GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the Intrinsic Pathway.

Previously we demonstrated that human glioblastoma cell lines induce apoptosis in peripheral blood T cells through partial involvement of secreted gangliosides. Here we show that GBM-derived gangliosides induce apoptosis through involvement of the TNF receptor and activation of the caspase cascade. Culturing T lymphocytes with GBM cell line derived gangliosides (10-20 μg/ml) demonstrated increased ROS production as early as 18 hrs as indicated by increased uptake of the dye H2DCFDA while western blotting demonstrated mitochondrial damage as evident by cleavage of Bid to t-Bid and by the release of cytochrome-c into the cytosol.

Myeloid derived suppressor cell infiltration of murine and human gliomas is associated with reduction of tumor infiltrating lymphocytes.

Myeloid derived suppressor cells (MDSCs) are bone marrow derived cells with immunosuppressive properties. We have shown previously that MDSCs numbers are elevated in the circulation of GBM patients and that they produce reversible T cell dysfunction. Here, we evaluated whether MDSCs infiltrate human GBM tissues, and whether a commonly used mouse model of GBM reproduces the biology of MDSCs that is observed in patients.

Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma.

To assess the accumulation of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of patients with glioma and to define their heterogeneity and their immunosuppressive function. Peripheral blood mononuclear cells (PBMCs) from healthy control subjects and from patients with newly diagnosed glioma were stimulated with anti-CD3/anti-CD28 and T cells assessed for intracellular expression of interferon (IFN)-γ. Antibody staining of PBMCs from glioma patients and healthy donors (CD33, HLADR, CD15, and CD14) followed by 4-color flow cytometry analysis-defined MDSC levels in the peripheral blood.

p300- and Myc-mediated regulation of glioblastoma multiforme cell differentiation.

Tumorigenic potential of glioblastoma multiforme (GBM) cells is, in part, attributable to their undifferentiated (neural stem cell-like) phenotype. Astrocytic differentiation of GBM cells is associated with transcriptional induction of Glial Fibrillary Acidic Protein (GFAP) and repression of Nestin, whereas the reciprocal transcription program operates in undifferentiated GBM cells. The molecular mechanisms underlying the regulation of these transcription programs remain elusive.

IL-8 is a mediator of NF-κB induced invasion by gliomas.

Glioblastoma (GBM) is the most common and deadly form of primary brain tumor with a median survival of eleven months, despite use of extensive chemotherapy, radiotherapy and surgery. We have previously shown that nuclear factor-kappa B (NF-κB) is aberrantly expressed in GBM tumors and primary cell lines derived from tumor tissue. Here we show that IL-8, a chemokine is also aberrantly expressed by GBM cell lines and expression of IL-8 is in large part, attributable to the aberrant activation of NF-κB.

Momordicatin purified from fruits of Momordica charantia is effective to act as a potent antileishmania agent.

Aqueous extract of the green fruits of the Indian plant Momordica charantia and purified Momordicatin structurally established as 4-(o-carboethoxyphenyl) butanol were evaluated in vitro and in vivo against kala-azar caused by Leishmania donovani. 50% inhibitory concentration (IC(50)) against Leishmania promastigotes in vitro for the crude extract and momordicatin were 0.6mg/L and 0.

Stat3 activation is required for the growth of U87 cell-derived tumours in mice.

Previously we reported that Stat3 is persistently activated in GBM tumours and derived cell lines. Hypoxia, necrosis and neo-angiogenesis are hallmarks of GBM. To unfold the contribution of activated Stat3 to the growth of GBM, we generated human GBM cell line (U87)-derived stable clones expressing a dominant negative mutant (DN)-Stat3 in a hypoxia-inducible manner, and examined their tumour-forming potentials in immune-compromised mice.

Pelvic fasciae in urology.

Introduction: Despite the vast literature on pelvic fascia, there is confusion over the periprostatic structures and their nomenclature, including their orientation, the neurovascular bundles and the existence of the prostatic 'capsule'. In this review, we seek to clarify some of these issues.

Materials And Methods: Review of published medical literature relating to the anatomy of the pelvic fascia including a Pubmed search using the terms - pelvic fascia, Denonvilliers' fascia, prostate capsule, neurovascular bundle of Walsh, puboprostatic ligament and the detrusor apron.

Depressed peroxisome proliferator-activated receptor gamma (PPargamma) is indicative of severe pulmonary sarcoidosis: possible involvement of interferon gamma (IFN-gamma).

Background And Aim: Recent evidence suggests that the transcription factor, PPARgamma, is an important negative regulator of inflammation. Because studies of murine adipocytes and macrophages implicate IFN-gamma, a key mediator of granuloma formation in sarcoidosis, as a PPARgamma antagonist, we investigated the relationship between PPARgamma and IFN-gamma in bronchoalveolar lavage (BAL) cells of sarcoidosis patients and healthy controls.

