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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer patients usually do not die of their primary cancers; they die of metastatic disease. Thus understanding the progression of breast cancer to the metastatic state and the changes that take place in highly malignant breast cells are important goals that could eventually result in new therapeutic approaches to highly progressive breast disease. Changes in the expression of certain genes or alterations in gene structures and encoded products can result in benign tumour cells progressing to the metastatic state. Experimentally, this has been performed by transferring dominantly acting oncogenes into susceptible cells and then testing the malignant properties of these cells in suitable animal models, but such rapid qualitative changes occur in vivo only rarely, and the natural progression of mammary cells to the metastatic state is thought to occur through a slow stepwise process that can take several years. Some of the slow stepwise changes in mammary cancer progression can be reversible and need not involve dominantly acting oncogenes or tumour suppressor genes, consistent with clinical observations. An important element of the natural progression of mammary tumours to malignancy may be their ability to circumvent microenvironmental controls that regulate growth and cellular diversity, a process that appears to involve mainly quantitative changes in gene expression, resulting in loss of normal cellular regulation. One of the important mechanisms of cellular regulation in epithelial tissues, such as those found in the breast, is mediated by intercellular junctional communication. Alterations in gene expression can result in loss of gap-junctional communication, concomitant with cellular diversification and progression. It is thought that the highly malignant cancer cells that have slowly evolved in vivo with only a few qualitative changes in gene structure have undergone extensive cycles of diversification and the accumulation of several quantitative changes in the expression of various genes that encode products related to malignancy. We have identified some of the genes that are related to progression and metastasis in breast cancer. For example, one of these genes, a novel gene called mta1 (in rodents) or MTA1 (in humans) appears to be involved in mammary cell motility and growth regulation. Thus highly malignant cellular phenotypes can arise rapidly due to specific qualitative changes in critical controlling genes, or more slowly via less critical qualitative genetic changes coupled with other cellular changes, such as loss of intercellular communication, and changes in gene expression, such as in the MTA1 gene, resulting in cellular diversification and ultimately tumour progression to the metastatic state.
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PMID:Breast cancer metastasis-associated genes: role in tumour progression to the metastatic state. 951 27

The main cause of morbidity and mortality in cancer is the formation of distant metastases. While alterations in c-oncogenes, tumour suppressor genes and DNA repair enzymes are the key molecules involved in carcinogenesis, increased expression of proteases, motility factors and altered expression of adhesion molecules are causally involved in metastasis. The proteases mediating metastasis include urokinase plasminogen activator, cathepsin B, D and L and various matrix metalloproteinases. Certain proteases involved in metastasis (e.g., urokinase plasminogen activator) have been shown to be strong and independent prognostic markers for a variety of cancers. Finally, molecules involved in cancer spread are potential targets for new forms of anti-metastatic therapies.
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PMID:Cancer metastasis: biological and clinical aspects. 954 Feb 88

The aim of this study was to compare the immunophenotype of the human colon cancer cell line HT29 tumour deposits in the lung which occurred spontaneously after subcutaneous implantation with those which arose after intravenous injection into severe combined immunodeficient (scid) mice. Irrespective of the route of implantation the colon cancer cells were readily observed in the lungs of the scid mice. Similar patterns of immunoreactivity for the proliferative markers (MiB-1, PCNA), and for the tumour suppressor gene (p53) were detected in both groups, and for carcinoembryonic antigen, with only minor quantitative differences in levels of marker expression. Whereas the marker CD44 variant 6 gave very little reaction after either route, cytokeratin expression varied amongst the different cytokeratins (CK 7, 18 or 20), and with the route of implantation. CA125 and E-cadherin were weakly expressed after intravenous injection, but generally not after subcutaneous implantation. Vimentin was not demonstrated in any of the specimens examined. In general, the expression of proliferative markers, and of oncogenes, appears to be independent of the implantation route, whilst expression of cell adhesion molecules can be dependent on the route of implantation.
Invasion Metastasis 1997
PMID:Immunophenotype of human HT29 colon cancer cell metastases in the lungs of scid mice: spontaneous versus artificial metastases. 956 Oct 26

Prognostic factors, e.g. metastatic disease, lymph node status, tumour size, histologic grade, estrogen and progesterone receptors, and markers of proliferation are used to predict the clinical course of breast cancer at the time of primary treatment. Patients with a poor prognosis are offered adjuvant therapy. For the choice of adjuvant therapy (endocrine or cytotoxic) treatment predictive factors, e.g. estrogen and progesterone receptor; are useful. Putative new prognostic factors (e.g. oncogenes, tumour suppressor genes, and invasive factors) should be evaluated together with the clinical established factors in multivariate analyses.
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PMID:Prognostic factors in breast cancer: a brief review. 970 79

