Publications by authors named "Eun Sook Lee"

296 Publications

0Reactive oxygen species-responsive dendritic cell-derived exosomes for rheumatoid arthritis.

Acta Biomater 2021 Apr 17. Epub 2021 Apr 17.

School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address:

Although tolerogenic dendritic cell-derived exosomes (tolDex) have emerged as promising therapeutics for rheumatoid arthritis (RA), their clinical applications have been hampered by their poor in vivo disposition after systemic administration. Herein, we report the development of stimuli-responsive tolDex that induce lesion-specific immunoregulation in RA. Responsiveness to reactive oxygen species (ROS), a physiological stimulus in the RA microenvironment, was conferred on tolDex by introducing a thioketal (TK) linker-embedded poly(ethylene glycol) (PEG) on tolDex surface via hydrophobic insertion. The detachment of PEG following overproduction of ROS facilitates the cellular uptake of ROS-responsive tolDex (TKDex) into activated immune cells. Notably, TolDex and TKDex downregulated CD40 in mature dendritic cells (mDCs) and regulated secretion of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at cellular level. In collagen-induced arthritis (CIA) mouse model, PEG prolonged the blood circulation of TKDex following intravenous administration and enhanced their accumulation in the joints. In addition, TKDex decreased IL-6, increased transforming growth factor-β, and induced the CD4CD25Foxp3 regulatory T cells in CIA mice. Overall, ROS-responsive tolDex might have potential as therapeutic agents for RA. Statement of Significance: Tolerogenic dendritic cell-derived exosomes (tolDex) are emerging immunoregulators of autoimmune diseases, including rheumatoid arthritis (RA). However, their lack of long-term stability and low targetability are still challenging. To overcome these issues, we developed reactive oxygen species (ROS)-responsive tolDex (TKDex) by incorporating the ROS-sensitive functional group-embedded poly(ethylene glycol) linker into the exosomal membrane of tolDex. Surface-engineered TKDex were internalized in mature DCs because of high ROS-sensitivity and enhanced accumulation in the inflamed joint in vivo. Further, for the first time, we investigated the potential mechanism of action of tolDex relevant to CD40 downregulation and attenuation of tumor necrosis factor (TNF)-α secretion. Our strategy highlighted the promising nanotherapeutic effects of stimuli-sensitive TolDex, which induces immunoregulation.
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http://dx.doi.org/10.1016/j.actbio.2021.04.026DOI Listing
April 2021

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea.

Cancer Res Treat 2021 Apr 15;53(2):323-329. Epub 2021 Mar 15.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.
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http://dx.doi.org/10.4143/crt.2020.1256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053855PMC
April 2021

Analysis of the tumor characteristics in young age breast cancer patients using collaborative stage data of the Korea Central Cancer Registry.

Breast Cancer Res Treat 2021 Feb 18. Epub 2021 Feb 18.

Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408, Korea.

Purpose: This study aimed to evaluate tumor characteristics in young age (20-39 years old) breast cancer (YABC) patients in Korea.

Materials And Methods: We identified 10,897 breast cancer patients from 2010 to 2015. The data were collected through 10% systematic sampling of the Korea National Cancer Incidence Database (KNCI DB). Tumor size, lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were collected according to the Collaborative Stage version 2 (CSv2) Data Collection System.

Results: Of the 10,897 patients, 1245 (11.4%) were YABC patients. They were found to have larger tumors (T2: 41.6% in 20-39 age group vs 36.4% in 40-49 age group vs 36.5% in 50-59 age group vs 38.4% in ≥ 60 age group; T3: 10.1% vs 7.3% vs 6.5% vs 6.2%, P < .0001), greater rates of lymph node involvement (41.2% vs 32.7% vs 35.7% vs 32.5%, P < .0001), higher tumor grade (High grade: 26.8% vs 19.4% vs 23.5% vs 22.1%, P < .0001), and a larger proportion of triple-negative subtype (18.2% vs 11.0% vs 12.2% vs 13.5%, P < .0001). Compared to the 40-49 age group, breast cancer-related survival (BCRS) rates were worse (91.74% vs 95.04%, P < .0001), and the characteristics of YABC patients were associated with higher risk of death from breast cancer.

Conclusion: YABC patients have more aggressive tumor characteristics and worse survival rates. Therefore, we need to identify high-risk groups among YABC patients and support active surveillance in them. These findings from a national cohort provide important information for establishing a national cancer care strategy to manage YABC patients.
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http://dx.doi.org/10.1007/s10549-021-06107-9DOI Listing
February 2021

Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score.

