Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To enable individualized risk-oriented adjuvant treatment of breast cancer, validated parameters are needed to help evaluate the individual relapse risk. The clinical significance of these factors is assessed by published evidence (level of evidence) and its utility in the clinical setting (utility score). The traditional prognostic factors (age, TNM stage, grading, and steroid hormone receptor status are of established clinical relevance, and their determination should be obligatory. Of the "new" tumor-biologic parameters, only the measurement of the urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in the primary tumor of node-negative patients has been adequately validated and can therefore be recommended for clinical application. Promising recent prognostic markers are the expression of Her2/neu, detection of disseminated tumor cells in bone marrow aspirates, various different surrogates for proliferative activity, and tumor-specific gene expression profiles. Currently, however, the data available are insufficient to allow recommendation of the parameters for routine clinical use at this time.
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PMID:[Prognostic factors in carcinoma of the breast. Thereupon depends success of the treatment]. 1286 97

The aim of this study was to assess the correlation of survival with clinical, surgical, histopathological, and biochemical parameters in patients with ovarian cancer. Age, surgical and histopathological data, the concentrations of estrogen and progesterone receptors, Her-2 neu, p53, U-PA, PAI-1, and Cathepsin D, DNA-and S-phase indexes of 111 ovarian cancer patients have been analyzed and correlated to survival. Progesterone receptors were correlated with prolonged survival. FIGO staging at the time of diagnosis is an independent prognostic factor for the patient's survival. Endometrioid and serous ovarian cancers have a better prognosis than mucinous and clear cell ovarian cancers. Survival of optimally debulked patients was substantially longer than that of not optimally debulked patients. This study shows, that an accurate clinical and surgical staging with an according histopathological assessment combined with optimal cytoreduction is of importance for the prognosis of ovarian cancer patients.
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PMID:Analysis of potential prognostic factors in 111 patients with ovarian cancer. 1501 65

Breast cancer represents a major health problem, with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade, in spite of an increasing incidence, breast cancer mortality has been declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments. Better knowledge of breast cancer biology now allows the cosmetic, physical and psychological consequences of radical mastectomy to be spared in the majority of breast cancer patients. Use of the sentinel node technique is rapidly expanding and this will further reduce the extent and the consequences of surgery. Several clinico-pathological factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse. Nodal status, tumour size, tumour grade and age are accepted universally as important factors to define risk categories. Newer factors such as uPA/PAI-1, HERer2-neu, proliferative indices and gene expression profile are promising and will allow better discrimination between patients at different risk. Endocrine manipulation with tamoxifen, ovarian ablation or both is the preferred option in the case of endocrine-responsive tumours. Tamoxifen administered for 5 years is the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen, with a different safety profile. At present, anastrozole can be used in the adjuvant setting in cases of tamoxifen intolerance or toxicity. Chemotherapy is the treatment of choice for steroid receptor-negative tumours. Polychemotherapy is superior to single agents and anthracycline-containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four of CMF are the recommended regimens. New regimens including the taxanes have produced a further improvement in risk reduction and are reasonable therapeutic options. The taxanes have been approved for adjuvant therapy in the USA, while European approval is pending. Combined endocrine-chemotherapy is the standard adjuvant treatment in high-risk patients with endocrine-responsive tumours. Endocrine manipulation is usually administered after completion of the chemotherapy programme. For HER2-neu overexpressing tumours, several rapidly accruing trials are exploring the potential additive effect of trastuzumab, a monoclonal antibody directed against the extramembrane portion of the HER2 receptor. Primary chemotherapy is increasingly used in the treatment of locally advanced and operable breast cancer, with increased rates of breast-conserving surgery. A proportion of patients achieve a pathological complete response and these patients have significantly better long-term outcomes. Twenty-five to forty percent of breast cancer patients develop distant metastases. At this stage the disease is incurable; however, treatments can assure a significant prolongation of survival, symptomatic control and maintenance of quality of life. In the case of hormone receptor positivity and in the absence of visceral, life-threatening disease, endocrine manipulation is the treatment of choice. Active treatments include tamoxifen, ovarian ablation, aromatase inhibitors, pure anti-oestrogens and progestins. Aromatase inhibitors are the most active agents, but the choice and the sequence of endocrine therapies are also dictated by prior adjuvant treatment. Chemotherapy has to be preferred in cases of receptor-negative tumours, acquired resistance to hormones and aggressive visceral disease. Combination regimens are usually associated with higher response rates and sometimes survival prolongation, and this approach should be recommended in young patients with good performance status and visceral disease. On the other hand, single agents have a better tolerability profile and should be tand should be the treatment of choice when a careful balance between activity and tolerability is needed. For HER2-neu positive tumours, the combination of trastuzumab and chemotherapy is significantly superior to chemotherapy alone in terms of both response rates and survival. Other useful palliative treatments include bisphosphonates for the control of metastatic bone disease and radiotherapy for painful bone lesions or local relapses.
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PMID:The curability of breast cancer and the treatment of advanced disease. 1510 48

In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely related to the plasminogen activator inhibitor (PAI-1) and estrogen receptor (ER) expression but not the progesterone receptor (PR) and urokinase plasminogen activator (uPA). A low Tiam1 expression was associated with p53 positivity without being related to HER2/neu status. The data show that Tiam1 expression decreases with the progression of breast carcinomas and is inversely associated with several established breast tumor markers. Therefore, we suggest that Tiam1 counteracts the progression of breast carcinomas and is suitable as a novel breast tumor marker.
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PMID:Progression of breast tumors is accompanied by a decrease in expression of the Rho guanine exchange factor Tiam1. 1908 65

Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients. For selecting likely response to endocrine therapy, both estrogen receptors (ER) and progesterone receptors (PR) should be measured. On the other hand, for identifying likely response to anti-HER2 therapy, determination of HER2 gene amplification or overexpression is necessary. To identify new prognostic and predictive biomarkers for breast cancer, current research is focusing on tumor and circulating DNA (ctDNA) and RNA (e.g., micro RNAs) and circulating tumor cells. A promising ctDNA biomarker is the mutational status of ER (ESR1) for predicting the emergence of resistance to aromatase inhibitors. Challenges for future research include the identification of biomarkers for predicting response to radiotherapy and specific forms of chemotherapy.
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PMID:Prognostic and predictive biomarkers in breast cancer: Past, present and future. 2888 52