Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunocytochemical assays were performed on frozen sections of inflammatory breast carcinomas (n = 22) using the following monoclonal antibodies (MoAb): anti-pHER2/neu, cathepsin, pS2, ER, PR and MoAb Ki67. The distribution of these proteins, known as prognostic indicators, was evaluated with an image analysis system (SAMBA, Alcatel TITN, France). On standard HE stained paraffin sections, only about 50% of inflammatory breast tumors exhibited intradermal tumor cell emboli. All tumors were strongly pHER/2neu positive. All tumors also, but to a lesser degree, were cathepsin and ki67 positive. Conversely, less than 40% were faintly ER, PR and pS2 immunoreactive. The results correlated with the high degree of malignancy of inflammatory breast carcinomas. Therefore the immuno-detection of these markers in addition to standard histological techniques appears to be a useful tool to evaluate the degree of malignancy of breast carcinomas.
 ...
PMID:Inflammatory breast carcinoma: an immunohistochemical study using monoclonal anti-pHER-2/neu, pS2, cathepsin, ER and PR. 135 40

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
 ...
PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97

Tumoral biological markers of breast cancer expand the predictive value of conventional prognostic factors, such as tumor size, axillary lymph node status, and histoprognostic grade. They include tumor estrogen and progesterone receptor levels, flow cytometric DNA analysis, to convey a prognostic value. Expression of the product of the gene pS2, which reflects the functional integrity of the estradiol receptor, indicates a good prognosis. In contrast, presence of growth factor receptors, such as the EGF receptor, or amplification of the HER2/neu or INT2 oncogene indicate a poor prognosis. Study of protein gp 170 and GST-pi predicts the response of tumors to chemotherapy, while the study of the potential doubling time (Tpot) provides an indication of the renewal capacity of the tumor. Markers of tumor invasiveness and metastatic potential include proteases (activators and inhibitors) produced either by tumor cells or by the cells of the stroma, gene nm 23, and membrane fatty acids. The place of the last markers in patients' treatment is not known yet. The knowledge of the tumor biological parameters along with clinical features should provide an accurate prediction of the aggressiveness of the tumor, allowing the best adjustment of treatment with the expected behavior of the disease.
 ...
PMID:[Intratumoral biological markers in breast cancers]. 148 91

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
 ...
PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

The distribution of PECAM-1/CD31 molecule was investigated in 133 breast carcinomas using monoclonal antibody and frozen sections. Anti-CD31 labels endothelial cells and reflects stromal angiogenesis. The CD31 immunoreactivity was evaluated by computer-assisted analysis of digitized microscopic images. The automatic screening of the whole preparation and the measurements of the mean CD31 immunostained surface was performed in each case. A similar procedure was achieved for p53, cathepsin D, P-gp, pHER-2/neu, Ki67, pS2 estrogen and progesterone antigenic sites immunodetection. The image analysis of positive CD31 surface was variable, ranging from 4% to 33% (mean 14.7%, SD = 5.43). The CD31 positive surface correlated (P < .01) with the Nottingham prognostic index, but not with the tumor size, the node status, the tumor grade, nor with the patient age. Also the CD31 immunoreactivity was independent of the pHER-2/neu, Ki67 antigen, p53, ER, PR and pS2 immunodetectable expression in tumors, but correlates with that of cathepsin D (P = .024) and P-gp (P = .028), which reflects the multi-drug resistance capacity of tumor cells. In conclusion, CD31 positive vessels assessed on frozen sections by image analysis constitute an excellent method of evaluating tumor stromal angiogenesis, and can be further used for clinical purposes. The results also suggest that the CD31/PECAM molecule may be involved in the spread of tumor by interacting with extracellular matrix lysis that results from the tumor cell proteasic activity and with multidrug resistance.
 ...
PMID:CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors. 772 41

The evaluation of molecular markers in breast carcinomas can be routinely assessed by (i) histochemistry for ploidy measurement (Feulgen stain) and for AgNORs counts, and by (ii) immunocytochemistry (Ki67, cathepsin D, pHER-2/neu, EGFR, ER, PR, pS2, p53). Immunocytochemical assays are correlated to biochemical assays and are particularly relevant in small tumors in which only small amount of tissue is available. Immunocytochemical assays provide for data additional to current histological methods, useful for prognostic evaluation and for the selection of node negative patients who may benefit from adjuvant therapy. Nevertheless, immunocytochemical assays can be used for clinical purposes only if they are standardized (frozen sections, image analysis).
 ...
PMID:[Molecular markers in breast cancer: practical aspects and morphologic evaluation]. 807 88

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.
 ...
PMID:Cell biological factors associated with the response of breast cancer to systemic treatment. 848 34

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.
 ...
PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mib1 (antiKi-67), pS2, GST pi, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P = 0.001). A high percentage of Mib1-positive tumour cells (> 40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P = 0.009 and P = 0.03). By multivariate analysis IHC-ER, Mib1 and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P = 0.0006), disease-free interval (DFI) (P = 0.03) and metastasis-free interval (MFI) (P = 0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.
 ...
PMID:Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi. 891 45

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


1 2 Next >>