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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of a human nuclear antigen associated with cell proliferation and recognized by monoclonal antibody Ki-67 was investigated during the cell cycle in a breast cancer cell line (MCF-7) and in a normal human fibroblastic cell line (MRC-5). Image cytometry was used to determine Ki-67 antigen and DNA amounts at the cell level. Results confirm Ki-67 antibody specificity for proliferating cells. The antigen expression increases with cell progression through the cycle. Image cytometry also permits the description of the Ki-67 topographic distribution at the various phases of the cell cycle. Ki-67 antigen is essentially localized in the nucleoli at G1 phase. A nucleoplasmic distribution appears later in the cell cycle. The parameters measured on the labelling allow the calculation of the growth fraction and an evaluation of the phase fractions. Other results in this study strongly suggest that nucleolar rRNA synthesis is required for Ki-67 antigen expression. Hypotheses on Ki-67 functions are proposed.
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PMID:Quantification and topographical description of Ki-67 antibody labelling during the cell cycle of normal fibroblastic (MRC-5) and mammary tumour cell lines (MCF-7). 248 98

The viability of human breast cancer cells (cell lines MCF-7 and MDA-MB 231) was inhibited in vitro in a dose-dependent manner by selenium supplementation. However, a normal diploid human cell line (MRC-5) was relatively resistant to selenium supplementation. The presence of selenium as Na2SeO3 at 1.1 X 10(-6) M reduced cancer cell viability by approximately 50%, whereas non-cancerous cells were not affected. Parenteral administration of sodium selenite also significantly inhibited the growth of the cancerous cell lines transplanted into nude mice. Selenium administration at 0.8 micrograms/g body wt resulted in an 80-93% reduction in the rate of tumor growth without apparent ill effects on the host.
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PMID:Inhibition of human breast cancer cells by selenium. 651 51

Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts (1949), leukemia (1952) and severe mental retardation among newborn infants after intrauterine exposure (1952). No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements (1956), the F1 mortality (1981), cytogenetic studies (1987) or biochemical genetic studies (1988). Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes (1968), and somatic cell mutations were found at the glycophorin A locus in erythrocytes (1992). Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia (1995), a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. Also, obligate heterozygote female relatives can be studied for increased susceptibility to radiation-induced breast cancer, as suggested by clinical studies. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others (1994). The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer.
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PMID:Delayed effects of external radiation exposure: a brief history. 748 Jun 42

The applications of DNA cloning and fluorescent in situ hybridization (FISH) techniques have strengthened the hypothesis of an ordered chromatin structure in interphase nuclei, strongly suspected to vary with functional state. The nonrandom distribution of the centromeres and their dynamic rearrangement during the cell cycle have been well documented. A close proximity of specific centromeres to nucleoli has also been reported, but the functional meaning of this association is still unknown. In order to investigate whether the chromosome 1 centromere region to nucleolus association depends on the cell cycle and chromosome status, we combined FISH of probes specific for the 1q12 region with Ki-67 nucleolar antigen fluorescent immunocytochemical (FICC) detection on the MCF-7 human breast cancer cell line and on the MRC-5 normal fibroblastic cell line. Both FISH and FICC signals were interactively localized in a one-step fluorescent microscopic observation and further analyzed using the Highly Optimized Microscope Environment (HOME) graphics microscope workstation, which provided computerized interactive marking of 1q12 to nucleolus associations (1q12-nu) at the individual nucleus and nucleolus levels. This study confirms that centromeric regions, other than those adjacent to the major ribosomal cistrons, contribute to the perinucleolar chromatin and demonstrate that, during the cell cycle, the heterochromatic band 1q12 is dynamically rearranged with regard to both the nuclear volume and the nucleoli. A relationship between the association of the chromosome 1 pericentromeric region with nucleoli and the nucleolar transcriptional activity is also strongly suggested.
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PMID:Interactive computer-assisted analysis of chromosome 1 colocalization with nucleoli. 798 93

We used Transwell chambers to study separately cellular motility and invasion. In order to assess the cellular motility, polycarbonate microporous filters were coated with extracellular matrix proteins which adsorbed on the filters without clogging the pores. To investigate the invasive behavior of tumor cells, filters were covered with a layer of Matrigel which clogged the pores. The motility and the invasion of breast cancer cell lines (MDA-MB-231, MCF-7/6 and MCF-7/AZ cells) were assessed quantitatively in different culture media: defined (serum-free), serum-containing and normal human fibroblast MRC-5 conditioned media. In serum-containing medium, tumor cells migrated and invaded through the coated and covered filters. Their motility and invasion potentials were considerably lower in defined medium, whereas medium conditioned by MRC-5 fibroblasts stimulated both motility and invasion but not growth. The MRC-5 conditioned medium induced also the spreading of clusters of MCF-7/6 cells grown on Matrigel-coated plates.
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PMID:Effect of MRC-5 fibroblast conditioned medium on breast cancer cell motility and invasion in vitro. 951 1

