Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 68
Filter
1.
Opt Express ; 29(14): 21502-21520, 2021 Jul 05.
Article in English | MEDLINE | ID: mdl-34265936

ABSTRACT

We present a novel method for modal decomposition of a composite beam guided by a large-mode-area fiber by means of direct far-field pattern measurements with a multi-variable optimization algorithm. For reconstructing far-field patterns, we use finite-number bases of Hermite Gaussian modes that can be converted from all the guided modes in the given fiber and exploit a stochastic parallel gradient descent (SPGD)-based multi-variable optimization algorithm equipped with the D4σ technique in order for completing the modal decomposition with compensating the centroid mismatch between the measured and reconstructed beams. We measure the beam intensity profiles at two different distances, which justifies the uniqueness of the solution obtained by the SPGD algorithm. We verify the feasibility and effectiveness of the proposed method both numerically and experimentally. We have found that the fractional error tolerance in terms of the beam intensity overlap could be maintained below 1 × 10-7 and 3.5 × 10-3 in the numerical and experimental demonstrations, respectively. As the modal decomposition is made uniquely and reliably, such a level of the error tolerance could be maintained even for a beam intensity profile measured at a farther distance.

2.
Cancer Med ; 9(20): 7781-7791, 2020 10.
Article in English | MEDLINE | ID: mdl-32857923

ABSTRACT

BACKGROUND: Regular clinic follow-up is a prerequisite for optimal antiviral therapy and surveillance of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). However, adherence to regular follow-up stays low in practice. This study investigated whether regular follow-up is associated with decreased liver cancer mortality in CHB patients. METHODS: A nationwide population-based historical cohort study was conducted using customized data from the National Health Insurance Service of Korea. The number of hospital visits every 3-month interval was counted for 2 years from the date of CHB diagnosis. Patients were classified into three follow-up groups: regular (four to eight visits), irregular (one to three visits), and no follow-up. The risk of liver cancer mortality was compared among the groups using Cox proportional hazard regression analysis. RESULTS: Of the 414 074 CHB patients, 22.9% had regular follow-up. In multivariable analysis, regular follow-up was independently associated with decreased risk of liver cancer mortality compared to no follow-up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50-0.63, P < .001). Regular follow-up was also associated with the lowest risk of all-cause mortality (HR, 0.60; 95% CI, 0.57-0.63, P < .001). Patients with regular follow-up received more curative treatment (23.1% vs 15.1%, P < .001). Patients were less motivated when they were female, >60 years, of low socioeconomic status, disabled, lived in a rural area, had a higher comorbidity rate, or did not have cirrhosis. CONCLUSIONS: Regular follow-up at least every 3-6 months is significantly associated with reduced liver cancer mortality in patients with CHB.


Subject(s)
Carcinoma, Hepatocellular/mortality , Hepatitis B, Chronic/epidemiology , Liver Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/therapy , Cause of Death , Cohort Studies , Female , Follow-Up Studies , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/therapy , Humans , Incidence , Kaplan-Meier Estimate , Liver Neoplasms/etiology , Liver Neoplasms/therapy , Male , Middle Aged , Proportional Hazards Models , Public Health Surveillance , Republic of Korea/epidemiology , Socioeconomic Factors , Young Adult
3.
J Liver Cancer ; 20(2): 148-153, 2020 Sep.
Article in English | MEDLINE | ID: mdl-37384326

ABSTRACT

Optimal treatments for patients with advanced hepatocellular carcinoma (HCC) are still limited and their prognosis remains dismal. Yet, there have been rare cases that have shed light on longer survival in these patients assisted by various treatments. This paper aims to present an extraordinary case of far advanced HCC that had been properly managed in spite of continuous recurrence. A patient visited the hospital with a ruptured large HCC with main portal vein tumor thrombosis but survived longer than 14 years owing to active and prompt interventions.

4.
Liver Int ; 38(10): 1751-1759, 2018 10.
Article in English | MEDLINE | ID: mdl-29377574

ABSTRACT

BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear. METHODS: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years. RESULTS: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women. CONCLUSIONS: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal.


