• Title/Summary/Keyword: Lung cancer screening

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Functional PstI/RsaI Polymorphisms in the CYP2E1 Gene among South Indian Populations

  • Lakkakula, Saikrishna;Maram, Rajasekhar;Munirajan, Arasambattu Kannan;Pathapati, Ram Mohan;Visweswara, Subrahmanyam Bhattaram;Lakkakula, Bhaskar V.K.S.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.179-182
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    • 2013
  • Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues. CYP2E1 is inducible by ethanol, acetone, and other low-molecular weight substrates and may mediate development of chemically-mediated cancers. CYP2E1 polymorphisms alter the transcriptional activity of the gene. This study was conducted in order to investigate the allele frequency variation in different populations of Andhra Pradesh. Two hundred and twelve subjects belonging to six populations were studied. Genotype and allele frequency were assessed through TaqMan allelic discrimination (rs6413419) and polymerase chain reaction-sequencing (-1295G>C and -1055C>T) after DNA isolation from peripheral leukocytes. The data were compared with other available world populations. The SNP rs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less polymorphic and followed Hardy-Weinberg equilibrium in all the populations studied. The -1295G>C and -1055C>T frequencies were similar and acted as surrogates in all the populations. Analysis of HapMap populations data revealed no significant LD between these markers in all the populations. Low frequency of $CYP2E1^*c2$ could be useful in the understanding of south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development. However, screening of additional populations and further association studies are necessary. The heterogeneity of Indian population as evidenced by the different distribution of $CYP2E1^*c2$ may help in understanding the population genetic and evolutionary aspects of this gene.

Screening of Photosensitizer for Photodynamic Therapy (광역동 항암치료를 위한 광과민제 스크리닝 연구)

  • Kim, So-Young;Yoo, Gui-Jae;Park, Keun-Hyoung;Lim, Byung-Lak;Kim, Shi-Surk;Yom, Heng-Cherl;Chae, Hee-Jeong
    • KSBB Journal
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    • v.22 no.5
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    • pp.318-321
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    • 2007
  • Photodynamic therapy (PDT) is a targeted-tumor treatment system using a photosensitizer, light and oxygen to treat malignant tumor. We have investigated the cytotoxicity of 4 types of phthalocyanine derivative (silver phthalocyanine, iron (III) phthalocyanine, copper (II) phthalocyanine, nickel (II) phthalocyanine) against lung and breast cancers based on photodynamic therapy. As a result, phthalocyanine derivatives indicated a higher anticancer activity on a breast cancer cell line. Among the tested phthalocyanines, silver phthalocyanine (AgPc) showed a lower cytotoxicity against a normal cell line. In addition AgPc gave a good color characteristic when it is solubilized in water. Finally AgPc was selected as a potential antitumor agent for breast cancer.

Predictors of Positive Bone Metastasis in Newly Diagnosed Prostate Cancer Patients

  • Chien, Tsu-Ming;Lu, Yen-Man;Geng, Jiun-Hung;Huang, Tsung-Yi;Ke, Hung-Lung;Huang, Chun-Nung;Li, Ching-Chia;Chou, Yii-Her;Wu, Wen-Jeng;Huang, Shu-Pin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1187-1191
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    • 2016
  • Background: The prevalence of prostate cancer (PCa) has been increasing in recent years. Treatment strategies are largely based on the results of bone scan screening. Therefore, our aim was to investigate predictors of positive bone metastasis in newly diagnosed PCa patients. Materials and Methods: After extensive review, 336 consecutive patients newly diagnosed with PCa between April 2010 and November 2013 at our institution were enlisted in the study. Patients were divided into two groups according to bone scan results. Univariate analyses (Chi-square test for discrete variables and independent t-test for continuous variables) were applied to determine the potentially significant risk factors associated with distant bone metastasis. Binary logistic regression analyses were used to further investigate the influence of these factors on bone metastasis. Results: The patient mean age was $71.9{\pm}8.6years$ (range: 48 to 94 years). The mean prostate specific antigen (PSA) level and biopsy Gleason score were $260.2{\pm}1107.8ng/mL$ and $7.4{\pm}1.5$, respectively. The body mass index (BMI) for the series was $24.5{\pm}3.4kg/m^2$. Sixty-four patients (19.0%) had a positive bone scan result. Patients with positive bone scan results had a significantly lower BMI ($23.3{\pm}3.5$ vs. $24.8{\pm}3.3$; p=0.003), a higher Gleason score ($8.5{\pm}1.1$ vs. $7.1{\pm}1.5$; p < 0.001), and a higher PSA level ($1071.3{\pm}2337.1$ vs. $69.4{\pm}235.5$; p < 0.001) than those without bone metastasis. Multivariate logistic regression analysis employing the above independent predictors demonstrated that a Gleason score of ${\geq}7$, clinical stage ${\geq}T3$, $BMI{\leq}22kg/m^2$, and an initial PSA level of ${\geq}20ng/mL$ were all independent predictors of bone metastasis. Conclusions: A bone scan might be necessary in newly diagnosed PCa patients with any of the following criteria: clinical stage T3 or higher, a Gleason score of 7 or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.