NPJ Breast Cancer 2021 Feb 12;7(1):13. Epub 2021 Feb 12.

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

Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.
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http://dx.doi.org/10.1038/s41523-021-00221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881194PMC
February 2021

Building a Diverse Workforce and Thinkforce to Reduce Health Disparities.

Int J Environ Res Public Health 2021 02 7;18(4). Epub 2021 Feb 7.

Xavier University of Louisiana, New Orleans, LA 70125, USA.

The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the "workforce") and the harnessing of the heterogeneity of thought (the "thinkforce") to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success.
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http://dx.doi.org/10.3390/ijerph18041569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915161PMC
February 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
February 2021

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

Ann Surg Oncol 2021 Jan 25. Epub 2021 Jan 25.

Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM.

Methods: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database.

Results: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively.

Conclusions: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.
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http://dx.doi.org/10.1245/s10434-021-09591-xDOI Listing
January 2021

Criteria for identifying residual tumours after neoadjuvant chemotherapy of breast cancers: a magnetic resonance imaging study.

Sci Rep 2021 Jan 12;11(1):634. Epub 2021 Jan 12.

Division of Surgery, Center for Breast Cancer, National Cancer Center, Goyang, Korea.

We investigated magnetic resonance imaging (MRI) criteria identifying residual tumours in patients with triple-negative and human epidermal growth factor receptor type 2-positive (HER2+) breast cancer following neoadjuvant chemotherapy. Retrospectively, 290 patients were included who had undergone neoadjuvant chemotherapy and definitive surgery. Clinicopathological features, as well as lesion size and lesion-to-background parenchymal signal enhancement ratio (SER) in early- and late-phase MRIs, were analysed. Receiver operating characteristic (ROC) analyses evaluated diagnostic performances. Maximal MRI values showing over 90% sensitivity and negative predictive value (NPV) were set as cut-off points. Identified MRI criteria were prospectively applied to 13 patients with hormone receptor-negative (HR-) tumours. The lesion size in HR-HER2-tumours had the highest area under the ROC curve value (0.92), whereas this parameter in HR + HER2 + tumours was generally low (≤ 0.75). For HR-tumours, both sensitivity and NPV exceeded the 90% threshold for early size > 0.2 cm (HR-HER2-) or > 0.1 cm (HR-HER2 +), late size > 0.4 cm, and early SER > 1.3. In the prospective pilot cohort, the criteria size and early SER did not find false negative cases, but one case was false negative with late SER. Distinguishing residual tumours based on MRI is feasible in selected triple-negative and HER2 + breast cancer patients.
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http://dx.doi.org/10.1038/s41598-020-79743-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804856PMC
January 2021

Engineering approaches for effective therapeutic applications based on extracellular vesicles.

J Control Release 2021 Feb 2;330:15-30. Epub 2020 Dec 2.

School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea; Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Republic of Korea; ExoStemTech Inc., Ansan 15588, Republic of Korea. Electronic address:

The biological significance of extracellular vesicles (EVs) as intercellular communication mediators has been increasingly revealed in a wide range of normal physiological processes and disease pathogenesis. In particular, regenerative and immunomodulatory EVs hold potential as innate biotherapeutics, whereas pathological EVs are considered therapeutic targets for inhibiting their bioactivity. Given their ability to transport functional cargos originating from the source cells to target cells, EVs can also be used as a therapeutic means to deliver drug molecules. This review aims to provide an updated overview of the key engineering approaches for better exploiting EVs in disease intervention. The emphasis is lying on the preconditioning methods for therapeutic EVs, drug loading and targeting technologies for carrier EVs, and activity control strategies for pathological EVs.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.062DOI Listing
February 2021

The Association between Alcohol Drinking Patterns and Health-Related Quality of Life in the Korean Adult Population: Effects of Misclassification Error on Estimation of Association.

Int J Environ Res Public Health 2020 10 23;17(21). Epub 2020 Oct 23.

College of Nursing, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongsangnam-do 52727, Korea.

