Corrigendum: Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells

The original version of this article contained error in the Figure 1.

Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells

BACKGROUND: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. METHODS: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. RESULTS: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. CONCLUSIONS: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.

Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis

Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1beta, TNFalpha, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.

Development of a therapeutic method in the HPV-related cervical lesion using pH/temperature sensitive polymer spray formulation / 부인종양

OBJECTIVE: The causal link between oncogenic HPV(Human Papilloma Viruses) and the development of CIN (rvical intraepithelial neoplasia) and cervical cancer are now well established. Several medical therapeutic candidates aimd at the treatment of precancerous lesions and invasive carcinoma of the cervix. The objective of this study was to develop the pH-sensitive chitosan/alginate gels (pH=3.8-4.5) and temperature sensitive multiblock copolymers of PEG/PLA (poly (L-lactic acid)/polyethylene glycol) gels (temperature=37 degrees C) for controlled delivery of the paclitaxel (PTX). We had also evaluated whether PTX entrapped in chitosan/alginate gels or multiblock copolymers of PEG/PLA 1 could inhibit tumor growth in vivo. METHODS: PTX entrapped as microsphere in Chitosan/Alginate Microspheres were obtained using a spray-drying method. PTX-entrapped PEG/PLA gels were prepared by the solvent displacement method. We had prepared the multiblock copolymers of PEG/PLA which has the sol-gel-sol transition temperature at body temperature. The in-vivo efficacy of PTX in chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. RESULTS: On 8 days after the transcutaneous treatment of PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer micelle. significant inhibition in tumor growth was observed in balb/c nu/nu nude mouse carrying xenograft tumors (HeLa cells; HPV-18 positive state). Among these formulations, PTX in PEG/PLA mutiblock copolymer have shown improved therapeutic efficacy as compared to PTX-ivgroup. CONCLUSION: PTX-containing chitosan microphere or PTX in PEG/PLA mutiblock copolymer nanoparticles are a unique pH-sensitive and temperature sensitive drug delivery system. These formulations elicits enhanced efficacy as an effective and minimally invasive treatment in mice bearing human cervical cancer (HeLa Cells) xenograft.

Characterization of a brain tumor cell line established from transgenic mice expressing the vasopressin SV-40 T antigen

We previously reported that transgenic mice produced with a transgene consisting of the SV40 T antigen and vasopressin without the 3'-flanking region exhibit brain tumors and lymphoma. In this study, transgenic mice were produced with the fusion gene containing the SV40 T antigen and the whole vasopressin gene with the 3'-flanking region. Six transgenic mice were generated, five which died after 2-6 weeks. The remaining founder mouse was investigated for fusion gene expression and tumor progression at the age of 6 weeks. Brain tumor cells were characterized for phenotypes and transgene expression. During in vitro cell cultures, the phenotypic appearances at 10, 20, and 30 passages were as a uniform monolayer with similar growth rates. The site of SV40 T antigen integration was in the A2 region of chromosome 11, and SV40 T antigen was expressed at the same level in cells of both earlier and later passages. Thirty passages were probably insufficient to reach crisis and immortalization. These cells enriched brain tumor cell compositions with astrocytes and neuronal cells.

The Comparison of Ropivacaine and Bupivacaine in Epidural Patient Controlled Analgesia (PCA) / 대한마취과학회지

BACKGROUND: Local anesthetics combined with an opiate are frequently used as a postoperative epidural PCA regimen. Ropivacaine is known to have a selective blockade of the sensory nerve without motor blockade. This study is designed to show advantages of ropivacaine over bupivacaine. METHODS: Patients undergoing elective abdominal and orthopedic surgeries were randomly selected and divided into two groups, B and R. The patients in group B and R received 0.2% bupivacaine and 0.2% ropivacaine respectively through an epidural catheter using a PCA pump. Both local anesthetic solutions were mixed with 4 microgram/ml of fentanyl. The PCA pumps of both groups were set in the same manner. A basal rate of 2 ml/hr was infused from 1hour after the onset of surgery. This basal rate was continued postoperatively. A bolus dose and lock out time were set at 2 ml and 20 minutes respectively. The Visual analogue pain scale (VAS), demand dose, complication and additional intramuscular analgesic requirements were checked up to 24 hours after surgery in 6-hour interval. RESULTS: The VAS was significantly lower in group R than in group B at 6, 12, 18 and 24 hours after the surgery (P < 0.05). Total additional bolus doses of the PCA pump were not significantly different in either group at 6, 12, 18 and 24 hours after surgery. The patients in group R showed more satisfaction and less additional intramuscular injections. CONCLUSIONS: 0.2% Ropivacaine, mixed with 4microgram/ml of fentanyl, was more effective than bupivacaine, mixed with the same concentration of fentanyl, in controlling postoperative pain using an epidural PCA pump.