Sex-specific Associations Between Serum Hemoglobin Levels and the Risk of Cause-specific Death in Korea Using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS)

  • An, Yoonsuk;Jang, Jieun;Lee, Sangjun;Moon, Sungji;Park, Sue K.
    • Journal of Preventive Medicine and Public Health
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    • v.52 no.6
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    • pp.393-404
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    • 2019
  • Objectives: The purpose of this study was to determine the associations between blood hemoglobin (Hgb) levels and the risk of death by specific causes. Methods: Using the National Health Insurance Services-National Health Screening Cohort (n=487 643), we classified serum Hgb levels into 6 sex-specific groups. Cox regression analysis was used to analyze the associations between Hgb levels and the risk of cause-specific death. Results: Hgb levels in male population showed a U-shaped, J-shaped, or inverse J-shaped association with the risk of death from ischemic heart disease, acute myocardial infarction, liver cancer, cirrhosis and chronic obstructive pulmonary disease (COPD) (all non-linear p<0.05; hazard ratio [HR]; 95% confidence interval [CI]) for the lowest and the highest Hgb levels for the risk of each cause of death in male population: HR, 1.14; 95% CI, 0.98 to 1.34; HR, 2.87; 95% CI, 1.48 to 5.57; HR, 1.16; 95% CI, 0.96 to 1.40; HR, 3.05; 95% CI, 1.44 to 6.48; HR, 1.36; 95% CI, 1.18 to 1.56; HR, 2.11; 95% CI, 1.05 to 4.26; HR, 3.64; 95% CI, 2.49 to 5.33; HR, 5.97; 95% CI, 1.44 to 24.82; HR, 1.62; 95% CI, 1.14 to 2.30; HR, 3.84; 95% CI, 1.22 to 12.13, respectively), while in female population, high Hgb levels were associated with a lower risk of death from hypertension and a higher risk of death from COPD (overall p<0.05; HR, 1.86; 95% CI, 1.29 to 2.67 for the lowest Hgb levels for hypertension; overall p<0.01, HR, 6.60; 95% CI, 2.37 to 18.14 for the highest Hgb levels for COPD). For the risk of lung cancer death by Hgb levels, a linear negative association was found in male population (overall p<0.01; the lowest Hgb levels, HR, 1.17; 95% CI, 1.05 to 1.33) but an inverse J-shaped association was found in female population (non-linear p=0.01; HR, 1.25; 95% CI, 0.96 to 1.63; HR, 2.58; 95% CI, 1.21 to 5.50). Conclusions: Both low and high Hgb levels were associated with an increased risk of death from various causes, and some diseases showed different patterns according to sex.

Development of Bone Metastasis Detection Algorithm on Abdominal Computed Tomography Image using Pixel Wise Fully Convolutional Network (픽셀 단위 컨볼루션 네트워크를 이용한 복부 컴퓨터 단층촬영 영상 기반 골전이암 병변 검출 알고리즘 개발)

