Silver Diamine Fluoride in Children Using Physiologically Based PK Modeling.

Silver diamine fluoride (SDF) is used topically to prevent or arrest dental caries and has been tested clinically in toddlers to elderly adults. Following SDF application, small quantities of silver can be swallowed and absorbed. To monitor silver concentrations, pharmacokinetic studies can be performed. However, pharmacokinetic studies are time-consuming, resource intensive, and challenging to perform in young children. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict silver disposition in children. The PBPK model for silver was developed using Simcyp software (version 17.0) based on information obtained from literature sources. The predictive performance of the model was assessed by comparing the predicted PK profiles and parameters with the observed data from published rat and human data following intravenous or oral silver administration. The predicted silver concentrations were within 2-fold of observed blood and tissue silver concentrations in rats and within the 95% confidence interval of observed plasma silver concentrations in healthy human adults. The PBPK model was applied to the pediatric population by accounting for developmental physiological changes. For a given SDF dose, the simulated peak silver concentrations were 5.2-, 4.3-, 2.7-, and 1.3-fold higher in children aged 1 to 2, 2 to 4, 5 to 10, and 12 to 17 y, respectively, compared to adults. As silver is reportedly excreted in the bile, the half-life of silver was comparable in all ages and plasma and tissue silver concentrations were predicted to return to baseline levels within 2 wk after SDF application. The simulation in children suggests that conventional SDF application to teeth to prevent or arrest dental caries results in plasma and tissue silver concentrations lower than toxic concentrations. PBPK modeling offers a novel approach to studying dental exposures in younger children, where pharmacokinetic studies would be difficult to conduct.

Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third deadliest cancer in the world with high morbidity and poor prognosis. CTCFL (CCCTC-binding factor like) is a member of the cancer testis antigen (CTA) family with oncogenic properties. To demonstrate whether the hypomethylation of CTCFL promoters in plasma could be used as a noninvasive biomarker to predict poor prognosis of HCC, we extracted cell-free DNA from the plasma and detected the methylation status of CTCFL in 43 HCC, 5 liver cirrhosis and 6 benign lesion samples using methylation specific PCR (MSP). Our study indicated that the hypomethylation of CTCFL promoters in HCC plasma samples (60.4%) was significantly different from that in benign lesion plasma samples (16.7%) with a p-value of 0.043. Analysis of clinicopathological data showed that the methylation status of CTCFL promoters was significantly correlated with microvascular involvement (MVI) (p=0.001) and postoperative recurrence (p=0.031). Furthermore, clinical prognosis data of 347 HCC patients from The Cancer Genome Atlas (TCGA) database displayed that the hypomethylated group had worse overall survival than the hypermethylated group (p=0.0056). In conclusion, we provide evidence that the hypomethylation of CTCFL promoters in cell-free DNA is a biomarker for monitoring HCC patients, which can be used as a noninvasive prediction index for tumor recurrence and provide the individualized decision-making for clinicians.

Photoinduced antibacterial activity of NRC03 peptide-conjugated dopamine/nano-reduced graphene oxide against Staphylococcus aureus.

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.

SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma.

This corrects the article DOI: 10.1038/onc.2014.445.

Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential.

The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy-N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA.

The prognostic value of combination of CD90 and OCT4 for hepatocellular carcinoma after curative resection.

CD90 has been identified as a candidate marker of cancer stem cells (CSCs) for HCC, whereas it also has been considered as a marker for tumor-associated fibroblasts (CAFs). OCT4, as a key transcription factor required to maintain pluripotency of human embryonic stem cell and cancer cells, has been characterized to be involved in malignant transformation and tumorigenesis of various cancers. This study aimed to examine expression patterns of CD90 in HCC and investigate whether combination of both CD90 and OCT4 could provide a more powerful predictor for prognosis of HCC than either one alone.CD90 and OCT4 were examined by immunohistochemistry. The relationship between CD90/OCT4 expression and clinicopathologic characteristics was analyzed. The correlation between CD90/OCT4 expression and overall survival and disease-free survival was determined with Kaplan-Meier analysis.CD90 was found mainly expressed in tumor-associated CAFs and OCT4 was mainly expressed in tumor cells. The expression of CD90 and OCT4 in HCC was significantly higher than in adjacent non-tumor and normal liver tissues. CD90 expression was correlated with pathological grade, satellite lesion, PVTT and recurrence. OCT4 expression was correlated with pathological grade, tumor size and recurrence. Data demonstrated no correlation between CD90 and OCT4. High expression of CD90 or OCT4 predicts a poor prognosis. Furthermore, combination of both CD90 and OCT4 provides a more sensitive predictor for prognosis of HCC than either marker alone.CD90 and OCT4 are both independent and reliable biomarker for predicting prognosis of HCC patients after hepatic resection. Our results indicated the accuracy of prediction can be enhanced by their combination.

SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma.

Epithelial-to-mesenchymal transition (EMT) is well known to involve in tumor invasion and metastasis. Src homology region 2 domain-containing phosphatase 1 (SHP-1) functions as a potent tumor suppressor and also acts as a negative regulator of p-STAT3(Tyr705) oncogenic signaling. However, little is known about the molecular mechanism(s) through which SHP-1 regulates EMT during hepatocellular carcinoma (HCC) progression. Here we first reported that endogenous SHP-1 protein levels were significantly downregulated in cells with mesenchymal characteristics and negatively correlated with p-STAT3(Tyr705) and vimentin but positively correlated with E-cadherin. SHP-1 overexpression abolished transforming growth factor-ß1 (TGF-ß1)-induced p-STAT3(Tyr705) and EMT, as well inhibited migration and invasion but further rescued by signal transducer and activator of transcription factor 3 (STAT3) overexpression. Depletion of SHP-1 could induce a more increase in TGF-ß1-induced p-STAT3(Tyr-705) and EMT characteristics, further supporting the mechanism that suppression of TGF-ß1-induced EMT is dependent on SHP-1-mediated STAT3 inactivation. Constitutively overexpressed SHP-1 tyrosine phosphatase activity by D61A-mutated SHP-1 markedly reduced TGF-ß1-induced p-STAT3(Tyr705) and EMT features but was not altered by C453S catalytic-dead mutant SHP-1. Consequently, SHP-1 acted as a powerful suppressor in preventing EMT by exerting its tyrosine phosphatase activity that directly downregulated p-STAT3(Tyr705). Most notably, we discovered a novel SHP-1 agonist SC-43 better than sorafenib to exert more potent anti-EMT effects in vitro as well as anti-metastatic growth in vivo. In conclusion, SHP-1 is a potent suppressor of HCC EMT and metastasis, thus highlighting that SC-43-SHP-1 axis may serve as a potential therapeutic target that antagonized p-STAT3(Tyr705) and thereby prevented HCC EMT and metastasis.

Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A.

Protein phosphatase 2A (PP2A) is a tumor suppressor, which is functionally defective in various cancers. Previously, we found that PP2A activity determined the anticancer effect of bortezomib and erlotinib in hepatocellular carcinoma (HCC) cells. Here, we tested a novel erlotinib derivative, TD52, in four HCC cell lines, PLC5, Huh-7, Hep3B and Sk-Hep1. Using MTT and flow cytometry, we showed that TD52 had more potent apoptotic effects than erlotinib in HCC cells. TD52-induced apoptosis was associated with dose- and time- dependent reactivation of PP2A and downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt. Inhibition of PP2A or ectopic expression of CIP2A or Akt in PLC5 cells abolished the effects of TD52. Furthermore, we demonstrated that TD52 affected the binding of Elk-1 to the proximal promoter of the CIP2A gene, thus downregulating transcription of CIP2A. Importantly, TD52-induced tumor inhibition was associated with reactivation of PP2A and downregulation of CIP2A and p-Akt in vivo. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A determines the apoptotic effect induced by TD52. Our findings disclose the therapeutic mechanism of this novel targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

Evaluation of the effects of nanoscale zero-valent iron (nZVI) dispersants on intrinsic biodegradation of trichloroethylene (TCE).

