Prostanoids and Their Mediated Inflammatory Responses in Lung Cancer

Prostanoids are biochemically important molecules with significant roles in pain and inflammatory responses. These responses are studied in several processes of cancer development, including lung cancer.The aim of this article is to review the existing literature on the inflammatory responses in lung cancer mediated by prostanoids. Information regarding different classes of prostanoids, lung cancer and their incidence are discussed.Nonetheless, the review also covers recent information on roles of prostanoids in lung cancer development and its risk factor.

Expression of Prostaglandin E2 Receptors in Acquired Middle Ear Cholesteatoma

OBJECTIVES: To investigate the expression of prostaglandin E2 receptor subtypes, E-prostanoid (EP) 1–4 receptors, in acquired cholesteatoma and its possible role in the pathologic process of this disorder. METHODS: Specimens of human acquired cholesteatoma were obtained from 29 patients and 19 skin biopsies of normal external auditory canal were as controls. The mRNA and protein expression of EP receptors was assessed by quantitative real-time polymerase chain reaction, immunohistochemistry and Western blot. RESULTS: In acquired cholesteatoma, EP1–EP4 receptors were mainly expressed on squamous epithelium and subepithelial infiltrated inflammatory cells. In external auditory canal skin, EP1–EP4 receptors were mainly expressed on squamous epithelium and glandular epithelium. The expression of EP4 receptor on mRNA and protein levels were significant lower in acquired cholesteatoma compared with controls. EP1–EP3 receptors had no significant difference between the experimental and control group. CONCLUSION: Low expression of EP4 may play a crucial role in the pathologic process of inflammation reaction and bone destruction in acquired cholesteatoma, but not EP1, EP2, or EP3 receptors.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-kappaB Pathways in Nasal Polyp-Derived Fibroblasts

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect. METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-kappaB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-kappaB was evaluated by western blot analysis. RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-kappaB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8. CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-kappaB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Effect of Prostaglandin E2 on Vascular Endothelial Growth Factor Production in Nasal Polyp Fibroblasts

PURPOSE: Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs). METHODS: Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay. RESULTS: All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP. CONCLUSIONS: PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

Medeical Therapy For Pulmonary Arterial Hypertention / 결핵및호흡기질환

Pulmonary arterial hypertension (PAH) is often difficult to diagnose and challenging to treat. Untreated, it is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. The past decade has seen remarkable improvements in therapy, driven largely by the conduct of randomized controlled trials. Still, the selection of most appropriate therapy is complex, and requires familiarity with the disease process, evidence from treatment trials, complicated drug delivery systems, dosing regimens, side effects, and complications. We tried to provide evidence?based treatment recommendations for physicians involved in the care of these complex patients. Due to the complexity of the diagnostic evaluation required, and the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center.

The Effect of Pentaspan on The Vascular Tone of The Isolated Rat Abdominal Aorta and Renal Artery / 대한마취과학회지

The Pentaspan is a high molecular weight(250,000), hyperosmolar(320 mOsm/l) colloid solution and blood volume expander in clinical practice. Many researches revealed the decreasing of systemic vascular resistance and pulmonary vascular resistance after Pentaspan administration in vivo. Some colloid solution is contraindicated in acute renal failure. We tried to confirm the direct effects of the Pentaspan and its mechanism on the abdominal aorta and renal artery in vitro. The rat abdominal aorta and renal artery were precontracted with norepinephrine(10(-7) M/1) in 50 ml Krebs solution and 5 ml Pentaspan was infused. Ten mininutes after, changes of the vascular tones were obtained. The results were as follows. 1) The vascular tones were significantly decreased in both vessels. 2) Abdominal aorta group, renal artery group and with or without endothelium group were not significant different each other. 3) The vascular tones were not affected by with or without endothelium, indomethacin and methylene blue pretreatment. Smooth muscles were induced relaxation by the Pentaspan infusion and the relaxation were not dependent to endothelium derived relaxing factor, prostanoid and cyclic guanosinemonophosphate.