  • Kim, Jooyoung;Lee, Siyoung;Kim, Kyuri;Cho, Kyeongwon;You, Sungmin;So, Soonwon;Park, Eunkyoung;Cho, Baek Hwan;Choi, Dongil;Park, Hoon Ki;Kim, In Young
    • Journal of Biomedical Engineering Research
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    • v.38 no.6
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    • pp.321-329
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    • 2017
  • This paper presents a bone metastasis Detection algorithm on abdominal computed tomography images for early detection using fully convolutional neural networks. The images were taken from patients with various cancers (such as lung cancer, breast cancer, colorectal cancer, etc), and thus the locations of those lesions were varied. To overcome the lack of data, we augmented the data by adjusting the brightness of the images or flipping the images. Before the augmentation, when 70% of the whole data were used in the pre-test, we could obtain the pixel-wise sensitivity of 18.75%, the specificity of 99.97% on the average of test dataset. With the augmentation, we could obtain the sensitivity of 30.65%, the specificity of 99.96%. The increase in sensitivity shows that the augmentation was effective. In the result obtained by using the whole data, the sensitivity of 38.62%, the specificity of 99.94% and the accuracy of 99.81% in the pixel-wise. lesion-wise sensitivity is 88.89% while the false alarm per case is 0.5. The results of this study did not reach the level that could substitute for the clinician. However, it may be helpful for radiologists when it can be used as a screening tool.

The VHR Dual-Specificity Protein Tyrosine Phosphatase (DS-PTPase) Inhibitor Isolated from Gastrodia elata (천마(Gastrodia elata)로부터 분리한 VHR DS-PTPase 저해 물질)

  • Lee, Myung-Sun;Oh, Won-Keun;Bae, Eun-Young;Ahn, Soon-Cheol;Sohn, Cheon-Bae;Osada, Hiroyuki;Ahn, Jong-Seog
    • Korean Journal of Food Science and Technology
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    • v.34 no.3
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    • pp.505-509
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    • 2002
  • In the course of screening program for VHR DS-PTPase (dual-specificity protein tyrosine phosphatase) from natural sources, Gastrodia elata was selected. One compound showing potent inhibitory activity was isolated by the solvent extraction and column chromatography including silica gel, ODS RP-18, Sephades LH-20, and HPLC. This compound was identified as baicalein by several NMR techniques such as $^1H-NMR$, $^{13}C-NMR$, and DEPT. Baicalein showed selective inhibitory activity against VHR DS-PTPase with $IC_{50}=2.4\;{\mu}M$, and showed cytotoxicity against several human cancer cell lines with an $GI_{50}$ of $5.26{\sim}12.93\;{\mu}g/mL$ range, including, melanoma (LOX-IMVI), lung cancer (NCI H23 and A549), colon cancer (HCT 116 and SW 620), prostate cancer (PC-3), and leukemia (MOLT 4F).

Risk assessment of di(2-ethylhexyl) phthalate in the workplace

  • Kim, Hyeon-Yeong
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.11.1-11.6
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    • 2016
  • Objectives A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. Methods Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor ("Survey on the work environment") and by the Ministry of Environment ("Survey on the circulation amount of chemicals"). Risk was determined according to exposure in workplaces and chemical hazard. Results In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be $0.990mg/m^3$, as compared to the threshold exposure level of $5mg/m^3$. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. Conclusions DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below $5mg/m^3$ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.

Fluorometric Detection of Low-Abundance EGFR Exon 19 Deletion Mutation Using Tandem Gene Amplification

  • Kim, Dong-Min;Zhang, Shichen;Kim, Minhee;Kim, Dong-Eun
    • Journal of Microbiology and Biotechnology
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    • v.30 no.5
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    • pp.662-667
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    • 2020
  • Epidermal growth factor receptor (EGFR) mutations are not only genetic markers for diagnosis but also biomarkers of clinical-response against tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Among the EGFR mutations, the in-frame deletion mutation in EGFR exon 19 kinase domain (EGFR exon 19-del) is the most frequent mutation, accounting for about 45% of EGFR mutations in NSCLCs. Development of sensitive method for detecting the EGFR mutation is highly required to make a better screening for drug-response in the treatment of NSCLC patients. Here, we developed a fluorometric tandem gene amplification assay for sensitive detection of low-abundance EGFR exon 19-del mutant genomic DNA. The method consists of pre-amplification with PCR, thermal cycling of ligation by Taq ligase, and subsequent rolling circle amplification (RCA). PCR-amplified DNA from genomic DNA samples was used as splint DNA to conjugate both ends of linear padlock DNA, generating circular padlock DNA template for RCA. Long stretches of ssDNA harboring multiple copies of G-quadruplex structure was generated in RCA and detected by thioflavin T (ThT) fluorescence, which is specifically intercalated into the G-quadruplex, emitting strong fluorescence. Sensitivity of tandem gene amplification assay for detection of the EGFR exon 19-del from gDNA was as low as 3.6 pg, and mutant gDNA present in the pooled normal plasma was readily detected as low as 1% fraction. Hence, fluorometric detection of low-abundance EGFR exon 19 deletion mutation using tandem gene amplification may be applicable to clinical diagnosis of NSCLC patients with appropriate TKI treatment.

