2.Impacts of Cytosolic Phospholipase A2, 15-Prostaglandin Dehydrogenase, and Cyclooxygenase-2 Expressions on Tumor Progression in Colorectal Cancer.
Sung Chul LIM ; Hoon CHO ; Tae Bum LEE ; Cheol Hee CHOI ; Young Don MIN ; Sung Soo KIM ; Kyung Jong KIM
Yonsei Medical Journal 2010;51(5):692-699
PURPOSE: In addition to cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) have been suggested to be related to carcinogenesis of colorectal cancer (CRC). The aim of this study was to investigate the roles of cPLA2, COX-2, mPGES-1, and 15-PGDH in tumor progression. MATERIALS AND METHODS: cPLA2, COX-2, mPGES-1, 15-PGDH, and vascular endothelial growth factor (VEGF) expressions were immunohistochemically examined in 89 CRC, and their expressions were compared with each other or clinicopathologic parameters as well as VEGF as tumor progression parameters. RESULTS: cPLA2 was expressed in 54.5%, COX-2 in 80.5%, mPGES-1 in 96.4%, 15-PGDH in 46.1%, and VEGF in 65.9%. The expression of cPLA2 correlated with VEGF expression. COX-2 expression was correlated with the depth of invasion, tumor stage, cPLA2, and VEGF expressions. Moreover, VEGF revealed the highest expression in the tissues positive for both cPLA2 and COX-2. Furthermore, 15-PGDH expression was inversely correlated with VEGF expression. CONCLUSION: The present study demonstrates that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression.
Aged
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Colorectal Neoplasms/*enzymology
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Cyclooxygenase 2/*metabolism
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Female
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*Gene Expression Regulation, Enzymologic
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Group IV Phospholipases A2/*metabolism
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Humans
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Hydroxyprostaglandin Dehydrogenases/*metabolism
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Immunohistochemistry
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Intramolecular Oxidoreductases/metabolism
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Male
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Middle Aged
3.Epidural Dexamethasone Decreased Inflammatory Hyperalgesia and Spinal cPLA2 Expression in a Rat Formalin Test.
Sam Hong MIN ; Jung Sub SOH ; Ji Yong PARK ; Sung Uk CHOI ; Hye Won LEE ; Jae Jin LEE ; Jae Hwan KIM
Yonsei Medical Journal 2014;55(6):1631-1639
PURPOSE: The aim of this study was to investigate the effect of epidural dexamethasone on analgesia and cytosolic phospholipase A2 (cPLA2) expression in the spinal cord in a rat formalin test. MATERIALS AND METHODS: Epidural dexamethasone injection was performed to Sprague-Dawley rats with a 25 gauge needle under fluoroscopy. Following the epidural injection, a formalin induced pain behavior test was performed. Next, the spinal cords corresponding to L4 dorsal root ganglion was extracted to observe the cPLA2 expression. RESULTS: There were no differences in pain response during phase I among the groups. The phase II pain response in 300 microg of epidural dexamethasone group decreased as compared to control, 30 microg of epidural dexamethasone, 100 microg of epidural dexamethasone, and 300 microg of systemic dexamethasone groups. The expression of cPLA2 decreased in Rexed laminae I-II in 300 microg of the epidural dexamethasone group compared with the ones in the control group. CONCLUSION: Taken together, these results suggest that 300 microg of epidural dexamethasone has an attenuating effect on the peripheral inflammatory tissue injury induced hyperalgesia and this effect is mediated through the inhibition of intraspinal cPLA2 expression and the primary site of action is the laminae I-II of the spinal cord.
Animals
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Anti-Inflammatory Agents/*pharmacology
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Dexamethasone/*pharmacology
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Formaldehyde/*adverse effects
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Group IV Phospholipases A2/*metabolism
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Hyperalgesia/*drug therapy
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Injections, Epidural
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Male
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Pain/chemically induced/*metabolism
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Pain Measurement
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Rats
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Rats, Sprague-Dawley
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Spinal Cord/*metabolism
4.Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model.
Ji Hwan LIM ; Joo Hyun KIM ; Nayoung KIM ; Byoung Hwan LEE ; Pyoung Ju SEO ; Jung Mook KANG ; So Young JO ; Ji Hyun PARK ; Ryoung Hee NAM ; Hyun CHANG ; Jin Won KWON ; Dong Ho LEE
Gut and Liver 2014;8(1):49-57
BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.
Animals
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Anti-Inflammatory Agents, Non-Steroidal/adverse effects
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Arachidonate 5-Lipoxygenase/drug effects
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Calcitonin Gene-Related Peptide/drug effects
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Cyclooxygenase 1/drug effects
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Cyclooxygenase 2/drug effects
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Disease Models, Animal
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Gastric Mucosa/chemistry/drug effects
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Group IV Phospholipases A2/drug effects
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Male
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Momordica/*chemistry
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Peroxidase/drug effects
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Plant Extracts/*pharmacology
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Rats
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Rats, Sprague-Dawley
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Seeds/*chemistry
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Stomach Ulcer/chemically induced/*prevention & control
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Treatment Outcome