PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. RESULTS: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC₅₀ of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. CONCLUSION: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.
Biliary Tract Neoplasms* ; Biliary Tract* ; Blotting, Western ; Cell Line ; Cisplatin ; Drug Therapy ; Fluorouracil ; Humans ; Immunohistochemistry ; Prognosis

BACKGROUND/AIMS: Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin. METHODS: We performed a retrospective chart review. After evaluation of cause of eosinophilia, the patients suspected of eosinophilia of unknown origin performed immunoglobulin G antibody specific assay for the Toxocara canis larval antigen by enzyme-linked immunosorbent assay. RESULTS: This study evaluated 113 patients, 69 patients (61%) were suspected of eosinophilia of unknown origin. Among these 69 patients, the frequency of T. canis infection was very high (45 patients, 65.2%), and albendazole treatment for 45 eosinophilia with toxocariasis was highly effective for a cure of eosinophilia than no albendazole group regardless of steroid (82.3%, p = 0.007). Furthermore, among the nonsteroid treated small group (19 patients), albendazole treatment for eosinophilia were more effective than no albendazole group, too (83.3% vs. 28.6 %, p = 0.045). CONCLUSIONS: The prevalence of toxocariasis was high among patients suspected of eosinophilia of unknown origin; therefore, evaluation for T. canis infection is recommended for patients with eosinophilia of unknown origin. Furthermore, for patients suspected of eosinophilia of unknown origin who have positive results for T. canis, albendazole treatment may be considered a valuable treatment option.
Albendazole ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia* ; Humans ; Hypereosinophilic Syndrome ; Immunoglobulin G ; Prevalence* ; Retrospective Studies ; Toxocara canis ; Toxocariasis*

BACKGROUND/AIMS: Eosinophilia has numerous diverse causes, and in many patients, it is not possible to establish the cause of eosinophilia. Recently, toxocariasis was introduced as one cause of eosinophilia. The aims of this study were to evaluate the prevalence of toxocariasis and the clinical impact of albendazole treatment for toxocariasis in patients suspected of eosinophilia of unknown origin. METHODS: We performed a retrospective chart review. After evaluation of cause of eosinophilia, the patients suspected of eosinophilia of unknown origin performed immunoglobulin G antibody specific assay for the Toxocara canis larval antigen by enzyme-linked immunosorbent assay. RESULTS: This study evaluated 113 patients, 69 patients (61%) were suspected of eosinophilia of unknown origin. Among these 69 patients, the frequency of T. canis infection was very high (45 patients, 65.2%), and albendazole treatment for 45 eosinophilia with toxocariasis was highly effective for a cure of eosinophilia than no albendazole group regardless of steroid (82.3%, p = 0.007). Furthermore, among the nonsteroid treated small group (19 patients), albendazole treatment for eosinophilia were more effective than no albendazole group, too (83.3% vs. 28.6 %, p = 0.045). CONCLUSIONS: The prevalence of toxocariasis was high among patients suspected of eosinophilia of unknown origin; therefore, evaluation for T. canis infection is recommended for patients with eosinophilia of unknown origin. Furthermore, for patients suspected of eosinophilia of unknown origin who have positive results for T. canis, albendazole treatment may be considered a valuable treatment option.
Albendazole ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia* ; Humans ; Hypereosinophilic Syndrome ; Immunoglobulin G ; Prevalence* ; Retrospective Studies ; Toxocara canis ; Toxocariasis*

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.
Animals ; Carcinogenesis ; Cell Line ; Colon* ; Colonic Neoplasms* ; Fibroblasts ; Genes, vif ; HCT116 Cells ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Reactive Oxygen Species

