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

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Query: EC:1.5.1.19 (NOS)
7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two pathologic (including estrogen and progesterone receptor status) and four clinical features of 950 node-negative stage I invasive breast cancers from 950 women enrolled in the National Surgical Adjuvant Breast and Bowel Project protocol B-06 were analyzed for their possible prognostic significance. Univariate analyses revealed 10 characteristics that were significant at the 1% level. Only three of these--notably nuclear grade, histologic tumor type, and race--were found to be significant when entered into a Cox regression model. Patients whose tumors exhibited a good nuclear grade fared significantly better than those whose tumors were scored as poor. Similarly, a significantly better prognosis was noted when the histologic type of cancer was found to be "favorable" (mucinous, tubular, or papillary) than when it was "intermediate" (NOS, "Not Otherwise Specified," combination; typical medullary; and lobular invasive) or "unfavorable" (NOS pure and atypical medullary). Blacks exhibited a worse prognosis than whites. Survival was 94% at 8 years when the nuclear grade was good and the tumor type favorable, but only 54% when the nuclear grade was poor and tumor type unfavorable. Patients with one favorable and one unfavorable feature exhibited an intermediate survival. A brief overview as well as our own preliminary experience indicates that the combined use of these two prognostic pathologic parameters may be as good as and in some instances a better predictor of survival in node-negative patients than information derived from more "objective" methodologies such as flow cytometry, receptor analyses and tumor labeling indices or the demonstration of oncogene overexpression. Assessment of the pathologic parameters is simple, universally available, and quick and requires only modest training to be reproducible.
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PMID:Prognostic factors in NSABP studies of women with node-negative breast cancer. National Surgical Adjuvant Breast and Bowel Project. 134 74

Determination of steroid receptors and several oestrogen-regulated proteins in mammary carcinomas is useful in the prediction of their evolution and of the likely success of endocrine therapy. Cathepsin D (Cat D), pS2 peptide and heat shock protein 27 (Hsp 27) were detected immunohistochemically in 63 infiltrating ductal (NOS) breast carcinomas, and our results were qualitatively correlated with several clinicopathological indicators and patients' overall survival. Cat D immunostaining of tumour cells was strongly associated with axillary nodal involvement (Pf = 0.0005) and so, it is directly connected with the metastatic capacity of malignant cells. pS2 immunoreactivity was correlated with oestrogen and progesterone receptor positivity (Pf = 0.0009 and Pf = 0.05 respectively) and, nonsignificantly, with good differentiation of the tumours (Pf = 0.06). Neoplastic cells expressing this protein are therefore characterised by a highly organised state of cellular physiology. Hsp 27 was expressed predominantly in tumours with one to four infiltrated lymph nodes (Pt = 0.05), and Hsp 27-positive patients were inclined to rather short survival, possibly due to chemotherapy resistance. In future, prognostic estimation of each one of the examined markers should be performed in specific large subgroups of patients. The findings of this study contribute to the establishment of criteria by which these subgroups should be formed.
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PMID:Prognostic evaluation of oestrogen-regulated protein immunoreactivity in ductal invasive (NOS) breast cancer. 755 43

In this study epidermal growth factor receptor (EGF-R), estrogen receptor (ER), and progesterone receptor (PR) status was evaluated in 326 primary breast carcinomas. Nineteen percent of samples were EGF-R positive, 63% were positive for ER, and 54% for PR. In 46% of the tumors both ER and PR were positive. These data are presented together, with grading, size of tumor, lymph node involvement, histological subtype, and age. Sixty-nine percent of EGF-R negative tumors were ER-positive and 51% were positive for ER as well as PR. In particular, negative correlation between EGF-R and steroid receptor status was found. A quantitative correlation was also shown. A combination of negative steroid receptor and positive EGF-R was found more often in the population of poorly differentiated tumors. Tumors bigger than 5 cm were related to a positive EGF-R status. No correlation between nodal status and any receptor status was found. Intraductal carcinomas were more often EGF-R positive than infiltrating ductal (NOS) or infiltrating lobular lesions. The age of patients correlated with the concentration of ER only. In our study we reaffirmed the negative correlation between steroid receptor status and the overexpression of EGF-R; furthermore the combination of EGF-R+ and ER- tumors was observed more often in histological high-risk tumors. Patient outcome did not show statistically significant differences concerning the EGF-R status, but was associated with the steroid receptor status.
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PMID:EGF-R and steroid receptors in breast cancer: a comparison with tumor grading, tumor size, lymph node involvement, and age. 839 51

