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

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.
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PMID:Pyridinium crosslinks as markers of bone resorption in patients with breast cancer. 193 10

Eighty-five breast cancer specimens were processed as part of a program in tumor acquisition, propagation, and preservation for biotherapy. Nine long-term culture cell lines were developed. Four cell lines were from solid tumor metastases, two lines were from pleural fluid specimens, and three were from xenograft tumors grown in nude mice. Two of the xenograft-derived cell lines were from biopsies which produced tumor cell lines as well. Success in establishing cultures did not correlate with the viability of the biopsy received. Poor tumor cell attachment to culture plastic was the most common problem. For certain specimens, attachment and growth were enhanced on collagen and extracellular matrix substrates. Collagen was beneficial in the development of one cell line. The cell lines were characterized and each of the lines contained more nuclear DNA than found in normal cells. Four of five lines tested were tumorigenic in nude mice. Five of nine were clonogenic in soft agar. Each of the cell lines tested reacted with at least two anti-tumor monoclonal antibodies. Xenograft and biopsy-derived cell lines from the same tumor were similar in their characteristics. While breast cancers are indeed difficult to establish and propagate in culture, the use of xenografts and special substrates appears to be beneficial in the development of cell lines from some tumors.
Breast Cancer Res Treat 1990 Dec
PMID:Cultured cell lines from human breast cancer biopsies and xenografts. 209 90

Collagen gel culture of rat mammary epithelial cells was used as an in vitro assay system for determination of the therapeutic efficacy of three cytotoxic agents commonly used in the treatment of human breast cancer, namely 5-fluorouracil (5-FU), methotrexate, and Adriamyin (ADR). The same three drugs were also evaluated in vivo, and a good correlation was obtained between the results in these two systems. A 9-d culture was shown to be more reliable than a 12-d culture, because nondrug-related cell mortality became a confounding factor after 12 d. Although further experiments are necessary, it is suggested that collagen gel culture may well prove to be a useful assay system for determination of sensitivity of tumor cells to cytotoxic drugs with possible clinical applications in the choice of treatment modality administered to cancer patients.
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PMID:Collagen gel culture of rat mammary tumor cells as an assay system for determination of therapeutic efficacy of chemotherapeutic agents. 339 30

The basis of the scirrhous reaction to human breast carcinoma was investigated. When normal human skin fibroblasts were plated on the preformed extracellular matrix of human breast tumor cells, a remarkable series of changes was observed. The matrix of the tumor cells was mitogenic for the fibroblasts. An increased growth rate and a fourfold increase in cell density was observed. There was also a change in cell morphology and in the pattern in which the cells grew, with an apparent loss of contact inhibition. The spindle-shaped fibroblasts became more elliptical and grew in a series of whorls and dense ridges with spaces between them. These observations were made with the use of newborn foreskin fibroblasts and the matrix of an established line of human breast cancer cells, ZR75-1. No such effect was seen when fibroblasts were plated on their own preformed matrix, on the matrixes of other cell types, on various type-specific collagen gels, or on a combination of collagen and fibronectin or when fibroblasts were grown in media conditioned by the ZR75-1 cells. A floating tumor cell matrix added to the cell media also did not provide the mitogenic stimulus. Apparently, fibroblasts required direct contact with the tumor cell matrix for the mitogenic response to occur. In vivo, the matrix of breast tumor cells may modulate the growth and the morphology of host stromal cells. Collagen is a major synthetic product of fibroblasts. The stimulation of stromal cells to proliferate by adjacent breast tumor matrix may be the basis of the desmoplastic reaction, the intense fibrotic response associated with human breast cancer.
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PMID:The matrix of human breast tumor cells is mitogenic for fibroblasts. 671 76

Collagen, a major component of the extracellular matrix, is important in maintaining the in vivo characteristics of epidermal cells in vitro. In the present study, the morphological and proliferative characteristics of two human mammary epithelial cell lines (T-47D and MCF-7) cultured in cowhide collagen (Vitrogen 100) were studied. When grown in collagen, the tumor cells displayed a spherical shape and formed multilayered, tumorlike aggregates; desmosomes were observed between cells. In contrast, both cell lines grew as monolayers on plastic substratum; cells were characteristically flat and polygonal. When grown in collagen matrix, the human breast cancer cells became more dependent on serum for growth: cells proliferated in the presence of 10% fetal bovine serum (FBS) but failed to grow in 1% serum. On the other hand, these cells proliferated rapidly in 1% serum when they were grown on plastic. Even in 10% serum the doubling time of cells cultured in collagen was longer than that of cells maintained on plastic. In addition, cells cultured in collagen proliferated rapidly in a serum-free medium containing insulin, epidermal growth factor (EGF), estrogen, and transferrin. The collagen gel system may be useful for characterizing physiologically important trophic factors that regulate the proliferation and other functions of human breast tumor cells.
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PMID:Morphological and proliferative characteristics of human breast tumor cells cultured on plastic and in collagen matrix. 674 55

