Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer.

The CXCL4 paralog CXCL4L1 is a less studied chemokine that has been suggested to exert an antiangiogenic function. However, CXCL4L1 is also expressed in patient tumors, tumor cell lines, and murine xenografts, prompting a more detailed analysis of its role in cancer pathogenesis. We used genetic and antibody-based approaches to attenuate CXCL4L1 in models of pancreatic ductal adenocarcinoma (PDAC).

The therapeutic response in Gorham's syndrome to the beta-blocking agent propranolol is correlated to VEGF-A, but not to VEGF-C or FLT1 expression.

Background: Gorham's syndrome is a rare illness of unknown etiology. It is characterized by a local proliferation of blood or lymphatic vessels that in bones leads to progressive resorption and destruction. The cause of the disease is not elucidated, and therapeutic options remain limited.

A Central Role for JNK/AP-1 Pathway in the Pro-Oxidant Effect of Pyrrolidine Dithiocarbamate through Superoxide Dismutase 1 Gene Repression and Reactive Oxygen Species Generation in Hematopoietic Human Cancer Cell Line U937.

Pyrrolidine dithiocarbamate (PDTC) known as antioxidant and specific inhibitor of NF-κB was also described as pro-oxidant by inducing cell death and reactive oxygen species (ROS) accumulation in cancer. However, the mechanism by which PDTC indices its pro-oxidant effect is unknown. Therefore, we aimed to evaluate the effect of PDTC on the human Cu/Zn superoxide dismutase 1 (SOD1) gene transcription in hematopoietic human cancer cell line U937.

Granulocyte-macrophage colony stimulating factor is anabolic and interleukin-1beta is catabolic for rat articular chondrocytes.

Objective: To study the effects of GM-CSF and IL-1beta, both implicated in tissue damage in arthritis, on articular chondrocyte proliferation and metabolism, and to explore their agonist/antagonist effects.

Methods: Chondrocytes were obtained from 1-month-old rats. First-passage monolayers were incubated for 24 h with or without GM-CSF and/or IL-1beta, and labeled with 3H-thymidine, 35S-SO4 and 14C-proline.

Reactive oxygen species and superoxide dismutases: role in joint diseases.

Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. The superoxide anion O(2)(-) is the main ROS. Increased ROS production leads to tissue damage associated with inflammation.

Tumor necrosis factor-alpha down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway.

Overexpression of Cu/Zn superoxide dismutase 1 (SOD1) in monocytes blocks reactive oxygen species-induced inhibition of cell growth and apoptosis and renders cells resistant to the toxic effect of tumor necrosis factor (TNF)-alpha, suggesting that TNF-alpha represses the SOD1 gene in these cells. We herein show that TNF-alpha decreases SOD1 mRNA, protein, and promoter activity in U937 cells. Electrophoretic mobility-shift assays (EMSA) show that TNF-alpha decreased binding of three different complexes.

Negative regulation of superoxide dismutase-1 promoter by thyroid hormone.

The role of thyroid hormone [L-3,5,3'-triiodothyronine (T3)] and the thyroid hormone receptor (TR) in regulating growth, development, and metabolic homeostasis is well established. It is also emerging that T3 is associated with oxidative stress through the regulation of the activity of superoxide dismutase-1 (SOD-1), a key enzyme in the metabolism of oxygen free radicals. We found that T3 reverses the activation of the SOD-1 promoter caused by the free radical generators paraquat and phorbol 12-myristate 13-acetate through the direct repression of the SOD-1 promoter by liganded TR.

Do arachidonic acid and its metabolites, secreted by rheumatoid and osteoarthritic synovial tissue, account for the strong inhibition of DNA synthesis in cultured human articular chondrocytes? A novel approach to the mechanism of tissue damage.

Aims: To further characterize factors secreted in vitro by osteoarthritic and rheumatoid arthritis synovial membranes that inhibit DNA synthesis by cultured human articular chondrocytes, and extend these findings to synovial fluid.

Material And Methods: Synovial tissue, synovial fluid and articular cartilage were obtained at surgery from two patients suffering rheumatoid arthritis and two other patients suffering from osteoarthritis. Synovial tissue was incubated in DMEM, then condition media and synovial fluids were extracted with methanol.

Method for selecting populations of rat articular chondrocytes that exhibit distinct growth and metabolic characteristics, and their responses to growth factors, PMA and vitamin D3.

Chondrocytes were released from articular cartilage fragments of 6-week-old Wistar rats by a 2-hour treatment with bacterial collagenase. The cells from one animal were seeded in a 25-cm2 culture flask at a density of 10(5) cells/cm2. After 1 h, the flask was gently shaken and the medium, containing nonadherent cells, was transferred to a new flask.

Vitamin D inhibits Fas ligand-induced apoptosis in human osteoblasts by regulating components of both the mitochondrial and Fas-related pathways.

Apoptosis plays an important role in the regulation of bone turnover. Previously, we showed that 1,25(OH)2D3, the active form of vitamin D, may increase osteoblast survival by inhibiting apoptosis induced by serum deprivation. Human osteoblasts express the Fas receptor on their surface and its interaction with Fas ligand has been closely associated with human osteoblast apoptosis.

Estradiol represses human T-cell leukemia virus type 1 Tax activation of tumor necrosis factor-alpha gene transcription.

Adult T-cell leukemia is caused by human T-cell leukemia virus type I (HTLV-I). The HTLV-I Tax protein is essential for clinical manifestations because it activates viral and cellular gene transcription. Tax enhances production of tumor necrosis factor-alpha (TNF-alpha), which may lead to bone and joint destruction.