Publications by authors named "Sun-Young Kong"

155 Publications

Metabolic Effects of Gastrectomy and Duodenal Bypass in Early Gastric Cancer Patients with T2DM: A Prospective Single-Center Cohort Study.

J Clin Med 2021 Sep 4;10(17). Epub 2021 Sep 4.

Center for Gastric Cancer, National Cancer Center, Goyang 10408, Korea.

We evaluated the metabolic effects of gastrectomies and endoscopic submucosal dissections (ESDs) in early gastric cancer (EGC) patients with type 2 diabetes mellitus (T2DM). Forty-one EGC patients with T2DM undergoing gastrectomy or ESD were prospectively evaluated. Metabolic parameters in the patients who underwent gastrectomy with and without a duodenal bypass (groups 1 and 2, = 24 and = 5, respectively) were compared with those in patients who underwent ESD (control, = 12). After 1 year, the proportions of improved/equivocal/worsened glycemic control were 62.5%/29.2%/8.3% in group 1, 40.0%/60.0%/0.0% in group 2, and 16.7%/50.0%/33.3% in the controls, respectively ( = 0.046). The multivariable ordered logistic regression analysis results showed that both groups had better 1-year glycemic control. Groups 1 and 2 showed a significant reduction in postprandial glucose (-97.9 and -67.8 mg/dL), body mass index (-2.1 and -2.3 kg/m), and glycosylated hemoglobin (group 1 only, -0.5% point) (all < 0.05). Furthermore, improvements in group 1 were more prominent when preoperative leptin levels were high ( for interaction < 0.05). Metabolic improvements in both groups were also observed for insulin resistance, leptin, plasminogen activator inhibitor-1, and resistin. Gastrectomy improved glycemic control and various metabolic parameters in EGC patients with T2DM. Patients with high leptin levels may experience greater metabolic benefits from gastrectomy with duodenal bypass.
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http://dx.doi.org/10.3390/jcm10174008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432535PMC
September 2021

Clinical impact of follow-up imaging on mortality in Korean breast cancer patients: A national cohort study.

Cancer Med 2021 Sep 1;10(18):6480-6491. Epub 2021 Sep 1.

Department of Surgery, National Cancer Center, Goyang, Korea.

Background: As the incidence of breast cancer has increased and the survival rate has improved, supporting the optimal follow-up strategy has become an important issue. This study aimed to evaluate follow-up imaging usage after breast cancer surgery and the implications on mortality in Korea.

Methods: This study included 96,575 breast cancer patients diagnosed during 2002-2010 and registered in the Korea Central Cancer Registry, Statistics Korea, and Korean National Health Insurance Service. We evaluated the frequency of breast imaging (mammography and breast MRI) and systemic imaging for evaluating the presence of distant metastasis (chest CT, bone scan, and PET-CT), and performed analyses to determine if they had an effect on mortality.

Results: The median follow-up period was 72.9 months (range: 12.0-133.3) and 7.5% of the patients died. Among all patients, 54.7%, 16.2%, 45.6%, and 8.5% received 3 or more mammograms, chest CTs, bone scans, and PET-CTs within 3 years after surgery, respectively. Among patients who developed recurrence after 3 or more years, a comparison of overall mortality and breast-cancer specific mortality according to the frequency of imaging by modality (<3 vs. ≥3) showed that only mammography had significantly reduced mortality (hazard ratio [HR]: 0.72, 95% CI: 0.61-0.84, p < 0.0001; HR: 0.72, 95% CI: 0.61-0.84; p < 0.0001).

Conclusions: This study showed that only frequent mammography reduced mortality and frequent imaging follow-up with other modalities did not when compared to less frequent imaging. This finding provides supportive evidence that clinicians need to adhere to the current guidelines for surveillance after breast cancer surgery.
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http://dx.doi.org/10.1002/cam4.3873DOI Listing
September 2021

Can computed tomography scanning in adults lead to an increased risk of thyroid cancer? A nationwide nested case-control study.

Eur Radiol 2021 Jul 10. Epub 2021 Jul 10.

Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea.

Objective: To evaluate the association between computed tomography (CT) scanning and newly diagnosed thyroid cancer cases in relation to the confounding effect of the healthcare utilization rate.

Methods: This nested case-control study used the Korean National Health Insurance Service-National Sample Cohort 2002-2015: 3557 adult thyroid cancer cases were matched to 17,785 controls by age, sex, and diagnosis date. Odds ratios (ORs) were estimated for thyroid cancer associated with cumulative exposure to CT scanning > 3 years before cancer diagnosis. Changes in estimated ORs with and without adjustment for outpatient visit frequency were investigated.

Results: ORs for newly diagnosed thyroid cancer increased according to the higher number of total CT scans and thyroid-exposing CT scans (CT scans of the head, neck, or chest compartment; OR and 95% confidence interval [CI], 1.09 [1.03-1.16] and 1.28 [1.05-1.57], respectively). ORs for thyroid cancer increased according to higher outpatient visit frequency. The association between thyroid cancer incidence and CT scans became insignificant when outpatient visit frequency was adjusted in the models (OR [95% CI], 1.03 [0.97-1.10]: total CT scans, 1.14 [0.93-1.41]: thyroid-exposing CT scans). Subgroup analyses stratified by age, sex, and history of other malignancies did not reveal independent associations between CT scanning and thyroid cancer.

