Thoracoscopic placement of phrenic nerve pacers for diaphragm pacing in congenital central hypoventilation syndrome.

Purpose: Congenital central hypoventilation syndrome (CCHS), or Ondine's curse, is a rare disorder affecting central respiratory drive. Patients with this disorder fail to ventilate adequately and require lifelong ventilatory support. Diaphragm pacing is a form of ventilatory support which can improve mobility and/or remove the tracheostomy from CCHS patients.

Tumor necrosis factor-related apoptosis-inducing ligand promotes microvascular endothelial cell hyperpermeability through phosphatidylinositol 3-kinase pathway.

Background: Microvascular hyperpermeability that occurs in hemorrhagic shock and burn trauma is regulated by the apoptotic signaling pathway. We hypothesized that tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) would promote hyperpermeability directly or by interacting with other signaling pathways.

Methods: Rat lung microvascular endothelial cells (RLMECs) grown on Transwell membranes (Corning Life Sciences, Lowell, MA) were treated with recombinant human TRAIL (10, 50, and 100 ng/mL) for 6 hours or TRAIL (100 ng/mL) + LY294002 (a PI3K inhibitor; 20 μmol/L), Z-DEVD-FMK (a caspase-3 inhibitor; 10 μmol/L), or the inhibitors alone.

The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON.

Background: Carcinoid tumors are associated with the carcinoid syndrome, a set of symptoms resulting from the peptide and amine products, including serotonin, secreted from the cancer cells. The purpose of this study was to investigate the relationship between the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) inhibitor PTEN (phosphatase and tensin homolog deleted on chromosome ten) and serotonin synthesis and secretion in the carcinoid cancer cell line BON.

Materials And Methods: PTEN was inhibited by pharmacological and molecular approaches, and the resultant secretion of serotonin and expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, was assessed.

mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.

Activation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with growth and progression of colorectal cancer (CRC). We have previously shown that the mTOR kinase, a downstream effector of PI3K/Akt signaling, regulates tumorigenesis of CRC. However, the contribution of mTOR and its interaction partners toward regulating CRC progression and metastasis remains poorly understood.

VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis.

Carcinoid tumors are slow growing and highly vascular neuroendocrine neoplasms that are increasing in incidence. Previously, we showed that carcinoid tumors express vascular endothelial growth factor receptor 2 (VEGFR-2) in the epithelial compartment of carcinoid tumor sections; yet, its role is not completely understood. The purpose of our study was to: (i) assess the expression of VEGFR-2 in the novel human carcinoid cell line BON, (ii) to determine the role of PI3K/Akt signaling on VEGFR-2 expression and (iii) to assess the effect of VEGFR-2 on BON cell invasion, migration and proliferation.

PTEN loss induces epithelial--mesenchymal transition in human colon cancer cells.

Background: The epithelial-mesenchymal transition is a critical early event in the invasion and metastasis of many types of cancer, including colorectal cancer (CRC). Chronic inflammation is an inducer of several cancer types and inflammatory cytokines have been implicated in tumor invasion.

Materials And Methods: Human colon cancer cell lines HCT116 and SW480 were transfected with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) siRNA or non-targeting control (NTC).

Targeted inhibition of mammalian target of rapamycin signaling inhibits tumorigenesis of colorectal cancer.

Purpose: The mammalian target of rapamycin (mTOR) kinase acts downstream of phosphoinositide 3-kinase/Akt to regulate cellular growth, metabolism, and cytoskeleton. Because approximately 60% of sporadic colorectal cancers (CRC) exhibit high levels of activated Akt, we determined whether downstream mTOR signaling pathway components are overexpressed and activated in CRCs.

Experimental Design: HCT116, KM20, Caco-2, and SW480 human CRC cells were used to determine the effects of pharmacologic (using rapamycin) or genetic (using RNAi) blockade of mTOR signaling on cell proliferation, apoptosis, cell cycle progression, and subcutaneous growth in vivo.

Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells.

Background: Toll-like receptors (TLRs) are involved in innate immunity. Overexpression of TLRs has been implicated in various types of cancer including colorectal cancer (CRC). The phosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway is involved in CRC growth and progression.

An analysis of trends and growth factor receptor expression of GI carcinoid tumors.

Introduction: The purpose of our study was twofold: (1) to determine the incidence, patient and tumor characteristics, and outcome of patients with gastrointestinal carcinoid tumors using the Surveillance, Epidemiology and End Results (SEER) database, and (2) to delineate the expression pattern of growth factor receptors (GFRs) in carcinoid tumors.

Materials And Methods: The SEER database search provided information on patients diagnosed with carcinoid tumors from 1990 to 2002. Carcinoid tumor sections (n = 46) were stained for the GFRs: epidermal growth factor receptor, insulin-like growth factor receptor (IGFR), vascular endothelial growth factor receptor (VEGFR), and HER-2/neu.

RESEARCH ADVANCES IN NEUROBLASTOMA IMMUNOTHERAPY.

Neuroblastoma is the third most common pediatric cancer in the United States and is responsible for 15% of pediatric cancer-related deaths. Despite major advances in multimodal therapy, the clinical outcome for several patients remains poor. Due to the desperate need for innovativation and improved success in the treatment and management of neuroblastoma, research interests in immunotherapy have been on the rise in recent years.

Recent advances in neuroblastoma.

Purpose Of Review: Although there have been recent advances with multimodal therapy, treatment of neuroblastoma remains a clinical challenge. Despite the identification of several genetic features, there has not been a significant increase in 5-year survival in the last decade. This review will highlight the current operative strategies along with new research developments aimed at improving survival.