Additive effect of TRAIL and p53 gene transfer on apoptosis of human lung cancer cell lines

TRAIL is a cytokine that can induce tumor-specific apoptosis through its specific death receptors (DR4 and DR5) and p53 has been proven to increase the expression of death receptors. To examine their interaction in tumor suppression, p53 and TRAIL genes were inserted in recombinant adenovirus vectors and transferred simultaneously into non-small cell lung cancer cell lines (NCI-H157, NCI-H358, NCI-H460 and A549). Western blot assay demonstrated production of TRAIL protein in NCI-H157 and A549 cell lines. Increased expressions of DR4 and DR5 of NCI-H157 and DR4 of A549 after p53 overexpression were confirmed by flow cytometry. p53 or TRAIL gene transfer increased sub-G1 fraction in cell cycle analysis and inhibited the tumor growth dose-dependently and the degree was potentiated by co-transfer. But isobologram analysis indicated an additive effect. Together, these data indicate that p53 and TRAIL interact additively on tumor apoptosis despite theoretical synergism.     

Identification of the products of the equine herpesvirus type 4 gI and gE genes

Summary.  In order to identify the products of the equine herpesvirus type 4 (EHV-4) gI and gE genes, we have constructed recombinant vaccinia viruses containing the putative gI or gE genes. These recombinant viruses synthesized EHV-4 gI and gE with apparent molecular masses of 75 and 80 kDa, respectively. Antibodies raised against both recombinant viruses detected a 75 kDa gI and a 95 kDa gE in EHV-4-infected cells. The results also suggest that the EHV-4 gI and gE would form a complex like in other herpesviruses. Received October 29, 1999 Accepted January 21, 2000     

Assessment of cyclooxygenase inhibitors using in vitro assay systems

Various inhibitors of cyclooxygenase are known to mediate cancer chemopreventive effects. We currently describe two in vitro assay systems for measuring cyclooxygenase activity. These assays can be used in combination and thereby provide a rapid, reliable, and economical approach that is applicable for large-scale evaluation of test samples. This approach employs peroxidase co-substrate oxidation and oxygen consumption assays. The former system, adapted to a 96-well plate format, detects inhibitors that function as a radical scavengers or interact with the enzyme directly. The latter system specifically monitors cyclooxygenase inhibitors that interact with the enzyme itself. Thus, the peroxidase co-substrate oxidation assay serves as a pre-screening method, whereas the oxygen consumption assay is used subsequently to investigate the mode of action mediated by samples which test positive.     

Alterations in extracellular matrix components in transplant glomerulopathy

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy. Received: 5 October 1999 / Accepted: 17 January 2000     

First serologic evidence of human spotted fever group rickettsiosis in Korea

To investigate the prevalence of spotted fever group rickettsioses in Korea, a serosurvey of Japanese spotted fever rickettsiosis in patients with acute febrile illness was conducted with an indirect immunofluorescence assay. Overall, 19.88% of the patients were found to have polyvalent antibody against Rickettsia japonica. This study is the first documentation of spotted fever group rickettsiosis in Korea.     

Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat

The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.     

Clinical Comparison of Distal Pancreatectomy with or without Splenectomy

The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis.     

Clinical prognostic values of vascular endothelial growth factor, microvessel density,and p53 expression in esophageal carcinomas

Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.     

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.