In this study, the biodegradability of nanoscale zero-valent iron (nZVI) dispersants and their effects on the intrinsic biodegradation of trichloroethylene (TCE) were evaluated. Results of a microcosm study show that the biodegradability of three dispersants followed the sequence of: polyvinyl alcohol-co-vinyl acetate-co-itaconic acid (PV3A) > polyoxyethylene (20) sorbitan monolaurate (Tween 20) > polyacrylic acid (PAA) under aerobic conditions, and PV3A > Tween 20 > PAA under anaerobic conditions. Natural biodegradation of TCE was observed under both aerobic and anaerobic conditions. No significant effects were observed on the intrinsic biodegradation of TCE under aerobic conditions with the presence of the dispersants. The addition of PAA seemed to have a slightly adverse impact on anaerobic TCE biodegradation. Higher accumulation of the byproducts of anaerobic TCE biodegradation was detected with the addition of PV3A and Tween 20. The diversity of the microbial community was enhanced under aerobic conditions with the presence of more biodegradable PV3A and Tween 20. The results of this study indicate that it is necessary to select an appropriate dispersant for nZVI to prevent a residual of the dispersant in the subsurface. Additionally, the effects of the dispersant on TCE biodegradation and the accumulation of TCE biodegrading byproducts should also be considered.

Hindering factors and suggestions related to organ donation decisions: perspective of the Taiwan Ali-Shan Tsou aboriginal tribe.

BACKGROUNDS AND AIMS: Ali-San Tsou (AST) is one of leading aboriginal tribes in Taiwan with traditional godly beliefs related to life and death. Lacking related knowledge, health professionals (HPs) often failed to help them reach good dying or organ donation (OD). This study aimed to explore hindering factors and suggestions related to OD for good dying from Taiwan AST's own perspective. METHODS: An explorative qualitative design was employed using a purposive sample of the AST tribes from Taiwan. Data were collected with AST residents by face-to-face interviews and analyzed by content analysis. RESULTS: Thirty AST residents (16 females and 14 males) with ages ranging from 28 to 78 (mean, 54.5) years completed interviews. Of them, 85% reported various diseases. In this study 73% were Catholics and Christians, 17% held traditional godly believes, and 10% had no religious affiliation. Eight hindering factors were reported: (1) limited information about organs and OD; (2) no qualified organs for donation; (3) worry about lack of forgiveness by ancestors; (4) tribe elders who might not accept concept of OD; (5) intact bodies were required at home during spirit-companion rituals; (6) earth burial with intact bodies was preferred; (7) bodies due to accidental and bad death were impermissible for OD; and (8) worry about possession by the donor's spirit. Seven suggestions were also reported for HPs to enhance AST's OD decisions: (1) starting with friendship and a caring relationship; (2) providing spiritual support from reverent religions; (3) stressing good deeds and honoring tribe folks by OD; (4) avoiding accidental/bad death; (5) providing relevant modern medical knowledge of human organs and OD; (6) introducing OD as part of a good-dying care plan; and (7) demonstrating a respectful discussion mindset about OD. CONCLUSIONS: Eight hindering factors and 7 types of suggestions for enhancing AST aboriginal people's OD decisions were first explored in this project. In the future, HPs are encouraged to invite AST to share the concepts of OT and try to clarify the related concerns with respect for their cultural contexts. With mutual respect, the efforts of sharing and integrating OD into good-dying care would be more possible.

Development of KMnO(4)-releasing composites for in situ chemical oxidation of TCE-contaminated groundwater.

The objective of this study was to develop a controlled-oxidant-release technology combining in situ chemical oxidation (ISCO) and permeable reactive barrier (PRB) concepts to remediate trichloroethene (TCE)-contaminated groundwater. In this study, a potassium permanganate (KMnO4)-releasing composite (PRC) was designed for KMnO4 release. The components of this PRC included polycaprolactone (PCL), KMnO4, and starch with a weight ratio of 1.14:2:0.96. Approximately 64% (w/w) of the KMnO4 was released from the PRC after 76 days of operation in a batch system. The results indicate that the released KMnO4 could oxidize TCE effectively. The results from a column study show that the KMnO4 released from 200 g of PRC could effectively remediate 101 pore volumes (PV) of TCE-contaminated groundwater (initial TCE concentration = 0.5 mg/L) and achieve up to 95% TCE removal. The effectiveness of the PRC system was verified by the following characteristics of the effluents collected after the PRC columns (barrier): (1) decreased TCE concentrations, (2) increased ORP and pH values, and (3) increased MnO2 and KMnO4 concentrations. The results of environmental scanning electron microscope (ESEM) analysis show that the PCL and starch completely filled up the pore spaces of the PRC, creating a composite with low porosity. Secondary micro-scale capillary permeability causes the KMnO4 release, mainly through a reaction-diffusion mechanism. The PRC developed could be used as an ISCO-based passive barrier system for plume control, and it has the potential to become a cost-effective alternative for the remediation of chlorinated solvent-contaminated groundwater.