In order to acquire a better understanding of the mechanism of radiation-induced fibrosis, we studied the differentiation of normal skin fibroblasts cultured from breast cancer radiotherapy patients with different risk of fibrosis. The differentiation state of fibroblasts was characterized in clonal cultures using established cytomorphological criteria. Collagen synthesis was determined by 3H-proline incorporation into pepsin-resistant protein. Radiation-induced inactivation of fibroblasts was paralleled by an increase in terminally differentiated fibrocytes, demonstrating that premature terminal differentiation is an important response to irradiation of fibroblasts from radiotherapy patients. Surviving colony-forming fibroblasts showed a change in differentiation with an increase in the ratio L:E of progenitor fibroblasts in late (L) compared to early (E) differentiation states. Furthermore, increased collagen production was observed after irradiation. The results provide evidence supporting a role of terminal fibroblast differentiation in radiation-induced fibrosis and imply that the progenitor population surviving radiotherapy might be more prone to terminal differentiation than before radiotherapy.
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PMID:Fibroblast differentiation in subcutaneous fibrosis after postmastectomy radiotherapy. 1098 35

Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD-DST and immunohistological examination of 6 biological markers (P-gp, erbB2, p53, BCL2, MIB1 and ER-alpha). As chemotherapy, cyclophosphamide 600 mg/m(2) plus epirubicin 60 mg/m(2) q3w (CE, n = 28) or docetaxel 60 mg/m(2) q3w (DOC, n = 42) was given. Interpretable results using the CD-DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD-DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD-DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD-DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD-DST exhibited a response to DOC therapy. P-gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P-gp was lower than that (87.0%) achieved by CD-DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER-alpha) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD-DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors.
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PMID:Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers. 1192 May 99

Collagen production plays a significant role in tumor development, especially in breast cancer, hepatocarcinomas, and colorectal carcinoma. However, collagen production is decreased during oncogenic transformation of cells in culture. This study demonstrates that methylation of the collagen alpha2(I) gene transcription start site occurs frequently in human cancer cell lines (9 of 10), including breast cancer cell lines (MCF-7 and Hs578T), hepatocellular carcinoma cell lines (SNU387, SNU449, SNU398, and PLC/PRF/5), a fibrosarcoma cell line (HT1080), and colorectal carcinoma cell lines (HCT116, SW480, and SW620). In addition, the collagen gene is more methylated in colorectal cancer tissues compared with normal mucosa. The increased DNA methylation of the collagen gene in cell lines is inversely correlated with collagen mRNA steady-state levels. Most importantly, treatment of fibrosarcoma or breast carcinoma cells with a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, resulted in lower methylation and reactivation of the collagen gene in a dose-responsive manner. This is the first demonstration that the collagen alpha2(I) gene is methylated in multiple cancer cell lines correlating with loss of collagen expression and also methylated in primary cancer tissues. These data also suggest that methylation-induced repression of collagen transcription may be a frequent occurrence in cancer.
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PMID:DNA hypermethylation near the transcription start site of collagen alpha2(I) gene occurs in both cancer cell lines and primary colorectal cancers. 1270 64

The expression of estrogen receptor alpha (ERalpha) is generally associated with a less invasive and aggressive phenotype in breast carcinoma. In an attempt to understand the role of ERalpha in regulating breast cancer cells invasiveness, we have demonstrated that cell adhesion on fibronectin (Fn) and type IV Collagen (Col) induces ERalpha-mediated transcription and reduces cell migration in MCF-7 and in MDA-MB-231 cell lines expressing ERalpha. Analysis of deleted mutants of ERalpha indicates that the transcriptional activation function (AF)-1 is required for ERalpha-mediated transcription as well as for the inhibition of cell migration induced by cell adhesion on extracellular matrix (ECM) proteins. In addition, the nuclear localization signal region and some serine residues in the AF-1 of the ERalpha are both required for the regulation of cell invasiveness as we have observed in HeLa cells. It is worth noting that c-Src activation is coincident with adhesion of cells to ECM proteins and that the inhibition of c-Src activity by PP2 or the expression of a dominant-negative c-Src abolishes ERalpha-mediated transcription and partially reverts the inhibition of cell invasiveness in ERalpha-positive cancer cells. These findings address the integrated role of ECM proteins and ERalpha in influencing breast cancer cell motility through a mechanism that involves c-Src and seems not to be related to a specific cell type.
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PMID:Fibronectin and type IV collagen activate ERalpha AF-1 by c-Src pathway: effect on breast cancer cell motility. 1546 44

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.
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PMID:Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. 1584 Dec 11


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