Purpose: The high mobility group A2 (HMGA2) nonhistone chromosomal protein can modulate transcription by altering chromatin architecture. HMGA2 is highly expressed during embryogenesis and in various benign and malignant tumors. Recent studies report that HMGA2 is negatively regulated by the let-7 microRNA (miRNA) family. However, no studies have examined the clinical significance of HMGA2 and its relationship to the let-7 miRNA family in gastric cancer. Experimental Design: Using quantitative real-time reverse transcription^PCR, we analyzed HMGA2 expression with respect to various clinicopathologic factors in 110 patients with gastric cancer. We also did an association study comparing HMGA2 expression and let-7 miRNA family expression in gastric cancer. Results: Expression of HMGA2 in cancerous tissues was significantly higher than in noncancerous tissues (P < 0.05). Elevated HMGA2 expression was significantly correlated with serosal invasion (P < 0.05) and poor clinical prognosis (P < 0.05). A multivariate analysis showed that HMGA2 expression status was an independent prognostic factor (P < 0.05). An inverse correlation between HMGA2 and let-7a was found in gastric cancer cell lines (P = 0.08). The expressions of let-7a, let-7b, and let-7c in gastric cancer patients with low HMGA2 expression were significantly higher than those with high HMGA2 expression (P < 0.05).Conclusions: High expression of HMGA2 in gastric cancer correlates with tumor invasiveness and is an independent prognostic factor. Furthermore, our findings suggest that HMGA2 is negatively regulated by the let-7 miRNA family in human gastric cancer.

This study consisted of 2 aims: (i) to determine genes associated with hepatocellular carcinoma (HCC) by microarray analysis; and (ii) to evaluate the clinicopathological significance of human ubiquitin-conjugating enzyme E2C (Ube2c) found to be overexpressed in HCC from microarray analysis. Laser microdissection and cDNA-microarray were performed to identify genes associated with HCC. We then focused on the Ube2c gene. Using realtime quantitative reverse transcription-polymerase chain reaction (RT-PCR), Ube2c expression status and clinicopathological significance were studied in 65 clinical HCC samples. A number of genes upregulated in HCC cells compared to noncancerous liver cells were identified, one of which was the Ube2c gene. Ube2c gene expression in the cancer tissue was higher than in the corresponding noncancerous tissue in 62 of the 65 cases (95.4%, p < 0.01). Tumors with high Ube2c expression showed higher frequencies of tumor invasion to capsular formation (fc-inf), invasion to portal vein (vp) and tumor de-differentiation (p < 0.05). Patients with high Ube2c expression also showed significantly worse disease-free survival rates than those with low Ube2c expression (p < 0.01). In addition, Ube2c expression was found to be an independent prognostic factor for disease-free survival rate in multivariate analysis. We identified differentially expressed genes between HCC and normal liver tissues. Of those, the Ube2c gene appeared to be associated with HCC progression, and may be useful as a prognostic indicator for HCC patients. ' 2007 Wiley-Liss, Inc.

1 The actions of troglitazone, pioglitazone, metformin and beza®brate, agents that improve insulinresistance, on voltage-dependent Ca 2+ channels in arterial smooth muscle cells were examined by use of the conventional and nystatin-perforated whole-cell clamp methods. Single cells were freshly isolated from resistance mesenteric arteries of guinea-pigs. The actions of these agents on 77 mM K + -induced contraction of the isolated arteries were also examined with the use of isometric tension recording. 2 The thiazolidinedione derivatives, troglitazone and pioglitazone, inhibited whole-cell Ca 2+ currents in a dose-dependent manner with dissociation constants of 3.0 mM and 44.9 mM and Hill coecients of 0.61 and 0.68, respectively. These two agents inhibited the 77 mM K + -induced contraction with similar potencies as those inhibiting the Ca 2+ currents. Metformin and beza®brate had no apparent eects on the Ca 2+ current or high K + -induced contraction. 3 The inhibitory action of troglitazone on Ca 2+ currents was not aected by the command potential, the holding potential, or the stimulation frequency, suggesting that its mode of the action diers from that of known organic Ca 2+ channel antagonists. 4 The inhibitory action of troglitazone on Ca 2+ currents was not aected by the addition of insulin to, or the removal of glucose from, the solutions. 5 In conclusion, the thiazolidinedione derivatives directly inhibited the voltage-dependent Ca 2+ channels in a dierent manner from that of organic Ca 2+ channel antagonists. This inhibitory action on Ca 2+ channels was not a common feature of insulin-sensitizing agents.

We investigated changes in blood pressure and blood variables, including plasma catecholamines, serum glucose and insulin concentrations, during dental surgery. The study included 11 normotensive patients (age, 22.5+/-0.7 years) who underwent tooth extraction at Kyushu Dental College Hospital. Three to 7 days prior to dental surgery, blood pressure, pulse rate, and heart rate variability were measured every 30 min over 24 h. The low frequency (LF: 0.05 to 0.15 Hz) and high frequency (HF: 0.15 to 0.40 Hz) powers were calculated, and the ratio of LF to HF (LF/HF) and HF were used as indexes of sympathetic and parasympathetic activities, respectively. Lidocaine, 2% with epinephrine (1:80,000), was used as the local anesthetic for all patients. Systolic blood pressures significantly increased during dental surgery (+10.8+/-3.5 mmHg); however, this increase failed to correlate not only with baseline systolic blood pressure but with 24-h averaged blood pressures, LF/HF or HF. On the other hand, plasma epinephrine and norepinephrine concentrations increased during dental surgery, and peak values of these variables were obtained after local anesthesia and during tooth extraction, respectively. Serum glucose level increased after local anesthesia (control vs. local anesthesia: 5.16+/-0.11 vs. 5.62+/-0.10 mmol/l; p<0.01); however, plasma insulin concentrations did not change significantly. These results suggest that 1) ambulatory measurements of blood pressure and heart rate variability over 24 h cannot predict the responses of blood pressure during dental surgery, and that 2) administration of local anesthetic and tooth extraction activate sympathoadrenal outflow, resulting in an increase in serum glucose level in normotensive subjects.