• Title/Summary/Keyword: Biomarker Detection

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Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

  • Yuan, Zhi-Jun;Zhou, Wen-Wu;Liu, Wei;Wu, Bai-Ping;Zhao, Jin;Wu, Wei;He, Yi;Yang, Shuo;Su, Jing;Luo, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4347-4351
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    • 2015
  • Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

Environmental Pollutants in Streams of Andong District and Insect Immune Biomarker (안동지역 하천의 환경오염물질과 곤충면역 생체지표 분석)

  • Ryoo Keon Sang;Ko Seong-Oon;Cho Sunghwan;Lee Hwasung;Kim Yonggyun
    • Korean journal of applied entomology
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    • v.44 no.2
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    • pp.97-108
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    • 2005
  • Samples of water, soil, and sediment were taken from 10 streams near Andong, Korea in May 2004. To assess the degree of environmental pollution of each stream, chemical pollutants such as total notrogen (T-N), total phosphorus (T-P), chemical oxygen demand (COD), heavy metals, organophosphorus pesticides, organochlorine pesticides, and dioxin-like PCB congeners were analyzed by standard process tests or U.S. EPA methods. In addition, biomarkers originated from insect immune systems of beet armyworm, Spodoptera exigua, were used to analysis of the environmental samples. Except Waya-chun stream showing T-N content of 9.12 mg/L, most streams were contaminated with relatively low levels of overall pollutants in terms of T-N, T-P, and COD, compared to their acceptable environmental levels designated by the Ministry of Environment. Contents of Pb and Cd in samples of each stream were much lower than environmentally permissible levels. However, several times higherconcentrations of Pb and Cd were found in locations at Mi-chun, Kilan-chun, and Hyunha-chun streams, in comparison with other streams. Diazinon, parathion, and phenthoate compounds among organophosphorus pesticides were detected as concentrations of 0.19, 0.40, and $1.13\;{\mu}g/g$, respectively, from soil sample collected in the vicinity of Mi-chun stream. On the other hand, 16 organochlorine pesticides and 12 dioxin-like PCB congeners, known as endocrine disrupting chemicals, selected in this study were not found above the limit of detection. Biomarker analyses using insect immune responses indicated that Waya-chun stream was suspected as exposure to environmental pollutants. Limitation and compensation of both environmental analysis techniques are discussed.

Expressed Sequence Tag Analysis of Toxic Alexandrium tamarense and Identification of Saxitoxin Biosynthetic Genes (독성 Alexandrium tamarense 의 EST 분석 및 삭시톡신 생합성 유전자의 확인)

  • Chang, Man;Lee, Juyun;Chung, Youngjae;Lee, Gunsup;Kim, Dongguin;Lee, Taek-Kyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.7
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    • pp.3582-3588
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    • 2013
  • Expressed sequence tag (EST) library was constructed from A. tamarense. Base sequences of EST clones were analyzed and saxitoxin biosynthesis-related genes were cloned. Sequences of 827 clones were analyzed and 564 EST were functionally clustered using Blast searches against GenBank. Main genes in the EST had functions on cellular organization, cell metabolism, energy, cell cycle and DNA processing, cellular transport and transport, cell rescue, defense, death and aging, and transcription. Moreover, expression of S-adenosylmethionine synthetase and H2A histone family genes were increased in the toxic A. tamarense. These results show that two genes could be a good biomarkers for the detection of saxitoxin biosynthesis in the A. tamarense.

Association of Biomarker Levels with Severity of Asbestos-Related Diseases

  • Park, Eun-Kee;Yates, Deborah H.;Creaney, Jenette;Thomas, Paul S.;Robinson, Bruce W.;Johnson, Anthony R.
    • Safety and Health at Work
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    • v.3 no.1
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    • pp.17-21
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    • 2012
  • Objectives: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs. Methods: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared. Results: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01). Conclusion: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.

Prostate Stem Cell Antigen Single Nucleotide Polymorphisms Influence Risk of Estrogen Receptor Negative Breast Cancer in Korean Females

  • Kim, Sook-Young;Yoo, Jae-Young;Shin, Ae-Sun;Kim, Yeon-Ju;Lee, Eun-Sook;Lee, Yeon-Su
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.41-48
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    • 2012
  • Introduction: Breast cancer is the second leading cancer in Korean women. To assess potential genetic associations between the prostate stem cell antigen (PSCA) gene in the chromosome 8q24 locus and breast cancer risk in Korean women, 13 SNPs were selected and associations with breast cancer risk were analyzed with reference to hormone receptor (HR) and menopausal status. Methods:We analyzed DNA extracted from buffy coat from 456 patients and 461 control samples, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based upon region-specific PCR followed by allelespecific single base primer extension reactions. Risks associated with PSCA genotypes and haplotypes were estimated with chi-square test (${\chi}^2$-test), and polytomous logistic regression models using odds ratios (OR) and 95% confidence intervals (CIs), by HR and menopausal status. Results: In case-control analysis, odds ratios (OR) of rs2294009, rs2294008, rs2978981, rs2920298, rs2976395, and rs2976396 were statistically significant only among women with estrogen receptor (ER) negative cancers, and those of rs2294008, rs2978981, rs2294010, rs2920298, rs2976394, rs10216533, and rs2976396 were statistically significant only in pre-menopausal women, and not in postmenopausal women. Risk with the TTGGCAA haplotype was significantly elevated in ER (-) status (OR= 1.48, 95% CI= 1.03~2.12, p<0.05). Especially risk of allele T of rs2294008 is significantly low in pre-menopausal breast cancer patients and AA genotype of rs2976395 in ER (-) status represents the increase of OR value. Conclusion: This report indicated for the first time that associations exist between PSCA SNPs and breast cancer susceptibility in Korean women, particularly those who are pre-menopausal with an estrogen receptor negative tumor status.

Applicability of Serum Krebs von den lungen-6 as a Biological Exposure Index for Workers Exposed to Indium (인듐 노출 근로자를 위한 생물학적 노출지표로써 혈청 Krebs von den lungen-6의 활용가능성)

  • Won, Yong Lim;Yi, Gwang Yong;Lee, Mi-Young;Kim, Eun-A
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.23 no.2
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    • pp.108-113
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    • 2013
  • Objectives: Although several cases of lung diseases caused by indium have been reported in Japan, the United States and China, South Korea, which is estimated to have been the world's largest consumer of indium, has not yet established a criteria for the diagnosis of lung diseases caused by indium exposure. In this study, we tried to determine the applicability of the Krebs von den lungen-6, which has been widely recognized for its use with interstitial lung disease in Japan, as a biological exposure index for indium. Methods: Methods: The analysis of indium in serum was conducted by inductively coupled plasma mass spectrometry and the analysis of KL-6 in serum was carried out using enzyme-linked immunosorbent assay kit. Results: The indium levels in serum were distributed from below the detection limit to a peak of $125.78{\mu}g/L$, and the values of the KL-6 were distributed from 104.5 U/mL to 2162.2 U/mL. The serum indium and KL-6 showed good correlation ($R^2$=0.389,pfortrend=0.000) and smoking did not affect the KL-6. Conclusions: The usefulness of KL-6 as a specific biomarker for interstitial lung disease has been recognized. In addition, it is expected that effective prevention of health problems can be achieved by determining the lung-damage progress at an early stage according to individual susceptibility.

Comparative Proteomic Analysis of Human Amniotic Fluid Supernatants with Down Syndrome Using Mass Spectrometry

  • Park, Ji-Sook;Cha, Dong-Hyun;Jung, Jin-Woo;Kim, Young-Hwan;Lee, Sook-Hwan;Kim, Young-Jun;Kim, Kwang-Pyo
    • Journal of Microbiology and Biotechnology
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    • v.20 no.6
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    • pp.959-967
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    • 2010
  • Down syndrome (DS) is an abnormality of the 21st chromosome that commonly occurs in children born to older women. Thus, amniotic fluid (AF) is usually collected from such women for prenatal diagnosis. This study analyzed human AF supernatants (AFS) using a mass spectrometric (MS) approach to search for candidate biomarkers of a DS pregnancy. The AFS were collected from older pregnant women at weeks 16-18 of their gestation by amniocentesis for cytogenetic analysis. The AFS from the pregnancies carrying DS (n=4) or chromosomally normal (n=6) fetuses, as revealed by the cytogenetic analysis, were then subjected to global protein profiling based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Affinity chromatography was also applied prior to the LC-ESI-MS/MS to minimize the masking effect of highly abundant albumin and immunoglobulin and thereby increase the diversity of the identified proteins. As a result, at least 30 new AFS proteins were identified and 44 AFS proteins were found to be differentially expressed between the DS and normal cases, where 6 of the proteins were unique to the DS cases and 11 were unique to the chromosomally normal cases. In addition, in the DS cases, 19 AFS proteins were downregulated and 8 were upregulated to varying degrees. A Western blot analysis confirmed the LC-ESI-MS/MS data, indicating that the combined detection of apolipoprotein A-II (apoA-II) and alpha-fetoprotein (AFP) could be a potential tool for diagnosing DS cases.