Nitric oxide (NO) is a major paracrine mediator of various biological processes, including vascular functions and inflammation. In blood vessels, NO is produced by the low-input constitutive endothelial NO synthase (eNOS) and is a potent vasodilator and platelet aggregation inhibitor. The inducible NOS isoform (iNOS) is capable of producing NO at high concentrations which have pro-inflammatory properties. Immunohistochemical and molecular studies of endometrial NOS expression, as well as animal experiments with NOS inhibitors, indicate that NO plays an important role in endometrial functions such as endometrial receptivity, implantation and menstruation. In rodents, both iNOS and eNOS are highly up-regulated in the implantation sites, and NOS inhibitors show synergistic effects with antiprogestins in inhibiting the establishment of pregnancy. In the human endometrium, eNOS have been localized in the glandular epithelium and in endometrial microvascular endothelium, primarily during the luteal phase. iNOS has been found in the endometrial epithelium during menstruation, in immunocompetent endometrial cells, and in decidualized stromal cells. In primates, NO may be involved in the initiation and maintenance of menstrual bleeding by inducing tissue breakdown and vascular relaxation as well as by inhibiting platelet aggregation. Endometrium-derived NO may also play a role in myometrial relaxation during menstruation. These studies open up new applications for NO-donating and -inhibiting agents in uterine disorders. NO donors may be useful in the treatment of dysmenorrhoea and for promoting fertility. Antiprogestins, progesterone receptor modulators and iNOS inhibitors may find applications in the treatment and prevention of abnormal uterine bleeding.
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PMID:Role of nitric oxide in implantation and menstruation. 1104 Dec 26

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent (P < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.
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PMID:Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study. 1472 Jan 38

While one current focus for studying mechanisms of disease is investigation of transgenic mice confounding effects of the background strain often are neglected. We investigated mRNA expression of known markers of hypoxic tolerance by a semiquantitative RT-PCR (adenosine receptors (A1 and A3), nitric oxide synthases (eNOS and nNOS), APP production, progesterone receptor, and estrogen receptors alpha and beta) in CD-1, C3H, and B6 mice. We found differences in the baseline mRNA expression of adenosine A3 receptors in C3H mice and neuronal NOS in B6 mice as well as a distinct regulation of adenosine A3 receptors and estrogen receptor beta (no changes in C3H and B6 compared to upregulation in CD-1) on treatment of animals with a low dosage of 3-nitropropionate (20mg/kg body weight, i.p.). We conclude that the choice of background strain may confound interpretation of the effects of specific transgens in the study of the mechanisms of primary and induced hypoxic tolerance.
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PMID:Strain dependence of receptor regulation on chemical preconditioning in mice hippocampus. 1524 42

Breast cancer is the most common malignant disease in women. It is rare before age 30, whereafter its prevalence rises to reach peak at age 50. Prognostic factors have a very important role in choosing the most appropriate treatment option and making long-term disease prognosis. Currently, the classic prognostic factors such as histologic type, tumor grade, tumor size, regional lymph node involvement, estrogen and progesterone receptor status still are of high prognostic value allowing for reliable prognosis. This retrospective study included female patients treated at Department of Surgery, University Hospital for Tumors in Zagreb over a two-year period (2002-2003). Only patients with histologically diagnosed invasive ductal breast cancer (NOS) undergoing radical modified mastectomy were included in the study. Analysis of the generally accepted prognostic parameters (tumor size, regional lymph node status, tumor grade, hormone receptor status) confirmed their known prognostic value. Study results were consistent with internationally reported data, reflecting appropriate approach by the surgery-pathology team of the hospital in the management of breast cancer.
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PMID:[Analysis of prognostic factors in breast cancer at University Hospital for Tumors]. 1680 70