Subject(s)
Alanine Transaminase/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/mortality , Adult , Age Distribution , Aged , Cohort Studies , Female , Humans , Liver/pathology , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Republic of Korea/epidemiology , Sex Distribution
5.
Nanotechnology ; 29(3): 035606, 2018 Jan 19.
Article in English | MEDLINE | ID: mdl-29176070

ABSTRACT

We have developed a facile single-step synthesis of silver nanocomposite using a conventional spray dryer. We investigated the synthetic conditions by controlling the concentrations of the chemical reactants. Further, we confirmed the effect of the molecular weight of polyvinylpyrrolidones, and revealed that the molecular weight significantly affected the properties of the resultant silver nanocomposites. The long-term stability of the silver nanocomposites was tested, and little change was observed, even after storage for three months. Most of all, the simple commercial implementation, in combination with large-scale synthesis, possesses a variety of advantages, compared to conventional complicated and costly dry-process synthesis methods. Thus, our method presents opportunities for further investigation, for both lab-scale studies and large-scale industrial applications.

7.
Small ; 13(43)2017 11.
Article in English | MEDLINE | ID: mdl-28902976

ABSTRACT

A novel room-temperature aqueous synthesis for gold nanoparticle-embedded silver cubic mesh nanostructures using AgCl templates via a template-assisted coreduction method is developed. The cubic AgCl templates are coreduced in the presence of AuCl4- and Ag+ , resulting in the reduction of AuCl4- into gold nanoparticles on the outer region of AgCl templates, followed by the reduction of AgCl and Ag+ into silver cubic mesh nanostructures. Removal of the template clearly demonstrates the delicately designed silver mesh nanostructures embedded with gold nanoparticles. The synthetic mechanism, structural properties, and surface functionalization are spectroscopically investigated. The plasmonic photocatalysis of the cubic mesh nanostructures for the degradation of organic pollutants and removal of highly toxic metal ions is investigated; the photocatalytic activity of the cubic mesh nanostructures is superior to those of conventional TiO2 catalysts and they are catalytically functional even in natural water, owing to their high surface area and excellent chemical stability. The synthetic development presented in this study can be exploited for the highly elaborate, yet, facile design of nanomaterials with outstanding properties.

8.
Clin Mol Hepatol ; 23(4): 331-339, 2017 12.
Article in English | MEDLINE | ID: mdl-28946736

ABSTRACT

BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation. RESULTS: In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P<0.0001), and week 240 (95.0% vs. 47.6%, P<0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.


Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Adolescent , Adult , Alanine Transaminase/blood , DNA, Viral/blood , Double-Blind Method , Drug Administration Schedule , Female , Guanine/therapeutic use , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Humans , Male , Middle Aged , Republic of Korea , Sustained Virologic Response , Treatment Outcome , Young Adult
9.
Biochem Biophys Res Commun ; 492(1): 128-134, 2017 10 07.
Article in English | MEDLINE | ID: mdl-28782520

ABSTRACT

Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcription regulator. Menin interacts with various proteins as a scaffold protein and is proposed to play important roles in multiple physiological and pathological processes by controlling gene expression, proliferation, and apoptosis. The mechanisms underlying menin's suppression of tumorigenesis are largely elusive. In this study, we showed that menin was essential for the regulation of canonical Wnt/ß-catenin signaling in cultured cells. The C-terminal domain of menin was able to directly interact with and promote ubiquitin-mediated degradation of ß-catenin. We further revealed that overexpression of menin down-regulated the transcriptional activity of ß-catenin and target gene expression. Moreover, menin efficiently inhibited ß-catenin protein levels, transcriptional activity, and proliferation of human renal carcinoma cells with an activated ß-catenin pathway. Taken together, our results provide novel molecular insights into the tumor suppressor activity of menin, which is partly mediated by proteasomal degradation of ß-catenin and inhibition of Wnt/ß-catenin signaling.


Subject(s)
Proteasome Endopeptidase Complex/metabolism , Proteolysis , Proto-Oncogene Proteins/metabolism , Ubiquitin/metabolism , beta Catenin/metabolism , Cells, Cultured , HEK293 Cells , Humans , Protein Binding
10.
Scand J Gastroenterol ; 52(9): 1029-1036, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28562104

ABSTRACT

OBJECTIVES: Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy. METHODS: The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3). RESULTS: The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93-75.01, p < .001), alcohol consumption (HR 3.84, 95% C.I. 1.99-7.39, p < .001), and older age (HR 1.06, 95% C.I. 1.01-1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314). CONCLUSIONS: LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Liver Cirrhosis/physiopathology , Liver Neoplasms/epidemiology , Adult , Age Factors , Alcohol Drinking/adverse effects , Ascites/etiology , Esophageal and Gastric Varices/etiology , Female , Humans , Hypertension, Portal/etiology , Incidence , Liver Cirrhosis/complications , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Republic of Korea , Retrospective Studies , Risk Assessment
11.
BMC Cancer ; 17(1): 388, 2017 05 30.
Article in English | MEDLINE | ID: mdl-28558668

ABSTRACT

BACKGROUND: Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population. METHODS: We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay. RESULTS: MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC. CONCLUSIONS: We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population.


