We have previously demonstrated in an in vitro study that Snail increased the invasion activity of hepatoma cells by upregulating matrix metalloproteinase (MMP) gene expression. In the present study, we examined whether Snail gene expression correlates with cancer invasion and prognosis of patients with hepatocellular carcinoma (HCC). Quantitative reverse transcription -polymerase chain reaction (RT -PCR) was performed to evaluate Snail, E-cadherin, and MMP mRNA expressions in eight nodule-in-nodule tumours and 47 ordinary HCC tissues. In the nodule-in-nodule tumours, Snail expression significantly increased with tumour dedifferentiation (P ¼ 0.047). In the ordinary HCC tissues, Snail expression was significantly correlated with portal vein invasion (P ¼ 0.035) and intrahepatic metastasis (P ¼ 0.050); it also showed a significant correlation with MT1-MMP expression (r ¼ 0.572, Po0.001). In recurrence-free survival, the group with high Snail expression showed significantly poorer prognosis (P ¼ 0.035). Moreover, high Snail expression was an independent risk factor for early recurrence after curative resection. During the progression of HCC, Snail expression may be induced and accelerate invasion activity by upregulating MMP expression, resulting in portal invasion, intrahepatic metastasis, and poor prognosis. British Journal of Cancer (2005) Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world and a frequent cause of cancer fatalities in Japan. Improvements in early diagnosis, surgical techniques, and perioperative management have contributed to decreases in mortality and morbidity among patients with HCC (Okuda et al, 1985;Fran et al, 1999). However, the long-term prognosis of patients with HCC after hepatectomy has been still poor because of a high incidence of recurrence after initial treatment (Fong et al, 1999;Poon et al, 2000b). Several centres have reported a cumulative 5-year recurrence rate ranging from 75 to 100% (Chen et al, 1994;Fong et al, 1999;Poon et al, 2000b). Pathological and genetic analyses have indicated two features in HCC recurrence: multicentric occurrence of new tumours (MO) and intrahepatic metastasis of the original tumour (im) (Tsuda et al, 1992;Matsumoto et al, 2001). It has been reported that MO is significantly influenced by the underlying liver status, such as the presence of active hepatitis (Belghiti et al, 1991;Ko et al, 1996). On the other hand, im is thought to be more closely associated with tumour factors, especially portal vein invasion (vp) (Vauthey et al, 1995;Shimada et al, 1999). Several published studies have demonstrated that vp plays an important role in the im process and influences the survival rate of patients with HCC (Fuster et al, 1996;Mitsunobu et al, 1996; The Liver Cancer Study Group of Japan, 1994). Therefore, it is important to elucidate the molecular mechanisms of vp and im; the subsequent establishment of markers for predicting vp and im may contribute to improvement in the prognosis of patients with HCC.Recently, the z...

The detection of human herpesvirus 6 (HHV-6) DNA was carried out in throat swabs of adults and children by the polymerase chain reaction, and isolation of virus was also attempted from peripheral mononuclear cells. Although virus was isolated only from peripheral blood mononuclear cells of infants with exanthem subitum, HHV-6 DNA was detected in one of 30 healthy adults (3%), two of nine adults (22%) with common cold, two of 10 infants (20%) with exanthem subitum, four of 39 febrile children (10%) with antibody to HHV-6 (including three of 10 infants aged under 1 year old, and one of 29 children aged over 1 year old). However, HHV-6 DNA was not detected in samples from healthy neonates.

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Abstract:To investigate the nature of viremia during the acute phase of varicella, we studied the viral load in nine otherwise healthy children with varicella. Plasma and peripheral blood mononuclear cells (PBMC) were obtained, then PBMC were divided into CD4+T, CD8+T, and B lymphocytes and monocyWmacrophage fractions. The viral DNA in each component was quantified using a real-time quantitative polymerase chain reaction assay. Varicella-zoster virus (VZV) DNA was detected in plasma, PBMC and all subpopulations. The amount of viral DNA was similar in each PBMC subpopulation, suggesting that each lymphocyte fraction and monocytes carry similar amounts of VZV DNA during viremia.Key words: Varicella-zoster virus, Lymphocyte subpopulations, Quantitative PCR assay Varicella (chickenpox) is characterized by febrile illness with pruritic vesicles, and is the result of primary infection with varicella-zoster virus (VZV). The pathogenesis is as follows: virus entry at the respiratory mucosa and primary viremia are believed to occur; then secondary viremia of greater magnitude occurs; finally, the rash results. Understanding the nature of the viremia is thought to be important in order to clarify the pathophysiology of varicella infections and complications of the disease (I, 7). Peripheral blood mononuclear cell (PBMC)-associated viremia has been demonstrated just before and after the onset of disease (2,5,6,13,15,16). Determining the phenotypes of the PBMC subpopulations is complicated by the low frequency of positive cells and the difficulty in achieving highly purified preparations of subpopulations.Recently, we established a quantitative real-time polymerase chain reaction (PCR) assay to quantify the VZV genome copies (8). Using this assay, we observed that there was a higher occurrence of viremic VZV in varicella than in zoster, and that acyclovir treatment marked-*Address correspondence to Dr. Yoshinori Ito, Department of PediatricslDevelopmental Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Fax: 81-52-744-2974. E-mail: yyito @med.nagoya-u.ac.jp 267 ly suppressed viremia in varicella (9). In this study, we quantified the viral load in the peripheral blood leukocyte subpopulations to determine which subpopulations harbor VZV during the acute phase of varicella. We also quantified the viral load in plasma to investigate whether viral DNA in blood is restricted to PBMC fraction.Nine healthy children with clinically diagnosed varicella (0 to 3 years old, median: I year) were enrolled in this study. None of these patients had a previous history of varicella. At the time of entry, none of the patients had received oral acyclovir therapy.All the specimens were obtained after informed consent. Blood samples were taken when the patients had clinical indications in the acute phase. Sampling occurred 2 to 5 days after the onset (mean: 2.3 days). Whole blood was obtained from the patients, and plasma and PBMC were separated by density gradient with Ficoll-P...

The pathogenesis of varicella and zoster and the effects of antiviral treatment were investigated using realtime PCR for varicella-zoster virus (VZV) DNA in skin lesions and peripheral blood. A higher occurrence of viremic VZV DNA was observed in varicella than in zoster. Acyclovir treatment resulted in marked suppression of viremia in varicella.