The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines

<p>Abstract</p> <p>Background</p> <p>The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines.</p> <p>Methods</p> <p>In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods.</p> <p>Results</p> <p>After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines.</p> <p>Conclusion</p> <p>In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.</p

Grading system for periodontitis by analyzing levels of periodontal pathogens in saliva

Periodontitis is an infectious disease that is associated with microorganisms that colonize the tooth surface. Clinically, periodontal condition stability reflects dynamic equilibrium between bacterial challenge and host response. Therefore, periodontal pathogen assessment can assist in the early detection of periodontitis. Here we developed a grading system called the periodontal pathogen index (PPI) by analyzing the copy numbers of multiple pathogens both in healthy and chronic periodontitis patients. We collected 170 mouthwash samples (64 periodontally healthy controls and 106 chronic periodontitis patients) and analyzed the salivary 16S rRNA levels of nine pathogens using multiplex, quantitative real-time polymerase chain reaction. Except for Aggregatibacter actinomycetemcomitans, copy numbers of all pathogens were significantly higher in chronic periodontitis patients. We classified the samples based on optimal cut-off values with maximum sensitivity and specificity from receiver operating characteristic curve analyses (AUC = 0.91, 95% CI: 0.87-0.96) into four categories of PPI: Healthy (1-40), Moderate (41-60), At Risk (61-80), and Severe (81-100). PPI scores were significantly higher in all chronic periodontitis patients than in the controls (odds ratio: 31.7, 95% CI: 13.41-61.61) and were associated with age, scaling as well as clinical characteristics including clinical attachment level and plaque index. Our PPI grading system can be clinically useful for the early assessment of pathogenic bacterial burden and follow-up monitoring after periodontitis treatment

Transparent, low resistance, and flexible amorphous ZnO-doped In2O3 Anode Grown on a PES Substrate

Transparent and low resistance amorphous ZnO-doped In2O3 (IZO) anode films were grown by radio-frequency (rf) sputtering on an organic passivated polyethersulfone (PES) substrate for use in flexible organic light-emitting diodes (OLEDs). Under optimized growth conditions, a sheet resistance of 15.2 /, average transmittance above 89% in the green range, and a root mean square roughness of 0.375 nm were obtained, even for the IZO anode film grown in a pure Ar ambient without the addition of oxygen as a reactive gas. All of the IZO anode films had an amorphous structure regardless of the rf power and the working pressure due to the low substrate temperature of 50°C and the structural stability of the amorphous IZO films. In addition, an X-ray photoelectron spectroscopy depth profile obtained for the IZO/PES showed no obvious evidence of interfacial reactions between the IZO anode and the PES substrate, except for some indiffusion of oxygen atoms from the IZO anode. Furthermore, the current-voltage-luminance of the flexible OLEDs fabricated on IZO anode was found to be critically dependent on the sheet resistance of the IZO anode.This work was supported by a Korea Research Foundation grant funded by the Korean Government (MOEHRD: Basic Research Promotion Fund)(KRF-2006-003-D00243) and the Ministry of Commerce, Industry and Energy

Enhancement of hole injection using ozone treated Ag nanodots dispersed on indium tin oxide anode for organic light emitting diodes

The authors report the enhancement of hole injection using an indium tin oxide (ITO) anode covered with ultraviolet (UV) ozone-treated Ag nanodots for fac tris (2-phenylpyridine) iridium Ir(ppy)3-doped phosphorescent organic light-emitting diodes (OLEDs). X-ray photoelectron spectroscopy and UV-visible spectrometer analysis exhibit that UV-ozone treatment of the Ag nanodots dispersed on the ITO anode leads to formation of Ag2O nanodots with high work function and high transparency. Phosphorescent OLEDs fabricated on the Ag2O nanodot-dispersed ITO anode showed a lower turn-on voltage and higher luminescence than those of OLEDs prepared with a commercial ITO anode. It was thought that, as Ag nanodots changed to Ag2O nanodots by UV-ozone treatment, the decrease of the energy barrier height led to the enhancement of hole injection in the phosphorescent OLEDs.This work was supported by Korea Research Foundation grant funded by Korean Government (MOEHRD: Basic Research Promotion Fund)(KRF-2006-003-D00243) and Ministry of Commerce, Industry, and Energy

Transparent Conducting Indium Zinc Tin Oxide Anode for Highly Efficient Phosphorescent Organic Light Emitting Diodes

The preparation and characteristics of a transparent conducting indium zinc tin oxide (IZTO) anode for highly efficient phosphorescent organic light emitting diodes (OLEDs) is described. The resistivity and transmittance of the IZTO anode are comparable to reference In2O3 (ITO) anode films even though it was prepared at room temperature. In addition, the work function of the ozone-treated amorphous IZTO anode (5.12±0.02 eV) is much higher than that of ozone-treated reference ITO anodes (4.94±0.02 eV). The current-voltage-luminance characteristics and efficiencies of OLEDs prepared on the IZTO anode are critically dependent on the sheet resistance of the IZTO anode. Furthermore, both the quantum efficiency and power efficiency of the OLED fabricated on the amorphous IZTO anode are much higher than those of an OLED with the reference ITO anode due to the higher work function of the IZTO anode than those of conventional ITO anode. This indicates that IZTO is an alternative material for conventional ITO anodes used in OLEDs and flexible displays.This work was supported by a Korea Research Foundation Grant funded by the Korea Government MOEHRD: Basic Research Promotion Fund grant no. KRF-2006-331-D00243 and the Ministry of Commerce, Industry, and Energy

The Breakdown of Preformed Peritoneal Advanced Glycation End Products by Intraperitoneal Alagebrium

It has been demonstrated that inhibitors of advanced glycation end products (AGE), such as aminoguanidine, can suppress peritoneal AGE in rats on peritoneal dialysis (PD). However, it is unknown whether late administration of a putative cross-link breaker, alagebrium, could reverse peritoneal AGE. We therefore compared alagebrium with aminoguanidine in their ability to reverse peritoneal AGE in rats on PD. Male Sprague-Dawley rats were randomly divided into 3 groups: group I dialyzed with 4.25% glucose solution for all exchanges; group II dialyzed with 4.25% glucose solution containing aminoguanidine, and group III dialyzed with 4.25% glucose solution containing alagebrium for last 8 weeks of 12-week dialysis period. Dialysis exchanges were performed 2 times a day for 12 weeks. Immunohistochemistry was performed using a monoclonal anti-AGE antibody. One-hour PET was performed for comparison of transport characteristics. The immunolabelling of AGE in peritoneal membrane was markedly decreased in the alagebrium group. Consistent with this, the alagebrium group exhibited significantly higher D/Do glucose and lower D/P urea, suggesting low peritoneal membrane transport. But there were no significant differences between the control and the aminoguanidine group. These results suggest that the alagebrium may be the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in rats on PD

Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease

Background The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans

Clinical Significance of Crescent Formation in IgA Nephropathy – a Multicenter Validation Study

Background/Aims: Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN). Methods: We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline. Results: Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P&#x3c; 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome. Conclusion: The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC