Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer

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.

Evaluation of the prevalence and clinical impact of toxocariasis in patients with eosinophilia of unknown origin

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.

Evaluation of the prevalence and clinical impact of toxocariasis in patients with eosinophilia of unknown origin

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.

The oncogenic effects of p53-inducible gene 3 (PIG3) in colon cancer cells

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.

Ape1/Ref-1 Stimulates GDNF/GFR alpha1-mediated Downstream Signaling and Neuroblastoma Proliferation

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor alpha1 (GFR alpha1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRalpha1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR alpha1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRalpha1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR alpha1-specific RNA experiments demonstrated that the downregulation of GFR alpha1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC gamma-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR alpha signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

On Fat Embolism Syndrome Occurred in the Recovery Room after an Intramedullary Nailing of Femur Fracture: A case report / 대한마취과학회지

The fat embolism syndrome is a serious and potentially life threatening complication of long bone trauma, blunt trauma and intramedullary manipulation. A 26-year-old woman underwent an intramedullary nailing of the femur under general anesthesia 45 hours after a traffic accident. The operation ended uneventfully and the patient was extubated in the operatirg room. About one hour after the patient arrived at the recovery room, she progressively developed tachycardia, tachypnea, cyanosis and drowsiness. The fat embolism syndrome was suspected because of the above clinical signs, and because pulmonary edema appeared on a simple chest A-P. During six days of intensive treatment in response to the fat embolism syndrome, the patient,s vital signs and ventilatory status progressively improved. The patient was uneventfully discharged from the hospital 19 days after her operation.

Comparative Maternal and Neonatal Effects of Propofol, Propofol-Ketamine and Ketamine as Induction Agents in Cesarean Section / 대한마취과학회지

BACKGROUND: Propofol and ketamine had been used for anesthesia induction and for total intravenous anesthesia. The nature of any hypnotic interactions occurring between propofol and ketamine are unknown. A comparison of maternal and neonatal effects among propofol-ketamine combination, ketamine and propofol were studied when used for anesthesia induction in Cesarean section. METHODS: Forty five patients in ASA class I or II scheduled for Cesarean section randomly assigned to either propofol 2 mg/kg (n=15), ketamine 1 mg/kg (n=15) or propofol 1 mg/kg - ketamine 0.5 mg/kg combination group (n=15) as an induction agent. Maternal systolic and diastolic blood pressure, heart rate, Apgar score and umbilical blood gas analysis were measured. RESULTS: Before intubation, systolic and diastolic pressure were decreased in propofol group but increased in ketamine and propofol-ketamine combination group. Heart rate were increased in all three groups. But there were no significant differences among three groups (p<0.05). After intubation, there were significant increase in systolic, diastolic pressure and heart rate in three groups but no significant differences among three groups (p<0.05). And there was no significant neonatal depression as assessed by Apgar scores and blood gas analyses. CONCLUSIONS: Propofol-ketamine combination was found to be similar to propofol or ketamine only in the effects on the mother and neonate. But propofol-ketamine gained more stable hemodynamic change than propofol or ketamine before intubation. Therefore propofol-ketamine appears to be a suitable alternatives to propofol or ketamine as an induction agent for anesthesia in Cesarean section.