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

A characteristic feature of colorectal cancer genesis is its stepwise progression, which offers unique possibilities for studying its development. There are two principal kinds of mutation leading to uncontrolled cell proliferation and cancer. The first renders a stimulatory gene hyperactive--generation of an oncogene--and the second is the inactivation of a tumour suppressor gene. Current knowledge suggest that the change from normal mucosa to a small adenoma may be mediated by mutations of the APC gene and MCC gene on chromosome 5, by chromosome 5 deletion, by c-myc activation, and by DNA hypomethylation. The development to a large adenoma may be caused by Ki-ras mutation and further change to a dysplastic adenoma by deletion of the DCC gene on chromosome 18. The ability to become an invasive carcinoma may then be mediated by p53 mutations and deletion of chromosome 17p. Identification of genetic markers for metastatic disease is under progress.
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PMID:Genetic aspects of colorectal cancer: the surgeon's view. 889 51

The important role of oncogene amplification and tumour suppressor gene deletion in human tumours is becoming increasingly apparent. However, extensive screening of human tumours is required before the prognostic significance of such genetic abnormalities can be fully appreciated. The present investigation describes a rapid non-radioactive and largely automated procedure for the analysis of aberrant gene copy number in large numbers of tissue samples of different human tumours. This procedure is based on the sequential use of the polymerase chain reaction (PCR) and high performance ion exchange liquid chromatography (HPIEX). Using this rapid PCR/HPIEX technique, we have identified amplification and deletion of the FGF-2 gene and the FGF-3, FGF-4 and c-erb-B2 oncogenes in human tumours of the breast, ovary and endometrium. Comparison of the data with tumour pathology has revealed possible associations between aberrant gene copy number and tumour type, invasiveness and metastases.
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PMID:Aberrant FGF-2, FGF-3, FGF-4 and C-erb-B2 gene copy number in human ovarian, breast and endometrial tumours. 896 18

Breast cancer is a major cause of morbidity and mortality in women in many parts of the world. Breast carcinomas are heterogenous in their biological and clinical behaviour and a greater understanding of how they develop and progress could lead to more directed forms of screening and therapy. It is important to determine the molecular mechanisms underlying the natural history of breast cancer. Developments in the techniques for molecular analysis have meant that they can now be applied to a large range of clinical material such as cytological preparations and fixed, embedded material, so increasing the potential for relating any molecular alterations to clinical behaviour and response to therapy. In this review we consider recent developments in three areas of importance to breast cancer; genetic analysis-oncogenes, tumour suppressor genes, loss of heterozygosity, microsatellite instability, familial breast cancer; steroid receptors, oestrogen regulated proteins, epidermal growth factor receptor, growth factors particularly transforming growth factor beta; and cell adhesion, invasion and metastasis-E-cadherin, integrins, proteases. These are discussed in relation to potential for screening, prognosis and treatment.
Cancer Metastasis Rev 1997 Jun
PMID:Molecular pathology of breast cancer and its application to clinical management. 915 78

There has long been a clinical need for improved molecular pathology in melanoma, particularly in the histopathology laboratory where the differentiation of melanoma from its benign counterparts is commonly difficult. The need for improved molecular pathology has recently increased as immunotherapeutic options for the treatment of the tumour evolve. It seems likely that in the relatively near future tumour typing before and during immunotherapy will be needed. The identification of the tumour suppressor gene coding for the protein p16 as an important gene in the pathogenesis of melanoma is of great interest but the identification of oncogenes having a significant role in melanoma carcinogenesis has been slow.
Cancer Metastasis Rev 1997 Jun
PMID:Molecular pathology of melanoma. 915 84