Microcantilever biosensor: sensing platform, surface characterization and multiscale modeling

  • Chen, Chuin-Shan;Kuan, Shu;Chang, Tzu-Hsuan;Chou, Chia-Ching;Chang, Shu-Wei;Huang, Long-Sun
    • Smart Structures and Systems
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    • v.8 no.1
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    • pp.17-37
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    • 2011
  • The microcantilever (MCL) sensor is one of the most promising platforms for next-generation label-free biosensing applications. It outperforms conventional label-free detection methods in terms of portability and parallelization. In this paper, an overview of recent advances in our understanding of the coupling between biomolecular interactions and MCL responses is given. A dual compact optical MCL sensing platform was built to enable biosensing experiments both in gas-phase environments and in solutions. The thermal bimorph effect was found to be an effective nanomanipulator for the MCL platform calibration. The study of the alkanethiol self-assembly monolayer (SAM) chain length effect revealed that 1-octanethiol ($C_8H_{17}SH$) induced a larger deflection than that from 1-dodecanethiol ($C_{12}H_{25}SH$) in solutions. Using the clinically relevant biomarker C-reactive protein (CRP), we revealed that the analytical sensitivity of the MCL reached a diagnostic level of $1{\sim}500{\mu}g/ml$ within a 7% coefficient of variation. Using grazing incident x-ray diffractometer (GIXRD) analysis, we found that the gold surface was dominated by the (111) crystalline plane. Moreover, using X-ray photoelectron spectroscopy (XPS) analysis, we confirmed that the Au-S covalent bonds occurred in SAM adsorption whereas CRP molecular bindings occurred in protein analysis. First principles density functional theory (DFT) simulations were also used to examine biomolecular adsorption mechanisms. Multiscale modeling was then developed to connect the interactions at the molecular level with the MCL mechanical response. The alkanethiol SAM chain length effect in air was successfully predicted using the multiscale scheme.

Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder

  • Matsumoto, Kazumasa;Ikeda, Masaomi;Matsumoto, Toshihide;Nagashio, Ryo;Nishimori, Takanori;Tomonaga, Takeshi;Nomura, Fumio;Sato, Yuichi;Kitasato, Hidero;Iwamura, Masatsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9927-9931
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    • 2014
  • The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinoma of the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings. Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakin antibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levels in patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normal controls (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelial carcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were 83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients with muscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportional hazards regression analysis, none of the clinicopathological factors was associated with an increased risk for progression and cancer-specific survival. Examination of the serum periplakin level may play a role as a non-invasive diagnostic modality to aid urine cytology and cystoscopy.

Common Variants in the PALB2 Gene Confer Susceptibility to Breast Cancer: a Meta-analysis

  • Zhang, Yi-Xia;Wang, Xue-Mei;Kang, Shu;Li, Xiang;Geng, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7149-7154
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    • 2013
  • Objective: Increasing scientific evidence suggests that common variants in the PALB2 gene may confer susceptibility to breast cancer, but many studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationship between PALB2 genetic variants and breast cancer risk. Methods: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI and CBM databases from their inception through September 1st, 2013. A meta-analysis was performed using the STATA 12.0 software and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Six case-control studies were included with a total of 4,499 breast cancer cases and 6,369 healthy controls. Our meta-analysis reveals that PALB2 genetic variants may increase the risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001; dominant model: OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup analyses by ethnicity indicated PALB2 genetic variants were associated with an increased risk of breast cancer among both Caucasian and Asian populations (all P < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05). Conclusion: The current meta-analysis indicates that PALB2 genetic variants may increase the risk of breast cancer. Thus, detection of PALB2 genetic variants may be a promising biomarker approach.