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Park, Charny,Yoon, Kyong‐,Ah,Kim, Jihyun,Park, In Hae,Park, Soo Jin,Kim, Min Kyeong,Jang, Wooyeong,Cho, Soo Young,Park, Boyoung,Kong, Sun‐,Young,Lee, Eun Sook John Wiley and Sons Inc. 2019 Cancer Science Vol.110 No.5
<P>Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor (ER)‐positive breast cancer by analyzing mutations and copy number variants (CNV), and by applying expression profiling. The whole exome and transcriptome of 47 Korean young breast cancer (KYBR) patients (age <35) were analyzed. Genomic profiles were constructed using mutations, CNV and differential gene expression from sequencing data. Pathway analyses were also performed using gene sets to identify biological processes. Our data were compared with young ER+ breast cancer patients in The Cancer Genome Atlas (TCGA) dataset. <I>TP53</I>,<I>PIK3CA</I> and <I>GATA3</I> were highly recurrent somatic mutation genes. APOBEC‐associated mutation signature was more frequent in KYBR compared with young TCGA patients. Integrative profiling was used to classify our patients into 3 subgroups based on molecular characteristics. Group A showed luminal A‐like subtype and IGF1R signal dysregulation. Luminal B patients were classified into groups B and C, which showed chromosomal instability and enrichment for APOBEC3A/B deletions, respectively. Group B was characterized by 11q13 (CCND1) amplification and activation of the ubiquitin‐mediated proteolysis pathway. Group C showed 17q12 (ERBB2) amplification and lower ER and progesterone receptor expression. Group C was also distinguished by immune activation and lower epithelial‐mesenchyme transition (EMT) degree compared with group B. This study showed that integrative genomic profiling could classify very young patients with breast cancer into molecular subgroups that are potentially linked to different clinical characteristics.</P>
Park, Boyoung,Choi, Ji-Yeob,Sung, Ho Kyung,Ahn, Choonghyun,Hwang, Yunji,Jang, Jieun,Lee, Juyeon,Kim, Heewon,Shin, Hai-Rim,Park, Sohee,Han, Wonshik,Noh, Dong-Young,Yoo, Keun-Young,Kang, Daehee,Park, Su Wolters Kluwer Health 2016 Medicine Vol.95 No.14
<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors.</P><P>Using matched case–control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes.</P><P>The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%–69.8%]; luminal B, 21.4% [95% CI = 18.6–24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%–74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%–32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (<I>P</I> heterogeneity ≤ 0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and −3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; <I>P</I> heterogeneity ≤ 0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (<I>P</I> heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, −3.1%; <I>P</I> heterogeneity ≤ 0.001).</P><P>Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.</P></▼2>
Deletion of the Serotonin Receptor Type 3A in Mice Leads to Sudden Cardiac Death During Pregnancy.
Park, Hyewon,Oh, Chang-Myung,Park, Junbeom,Park, Hyelim,Cui, Shanyu,Kim, Hyung Suk,Namkung, Jun,Park, Sang-Kyu,Pak, Hui-Nam,Lee, Moon-Hyoung,Kim, Hail,Joung, Boyoung Japanese Circulation Society 2015 CIRCULATION JOURNAL Vol.79 No.8
<P>The serotonin receptor type 3 (Htr3) blocker is associated with QT prolongation and torsades de pointes. However, little is known about effects of Htr3 on the heart arrhythmia.Methods?and?Results:An electrophysiological study Involving knock-out (KO) female mice lacking functional Htr3a (Htr3a(-/-)) and their wild-type littermates during non-pregancy (NP) and late pregnancy (LP) was performed. Htr3a mRNA was present in the wild-type, but not in theHtr3a(-/-)mouse hearts. Serotonin and tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme of serotonin synthesis in hearts, is increased during pregnancy. The heart weight and size were increased in the pregnant mice regardless of a mutation. The QTc intervals were prolonged after pregnancy in both the wild (NP: 171.216.8 vs. LP: 247.714.3 ms; P<0.001) andHtr3a(-/-)mice (NP: 187.918.7 vs. LP: 275.611.0 ms, P<0.001). Compared with wild-type LP mice,Htr3a(-/-)LP mice had increased spontaneous ventricle tarchycardia (VT; 56% vs. 0%, P=0.002), VT inducibility (66% vs. 25%, P=0.002) and mortality (56% vs. 0%, P=0.002). Pharmacologic administration of serotonin and Htr3 agonists (m-CPBG) decreased the QT interval in wild mice, but not inHtr3a(-/-)mice.</P>
Park, Boyoung,Shin, Aesun,Jung-Choi, Kyunghee,Ha, Eunhee,Cheong, Hae-Kwan,Kim, Hyun Jeong,Park, Kyung Hwa,Jang, Sungmi,Moon, Byung-In,Ha, Mina Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7
While several reproductive and lifestyle-related factors are already well-known as established risk factors for breast cancer, environmental factors have attracted attention only recently. The objective of the current study was to assess the association between the breast cancer incidences in females, the mortality rate and the number of motor vehicles on the one side and the consumption of gasoline which could work as a major source of air pollution at the other side. The breast cancer incidences and the mortality trends were compared with various indices of westernization like dietary patterns or industrialization with 10 years lag of time. Geographical variations with 10, 15 and 20 years lag of time were assessed between the breast cancer incidence in 2010 and the number of motor vehicles as well as the consumption of gasoline. The upward trend of motor vehicle numbers proved to be comparable to those of breast cancer incidence and mortality. However, the consumption of gasoline started to decrease since the mid-1990s. The geographic distribution of motor vehicle numbers and gasoline consumption in 1990 is in a positive correlation with the breast cancer incidence rates in 2010 and the 20-year lag time ($R^2$ 0.379 with the number of motor vehicles and 0.345 with consumption of gasoline). In a linear relationship between the breast cancer incidences in 2010 and the log transformed number of motor vehicles, the log transformed consumption of gasoline in 2000 also showed a positive relationship ($R^2$ 0.367 with the number of motor vehicles and 0.329 with consumption of gasoline). The results of the current study indicate that there may be a positive relation between the number of vehicles, gasoline consumption and the incidence of breast cancer from the aspects of long-term trends and geographical variation.
