Increase in the Colorectal Cancer Screening Rate by a Round-Mailed Fecal Immunochemical Testing Kit and Associated Factors in Underserved Regions of Korea: A Community-Based Intervention Study.

Background/Aims: Postal distribution of a fecal immunochemical test (FIT) kit has been recommended as an effective method of increasing participation in colorectal cancer (CRC) screening. The present study was performed to assess the impact of the round-mailed FIT kit on screening participation in underserved regions of Korea and to identify factors related to nonparticipation. Methods: Residents were recruited from three rural regions of Korea that lack screening units for the National Cancer Screening Program. A package containing a FIT kit for stool self-sampling and a return envelope addressed to the local health center was postally distributed to each subject. Thirty days after the kits were mailed, nonresponders were reminded via telephone as the second intervention. The participation rates and odds ratios with 95% confidence intervals (CIs) for each intervention response were calculated to evaluate the effect of the interventions and factors related to screening participation in response to the interventions. Results: CRC screening participation rates increased from 24.5% (95% CI, 21.6% to 27.4%) to 42.6% (95% CI, 39.3% to 46.0%) as a result of postal screening and increased further to 51.4% (95% CI, 48.0% to 54.9%) after the telephone reminder. After controlling for the sex, age, and household type of each subject, factors associated with poor response to postal screening were identified as low educational attainment and poor previous participation in the National Cancer Screening Program. Conclusions: Round-mailed FIT kits with phone call reminders were an effective intervention, nearly doubling the screening rate in underserved regions of Korea.

Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

BACKGROUND: Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. OBJECTIVES: For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. STUDY DESIGN: The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. RESULTS: The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off CT value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the CT threshold. CONCLUSIONS: Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off CT value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs.

Magnetic nanowires for rapid and ultrasensitive isolation of DNA from cervical specimens for the detection of multiple human papillomaviruses genotypes.

Detecting human papillomavirus (HPV) is central in diagnosing and monitoring HPV-related disease. However, limited sensitivity and the wide variability of the HPV genome pose challenges in the identification of HPV genes, particularly high-risk types. This study reports the development of polyethyleneimine-conjugated magnetic nanowires (PEI-MNWs) and their use in the isolation, identification, and analysis of multiple genotypes of HPV DNA from cervical cancer specimens. The nanowires are electrochemically doped with a high density of magnetic nanoparticles and biotin moieties during potentiostatic deposition, thereby allowing conjugating cationic branched polymers to direct the attachment of negatively charged DNA molecules with strong magnetic response. For proof of concept, the rapid and ultrasensitive isolation of HPV DNA is performed at concentrations as low as 10pg/mL with an efficiency of >95%. For clinical optimization, the analytical and clinical sensitivity of PEI-MNWs is compared with that of the Roche Cobas 4800 HPV Test and demonstrates excellent correlation for multiple HPV DNA genotypes with superior threshold cycle values. The high sensitivity, specificity, and good reproducibility of PEI-MNWs are particularly well suited for the recovery of DNA and provide significant and clinically meaningful evidence for the early detection and treatment of HPV-associated cancers.

Comparison of DRY and WET vaginal swabs with cervical specimens in Roche Cobas 4800 HPV and Abbott RealTime High Risk HPV tests.

BACKGROUND: Self-collected vaginal swab samples have been proposed as an alternative specimen collection method for human papillomavirus (HPV) DNA detection. OBJECTIVES: Two vaginal swabs (a cone-shaped flocked swab (DRY) and a L-shape FLOQSwab with 2mL eNAT transport medium (WET)) were compared to standard cervical samples for HPV DNA testing. Additionally, they were also compared by using Roche Cobas 4800 HPV (Roche_HPV) and Abbott Real-time High Risk HPV (Abbott_HPV) tests. STUDY DESIGN: Ninety-six women were prospectively enrolled from the National Cancer Center in Korea between June and August 2015. WET and DRY vaginal swabs and cervical specimens were collected. Roche_HPV and Abbott_HPV tests were performed. The Roche_HPV test on cervical specimens was used as reference. RESULTS: The observed agreements (kappa) of Roche_HPV and Abbott_HPV between WET and DRY swabs were 89.6% (0.790, 95% confidence interval (95% CI): 0.667-0.913) and 91.7% (0.833, 95%CI: 0.723-0.943), respectively. No statistical difference was observed between WET and DRY swabs (p>0.05 for all comparisons). For HPV16/18, the sensitivity/specificity of Roche_HPV on the DRY and WET samples presented 93.8%/96.3% and 87.5%/97.5%, respectively. For other High Risk HPV (hrHPV), the sensitivity/specificity of Roche_HPV on the DRY and WET swabs presented 91.9%/91.5% and 97.3%/98.3, respectively. The sensitivity/specificity of the Abbott_HPV on the DRY and WET swabs were 93.8%/98.8%, 87.5%/98.8% for HPV16/18, and 91.9%/93.2%, 100.0%/93.2% for other hrHPV, respectively. CONCLUSIONS: HPV tests performed similarly when using vaginal DRY and WET swab samples. Using DRY and WET swabs to collect vaginal specimens could be an alternative to collecting cervical samples for HPV DNA testing.

Comparison of the performance of Anyplex II HPV HR, the Cobas 4800 human papillomavirus test and Hybrid Capture 2.