Comparison between High Flow and Low Flow Anesthesia for Positive Pressure Ventilation in Pediatrics Using the Laryngeal Mask Airway / 대한마취과학회지

BACKGROUND: Low flow anesthesia provides many advantages, including reduced cost, conservation of body heat and airway humidity. This study was performed to compare low flow anesthesia with high flow anesthesia and to investigate whether the advantages of low flow anesthesia during positive pressure ventilation can be combined with the laryngeal mask airway in paralyzed pediatric patients. METHODS: Thirty-one pediatric patients of ASA physical status 1 or 2 were studied and divided into two groups according to the fresh gas flow (FGF) in the breathing system; low flow group (FGF approximation 1 L/min, n = 17) or high flow group (FGF approximation 4 L/min, n = 14). Each respiratory parameter was measured when a steady state was reached at 20 min after induction. RESULTS: There were no significant differences of respiratory data between the two groups except that the inspired oxygen concentration was lower in the low flow group than in the high flow group. Hemodynamic changes with the laryngeal mask airway insertion were not statistically significant. CONCLUSIONS: A laryngeal mask airway is an effective airway device for low flow anesthesia as well as for high flow anesthesia in paralyzed pediatric patients.

Lumbar Root Compression Secondary to Epidural Air Retension: A case report / 대한마취과학회지

Air can be introduced into the epidural space during the loss of resistance technique used to identify needle entry into the epidural space. Complications resulting from the injection of air into the epidural space include pneumocephalus, spinal cord and nerve root compression, retroperitoneal air collection, subcutaneous emphysema, venous air embolism, and possibly, incomplete analgesia and anesthesia. We experienced a case of a large epidural collection of air following epidural anesthesia attempted one month before. The CT scan revealed epidural air extending from L1-S1 with moderate compression of nerve root at L4-5.

A Comparison of the Antiemetic Effect of Ondansetron and Metoclopramide on Nausea and Vomiting Associated with Epidural Buprenorphine / 대한마취과학회지

BACKGROUND: Epidural buprenorphine provides good pain relief after Cesarean section, but is often associated with nausea and vomiting. Ondansetron, a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, is known to prevent and treat emesis after chemotherapy in cancer patients and after general anesthesia. The purpose of this study was to compare the prophylactic antiemetic effect of ondansetron and metoclopramide on nausea and vomiting after epidural buprenorphine. METHODS: Sixty women undergoing Cesarean section were studied. The patients were given subarachnoid injections of 0.5% tetracaine 9 mg and were inserted with epidural catheters for postoperative pain control. Prior to closure of the peritoneum, we injected a mixture of buprenorphine and bupivacaine through the epidural catheters and gave intravenous boluses of saline 6 ml, metoclopramide 10 mg and ondansetron 4 mg randomly. The incidence of nausea and vomiting and the degree of satisfaction were evaluated until 24 hr after the injection of epidural buprenorphine. RESULTS: The number of patients who became nauseated or vomited did not differ significantly between the ondansetron group and the metoclopramide group. Also, subjective ratings of satisfaction and incidence of other side effects did not differ significantly between the groups. CONCLUSIONS: Ondansetron, administered intravenously, prevented postoperative nausea and vomiting associated with epidural buprenorphine equally as well as metoclopramide.

The Effects of Flumazenil and Verapamil on the Relaxation of Midazolam in Isolated Guinea-pig Tracheal Smooth Muscle / 대한마취과학회지

BACKGROUND: Midazolam relaxes airway smooth muscle. The aim of this study is to evaluate the influence of flumazenil or verapamil on the relaxation effects of midazolam in tracheal smooth muscle of guinea pig. METHODS: After isolating guinea-pig tracheal preparations, the maximal tracheal tones were induced by 2 10(-7) M carbachol. When tracheal tones stabilized, midazolam was added cumulatively (10(-6), 3 10(-6), 10(-5), 3 10(-5), 10(-4) M, n=14) with or without flumazenil (10(-6) M, n=15) and verapamil (10(-5) M, n=13) to obtain the concentration-relaxation curves, and then the ED50 and ED95 calculated. RESULTS: Midazolam decreased maximal tracheal smooth muscle tones in concentration-dependent manners. Pretreatment with flumazenil had no effect on the midazolam-induced relaxation. Verapamil enhanced the relaxation effect of midazolam. CONCLUSIONS: Midazolam relaxes airway smooth muscle and has synergistic effect with calcium channel blocker, verapamil.