Application of polycolloid-releasing substrate to remediate trichloroethylene-contaminated groundwater: a pilot-scale study.

The objectives of this pilot-scale study were to (1) evaluate the effectiveness of bioremediation of trichloroethylene (TCE)-contaminated groundwater with the supplement of slow polycolloid-releasing substrate (SPRS) (contained vegetable oil, cane molasses, surfactants) under reductive dechlorinating conditions, (2) apply gene analyses to confirm the existence of TCE-dechlorinating genes, and (3) apply the real-time polymerase chain reaction (PCR) to evaluate the variations in TCE-dechlorinating bacteria (Dehalococcoides spp.). Approximately 350L of SPRS solution was supplied into an injection well (IW) and groundwater samples were collected and analyzed from IW and monitor wells periodically. Results show that the SPRS caused a rapid increase of the total organic carbon concentration (up to 5794mg/L), and reductive dechlorination of TCE was significantly enhanced. TCE dechlorination byproducts were observed and up to 99% of TCE removal (initial TCE concentration=1872µg/L) was observed after 50 days of operation. The population of Dehalococcoides spp. increased from 4.6×10(1) to 3.41×10(7)cells/L after 20 days of operation. DNA sequencing results show that there were 31 bacterial species verified, which might be related to TCE biodegradation. Results demonstrate that the microbial analysis and real-time PCR are useful tools to evaluate the effectiveness of TCE reductive dechlorination.

Mcl-1-dependent activation of Beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells.

We investigated the molecular mechanisms underlying the effect of sorafenib and SC-59, a novel sorafenib derivative, on hepatocellular carcinoma (HCC). Sorafenib activated autophagy in a dose- and time-dependent manner in the HCC cell lines PLC5, Sk-Hep1, HepG2 and Hep3B. Sorafenib downregulated phospho-STAT3 (P-STAT3) and subsequently reduced the expression of myeloid cell leukemia-1 (Mcl-1). Inhibition of Mcl-1 by sorafenib resulted in disruption of the Beclin 1-Mcl-1 complex; however, sorafenib did not affect the amount of Beclin 1, suggesting that sorafenib treatment released Beclin 1 from binding with Mcl-1. Silencing of SHP-1 by small interference RNA (siRNA) reduced the effect of sorafenib on P-STAT3 and autophagy. Ectopic expression of Mcl-1 abolished the effect of sorafenib on autophagy. Knockdown of Beclin 1 by siRNA protected the cells from sorafenib-induced autophagy. Moreover, SC-59, a sorafenib derivative, had a more potent effect on cancer cell viability than sorafenib. SC-59 downregulated P-STAT3 and induced autophagy in all tested HCC cell lines. Furthermore, our in vivo data showed that both sorafenib and SC-59 inhibited tumor growth, downregulated P-STAT3, enhanced the activity of SHP-1 and induced autophagy in PLC5 tumors, suggesting that sorafenib and SC-59 activate autophagy in HCC. In conclusion, sorafenib and SC-59 induce autophagy in HCC through a SHP-1-STAT3-Mcl-1-Beclin 1 pathway.

Evidence for direct CP violation in B±â†’ηh± and observation of B0→ηK0.

We report measurements of the branching fractions and CP asymmetries for B(±)→ηh(±) (h=K or π) and the observation of the decay B(0)→ηK(0) from the final data sample of 772×10(6) B ̅B pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The measured branching fractions are B(B(±)→ηK(±))=(2.12±0.23±0.11)×10(-6), B(B(±)→ηπ(±))=(4.07±0.26±0.21)×10(-6), and B(B(0)→ηK(0))=(1.27(-0.29)(+0.33)±0.08)×10(-6), where the last decay is observed for the first time with a significance of 5.4 standard deviations (σ). We also find evidence for CP violation in the charged B modes, A(CP)(B(±)→ηK(±))=-0.38±0.11±0.01 and A(CP)(B(±)→ηπ(±))=-0.19±0.06±0.01 with significances of 3.8 σ and 3.0 σ, respectively. For all measurements, the first and second uncertainties are statistical and systematic, respectively.

In situ oxidation of petroleum-hydrocarbon contaminated groundwater using passive ISCO system.