BACKGROUND: Anyplex II HPV HR (Anyplex_HR; Seegene, Seoul, Korea) is a new multiplex real-time polymerase chain reaction assay for screening cervical cancer, and it is designed to detect 14 high-risk human papillomaviruses along with all the genotype information in a single tube. The aim of this study was to evaluate the performance of the Anyplex_HR in comparison to that of the Cobas 4800 HPV (Cobas_4800; Roche Molecular Diagnostics, Pleasanton, CA, USA) and the Hybrid capture 2 (HC2; Qiagen GmbH, Hilden, Germany). METHODS: The performance of the Anyplex_HR for high-risk human papillomavirus genotype detection was prospectively evaluated against that of the HC2 and the Cobas_4800 at the National Cancer Center using 400 cervical samples. All discrepant samples were confirmed by polymerase chain reaction with type-specific primers followed by sequencing. RESULTS: The overall agreement and kappa value of the Anyplex_HR with the Cobas_4800 were 98.0% and 0.96, respectively. The level of agreement between the two assays and the corresponding kappa values for human papillomavirus16, human papillomavirus18 and other high-risk human papillomaviruses were 99.5%, 99.8% and 98.8%, and 0.98, 0.96 and 0.97, respectively. The agreement and kappa value of the HC2 with the Cobas_4800 were 95.3% and 0.91. The human papillomavirus positivity of the Anyplex_HR and the Cobas_4800 in low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion samples demonstrated 100% concordance. Both the Anyplex_HR and the Cobas_4800 showed excellent results in the precision test. CONCLUSIONS: The Anyplex_HR is comparable with the Cobas_4800 and the HC2 for human papillomavirus DNA testing, and it may prove more useful for follow-up testing and patient management by providing genotyping information additional to human papillomavirus16 and human papillomavirus18.

Hexabromocyclododecanes in crucian carp and sediment from the major rivers in Korea.

The concentration of hexabromocyclododecanes (HBCDs) was measured in crucian carp muscles and eggs and in surrounding sediments collected from the 3 major rivers in Korea. HBCDs were detected in all carp and sediment samples, indicating widespread contamination of this area by HBCD flame retardants. The ∑HBCD (sum of α-, ß-, and γ-HBCDs) concentrations ranged from 0.19 to 13 ng g(-1)dry wt in sediments, 1.7 to 7.2 ng g(-1)lipid wt in carp eggs, and 4.8 to 6.6 ng g(-1)lipid wt in the muscle of carp. The α-diastereomer predominated in the crucian carp and γ-diastereomer predominated in sediments, accounting for 76% and 77% to the ∑HBCD, respectively. The ∑HBCD concentrations in carp and sediment samples collected along the rivers were higher than those in samples collected from an isolated pond, suggesting that the rivers are likely contaminated by HBCDs from the upstream or the environment surrounding the rivers. The diastereomer ratios in carp were different from those in commercial mixtures due to the enrichment of α-diastereomer in carp. The origin of this transition, however, is yet not known, since various transformation processes can lead to a change from the diastereomer ratio in commercial mixtures to that observed in the environment.

Oxidative modifications of glyceraldehyde-3-phosphate dehydrogenase play a key role in its multiple cellular functions.

Knowledge of the cellular targets of ROS (reactive oxygen species) and their regulation is an essential prerequisite for understanding ROS-mediated signalling. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is known as a major target protein in oxidative stresses and becomes thiolated in its active site. However, the molecular and functional changes of oxidized GAPDH, the inactive form, have not yet been characterized. To examine the modifications of GAPDH under oxidative stress, we separated the oxidation products by two-dimensional gel electrophoresis and identified them using nanoLC-ESI-q-TOF MS/MS (nano column liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem MS). Intracellular GAPDH subjected to oxidative stress separated into multiple acidic spots on two-dimensional gel electrophoresis and were identified as cysteine disulfide and cysteic acids on Cys152 in the active site. We identified the interacting proteins of oxidized inactive GAPDH as p54nrb (54 kDa nuclear RNA-binding protein) and PSF (polypyrimidine tract-binding protein-associated splicing factor), both of which are known to exist as heterodimers and bind to RNA and DNA. Interaction between oxidized GAPDH and p54nrb was abolished upon expression of the GAPDH active site mutant C152S. The C-terminal of p54nrb binds to GAPDH in the cytosol in a manner dependent on the dose of hydrogen peroxide. The GAPDH-p54nrb complex enhances the intrinsic topoisomerase I activation by p54nrb-PSF binding. These results suggest that GAPDH exerts other functions beyond glycolysis, and that oxidatively modified GAPDH regulates its cellular functions by changing its interacting proteins, i.e. the RNA splicing by interacting with the p54nrb-PSF complex.

Heat shock responses for understanding diseases of protein denaturation.

Extracellular stresses induce heat shock response and render cells resistant to lethal stresses. Heat shock response involves induction of heat shock proteins (Hsps). Recently the roles of Hsps in neurodegenerative diseases and cancer are attracting increasing attention and have accelerated the study of heat shock response mechanism. This review focuses on the stress sensing steps, molecules involved in Hsps production, diseases related to Hsp malfunctions, and the potential of proteomics as a tool for understanding the complex signaling pathways relevant to these events.