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  • 1
    Digitale Medien
    Digitale Medien
    [s.l.] : Nature Publishing Group
    Nature genetics 16 (1997), S. 332-333 
    ISSN: 1546-1718
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Medizin
    Notizen: [Auszug] The use of positional cloning has yielded two genes (BRCA1 and BRCA2) that are involved in a substantial proportion of familial breast cancers. In contrast to the behaviour of most tumour-suppressor genes, however, these two genes have not been found to be associated with a significant number of ...
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of mammary gland biology and neoplasia 1 (1996), S. 163-175 
    ISSN: 1573-7039
    Schlagwort(e): Breast cancer ; p53 ; apoptosis ; cell cycle ; MDM2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining the genetic integrity of the cell by preventing cells with damaged DNA from further proliferation. Mutation and deletion of p53 are the most common genetic defects seen in clinical cancer. About 40% of breast carcinomas show high levels of stabilized, often mutant, p53 protein in their cells as detected by immunohistochemistry. p53-related defects in tumor cells correlate with a poor prognosis and may also indicate a poor response to chemotherapy. In experimental systems, the p53 status of cells is important in determining their sensitivity to radiation and chemotherapeutic drugs. Cells with functional p53 die by apoptosis, whilst similar cells lacking p53 function continue to proliferate, perpetuating potentially oncogenic mutations. Not only may p53 status be a marker of the biological aggressiveness of individual tumors and of their likely response to therapy, but restoration of normal p53 function is itself already a goal of cancer therapy.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1573-7217
    Schlagwort(e): c-erbB-2 ; immunohistochemistry ; thymidine labelling index ; breast carcinomain situ
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The relationship between the presence of the c-erbB-2 protein, demonstrated immunohistochemically with antibody 21N, and thymidine labelling index (TLI) has been studied in thein situ component of 70 cases of carcinoma of the breast. A significant association was found between high TLI and positive staining. Twenty of the 70 cases stained (29%) and of those that were stained 75% had a high TLI; 43% of those with a high TLI stained positively but only 14% of those with a low TLI stained positively. Strong correlations were seen between nuclear size and histological pattern and both 21N staining and TLI. The majority of carcinomas of comedo pattern with large nuclei were 21N positive and had a high TLI, whilst those with small nuclei and a predominantly cribriform/micropapillary appearance did not stain and had a low TLI. In tumours of mixed histological pattern there was less concordance between staining and TLI. The significance of these findings in relation to the biological behaviour of these tumours and their clinical management is discussed.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 52 (1998), S. 1-15 
    ISSN: 1573-7217
    Schlagwort(e): cyclin D1 ; estrogen receptor ; p27 ; breast cancer ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cyclin D1 protein plays an important part in regulating the progress of the cell during the G1 phase of the cell cycle. The cyclin D1 gene, CCND1, is amplified in approximately 20% of mammary carcinomas, and the protein is over- expressed in approximately 50% of cases. This has led to intensive study to ascertain whether cyclin D1 is a biological marker in breast cancer; however, the clinical work has produced unexpected results. Work in cell lines and in transgenic mice indicate that CCND1 is a weak oncogene and it was expected that, like c- erbB-2, over-expression of cyclin D1 protein would be associated with a poor prognosis. Early immunohistochemical prognostic studies produced equivocal results but we, and others, have recently shown that strong staining for cyclin D1 is more likely to be seen in well differentiated, estrogen receptor positive carcinomas. Furthermore, we have found that over-expression of cyclin D1 is actually associated with a good outcome, both in terms of prognosis and response to endocrine treatment. Cyclin D1 is frequently over- expressed in ductal carcinoma in situ but not in benign breast disease, including atypical ductal hyperplasia; hence its expression appears to be closely linked with carcinogenesis. In order to help explain the apparent beneficial effects of cyclin D1 over- expression, a number of closely associated cell cycle proteins have also been evaluated, including the cyclin dependent kinase inhibitor p27, which blocks the activating effects of cyclin D1. Initial reports show that high levels of p27 are associated with a good prognosis and we have shown a positive association between p27 and cyclin D1 expression. These clinical results of cyclin D1 are an example of how information obtained from basic cell biology studies needs to be complemented by clinical studies to ascertain the true worth of a prognostic marker.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 132-138 
    ISSN: 0730-2312
    Schlagwort(e): Breast ; c-erbB-2 ; DCIS classification ; immunohistochemistry ; nuclear size ; prognosis ; treatment response ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: The c-erbB-2 oncogene has been extensively studied in mammary carcinomas since Slamon and colleagues demonstrated the association between amplification and poor prognosis in 1987. Further work found that amplification was accompanied by overexpression of the protein; however, this relationship is not perfect. Recently, Hollywood and Hurst have shown increased transcription in some cell lines containing a single copy of the gene, causing mRNA accumulation in overexpressing cells. Protein expression appears to be a good indicator of various abnormalities in the c-erbB-2 gene. Fortunately, c-erbB-2 protein, unlike epidermal growth factor (EGF) receptor, survives most fixation procedures used in routine histopathology laboratories. This has enabled immunohistochemical studies to be carried out on archival material.A higher incidence of c-erbB-2 positivity occurs in ductal carcinoma in situ (DCIS) than in infiltrating carcinomas. In DCIS there is a very close association between protein expression and high grade (comedo type). This explains the very high incidence of c-erbB-2 positivity in Paget's disease of the nipple which is nearly always associated with high grade DCIS. A lower proportion of high grade infiltrating carcinomas express the protein, highlighting the difference in incidence of positivity in the two types of ductal lesion.As well as having a potential role in the biological classification of mammary carcinomas, c-erbB-2 expression has been used to predict response to treatment. There have been reports that tumors expressing c-erbB-2 fail to respond to either chemotherapy or endocrine therapy. It is extremely difficult to conduct satisfactory trials to confirm these results since only a quarter of infiltrating mammary carcinomas are c-erbB-2-positive, and a very large number of stage-matched patients is necessary in order to achieve comparable treatment and control groups. However, two small studies carried out at Guy's Hospital have found that the presence of c-erbB-2 protein does not preclude a successful response to either adjuvant chemotherapy or endocrine therapy for metastatic disease.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 248-248 
    ISSN: 0730-2312
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: In human mammary carcinoma, positive immunohistochemical staining for p53 protein is not always indicative of mutation in the p53 gene. Although positive staining is seen in excess of 50% of tumours, mutations have been found in only some 20% of cases. In this presentation, positive p53 staining in mammary carcinomas will be related to the presence and absence of mutation and other possible underlying mechanisms.In some positively stained tumours a mutation has been found. In others, no mutation has been demonstrated and apart from possible stabilisation by a protein such as MDM2, there are alternative underlying mechanisms for this discrepancy. Wild type p53 is elevated in response to DNA damage. This effect can be seen in patients given pre-operative chemotherapy and in cell lines irradiated with UV light and with x-rays. Strong positive staining in scattered nuclei has been found in cell lines with activated ras and myc genes. We postulate that this may also be the reason for similar patterns observed in human tumours.Comparable mechanisms may be active in inherited cancers. Although positive p53 staining in some Li-Fraumeni syndrome patients is associated with mutation, in other Li-Fraumeni-like families, no mutation has been found despite positive staining in tumour and normal tissues.Whatever the mechanism underlying the stabilisation of the protein, increased expression of p53 protein in the majority of tumour cells appears to be associated with poor prognosis in breast carcinoma.
    Materialart: Digitale Medien
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