Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the c-erbB-2 proto-oncogene product was investigated immunohistochemically in 474 formalin-fixed and paraffin-embedded human breast tissue samples. The series included 32 benign and 26 hyperplastic lesions, 32 carcinomas in situ and 384 invasive breast carcinomas, 107 of which were less than 1 cm in diameter. Cytometric DNA assessments were performed on histopathologically or cytodiagnostically identified cell nuclei, using image analysis. C-erbB-2 immunoreactivity was not seen in normal parenchyma or in benign and hyperplastic lesions. Mammary carcinomas in situ were more frequently immunoreactive (59%) than invasive neoplasms (23%). Invasive tumours more than 1 cm in diameter immunoreacted more often (26%) than small invasive carcinomas (16%). C-erbB-2 expression in regional lymph node metastases was the same as in the corresponding primary tumours. Significant differences were observed between the c-erbB-2 expression in DNA diploid and aneuploid lesions; for carcinomas in situ the figures were 40% and 72%, respectively. Invasive carcinomas of DNA diploid type rarely showed c-erb-B-2 expression, irrespective of tumour size and nodal status (7-11%). DNA aneuploid tumours were more frequently immunoreactive with increasing levels during progression (32-41%). Our data indicate that genetically stable invasive mammary tumours seem rarely to express the c-erbB-2 protein, even during progression, whereas genetically unstable invasive neoplasms frequently show c-erbB-2 immunoreactivity which increases during tumour progression.
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PMID:Expression of the c-erbB-2 proto-oncogene product and nuclear DNA content in benign and malignant human breast parenchyma. 135 Jun 95

The mammalian immune system is essential for surviving challenge infections with a great range of potential pathogens. The protective effect produced is dependent on many different types of cells which require flexible and independent production and regulation. In particular, many important responses are carried out by lymphocytes, which recognise foreign antigen through exquisitely specific receptors: i.e. surface immunoglobulin (sIg) on B lymphocytes and the T cell receptor (TCR) on T lymphocytes. Each lymphocyte displays receptors with a single specificity, allowing cells with particular specificities to be regulated independently. Since millions of different Igs and TCRs are expressed, the precise selection and regulation of each T and B cell population to produce a useful self-tolerant repertoire is a very complex process. Control of cell populations can, in theory, be exercised at a number of levels, including modulation of active cell death by apoptosis. Recent research has demonstrated that regulation of apoptosis is indeed a crucial element in the control of the immune system in general, and in the development of the TCR and Ig repertoires in particular. The molecular analysis of apoptosis now takes a high priority and the proto-oncogene bcl-2 appears to be responsible for specific suppression of apoptosis in several important situations. It is also clear that malfunctions affecting apoptosis, and in particular bcl-2, can result in significant progression towards malignancy.
Cancer Metastasis Rev 1992 Sep
PMID:Apoptosis in the development of the immune system: growth factors, clonal selection and bcl-2. 139 95

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.
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PMID:Expression of the epidermal growth factor receptor gene in human brain metastases. 152 Apr 84

Tumors of the peripheral nervous system include neuroblastomas, pheochromocytomas, and neuroepitheliomas. Neuroblastomas and pheochromocytomas are adrenergic in origin and share certain genetic features, whereas neuroepitheliomas are thought to be cholinergic and are characterized by distinct genetic features. Neuroblastomas are characterized by deletion of the short arm of chromosome 1 (1p), amplification of the MYCN proto-oncogene, and hyperdiploidy in subsets of tumors. All three of these genetic features have prognostic value in subsets of patients. Allelic loss of 14q also occurs with increased frequency, but the prognostic importance of this abnormality is not known yet. Pheochromocytomas have not been studied as extensively, but allelic loss for 1p appears to be a frequent change, and no clear examples of oncogene activation have been identified to date. Neuroepitheliomas are characterized by translocation between chromosomes 11 and 22. Although they have a characteristic pattern of proto-oncogene expression, it is not clear that any of these oncogenes are activated specifically, and no sites of allelic loss have been identified to date. Thus, cytogenetic and molecular analysis of neuroblastomas, pheochromocytomas, and neuroepitheliomas are useful in distinguishing them from each other and from other tumors in selected cases. Furthermore, certain genetic markers are useful in predicting clinical behavior, especially for neuroblastoma.
Cancer Metastasis Rev 1991 Dec
PMID:Biology of tumors of the peripheral nervous system. 178 33