Hepatocyte growth factor/scatter factor (HGF/SF), a cytokine associated with cancer cell migration and invasion, is synthesised as pro-HGF/SF and requires activation by factors such as the HGF activator (HGFA). The present study examined the expression of HGF/SF, HGFA, the two inhibitors to HGFA action known as hepatocyte growth factor activator inhibitors type 1 and 2 (HAI-1 and HAI-2), and the HGF/SF receptor, c-Met. We examined a variety of normal and cancer cells, which included breast, prostate, colon, bladder, liver, lung, and pancreatic cancer cell lines. The cell lines all displayed different patterns of expression, and in some of the cancer cell lines the concomitant expression of the HGF/SF, c-Met, HGFA and HAI genes was observed. The only cell line to produce a significant amount of HGF/SF was the human fibroblasts (MRC-5) which also co-expressed the c-Met and HGFA genes to allow autocrine regulation of HGF/SF stimulation, and importantly displayed little or no inhibitor presence to suppress the biological function of HGF/SF. The highly invasive breast cancer cells (MDA MB-231) expressed large amounts of both c-Met and HGFA, to enable maximum influence from HGF/SF and did not express the HAI-1 gene at all, which suggests a shift in the activation-inhibition balance to enhance metastatic potential. In contrast, the breast cancer cells of low invasive nature (MCF-7) displayed a low level of c-Met and HGFA expression, while expressing the HAI genes to a high degree. However, there was no correlation between HAI-1 and HAI-2 expression. Interestingly, there appeared to be an inverse correlation between the degree of HGFA and HAI-1 expression, which may influence the metastatic ability of the cancer cells. This study has shown that c-Met, HGF/SF and its activator and inhibitors are expressed in different patterns in cancer cells and in normal cells. The balance between HGF/SF activation and HGFA inhibition is critical to the metastatic potential of the tumour cells, and the invasive nature of the cancer cell lines correlated to the degree of c-Met and/or HGFA presence along with HAI-1 expression.
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PMID:Expression of hepatocyte growth factor/scatter factor, its activator, inhibitors and the c-Met receptor in human cancer cells. 1156 67

ErbB-3 (HER3) is a member of the epidermal growth factor receptor family. Increasing evidence suggests that elevated expression of ErbB-3 is important for malignancy. In this study, we found that elevated levels of ErbB-3 expression did not occur in the absence of AP-2gamma in a panel of human mammary epithelial and fibroblasts cell lines. In contrast, there was no association between the expression of AP-2alpha or AP-2beta and the level of ErbB-3, or between AP-2alpha and AP-2gamma double positivity and ErbB-3 expression. In co-transfection experiments, exogenous expression of AP-2gamma robustly activated ErbB-3 promoter activity. Moreover, expression of a dominant negative AP-2 protein, AP-2delta (deleted residues 31-117), not only repressed the ErbB-3 promoter activity but also suppressed endogenous ErbB-3 transcription in the ErbB-3 overexpressing cell line MRC-5VA. Overexpression of AP-2A resulted in a decreased proliferation rate and inhibitin of colony formation. Taken together, these data strongly support a role for the AP-2 gene family, in particular, AP-2gamma, in the control of ErbB-3 expression. Interference with the function of transcription factor AP-2 might provide a potential strategy for modulation of the malignant phenotype.
Breast Cancer Res Treat 2002 Jan
PMID:Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth. 1185 73