Conclusions: The high incidence of thyroid cancer in adults exposed to ionizing radiation during CT scanning can be largely explained by the confounding effect of the healthcare utilization rate. These effects should be considered to avoid overestimation of the CT scanning-associated risk of thyroid cancer.

Key Points: • Studies indicate that diagnostic imaging using low-ionizing radiation may increase risks for thyroid cancer in adults. • Our findings suggest that the risk for radiation-induced thyroid cancer following CT scanning in adults may have been overestimated in observational studies due to medical surveillance-related biases.
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http://dx.doi.org/10.1007/s00330-021-08186-0DOI Listing
July 2021

Increased Incidence and Associated Risk Factors of Aspergillosis in Patients with Bronchiectasis.

J Pers Med 2021 May 17;11(5). Epub 2021 May 17.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07441, Korea.

There are insufficient data regarding the relationship between non-cystic fibrosis bronchiectasis and incident aspergillosis. We performed a population-based, matched cohort study using data from the Korean National Health Insurance database between 2003 and 2013. The incidence of aspergillosis was 50/100,000 person-years in the bronchiectasis cohort and 11/100,000 person-years in the matched cohort (subdistribution hazard ratio, 4.53; 95% confidence interval (CI), 3.25-6.32). Among the bronchiectasis cohort, chronic obstructive pulmonary disease (adjusted HR, 1.95; 95% CI, 1.07-3.57), previous pulmonary tuberculosis (adjusted HR, 3.67; 95% CI, 2.03-6.64), and non-tuberculous mycobacterial pulmonary disease (adjusted HR, 11.25; 95% CI, 1.49-85.18) increased the risk of incident aspergillosis. The incidence of aspergillosis in patients with bronchiectasis was approximately 4.5-fold that in those without bronchiectasis. Comorbid pulmonary diseases-chronic obstructive pulmonary disease, previous pulmonary tuberculosis, and non-tuberculous mycobacterial pulmonary disease-significantly increased the risk of aspergillosis in patients with bronchiectasis. Our study indicates that close monitoring is warranted for aspergillosis in patients with bronchiectasis.
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http://dx.doi.org/10.3390/jpm11050422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155934PMC
May 2021

A Population-Based Analysis of / Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study.

Cancers (Basel) 2021 May 2;13(9). Epub 2021 May 2.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

In this study, we performed a comprehensive analysis of / variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in and . This study included 5433 Korean participants who were tested for genes. The variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had or PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for VUS than those of VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1-73.6%) for and 58.3% (95% CI: 43.2-73.0%) for carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4-53.9%) for and 14.9% (95% CI: 7.4-28.5%) for carriers.
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http://dx.doi.org/10.3390/cancers13092192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125125PMC
May 2021

Survival in untreated hepatocellular carcinoma: A national cohort study.

PLoS One 2021 4;16(2):e0246143. Epub 2021 Feb 4.

Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.

This study aimed to analyze the proportion, characteristics and prognosis of untreated hepatocellular carcinoma (HCC) patients in a large representative nationwide study. A cohort study was conducted using the National Health Insurance Service (NHIS) database in Korea. A total of 63,668 newly-diagnosed HCC patients between January 2008 and December 2013 were analyzed. Patients were categorized into treatment group and no treatment group using claim codes after HCC diagnosis. The proportion of untreated HCC patients was 27.6%, decreasing from 33.4% in 2008 to 24.8% in 2013. Compared to treated patients, untreated patients were more likely to be older (P < 0.001), female (P < 0.01), to have a distant SEER stage (P < 0.001), severe liver disease (P < 0.001), and lower income (P < 0.001). The fully-adjusted hazard ratio for all-cause mortality comparing untreated to treated patients was 3.11 (95% CI, 3.04-3.18). The risk of mortality was higher for untreated patients in all pre-defined subgroups, including those with distant SEER stage and those with severe liver disease. About one fourth of newly diagnosed HCC patients did not receive any HCC-specific treatment. Untreated patients showed higher risk of mortality compared to treated patients in all subgroups. Further studies are needed to identify obstacles for HCC treatment and to improve treatment rates.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246143PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861368PMC
July 2021

Body mass index change and incident asthma in adults: A nationwide cohort study.

Allergy 2021 06 23;76(6):1896-1899. Epub 2020 Dec 23.

Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1111/all.14703DOI Listing
June 2021

Analysis of laboratory parameters for optimal autologous peripheral blood stem cell collection from lymphoma and myeloma patients.

J Clin Apher 2021 Feb 28;36(1):135-142. Epub 2020 Nov 28.

Department of Laboratory Medicine, National Cancer Center, Goyang, South Korea.

Background: Peripheral blood stem cell (PBSC) collection is important for successful hematopoietic stem cell transplantation. This study aimed to investigate the laboratory parameters associated with the optimal timing of autologous PBSC collection from lymphoma and multiple myeloma patients.

Methods: We retrospectively evaluated data from 1105 PBSC apheresis procedures performed on 379 adult patients at the National Cancer Center between June 2005 and December 2019. Laboratory parameters, including cutoff values for the number of hematopoietic progenitor cells (HPCs) and circulating CD34+ cells, were analyzed to determine their association with CD34+ cell yield.