Does Phenylephrine Affect Hypoxic Pulmonary Vasoconstriction and Arterial Oxygenation during One Lung Ventilation? / 대한마취과학회지

BACKGROUND: Vasoconstricting drugs such as dopamine, phenylephrine (PE) and epinephrine constrict normoxic lung vessels preferentially, thereby disproportionately increasing normoxic lung pulmonary vascular resistance (PVR) and inhibit hypoxic pulmonary vasoconstriction (HPV). In this study, we evaluated the effect of PE on HPV and arterial oxygenation. METHODS: This study was performed on 21 patients undergoing thoracotomy. After induction of anesthesia, Swan-Ganz catheter was inserted. After one lung ventilation was started, systolic blood pressure (SBP) of the patient was reduced to 100 mmHg using inhalation anesthetic agent and then the blood pressure was raised up to 140 mmHg by PE infusion. Hemodynamic variables were measured and arterial blood gas was analyzed at the start of one lung ventilation (control), SBP of 100 mmHg and SBP of 140 mmHg. RESULTS: The mean dose of PE infused was 5.9 +/- 3.8 microgram/kg. Infusion of PE did not increase pulmonary vascular resistant index (PVRI) significantly and did not reduce arterial PO2. There was no statistically significant difference in intrapulmonary shunt fraction (Qs/Qt) between the time of low and high blood pressures. CONCLUSION: Pulmonary vasomotor changes induced by PE are minimal and so should not affect the distribution of blood flow during one lung ventilation. On the basis of this result, PE appears to a reasonable vasoconstrictor to be used in patients undergoing thoracotomy.

The Effect of Pneumonectomy on Right Ventricular Function / 대한마취과학회지

BACKGREOUND: The pneumonectomy may depress the right ventricular (RV) function transiently. The thermodilution ejection/volumetric catheter is known to be most useful method assessing the changes in RV performance during pulmonary resection. The purpose of this study was to examine the RV function during and immediately after pneumonectomy using thermodilution methods. METHODS: 16 patients undergoing pneumonectomy were studied. After induction of anesthesia, a multilumen thermodilution catheter mounted with a rapid response thermister was inserted. Using computer system, RV ejection fraction (RVEF), cardiac output, and RV end-diastolic volume (RVEDV) were measured when the patient was in lateral position (control), after one lung ventilation (OLV) and the main pulmonary artery ligated, and at the completion of resection. Arterial blood gases were analyzed and pulmonary vascular resistance (PVR) was calculated. RESULTS: Systolic pulmonary blood pressure (SPAP)(28.3 +/- 6.2 mmHg) increased compared to the control (24.6 +/- 5.9) without a significant change of PVR. No statistically significant difference was found in either RVEF or RVEDV at each times. CONCLUSIONS: Our study demonstrate the pneumonectomy do not depress the RV function immediately and RVEF do not show any correlation with PVR or RVEDV.

A Study on Indoor Environment of Operating Room / 대한마취과학회지

BACKGROUND: The operating room should provide an optimum environment that is safe for the patient and the working personnel. In this point of view, we investigated 8 items of temperature, humidity, air flow, noise, brightness, dust, CO2 and NO2. METHODS: Operating rooms, corridors and recovery rooms were tied as region I, II and III depending on their characteristics. 29 points were measured using appropriate instruments. After that, averaged values were calculated. RESULTS: Indoor climate (temperature, humidity and air flow) in region I were averaged 24.7, 65, 0.18/II were 25.5, 68, 0.18/III were 22.3 (degrees C), 56 (%), 0.22 (m/sec). Physcial condition (noise, brightness and dust) in region I were averaged 63, 295, 63/II were 67, 138, 87/III were 63 (db), 139 (lux), 26 (microgram/m3). Harmful gas (CO2 and NO2) concentration in region I were averaged 1152, 0.008/II were 913, 0.009/III were 1367 (ppm), 0.013 (ppm). CONCLUSIONS: Temperatures were appropriate but humidities were high except partial points. Air flow showed low values in average. Values of noise, dust and CO2 were relatively high. NO2 was low but brightness was variable. These mean that adequate improvement for quiet condition and air ventilation should be considered.

Atrial Fibrillation during Repair of Esophageal Hiatal Hernia: A case report / 대한마취과학회지

Postoperative atrial arrhythmia after thoracotomy is relatively common, with a reported incidence ranging from 8% to 30%. These arrhythmias may cause hypotension, congestive heart failure and lengthen the period of postoperative hospitalization. The most important precipitating factor is atrial dilation and identified risk factor is an advanced age of the patient. The effect of various prophylactic regimens to reduce atrial arrhythmias is controversial. We report a case of postoperative atrial fibrillation in a 73 year-old female patient undergoing repair of esophageal hiatal hernia.

