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)

nma, a novel gene, was isolated by using a subtractive hybridization technique in which the gene expression was compared in a panel of human melanoma cell lines with different metastatic potential. nma mRNA expression (1.5 kb) is high in poorly metastatic human melanoma cell lines and xenografts and completely absent in highly metastatic human melanoma cell lines. Fluorescence in situ hybridization combined with the analysis of a panel of human-rodent somatic cell hybrids indicated that the nma gene is located on human chromosome 10, in the region p11.2-p12.3. Sequence analysis of nma showed no homologies with other known genes or proteins, except for several partially sequenced cDNAs. The predicted amino acid sequence suggests that the protein encoded by nma contains a transmembrane domain. Expression of nma is high in human kidney medulla, placenta and spleen, low in kidney cortex, liver, prostate and gut and absent in lung and muscle. Whereas nma is not expressed in normal skin tissue, expression is high in melanocytes and in 3 out of 11 melanoma metastases tested.
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PMID:Expression of nma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts. 862 Dec 28

B16-F10 and B16-BL6 are B16 mouse melanoma sublines that preferentially metastasize to the lung following i.v. and s.c. injections, respectively. To study molecular mechanisms underlying the different metastatic behaviors exhibited by the B16 melanoma sublines, we performed differential hybridization of the genes transcribed in these cells and compared their expression levels. We isolated four genes that were highly expressed in B16-F10 cells but not in B16-BL6 cells: TI-225 (polyubiquitin), TI-229 (pyruvate kinase), TI-241 (LRF-1 homologue), and TI-227 (novel gene). Triosephosphate isomerase, 10-formyltetrahydrofolate dehydrogenase, tyrosinase-related protein 2, cytochrome c oxidase, ATP synthetase alpha subunit, RNA helicase, and ribosomal protein (L37, J1, acidic phosphoprotein), however, showed higher expression in B16-BL6 cells than in B16-F10 cells. Among these clones, transfection of TI-241 into the low metastatic clone F1 converted the parental cells from low- into high-metastatic cells. TI-241 may regulate the expression of various genes as a transcription factor in the complex process of metastasis.
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PMID:Identification of genes differentially expressed in B16 murine melanoma sublines with different metastatic potentials. 863 Oct 27

Melanoma lines MEL.A and MEL.B were derived from metastases removed from patient LB33 in 1988 and 1993, respectively. The MEL.A cells express several antigens recognized by autologous cytolytic T lymphocytes (CTL) on HLA class I molecules. The MEL.B cells have lost expression of all class I molecules except for HLA-A24. By stimulating autologous lymphocytes with MEL.B, we obtained an HLA-A24-restricted CTL clone that lysed these cells. A novel gene, PRAME, encodes the antigen. It is expressed in a large proportion of tumors and also in some normal tissues, albeit at a lower level. Surprisingly, the CTL failed to lyse MEL.A, even though these cells expressed the gene PRAME. The CTL expresses an NK inhibitory receptor that inhibits its lytic activity upon interaction with HLA-Cw7 molecules, which are present on MEL.A cells and not on MEL.B. Such CTL, active against tumor cells showing partial HLA loss, may constitute an intermediate line of anti-tumor defense between the CTL, which recognize highly specific tumor antigens, and the NK cells, which recognize HLA loss variants.
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PMID:Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. 904 41

