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

Hormonal receptors and markers for prognostic evaluation were detected immunohistochemically in 196 infiltrating ductal breast carcinomas. Immunohistochemical detection of progesterone and oestrogen receptor is a method giving results generally concordant with those of the binding assay. However, immunohistochemical detection seems better. It allows the detection of hormonal receptors on small carcinomas, it is not modified by the endogenous hormones, and it has a slightly better correlation with prognosis and with the response to hormone therapy. Immunohistochemical detection of progesterone receptor has a prognostic value, sorting a negative subgroup with a poor prognosis from the oestrogen receptor positive tumours. These results can be obtained without quantitative immunohistological methods. ERD5, pS2, HSP27 and cathepsin D are associated with oestrogen receptor positivity. pS2 and HSP27 are interesting markers. They characterize a subgroup of oestrogen receptor negative tumours with a good prognosis. Moreover, pS2 is a marker of response to hormone therapy. ERD5 and cathepsin D do not appear to be of value as markers of prognosis.
 ...
PMID:Oestrogen receptor, progesterone receptor, pS2, ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas. 822 42

Vimentin, p53 protein and cathepsin D positivity were assessed by immunohistochemistry, and oestrogen receptor (ER) by an enzyme immunoassay, in invasive lobular carcinomas (LC) of the breast. While vimentin was positive in only 5% (3/57) and p53 protein was positive only in 3% (2/63), cathepsin D was expressed in 86% (48/56) and ER in 78% (25/32). Classical LC were negative for p53 protein and all except one were cathepsin D positive. These results are in contrast to invasive ductal breast carcinomas (DC), where the reported average incidence of vimentin and p53 protein is much higher (19% and 33% respectively) and that of cathepsin D and ER lower (63% and 67% respectively). Thus lack of expression of vimentin and lack of p53 positivity together with high incidence of expression of cathepsin D and ER are more often associated with lobular than with ductal differentiation of invasive breast cancer. The results show that LC, distinguished morphologically, can further be defined by its immunohistochemical profile. This in turn may point to underlying biological differences between LC and DC.
 ...
PMID:Immunohistochemical profile of invasive lobular carcinoma of the breast: predominantly vimentin and p53 protein negative, cathepsin D and oestrogen receptor positive. 829 Dec 22

Of 139 node-positive breast cancer patients treated with adjuvant chemotherapy, the pre-treatment levels of glutathione S-transferase (GST) classes alpha, mu and pi, were determined by immuno-quantification on Western blots in cytosols of the primary tumours. Their expression was studied with respect to cytosolic oestrogen-receptor, progesterone-receptor and cathepsin D levels, and to the length of disease-free survival. GST class pi was negatively correlated with oestrogen receptor and progesterone receptor, and positively correlated with cathepsin D. There was no correlation between GST isoenzymes and the length of disease-free survival. These data suggest that glutathione S-transferases are not useful as markers to predict the response to adjuvant chemotherapy in human breast cancer.
 ...
PMID:Response to adjuvant chemotherapy in primary breast cancer: no correlation with expression of glutathione S-transferases. 831 26

Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present at high levels in breast cyst fluid, has been measured in 104 breast tumour cytosols by using an immunoenzymatic assay. Concentrations of Zn-alpha 2-gp ranged from 0 to 23.5 micrograms/mg of total soluble protein, with an average value of 2.4 micrograms/mg. There was no significant correlation between Zn-alpha 2-gp and menopausal status, tumour size or lymph node involvement, or between this protein and biochemical parameters such as oestrogen receptor, cathepsin D or pS2 levels. However, there was a significant association between Zn-alpha 2-gp and histological grade of tumours, with higher Zn-alpha 2-gp levels in well-differentiated tumours (mean 4.6 micrograms/mg) than in moderately (1.8 micrograms/mg) or poorly (0.9 micrograms/mg) differentiated tumours. On the basis of these results, we propose that Zn-alpha 2-gp may be considered as a biochemical marker of differentiation in breast cancer.
 ...
PMID:Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. 834 63

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.
 ...
PMID:Cathepsin D levels in primary breast cancers: relationship with epidermal growth factor receptor, oestrogen receptor and axillary nodal status. 839 46

