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  • ONCOLOGY  (5)
Keywords
  • 1
    Keywords: ANGIOGENESIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; INVASION ; tumor ; BLOOD ; CELL ; Germany ; IN-VIVO ; INHIBITION ; MODEL ; THERAPY ; VIVO ; imaging ; TISSUE ; SKIN ; fibroblasts ; PROGRESSION ; REQUIRES ; skin cancer ; EXTRACELLULAR-MATRIX ; INHIBITORS ; CYTOKINE ; ONCOLOGY ; fibroblast ; MATRIX METALLOPROTEINASES ; STROMAL CELLS ; matrix metalloproteinase ; MATRIX-METALLOPROTEINASE INHIBITORS ; EPITHELIAL TUMOR PHENOTYPE ; MMP inhibition
    Abstract: Tumor invasion requires intense interactions with stromal cells and a profound extracellular matrix remodelling by matrix metalloproteinases (MMPs). Here, we assessed the specific contribution of fibroblasts to tumor invasion, MMPs, tissue inhibitors of MMPs and angiogenesis-related cytokine expression in organotypic cultures of highly malignant HaCaT-ras A-5RT3 cells, with and without MMP inhibition. Collagen degradation, the hallmark of tumor invasion, was dependent on fibroblasts and active MMP-2. Additionally, MMP blockade down-regulated VEGF-A and up-regulated PDGF-BB. These results were paralleled in xenotransplants in vivo, demonstrating strong inhibitory effects of MMP blockade on tumor invasion and vascularization, as shown by the almost complete absence of VEGF-A and MMP-14 and by the decrease in relative blood volume. MMP blockade also increased the fraction of mature vessels, as demonstrated by an increased mean tumor vessel diameter and a higher ratio of Ng2-positive vessels. Thus, this study highlights the importance of targeting the tumor stroma to defeat cancer
    Type of Publication: Journal article published
    PubMed ID: 20392987
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  • 2
    Keywords: CELLS ; GROWTH ; CELL ; Germany ; DRUG ; SERA ; mechanisms ; culture ; EFFICACY ; PRODUCT ; VARIABILITY ; CYTOTOXICITY ; METHOTREXATE ; GROWTH ARREST ; ARREST ; SERUM ; ONCOLOGY ; RE ; PRODUCTS ; LEVEL ; methods ; TESTS ; BOVINE ; KB cells ; DRUGS ; ANTITUMOR ACTIVITIES ; MEDIA ; antifolate resistance ; antifolate salvage ; CCRF-CEM cells ; FBS gold ; FCS gold ; fetal bovine serum ; LY231514
    Abstract: Background: Batch variability of sera used for cell culture is of considerable experimental concern. A novel fetal calf serum product, FCS Gold, was claimed to be the first defined fetal calf serum free of batch variation. Materials and Methods: The efficacy of methotrexate (MTX) and LY231514 (multitargeted antifolate, MTA) in CCRF-CEM cells and KB cells was compared using media supplemented with FCS Gold or conventional fetal bovine serum. Results: IC50 values from tests using conventional serum corresponded to published data. FCS Gold fully protected the cells from antifolate drug cytotoxicity. Dialysis of FCS Gold restored responsiveness to antifolate drugs. Elevated levels of hypoxanthine and thymidine were present in FCS Gold. They were approximately 10-fold greater than the concentrations required to overcome growth arrest mediated by 2 mu M MTX. Conclusion: FCS Gold or identical products, e.g. FBS Gold, should not be used in studies on antifolate drug action
    Type of Publication: Journal article published
    PubMed ID: 17465201
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  • 3
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; carcinoma ; CELL ; Germany ; incidence ; PROTEIN ; MICE ; FAMILY ; CARCINOGENESIS ; INDUCTION ; SKIN ; SUSCEPTIBILITY ; MOUSE ; TRANSGENIC MICE ; PROGRESSION ; CELL-DEATH ; MOUSE SKIN ; skin carcinogenesis ; skin cancer ; TRANSFORMATION ; STEM-CELLS ; CARCINOMAS ; CARCINOGENS ; squamous cell carcinoma ; C-MYC ; OVEREXPRESSION ; epidermis ; INITIATION ; LAYER ; SKIN-CANCER ; Bcl-2 ; CELL CARCINOMA ; ONCOLOGY ; RE ; INCREASE ; HAIR FOLLICLE ; PROTOCOL ; MALIGNANT PROGRESSION ; hair ; stem cells ; methods ; NORMAL SKIN ; INDUCED TUMORIGENESIS ; NOR ; SQUAMOUS-CELL ; STEM ; BASAL-CELL ; PAPILLOMAS ; sensitize