Ex vivo genetically engineered cytokine-secreting tumor cell vaccines have been shown to prevent metastatic disease in animal models of lung and breast cancer. Because of the inefficiency of existing modes of gene delivery in transducing primary human tumor cells, it has been difficult to clinically apply this strategy. In this study, liposome-mediated delivery of an adeno-associated virus (AAV)-based plasmid containing the sequence for murine gamma-interferon (gamma-IFN) (pMP6A-mIFN-gamma) was used to generate cytokine-secreting murine tumor cell vaccines. High levels of gamma-IFN and elevated class I major histocompatibility complex expression after transfer of pMP6A-mIFN-gamma into the murine lung cancer cell line, D122, was demonstrated. The efficiency of gene transfer was determined by two different methods and was estimated to be 10-15%. Irradiated gamma-IFN D122 cells generated by this novel gene delivery system (D122/pMP6A-mIFN-gamma) and also by standard retroviral methods (DIF2) were administered as weekly vaccinations by intraperitoneal injection to animals bearing 7-day-old intrafootpad D122 tumors. Hindlimb amputation was performed when footpad diameters reached 7 mm, and lungs were harvested 28 days later. Animals vaccinated with gamma-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in footpad tumor growth when compared with controls and DIF2 cells. Fifty-seven percent of animals vaccinated with D122/pMP6A-mIFN-gamma were free of pulmonary metastases 28 days after amputation, significantly improved from the 0, 7, and 15% observed in animals vaccinated with irradiated parental D122 cells, irradiated D122 cells lipofected with an empty-cassette vector (pMP6A), or DIF2 cells, respectively. These results and the ability to transfer genes with this delivery system to a broad range of tumor types support its use in the generation of cytokine-secreting tumor cell vaccinations for use in clinical trials.
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PMID:Active immunization with tumor cells transduced by a novel AAV plasmid-based gene delivery system. 910 11

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

We have used differential cDNA display to search for genes whose expression correlates with an aggressive phenotype in variants of the B16 murine melanoma line, B16-F1 and B16-F10. This analysis identified a novel gene, termed melastatin, that is expressed at high levels in poorly metastatic variants of B16 melanoma and at much reduced levels in highly metastatic B16 variants. Melastatin was also found to be differentially expressed in tissue sections of human melanocytic neoplasms. Benign nevi express high levels of melastatin, whereas primary melanomas showed variable melastatin expression. Melastatin transcripts were not detected in melanoma metastases. Within the set of human primary cutaneous melanomas examined, melastatin expression appeared to correlate inversely with tumor thickness. The expression pattern observed suggests that loss of melastatin expression is an indicator of melanoma aggressiveness.
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PMID:Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. 953 57

The morbidity in most cancer patients is not due to their primary cancers; it is due to metastatic disease. Thus understanding the progression of tumors to the metastatic state and the changes that take place in highly malignant cells are important in the development of new therapeutic approaches to diagnose, prognostically assess and treat highly progressive malignancies. Changes in the expression of certain genes or alterations of gene structures and encoded products can result in benign tumor cells progressing to the invasive and metastatic states. This has been shown in the laboratory by transferring dominantly acting oncogenes into susceptible cells and then testing the malignant properties of these cells in vivo. Usually such rapid qualitative changes in malignant state occur only rarely; the natural progression of tumor cells to the invasive or metastatic state occurs through a slow stepwise process of change. Tumor progression, in some instances, can be reversible, involving changes in dominantly acting oncogenes or tumor suppressor genes. The natural progression of tumors to highly malignant states also involves their ability to circumvent host microenvironmental controls that regulate cellular growth and diversity. Quantitative changes in gene expression rather than qualitative changes in gene structure are important in microenvironmental effects on progression. One of the important mechanisms of cellular regulation in epithelial tissues, such as breast epithelium, appears to be mediated by intercellular junctional communication. Changes in gene expression can result in loss of junctional communication, followed by cellular diversification and progression. Highly malignant tumor cells that have slowly evolved in vivo with only a few qualitative changes in gene structure have probably undergone extensive cycles of diversification and have multiple quantitative differences in gene expression. Some of these genes are related to metastasis. For example, we have identified a novel gene called mta1 (rat) or MTA1 (human) that appears to be involved in mammary cell motility and growth regulation. This may be an example of a gene that regulates highly malignant cellular phenotypes. When coupled with other cellular changes, such as loss of intercellular communication, specific changes in gene expression may result in cellular diversification and tumor progression.
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PMID:Metastasis-Associated genes and metastatic tumor progression. 989 Dec 20