Park, Boyoung Y.,Ryu, Ka Yeon,Park, Jung Hwan,Lee, Sang-gi Royal Society of Chemistry 2009 GREEN CHEMISTRY Vol.11 No.7
<P>The catalytic activity of lanthanide triflates, particularly scandium triflate, increased dramatically in [bmim][SbF<SUB>6</SUB>], allowing the cyanosilylation of a variety of aldehydes and ketones with a turnover frequency up to 48 000 mol h<SUP>−1</SUP> and a total turnover number of 100 000.</P> <P>Graphic Abstract</P><P>Highly efficient Sc(OTf)<SUB>3</SUB>-catalyzed cyanosilylations of carbonyl compounds have been achieved in an ionic liquid. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b900254e'> </P>
Park, Hyelim,Park, Hyewon,Mun, Dasom,Kim, Michael,Pak, Hui-Nam,Lee, Moon-Hyoung,Joung, Boyoung Elsevier 2018 Heart rhythm Vol.15 No.5
<P><B>Background</B></P> <P>Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses.</P> <P><B>Objective</B></P> <P>The purpose of this study was to evaluate the effect of left stellectomy on CAIP using rat experimental autoimmune myocarditis (EAM) models.</P> <P><B>Methods</B></P> <P>EAM was produced by injecting 2 mg of porcine cardiac myosin into the footpads of rats. Left stellectomy was performed before EAM induction. We evaluated the effect of left stellectomy on arrhythmic events, survival, inflammation, and CAIP in rats without and with EAM.</P> <P><B>Results</B></P> <P>Left stellectomy prevented arrhythmia and improved survival in EAM rats. Left stellectomy decreased the levels of tumor necrosis factor α, interleukin 6, and high mobility group box 1 (<I>P</I> < .05 vs EAM) in serum and heart tissues from EAM rats. In heart rate variability analysis, high-frequency peaks of the power spectrum densities, reflecting parasympathetic cardiovagal tone, were significantly decreased in EAM rats, but increased after left stellectomy. The ratios of phosphorylated STAT3/STAT3 (signal transducer and activator of transcription 3) and phosphorylated JAK2/JAK2 (Janus kinase 2) decreased in cell lysates of the spleen, liver, and heart in EAM rats. However, the same ratios significantly increased after left stellectomy. Nuclear factor κB in cell lysates of the spleen, liver, and heart increased in EAM rats, but decreased after left stellectomy.</P> <P><B>Conclusion</B></P> <P>In EAM models, left stellectomy increased survival of the rats while showing antiarrhythmic effects with reduced inflammation via activation of the JAK2-STAT3–mediated signaling cascade. Our findings suggest an exciting opportunity to develop new and novel therapeutics to attenuate cardiac inflammation.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Park, Boyoung,Sohn, Ji Yeon,Yoon, Kyong-Ah,Lee, Keun Seok,Cho, Eun Hae,Lim, Myong Cheol,Yang, Moon Jung,Park, Soo Jin,Lee, Moo Hyun,Lee, See youn,Chang, Yoon Jung,Lee, Dong Ock,Kong, Sun-Young,Lee, Eu Springer US 2017 Breast cancer research and treatment Vol.163 No.1
<P><B>Purpose</B></P><P>We investigated the prevalence of <I>BRCA1/2</I> small mutations and large genomic rearrangements in high risk breast cancer patients who attended a genetic counseling clinic.</P><P><B>Methods</B></P><P>In total 478 patients were assessed for <I>BRCA1/2</I> mutations by direct sequencing, of whom, 306 were identified as non-carriers of <I>BRCA1/2</I> mutation and assessed for large rearrangement mutations by multiplex ligation-dependent probe amplification. Family history and clinicopathological characteristics of patients were evaluated.</P><P><B>Results</B></P><P>Sixty-three mutation carriers (13.2%) were identified with <I>BRCA1</I> mutations (6.3%) and <I>BRCA2</I> mutations (6.9%), respectively. Mutation frequency was affected by familial and personal factors. Breast cancer patients with family history of breast and ovarian cancer showed the highest prevalence of <I>BRCA1/2</I> mutations (67%), and triple-negative breast cancer (TNBC) patients showed high <I>BRCA1</I> mutation prevalence (25%). The three probands of <I>BRCA1</I> deletion (1%) represented both familial risk and personal or clinicopathological risk factors as two with TNBC and one with bilateral ovarian cancer.</P><P><B>Discussion</B></P><P>This is the largest study assessing large genomic rearrangement prevalence in Korea and <I>BRCA1</I> deletion frequency was low as 1% in patients without <I>BRCA1/2</I> small mutations. For clinical utility of large genomic rearrangement testing needs further study.</P>