Screening of Anti-cancer Compounds Originated from Filamentous Fungi (Monascus sp.) (사상성 곰팡이 (Monascus sp.) 유래 항암 물질의 탐색)

  • Sin, Yeong-Min;Park, Hae-Ryoun;An, Won-Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.671-676
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    • 2005
  • In this study, we investigated the antioxidant effect of extract from Monascus pillosus, on the human wild-type p53 and p21 expressing A549 lung epithelial cell line and MCF-7 mammary adenocarcinoma cell line stimulated by NO. $P21^{waf/cip1}$ was identified as a gene induced in senescent cells. It is a cyclin-dependent kinase inhibitor and has been shown to cause cell cycle arrest and apoptosis. While p53-regulated stimulation of p21 appears to be central for the permanent growth-arrest, the role of p21 in p53-triggered cell death is unclear. Low dose of sodium nitroprusside (SNP) induced the development of senescence associated with increased expression of p53 and p21 in A549 cells. Inhibition of p21 transactivating activity requires high level correlates with the amount of p53 necessary to cause cell death. Association of p21 and p53 results in inhibition of p21-stimulated transcription. This requires a higher p53 level than is necessary for transcriptional activation of endogenous p53-responsive gene but correlates well with the level of p53 necessary to cause cell death. Exposure to W-1 inhibited oxidative stresses-induced senescence-like arrest, resulting in a significant reduction in p53 and p21 steady state levels. These results suggest that p53 and p21 play a central role in the onset of senescence. Thus, it is important to emphasize control of oxidative balance in tumor prevention and aging.

Usefulness and Limitations of Fine Needle Aspiration Cytology in Adult Cervical Lymph Node Enlargement Patients: An analysis of 342 cases (성인 경부 림프절 비대 환자들에서 미세침 흡인 세포검사법의 유용성과 문제점: 342 증례의 분석)

  • Lee, Jaeho
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.18-28
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    • 2004
  • Background : Many diseases like lung cancer and tuberculosis can involve cervical lymph node. Fine needle aspiration cytology(FNAC) was known as a useful screening test for the evaluation of enlarged lymph node. But the usefulness and limitations of FNAC according to disease category or physical characteristics of lymph node were not yet fully established. Methods : Retrospective analysis of three hundred forty two adult patients who performed FNAC due to enlarged cervical lymph nodes at the Seoul Municipal Boramae Hospital during the period from January 1999 to December 2002 and final diagnosis could be made by surgical biopsy, microbiology or clinical observation. Results : Among the 342 cases, 176(51.5 %) were finally diagnosed as benign nature ncluding reactive hyperplasia, Kikuchi's disease and acute suppuration. Eighty eight(25.7 %) were diagnosed as tuberculous lymphadenitis, 66(19.3 %) as metastasis, and 12(3.5 %) as lymphoma. Tuberculosis, metastasis, and lymphoma all showed significantly larger diameter, longer duration of lymph node enlargement. There were higher frequency of supraclavicular involvement in the cases of tuberculosis and metastasis. The overall diagnostic sensitivity of FNAC was 88.0 %, and 88.6 % in benign nature lesion, 77.3 % in tuberculosis, 90.1% in metastasis and 58.3 % in lymphoma. The diagnosis of tuberculosis was made by FNAC in 68 cases (77.3 %) among 88 cases. Lung cancer(43.9 percent) was most frequent cause of cervical lymph node metastasis. Diagnostic sensitivity of FNAC was significantly lower in the supraclavicular than other cervical lymph node(80 % vs. 91.3 %) and not correlated with disease nature, node size or number. Conclusion : Though FNAC was a reliable screening test for enlarged cervical lymph node enlargement, the diagnostic sensitivity was low in the case of lymphoma or when the enlarged lymph node was located at the supraclavicular area.