Results: The pre-apheresis HPC and CD34+ cell count were statistically significant variables associated with harvested CD34+ cell in lymphoma and MM patients. The optimal cutoff values were 18 × 10 /L for pre-HPC count (66.8% sensitivity, 66.4% specificity) and 11/μL for pre-CD34+ cell count (85.8% sensitivity, 87.2% specificity), to achieve CD34+ cell yields ≥ 1.0 × 10 /kg for each apheresis procedure. Moreover, the optimal cutoff values were 23 × 10 /L for pre-HPC count (71.0% sensitivity, 69.0% specificity) and 18/μL for pre-CD34+ cell count (87.5% sensitivity, 86.3% specificity) to achieve CD34+ cell yields ≥ 2.0 × 10 /kg for each apheresis procedure.

Conclusion: HPC count is a potential surrogate marker for monitoring the starting time for PBSC collection. Applying cutoff values for the number of HPC and CD34+ cells may be clinically useful for optimizing the timing of PBSC collection.
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http://dx.doi.org/10.1002/jca.21855DOI Listing
February 2021

Fluorescence-Combined Interferometric Scattering Imaging Reveals Nanoscale Dynamic Events of Single Nascent Adhesions in Living Cells.

J Phys Chem Lett 2020 Dec 18;11(23):10233-10241. Epub 2020 Nov 18.

Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science, Seoul 02841, Korea.

Focal adhesions (FAs) are dynamic protein nanostructures that form mechanical links between cytoskeletal actin fibers and the extracellular matrix. Here, we demonstrate that interferometric scattering (iSCAT) microscopy, a high-speed and time-unlimited imaging technique, can uncover the real-time dynamics of nanoscopic nascent adhesions (NAs). The high sensitivity and stability of the iSCAT signal enabled us to trace the whole life span of each NA spontaneously nucleated under a lamellipodium. Such high-throughput and long-term image data provide a unique opportunity for statistical analysis of adhesion dynamics. Moreover, we directly revealed that FAs play critical roles in both the extrusion of filopodia as nucleation sites on the leading edge and the one-dimensional transport of cargos along cytoskeletal fibers as fiber docking sites. These experimental results show that iSCAT is a sensitive tool for tracking real-time dynamics of nanoscopic objects involved in endogenous and exogenous biological processes in living cells.
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http://dx.doi.org/10.1021/acs.jpclett.0c02103DOI Listing
December 2020

A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis.

Br J Cancer 2021 01 18;124(1):290-298. Epub 2020 Nov 18.

College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.

Background: Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated.

Methods: Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed.

Results: In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments.

Conclusions: Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.
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http://dx.doi.org/10.1038/s41416-020-01146-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782829PMC
January 2021

Reclassification of and variants found in ovarian epithelial, fallopian tube, and primary peritoneal cancers.

J Gynecol Oncol 2020 Nov;31(6):e83

Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.

Objective: We investigated the proportions of and reclassified variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers.

Methods: Data from 805 patients who underwent genetic testing for from January 1, 2006 to August 31, 2018 were included. The VUS in were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines.

Results: A pathogenic variant was found in 17.0% (137/805) of the patients, and VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a pathogenic variant and 18.4% (148/805) of the patients possessed VUS. Fifty-three specific VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For , 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants.

Conclusions: Approximately 33.3% (36/108) of the specific variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.
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http://dx.doi.org/10.3802/jgo.2020.31.e83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593220PMC
November 2020

Comparison of spectra optia and amicus cell separators for autologous peripheral blood stem cell collection.

J Clin Apher 2021 Feb 3;36(1):28-33. Epub 2020 Sep 3.

Department of Laboratory Medicine, National Cancer Center, Goyang, South Korea.

Introduction: Autologous peripheral blood stem cell (PBSC) transplantation has become a standard treatment option for many oncology patients. The aim of this study was to evaluate the performance of two cell separators, Spectra Optia (Terumo BCT, Japan) and Amicus (Fresenius-Kabi) for autologous PBSC collection.

Methods: We retrospectively evaluated 56 apheresis by Spectra Optia with Continuous Mononuclear Cell Collection (cMNC) from 20 patients, and 50 apheresis by Amicus from 27 patients between December 2018 and December 2019. CD34+ collection efficiency (CE2) and platelet (PLT) loss were evaluated.

Results: There was no significant difference in CD34+ CE2 between Spectra Optia with cMNC (median, 28.8%) and Amicus (median, 33.1%; P = 0.537). PLT loss was significantly lower in Amicus (median, 28.6%) than in Spectra Optia with cMNC (median, 37.8%; P = 0.009).

Conclusion: CD34+ CE2 was comparable between Spectra Optia and Amicus, and PLT loss was significantly lower in Amicus. To the best of our knowledge, this is the first report comparing autologous PBSC collection of the Spectra Optia and Amicus. These results may provide general guidance with regard to device selection to apheresis clinics that use both separators for optimal outcomes depending on each patient's characteristics.
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http://dx.doi.org/10.1002/jca.21835DOI Listing
February 2021

Exon splicing analysis of intronic variants in multigene cancer panel testing for hereditary breast/ovarian cancer.

