Permanent Chemotherapy‐Induced Alopecia in Patients with Breast Cancer: A 3‐Year Prospective Cohort Study

Kang, Danbee,Kim, Im&#x2010,Ryung,Choi, Eun‐,Kyung,Im, Young Hyuck,Park, Yeon Hee,Ahn, Jin Seok,Lee, Jeong Eon,Nam, Seok Jin,Lee, Hae Kwang,Park, Ji&#x2010,Hye,Lee, Dong&#x2010,Youn,Lacouture, M AlphaMed Press 2019 The oncologist Vol.24 No.3

<P>Chemotherapy‐induced alopecia is (CIA) considered temporary; however, some patients report persistent alopecia several years after chemotherapy. Long‐term prospective data on the incidence and impact of permanent CIA is scarce. This article reports the results of a study conducted to estimate the long‐term incidence of persistent CIA in a cohort of breast cancer patients with measurements of hair volume and density before and after chemotherapy.</P><P><B>Background.</B></P><P>Although chemotherapy‐induced alopecia (CIA) is considered temporary, some patients report persistent alopecia several years after chemotherapy. There is, however, a paucity of long‐term prospective data on the incidence and impact of permanent CIA (PCIA). The objective of our study was to estimate the long‐term incidence of PCIA in a cohort of patients with breast cancer whose hair volume and density were measured prior to chemotherapy and who were followed for 3 years after chemotherapy.</P><P><B>Materials and Methods.</B></P><P>Prospective cohort study of consecutive patients ≥18 years of age with postoperative diagnosis of stage I–III breast cancer expected to receive adjuvant chemotherapy at the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, from February 2012 to July 2013 (<I>n</I> = 61). Objective hair density and thickness were measured using a noninvasive bioengineering device.</P><P><B>Results.</B></P><P>The proportion of participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%, respectively. PCIA was characterized in most patients by incomplete hair regrowth. Patients who received a taxane‐based regimen were more likely to experience PCIA compared with patients with other types of chemotherapy. At a 3‐year follow‐up, hair thinning was the most common problem reported by study participants (75.0%), followed by reduced hair volume (53.9%), hair loss (34.6%), and gray hair (34.6%).</P><P><B>Conclusion.</B></P><P>PCIA is a common adverse event of breast cancer adjuvant cytotoxic chemotherapy. Clinicians should be aware of this distressing adverse event and develop supportive care strategies to counsel patients and minimize its impact on quality of life.</P><P><B>Implications for Practice.</B></P><P>Knowledge of permanent chemotherapy‐induced alopecia, an under‐reported adverse event, should lead to optimized pretherapy counseling, anticipatory coping techniques, and potential therapeutic strategies for this sequela of treatment.</P>

Effect of Ionizing Radiation on Rat Tissue: Proteomic and Biochemical Analysis

Park*, Eui&#x2010,Chul,Yoon, Jong&#x2010,Bok,Seong*, Jin&#x2010,Sil,Choi, Kyoung&#x2010,Soo,Kong, Eung&#x2010,Sik,Kim, Yun&#x2010,Jeong,Park, Young&#x2010,Mee,Park, Eun‐,Mi Taylor Francis 2006 Preparative biochemistry & biotechnology Vol.36 No.1

<P>Reactive oxygen species (ROS), generated by ionizing radiation, has been implicated in its effect on living tissues. We confirmed the changes in the oxidative stress markers upon irradiation. We characterized the changes in the proteome profile in rat liver after administering irradiation, and the affected proteins were identified by MALDI-TOF-MS and ESI-MS/MS. The identified proteins represent diverse sets of proteins participating in the cellular metabolism. Our results demonstrated that proteomics analysis is a useful method for characterization of a global proteome change caused by ionizing radiation to unravel the molecular mechanisms involved in the cellular responses to ionizing radiation.</P>

3′‐Sialyllactose protects against osteoarthritic development by facilitating cartilage homeostasis

Jeon, Jimin,Kang, Li&#x2010,Jung,Lee, Kwang Min,Cho, Chanmi,Song, Eun Kyung,Kim, Wook,Park, Tae Joo,Yang, Siyoung John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.1

