Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As the prognostic significance of the three most frequently amplified oncogenes in breast cancer (c-myc, int-2/FGF3, and c-erbB-2/neu) is still unclear, and as the amplification of these genes appears to be mutually exclusive, we investigated the prognostic significance of oncogene amplification per se by multivariate analysis in a group of 112 primary human breast cancer cases. Amplification of at least one gene (c-myc, int-2/FGF3, or c-erbB-2/neu), progesterone receptor status, and pathological tumor size were the only independent variables predictive of metastasis-free survival. Moreover, we constructed prognostic profiles by computing risks associated with the three parameters predictive of poor survival and discriminated high-, moderate-, and low-risk categories.
 ...
PMID:Oncogene amplification per se: an independent prognostic factor in human breast cancer. 799 60

Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease. Apart from a growth stimulatory effect, the molecule plays an important role in cell motility of tumor cells by the activity of a motility factor, which acts as a specific ligand for the neu-protein. The motility factor induces chemotaxis of neu-overexpressing breast cancer cells. The motility function of the neu-protein may lead to an increased metastatic potential of neu-overexpressing breast tumors. Also in Paget's disease of the breast, a motility factor secreted by epidermal keratinocytes attracts the neu-overexpressing Paget's cells by chemotaxis and leads to invasion of the epidermis by the tumor cells.
 ...
PMID:The neu-oncogene: more than a prognostic indicator? 800 19

Breast cancer is an important disease site for chemopreventive intervention. The current in vivo rodent models for breast cancer do not adequately approximate the human disease. Thus, we developed a new series of models based on the direct introduction of activated oncogenes into in situ mammary ductal cells in the rat. So far we have introduced both activated ras and neu into the mammary parenchyma of the rat. Both oncogenes cause the development of mammary carcinomas without any additional exogenous intervention. The activated neu gene is, however, 200 times more penetrant than the activated ras gene. The carcinomas induced by both genes are more aggressive than those induced by chemical carcinogens. They are more often transplantable, locally invasive, and metastatic. Tumors arising from the introduction of the neu oncogene have a greater histopathological resemblance to human breast cancers than those associated with ras insertion. For example, within a week post-introduction of neu, lesions resembling ductal carcinomas in situ are observed in the rat mammary gland. These do not occur following ras introduction or exposure to chemical carcinogens. These models are helping to better define the cellular and molecular events associated with the multistage progression of breast cancer. They are also being used to develop models to evaluate chemopreventive approaches for breast cancer. For example, in the area of cancer prevention we have shown that hormonal intervention is more effective in preventing neu-initiated breast cancers than ras-initiated breast cancers. We have also shown that the chemopreventive monoterpene, d-limonene, can prevent ras-induced mammary tumors in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The introduction of activated oncogenes to mammary cells in vivo using retroviral vectors: a new model for the chemoprevention of premalignant and malignant lesions of the breast. 800 12

Diagnostic quantitative pathological (QP) determinations are increasingly used in our hospital. The number of requests for QP for reference materials is rising rapidly. This is understandable; quantitative assessments have a strong prognostic value and can be very reproducible, depending on the care taken with a number of factors including cell and tissue processing, application of the appropriate stains, and the measurement protocol used. As to the latter, systematic random sampling gives the best intra- and interobserver agreement (with correlation coefficients between observers for certain features > or = 0.94). Flow cytometric determinations are often regarded as more reproducible than interactive morphometry due to the high speed of the assessments, the large number of objects measured per specimen, and the lack of observer interaction. Indeed, flow cytometrically assessed DNA ploidy is very reproducible, even though the % S-phase fraction is much more variable. Unlike image cytometry (ICM), visual inspection of cells is not easily accomplished with flow cytometry (FCM). With ICM, the fully automated measurement of DNA in thousands of cells is possible in 3-5 minutes, with a very low coefficient of variation (< or = 2% for the diploid and tetraploid peak of liver cell nuclei). ICM also allows measurement of texture features. However, quantitative immunohisto/cytochemical determinations may not always be as reproducible as sometimes believed. Recently, we found large variations in the measurements, made by a commercially available image processing instrument, of the estrogen and progesterone receptors, Ki-67, cathepsin D, and neu protein overexpression in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Quantitative microscopical and confocal laser scanning microscopy for intermediate endpoint biomarkers in breast cancer: potential and reproducibility. 800 17

For the integration of new cell biological prognostic factors in daily clinical practice, we need to know not only their prognostic power with respect to prediction of relapse free and overall survival, but also their possible relation to response to endocrine therapy or chemotherapy in order to select adequate treatment for each patient. A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficult to predict the response to treatment accurately. A valuable prognostic factor can be a worthless predictive factor for endocrine therapy or chemotherapy, and vice versa. High tumour levels of ER, PGR, AR and PS2 protein predict a relatively good response to endocrine therapy, whereas EGFR positivity, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high u-PA levels indicate a good chance of a 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, whereas 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 and type of systemic treatment and can be used as targets for new treatment modalities.
 ...
PMID:Prognostic factors and response to therapy in breast cancer. 801 96