The purpose of this study was to investigate the association between drinking patterns and health-related quality of life (HRQoL) in the Korean general population and to validate the estimation of the association of alcohol use on HRQoL when former drinkers are separated from never drinkers and low-risk drinkers depending on gender. Data were collected from 23,055 adults (over 19 years old) who completed the Korean National Health and Nutritional Examination Survey (2010-2013). Multivariate logistic and linear regression analyses were performed to investigate the association between drinking patterns and HRQoL. When former drinkers were separated from never drinkers and low-risk drinkers to control for misclassification bias, there were gender differences in the associations between alcohol use and HRQoL. Although the estimation of the association of alcohol use was not valid in men, the estimation of association was valid in women, as low-risk women drinkers showed better HRQoL than nondrinkers. Therefore, when conducting research related to alcohol and health, analyses should correct for the various confounding variables and minimize the misclassification bias of drinking patterns. It is also necessary to consider gender characteristics when intervening to improve HRQoL related to drinking.
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http://dx.doi.org/10.3390/ijerph17217758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660298PMC
October 2020

Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization.

FASEB J 2020 12 20;34(12):16276-16290. Epub 2020 Oct 20.

Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Clusterin (CLU) is a heterodimeric glycoprotein involved in a range of biological processes. We investigated the function of CLU as a novel regulator of adipogenesis. CLU expression increased during 3T3-L1 preadipocyte differentiation. CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). Conversely, knockdown of CLU attenuated adipogenesis and reduced transcript levels of Pparg and Cebpa. However, the promoter activities of both the Pparg and the Cebpa gene were not affected by alteration of CLU expression on its own. Additionally, the protein level of Krüppel-like factor 5 (KLF5), an upstream transcription factor of Pparg and Cebpa involved in adipogenic differentiation, was upregulated by CLU overexpression, although the mRNA level of Klf5 was not altered by changes in the expression level of CLU. Cycloheximide chase assay showed that the increased level of KLF5 by CLU overexpression was due to decreased degradation of KLF5 protein. Interestingly, CLU increased the stability of KLF5 by decreasing KLF5 ubiquitination. CLU inhibited the interaction between KLF5 and F-box/WD repeat-containing protein 7, which is an E3 ubiquitin ligase that targets KLF5. The adipogenic role of CLU was also addressed in mesenchymal stem cells (MSCs) and Clu mouse embryonic fibroblasts (MEFs). Furthermore, CLU enhanced KLF5-mediated transcriptional activation of both the Cebpa and the Pparg promoter. Taken together, these results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5.
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http://dx.doi.org/10.1096/fj.202000551RRDOI Listing
December 2020

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs.

Immune Netw 2020 Aug 4;20(4):e29. Epub 2020 Aug 4.

Department of Biochemistry, Cancer Biology, Neurosciences and Pharmacology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.
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http://dx.doi.org/10.4110/in.2020.20.e29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458798PMC
August 2020

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

Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer.

Breast Cancer Res 2020 05 27;22(1):54. Epub 2020 May 27.

Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic ro 43 gil, song pa gu, Seoul, 138-736, South Korea.

Introduction: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer.

Patients And Methods: In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints.

Results: A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6-44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4-24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group.

Conclusions: Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET.

Trial Registration: Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.
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http://dx.doi.org/10.1186/s13058-020-01288-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251809PMC
May 2020

Efficacy of health coaching and a web-based program on physical activity, weight, and distress management among cancer survivors: A multi-centered randomised controlled trial.

Psychooncology 2020 07 23;29(7):1105-1114. Epub 2020 Apr 23.

Department of Family Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Objectives: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients.

Methods: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months.

Results: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight.

Conclusion: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.
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http://dx.doi.org/10.1002/pon.5394DOI Listing
July 2020

Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women.

Sci Rep 2020 04 16;10(1):6564. Epub 2020 Apr 16.

Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Korea.

The associations between genetic polymorphisms in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, the effect of a combination of the two polymorphisms, and breast cancer risk were studied in a population of East-Asian women. In this study, 623 breast cancer cases and 1845 controls, aged 40 or above, were included. The association between ALDH2 polymorphism and breast cancer risk was validated in 2143 breast cancer cases and 3977 controls. Alcohol consumption increased the risk of breast cancer regardless of ADH1B and ALDH2 genotypes. The rs671 polymorphism of ALDH2 was independently associated with increased breast cancer risk (OR = 1.27, 95% CI = 1.02-1.58 per increment of A). The ADH1B rs1229984 polymorphism, and combined effects of the rs671 and rs1229984 polymorphisms, did not reveal any significant association with breast cancer. Stratification by menopausal status revealed that rs671 gene polymorphisms were significantly associated with breast cancer only in postmenopausal women (OR = 1.45, 95% CI = 1.03-2.05 per increment of A). This is the first study to demonstrate an independent association between ALDH2 gene variants and breast cancer in Asian women. Further studies are warranted to further elucidate the etiology of breast cancer as it relates to alcohol consumption in Asian women.
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http://dx.doi.org/10.1038/s41598-020-62361-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162854PMC
April 2020

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2017.