To evaluate the hepatotoxicity and nephrotoxicity of Galla Rhois (GR) toward the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration of 250, 500 and 1,000 mg/kg body weight/day of gallotannin-enriched extract of GR (GEGR) for 14 days. GEGR contained 68.7+/-2.5% of gallotannin, 25.3+/-0.9% of gallic acid and 4.4+/-0.1% of methyl gallate. Also, the level of malondialdehyde (MDA), a marker of lipid peroxidation, was decreased with 19% in the serum of high dose GEGR (HGEGR)-treated mice. The body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ among GEGR-treated groups and the vehicle-treated group. Furthermore, no significant increase was observed in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the GEGR-treated group relative to the vehicle-treated group. Moreover, the specific pathological features induced by most toxic compounds such as CCl4 were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that GEGR does not induce any specific toxicity in liver and kidney organs of ICR at doses of 1,000 mg/kg body weight/day, indicating that this is no observed adverse effect level (NOAEL).
Administration, Oral ; Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Blood Urea Nitrogen ; Body Weight ; Creatinine ; Gallic Acid ; Kidney ; L-Lactate Dehydrogenase ; Lipid Peroxidation ; Liver ; Malondialdehyde ; Mice ; Mice, Inbred ICR* ; Mortality ; No-Observed-Adverse-Effect Level ; Organ Size ; Pathology ; Phenotype

Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17beta-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata.
Animals ; Chorionic Gonadotropin ; Collagen ; Endocrine System ; Estradiol ; Estrogens ; Ethinyl Estradiol ; Oxytocin* ; Pituitary Gland ; Placenta ; Rats* ; RNA, Messenger ; Uterine Contraction ; Uterus

Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-kappaB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.
Acid Phosphatase/genetics/metabolism ; Animals ; Anticholesteremic Agents/*pharmacology ; Blotting, Western ; *Cell Differentiation ; Cells, Cultured ; Hydrogen Peroxide/pharmacology ; Isoenzymes/genetics/metabolism ; Macrophages/cytology/drug effects/metabolism ; Mice ; Mitogen-Activated Protein Kinases/genetics/metabolism ; NF-kappa B/genetics/metabolism ; Osteoclasts/*cytology/*drug effects/metabolism ; RANK Ligand/metabolism ; RNA, Messenger/genetics ; Reactive Oxygen Species/*metabolism ; Real-Time Polymerase Chain Reaction ; Simvastatin/*pharmacology

BACKGROUND: Endotracheal intubation usually causes transient hypertension and tachycardia. The cardiovascular and arousal responses to endotracheal and endobronchial intubation were determined during rapid-sequence induction of anesthesia in normotensive and hypertensive elderly patients. METHODS: Patients requiring endotracheal intubation with (HT, n = 30) or without hypertension (NT, n = 30) and those requiring endobronchial intubation with (HB, n = 30) or without hypertension (NB, n = 30) were included in the study. Anesthesia was induced with intravenous thiopental 5 mg/kg followed by succinylcholine 1.5 mg/kg. After intubation, all subjects received 2% sevoflurane in 50% nitrous oxide and oxygen. Mean arterial pressure (MAP), heart rate (HR), plasma catecholamine concentration, and Bispectral Index (BIS) values, were measured before and after intubation. RESULTS: The intubation significantly increased MAP, HR, BIS values and plasma catecholamine concentrations in all groups, the peak value of increases was comparable between endotracheal and endobronchial intubation. However, pressor response persisted longer in the HB group than in the HT group (5.1 +/- 1.6 vs. 3.2 +/- 0.9 min, P < 0.05). The magnitude of increases in MAP and norepinephrine from pre-intubation values was greater in the hypertensive than in the normotensive group (P < 0.05), while there were no differences in those of HR and BIS between the hypertensive and normotensive groups. CONCLUSIONS: Cardiovascular response and arousal response, as measured by BIS, were similar in endobronchial and endotracheal intubation groups regardless of the presence or absence of hypertension except for prolonged pressor response in the HB group. However, the hypertensive patients showed enhanced cardiovascular responses than the normotensive patients.
Aged ; Anesthesia ; Arousal ; Arterial Pressure ; Heart Rate ; Humans ; Hypertension ; Intubation ; Intubation, Intratracheal ; Methyl Ethers ; Nitrous Oxide ; Norepinephrine ; Oxygen ; Plasma ; Succinylcholine ; Tachycardia ; Thiopental

