DCC Gene and Protein Expression in Colorectal Cancer

PURPOSE: The germline, or somatic, inactivation of tumor suppressor genes, through point mutation, or deletion, plays an important role in carcinogenesis. Several gene alterations, such as adenomatous polyposis coli (APC), deleted in colorectal cancer (DCC) and p53, have been detected in the development of colorectal cancer. Within these genes, a loss of heterozygosity (LOH) at the DCC gene locus was frequently associated with colorectal tumors, and the LOH of the DCC gene, and the expression of the DCC protein, might be related to malignant formation and metastasis. The aim of this study was to determine the DCC LOH and the expression of DCC protein in colorectal cancers, and evaluate their prognostic value and relationship with the clinicopathological data. MTHODE: Fifty colorectal cancer tissues were obtained from resected specimens. Using formalin-fixed paraffin- embedded sections as a source of DNA, we examined the DCC protein in the tissue through immunohistochemical stainings and immunoblotting analysis, the DCC LOH through a polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP). RESULTS: DCC LOH was observed in 24 of the 50 patients (48.0%). The expression of the DCC protein was decreased in the cancer tissue (62.3 23.6%) compared with the adjacent normal mucosa inform the immunoblotting analysis. A decreased DCC protein expression was also observed from the immunohistochemistry, which coincided with the immunoblotting analysis. However, both the DCC LOH and the decreased DCC protein were not related to the clinical and pathological parameters, such as location of tumor, tumor size, histological type and the venous, and lymphatic invasions. There were significant correlations between the DCC protein expression and tumor progression, and hematogenous metastasis (P<.05). CONCLUSIONS: A decreased expression of the DCC protein was noted in human colorectal cancers, and there was a significant relationship between the expression of the DCC protein and distant metastasis, but there was no correlation between the DCC LOH and distant metastasis. These results suggest that the expression of the DCC protein might be related to tumor progression and metastatic potential, and the DCC protein immunoreactivity may be a useful prognostic factor in patients with colorectal cancers.

The Pattern of beta-Catenin Expression in Adenomas and Carcinomas of the Gallbladder

PURPOSE: beta-catenin is a key regulator of the cadherin-mediated cell adhesion system and also plays a role as a transcription regulating factor. Nuclear expression and mutation of beta-catenin have been identified in some benign and malignant tumors, and over expression of beta-catenin indicates an oncogenic potential. This study was designed to clarify the role of beta-catenin in the histogenesis of gallbladder carcinoma. METHODS: In benign hyperplastic lesions, adenomas, and carcinomas of the gallbladder, intracellular expression of beta-catenin was investigated by immunohistochemical stainings. Cyclin D1 and Ki-67 were also examined. RESULTS: All of the hyperplastic lesions showed membranous expression of beta-catenin. Adenomas and polypoid carcinomas showed significantly higher incidence of cytoplasmic and nuclear expression of beta-catenin than hyperplastic lesions and infiltrative carcinomas (P<0.01). Loss of beta-catenin expression was frequently noticed in infiltrative and poorly differentiated carcinomas. Nuclear expression of beta-catenin in carcinomas had unique pathologic characteristics, including polypoid growing, well differentiated tubular type, and early stage. Cytoplasmic and nuclear expression of beta-catenin showed good correlations with cyclin-D1 expression (P<0.05). The Ki-67 index was significantly higher in infiltrative carcinomas than in adenomas or polypoid carcinomas (P<0.05). CONCLUSION: Our results suggest that beta-catenin as a molecular marker may play a role in the carcinogenesis of the adenoma-carcinoma sequence of polypoid carcinomas. Infiltrative carcinomas, however, may have different mechanisms.

Clinicopathologic Significance of HBV X, Core promoter, Precore Mutants in Patients with Chronic HBV Infection / 대한간학회지

BACKGROUND/AIMS: There have been much debates on the effects of HBV mutants on the clinical course of HBV-associated chronic liver diseases. The purpose of this study was to define the relationship among HBV mutants, severity of hepatitis and expression patterns of HBcAg METHODS: HBV DNA was extracted from the liver tissue of 31 patients who had been HBsAg positive for more than 6 months. The amplification of X was performed as well as core promoter/precore region of HBV DNA by polymerase chain reaction and then direct sequencing of them. Pathologic severity was classified utilizing Scheuer's scoring system and immunohistochemical staing for HBcAg in hepatocytes was performed. The expression patterns of HBcAg were divided into four types according to expression location of HBcAg: Type I as a nuclear predominant expression of HBcAg; Type II as mixed patterns, combined expression of cytoplasmic and nuclear localization of HBcAg; Type III as a diffuse cytoplasmic expression of HBcAg; and Type II as an inclusive body-like expression in cytoplasm. RESULTS: In investigating the relationship between HBV mutants and clinical findings, ALT, HBV DNA and hepatitis activity index (HAI) in hepatitis with wild HBV were normal to high but those in hepatitis with core promoter or precore mutants were high . There were no statistically significant differences (p=0.062). In terms of the relationship between HBV mutants and the expression pattern of HBcAg, type I, II, IV were noticed in hepatitis with wild HBV but in almost all mutants cases type III, II were noticed (p<0.01). The score of HAI increased as the number of the expression pattern of HBcAg increased from type I to type III or IV(p<0.05). No relationships among the mutation in X region, the mutations in other regions and clinicopathological severity could be found. CONCLUSION: The mutation in X, core promoter and precore region had little association with the severity of hepatitis. And the relationship did not exist between precore mutants and X mutants. The expression pattern of HBcAg could be a useful indicator in determining what stage of chronic hepatitis B is in and whether mutant strains exist.