Cancer Sci 2020 Oct 2;111(10):3912-3925. Epub 2020 Sep 2.

Division of Translational Science, Research Institute, National Cancer Center, Goyang, Korea.

The use of multigene panel testing for patients with a predisposition to breast/ovarian cancer is increasing as the identification of variants is useful for diagnosis and disease management. We identified pathogenic and likely pathogenic (P/LP) variants of high-and moderate-risk genes using a 23-gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P/LP variants was 12.4% (64/518) for high- and moderate-penetrant genes, namely, BRCA2 (5.6%), BRCA1 (3.3%), CHEK2 (1.2%), MUTYH (0.8%), PALB2 (0.8%), MLH1 (0.4%), ATM (0.4%), BRIP1 (0.4%), TP53 (0.2%), and PMS2 (0.2%). Five patients possessed two P/LP variants in BRCA1/2 and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT-PCR product sequences in six P/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P/LP intronic variants in BRCA1, BRIP1, CHEK2, PARB2, and PMS2. Notably, we identified an in-frame deletion of the BRCA1 C-terminal (BRCT) domain by exon skipping in BRCA1 c.5152+6T>C-as known VUS-indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.
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http://dx.doi.org/10.1111/cas.14600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540976PMC
October 2020

The relationships between systemic cytokine profiles and inflammatory markers in colorectal cancer and the prognostic significance of these parameters.

Br J Cancer 2020 08 3;123(4):610-618. Epub 2020 Jun 3.

Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.

Background: Immunomodulatory cytokines and systemic inflammatory markers are important during cancer development and progression. This study investigated the association and prognostic impact of systemic cytokine profiles and inflammatory markers in colorectal cancer (CRC).

Methods: Interleukin (IL)-1β, IL-6, IL-8, IL-9, IL-10, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) serum levels were measured using multiplex bead assays in CRC patients. Data on systemic inflammatory markers, such as the modified Glasgow prognostic score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI) and fibrinogen, were collected. Survival analysis was performed to identify factors associated with progression-free survival (PFS) and overall survival (OS).

Results: There were moderate-to-strong correlations within serum cytokines, as well as within systemic inflammatory markers, whereas the associations between serum cytokines and systemic inflammatory markers were generally weak. IL-8 and the LMR were independent significant prognostic factors for PFS and OS. The low IL-8 and high LMR group had the best survival (both PFS and OS) of all groups.

Conclusions: Systemic cytokine profiles and inflammatory markers have relatively weak intergroup correlations. A composite classification of systemic cytokine profiles and inflammatory markers has an enhanced prognostic value in CRC.
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http://dx.doi.org/10.1038/s41416-020-0924-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435263PMC
August 2020

CYFRA 21-1 levels in cerebrospinal fluid as a putative therapeutic monitoring biomarker for patients with leptomeningeal carcinomatosis: A pilot study.

Cancer Biomark 2020 ;28(1):81-89

Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.

Background: To investigate the feasibility of cerebrospinal fluid (CSF) CYFRA 21-1 levels as a therapeutic monitoring biomarker in leptomeningeal carcinomatosis (LMC) patients undergoing ventriculo-lumbar perfusion (VLP) chemotherapy.

Methods: The levels of CYFRA 21-1 in 42 CSF samples from 15 LMC patients were analyzed using an electrochemiluminescence immunoassay. Samples were collected at individual time points during VLP chemotherapy. Therapeutic outcomes were measured as improvements in the Karnofsky Performance Status (KPS) score and decreasing intracranial pressure (ICP) as the main endpoint of VLP chemotherapy. Changes in CSF CYFRA 21-1 levels, protein levels, and cytology results were also investigated. We subsequently evaluated whether these changes were correlated with KPS score and ICP.

Results: The CSF CYFRA 21-1 levels at individual time points were associated with KPS score and ICP. The KPS scores (p= 0.007) and ICP (p= 0.018) of patients with high CSF CYFRA 21-1 levels were significantly different from those of patients with low CSF CYFRA 21-1 levels. By contrast, CSF protein levels and cytological responses were not significantly associated with KPS scores and ICP.

Conclusions: CSF CYFRA 21-1 may have utility as a therapeutic monitoring biomarker to design personalized therapeutic strategies in LMC patients undergoing VLP chemotherapy.
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http://dx.doi.org/10.3233/CBM-190187DOI Listing
February 2021

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.

Nat Commun 2020 03 5;11(1):1217. Epub 2020 Mar 5.

Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
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http://dx.doi.org/10.1038/s41467-020-15046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057957PMC
March 2020

Development of an Automated Image Analyzer for Microvessel Density Measurement in Bone Marrow Biopsies.

Ann Lab Med 2020 Jul;40(4):312-316

Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea.

Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and an increase in MVD can be used as a marker of poor prognosis in MM patients. We developed an automated image analyzer to assess MVD from images of BM biopsies stained with anti-CD34 antibodies using two color models. MVD was calculated by merging images from the red and hue channels after eliminating non-microvessels. The analyzer results were compared with those obtained by two experienced hematopathologists in a blinded manner using the 84 BM samples of MM patients. Manual assessment of the MVD by two hematopathologists yielded mean±SD values of 19.4±11.8 and 20.0±11.8. The analyzer generated a mean±SD of 19.5±11.2. The intraclass correlation coefficient (ICC) and Bland-Altman plot of the MVD results demonstrated very good agreement between the automated image analyzer and both hematopathologists (ICC=0.893 [0.840-0.929] and ICC=0.906 [0.859-0.938]). This automated analyzer can provide time- and labor-saving benefits with more objective results in hematology laboratories.
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http://dx.doi.org/10.3343/alm.2020.40.4.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054689PMC
July 2020

Reliability and Validity of the Korean Language Version of the U.S. National Cancer Institute's Patient-Reported Outcomes Common Terminology Criteria for Adverse Events.

J Pain Symptom Manage 2020 05 8;59(5):1082-1088.e6. Epub 2020 Feb 8.

Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland, USA.

Context: To improve precision and accuracy in the capture of symptomatic adverse events (AEs) by self-report, the U.S. National Cancer Institute has developed a library of 124 patient-reported outcome (PRO) items reflecting 78 symptomatic AEs drawn from the Common Terminology Criteria for Adverse Events (CTCAE). The PRO-CTCAE™ item library has been translated and linguistically validated in the Korean language.

Objectives: The aim of this study was to examine the psychometric properties of PRO-CTCAE-Korean.

Methods: PRO-CTCAE-Korean and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core 30 (QLQ-C30) were administered to 1358 Korean-speaking individuals receiving treatment for cancer at two medical centers in Korea (mean age 55.1 years; SD ±11.9; 60% females; and 61% high school education or less). A subset of 82 study participants completed the same two measures on a second occasion approximately three days later.

Results: Correlations between PRO-CTCAE-Korean and conceptually relevant QLQ-C30 items were all greater than r = 0.30 except for headache severity. Most PRO-CTCAE-Korean items correlated at least moderately with QLQ-C30 summary scores. Monotonically decreasing total QLQ-C30 scores were observed across worsening levels of symptom frequency, severity, and interference (all P < 0.01), indicating that PRO-CTCAE-Korean response choices are well comprehended, and that PRO-CTCAE-Korean discriminates respondents with different levels of symptom burden. PRO-CTCAE-Korean also demonstrated generally acceptable to good reliability (88% of items intraclass correlation coefficient >0.50).

Conclusion: PRO-CTCAE-Korean is a reliable and valid instrument to capture symptomatic AEs by self-report in patients on cancer clinical trials.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.01.015DOI Listing
May 2020

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test.

Cancer Res Treat 2020 Jul 4;52(3):697-713. Epub 2020 Feb 4.

Department of Surgery, Seoul National University Hospital, Seoul, Korea.

Purpose: Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an next-generation sequencing (NGS)-based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).

Materials And Methods: A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.

Results: Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.

Conclusion: NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.
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http://dx.doi.org/10.4143/crt.2019.559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373875PMC
July 2020

Use of Gadoxetic Acid-enhanced Liver MRI and Mortality in More than 30 000 Patients with Hepatocellular Carcinoma: A Nationwide Analysis.

Radiology 2020 04 4;295(1):114-124. Epub 2020 Feb 4.

From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (T.W.K., Y.K.K., S.H.K.); Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, South Korea (S.Y.K., E.S.L., S.M.W.); Department of Laboratory Medicine, Hospital, National Cancer Center, Goyang, South Korea (S.Y.K.); Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea (D.K., E.G., J.C.); Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (D.K., M.W.K., E.G., J.C.); Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (D.H.S.); National Cancer Control Institute, National Cancer Center, Goyang, South Korea (Y.A.K., K.S.C.); Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea (K.S.C.); Center for Breast Cancer, Hospital, National Cancer Center, Goyang, South Korea (E.S.L.); Center for Liver Cancer, Hospital, National Cancer Center, Goyang, South Korea (S.M.W.); Health Insurance Policy Research Institute, National Health Insurance Service, Wonju, South Korea (J.H.B.); and Department of Epidemiology, and Welch Center for Epidemiology, Prevention, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 E Monument St, Baltimore, MD 21205 (E.G., J.C.).

Background The impact on survival of gadoxetic acid-enhanced MRI in addition to multiphase contrast material-enhanced CT for initial staging in patients with hepatocellular carcinoma (HCC) is unknown. Purpose To compare all-cause mortality in patients with HCC who underwent CT only, CT plus non-gadoxetic acid-enhanced MRI, or CT plus gadoxetic acid-enhanced MRI as part of their initial diagnostic work-up. Materials and Methods The authors performed a nationwide retrospective cohort study of patients diagnosed with HCC in South Korea between January 2008 and December 2010. Follow-up extended through December 2014. The primary outcome was all-cause mortality. Cox proportional hazards regression model with adjustment of confounding factors was used to estimate hazard ratios (HRs) for all-cause mortality. Results Among 30 023 patients with HCC (mean age ± standard deviation, 58.5 years ± 10.7, 23 978 men), the proportions of patients in whom HCC was diagnosed using CT only, CT plus non-gadoxetic acid-enhanced MRI, and CT plus gadoxetic acid-enhanced MRI were 56.1%, 12.9%, and 31.0%, respectively. In adjusted analysis using CT only as the reference category, the HR for mortality for CT plus gadoxetic acid-enhanced MRI was 0.64 (95% confidence interval [CI]: 0.62, 0.67; < .001), and the HR for CT plus non-gadoxetic acid-enhanced MRI was 0.71 (95% CI: 0.68, 0.75; < .001). Use of CT plus gadoxetic acid-enhanced MRI was associated with lower mortality compared with CT plus non-gadoxetic acid-enhanced MRI (adjusted HR, 0.90; 95% CI: 0.85, 0.95; < .001), but this survival advantage was restricted to patients with localized disease. Conclusion In patients with hepatocellular carcinoma, additional use of contrast-enhanced MRI was associated with lower mortality. Furthermore, CT plus gadoxetic acid-enhanced MRI was associated with better survival than CT plus non-gadoxetic acid-enhanced MRI but only in patients with localized disease. © RSNA, 2020 See also the editorial by Kim in this issue.
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http://dx.doi.org/10.1148/radiol.2020190639DOI Listing
April 2020