Cancer Res Treat 2020 Apr 16;52(2):335-350. Epub 2020 Mar 16.

Korea Central Cancer Registry, National Cancer Center, Goyang, Korea.

Purpose: This study reports the cancer statistics and temporal trends in Korea on a nationwide scale, including incidence, survival, prevalence, and mortality in 2017.

Materials And Methods: The incidence, survival, and prevalence rates of cancer were evaluated using data from the Korea National Cancer Incidence Database from 1999 to 2017 with follow-up until December 31, 2018. Deaths from cancer were assessed using cause-of-death data from 1983 to 2017, obtained from Statistics Korea. Crude and age-standardized rates (ASRs) for incidence, mortality, and prevalence, and 5-year relative survival rates were calculated and trend analysis was performed.

Results: In 2017, newly diagnosed cancer cases and deaths from cancer numbered 232,255 (ASR, 264.4 per 100,000) and 78,863 (ASR, 76.6 per 100,000), respectively. The overall cancer incidence rates increased annually by 3.5% from 1999 to 2011 and decreased by 2.7% annually thereafter. Cancer mortality rates have been decreasing since 2002, by 2.8% annually. The 5-year relative survival rate for all patients diagnosed with cancer between 2013 and 2017 was 70.4%, which contributed to a prevalence of approximately 1.87 million cases by the end of 2017.

Conclusion: The burden of cancer measured by incidence and mortality rates have improved in Korea, with the exception of a few particular cancers that are associated with increasing incidence or mortality rates. However, cancer prevalence is increasing rapidly, with the dramatic improvement in survival during the past several years. Comprehensive cancer control strategies and efforts should continue, based on the changes of cancer statistics.
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http://dx.doi.org/10.4143/crt.2020.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176962PMC
April 2020

Prediction of Cancer Incidence and Mortality in Korea, 2020.

Cancer Res Treat 2020 Apr 16;52(2):351-358. Epub 2020 Mar 16.

Korea Central Cancer Registry, National Cancer Center, Goyang, Korea.

Purpose: This study aimed to report the projected cancer incidence and mortality for the year 2020 to estimate Korea's current cancer burden.

Materials And Methods: Cancer incidence data from 1999 to 2017 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2018 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against observed years and then by multiplying the projected age-specific rates by the age-specific population. A Joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend.

Results: In total, 243,263 new cancer cases and 80,546 cancer deaths are expected to occur in Korea in 2020. The most common cancer site is expected to be the lung, followed by the stomach, thyroid, colon/rectum, and breast. These five cancers types are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer among people who die is expected to be lung cancer, followed by liver, colon/rectal, pancreatic, and stomach cancers.

Conclusion: The incidence rates for all types of cancer in Korea are estimated to decrease gradually. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.
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http://dx.doi.org/10.4143/crt.2020.203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176954PMC
April 2020

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

Comparing the Characteristics and Outcomes of Male and Female Breast Cancer Patients in Korea: Korea Central Cancer Registry.

Cancer Res Treat 2020 Jul 13;52(3):739-746. Epub 2020 Feb 13.

Center for Breast Cancer, National Cancer Center, Goyang, Korea.

Purpose: This study aimed to determine the incidence of male breast cancer (MBC) and its survival outcomes in Korea, and to compare these results to those for female breast cancer (FBC).

Materials And Methods: We searched the Korea Central Cancer Registry and identified 227,122 breast cancer cases that were diagnosed between 1999 and 2016. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to sex, age, histological type, and cancer stage.

Results: The 227,122 patients included 1,094 MBC cases and 226,028 FBC cases. Based on the age-standardized rate, the male: female ratio was 0.0055:1. The most common ages at diagnosis were 60-69 years for MBC and 40-49 years for FBC (p < 0.001). Male patients were less likely than female patients to receive adjuvant radiotherapy (7.5% vs. 21.8%, p < 0.001) or adjuvant chemotherapy (40.1% vs. 55.4%, p < 0.001). The 5-year OS rates after diagnosis were 88.8% for all patients, although it was significantly lower for MBC than for FBC (76.2% vs. 88.9%, p < 0.001). In both groups, older age (≥ 60 years) was associated with shorter survival. The 5-year OS rates for the invasive histological types were 75.8% for men and 89.0% for women. The 5-year OS rates in both groups decreased with increasing cancer stage.