BACKGROUND AND OBJECTIVES: Pioglitazone has been known for its anti-atherogenic effects. We compared the effects of pioglitazone in reducing atherosclerosis progression and neointima volume in type 2 diabetic patients. SUBJECTS AND METHODS: This was a prospective, randomized single-blinded, 8-month follow-up study. Patients with significant coronary artery stenosis were randomly assigned to either pioglitazone (n=19) or placebo (n=18) following zotarolimus-eluting stent (ZES) implantation. Intravascular ultrasonography of the culprit vessel was performed from 20 mm distal and proximal to the stent at baseline. and at 8-month, and volumetric analysis was performed. Changes in inflammation markers, insulin resistance and lipid profile were compared. RESULTS: Changes in atherosclerosis progression from baseline in the pioglitazone group was significantly lower than that of the placebo group (0.06+/-0.73 vs. 1.16+/-1.41 mm3/mm, p=0.024, respectively), and neointima volume was significantly lower in the pioglitazone group compared to the placebo group (1.74+/-0.93 vs. 2.42+/-1.98 mm3/mm, p=0.007, respectively). Homeostatic model assessment-index, interleukin-6, and tumor necrosis factor-alpha levels were significantly lower in the pioglitazone group at 8 months. Adiponectin levels increased significantly only in the pioglitazone group. No significant differences in retinol binding protein-4 levels between the 2 groups were seen during the 8-month follow-up period. CONCLUSION: Compared to placebo, pioglitazone was associated with significant reduction in atherosclerosis progression and neointima formation in type 2 diabetic patients with ZES implantation.
Adiponectin ; Atherosclerosis ; Coronary Stenosis ; Diabetes Mellitus ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Inflammation ; Insulin Resistance ; Interleukin-6 ; Neointima ; Prospective Studies ; Stents ; Thiazolidinediones ; Tumor Necrosis Factor-alpha ; Ultrasonography, Interventional ; Vitamin A

PURPOSE: We wanted to evaluate the mechanical strength of proximal tibia as resection distance increased from the joint surface. MATERIALS AND METHODS: We obtained the CT images of twenty knee osteoarthritis patients undergoing total knee arthroplasty. The finite element models were created based on the computed tomography images. The 8-node hexahedron element was made from BIONIX(TM) (CANTIBio. Co, Suwon, Korea), which is automatic mesh generation software program. The finite element model of the proximal tibia was resected at 6 mm, 8 mm, 10 mm, 12 mm, 15 mm and 18 mm from the lateral joint surface. A 1% strain rate was applied to a model by using HyperMesh(TM) software (Altair Engineering. Inc, Seattle, USA). The ultimate stress was calculated from the finite element analysis with using ANSYS 9.0 (ANSYS. Inc, Orlando, USA). RESULTS: The mean ultimate stress was 906.84 MPa, 877.22 MPa, 895.93 Mpa, 852.70 MPa, 742.90 Mpa and 585.51 Mpa at the 6 mm, 8 mm, 10 mm, 12 mm, 15 mm and 18 mm resection levels. As compare to the 6 mm resection level, the bone strengths at 15 mm and 18 mm were decreased with statistical significance (15 mm: p=0.005, 18 mm: p=0.000). CONCLUSION: The ultimate stress was decreased as the resection distance increased from the joint surface. But within a 12 mm resection distance from the lateral condyle articular surface of the tibia, the ultimate stress was not significantly decreased (p>0.05).
Arthroplasty ; Finite Element Analysis ; Humans ; Joints ; Knee ; Osteoarthritis ; Osteoarthritis, Knee ; Sprains and Strains ; Tibia