Breast cancer cells oversecrete the lysosomal peptidase cathepsin D as a pro-enzyme. In this study, we assessed the effect of media conditioned by MRC-5 fibroblasts or MCF-7/6 breast cancer cells on cathepsin D (CD) production and secretion by these two cell types. We also considered the influence of estrogens and matrix components (type I or type IV collagen, or Matrigel) on the expression and activity of CD produced by breast cancer cells of different invasive potentials (MCF-7/AZ, MCF-7/6, MDA-MB-231). In our system, fibroblasts conditioned medium does not significantly affect CD levels produced and secreted by the MCF-7/6 cells. However, we found that fibroblasts are able to capture the pro-CD secreted by these tumor cells by a mannose 6-phosphate-dependent process. We also found a positive correlation between the proportion of extracellular CD levels and the invasive potentials of the tumor cell types considered. If estrogens are able to upregulate CD production and secretion by receptor-positive cells, it is not the case of extracellular matrix components. On the other hand, our results indicate that matrix components are able to influence the distribution of the different CD forms in and out of the cells. Our data suggest that tumor fibroblasts, by enhancing their intracellular CD levels, could assist cancer cells in the digestion of extracellular matrix during the invasion of tissues.
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PMID:Fibroblasts capture cathepsin D secreted by breast cancer cells: possible role in the regulation of the invasive process. 1189 22

Endostatin has been considered a highly specific inhibitor of endothelial cell proliferation and/or migration. To explore the use of endostatin in antiangiogenic gene therapy, we generated a recombinant adenovirus, AdEndo, carrying the gene for mouse endostatin. Injection of 10(9) PFU of AdEndo resulted in a low but significant suppression (25%) of preestablished tumor growth in murine models involving murine Lewis lung carcinoma (LLC) and human breast cancer MDA-MB-231 tumors. Greater anticancer activity was observed when the same dose of AdEndo was injected into two other preestablished murine models involving C51 murine colon cancer and HT29 human colon cancer (55 and 47% tumor growth reduction, respectively). In vitro, endostatin derived from AdEndo-infected MRC-5 fibroblasts inhibited the growth of C51 and HT29 cell lines (72 and 61%, respectively). The extent of this inhibition was comparable to that observed in endothelial cells: 75% for microcapillary endothelial cell line HMEC-1, 52% for human dermal microvascular endothelial cells, 46% for human umbilical vein endothelial cells, and 67% for calf pulmonary arterial endothelial cells. Both endothelial and colon cancer cells showed a clear increase in cell apoptosis (4- to 5-fold for endothelial cells and 5- to 10-fold for colon cancer cells) and an accumulation in the G(1) phase of the cell cycle. This antiproliferative activity was not observed in other tumor cell lines: LLC, MDA-MB-231, murine colon adenocarcinoma MC38, human prostate cancer cell line DU145, and human breast cancer cell line CAL51. Taken together, these results provide evidence that, in addition to its antiangiogenic activity, endostatin exerts a direct anticancer action that appears to be restricted to some tumor cell lines. Thus, endostatin could be used in some colon cancer treatments and its clinical efficacy would depend on the response of tumor cells themselves.
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PMID:Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells. 1286 17

Lymphangiogenesis is key to the lymphatic spread of cancer cells. The current study examined the potential effect of hepatocyte growth factor (HGF), a factor known to have strong biological effects on endothelial cells, on the lymphangiogenic function of endothelial cells and the formation of lymphatic vessels using both in vitro and in vivo models. Human endothelial cells that have lymphatic characteristics, human prostate and breast cancer cells PC-3 and MDA MB 231, were used. Expression of lymphatic markers, podoplanin, Prox-1, vascular endothelial growth factor receptor 3 (VEGF-R3) and LYVE-1 was determined using reverse transcription polymerase reaction and quantitative PCR. In nude mice prostate and breast xenograft tumour models, either HGF or an HGF-producing fibroblast cell line MRC-5 was given with or without the HGF antagonist, NK4. The lymphangiogenic marker and lymphatic vessels in tumour tissues were also assessed using quantitative PCR and immunohistochemistry, respectively. In the mice tumour models, infusion of rhHGF significantly increased the levels of podoplanin and LYVE-1 in the tumour (p=0.05 for podoplanin and p<0.05 for LYVE-1 vs. without HGF in the prostate tumour model, p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF for the breast tumour model; p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF in the breast tumour model). The increased level of LYVE-1 transcript was supported by an increase in the number of LYVE-1-positive lymphatic vessels in tumours, using immunohistochemical analysis. Co-injection of MRC5 cells also increased the levels of LYVE-1 and number of LYVE-1-positive vessels in tumour tissues. The effects of HGF and MRC5 were significantly reduced by the HGF antagonist, NK4. In the in vitro models, rhHGF significantly increased the level of both podoplanin and LYVE-1, as shown by quantitative PCR analysis. Hepatocyte growth factor has potential lymphangiogenic activities, and this may have important implications in the nodal spread of cancer cells.
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PMID:The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo. 1614 11


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