Methods: BAL cells were analyzed for PPARgamma and IFN-gamma mRNA expression by quantitative PCR and for PPARgamma protein by immunocytochemistry and western blotting.

Laparoscopic nephrectomy in a patient with ankylosing spondylitis: surgical and anesthetic challenges.

A 55-year-old man with ankylosing spondylitis was referred with left sided loin pain, loin mass, and painless macroscopic hematuria. Physical examination revealed a palpable loin mass, fixed flexion deformity of the lumbar and cervical spines, with severely restricted cervical movement and mouth opening. An ultrasound and computed tomography scan confirmed a 7-cm solid mass in the left kidney.

Aberrant constitutive activation of nuclear factor kappaB in glioblastoma multiforme drives invasive phenotype.

Several recent studies have shown that aberrant constitutive activation of nuclear factor kappaB (NF-kappaB) is present in a variety of cancers including gliomas. NF-kappaB is known to play important roles in the physiological regulation of diverse cellular processes such as inflammation, growth and immunity. In contrast, aberrant activation of this latent transcription factor promotes cancer cell migration, invasion and resistance to chemotherapy.

An inverse relationship between peroxisome proliferator-activated receptor gamma and allergic airway inflammation in an allergen challenge model.

Background: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) expression has not been evaluated in bronchoalveolar lavage (BAL) cells from allergic asthmatic patients.

Objective: To determine whether inappropriate down-regulation of PPAR-gamma in alveolar macrophages may contribute to persistent airway inflammation in allergic asthma.

Methods: We used segmental allergen challenge as a model of in vivo experimental allergic asthmatic exacerbation and airway inflammation.

Elevated IL-10 inhibits GM-CSF synthesis in pulmonary alveolar proteinosis.

Pulmonary alceolar proteinosis (PAP) is an autoimmune lung disease characterized by accumulation of surfactant material within the lung. Autoantibodies to GM-CSF as well as high levels of IL-10 are also found in the lungs in PAP. Previous studies suggest that treatment with recombinant GM-CSF is beneficial for patients with low levels of GM-CSF antibodies.

Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis.

The ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR gamma), has pleiotropic effects on lipid and glucose metabolism as well as modulating immune activity. In Th1-predominant models of inflammatory bowel disease and arthritis, PPAR gamma ligands can ameliorate clinical disease severity, partly by downregulating a range of inflammatory cytokines. However, PPAR gamma has not been evaluated in chronic sarcoidosis, a disease characterized by persistent activation of Th1 immune responses in alveolar macrophages.

Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages.

Surfactant plays an important role in lung homeostasis and is also involved in maintaining innate immunity within the lung. Lipopolysaccharide (LPS) from gram-negative bacteria is known to elicit acute proinflammatory responses in lung diseases such as acute respiratory distress syndrome and pneumonia, among others. Our previous studies demonstrated that the clinically used, natural surfactant product Survanta inhibited proinflammatory cytokine secretion from LPS-stimulated human alveolar macrophages.

PU.1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically implicated in lung homeostasis in the GM-CSF knockout mouse model. These animals develop an isolated lung lesion reminiscent of pulmonary alveolar proteinosis (PAP) seen in humans. The development of the adult form of human alveolar proteinosis is not due to the absence of a GM-CSF gene or receptor defect but to the development of an anti-GM-CSF autoimmunity.

Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated, nuclear transcription factor that regulates genes involved in lipid and glucose metabolism, inflammation, and other pathways. The hematopoietic growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is essential for lung homeostasis and is thought to regulate surfactant clearance, but mechanisms involved are unknown. GM-CSF is reported to stimulate PPAR-gamma, but the activation status of PPAR-gamma in human alveolar macrophages has not been defined.

Circulating monocytes from patients with primary pulmonary hypertension are hyporesponsive.

Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology characterized by arterial thickening and remodeling. The transcription factor NF-kappaB is responsible for the activation of several cytokines and growth factor genes reported to be associated with PPH. Our previous study showed NF-kappaB activation in alveolar macrophages from PPH patients, suggesting the presence of a localized pulmonary inflammatory response.

Nitric oxide blocks inflammatory cytokine secretion triggered by CD23 in monocytes from allergic, asthmatic patients and healthy controls.

Background: In allergic asthma, monocytes/macrophages may be activated to produce inflammatory cytokines through triggering of the low-affinity IgE receptor (CD23). Elevated airway levels of nitric oxide (NO) are associated with asthmatic exacerbations. Our previous work suggested that NO may function in an anti-inflammatory capacity by downregulating endotoxin-stimulated cytokine production by alveolar macrophages and matured monocytes.

The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages.

Primary pulmonary hypertension (PPH) is characterized by increased pulmonary arterial pressure and vascular resistance. We and others have observed that inflammatory cytokines and infiltrates are present in the lung tissue, but the significance is uncertain. Treprostinil (TRE), a prostacyclin analogue with extended half-life and chemical stability, has shown promise in the treatment of PPH.