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

---

Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostate-specific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.
...
PMID:Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer. 888 11

Large core biopsy is a recently introduced method for pre-operative evaluation of breast lumps. The aim of this study was to evaluate the usefulness of this technique in providing pre-operative diagnostic and prognostic information that can lead to a correct line of treatment. We compared 41 cases of breast carcinomas diagnosed both by core biopsies and surgically removed samples. A high (93%) diagnostic agreement was obtained. Moreover, we found a significant correlation for mitotic count (r = 0.76), oestrogen receptor (r = 0.78), progesterone receptor (r = 0.80), p53 (r = 0.86) and c-erbB-2 (r = 0.90) analysis between core biopsy and definitive surgical pathology. An agreement for histological grading evaluation between the two techniques was obtained in 32 out of 40 cases (k = 0.65) whereas in the other cases, a lower grade was assigned by evaluating core biopsies. These findings suggest that percutaneous core breast biopsy is a valid tool for pre-operative management of breast lesions, but this should be confirmed in larger, prospective studies.
...
PMID:Large core biopsy for diagnostic and prognostic evaluation of invasive breast carcinomas. 898 76

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.
...
PMID:Tumour biological features of BRCA1-induced breast and ovarian cancer. 915 18

This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.
...
PMID:Cytological evaluation of biological prognostic markers from primary breast carcinomas. 916 79

The aim of this study was to evaluate p53 expression, determined by immunohistochemistry, in 151 infiltrating ductal breast carcinomas with negative axillary lymph nodes, and to determine whether p53 can be considered as an independent prognostic value for overall and disease-free survival. A monoclonal antibody (DO-7) that reacts with an epitope on the N terminal portion of the human protein p53 was used to detect p53 in paraffin-embedded sections, utilising a standard avidin-biotin-peroxidase complex (ABC) technique with a microwave oven antigen retrieval. Overexpression of p53 (more than 50% of stained cells) was found in 45 cases (30%). Forty-five cases were negative and occasionally or moderately stained cells were present in 61 cases. p53 protein overexpression was significantly associated with high histological grade and tumour necrosis, high MIB-1 value (MIB-1 > 30%) and negative oestrogen receptor status. Univariate analysis (log-rank) showed a shorter overall survival (P = 0.003) in patients with high tumour p53 positivity. This statistical significance was also seen on multivariate analysis (Cox's logistic regression, P = 0.004). p53 protein overexpression is an independent prognostic marker in node-negative breast carcinoma for overall survival and should be used with other prognostic factors.
...
PMID:p53 expression is of independent predictive value in lymph node-negative breast carcinoma. 930 54

Cyclin E is a G1 cyclin that is essential for the transition from G1 to S phase in the cell cycle. Alterations to cyclin E expression or regulation could be important in tumorigenesis. Previous immunohistochemical and immunoblotting studies have investigated the expression of cyclin E in breast carcinomas. In this study, cyclin E has been investigated in a range of non-malignant and malignant breast using immunohistochemistry. Normal and benign tissue from pre- and post-menopausal women (39 cases), non-involved tissue from cancer-containing breasts (47 cases), ductal carcinoma in situ (22 cases) and invasive breast carcinomas (109 cases) have been examined. There was no reactivity in any of the non-malignant breast. Only one ductal carcinoma in situ contained more than 5% reactive cells. A total of 28% of invasive carcinomas had > 5% of reactive cells (range 0-88% positive cells, mean 12.59%, median 1.0%). A significant association was found with poorer differentiation (P < 0.001), high MIB1 index (P < 0.001), lack of oestrogen receptor (0.05 > P > 0.025) and the presence of p53 protein (0.05 > P > 0.025). Virtually all cases with cyclin E and p53 were poorly differentiated. The presence of cyclin E is therefore only found in breast malignancies and is associated with more aggressive features, including high proliferation.
...
PMID:Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer. 937 73