Subject(s)
Helicobacter Infections/genetics , Interleukin-8/genetics , Mannose-Binding Lectin/genetics , Stomach Neoplasms/genetics , Adult , Aged , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/pathogenicity , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Republic of Korea , Risk Factors , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology
12.
J Back Musculoskelet Rehabil ; 30(5): 999-1004, 2017 Sep 22.
Article in English | MEDLINE | ID: mdl-28505954

ABSTRACT

BACKGROUND: Studies have shown late post-operative physical disability and residual pain in patients following lumbar disc surgery despite growing evidence of its beneficial effects. Therefore, rehabilitation is required to minimise the late post-operative complications. OBJECTIVE: To assess the feasibility of manipulative rehabilitation to improve late post-operative outcomes. METHODS: Twenty-one patients aged 25-65 years undergoing lumbar microdiscectomy were randomly assigned to the rehabilitation group (n= 14) or active control group (n= 7) by simple randomisation. Eight rehabilitation sessions were initiated 2-3 weeks after surgery. Thirty-minute sessions were conducted twice weekly for four weeks. Post-operative physical disability and pain were assessed at baseline and at the two-year follow-up. RESULTS: Post-operative physical disability improved more in patients who had undergone rehabilitation than in those who had received control care (63% vs. -23%, P< 0.05). Post-operative residual low back and leg pain were alleviated in the treatment group (26% and 57%, respectively), but intensified in the control group (-5% and -8%, respectively). CONCLUSIONS: This study demonstrated the potential of manipulative rehabilitation and importance of post-operative management after lumbar disc surgery. Definitive trials with larger sample sizes are required to confirm the feasibility and potential therapeutic effectiveness of this approach.


Subject(s)
Diskectomy/rehabilitation , Lumbar Vertebrae/surgery , Musculoskeletal Manipulations/statistics & numerical data , Adult , Female , Follow-Up Studies , Humans , Lumbosacral Region , Male , Middle Aged , Pain/surgery , Pain Measurement , Pilot Projects , Postoperative Period , Treatment Outcome
13.
Gut Liver ; 10(6): 962-968, 2016 Nov 15.
Article in English | MEDLINE | ID: mdl-27282260

ABSTRACT

BACKGROUND/AIMS: The benefit of oral antiviral therapy in preventing hepatocellular carcinoma (HCC) in the general population is not well understood. We used a novel prediction method to estimate the risk of HCC in the Korean population based on various treatment guidelines. METHODS: The 5-year risk of HCC following antiviral therapy was calculated using an HCC risk prediction model. A virtual cohort that represented Koreans (>40 years old) with chronic hepatitis B virus (HBV) infection was established using the fifth National Health and Nutrition Examination Survey. The antiviral indications tested were the Korean National Health Insurance (NHI) and European Association for the Study of the Liver (EASL) guidelines as well as a new extended indication (serum HBV DNA >2,000 IU/mL regardless of serum aminotransferase level). RESULTS: A total of 993,872 subjects were infected with HBV in the general Korean population. Over a 5-year period, 2,725 HCC cases were predicted per 100,000 persons (0.55%/yr). When the cohort was treated based on the Korean NHI, the EASL, and the newly extended indications, HCC risks decreased to 2,531 (-7.1%), 2,089 (-23.3%), and 1,122 (-58.8%) cases per 100,000 persons, respectively (p<0.0001). CONCLUSIONS: Simulated risk prediction suggests that extending of oral antiviral indication may reduce the HCC risk in the general population.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/virology , Hepatitis B, Chronic/drug therapy , Liver Neoplasms/virology , Risk Assessment/methods , Adult , DNA, Viral/blood , Female , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Humans , Male , Middle Aged , Nutrition Surveys , Predictive Value of Tests , Republic of Korea , Risk Factors , Transaminases/blood
14.
J Back Musculoskelet Rehabil ; 29(1): 23-9, 2016.
Article in English | MEDLINE | ID: mdl-25792303