Views on Precision Medicine among Health Professionals in Korea: A Mixed Methods Study.

Yonsei Med J 2020 Feb;61(2):192-197

Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.

This study aimed to investigate awareness, attitudes, and perspectives on precision medicine among health professionals in Korea and to identify issues that need to be addressed before implementing precision medicine. Mixed methods research was applied. For qualitative research, a semi-structured focus group interview was conducted with six health professionals. For quantitative research, a self-reported survey was administered. A total of 542 health professionals participated in the survey, and 526 completed the entire questionnaire. Health professionals showed positive attitudes toward precision medicine. About 95-96% of respondents agreed that precision medicine will be effective in treatment and precise diagnosis, and 69.9% reported that they would participate as study subjects. Meanwhile, they expressed concerns regarding educating patients and health professionals in precision medicine and developing research and data sharing infrastructure. Also, they emphasized the importance of developing precision medicine in an equitable way. Despite varying levels of awareness of precision medicine, the health professionals expressed a willingness to engage in precision medicine research, and recommended that health professionals work closely with policymakers to design precision medicine in a way that can be effectively adopted. Health professionals showed had a positive, but cautious, attitude toward precision medicine. The results of this study suggest areas to be addressed before ushering in precision medicine in Korea.
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http://dx.doi.org/10.3349/ymj.2020.61.2.192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992457PMC
February 2020

Aspirin Use Is Not Associated with Lower Thyroid Cancer Risk: A Nationwide Nested Case-Control Study.

Thyroid 2020 06 14;30(6):829-837. Epub 2020 Feb 14.

Department of Laboratory Medicine, National Cancer Center, Goyang, Republic of Korea.

While aspirin use is known to be associated with reduced incidence of various cancer types, it is unclear whether this benefit extends to thyroid cancer. We aimed to evaluate the association between aspirin use and thyroid cancer development. This nested case-control study used nationwide data from the Korean National Health Insurance Service-National Sample Cohort 2002-2015. In total, 4547 individuals with newly developed thyroid cancer were matched with 13,641 controls based on age, sex, and follow-up period. Odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid cancer development according to aspirin use were analyzed using a multivariable conditional logistic regression model. The number of days for which patients with thyroid cancer used aspirin (the proportions of no use, <30 days/year, 30-90 days/year, and ≥90 days/year were 93.03%, 6.51%, 0.31%, and 0.15%, respectively) was comparable with that of the controls ( = 0.371, chi-squared test). The risk of thyroid cancer development was not associated with the duration of aspirin use (ORs [CI] for aspirin use <30 days/year, 30-90 days/year, and ≥90 days/year were 1.11 [0.96-1.28], 1.01 [0.54-1.88], and 1.23 [0.50-3.06], respectively, compared with no use) after adjusting for body mass index, smoking status, hypertension, Charlson comorbidity index, and number of outpatient visits per year. In addition, subgroup analyses stratified by age, sex, and follow-up duration did not reveal any significant association between aspirin use and thyroid cancer. Our findings suggest that even extended aspirin use may not impact the prevention or onset of thyroid cancer.
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http://dx.doi.org/10.1089/thy.2019.0641DOI Listing
June 2020

Comparison of ABO isoagglutinin titres by three different methods: tube haemagglutination, micro-column agglutination and automated immunohematology analyzer based on erythrocyte-magnetized technology.

Vox Sang 2020 Apr 26;115(3):233-240. Epub 2019 Dec 26.

Department of Laboratory Medicine, National Cancer Center, Goyang, Korea.

Background And Objectives: ABO isoagglutinin titre is important for evaluating and monitoring ABO-incompatible (ABOi) stem cells or solid organ transplantations. There are several methods to measure the titre level, including the tube haemagglutination method, micro-column agglutination and erythrocyte-magnetized technology (EMT). However, few studies have reported isoagglutinin measured by EMT. Here, we compared the isoagglutinin titre of normal individuals obtained by an automated instrument with that obtained by conventional manual methods to evaluate the feasibility of replacing the manual method with the automated instrument.

Materials And Methods: The ABO isoagglutinin titre was measured on residual samples of healthy individuals who visited the health promotion centre of the National Cancer Center, Korea, from April to October 2015. Samples from 120 patients were collected, which included 20 males and 20 females for each blood group (A, B and O). IgM and IgG ABO isoagglutinin titres of each blood group were measured by the tube haemagglutination, micro-column agglutination and EMT techniques. The median (minimum-maximum) titres were compared, and the concordance between two methods was evaluated with the rate of results showing within one titre difference.