    Abstract: Background: BCL-2 overexpression is firequently detected in nonmelanoma skin cancer. In normal skin, BCL-2 expression is restricted to the basal cell layer and the hair follicle bulge. Both contain stem cells targeted by carcinogens upon initiation of mouse skin carcinogenesis. It is unknown whether the anti-apoptotic activity, of BCL-2 is involved in the susceptibility of this cell type to malignant transformation. If so, extending the pool of BCL-2-expressing cells to suprabasal skin layers should increase the likelihood of skin tumour formation. Materials and Methods: To resolve this issue, we generated a novel transgenic mouse line overexpressing BCL-2 in suprabasal layers of the epidermis. The influence of suprabasal BCL-2 on tumour formation was then tested by chemically inducing skin cancer using the two-stage initiation-promotion protocol. Results: Bcl-2 expression neither influenced the incidence nor the multiplicity of papillomas upon chemical tumour induction with 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), nor their progression to carcinomas. Conclusion: Suprobasal expression of BCL-2 in skin does not increase the formation of papillomas or their malignant progression to squamous cell carcinomas in two-stage mouse skin carcinogenesis
    Type of Publication: Journal article published
    PubMed ID: 19035317
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  • 4
    Keywords: CELLS ; AGENTS ; CELL ; CELL-PROLIFERATION ; Germany ; human ; IN-VIVO ; MODEL ; MODELS ; VIVO ; imaging ; VISUALIZATION ; DISEASE ; DRUG ; MICE ; prognosis ; MR ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; BREAST-CANCER ; MOUSE ; NO ; STAGE ; SCID MOUSE ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; MOUSE MODEL ; CHILDREN ; TRACER ; ANTICANCER DRUGS ; neuroblastoma ; AGENT ; ONCOLOGY ; RE ; monitoring ; WEIGHT ; MOUSE MODELS ; methods ; DRUGS ; NEUROENDOCRINE TUMORS ; SCANS ; animal ; FDG ; anticancer drug ; xenograft ; small animal imaging ; FLT ; SCAN ; FDG UPTAKE ; MRT ; F-18-FLT PET ; GRANULATION TISSUES ; PET-CT ; THORACIC TUMORS ; [F-18]FLT
    Abstract: Background: Finding new therapeutic agents is of great clinical interest in neuroblastoma research because prognosis of children with disseminated stages of disease is still poor. As xenograft mouse models are frequently used for studying anticancer drugs in vivo, small animal imaging is an important method of monitoring in anticancer research. Materials and Methods: SCID mice inoculated with human neuroblastoma SK-N-SH cells were examined with positron-emission tomography-computed tomography (PET-CT) using [F-18]fluorodeoxyglucose (FDG) or [F-18]fluoro-L-thymidine (FLT) and with magnetic resonance imaging (MRI). Results: All neuroblastomas were detected by MRI. In PET-CT imaging, no tumour was visualized with [F-18]FDG, but 13 out of 14 (93%) were found with [F-18]FLT. Uptake of [F-18]FLT was significantly associated with tumour weight. Necrotic areas could not be identified either by MR imaging or on PET-CT scans. Conclusion: Both MR and PET-CT imaging with [F-18]FLT are highly qualified for the detection of neuroblastomas grown in SCID mice. However, [F-18]FDG, which is the standard tracer in clinical PET-CT imaging, is not suited for PET-CT imaging in the neuroblastoma model
    Type of Publication: Journal article published
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  • 5
    Keywords: COLORECTAL-CANCER ; PROSPECTIVE COHORT ; colorectal cancer ; RECURRENCE ; ONCOLOGY ; RE ; CANCER ; COHORT ; PATIENT ; flavonoid ; comparison ; prospective
    Type of Publication: Meeting abstract published
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