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Background/aim Phosphoserine aminotransferase 1 (PSAT1) is an enzyme implicated in serine biosynthesis, and its overexpression has been linked to cancer cell proliferation. Therefore, targeting PSAT1 is considered to be an anticancer strategy. Materials and methods The viability of non-small cell lung cancer (NSCLC) cells was measured by MTT assay. Protein and mRNA expression were determined by western blot and reverse transcription polymerase chain reaction, respectively. Results Glutamine-limiting conditions were generated through glutamine deprivation or CB-839 treatment, which induced PSAT1 expression in NSCLC cells. PSAT1 expression induced by glutamine-limiting conditions was regulated by activating transcription factor 4. Knock-down of PSAT1 enhanced the sensitivity of NSCLC cells to glutamine-limiting conditions. Interestingly, ionizing radiation induced PSAT1 expression, and knocking down PSAT1 increased cell sensitivity to ionizing radiation. Conclusion Inhibiting PSAT1 might aid in the treatment of lung cancer, and PSAT1 may be a therapeutic target for lung cancer.

Precision medicine has received increased attention as an effective approach for the treatment of cancer patients. Because of challenges associated with the availability of archived tissue, liquid biopsies are often performed to detect cancer-specific mutations. One of the major advantages of the liquid biopsy is that the treatment can be monitored longitudinally, even after the tumor tissue is no longer available. In a clinical setting, one component of precision medicine is the detection of cancer-specific mutations using archived samples. In this study, we evaluated the epidermal growth factor receptor (EGFR) mutation status of samples of lung cancer patients stored before introduction of the plasma EGFR test at our institution. The aim of this study was to validate the utility of archived plasma samples for detection of the EGFR mutation in nonsmall cell lung cancer (NSCLC) patients. The Cobas® EGFR Mutation Test v2 was the first liquid biopsy test approved as a companion diagnostic test for patients with NSCLC treated with tyrosine kinase inhibitors. We tested for the EGFR mutation in 116 plasma samples archived in the biobank, and the results were compared with those obtained in the tissue or cytology EGFR mutation test. The EGFR mutation-positive rate from archived plasma was lower than that determined from tissue or cytology at 19.0% and 53.4%, respectively, and the concordance rate between the two tests was 58.6%. Of interest, five (4.3%) samples showed the T790M mutation in the plasma test, whereas this mutation was only detected in two (1.7%) tissue/cytology samples. Five (4.3%) samples were additionally positive in the plasma test. Overall, these results indicate that archived plasma samples can serve as an alternative source for the plasma EGFR mutation test when tissue samples are not available, and can improve precision medicine and long-term follow-up in a noninvasive manner.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyses the conversion of prostaglandin E2 to a keto metabolite. The expression of 15-PGDH is ubiquitously repressed in vari...

Fathers are more than social accidents. Research has demonstrated that fathers matter to children's development. Despite noted progress, challenges remain on how best to conceptualize and assess fathering and father-child relationships. The current monograph is the result of an SRCD-sponsored meeting of fatherhood scholars brought together to discuss these challenges and make recommendations for best practices for incorporating fathers in studies on parenting and children's development. The first aim of this monograph was to provide a brief update on the current state of research on fathering and to lay out a developmental ecological systems perspective as a conceptual framework for understanding the different spaces fathers inhabit in their children's lives. Because there is wide variability in fathers' roles, the ecological systems perspective situates fathers, mothers, children, and other caregivers within an evolving network of interrelated social relationships in which children and their parents change over time and space (e.g., residence). The second aim was to present examples of empirical studies conducted by members of the international working group that highlighted different methods, data collection, and statistical analyses used to capture the variability in father-child relationships. The monograph ends with a commentary that elaborates on the ecological systems framework with a discussion of the broader macrosystem and social-contextual influences that impinge on fathers and their children. The collection of articles contributes to research on father-child relationships by advancing theory and presenting varied methods and analysis strategies that assist in understanding the father-child relationship and its impact on child development.

Cytogenetic dosimetry is useful for evaluating the absorbed dose of ionizing radiation based on analysis of radiation-induced chromosomal aberrations. We created two types of in vitro dose-response calibration curves for dicentric chromosomes (DC) and translocations (TR) induced by X-ray irradiation, using an electron linear accelerator, which is the most frequently used medical device in radiotherapy. We irradiated samples from four healthy Korean individuals and compared the resultant curves between individuals. Aberration yields were studied in a total of 31,800 and 31,725 metaphases for DC and TR, respectively, obtained from 11 X-ray irradiation dose-points (0, 0.05, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 5 Gy). The dose-response relationship followed a linear-quadratic equation, Y=C+αD+βD², with the coefficients C=0.0011 for DC and 0.0015 for TR, α=0.0119 for DC and 0.0048 for TR, and β=0.0617 for DC and 0.0237 for TR. Correlation coefficients between irradiation doses and chromosomal aberrations were 0.971 for DC and 0.6 for TR, indicating a very strong and a moderate correlation, respectively. This is the first study implementing cytogenetic dosimetry following exposure to ionizing X-radiation.