Results: The median ABO IgM and IgG titres of all blood groups obtained by the EMT method were higher than that obtained by the conventional tube haemagglutination and micro-column agglutination.

Conclusion: The agreement between the two methods was comparable in case of IgM but low in IgG.
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http://dx.doi.org/10.1111/vox.12878DOI Listing
April 2020

Genetic Counseling Status and Perspectives Based on a 2018 Professional Survey in Korea.

Ann Lab Med 2020 May;40(3):232-237

Department of Laboratory Medicine, National Health Insurance Service, Ilsan Hospital, Goyang, Korea.

Background: Genetic counseling (GC) provides many benefits, including the identification of patients appropriate for testing, patient education, and medical management. We evaluated the current status of and challenges faced by GC practitioners in Korean hospitals.

Methods: An electronic survey was designed and conducted in 52 certified laboratory physicians belonging to the Korean Society of Laboratory Medicine, from August to September 2018. The questionnaires addressed three main categories of information: (1) current status of GC in hospitals; (2) essential qualifications of GC practitioners; and (3) challenges and perspectives for GC. Fisher's exact test was applied to analyze categorical data.

Results: Among a total of 52 participants who initially responded, 12 (23.1%) were performing GC either by direct or indirect care. GC clinics were opened regularly for one (33.3%) or more than three sessions (25.0%) per week; most respondents spent more time for pre-visit activities than in-person visits, both for a initial visit patient and for a follow-up visit patient. All laboratory physicians provided genetic information to their patients. Most recommended family genetic testing when indicated (91.7%), discussed disease management (75.0%), and/or ordered additional genetic testing (58.3%), and some referred patients to other specialists (8.3%).

Conclusions: Both patients and laboratory physicians concede the advantage of GC performed by clinical geneticists; however, the practice of GC involves several challenges and raises some concerns. The cost and support required to implement GC need to be addressed in order to provide qualified GC in Korea.
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http://dx.doi.org/10.3343/alm.2020.40.3.232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933060PMC
May 2020

Analysis of factors associated with successful allogeneic peripheral blood stem cell collection in healthy donors.

Transfus Apher Sci 2020 Apr 24;59(2):102679. Epub 2019 Nov 24.

Department of Laboratory Medicine, National Cancer Center, Goyang, South Korea. Electronic address:

Background: The collection of a sufficient number of stem cells is important for success of allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the factors associated with successful allogeneic peripheral stem cell (PBSC) collection in healthy donors.

Methods: We retrospectively reviewed clinical data of allogeneic PBSC collection in 175 donors from 2007 to 2017 at the National Cancer Center, Korea. This study analyzed factors associated with the CD34+ cell yield such as the characteristics of donors, including age, laboratory results before apheresis, and data of procedures on the first day. The CD34+ cell dose of ≥ 4.0 × 10/kg have recently been the accepted minimum recommended dose in allogeneic HSCT settings, and this was the target dose in our study.

Results: The factors associated with the CD34+ cell yield were age (p = 0.007), baseline platelet (PLT) (p = 0.014), and pre-collection hematopoietic progenitor cells (HPCs) (p = 0.001) by multivariate analysis. This study represented that age, baseline platelet count, and pre-collection HPC count are important predictive factors as shown in other previous studies.

Conclusion: Our data suggest that young age, high baseline platelet counts and high HPC counts before collection might be useful for identifying successful mobilizers.
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http://dx.doi.org/10.1016/j.transci.2019.102679DOI Listing
April 2020

Circulating tumor DNA as a prognostic indicator in resectable pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Sci Rep 2019 11 18;9(1):16971. Epub 2019 Nov 18.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in various cancers. Due to the high recurrence rate of resectable pancreatic ductal adenocarcinoma (PDAC), effective strategies for prognostic stratification are necessary. Yet, for resectable PDAC, prognostic impact of ctDNA lacks systemic evidence. We sought to investigate the prognostic significance of baseline ctDNA and postoperative ctDNA in patients with resectable PDAC. PubMed, EMBASE, and the Cochrane library were searched up to March 2019. Five studies met the inclusion criteria, and 375 patients were pooled for the meta-analysis. Positive ctDNA significantly indicated poor overall survival (at baseline, hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.13-4.56; postoperative, HR 3.66, 95% CI 1.45-9.28). Patients with detectable ctDNA showed the trend to have higher risk for disease recurrence than those without detectable ctDNA (at baseline, HR 1.96, 95% CI 0.65-5.87; postoperative, HR 2.20, 95% CI 0.99-4.87). The results were consistent regardless of pre- or post-operative ctDNA. There was no significant heterogeneity among the included studies. In conclusion, our meta-analysis revealed that ctDNA, either at baseline or postoperative, might be a useful prognostic biomarker for stratifying risk of death and recurrence in resectable PDAC.
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http://dx.doi.org/10.1038/s41598-019-53271-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861312PMC
November 2019

Genomic Characteristics of Triple-Negative Breast Cancer Nominate Molecular Subtypes That Predict Chemotherapy Response.

