors, pS2 and Cathepsin D (Cat D) content. At a cut-off level of 260 fmol/mg protein, 53 of the 346 tumors (15%) were p185-positive. A significant positive correlation was observed between p185 levels and those of Cat D, and a weaker, though significant, positive correlation with ER, and pS2 levels, but not with those of PR. However, when only the 293 p185-negative tumors were considered, the correlation between p185 and ER improved substantially, and statistical significance was reached for PR. p185-positive tumors exhibited lower ER and PR content and higher Cat D content than p185-negative tumors. The pS2 content, in contrast, did not undergo significant variation. Tumors considered to be p185-positive were significantly more frequently positive for Cat D at the cut-off of 45 pmol/mg protein, and were more frequently negative for ER and/or PR, but only significant at the cut-off of 15 fmol/mg or higher for both steroid receptors. Finally, p185 status was not associated with menopausal status, tumor size, axillary-lymph-node invasiveness or distant metastases. These results suggest that 260 fmol/mg protein as the cut-off for p185 allows the identification of a tumoral sub-population with a more aggresive phenotype.
 ...
PMID:Quantitative analysis of p185(HER-2/neu) protein in breast cancer and its association with other prognostic factors. 913 51

We used enzymatic activity and immunochemical quantifications to analyse the expression and secretion of cathepsin D by human breast cancer cell lines of different invasive potentials (MCF-7/6, MCF-7/AZ, MDA-MB-231). This study does not directly prove that cathepsin D or procathepsin D is involved in human breast cancer cell invasion and metastasis but it shows that the proportion of procathepsin D (activity and antigen) secreted by the human breast cancer cell lines tested correlates with their invasive potential. In the estrogen receptor-positive MCF-7 subclones, this proportion is increased by estradiol only in the invasive MCF-7/6 variant. The cell content in procathepsin D is increased by estrogens to a greater extent in MCF-7/6 cells as compared to non-invasive MCF-7/AZ cells. Tamoxifen appears to be an estrogen agonist concerning cathepsin D regulation, whereas ICI 182,780 is a true antagonist. Our results suggest that synthesis and secretion of cathepsin D are regulated at two distinct levels and differentially affected by estrogens. Synthesis only seems to be affected in non-invasive MCF-7/AZ cells, whereas in invasive MCF-7/6 cells, both synthesis and the efficiency of secretion are increased by estrogens. Our results also confirm that the key site of regulation leading to lysosomal enzyme oversecretion is the Golgi apparatus insulin-like growth factor-II/mannose 6-phosphate receptor.
Clin Exp Metastasis 1997 Jul
PMID:Western immunoblotting and enzymatic activity analysis of cathepsin D in human breast cancer cell lines of different invasive potential. Regulation by 17beta-estradiol, tamoxifen and ICI 182,780. 921 23

We have proposed that an early step in estrogen carcinogenesis in the hamster kidney is tubular damage followed by reparative cell proliferation. This tubular injury is progressive and increases in severity with continued estrogen treatment; one pertinent feature is a marked rise in the number of both secondary and tertiary lysosomes. Data presented herein indicate that cathepsin D, an estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney following estrogen treatment in the hamster. Three isoforms of cathepsin D were detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa. At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4- to 1.6-fold. These changes coincided with a rise in renal estrogen receptor levels during the same estrogen treatment periods. More pronounced rises in cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen receptor content was also observed. At 5 months of estradiol or DES treatment, both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the 52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen treatment prevented the rise in cathepsin D and estrogen receptor content observed after estrogen treatment alone. Primary estrogen-induced renal tumors and their metastases exhibited markedly elevated levels of all three isoforms of cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections confirmed the Western blot findings. These data suggest a novel role for estrogen-induced cathepsin D in the hamster kidney during tumorigenesis; that is, mediating renal tubular damage as a prelude to reparative cell proliferation, thus initiating a multi-step estrogen-driven process which leads to renal tumor formation.
 ...
PMID:Induction of cathepsin D protein during estrogen carcinogenesis: possible role in estrogen-mediated kidney tubular cell damage. 923 Feb 83

Previously a higher preoperative sensitivity of the mucin like glycoprotein Mammary Serum Antigen (MSA) compared to established tumor markers was reported. The aim of our study was the comparison of MSA and CA 549, CA 15-3 and CEA in primary breast cancer and the correlation to prognostic factors. In 119 patients MSA and CA 549 serum levels were analysed by ELISA, CEA and CA 15-3 levels by LIA. We received the following sensitivities: 30.2% for MSA (cut off = 55 U/mL), 21.8% for CA 549 (cut off = 12.6 U/mL), 20.5% for CA 15-3 (cut off = 25 U/ml) and 10.7% for CEA (cut off = 6 ng/ml). Significant correlations were found between MSA concentrations and grading (p = 0.006), tumor size (p = 0.005) and metastases (p = 0.03). No correlations were found to tumor type, hormone receptors, lymph node status and cathepsin D. MSA is a valuable tumor marker with the highest preoperative sensitivity. Further studies on the value of MSA in the follow-up are necessary.
 ...
PMID:Mammary serum antigen (MSA), Ca 549, CA 15-3 and CEA in breast cancer preoperative sensitivity and correlation to prognostic factors. 932 73


<< Previous 1 2 3 4 5 6 7 8 9 Next >>