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Synthesis of 3-functionalized (Z)-silyl enol ethers from readily available 1-arylallyic alcohols was achieved by C,O-difunctionalization of dipotassio α,β-dianion intermediates.

This paper describes the regio- and diastereoselective synthesis of unsymmetrical 1,4-diketone-derived (Z)-monosilyl enol ethers from 1-arylallyloxysilanes and Weinreb amides using (trimethylsilyl)methylpotassium as a base.

This paper describes the regio- and diastereoselective synthesis of unsymmetrical 1,4-diketone-derived (Z)-monosilyl enol ethers from 1-arylallyloxysilanes and Weinreb amides using (trimethylsilyl)methylpotassium as a base. The metalation of 1-arylallyloxysilanes to generate siloxyallylpotassiums is the key step in this transformation. The products can be transformed into diverse α-monofunctionalized unsymmetrical 1,4-diketones.

AIM To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication. METHODS In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression. CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.

BACKGROUND AND AIM Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection. METHODS Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method. RESULTS Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P

Aim Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection. Methods Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan–Meier analysis. Results Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0–38.6; P

Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs), similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover, the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered preneoplastic conditions for HCC, has not been fully elucidated. The aim of this study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC tissue samples compared to corresponding non-tumorous liver tissues (NTs), comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the significance of molecular changes at the preneoplastic stages of HCC. Immunohistochemical analysis demonstrated that the median expression levels of AKR1B10 were higher in HCCs than in NTs (p < 0.001) and higher in NTs than NLs (p < 0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs, respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs and NLs with no significant difference between expression in NTs and NLs. Furthermore, a multivariate analysis identified an association between hepatic steatosis and AKR1B10 expression in NTs (p = 0.020). Of the three protein expressed in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic conditions, and a steatosis-related factor might influence its expression.

Background and Aim The purpose of this study was to evaluate the usefulness of liver stiffness measurement (LSM) for assessing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN) therapy. Methods One hundred fifty-one CHC patients who underwent LSM and received IFN therapy were included in the estimation cohort, and 56 were included in the validation study. The cumulative HCC incidences were evaluated using Kaplan–Meier plot analysis and the log-rank test. Multivariate Cox proportional hazard analyses were used to estimate the hazard ratios (HRs) of variables for HCC. Results In the estimation cohort, 9 of 151 patients developed HCC during the median follow-up time of 722 days. Multivariate analysis identified three independent risk factors for HCC: LSM (≥ 14.0 kPa, HR 5.58, P = 0.020), platelet count (

OBJECTIVE Genotype 1 chronic hepatitis C (G1CHC) is generally accompanied by metabolic disturbances related to visceral obesity, such as insulin resistance, steatosis, or dyslipidemia. Because these abnormalities negatively influence the clinical course of G1CHC, we sought to clarify the effect of visceral obesity on the pathophysiology of G1CHC. METHODS We evaluated 180G1CHC patients for the presence of visceral obesity on the basis of computed tomography findings. Multivariate analysis was performed to estimate the relationship between visceral obesity and demographic, viral, and biochemical characteristics of patients. The associations of visceral obesity with histological findings and serum adipokine levels were also analyzed. RESULTS Multiple logistic regression analysis revealed that visceral obesity was independently associated with metabolic syndrome, platelet count, high-density lipoprotein level, and serum viral load in elderly patients (≥65 years). Multiple linear regression analysis confirmed the association between visceral obesity and high viral load. However, visceral obesity was not correlated with viral load in non-elderly patients (

Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection.Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan-Meier analysis.Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0-38.6; P 0.001). The 5-year cumulative incidences of HCC were 20.6% and 2.6% in patients with high and low AKR1B10 expression, respectively (P 0.001). Patients with high AKR1B10 expression had significantly higher alanine aminotransferase levels during follow-up than those with low expression, even though antiviral treatment decreased HBV-DNA levels in both groups.Chronic HBV-infected patients with high hepatic AKR1B10 expression had an increased risk of HCC development. This suggests that AKR1B10 upregulation might play a role in the early stages of HBV-related hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide 1. Approximately 70–90% of patients with HCC have an established background of chronic liver disease and cirrhosis 1. Persistent infection with the hepatitis C virus (HCV) is one of the major causes of chronic liver disease leading to the development of HCC. Persistent HCV infection is responsible for 27–75% of the HCC cases in Europe and the United States and >80% of the HCC cases in Japan 2, 3. The annual incidence of HCC development is 2–8% in cirrhotic patients with chronic HCV infection 4, 5. Persons with anti-HCV positivity were shown to have a 20-fold increased risk of developing HCC in comparison with those who were negative for anti-HCV 6. Thus, the carcinogenic role of persistent HCV infection appears to be significant. However, the molecular mechanism of HCV-related hepatocarcinogenesis is not completely understood, particularly in its early stages. Alpha-fetoprotein (AFP) is the most thoroughly characterized carcinofetal gene product and its usefulness in the surveillance and diagnosis of HCC is well established. On the other hand, AFP elevation is recognized not only in patients with HCC but also in patients with chronic viral hepatitis or cirrhosis, who have no evidence of HCC. AFP elevation was observed in over 15% of patients with chronic hepatitis C in the absence of HCC 7. In addition, several studies have indicated that AFP elevation is a significant predictor of HCC development 8–10. Recent reports reveal that the estimated HCC risk in patients with elevated AFP is over three-fold higher than that in patients with normal AFP 11, 12. These observations suggest that the molecular alterations associated with the very early stages of hepatocarcinogenesis have occurred in the livers of patients with chronic hepatitis C with AFP elevation. In this study, we attempted to identify a specific gene expression signature by performing microarray analysis on the livers of patients with chronic hepatitis C and AFP elevation, which is considered high risk for development of HCC.

Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection.Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method.Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P 0.001). The 5-year cumulative incidences of HCC were 22.8% and 2.2% in patients with high and low AKR1B10 expression, respectively (P 0.001). In subgroup analyses, the effects of high AKR1B10 expression on HCC development risk were significant over strata. In particular, HRs attributed to high AKR1B10 expression were significant in the subgroups that had been considered at a lower risk of HCC, such as in patients with younger age and mild hepatic fibrosis or those who achieved sustained virological response after interferon therapy.Various degrees of AKR1B10 upregulation in the liver were observed in patients with chronic HCV infection, and high AKR1B10 expression could be a novel predictor of HCC.

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.

We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA+-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA+-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA+-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA+-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA+-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA+-M2BP level is a useful predictor for HCC development after achieving SVR.

The purpose of this study was to evaluate the usefulness of liver stiffness measurement (LSM) for assessing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN) therapy.One hundred fifty-one CHC patients who underwent LSM and received IFN therapy were included in the estimation cohort, and 56 were included in the validation study. The cumulative HCC incidences were evaluated using Kaplan-Meier plot analysis and the log-rank test. Multivariate Cox proportional hazard analyses were used to estimate the hazard ratios (HRs) of variables for HCC.In the estimation cohort, 9 of 151 patients developed HCC during the median follow-up time of 722 days. Multivariate analysis identified three independent risk factors for HCC: LSM (≥ 14.0 kPa, HR 5.58, P = 0.020), platelet count ( 14.1 × 10(4) /μL, HR 5.59, P = 0.034), and non-sustained virological response (HR 8.28, P = 0.049). The cumulative incidence of HCC development at 3 years was 59.6%, 8.2%, and 0.0% in patients with all three risk factors, one to two risk factors, and none of these risk factors, respectively. The incidence of HCC was significantly different between these groups (P 0.001). In the validation cohort, HCC incidence was also significantly different with respect to these risk factors (P = 0.037).LSM, platelet count, and IFN-therapeutic effect could be used to successfully stratify the risk of HCC in patients receiving IFN therapy and demonstrate the usefulness of LSM before IFN therapy for the management of CHC patients.

The serum hepatitis C virus (HCV) load is persistently stable in patients with untreated chronic hepatitis C, but its differences between individuals vary widely (above 4 logU/mL). Because serum viral load is an important factor for predicting clinical outcome of interferon-based antiviral therapy, this study was performed to clarify the factors associated with serum viral load in chronic hepatitis C patients. We retrospectively analyzed data from 669 chronic hepatitis C patients with HCV genotype 1 or 2 infection. Stepwise regression analysis was used to estimate the relationship between demographic, viral, or biochemical variables and serum viral load. In univariate analysis, serum lipid profiles, such as total cholesterol, low-density lipoprotein (LDL) and triglyceride levels, and hemoglobin A1c (HbA1c) were correlated with the serum HCV viral load. In multivariate analysis, HCV genotype 1 infection and higher total cholesterol levels were associated with higher viral load. After stratification by HCV genotype, the serum viral load was associated with triglyceride and HbA1c in genotype 1 and with platelet counts and LDL in genotype 2. Histological data (413 patients) showed correlation between severe liver fibrosis and decreased serum viral load in patients with HCV genotype 2 but not genotype 1 infection. These results suggest that viral kinetics is affected by different host factors for genotypes 1 and 2.