Mol Cancer Res 2020 02 8;18(2):253-263. Epub 2019 Nov 8.

Bioinformatics Analysis Team, Research Institute, National Cancer Center, Goyang, Republic of Korea.

The heterogeneity of triple-negative breast cancer (TNBC) poses difficulties for suitable treatment and leads to poor outcome. This study aimed to define a consensus molecular subtype (CMS) of TNBC and thus elucidate genomic characteristics and relevant therapy. We integrated the expression profiles of 957 TNBC samples from published datasets. We identified genomic characteristics of subtype by exploring the pathway activity, microenvironment, and clinical relevance. In addition, drug response (DR) scores ( = 181) were computationally investigated using chemical perturbation gene signatures and validated in our own patient with TNBC ( = 38) who received chemotherapy and organoid biobank data ( = 64). Subsequently, cooperative functions with drugs were also explored. Finally, we classified TNBC into four CMSs: stem-like; mesenchymal-like; immunomodulatory; luminal-androgen receptor. CMSs also elucidated distinct tumor-associated microenvironment and pathway activities. Furthermore, we discovered metastasis-promoting genes, such as secreted phosphoprotein 1 by comparing with primary. Computational DR scores associated with CMS revealed drug candidates ( = 18), and it was successfully evaluated in cisplatin response of both patients and organoids. Our CMS recapitulated in-depth functional and cellular heterogeneity encompassing primary and metastatic TNBC. We suggest DR scores to predict CMS-specific DRs and to be successfully validated. Finally, our approach systemically proposes a relevant therapeutic prediction model as well as prognostic markers for TNBC. IMPLICATIONS: We delineated the genomic characteristic and computational DR prediction for TNBC CMS from gene expression profile. Our systematic approach provides diagnostic markers for subtype and metastasis verified by machine-learning and novel therapeutic candidates for patients with TNBC.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-0453DOI Listing
February 2020

Night-shift work and risk of breast cancer in Korean women.

Clin Epidemiol 2019 21;11:743-751. Epub 2019 Aug 21.

Department of Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.

Purpose: This study evaluated the association between night-shift work (NSW) and breast cancer risk as well as subtypes of breast cancer in Korean women.

Patients And Methods: The study population included 1721 female breast cancer cases and 1721 female controls matched by age. The subtypes of breast cancer were determined based on estrogen, progesterone, and human epidermal growth factor receptor 2 statuses by reviewing pathology reports. Odds ratios (ORs) for NSW experience, age at commencement of NSW, frequency, and duration were estimated using conditional logistic regression and were adjusted for confounders such as parity and socioeconomic status-related factors.

Results: Among 1721 pairs, 10.58% of cases and 9.59% of controls had ever engaged in NSW. NSW was not associated with breast cancer risk in terms of ever having night-shift exposure (adjusted OR was 1.11, 95% confidence interval [CI] =0.89-1.40), duration, frequency, or cumulative working time. The OR for >10 years of lifetime duration of NSW was 1.55 (95% CI 0.89-2.69, =0.124). In addition, the OR for >35,000 hrs for cumulative frequency of night work was OR=1.42 (95% CI=0.73-2.74, =0.304). There was no heterogeneity in ORs of ever having NSW and cumulative duration of NSW between four subtypes of breast cancer.

Conclusion: NSW including long-term and heavy working exposure was not associated with breast cancer risk.
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http://dx.doi.org/10.2147/CLEP.S199521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709512PMC
August 2019

Development of Patient-Derived Preclinical Platform for Metastatic Pancreatic Cancer: PDOX and a Subsequent Organoid Model System Using Percutaneous Biopsy Samples.

Front Oncol 2019 13;9:875. Epub 2019 Sep 13.

Division of Convergence Technology, Research Institute of National Cancer Center, Goyang, South Korea.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignant tumor and more than 50% patients are diagnosed at metastatic stage. The preclinical model systems that reflect the genetic heterogeneity of metastatic tumors are urgently needed to guide optimal treatment. This study describes the development of patient-derived preclinical platform using very small sized-percutaneous liver gun biopsy (PLB) of metastatic pancreatic cancer, based on patient-derived xenograft (PDX)-mediated tissue amplification and subsequent organoid generation. To increase the success rate and shorten the tumor growth period, patient-derived orthotopic xenograft (PDOX) model was developed to directly implant threadlike PLB samples into the pancreas. The engraftment success rate of PDOX samples from 35 patients with metastatic PDAC was 47%, with these samples showing the potential to metastasize to distant organs, as in patients. The PDOX models retained the genetic alterations and histopathological features of the primary tumors. Tumor organoids were subsequently generated from first passage cancer cells isolated from F1 tumor tissue of PDOX that preserve the epithelial cancer characteristics and KRAS mutations of primary tumors. The response to gemcitabine of PDOX-derived organoids correlated with clinical outcomes in corresponding patients as well as PDOX models , suggesting that this PDOX-organoid system reflects clinical conditions. Collectively, these findings indicate that the proposed PDOX-organoid platform using PLB samples assessed both and could predict drug response under conditions closer to those found in actual patients, as well as enhancing understanding of the complexity of metastatic PDAC.
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http://dx.doi.org/10.3389/fonc.2019.00875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753223PMC
September 2019
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