ABSTRACT

BACKGROUND: Lumbar open laser microdiscectomy has been shown to be an effective intervention and safe approach for lumbar disc prolapse. However early post-operative physical disability affecting daily activities have been sporadically reported. OBJECTIVE: To evaluate the feasibility of using early individualised manipulative rehabilitation to improve early post-operative functional disability following lumbar discectomy. METHODS: Randomised controlled pilot trial. Setting at a major metropolitan spine surgery hospital. Twenty-one patients aged 25-69 years who underwent lumbar microdiscectomy were randomised to either the manipulative rehabilitation treatment group or the active control group. Rehabilitation was initiated 2-3 weeks after surgery, twice a week for 4 weeks. Each session was for 30 minutes. Primary outcomes were the Roland-Morris disability questionnaire and the visual analogue pain scale. Outcome measures were assessed at baseline and post-intervention. RESULTS: Early post-operative physical disability was improved with a 55% reduction by early individualised manipulative rehabilitation, compared to that of control care with a 5% increase. Early post-operative residual leg pain decreased with rehabilitation (55%) and control care (9%). CONCLUSION: This pilot study supports the feasibility of a future definitive randomised control trial and indicates this type of rehabilitation may be an important option for post-operative management after spinal surgery.


Subject(s)
Diskectomy , Intervertebral Disc Displacement/rehabilitation , Intervertebral Disc Displacement/surgery , Manipulation, Spinal , Postoperative Care , Adult , Aged , Female , Humans , Laser Therapy , Lumbar Vertebrae/surgery , Male , Middle Aged , Pilot Projects , Visual Analog Scale
15.
Intest Res ; 13(3): 242-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26130999

ABSTRACT

BACKGROUND/AIMS: Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-α) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-α. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans. METHODS: Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively). CONCLUSIONS: Our results suggest that the T507C SNP in PRKCDBP, a TNF-α-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

16.
BMB Rep ; 48(12): 685-90, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26058396

ABSTRACT

The eukaryotic genome is packed into chromatin, which is important for the genomic integrity and gene regulation. Chromatin structures are maintained through assembly and disassembly of nucleosomes catalyzed by histone chaperones. Asf1 (anti-silencing function 1) is a highly conserved histone chaperone that mediates histone transfer on/off DNA and promotes histone H3 lysine 56 acetylation at globular core domain of histone H3. To elucidate the role of Asf1 in the modulation of chromatin structure, we screened and identified small molecules that inhibit Asf1 and H3K56 acetylation without affecting other histone modification. These pyrimidine-2,4,6-trione derivative molecules inhibited the nucleosome assembly mediated by Asf1 in vitro, and reduced the H3K56 acetylation in HeLa cells. Furthermore, production of HSV viral particles was reduced by these compounds. As Asf1 is implicated in genome integrity, cell proliferation, and cancer, current Asf1 inhibitor molecules may offer an opportunity for the therapeutic development for treatment of diseases.


Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Chromatin/drug effects , Small Molecule Libraries/pharmacology , Acetylation , Chromatin/metabolism , Chromatin Assembly and Disassembly/drug effects , Histones/metabolism , Humans , Molecular Chaperones , Nucleosomes/drug effects , Nucleosomes/metabolism
17.
Biochem Biophys Res Commun ; 451(2): 308-13, 2014 Aug 22.
Article in English | MEDLINE | ID: mdl-25088994

ABSTRACT

Menin is a gene product of multiple endocrine neoplasia type1 (Men1), an inherited familial cancer syndrome characterized by tumors of endocrine tissues. To gain insight about how menin performs an endocrine cell-specific tumor suppressor function, we investigated the possibility that menin was integrated in a cancer-associated inflammatory pathway in a cell type-specific manner. Here, we showed that the expression of IL-6, a proinflammatory cytokine, was specifically elevated in mouse islet tumor cells upon depletion of menin and Men(-/-) MEF cells, but not in hepatocellular carcinoma cells. Histone H3 lysine (K) 9 methylation, but not H3 K27 or K4 methylation, was involved in menin-dependent IL-6 regulation. Menin occupied the IL-6 promoter and recruited SUV39H1 to induce H3 K9 methylation. Our findings provide a molecular insight that menin-dependent induction of H3 K9 methylation in the cancer-associated interleukin gene might be linked to preventing endocrine-specific tumorigenesis.