Breast cancer emerges by a multistep process which can be broadly equated to transformation of normal cells via the steps of hyperplasia, premalignant change and in situ carcinoma. The elucidation of molecular interdependencies, which lead to development of primary breast cancer, its progression, and its formation of metastases is the main focus for new strategies targetted at prevention and treatment. Cytogenetic and molecular genetic analysis of breast cancer samples demonstrates that tumour development involves the accumulation of various genetic alterations including amplification of oncogenes and mutation or loss of tumour suppressor genes. Amplification of certain oncogenes with concomitant overexpression of the oncoprotein seems to be specific for certain histological types. Loss of normal tumour suppressor protein function can occur through sequential gene mutation events (somatic alteration) or through a single mutational event of a remaining normal copy, when a germline mutation is present. The second event is usually chromosome loss, mitotic recombination, or partial chromosome deletion. Chromosome loci 16q and 17p harbour tumour suppressor genes, which seem to be pathognomonic for the development or progression of a specific histological subtype. There are an overwhelming number of abnormalities that have been identified at the molecular level which fit the model of multistep carcinogenesis of breast cancer. When the functions of all of these genes are known and how they participate in malignant progression, we will have the tools for a more rational approach to diagnosis, prevention and treatment. This review deals only with the factors that are involved in the conversion of a normal breast cell into a malignant cell rather than those required for invasion and metastases. A key critical long-term step in the molecular analysis of breast cancer will be to link the specific molecular damage with the effects of environmental carcinogens.
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PMID:Multistep carcinogenesis of breast cancer and tumour heterogeneity. 923 83

This short report describes the detection of mutations of the TP53 tumour suppressor gene in sporadic ovarian carcinomas using archival paraffin-embedded tissues and automated fluorescent DNA sequencing. TP53 mutations were detected in eight tumours. Missense mutations predominated and all were transitions. Mutations were commonest in late-stage serous tumours. In three cases, where tissue was available, the mutations were homogeneous throughout several sections of the bilateral ovarian tumours and in omental metastases. These data confirm the findings of previous investigations describing TP53 mutation in ovarian carcinoma and demonstrate that archival paraffin-embedded tissues can be used for such analyses.
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PMID:TP53 mutation in ovarian carcinoma. 930 56

In order to investigate the role of TP53 in tumour progression and metastasis, we analysed 33 liver metastases of colorectal carcinomas and 19 primary colon carcinomas from the same hospital with respect to mutational changes, loss of heterozygosity and expression of the TP53 tumour suppressor gene. Direct sequencing of PCR products corresponding to the coding region of TP53 revealed that 13 of 19 primary tumours (68%) and 23 of 33 liver metastases (70%) had mutations in the TP53 gene. The distribution of mutations along the coding region of TP53 was similar in liver metastases compared to primary tumours. Thus, codon specificity did not seem to be a relevant factor and cells carrying specific TP53 mutations seem to have no selective advantage in the metastasising process. Comparing our data with the mutational spectra found in other countries did not reveal differences in the distribution of mutations along the coding region. Most of the metastases analysed showed loss of heterozygosity (LOH, 9 of 12 cases, 75%) and strong nuclear staining in immunohistochemistry (10 of 17 cases, 59%). Furthermore, with respect to mRNA expression levels, tumours carrying TP53 mutations showed significantly higher p53 mRNA levels compared to those without TP53 mutations. Thus, regulation of p53 mRNA levels seems to be subject to selection processes in tumourigenesis.
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PMID:The status of p53 in the metastatic progression of colorectal cancer. 930 61

