Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction. MATERIALS AND METHODS: Using the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT. RESULTS: During a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001). CONCLUSION: Our results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma

Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27Kip1 protein level specifically increased after KIF14 knockdown. The increase in p27Kip1 was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27Kip1 accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27Kip1 for degradation by the 26S proteasome, leading to accumulation of p27Kip1. The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 x 10(-7)). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 x 10(-5)). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 +/- 10(-10)). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.

Integrated analysis of copy number alteration and RNA expression profiles of cancer using a high-resolution whole-genome oligonucleotide array

Recently, microarray-based comparative genomic hybridization (array-CGH) has emerged as a very efficient technology with higher resolution for the genome-wide identification of copy number alterations (CNA). Although CNAs are thought to affect gene expression, there is no platform currently available for the integrated CNA-expression analysis. To achieve high-resolution copy number analysis integrated with expression profiles, we established human 30k oligoarray-based genome-wide copy number analysis system and explored the applicability of this system for integrated genome and transcriptome analysis using MDA-MB-231 cell line. We compared the CNAs detected by the oligoarray with those detected by the 3k BAC array for validation. The oligoarray identified the single copy difference more accurately and sensitively than the BAC array. Seventeen CNAs detected by both platforms in MDA-MB-231 such as gains of 5p15.33-13.1, 8q11.22-8q21.13, 17p11.2, and losses of 1p32.3, 8p23.3-8p11.21, and 9p21 were consistently identified in previous studies on breast cancer. There were 122 other small CNAs (mean size 1.79 mb) that were detected by oligoarray only, not by BAC-array. We performed genomic qPCR targeting 7 CNA regions, detected by oligoarray only, and one non-CNA region to validate the oligoarray CNA detection. All qPCR results were consistent with the oligoarray-CGH results. When we explored the possibility of combined interpretation of both DNA copy number and RNA expression profiles, mean DNA copy number and RNA expression levels showed a significant correlation. In conclusion, this 30k oligoarray-CGH system can be a reasonable choice for analyzing whole genome CNAs and RNA expression profiles at a lower cost.

Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis

Molecular mechanism of lung carcinogenesis and its aggressive nature is still largely elusive. To uncover the biomarkers related with tumorigenesis and behavior of lung cancer, we screened novel differentially expressed genes (DEG) in A549 lung cancer cell line by comparison with CCD-25Lu, normal pulmonary epithelial cell line, using annealing control primer(ACP)- based GeneFishing system. Of the DEGs, over-expression of leucyl-tRNA synthetase 1 (LARS1) was prominent and this up-regulation was confirmed by immunoblotting and real-time quantitative RT-PCR analysis. In addition to A549 cell line, primary lung cancer tissues also expressed higher level of LARS1 mRNA than their normal counter tissues. To explore the oncogenic potential of LARS1 over-expression in lung cancer, we knocked-down LARS1 by treating siRNA and observed the tumor behavior. LARS1 knock-down cells showed reduced ability to migrate through transwell membrane and to form colonies in both soft agar and culture plate. Taken together, these findings suggest that LARS1 may play roles in migration and growth of lung cancer cells, which suggest its potential implication in lung tumorigenesis.

Comparison of Normalization Methods for Defining Copy Number Variation Using Whole-genome SNP Genotyping Data

Precise and reliable identification of CNV is still important to fully understand the effect of CNV on genetic diversity and background of complex diseases. SNP marker has been used frequently to detect CNVs, but the analysis of SNP chip data for identifying CNV has not been well established. We compared various normalization methods for CNV analysis and suggest optimal normalization procedure for reliable CNV call. Four normal Koreans and NA10851 HapMap male samples were genotyped using Affymetrix Genome-Wide Human SNP array 5.0. We evaluated the effect of median and quantile normalization to find the optimal normalization for CNV detection based on SNP array data. We also explored the effect of Robust Multichip Average (RMA) background correction for each normalization process. In total, the following 4 combinations of normalization were tried: 1) Median normalization without RMA background correction, 2) Quantile normalization without RMA background correction, 3) Median normalization with RMA background correction, and 4) Quantile ormalization with RMA background correction. CNV was called using SW-ARRAY algorithm. We applied 4 different combinations of normalization and compared the effect using intensity ratio profile, box plot, and MA plot. When we applied median and quantile normalizations without RMA background correction, both methods showed similar normalization effect and the final CNV calls were also similar in terms of number and size. In both median and quantile normalizations, RMA background correction resulted in widening the range of intensity ratio distribution, which may suggest that RMA background correction may help to detect more CNVs compared to no correction.