A candidate tumour suppressor gene, PTEN, has recently been identified within chromosome 10q23, the locus of the Cowden syndrome/Lhermitte Duclos disease susceptibility gene. Cowden disease is an autosomal dominant cancer predisposition syndrome associated with tumours of the breast, thyroid and, less frequently, malignant melanoma. Based on the identification of mutations in sporadic breast, brain and prostate tumours, we decided to examine the potential role of PTEN in sporadic malignant melanoma. Frozen tissue from primary cutaneous melanomas (n = 23) and metastases (n = 17) were microdissected, and microsatellite markers D10S541 and D10S547, flanking the gene on both sides, were used to search for loss of heterozygosity (LOH) in the PTEN gene locus. To identify mutations within the putative tumour suppressor gene, we performed single strand conformation polymorphism (SSCP) analysis using intronic primers to amplify exons 5, 6, 7 and 8 of the PTEN gene. No LOH was detected using the polymorphic markers D10S541 and D10S547. SSCP analysis revealed no aberrant bands in the tumour specimen. Our results suggest that the PTEN gene does not play a major role in the initiation and progression of melanoma.
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PMID:The PTEN tumour suppressor gene and malignant melanoma. 976 4

The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher's exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis.
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PMID:p53 mutations and DNA ploidy in colorectal adenocarcinomas. 980 34

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
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PMID:Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. 989 67

Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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PMID:Loss of expression or mutations in the p73 tumour suppressor gene are not involved in the pathogenesis of malignant melanomas. 991 12

S100 is an acidic-calcium-binding protein, composed as a heterodimer of two isomeric subunits alpha and beta and was first described in cells of neuroendocrine origin. It plays an important role in various cellular processes such as cell differentiation and proliferation and interacts with the tumour suppressor gene p53.S100 is also present in melanoma cells and its immunhistochemical detection is widely used in the histopathological diagnosis of malignant melanoma. S100 has been detected in the serum of patients with malignant melanoma and many clinical studies have been performed to establish this protein as a tumor marker in different stages of the disease. The data suggest that S-100 beta-protein in serum of patients with malignant melanoma could be an independent prognostic marker and an additional clinical parameter for progression of metastatic disease and serological monitoring during systemic therapy. However there are patients in stage of lymph node- or systemic metastasis with negative S-100 beta-serum levels and no correlation to the course of disease. Our results confirm the findings for patients in stage III/IV. However, the percentage of S-100 beta-positive patients in stage III/IV is lower than reported in the literature, if repeatedly positive samples are excluded from statistical analysis. For monitoring in stage I and II it seems to be not helpful.
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PMID:[S-100 beta protein in serum, a tumor marker in malignant melanoma-- current state of knowledge and clinical experience]. 1035 16

During the initiation and progression of malignant melanoma a series of genetic events accumulate, including alterations of chromosome 11q. Recently, an important tumour suppressor gene, the multiple endocrine neoplasia type 1 (MEN1) gene, has been mapped on 11q13 and has been cloned. To assess whether the MEN1 region is involved in tumour initiation and progression, we analysed 23 primary cutaneous melanomas and 17 metastases for loss of heterozygosity (LOH) using two informative polymorphic markers closely linked to the MEN1 gene (PYGM and D11S449). To search for mutations within the gene, single-strand conformation polymorphism (SSCP) analysis was performed using 13 primer sets with designed intronic sequences to amplify the MEN1 coding sequence exons 2 to 10. None of the cases showed LOH at the MEN1 gene locus. By SSCP analysis, no aberrant bands were identified on exons 3 to 10. Analysis of exon 2 revealed the presence of aberrant bands in two of the analysed melanomas. Sequencing analysis revealed a genetic polymorphism at S145S (AGC-->ACT) in both sections. None of the cases analysed showed MEN1 gene mutations. This study represents the first genetic analysis of the MEN1 gene in sporadic melanomas. Our data demonstrate no evidence of deletion or mutation of the MEN1 gene in primary or metastatic melanoma. Therefore, MEN1 gene alterations appear not to be associated with tumorigenesis of malignant melanoma. The MEN1 gene appears to be a highly specific tumour suppressor gene only involving tumours within the spectrum of MEN1 disease.
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PMID:Mutation analysis of the MEN1 tumour suppressor gene in malignant melanoma. 1046 80


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