A novel oestrogen-responsive breast-tumour cell line, EFF-3, has been established from a pleural exudate of a patient with metastatic breast cancer. The cells show morphological and immunohistochemical features consistent with their origin from a metastatic breast carcinoma. The cells aggregate and form sheets in culture, and electron microscopy confirms the presence of cell-surface microvilli and intercellular tight junctions. The epithelial origin of EFF-3 cells was confirmed by their expression of low-molecular-weight cytokeratins and carcinoembryonic antigen. The karyotype of the cells is markedly abnormal and there are large numbers of structurally abnormal chromosomes. EFF-3 cells express oestrogen receptor, oestrogen-receptor mRNA, their growth is oestrogen-responsive, and specific genes are regulated by oestrogens. The pNR-2/pS2 and pNR-25 oestrogen-regulated mRNAs are induced 15- and 13-fold respectively by oestrogen, whereas the oestrogen-receptor and cathepsin D mRNAs are not regulated. This pattern of regulation differs from that reported previously for other cell lines. The EFF-3 cell line should be useful for studying the mechanisms involved in oestrogen-stimulated proliferation and the factors determining the regulation of specific genes by oestrogens.
 ...
PMID:Isolation and characterization of an oestrogen-responsive breast-cancer cell line, EFF-3. 842 92

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.
 ...
PMID:Oestrogen- and anti-oestrogen-regulated genes in human breast cancer. 858 2

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.
 ...
PMID:Prospective evaluation of prognostic factors in operable breast cancer. 891 47

By using a commercially available immunoradiometric technique (Cath-D-IRMA, Cis BioInt.) the distribution of total cathepsin D (cath-D) in 30 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer was investigated. In both tissues the oestrogen and progesterone receptors were also assayed. In 17 out of the 30 samples, the cath-D was also assayed by immunohistochemistry using the M1G8, a mouse monoclonal antibody raised against cath-D (Cis BioInt.). Our data indicate that cath-D is present in prismatic cells of the normal laryngeal epithelium and in the cancerous cells. In cancerous larynx, the outer cell layer of large tumour nests showed the highest degree of immunoreactivity, while fibroblasts and inflammatory cells always showed a very faint staining. Cathepsin D levels were significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cath-D and progesterone receptor (PR) concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cath-D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regard the oestrogen receptor, no significant relationship between this and cath-D was observed. We conclude that cath-D measured by IRMA in tissue cytosols is mainly derived from cancerous cells, the contribution from fibroblasts and inflammatory cells being negligible. Cathepsin D overexpression and association with the PR in the malignant part of the larynx could indicate a possible role of the receptor in the biology of this disease.
 ...
PMID:Immunohistochemical and immunoradiometric evaluations of total cathepsin D in human larynx. 913 74

In 87 breast cancer patients, the immunohistochemical expression of the basement membrane (BM)-degrading enzyme cathepsin D (CD) was correlated with the expression of extracellular matrix components, with growth fraction, steroid receptor content and with the other conventional prognostic variables in breast cancer. Only 6.25% of tumours had laminin-defined BM, while 86.8% showed staining for fibronectin. CD was also identified in carcinoma cells (cancer cell CD; CCCD) and in stromal cells (stromal cell CD; SCCD). Forty-five percent of tumours showed CCCD and 47.5%, SCCD expression. CCCD expression was significantly correlated with positive oestrogen receptor content, with low Ki-67 and high PCNA score and with SCCD expression. There was no correlation with collagen type IV, laminin or fibronectin. SCCD expression was positively correlated with collagen type IV, laminin expression and tumour grade. The data suggest that the CD of tumour cells and the CD of tumour-associated macrophages have different roles in breast cancer. CCCD correlates with cell proliferation and is regulated by oestrogens, while SCCD relates to cell differentiation, is oestrogen-independent, and has a proteolytic role in the breakdown of BM components.
 ...
PMID:Immunohistochemical expression of cathepsin D in correlation with extracellular matrix component, steroid receptor status and proliferative indices in breast cancer. 946 71


<< Previous 1 2 3 Next >>