Reactive oxygen species (ROS), including nitric oxide (NO(*)), are associated with all steps of carcinogenesis. Hyaluronan (HA), a high-molecular-mass glycosaminoglycan overexpressed in a variety of human malignancies also has ROS-scavenging properties. We histochemically studied the level of HA in breast carcinoma cells and their stroma and compared it with the expression of NO(*) synthases (NOSs), major antioxidant enzymes, and nitrotyrosine. We also assessed whether the level of HA correlates with traditional prognostic factors of breast cancer and survival. Stromal HA level was moderate or high in all the samples studied (n=185), and 84% of the lesions showed HA-positive carcinoma cells. Intense stromal HA signal was associated with high neuronal NOS expression (p=0.009), whereas tumor-cell associated HA was inversely correlated with nitrotyrosine expression (p=0.027). Of the traditional prognostic factors, tumor cell-associated HA was correlated with poor differentiation (p=0.011), and high stromal HA levels were associated with aggressive features of the carcinomas such as large primary tumor (p=0.002), poor differentiation (p=0.019), and estrogen (p=0.012) and progesterone receptor negativity (p=0.009). High stromal HA level also significantly predicted poorer survival. The strong positive correlation between neuronal NOS and stromal HA could reflect NO(*)-stimulated synthesis of HA, an extracellular matrix alteration that favors breast cancer progression. Furthermore, it is suggested that, while acting as a scavenger of NO(*)-derived radicals, cell-associated HA undergoes partial fragmentation, release from receptors, and further degradation in lysosomes, and thus becomes undetectable in histological sections.
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PMID:Hyaluronan in breast cancer: correlations with nitric oxide synthases and tyrosine nitrosylation. 1782 65

Breast carcinoma is a rare disease in men. The incidence is 1 per cent of the incidence in women. Relative hyperestrogenemia and environmental factors seem to be important for the development of the disease. In recent years, germline mutations have been observed in male breast carcinoma patients in several genes, BRCA2, the androgene receptor gene and PTEN. Suspected genetic factors include the cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC that has been shown to confer a 10-fold increase of breast cancer risk in men. The c.1-34T > C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with male breast cancer risk, hemochromatosis gene (HFE) mutations, the mismatch repair genes (hMSH2, hMLH1,hPMS1,hPMS2) and PTEN mutations (Cowden syndrome) are associated with male breast cancer. The majority of tumors is seen retromamillarly. Ductal carcinoma in situ comprises 5-10 % of all cancers. In case of invasive growth, 85-90 % are invasive ductal carcinomas (NOS), 2.5 % are papillary tumors; lobular cancers are exceptionally rare. About 3/4 of all cancers express estrogen and progesterone receptor with increasing positivity with increasing patient age. HER-2 / neu overexpression is seen in the same frequency as in female breast cancer. Poor prognostic factors are tumor size > 2 cm, poorly differentiated tumors, receptor negativity, axillary lymph node involvement and more than four affected nodes.
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PMID:[Male breast cancer: history, epidemiology, genetic and histopathology]. 1790 78

The aims of this study were twofold: (i) to determine the occurrence frequency of apocrine carcinoma of the breast (ApBCa) in Turkish breast cancer (BCa) patients; and (ii) to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), gross cystic disease protein-15 (GCDFP-15), c-erbB-2, and p53 in these cases. Six hundred and twenty-six cases of BCa were studied immunohistochemically (streptoavidin-biotin horseradish peroxidase method). The results of ApBCa were compared with those of invasive ductal carcinoma not otherwise specified type (IDC-NOS) cases of similar grade. Thirteen cases of ApBCa were encountered, accounting for 2.1% of all BCa cases. Immunohistochemically, ApBCa positivity was as follows: GCDFP-15 (100%), ER (39%), PR (8%), AR (54%), p53 (39%), and c-erbB-2 (85%). In the IDC-NOS group, GCDFP-15* was expressed in less than 50% of the tumors. The occurrence frequencies of the other markers were as follows: ER (69%), PR (69%)*, AR (46%), c-erbB-2 (0%)*, and p53 (31%), (*) indicating significant differences between the two groups. For Turkish BCa patients, (i) the occurrence rate of ApBCa (2.1%) was high; and (ii) the following combination would allow for an immunohistochemical identification of ApBCa: GCDFP-15(+), c-erbB-2(+), and PR(-).
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PMID:Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2 and p53 immunoexpression. 1834 52


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