Groundwater contamination by gasoline spill is a worldwide environmental problem. Gasoline contains methyl tertiary-butyl ether (MTBE) (a fuel oxygenates) and benzene, which are the chemicals of concerns among the gasoline components. In this study, an in situ chemical oxidation (ISCO) barrier system was developed to evaluate the feasibility of applying this passive system on the control of MTBE and benzene plume in aquifer. The developed ISCO barrier contained oxidant-releasing materials, which could release oxidants (e.g., persulfate) when contact with water for the contaminants' oxidation in groundwater. In this study, laboratory-scale fill-and-draw experiments were conducted to determine the component ratios of the oxidant-releasing materials and evaluate the persulfate release rates. Results indicate that the average persulfate-releasing rate of 7.26 mg S(2)O(8)(2-)/d/g was obtained when the mass ratio of sodium persulfate/cement/sand/water was 1/1.4/0.24/0.7. The column study was conducted to evaluate the efficiency of in situ application of the developed ISCO barrier system on MTBE and benzene oxidation. Results from the column study indicate that approximately 86-92% of MTBE and 95-99% of benzene could be removed during the early persulfate-releasing stage (before 48 pore volumes of groundwater pumping). The removal efficiencies for MTBE and benzene dropped to approximately 40-56% and 85-93%, respectively, during the latter part of the releasing period due to the decreased persulfate-releasing rate. Results reveal that acetone, byproduct of MTBE, was observed and then further oxidized completely. Results suggest that the addition of ferrous ion would activate the persulfate oxidation. However, excess ferrous ion would compete with organic contaminants for persulfate, and thus, cause the decrease in contaminant oxidation rates. The proposed treatment scheme would be expected to provide a more cost-effective alternative to remediate MTBE, benzene, and other petroleum-hydrocarbon contaminated aquifers. Results from this study will be useful in designing a scale-up system for field application.

US national estimation of emergency department utilization by patients given 'HIV/AIDS-related illness' as their primary diagnosis.

BACKGROUND: The emergency department (ED) is one of the most frequent sources of medical care for many HIV-infected individuals. However, the characteristics and ED utilization patterns of patients with HIV/AIDS-related illness as the primary ED diagnosis (HRIPD) are unknown. METHODS: We identified the ED utilization patterns of HRIPD visits from a weighted sample of US ED visits (1993-2005) using the National Hospital Ambulatory Medical Care Survey, a nationally representative survey. Data on visits by patients≥18 years old were analysed using procedures for multiple-stage survey data. We compared the utilization patterns of HRIPD vs. non-HRIPD visits, and patterns across three periods (1993-1996, 1997-2000 and 2001-2005) to take into account changes in HIV epidemiology. RESULTS: Overall, 492 000 HRIPD visits were estimated to have occurred from 1993 to 2005, corresponding to 5-in-10 000 ED visits. HRIPD visits experienced longer durations of stay (5.2 h vs. 3.4 h; P=0.001), received more diagnostic tests (5.1 vs. 3.3; P<0.001), were prescribed more medications (2.5 vs. 1.8; P<0.001) and were more frequently seen by physicians (99.5%vs. 93.8%; P<0.001) compared with non-HRIPD visits. HRIPD visits were more likely to result in admission [adjusted odds ratio (OR) 7.67; 95% confidence interval (CI) 5.14-11.44]. The proportion of HRIPD visits that required emergent/urgent care or were seen by attending physicians, and the number of diagnostic tests ordered, significantly increased over time (P<0.05), while the wait time (P=0.003) significantly decreased between the second and third study periods (P<0.05). CONCLUSIONS: Although HRIPD visits were infrequent relative to all ED visits, HRIPD visits utilized significantly more resources than non-HRIPD visits and the utilization also increased over time.

Application of persulfate-releasing barrier to remediate MTBE and benzene contaminated groundwater.

