Search results for "Tumor Physiology"
showing 6 items of 6 documents
Carboxyamidotriazole-Orotate Inhibits the Growth of Imatinib-Resistant Chronic Myeloid Leukaemia Cells and Modulates Exosomes-Stimulated Angiogenesis
2012
The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous leukaemia (CML) by imatinib mesylate. While imatinib has been extremely effective for chronic phase CML, blast crisis CML are often resistant. New therapeutic options are therefore needed for this fatal disease. Although more common in solid tumors, increased microvessel density was also reported in chronic myelogenous leukaemia and was associated with a significant increase of angiogenic factors, suggesting that vascularity in hematologic malignancies is a controlled process and may play a role in the leukaemogenic process thus representing an alternative therapeutic target. Carboxyamidotriazole-orotate (CTO) is …
Glucocorticoid receptor knockdown decreases the antioxidant protection of B16 melanoma cells: an endocrine system-related mechanism that compromises …
2014
We previously reported an interorgan system in which stress-related hormones (corticosterone and noradrenaline), interleukin-6, and glutathione (GSH) coordinately regulate metastatic growth of highly aggressive B16-F10 melanoma cells. Corticosterone, at levels measured in tumor-bearing mice, also induces apoptotic cell death in metastatic cells with low GSH content. In the present study we explored the potential role of glucocorticoids in the regulation of metastatic cell death/survival during the early stages of organ invasion. Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in …
Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide
2012
Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50) values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways…
Ultrasound-Guided Intramural Inoculation of Orthotopic Bladder Cancer Xenografts: A Novel High-Precision Approach
2013
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected b…
MMP-10/stromelysin-2 promotes invasion of head and neck cancer.
2011
BackgroundPeriostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data s…
Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells
2011
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…