We examined the effect of the stable transfection of latent TGF-beta 1 cDNA, under the control of a cytomegalovirus promoter in the expression vector pcDNA3, into a 4NQO-induced clonal rat oral keratinocyte cell line that formed undifferentiated spindle cell tumours following subcutaneous transplantation to athymic mice. Test cells containing latent TGF-beta 1 cDNA produced a 2.3-fold increase in TGF-beta 1 protein compared to pcDNA3 controls as demonstrated by ELISA. Neutralisation experiments indicated that the majority of the protein was in the latent form. Untransfected and transfected (containing either TGF-beta 1 cDNA or pcDNA3) cell lines were keratin negative and vimentin positive. Cells transfected with TGF-beta 1 were inhibited more than pcDNA3 controls when cultured in an anchorage dependent or independent environment. Subcutaneous transplantation of cells overproducing TGF-beta 1 resulted in tumours of significantly smaller volume than vector-only controls. Further, orthotopic transplantation of cells containing TGF-beta 1 cDNA to the floor of the mouth in athymic mice markedly inhibited the development of pulmonary metastases compared to vector-only controls. Both test and control cell lines in athymic mice formed undifferentiated tumours with a complete absence of keratin elaboration. Subcutaneous xenografts were recultured and cells containing the TGF-beta 1 cDNA produced a similar amount of TGF-beta 1 peptide as the cells containing pcDNA3 only. The production of TGF-beta 1 by both of the xenograft-derived cell lines was significantly less than the parent, pre-transplanted cell lines and the untransfected cell line. All of the cell lines were inhibited by exogenous TGF-beta 1. Our results demonstrate that autocrine TGF-beta 1 functions as a tumour suppressor in vitro and in vivo in 4NQO-induced spindle tumour cells that are growth inhibited by the ligand. Furthermore, tumour formation in athymic mice is associated with selection for a cell phenotype with diminished autocrine TGF-beta 1 production.
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PMID:Overexpression of autocrine TGF-beta 1 suppresses the growth of spindle epithelial cells in vitro and in vivo in the rat 4NQO model of oral carcinogenesis. 933 12

Breast cancer is the commonest malignancy in women and although identification of this multi-system disease has increased, the survival rates have not dramatically altered over the past four decades. Optimium treatment of patients with breast cancer is a subject of great debate and traditionally may be divided into surgery, radiotherapy, chemotherapy and hormone manipulation. Halsted's radical mastectomy, although initially superseded by more mutilating surgery involving removal of tumour, breast, pectoral muscles and axillary contents, has given way to more conservative surgery and breast conservation, so now removal of the tumour with a marginal of healthy tissue is possible. Additional loco-regional radiotherapy has added to the increasing number of treatment options available to both doctor and patient. Systemic adjuvant therapy, primarily hormonal therapy, is used with the aim of decreasing the incidence of recurrence and distant tumour development. Through the process of randomized controlled trials these new therapeutic treatments have shown to be effective in the treatment of locoregional disease. Surgery in patients with advanced systemic disease is limited, however radiotherapy is of considerable importance and can be used to treat or palliate sites of metastases. In recent years trials have assessed chemotherapeutic regimens. However, limited number of patients and adequate randomization have hindered the confident acceptance of these results. Cyclophosphamide, methotrexate and 5 fluorouracil still remain the standard chemotherapeutic regimen, however many new drugs are currently undergoing trials and these or combinations of these may prove to be of future clinical use. Dramatic advances in cell and molecular biology have allowed the development of novel breast cancer therapies. Specific oncogenes and loss of tumour suppressor genes have been associated with decrease patient survival, with the presence of lymph node metastases and with decreased relapse free survival. Growth factor receptor blockers and tyrosine kinase inhibitors may be developed to specifically eradicate breast cancer cells. Immunotherapy and gene therapy may produce effective therapies. Trials utilizing cytokines and trials increasing the immunogenicity of tumours have already reported promising results. Surgery, chemotherapy, radiotherapy and hormone manipulation are the major treatment arms of breast cancer therapy. However, breast cancer still accounts for 20 percent of all female cancer deaths and the overall survival of patients has remained relatively static over the past forty years. From our increasing understanding of the pathological processes involved in the development and spread of breast cancer, new pharmaceutical, immunological and gene therapies may dramatically increase the cure rate of this serious disease.
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PMID:The increasing efficacy of breast cancer treatment. 936 31

Mouse mammary tumour virus (MMTV)/neu transgenic mice develop clonal or oligoclonal mammary tumours stochastically. The pathology of these tumours is very similar to that of human breast tumours. Moreover, these mouse tumours metastasize in the lungs. We present evidence that this mouse model of human breast tumours can be instrumental in identifying novel genes of two distinct classes (activated oncogenes or tumour suppressor genes) which may collaborate with the c-erbB-2/neu transgenic oncogene.
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PMID:Use of mouse mammary tumour virus (MMTV)/neu transgenic mice to identify genes collaborating with the c-erbB-2 oncogene in mammary tumour development. 951 20


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