Analysis of Effect of Coagulation Management Based on the Changes of Thromboelastographic Variables during Orthotopic Liver Transplantation / 대한마취과학회지

Introduction: Thromboelastography (TEG) provides an overall assessment of the platelet-coagulation protein cascade interaction. The information generated from the TEG is rapidly obtained and made useful to guide replacement therapy. The purpose of this study was to evaluate the efficacy of the TEG as its guided blood replacement therapy and pharmacological therapy during liver transplantation. METHODS: This study was carried out in 13 consecutive patients who were subjected to TEG-guided replacement therapy during liver transplantation. A prepared mixture of blood products used for continuous replacement therapy was a fluid composed of red blood cells(2 units), fresh frozen plasma (2 units), and normal saline(500 ml). The pharmacological therapy was performed by comparing TEG of untreated blood and blood treated with antifibrinolytic and heparin neutralizing agent. Based on the findings of TEG, platelet concentrates were given. The TEG samples were obtained at various intervals. Additional TEG tracing was obtained as needed to see the effect of therapeutic intervention. RESULTS: In all patients the reaction time was kept in an acceptable range in the preanhepatic stage by administration of the mixture of blood products. Heparin-induced anticoagulation was observed in 3 cases in the anhepatic stage and in 11 cases upon reperfusion. Fibrinolysis was seen in all but one patients: 8% in the preanhepatic stage, 41% in the anhepatic stage, 69% at reperfusion, and 2% in the postanhepatic stage. Early and aggressive treatment with epsilon-aminocaproic acid effectively inhibited fibrinolysis without complications. Ten patients needed platelet transfusion in the postanhepatic stage with significant improvement in the TEG. CONCLUSIONS: The results of this study suggest that TEG monitoring and TEG-guided replacement and pharmacological therapy are clinically effective in maintaining blood coagulability.

The Assessment of Change in Total Oxygenation by Continuous Monitoring of Mixed Venous Oxygen Saturation during Canine Orthotopic Liver Transplantation / 대한마취과학회지

There are many hemodynamic and physiologic changes during liver transplantation much more than other surgical interventions. The oxygen delivery and oxygen consumption are af- fected by depressed hemodynamic and metabolic status during the operation. At the lower levels of oxygen present in venous blood, a linear relationship exists between saturation and tension. The use of fiberoptic oximetry system in conventional pulmonary artery flotation catheters has made the bedside application of this relationship of practical value in the continuous assessment of mixed venous oxygen saturation. This study was performed to determine changes in SvO2 and other variables of oxygen kinetics during canine OLT and study the correlation between SvO2 and cardiac output, SvO2 and oxygen consumption and oxygen utilization ratio. The continuous rnixed venous oxygen saturation and cardiac output by SO2/CO computer were monitored and the oxygen delivery, oxygen consumption and oxygen utilization ratio were calculated by arterial and venous blood gas analysis and modified Fick's equation during orthotopic liver transplantation in 20 dogs. The results were as follow as ; 1. There was no significant difference in tissue oxygen extraction between preoperative control and anhepatic phase, while cardiac output were decreased during anhepatic phase. 2. By utilizing centrifugal pump(venovenous bypass) oxygen delivery and oxygen utilization ratio were well maintained even though suppressed the change of oxygen delivery and oxygen consumption during anhepatic phase. 3. There was a significant decrease in SvO2 immediately after declamping the suprahepatic vena cava, whereas the oxygen utilization rate and oxygen consumption following reperfusion were significantly increased than just prior to reperfusion of transplanted liver. 4. A Statistically significant correlation was found between SvO2 and cardiac output, oxygen consumption in all surgical stages except reperfusion(CO;r=0.478, p<0.001, VO2,r=-0. 272, p=0.004), but their correlations were relatively poor. However, there was highly significant correlation among SvO2 and oxygen utilization ratio in all surgical stages(O2UR; r=- 0.834, P<0.001). In conclusion, continuous monitoring mixed venous oxygen via a fiberoptic pulmonary catheter could be used as the index for evaluation of hemodynamics and oxygen kinetics during canine OLT, but further research should be performed to determine whether these measurements indicate viability of the grafted liver.