The erbB-2 (or HER-2 or neu) gene is amplified and overexpressed in approximately one-third of cancers of the breast, stomach, and ovary. Evidence is accumulating that erbB-2 overexpression is associated with decreased survival of breast cancer patients. In an effort to understand how erbB-2 overexpression might impart a more malignant potential to breast cancer cells, we have searched for evidence of changes in gene expression associated with erbB-2 overexpression. Using differential screening of a complementary DNA library we identified several complementary DNAs that represent mRNAs the expression of which may vary according to erbB-2 level. One complementary DNA was studied in detail. The mRNA encoding the ribosomal protein L19 (1.9 kilobases) was more abundant in breast cancer samples that express high levels of erbB-2 (P < 6 x 10(-7)). The level of L19 mRNA expression varied over a 1- to 64-fold range among the tumor samples. No evidence of gene amplification for L19 was identified. The L19 overexpression in these breast tumor samples was not associated with the increased expression of the mRNAs for other ribosomal proteins (S16 and L26).
 ...
PMID:High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2. 809 82

Proliferative capacity provides an independent prognostic marker of progression in breast cancer. Little is known about the molecular mechanisms influencing the cell division rate in mammary carcinomas. In order to address this issue, the copy numbers of c-erbB-2 (HER/neu) and c-myc protooncogenes that have been shown to be amplified in aggressive types of cancers were determined in 60 mammary carcinomas and related to the proliferation rate. The proliferative activity was determined by labeling of the proliferation-associated nuclear antigen which is defined by the recently described monoclonal antibody Ki-S1. Approximately one-third of samples under investigation displayed a Ki-S1 labeling index exceeding 30%. In this subgroup, amplification of c-myc was found in 52.6%, whereas in the remaining cases, 26.1% exhibited an enhanced copy number of c-myc (P < 0.025). By contrast, c-erbB-2 amplification was not found to be associated with a higher proliferation index. Except for one case of invasive lobular carcinoma, both protooncogenes exhibited regular copy numbers in the low proliferation subgroup (< 20%; P < 0.03). We conclude from our findings that c-myc amplification may be one of the molecular causes underlying the highly proliferating phenotype of mammary carcinoma, known to be associated with an unfavorable clinical course.
 ...
PMID:Amplification of c-myc but not of c-erbB-2 is associated with high proliferative capacity in breast cancer. 809 98

A molecule that is immunologically related to the c-erbB-2 oncogene product (p185HER2/neu) was detected in the conditioned culture medium from neu-overexpressing tumor cell lines and in sera of advanced-stage breast carcinoma patients. Using a sensitive (in the range of 0.5 ng ml-1) double-determinant radioimmunoassay (DDIRMA) with two monoclonal antibodies (MAbs) directed against the neu extracellular domain (ECD), soluble oncoproteins were detected in supernatants from several neu-positive tumor cell lines, independent of the levels of membrane p185HER2 expression. The molecule detected did not react with a MAb directed against an intracytoplasmic epitope of the p185HER2. Western blot analysis of the concentrated supernatant revealed a protein of approximately 110 kDa molecular mass, which closely matches the predicted size of the glycosylated p185HER2 ECD. Immunoprecipitation of culture supernatant from cell surface-radioiodinated cells confirmed the 110 kDa molecular mass of the glycosylated shed protein, which migrated to 86 kDa after deglycosylation. Proteolytic cleavage of the p185HER2 molecule was demonstrated in release assays carried out with protease inhibitors. The combined use of leupeptin and EDTA completely inhibited release of the molecule. Analysis of sera from breast carcinoma patients and healthy donors by DDIRMA revealed the presence of soluble neu in 15% of pathologic sera but none of the normal sera. A good correlation was found between neu-overexpression in the primary tumor and the soluble marker in serum of patients with advanced disease; sera of early-stage patients were always negative, independent of neu-overexpression in the tumor. These results suggest the usefulness of soluble neu as an indicator of tumor aggressiveness but not as a diagnostic marker of breast cancer.
 ...
PMID:The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. 810 38

Some of the genetic abnormalities that give rise to human breast cancer have been identified. This article reviews the biology of the oncogenes c-myc and neu and the antioncogene p53. Data supporting the role of these genes in the pathogenesis of human breast cancer are reviewed. Potential diagnostic and therapeutic applications that have developed out of our understanding of the molecular genetics of breast cancer are also discussed.
 ...
PMID:The genetics of breast cancer. 815 Jul 76

Oncogenes have been expressed in mammary epithelium by reconstituting epithelium in vivo from mammary cells. Genetically manipulated primary cultures are transplanted into a mammary fat pad from which the natural epithelium has been removed, where they reform an epithelium in which a few cells express the oncogene. Genes can be expressed in other tissues in a similar way. A wide variety of oncogenes have a clearly observable effect on the pattern of growth of mammary epithelium. Expression of individual oncogenes usually produces stable, characteristic patterns of abnormal growth that can be regarded as preneoplastic states. Different oncogenes produce a very diverse variety of such growth patterns, by altering branching pattern, inducing formation of alveoli, causing epithelium to multilayer and/or altering hormone dependence. Myc and wnt1 seem to enable cells to overgrow neighbouring normal cells, suggesting that they promote clonal expansion, whereas others give focal lesions. Oncogene co-operation can be studied by introducing further oncogenes into preneoplastic epithelium, for example the introduction of ras into epithelium that already expresses activated myc gives tumours. The effects of both neu/c-erbB2 and myc on mouse mammary epithelium may mimic events in human breast, encouraging the hope that this will prove a way to model human breast cancer. The tissue reconstitution approach promises to reconstruct tumour development in more detail than the transgenic systems are able to, showing the development of focal lesions, the restraining effects of normal on transformed cells and the expansion of clones of hyperplastic cells at the expense of their normal neighbours.
 ...
PMID:Tissue reconstitution models of breast cancer. 834 40


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