The objective of this study was to assess the potential of using an in situ oxidation barrier system to remediate gasoline-contaminated groundwater. The passive remedial system included a persulfate-releasing barrier containing persulfate-releasing materials to release persulfate for contaminant oxidation. Bench experiments were performed to determine the components and persulfate-releasing rate of the persulfate-releasing materials. Column experiments were conducted to evaluate the effectiveness of the designed persulfate-releasing materials on the control of petroleum-hydrocarbon plume. In this study, methyl tert-butyl ether (MTBE) and benzene were used as the target compounds. The optimal persulfate releasing rate was obtained when the mass ratio of persulfate/cement/sand/water was 1/1/0.16/0.5, and the rate varied from 31 to 8 mg persulfate per day per g of material. Significant amounts of MTBE and benzene were removed through the oxidation process due to the release of persulfate, and the produced tert-butyl formate (TBF) and tert-butyl alcohol (TBA), byproducts of MTBE, were further oxidized in the system. Results suggest that the oxidation rate would be affected by the oxidant reduction potential and concentrations of ferrous iron and persulfate.

Observation of B(s)(0) → D(s)(*-) π+ and B(s)(0) → D(s)(*-) ρ+ and measurement of the B(s)(0) → D(s)(*-) ρ+ longitudinal polarization fraction.

First observations of the B(s)(0) → D(s)(*-) π+, B(s)(0) → D(s)(-) ρ+ and B(s)(0) → D(s)(*-) ρ+ decays are reported together with measurements of their branching fractions: B(B(s)(0) → D(s)(*-) π+) = [2.4(-0.4)(+0.5)(stat) ± 0.3(syst) ± 0.4(f(s))]×10(-3), B(B(s)(0) → D(s)(-) ρ+) = [8.5(-1.2)(+1.3)(stat) ± 1.1(syst) ± 1.3(f(s))]×10(-3) and B(B(s)(0) → D(s)(*-) ρ+) = [11.9(-2.0)(+2.2)(stat) ± 1.7(syst) ± 1.8(f(s))]×10(-3) (f(s) = N(B(s)(*) B(s)(*))/N(bb)). From helicity-angle distributions, we measured the longitudinal polarization fraction in B(s)(0) → D(s)(*-) ρ+ decays to be f(L)(B(s)(0) → D(s)(*-) ρ+) = 1.05(-0.10)(+0.08)(stat)(-0.04)(+0.03)(syst). These results are based on a 23.6 fb(-1) data sample collected at the Υ(5S) resonance with the Belle detector at the KEKB e+ e- collider.

CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells.

Previously, we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. In this study, we report that cancerous inhibitor of protein phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediates the apoptotic effect of bortezomib in HCC. Silencing PP2A by small interference RNA (siRNA) abolishes bortezomib-induced down-regulation of phospho-Akt and apoptosis. Bortezomib increases PP2A activity in sensitive HCC cells, including Sk-Hep1, Hep3B and Huh-7, but not in resistant PLC5 cells. Bortezomib down-regulates CIP2A in a dose- and time-dependent manner in all sensitive HCC cells, whereas no alterations in CIP2A were found in resistant PLC5 cells. Knockdown of CIP2A by siRNA restored bortezomib's effects on apoptosis and PP2A activity in PLC5 cells. Moreover, over-expression of CIP2A up-regulated phospho-Akt and protected Sk-Hep1 cells from bortezomib-induced apoptosis. It is significant that, ectopic expression of CIP2A decreased Akt-related PP2A activity, whereas silencing CIP2A increased this activity, indicating that CIP2A negatively regulates Akt-related PP2A activity in HCC cells, furthermore, our in vivo data showed that bortezomib down-regulates CIP2A and up-regulates PP2A activity in Huh-7 tumors, but not in PLC5 tumors. In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.

Interleukin-10 -819 promoter polymorphism associated with gastric cancer among Asians.

Studies investigating the association between interleukin-10 -819 promoter polymorphism and gastric cancer risk report conflicting results. This study aimed to summarize quantitatively the evidence for such a relationship. Two investigators independently searched the Medline (January 1966-January 2009) and Embase (January 1980-January 2009) databases for eligible studies to be included in a meta-analysis. Six case-control studies, which included 681 gastric cancer cases and 1621 control subjects were selected. Combined results for all studies showed that there was no significant difference in genotype distribution (TT, TC or CC) between gastric cancer patients and control subjects. When stratifying for race, results were similar except that Asian patients with gastric cancer had a significantly lower frequency of TT and a higher frequency of TC than Asian control subjects. When stratifying by location and Lauren's classification of gastric cancer, there was no significant difference in genotype distribution between patients with gastric cancer and control subjects. This meta-analysis suggests that the interleukin-10 -819 promoter polymorphism may be associated with gastric cancer in Asians.