Effect of Computer-Assisted Cognitive Rehabilitation Program for Patients with Brain Injury

OBJECTIVE: To evaluate the effect of computer-assisted cognitive rehabilitation program on cognitive function of the patients with brain injury. METHOD: Twenty seven subjects with brain injury (23males, 4 females) were enrolled and classified into two groups, experimental and control group. There was no significant difference between two groups in age and postonset duration. Control group received conventional rehabiliation therapy including physical and occupational therapy. Experimental group received additional computer-assisted cognitive training using PSS CogRehab software (USA, 1995), 3 times per a week, 30 minutes per session, for 4 weeks. The PSS CogRehab software consisted of foundation, memory, visual spatial and problem solving categories with 45 indivisualized training programs. These 45 programs are arranged according to the degree of difficulty. All patients were assessed their cognitive function using Computerized Neuropsychological Test (Mirae engineering, 1999) before treatment and at 1 month after treatment. RESULTS: Before the treatment, two groups showed no difference in their cognitive function. After 1 month treatment, the experimental group showed significantly higher performance in forward digit span, forward visual span, auditory continuous performance test and visual controlled continuous performance test than control group (p<0.05). CONCLUSION: Computer-assisted cognitive training would be useful as a additional tool of cognitive rehabilitation in patients with brain injury.

Effect of Donepezil on Cognitive Function in Patients with Brain Injury

OBJECTIVE: To evaluate the effect of donepezil on cognitive function in patients with brain injury who had cognitive impairment. METHOD: Twenty one subjects with brain injury (18 males,3 females) were enrolled and classified into two groups, experimental and control group. There was no significant difference between two groups in age, postonset duration, and level of education. For the experimental group, one tablelet of Aricept(R) (5 mg of donepezil per tablet) was administered daily for 6 weeks. The baseline and follow up cognitive assessments were performed before and 6 weeks after. Mini- mental Status Examination (MMSE), Computerized Neuropsychologic Test (CNT), Judgement of Line Orientation (JLO), and visuospatial Wechsler memory test were used for the assessment of cognitive function. RESULTS: In baseline study, two groups showed no difference in their cognitive function. After 6 weeks, the experimental group showed significantly higher performance in forward digit span, verbal learning test, backward visual span, visual learning test, non-verbal Wechsler memory test, and judgement of line orientaion than control group (p<0.05). CONCLUSION: These results suggested that the administration of Aricept(R) was beneficial in improving the cognitive func tion, especially verbal and visual memory and visuospatial perception in patients with brain injury.

Quantitative Measurement of Eotaxin and RANTES mRNA in the Nasal Polyps / 대한임상병리학회지

BACKGROUND: Nasal polyps were developed from eosinophil infiltrations and activation by chronic inflammatory reactions. Eotaxin and RANTES have been postulated to be involved in the recruitment and activation of eosinophils to the inflamed tissues. The aim of this study is to estimate the mRNA expression of eotaxin and RNATES in the nasal polyps and it's effect on tissue eosinophils. METHODS: At first, we evaluated the linearity and precision of GeneAmp 5700R(PE Applied Biosystems, Foster, U.S.A) with M. tuberculosis DNA. We collected 17 allergic, 30 non-allergic nasal polyps and 15 normal inferior turbinates from the patients visiting Catholic University Hospital of Taegu Hyosung. We performed the quantitative polymerase chain reaction(PCR) for the eotaxin and RNATES, and the tissue immunohistochemical stain for the major basic protein. RESULTS: GeneAmp 5700R disclosed good linearity and precision. Compared with the normal inferior turbinates, eotaxin mRNA levels were increased in the allergic and non-allergic polyps, and showed significant correlation with eosinophils infiltration and activation. But the RANTES didn't revealed any significant differences among these groups, and no correlation with tissue eosinophils. The patients with allergic polyps showed increased eosinophils infiltration and activation in the tissue, while those with non allergic polyps disclosed increased eosinophils activation. CONCLUSIONS: Since eotaxin expression were increased in the tissue of the patients with nasal polyps and showed good correlation with eosinophils infiltration and activation in the tissue, it had been considered that eotaxin played an important role in the pathogenesis of allergic polyps and tissue eosinophilia.

A clinical investigation of new diuretics, azosemide(SK-110) / 대한신장학회잡지

No abstract available.

Clinical features ofdiabetic end-stage renal disease on hemodialysis / 대한신장학회잡지

No abstract available.

A study of complications related to subclavian catheters for hemodialysis / 대한신장학회잡지

No abstract available.

A clinical study on 24 cases of renal transplantation / 대한신장학회잡지

No abstract available.

A Case of Myotonic Dystrophy with Prolonged Atrial Flutter

Myotonic dystrophy is a multisystemic disorder inherited as an autosomal dominant trait. The characteristic clinical features include the presence of myotonia, atrophy of the muscles of the face and the sternocleidomastoids and numerous nonmusclar manifestations such as cataracts, frontal baldness, gonadal dysfunctions and cardiac abnormalities. We experienced one case of myotonic dystrophy with prolonged atrial flutter in 30-year-old male who was admitted because of palpitation. We present this case with reviewing literatures.