<P><B>Abstract</B></P><P>3′‐Sialyllactose has specific physiological functions in a variety of tissues; however, its effects on osteoarthritic development remain unknown. Here, we demonstrated the function of 3′‐sialyllactose on osteoarthritic cartilage destruction. <I>In vitro</I> and <I>ex vivo</I>, biochemical and histological analysis demonstrated that 3′‐sialyllactose was sufficient to restore the synthesis of Col2a1 and accumulation of sulphated proteoglycan, a critical factor for cartilage regeneration in osteoarthritic development, and blocked the expression of Mmp3, Mmp13 and Cox2 induced by IL‐1β, IL‐6, IL‐17 and TNF‐α, which mediates cartilage degradation. Further, reporter gene assays revealed that the activity of Sox9 as a transcription factor for Col2a1 expression was accelerated by 3′‐sialyllactose, whereas the direct binding of NF‐κB to the <I>Mmp3</I>,<I> Mmp13</I> and <I>Cox2</I> promoters was reduced by 3′‐sialyllactose in IL‐1β‐treated chondrocytes. Additionally, IL‐1β induction of Erk phosphorylation and IκB degradation, representing a critical signal pathway for osteoarthritic development, was totally blocked by 3′‐sialyllactose in a dose‐dependent manner. <I>In vivo</I>, 3′‐sialyllactose protected against osteoarthritic cartilage destruction in an osteoarthritis mouse model induced by destabilization of the medial meniscus, as demonstrated by histopathological analysis. Our results strongly suggest that 3′‐sialyllactose may ameliorate osteoarthritic cartilage destruction by cartilage regeneration <I>via</I> promoting Col2a1 production and may inhibit cartilage degradation and inflammation by suppressing Mmp3, Mmp13 and Cox2 expression. The effects of 3′‐sialyllactose could be attributed in part to its regulation of Sox9 or NF‐κB and inhibition of Erk phosphorylation and IκB degradation. Taken together, these effects indicate that 3′‐sialyllactose merits consideration as a natural therapeutic agent for protecting against osteoarthritis.</P>

Anti‐inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide‐stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase‐1 expression

Jung, Ji&#x2010,Sun,Shin, Jin A.,Park, Eun‐,Mi,Lee, Jung&#x2010,Eun,Kang, Young&#x2010,Sook,Min, Sung&#x2010,Won,Kim, Dong&#x2010,Hyun,Hyun, Jin&#x2010,Won,Shin, Chan&#x2010,Young,Kim, Hee&#x201 Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.115 No.6

<P> <I>J. Neurochem.</I> (2010) <B>115,</B> 1668–1680.</P><P><B>Abstract</B></P><P>Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase‐2, and pro‐inflammatory cytokine expression in lipopolysaccharide (LPS)‐stimulated microglia, while Rh1 increased anti‐inflammatory IL‐10 and hemeoxygenase‐1 (HO‐1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS‐induced MAPK phosphorylation and nuclear factor‐κB (NF‐κB)‐mediated transcription without affecting NF‐κB DNA binding. As the increase of pCREB (cAMP responsive element‐binding protein) is known to result in suppression of NF‐κB‐mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti‐inflammatory effect of Rh1 because pre‐treatment with protein kinase A inhibitors attenuated the Rh1‐mediated inhibition of nitric oxide production and the up‐regulation of IL‐10 and HO‐1. Furthermore, treatment of HO‐1 shRNA attenuated Rh1‐mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO‐1, play a critical role in the anti‐inflammatory mechanism of Rh1 by modulating pro‐ and anti‐inflammatory molecules in activated microglia.</P>

Vitamin C deficiency attenuates liver fibrosis by way of up‐regulated peroxisome proliferator‐activated receptor‐gamma expression in senescence marker protein 30 knockout mice

Park, Jin&#x2010,Kyu,Ki, Mi&#x2010,Ran,Lee, Hye&#x2010,Rim,Hong, Il&#x2010,Hwa,Ji, Ae&#x2010,Ri,Ishigami, Akihito,Park, Se&#x2010,Il,Kim, Ji&#x2010,Min,Chung, Hae&#x2010,Young,Yoo, Sung&#x2010,Eun,Jeo Wiley Subscription Services, Inc., A Wiley Company 2010 Hepatology Vol.51 No.5

<P><B>Abstract</B></P><P>Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the <I>in vivo</I> results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl<SUB>4</SUB>)‐induced liver fibrosis and the nuclear translocation of p‐Smad2/3, the immediate downstream of transforming growth factor beta (TGF‐β), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up‐regulation of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl<SUB>4</SUB>‐induced liver fibrosis in SMP30 KO mice. <I>Conclusion:</I> Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up‐regulated PPAR‐γ expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR‐γ up‐regulation in liver fibrosis of SMP30 KO mice. (H<SMALL>EPATOLOGY</SMALL> 2010.)</P>

p53 Controls Autoimmune Arthritis via STAT‐Mediated Regulation of the Th17 Cell/Treg Cell Balance in Mice