Factors Affecting the Length of Time to Remove the Air Bubble in Left Ventricle Detected by Echocardiography after Cardiopulmonary Bypass / 대한마취과학회지

BACKGROUND: Air trapped in left ventricle(LV) after cardiopulmonary bypass(CPB) is a major source of air embolism. We tried to measure the length of time(T) to remove the air bubbles from release of aortic cross clamp(ACC) and to find the factors affecting the length of time. METHODS: With Institutional Review Board(IRB) approval, 125 patients undergoing valvular replacement and repair of atrial septal defect(ASD) were included in this prospective study. After induction of anesthesia, a 5-MHz phased-array transesophageal echocardiographic(TEE) probe was inserted into the esophagus and then connected to the TEE system. TEE was continuously monitored from the time of release ACC to the end of operation. And the length of time from release of ACC to disappearance of the air bubbles in LV was recorded. RESULTS: The mean T was 27.5+/-12.0 minutes and was statistically longer in patients undergoing mitral valve replacement than in patients with ASD. There was significant difference in T between surgeon 1 and surgen 2. In patients with atrial fibrillation(A-fib) the air bubbles were removed more slowly than in patients with normal sinus rhythm preoperatively and there was negative correlation between preoperative ejection fraction(EF) and the length of time to remove air bubbles(r= 0.23). CONCLUSIONS: Careful management to remove the air bubbles from the LV after release of ACC is required in patients with low EF or A-fib preoperatively and surgeon's attention is required because they are the important factor affecting the length of time to remove the air bubble.

Effects of Autologous Platelet-Rich Plasma on Postoperative Blood Loss and Transfusion Requirements in Cardiac Surgery / 대한마취과학회지

BACKGROUND: Patients undergoing cardiac surgery employing cardiopulmonary bypass frequently require transfusion of homologous blood products and, therefore, are exposed to the risk of transfusions. A administration of autologous platelet-rich plasma may reduce homologous transfusion and attendant risks. This study was designed to investigate the effect of preoperative collection of platelet-rich plasma on the requirement of homologous transfusion and postoperative blood loss in patients undergoing open heart surgery. METHODS: Twenty seven patients undergoing cardiac surgery were divided into control group(n=11) and autologous platelet-rich plasmaphereris(PRP) group(n=16). Autologous platelet-rich plasma was retransfused after offbypass. Hematocrit, platelet count, PT(prothrombin time), PTT(partial thromboplastin time), postoperative blood loss and transfusion requirement were measured. RESULTS: There was no statistical significance between control and PRP group in homologous transfusion and postoperative blood loss. There was no difference in hemoatocrit, platelet count, PT or PTT on immediate post surgery or on day 1. CONCLUSIONS: Autologous platelet-rich plasma did not reduce postoperative blood loss or transfusion reguirements in cardiac surgery.

Clinical Experiences of Balanced Anesthesia with Nalbuphine or Fentanyl in Cesarean Section / 대한마취과학회지

The effect of fentanyl and nalbuphine used as analgesics in balanced anesthesia were evaluated in 60 full term parturients, ASA physical status class I or II, sheduled for elective cesarean section. They were injected intramusculary with 0.2 mg of glycopyrrolate 30 minutes to one hour prior to the induction of anesthesia. Four mg/kg of thiopental sodium and one mg/kg of succinylcholine were administered intravenously for the induction and endotracheal intubation. Anesthesia was maintained with 66% of nitrous oxide in oxygen until delivery. Following the intravenous injection of 4 mg-vecuronium, controlled ventilation was applied to maintain at PCO1 30 to 40 mmHg. Immediately after clamping of the umbilical cord, 3 ug/kg of fentanyl(F group) or 0.3 mg/kg of nalbuphine(N group) with 5 mg of droperidol were administered. In the F group, the systolic and diastolic blood pressures at three minutes after fentanyl were significantly lower than those during the preinduction period and during recovery room stay. The systolic BP in the preinduction period was significantly higher than those of three minutes after nalbuphine, and the diastolic BP at the preinduction period was also higher than those of three minutes after nalbuphine and during recovery room stay. Heart rates were significantly increased three minutes after nalbuphine than at recovery room. The blood presures and heart rates were not significantly different between the two groups. The time intervals from the end of the operation to the first analgesics were significantly longer in the N group(mean 11.3 hours) in contrast to the F group(mean 6.9 hours). There were a few complications such as nausea, headache, dizziness, somnolence and euphoria. The incidences of awareness was 13.3 and 6.7% in the F and N group, respectively. We concluded that the balanced anesthetic technique using nalbuphine with droperidol nuder the inhalation of 66%-nitrous oxide resulted in a satisfactory anesthesia for cesarean seetion with good postoperative analgesia.