A novel gene, termed p73 with significant homology to p53, has been identified at 1p36, a chromosomal region which is frequently deleted in malignant melanoma. To determine whether p73 is involved in melanoma development we analyzed 8 benign melanocytic nevi, 17 primary melanomas, 34 melanoma metastases and 9 melanoma cell lines for p73 alterations. Allelic loss at the p73 locus was observed in 2 of 10 cases (20%) and occurred only in metastatic tumors. Mutation analysis of the DNA-binding domain of p73 revealed no somatic mutations in the tumor specimens and melanoma cell lines analyzed, whereas the p53 gene was mutated in 5 of 9 melanoma cell lines. Expression analysis of p73 using semiquantitative RT-PCR demonstrated that p73 is not expressed or at exceedingly low levels in benign melanocytic nevi, primary melanomas and lymph node metastases, but at various levels in melanoma cell lines. Our data indicate that p73 does not play a role as a tumor suppressor in melanoma development.
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PMID:Lack of p73 mutations and late occurrence of p73 allelic deletions in melanoma tissues and cell lines. 1040 74

Clinical and experimental evidence suggests that tumor cells shed into the circulation from solid cancers are ineffective in forming distant metastasis unless the cells are able to respond to growth conditions offered by the secondary organs. To identify the phenotypic properties that are specific for such growth response, we injected carcinoma cells, which had been recovered from bone marrow micrometastases in a breast cancer patient who was clinically devoid of overt metastatic disease and established in culture, into the systemic circulation of immunodeficient rats. The animals developed metastases in the central nervous system, and metastatic tumor cells were isolated with immunomagnetic beads coated with an antibody that was reactive with human cells. The segregated cell population was compared with the injected cells by means of differential display analysis, and two candidate fragments were identified as up-regulated in the fully metastatic cells. The first was an intracellular effector molecule involved in tyrosine kinase signaling, known to mediate nerve growth factor-dependent promotion of cell survival. The second was a novel gene product (termed candidate of metastasis-1), presumably encoding a DNA-binding protein of helix-turn-helix type. Constitutive expression of candidate of metastasis-1 seemed to distinguish breast cancer cells with metastatic potential from cells without metastatic potential. Hence, our experimental approach identified factors that may mediate the growth response of tumor cells upon establishment in a secondary organ and, thereby, contribute to the metastatic phenotype.
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PMID:Expression of a novel factor in human breast cancer cells with metastatic potential. 1212 56

Metastasis, a major factor contributing to poor prognosis of cancer patients, is caused by a complex series of events that involve many genes. To investigate this process, we analyzed by differential display three cell lines that had been established from a murine colon adenocarcinoma (colon 26), NL4, NL17, and NL22, each of which possessed a different potential for metastasis in mice. We report here the identification of a novel gene, ream (reduced expression associated with metastasis), which showed significantly lower expression in NL17 and NL22 with a high potential for metastasis than in NL4 without a metastatic potential. The human counterpart of murine ream expressed two sizes of transcript, 4.4 kb and 1.8 kb, both encoding the same 367-amino acid peptide, which appeared to contain four membrane-spanning regions. The cDNA showed no significant homology to any known genes in the public database. Human REAM was found to lie within an 800-kb segment of 8p21.3-22, where we had previously identified a commonly deleted region in colorectal and hepatocellular carcinomas. Its expression was reduced in more than half of the human colorectal cancers we examined, particularly in advanced stages with liver metastasis. Furthermore, we identified somatic mutations of this gene in a colorectal cancer, a hepatocellular carcinoma, and a nonsmall lung cancer among 111 human tumors of various stages examined.
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PMID:Isolation of a novel gene on 8p21.3-22 whose expression is reduced significantly in human colorectal cancers with liver metastasis. 1091 88


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