Park, Jin&#x2010,Sil,Lim, Mi&#x2010,Ae,Cho, Mi&#x2010,La,Ryu, Jun&#x2010,Geol,Moon, Young&#x2010,Mee,Jhun, Joo&#x2010,Yeon,Byun, Jae&#x2010,Kyeong,Kim, Eun‐,Kyung,Hwang, Sue&#x2010,Yun,Ju, Ji Hy Wiley Subscription Services, Inc., A Wiley Company 2013 Vol.65 No.4

<P><B>Abstract</B></P><P><B>Objective</B></P><P>To investigate the connection between p53 and interleukin‐17–producing Th17 cell/Treg cell balance in rheumatoid arthritis (RA).</P><P><B>Methods</B></P><P>Th17 cell and Treg cell frequencies were analyzed by flow cytometry, and cytokine levels in the supernatant were determined using enzyme‐linked immunosorbent assays. The expression of transcription factors was analyzed by immunostaining and Western blotting, and the interactions between p53 and STAT‐3 or STAT‐5 were determined by immunoprecipitation–Western blot analysis. A p53 agonist was administered in the collagen‐induced arthritis (CIA) model, and the effects in vivo were determined.</P><P><B>Results</B></P><P>CD4+ T cells from p53<SUP>–/–</SUP> mice decreased the activity of STAT‐5, lowered the level of phosphorylated STAT‐5, and compromised Treg cell differentiation. The protein p53 bound STAT‐5 directly, and this interaction was enhanced with increasing p53 activity. Under inflammatory conditions, p53 suppressed Th17 cell differentiation and skewed T cells toward Treg cell differentiation through the activation of STAT‐5 signaling cascades. In mice with CIA, injection of a p53 overexpression vector or an antagonist of Mdm2 had the effect of controlling arthritis development in vivo. The regulatory effect of p53 was recapitulated in the cells of RA patients, with more pronounced suppression due to the repressed status of p53 in RA.</P><P><B>Conclusion</B></P><P>We demonstrated a link between p53‐mediated and STAT‐mediated regulation of Th17 cells/Treg cells in RA. Our results suggest that factors involved in this pathway might constitute novel therapeutic targets for the treatment of RA.</P>

Polymer‐Stabilized Chromonic Liquid‐Crystalline Polarizer

Park, Seul&#x2010,Ki,Kim, So&#x2010,Eun,Kim, Dae&#x2010,Yoon,Kang, Shin&#x2010,Woong,Shin, Seunghan,Kuo, Shiao&#x2010,Wei,Hwang, Seok&#x2010,Ho,Lee, Seung Hee,Lee, Myong&#x2010,Hoon,Jeong, Kwang&#x201 WILEY‐VCH Verlag 2011 Advanced functional materials Vol.21 No.11

<P><B>Abstract</B></P><P>Robust coatable polarizer is fabricated by the self‐assembly of lyotropic chromonic liquid crystals and subsequent photo‐polymerizing processes. Their molecular packing structures and optical behaviors are investigated by the combined techniques of microscopy, scattering and spectroscopy. To stabilize the oriented Sunset Yellow FCF (H‐SY) films and to minimize the possible defects generated during and after the coating, acrylic acid (AA) is added to the H‐SY/H<SUB>2</SUB>O solution and photo‐polymerized. Utilizing cross‐polarized optical microscopy, phase behaviors of the H‐SY/H<SUB>2</SUB>O/AA solution are monitored by varying the compositions and temperatures of the solution. Based on the experimental results of two‐dimensional wide angle X‐ray diffraction and selected area electron diffraction, the H‐SY crystalline unit cell is determined to be a monoclinic structure with the dimensions of <I>a</I> = 1.70 nm, <I>b</I> = 1.78 nm, <I>c</I> = 0.68 nm, <I>α</I> = <I>β</I> = 90.0° and <I>γ</I> = 84.5°. The molecular arrangements in the oriented H‐SY films were further confirmed by polarized Fourier‐transform infrared spectroscopy. The polymer‐stabilized H‐SY films show good mechanical and chemical stabilities with a high polarizability. Additionally, patterned polarizers are fabricated by applying a photo‐mask during the photo‐polymerization of AA, which may open new doors for practical applications in electro‐optic devices.</P>

Mixed grain containing giant embryonic brown rice improves postprandial glycaemic response in healthy subjects

Park, Eun‐,Ock,Oh, Mi&#x2010,Ra,Choi, Eun‐,Kyung,Shin, Dong&#x2010,Hwa,Doo, Jae&#x2010,Kyun,Kim, Young&#x2010,Soo,Park, Young&#x2010,Min,Jung, Eun‐,Soo,Park, Byung&#x2010,Hyun,Chae, John WileySons Australia, Ltd 2016 Nutrition & dietetics Vol.73 No.2