Conclusion: MBC was diagnosed at older ages than FBC, and male patients were less likely to receive radiotherapy and chemotherapy. The survival outcomes were worse for MBC than for FBC, with even poorer outcomes related to older age, the inflammatory histological types, and advanced stage. It is important that clinicians recognize the differences between FBC and MBC when treating these patients.
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http://dx.doi.org/10.4143/crt.2019.639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373857PMC
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

Effects of enzymatically modified chestnut starch on the gut microbiome, microbial metabolome, and transcriptome of diet-induced obese mice.

Int J Biol Macromol 2020 Feb 20;145:235-243. Epub 2019 Dec 20.

Department of Food Science and Technology, College of Agriculture and Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea. Electronic address:

Modification of chestnut starch with amylosucrase from Deinococcus geothermalis (DGAS) increases the proportion of resistant starch. DGAS-modified chestnut starch (DMCS) attenuates obesity in diet-induced obese mice via a receptor of short chain fatty acids (SCFAs), G-protein-coupled receptor 43. SCFAs are gut microbial metabolites produced by fermenting resistant starch and have key roles in the obesity-ameliorating effects of DMCS. Here, we evaluated the mechanical links among DMCS-induced changes in the gut microbiota, consequent production of microbial metabolites, and host genetic responses. Supplementation with DMCS altered the proportions of cecal microbiota, such as Ruminococcaceae and Bacteroides; microbial metabolites, such as acetic acid; and some carbohydrate metabolites. DMCS also induced changes in the expression of some genes in cecal epithelial cells, including genes involved in energy production, the cell cycle, and cellular junctions. Changes in the gut microbiota, microbial metabolites, and host gene expression were found to be significantly correlated. Our findings demonstrated the integrated and incorporated association among the gut microbiota, their beneficial metabolites, and the host transcriptome, which contributed to clarifying the anti-obesity effects of DMCS as a prebiotic. Therefore, fortifying resistant starch by modification of chestnut starch using DGAS may be a good strategy in the functional food industry.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.12.169DOI Listing
February 2020

Adherence to the American Cancer Society Guidelines for Cancer Survivors and Health-Related Quality of Life among Breast Cancer Survivors.

Nutrients 2019 Dec 3;11(12). Epub 2019 Dec 3.

Department of Food and Nutrition, Seoul National University, Seoul 08826, Korea.

The development and validation of guidelines for breast cancer survivors are of importance due to the increased survival rate for breast cancer. In this cross-sectional study, we aimed to examine the association between adherence to the American Cancer Society (ACS) guidelines for cancer survivors and health-related quality of life (HRQoL). A total of 618 breast cancer survivors aged 30 to 81 years who had been diagnosed with stage I to III primary breast cancer and had surgery at least a year before enrollment were included. The participants completed the 36 Item Short-Form Health Survey (SF-36) to evaluate HRQoL, and adherence scores were calculated based on the Nutrition and Physical Activity Guidelines for Cancer Survivors, which were released by the ACS. Increasing adherence scores were associated with increasing scores on the physical component summary (PCS) and the physical functioning (PF), bodily pain (BP), and vitality (VT) domains ( for trend <0.001 for PCS and PF, 0.01 for BP, and 0.02 for VT); these scores were mainly driven by the associations among survivors with stage II-III cancer. Further prospective studies are needed to evaluate whether adherence to these guidelines improves HRQoL scores among breast cancer survivors.
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http://dx.doi.org/10.3390/nu11122924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950022PMC
December 2019

Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery.

Pharmaceutics 2019 Nov 28;11(12). Epub 2019 Nov 28.

School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Korea.

Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy.
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http://dx.doi.org/10.3390/pharmaceutics11120636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956368PMC
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

Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.

J Clin Oncol 2020 02 16;38(5):434-443. Epub 2019 Sep 16.

Korea Cancer Center Hospital, Seoul, Republic of Korea.

Purpose: The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor-positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy.

Patients And Methods: We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event.

Results: A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; = .029).

Conclusion: The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.
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http://dx.doi.org/10.1200/JCO.19.00126DOI Listing
February 2020