Subject(s)
Insulinoma/genetics , Insulinoma/metabolism , Interleukin-6/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Proto-Oncogene Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Cell Line, Tumor , Cells, Cultured , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , HeLa Cells , Hep G2 Cells , Histamine N-Methyltransferase/metabolism , Humans , Interleukin-6/metabolism , Mice , Mice, Knockout , Promoter Regions, Genetic , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/deficiency , Proto-Oncogene Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Suppressor Proteins/deficiency , Tumor Suppressor Proteins/genetics
18.
Dig Dis Sci ; 59(12): 2947-57, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25052149

ABSTRACT

BACKGROUND: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α. AIMS: To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy. METHODS: In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies. RESULTS: A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%, and that of TNF-α decreased from 54.5 to 36.2%. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P = 0.001, respectively). CONCLUSIONS: These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colitis, Ulcerative/drug therapy , Gene Expression Regulation/drug effects , Intracellular Signaling Peptides and Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis, Ulcerative/metabolism , Female , Humans , Infliximab , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Tumor Necrosis Factor-alpha/genetics , Young Adult
19.
J Gastroenterol Hepatol ; 29(9): 1699-705, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24730702

ABSTRACT

BACKGROUND AND AIMS: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. METHODS: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. RESULTS: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. CONCLUSIONS: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB.


Subject(s)
Antiviral Agents/administration & dosage , Arabinofuranosyluracil/analogs & derivatives , Guanine/analogs & derivatives , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Lamivudine/administration & dosage , alpha-Fetoproteins/analysis , Administration, Oral , Adult , Aged , Arabinofuranosyluracil/administration & dosage , Biomarkers/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/etiology , Female , Guanine/administration & dosage , Hepatitis B, Chronic/complications , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/etiology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Time Factors
20.
J Environ Radioact ; 132: 57-64, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24556176

ABSTRACT

Pot experiments were performed in a greenhouse to investigate the soil-to-soybean transfer of (99)Tc in two different upland soils labeled with (99)TcO4(-) in two contrasting ways. One was to mix the soil with a (99)TcO4(-) solution 26 d before sowing (pre-sowing deposition: PSD), and the other was to apply the solution onto the soil surface 44 d after sowing (growing-period deposition: GPD). The soil-to-plant transfer was quantified with the transfer factor (TF, ratio of the plant concentration to the average of at-planting and at-harvest soil concentrations) or the aggregated transfer factor (TFag, ratio of the plant concentration to the deposition density). For both the depositions, the transfer of (99)Tc to aerial parts decreased in the order of leaf > stem > pod > seed. TF values (dimensionless) from the PSD were 0.22 and 0.27 (no statistically significant difference) for mature dry seeds in the respective soils, whereas a 600-fold higher value occurred for dry leaves. The post-harvest concentrations of the PSD (99)Tc in the top 20 cm soils as a whole were about half the initial concentrations. Around 25% of the total applied activity remained in the GPD soils after the harvest. The post-harvest depth profiles of the GPD (99)Tc in the two soils showed similar patterns of logarithmic activity decrease with increasing soil depths. Only 1.5-4.3% of the total applied activity was removed through the harvested biomass (seeds, pods and stems), and it was estimated that a great part of the total pant uptake returned to the soil through the fallen leaves. TFag values (m(2) kg(-1)) were about 2-4 times higher for the GPD than for the PSD. This finding and generally high root uptake of Tc may indicate that the use of empirical deposition time-dependent TFag data is particularly important for predicting the plant concentrations of Tc after its growing-period deposition.


Subject(s)
Food Contamination, Radioactive/analysis , Glycine max/radiation effects , Radioisotopes/analysis , Soil Pollutants, Radioactive/analysis , Technetium/analysis , Environmental Pollution , Hydrogen-Ion Concentration , Plant Leaves/radiation effects , Plant Roots/radiation effects , Plant Stems/radiation effects , Radiation Monitoring/methods , Radioactive Waste , Republic of Korea , Seeds/radiation effects , Soil , Soil Pollutants
SELECTION OF CITATIONS
SEARCH DETAIL
...