<P>Aim: Mixed grain, which contributes to lowered glycaemic responses, has been shown to be effective in dietary management of patients with impaired glucose tolerance or diabetes. Methods: The present study determined the postprandial blood glucose response of 20 healthy volunteers to mixed grains containing giant embryonic rice (MG-GER) or giant embryonic brown rice (MG-GEBR) compared with white rice (WR) in a randomised crossover design. Plasma glucose and serum insulin at 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes were measured, and glycaemic index (GI) and incremental area under the curve (iAUC) were calculated. Results: The GIs for WR, MG-GER and MG-GEBR were 86.75 5.78, 76.09 +/- 7.01 and 69.33 +/- 6.54, respectively. The 120-minute iAUCs after administration of MG-GER or MG-GEBR were significantly lower than that of WR. In addition, the MG-GEBR diet group had a significantly lower C-peptide concentration at the 120-minute time point when compared to the WR group. Conclusions: These results suggest that consumption of MG-GER or MG-GEBR instead of WR is more effective to reduce postprandial glucose levels without increasing insulin secretion.</P>

MicroRNA‐320a and microRNA‐4496 attenuate <i>Helicobacter pylori</i> cytotoxin‐associated gene A (CagA)‐induced cancer‐initiating potential and chemoresistance by targeting β‐catenin and ATP‐binding casse

Kang, Dong Woo,Yang, Eun Sun,Noh, Yu Na,Hwang, Won Chan,Jo, Se&#x2010,Young,Suh, Young&#x2010,Ah,Park, Won Sang,Choi, Kang&#x2010,Yell,Min, Do Sik John Wiley Sons, Ltd 2017 The Journal of pathology Vol.241 No.5

<P><B>Abstract</B></P><P>Infection with <I>Helicobacter pylori</I> is closely linked to an increased risk of gastric cancer. Although cytotoxin‐associated gene A (CagA), a major virulence factor of <I>H. pylori</I>, is known to be a causal factor for gastric carcinogenesis, the molecular link between CagA and gastric cancer‐initiating cell (CIC)‐like properties remains elusive. Here, we demonstrate that CagA is required for increased expression of β‐catenin and its target CIC markers via downregulation of microRNA (miR)‐320a and miR‐4496. CagA promoted gastric CIC properties and was responsible for chemoresistance. miR‐320a and miR‐4496 attenuated the <I>in vitro</I> self‐renewal and tumour‐initiating capacity of CagA‐expressing CICs by targeting β‐catenin. Moreover, miR‐320a and miR‐4496 decreased CagA‐induced chemoresistance by targeting ATP‐binding cassette, subfamily G, member 2 (ABCG2) at the transcriptional and post‐transcriptional levels, respectively. Combination therapy with 5‐fluorouracil and miR‐320a/miR‐4496 suppressed gastric tumourigenesis and metastatic potential in an orthotopic mouse model, probably via suppression of CagA‐induced CIC properties and chemoresistance. Our results provide novel evidence that CIC properties, chemoresistance and tumourigenesis associated with <I>H. pylori</I> are linked to CagA‐induced upregulation of β‐catenin and ABCG2. These data provide novel insights into the molecular mechanisms of CagA‐induced carcinogenisis and the therapeutic potential of of miR‐320a and miR‐4496. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Neural Network‐Based Analysis of Thiol Proteomics Data in Identifying Potential Selenium Targets

Lee, Jong&#x2010,Sik,Ma, Yong&#x2010,Beom,Choi, Kyoung&#x2010,Soo,Park, Soo&#x2010,Yeon,Baek, Sun&#x2010,Hee,Park, Young&#x2010,Mee,Zu, Ke,Zhang, Haitao,Ip, Clement,Hong Kim, Yeul,Park, Eun‐,Mi MARCEL DEKKER, INC 2006 PREPARATIVE BIOCHEMISTRY AND BIOTECHNOLOGY Vol.36 No.1

<P>Generation of a monomethylated selenium metabolite is critical for the anticancer activity of selenium. Because of its strong nucleophilicity, the metabolite can react directly with protein thiols to cause redox modification. Here, we report a neural network-based analysis to identify potential selenium targets. A reactive thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D gel. We constructed a dynamic model and evaluated the relative importance of proteins mediating the cellular responses to selenium. Information from this study will provide new clues to unravel mechanisms of anticancer action of selenium. High impact selenium targets could also serve as biomarkers to gauge the efficacy of selenium chemoprevention.</P>