To elucidate potential mechanisms involved in the increased incidence of endometrial carcinomas in tamoxifen-treated patients, we examined the in-vitro effects of tamoxifen on endometrial cancer cells. The effects of tamoxifen, alone and in combination with oestradiol, on cell proliferation, plasminogen activator (PA) activity, glycogen synthase and phosphorylase activities, p53 protein concentration, and collagenase expression were assessed in two human adenocarcinoma cell lines. These lines were the oestrogen receptor-positive (Ishikawa) cells, representing a well-differentiated endometrial adenocarcinoma, and oestrogen receptor-negative (HEC-1A) cells, derived from a poorly differentiated endometrial adenocarcinoma. Tamoxifen or oestradiol alone and their combination significantly enhanced cellular proliferation of Ishikawa but not of HEC-1A cells. Both lines produced appreciable PA activity, most of which was of the urokinase type. Tamoxifen and oestradiol stimulated this activity in Ishikawa cells but not in HEC-1A cells. The effect of oestradiol was dose-dependent in a linear fashion, while tamoxifen produced a stimulation peaking at 10(-8) M and declining at higher concentrations. Tamoxifen in combination with oestradiol exhibited a synergistic effect on proliferation and on PA activity. The response of PA extended beyond the increase in proliferation, leading to higher specific activity of PA in the tamoxifen-treated cultures. In Ishikawa cells, oestradiol also increased glycogen synthase and glycogen phosphorylase activities, while tamoxifen markedly suppressed these enzymes. Oestradiol, tamoxifen, and their combination had no apparent effect on the expression of protein p53 in Ishikawa cells, or on gelatinase activity in either Ishikawa or HEC-1A cells. The present findings imply that tamoxifen produces oestrogen-agonistic effects on cell proliferation and PA activity, and oestrogen antagonistic effects on glycogen synthase and glycogen phosphorylase activities, but fails to regulate p53 and gelatinase expression. The tamoxifen-responsive systems were only observed in oestrogen-responsive adenocarcinoma cells. Thus, only certain potential oncogenic effects of tamoxifen can be simulated in vitro, and when present, these effects are enhanced in the presence of oestradiol.
...
PMID:Tamoxifen exerts oestrogen-agonistic effects on proliferation and plasminogen activation, but not on gelatinase activity, glycogen metabolism and p53 protein expression, in cultures of oestrogen-responsive human endometrial adenocarcinoma cells. 946 46

Oestrogen is assumed to play a significant role in cell cycle regulation of cells expressing the oestrogen receptor, although its mechanism of action is not yet well defined. To examine this, a mutant p53-expressing human endometrial adenocarcinoma cell line of the oestradiol-inhibited growth phenotype was treated with oestradiol for 2 weeks (short-term) and 6 months (long-term). With short-term treatment, cells were treated with increasing doses of oestradiol. The highest dose, 1 microM, was used in the long-term interval. The influence of the hormone on growth, proliferation and expression of some cell cycle and apoptosis-related proteins was evaluated. In cells treated for 2 weeks, there was a dose-dependent inhibition of both growth and proliferation with a significant decrease in labelling index (LI) and S-phase fraction (SPF) and a simultaneous increase in the fraction of cells in G0/G1. Extending the oestradiol treatment to 6 months showed further growth retardation and decreased proliferation with cells accumulating in G0/G1. Analysis of the expression of p21WAF1/Cip1 showed a nearly 2-fold increase after 2 weeks treatment with 1 microM oestradiol, which was also observed after long-term treatment without any further increase in protein levels. Expression of the anti-apoptotic protein bcl-2 was not affected after short-term treatment but decreased significantly after 6 months treatment compared to control cells. Our results suggest the existence of a p53-independent pathway of oestradiol regulation of growth and proliferation in this human endometrial adenocarcinoma, resulting in accumulation of cells in G0/G1 through p21WAF1/Cip1 induction and, after prolonged treatment, downregulation of bcl-2 protein.
...
PMID:Short- and long-term oestradiol treatment inhibits growth and alters expression of p21WAF1/Cip1 in an endometrial adenocarcinoma cell line lacking functional p53. 947 Aug 15

Forty-two patients with clinical stage IIIA or IIIB breast cancer were treated with neoadjuvant chemotherapy followed by mastectomy and radiotherapy. The median follow-up was 32 months (range 10-72 months) and the median time to progression was 17 months (range 10-30 months). A multivariate analysis showed that a longer disease-free survival (DFS) was related to more chemotherapy cycles given (P = 0.003), a better pathological response to chemotherapy (P = 0.04) and fewer positive axillary lymph nodes (P = 0.05). A better overall survival (OS) was related to more chemotherapy cycles given (P = 0.03) and better pathological response to chemotherapy (P = 0.04). In patients with residual tumour after neoadjuvant chemotherapy, high levels of staining for Ki-67 was correlated with a worse DFS (P = 0.008). Other biological characteristics, including oestrogen receptor status, microvessel density (CD31 staining), P-glycoprotein (P-gp) staining and nuclear accumulation of p53, were not independent prognostic factors for either DFS or OS. If both P-gp and p53 were expressed, DFS and OS were worse in the uni- and multivariate analysis. The preliminary results of this phase II study suggest that coexpression of P-gp/p53 and a high level of staining for Ki-67 after chemotherapy are associated with a worse prognosis, and that prolonged neoadjuvant chemotherapy and the attainment of a pathological complete remission are important factors in determining outcome for patients with this disease.
...
PMID:Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. 948 20

Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell and even programmed cell death, although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53.
...
PMID:Involvement of p85 in p53-dependent apoptotic response to oxidative stress. 949 Apr 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---