Polymerization of 2-oxazolines was carried out using bifunctional and tetrafunctional initiators. Allyl-type dihalides and xylylene dihalides were used as bifunctional initiators. The allyl-type dihalides employed are 1,4-dibromo-2-butene and 3-iodo-2-(iodomethyl)-1-propene and the xylylene dihalides are p-xylylene diiodies and p-, m-, and o-xylylene dibromides. The degree of polymerization (DP) of the resulting polymer was very close to the feed ratio of the monomer to initiator. From a kinetic study, it was found that the polymerization using these bifunctional initiator for 2-oxazoline in a fast initiation-slow propagation system

Propagylic halide type compounds such as propagyl bromide, 1,4-dibromo-2-butyne, and 1,6-dibromo-2,4-hexadiyne, were used for the polymerization of 2-oxazolines. The polymerization initiated by the...

Preparation des ionenes par polymerisation cationique de la 2-methyl-2-oxazoline puis polyaddition avec une diamine (TMEDA, DABCO, bipyridine) de la poly(N-acetylethyleneimine) vivante obtenue. Etude du comportement viscosimetrique de ces polymeres en solution aqueuse

To elucidate the effect of saliva stimulation by nizatidine on oral symptoms of primary biliary cirrhosis (PBC) by administering it to PBC cases.From among 73 cases that had been definitively diagnosed as PBC at our hospital by February 2010, we selected 27 cases of PBC, 4 males and 23 females, as subjects. We obtained subjects' consent after giving them a full explanation of the administration of nizatidine. Nizatidine 150 mg was administered internally twice daily, after morning and evening meals. To observe changes in the quantity of saliva secreted, chewing gum tests were carried out four times: before the initial dose, and after 6 mo, 12 mo and 24 mo of administration. For subjective dry mouth symptoms, a visual analog scale (VAS) method was used to assess their feelings of oral dryness and eating difficulty, five times: before the initial dose, and after 1, 6, 12 and 24 mo of administration in 8 cases. The nutritional condition and the hepatic functional reserve were compared between before and after the nizatidine treatment.The result of a chewing gum test on the subjects before the administration of nizatidine showed that 50% produced less than 10 mL of saliva, i.e., the standard under which cases are considered to have hyposalivation. The results of these tests showed that the quantity of saliva secreted was 10.5 ± 6.8 mL before administration of nizatidine, 10.9 ± 6.0 mL after 6 mo, 10.6 ± 4.9 mL after 12 mo, and 11.8 ± 6.8 mL after 24 mo administration. Thus, there was a slowly increasing trend in the quantity of saliva in the whole group. The percentage of subjects with saliva production above 10 mL was 45.8% after 6 mo administration of nizatidine, that is, only a slight change from before its administration, but it was 64.3% after 12 mo, that is, a significant increase. The saliva secretion by subject patients was examined before the beginning of administration of nizatidine, 12 mo later, and 24 mo later, and Fisher's combined probability test was used to examine the results for increases in saliva secretion. The analysis yielded P values of 0.51 and 0.53 for 12 mo later and 24 mo later, respectively. Thus, although there was no statistically significant increase, it was confirmed that saliva secretion tended to increase. A VAS method was employed to study the intensities of subjective symptoms of oral dryness and eating difficulty. Almost every case indicated some improvement of subjective oral dryness on the VAS early in the administration, i.e., one month after. We also studied the effects of the administration of nizatidine on nutritional condition, hepatic functional reserve, and long-term prognosis of PBC. No significant improvements in cholinesterase (ChE) level, albumin (Alb) level, or Child-Pugh score were found during the period of observation from the beginning to the end of administration of nizatidine, nor in comparison with the non-administration group. A comparative analysis between before administration and 24 mo later yielded P values of 0.41 for Alb, 0.56 for ChE, and 0.59 for the Child-Pugh scores.It was confirmed that administering nizatidine to cases of PBC with dry mouth increased the secretion of saliva and improved the symptoms.

Les composes CH 2 X−CH=CH−CH 2 X (X=Cl, Br) et CH 2 =C(CH 2 X) CH 2 X (X=I, Cl) sont des amorceurs d'initiation rapide et de propagation lente de la polymerisation cationique d'alkyl-2 oxazolines-2