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

Transfection of the immortalized human breast epithelial cells MCF-10A with the mutated ras oncogene resulted in cell transformation (MCF-10A-neoT). Since the transformed state is usually associated with enhanced migratory activity, increased capability to invade basement membranes and to grow in a three-dimensional basement membrane gel (growth in matrigel), we compared these properties in MCF-10A-neoT cells with those of MCF-10A cells transfected with either the neomycin resistance gene alone (MCF-10A-neo cells) or with the normal ras proto-oncogene (MCF-10A-neoN cells). MCF-10A-neoT cells exhibited enhanced migratory activity, as assessed by chemotaxis and chemokinesis assays. and increased capability to invade the basement membrane. These cells also formed large colonies in matrigel. MCF-10A-neo and MCF-10A-neoN cells, on the other hand, showed only marginal migratory, invasive and semisolid medium growth properties. These results indicate that the mutated ras oncogene induces in human breast epithelial cells phenotypic characteristics of malignant transformation.
Invasion Metastasis 1991
PMID:Increased invasive, chemotactic and locomotive abilities of c-Ha-ras-transformed human breast epithelial cells. 206 Oct 3

Cytogenetic analysis was performed on 11 benign and borderline ovarian tumors. Trisomy 12, identified as a sole abnormality in 6 tumors, is likely a specific karyotypic change in different benign and borderline tumors and may well be a primary chromosomal lesion in these tumors. The possible association between amplification of the proto-oncogene K-ras-2 which is located on chromosome 12 and trisomy 12 was investigated. DNA blotting analysis of 64 tumors indicates that trisomy 12 does not seem to be related to K-ras-2 amplification in ovarian tumors. K-ras-2 amplification was observed in 3 high-grade tumors from 3 patients with metastases.
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PMID:Trisomy 12 and K-ras-2 amplification in human ovarian tumors. 207 Dec 29

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.
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PMID:Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m. 217 17

The biological behavior of early-stage invasive carcinoma of the uterine cervix is not always predictable. Therefore it is important to identify new biological markers which could more accurately predict the evolution of the disease. Amplification and/or overexpression of the c-myc gene were frequently observed in advanced-stage cervical cancers and were shown to be associated with tumor progression. More interesting was the study on 93 patients with early-stage carcinoma showing that c-myc gene overexpression was significantly related to a higher risk of relapse. A combination of c-myc expression and nodal status provided a very accurate indication of the risk of relapse. Indeed, in the subgroup of patients with negative nodes, the 3-year disease-free survival rate was 93% (95% confidence interval CI: 79-98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% CI: 26-63%) when c-myc was overexpressed. Moreover the c-myc overexpression was related to a 6.1-times higher risk of distant metastases, suggesting that activation of this proto-oncogene may lead to metastatic ability of tumor cells. These data clearly show that patients with c-myc overexpression are high risk patients who thus might benefit from intensive treatment.
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PMID:The c-myc proto-oncogene in invasive carcinomas of the uterine cervix: clinical relevance of overexpression in early stages of the cancer. 217 73

int-2 is a proto-oncogene that is partially homologous to angiogenesis-inducing fibroblast growth factor and is believed to play a role in mouse mammary carcinogenesis. Recent evidence has suggested that this proto-oncogene may also play a role in human breast cancer. In the present study, we used Southern hybridization analysis to examine DNA from 79 primary and 11 recurrent human breast cancers for evidence of activation of int-2 through either gene rearrangement or amplification. A similar analysis was performed for two other proto-oncogenes, c-erbB-2 and c-myc, also suspected of playing a role in the development of human breast cancer. Proto-oncogene status was correlated with estrogen (ER) and progesterone (PR) receptor status, patient age, and lymph node (LN) status at the time of surgery. Gene rearrangement was not a frequent occurrence with any of the proto-oncogenes. However, amplification of int-2 occurred at a significantly higher frequency in recurrent breast cancers than in primary cancers and in patients with primary cancers who were less than or equal to 50 years of age versus greater than 50 years of age at surgery. Although amplification of all three proto-oncogenes occurred at a greater frequency in primary tumors from patients with lymph node metastases than from those without lymph node metastases, a significant difference was noted only in the case of c-myc amplification. These findings confirm and extend earlier results of studies of int-2, c-erbB-2 and c-myc amplification in human breast cancers and point to a role for int-2 activation in certain cases of recurrent breast malignant neoplasia.
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PMID:Amplification of the proto-oncogenes int-2, c-erb B-2 and c-myc in human breast cancer. 261 95


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