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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of surgical oncology 7 (2000), S. 685-691 
    ISSN: 1534-4681
    Keywords: Taurolidine ; Peritoneal metastases ; Tumor inhibition ; Animal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo. Methods: In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25 μg/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, BD IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity. Results: Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25 ± 4% vs. 100 ± 28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403 ± 28% vs. 100 ± 26% for controls), at a Taurolidine concentration of 25 μg/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3 ± 1 nodules in Group B animals vs. 649 ± 101 nodules in Group A animals). Conclusions: Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1534-4681
    Keywords: Vascular endothelial growth factor ; Transforming growth factor β-1 ; Breast cancer ; Angiogenesis ; Metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P〈.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1534-4681
    Keywords: Vascular endothelial growth factor ; Human macrophage ; Hypoxia ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Breast tumors contain high numbers of infiltrating macrophages. The role and function of these cells within the tumor remain unclear, but a number of studies have found an association between poor prognosis and macrophage content in human breast cancer. Both hypoxia and TGFβ-1 have been shown to regulate VEGF in other cell types. We hypothesized that breast tumor-associated macrophages produce VEGF and that macrophage production of this factor is regulated by both hypoxia and TGFβ-1. Methods: Paraffin-embedded breast tumor sections were stained immunohistochemically with anti-VEGF, anti-CD68, and anti-cytokeratin. Monocytes were matured for 3 days in 20% autologous plasma and activated with 1000 U/mL interferon-γ for 24 hours. Supernatants were assayed for VEGF protein by ELISA. Total RNA was isolated from cells and reverse transcribed to cDNA, which was used as a template in PCR reactions for VEGF and β-actin. Results: Both tumor cells and tumor macrophages produce VEGF in human breast tumors. Hypoxia increases VEGF protein and mRNA levels in monocyte-derived macrophages, whereas TGFβ-1 increases VEGF protein but not mRNA under hypoxic growth conditions. Conclusions: Breast tumor-associated macrophages may contribute to the angiogenic activity of human breast tumors by producing VEGF. Macrophage production of VEGF is upregulated by hypoxia and TGFβ-1, both of which occur in the tumor environment. Macrophage production of VEGF is regulated at both the mRNA and protein levels.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Sepsis 2 (1998), S. 47-53 
    ISSN: 1573-7411
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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