Early childhood is critical to the development of children's social-emotional competence, which predicts peer relations and school adjustment in later periods of childhood. The effects of experiencing or witnessing aggression on children's social-emotional development are well known, yet the role of conflict resolution within the family has not been sufficiently studied. Social information processing models suggests that children who experience positive forms of conflict resolution within the family are likely to generalize these experiences and related skills outside the family, and thus develop greater social-emotional competence. In this longitudinal study, 128 parents (representing 79 families) participated in four quarterly telephone interviews in which they described aggressive conflicts that occurred in their family for which their children were present, including the degree to which each conflict was resolved. They also reported on the frequency of intimate partner aggression (IPA) and parent-to-child aggression (PCA) that occurred while the child was in toddlerhood and preschool as well as children's social-emotional competence at the end of the study. Multi-level models reveal that parents' reports of positive conflict resolution mitigated the concurrent and longitudinal negative effects of children's exposure to both IPA and PCA on their social-emotional competence. These findings reinforce prevention scientists' emphasis on conflict resolution skills as an essential component of parent education programs.La primera infancia es fundamental para el desarrollo de la competencia socioemocional de los niños, la cual predice las relaciones entre pares y la adaptación escolar en periodos posteriores de la niñez. Se conocen muy bien los efectos que producen el sufrir o ser testigos de agresión en el desarrollo socioemocional de los niños, sin embargo, aún no se ha estudiado de manera suficiente el papel que desempeña la resolución de conflictos dentro de la familia. Los modelos de procesamiento de la información social sugieren que los niños que viven formas positivas de resolución de conflictos dentro de la familia son propensos a generalizar estas experiencias y las habilidades afines fuera de la familia y, por lo tanto, a desarrollar una mayor competencia socioemocional. En este estudio longitudinal, 128 padres (que representaban 79 familias) participaron en cuatro entrevistas telefónicas cada tres meses en las cuales describieron conflictos agresivos que hubo en su familia en los cuales sus hijos estuvieron presentes, incluido el grado en el cual se resolvió cada conflicto. También informaron la frecuencia de agresión en la pareja y de agresión de padres a hijos que tuvo lugar durante sus primeros años de vida y en la etapa del preescolar, así como la competencia socioemocional de los niños al final del estudio. Los modelos multinivel indican que los informes de los padres sobre la resolución positiva de los conflictos mitigaron los efectos negativos longitudinales y simultáneos de la exposición de los niños a la agresión en la pareja y a la agresión de padres a hijos en su competencia socioemocional. Estos resultados refuerzan el énfasis en las habilidades de resolución de conflictos de los científicos de la prevención como componente esencial de los programas de educación para padres.幼儿期对儿童社会情感能力的发展至关重要，这预示着儿童后期的同伴关系和学校适应。经历或目睹攻击性行为对儿童社会情感发展的影响是众所周知的，家庭内部冲突解决对儿童社会情绪发展的作用却没有进行充分的研究。社会信息处理模型表明，在家庭内部经历过积极的冲突解决方式的儿童有可能将这些经验和相关技能推广到家庭之外，从而发展出更大的社会情感能力。在这项长期研究中，128位父母（代表79个家庭）参加了四个季度的电话访谈。在访谈中他们描述了发生在孩子家庭中的、孩子在场的攻击性冲突，包括每个冲突被解决的程度。他们还报告了孩子在学步期和学前期发生的亲密伴侣攻击性行为和父母对孩子攻击性行为的频率，以及研究结束时孩子的社会情感能力情况。多层次模型显示，父母对报告的积极解决冲突缓解了儿童接触亲密伴侣攻击和父母对儿童的施暴击对其社会情感能力的并发和长期性的负面影响。这些发现进一步强调了预防科学家们对冲突解决技能的强调，这些技能将作为父母教育计划的重要组成部分。.

Background Analytical performance should be evaluated before a new coagulation analyzer is adopted in a clinical laboratory. The objective of this study was to evaluate analytical performances of three new coagulation analyzers (STA-R Max3, CN-6000, and Cobas t511) and compare them based on the following four coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer. Methods A total of 427 plasma samples, including fresh and frozen/thawed plasma spanning wide ranges. Each of the manufacturers' quality control samples were used for the evaluation. Analytical performances were evaluated. Parameters considered were precision, carryover, verification of analytical measurement range, auto-dilution, and reference range according to the CLSI guidelines (H57-A). The results of each parameter were compared between STA-R compact (currently in use) and three new analyzers using fresh plasma. The results were compared among three new analyzers using fresh and frozen/thawed plasma, and samples with interferences of hemolysis/icterus/ lipemia (H/I/L). Results Analytical performances were excellent for all analyzers within each manufacturer's target based on results of precision, carryover, linearity, and verifications of auto-dilution, and reference range. Results for four parameters (PT/aPTT/fibrinogen/D-dimer) with the three new analyzers using fresh samples were well-correlated with those of STA-R Compact except for D-dimer tests (Pearson's r: 0.84 to 1.00). Good correlations were observed between the new analyzers with the total samples (fresh and frozen/thawed samples) (Pearson's r, 0.86 to 0.97). However, weaker correlation and/or higher mean bias% were observed for aPTT and D-dimer with total samples and for four parameters with normal samples rather than abnormal samples across the three analyzers. Differences were more prominent with H/I/L samples, especially between STA-R Max3 and CN-6000 or Cobas t511 for PT, aPTT, and D-dimers. Conclusions With excellent analytical performances, the three new coagulation analyzers demonstrated good correlations, although high variabilities were seen for aPTT and D-dimers. High variability in comparison analysis might be mainly attributed to differences in reference and reportable ranges of each parameter across the three different analyzers.

Background Dual inhibition of transforming growth factor beta (TGF-β) signaling and PD-1 is a promising strategy to reverse immunosuppressive tumor microenvironment and poor responses to immunotherapy. Based on preliminary clinical data with vactosertib, a highly selective and potent inhibitor of TGF-β receptor type 1, in combination with pembrolizumab, this study aimed to explore a biomarker with predictive value for this regimen in metastatic microsatellite stable (MSS) colorectal cancer (CRC). Methods Tumor biopsy samples were obtained from 24 CRC patients at baseline and cycle 2 in the ongoing MP-VAC-204 study and analyzed by RNAseq and DNAseq. Consensus molecular subtype (CMS), TGF-β responsive gene signatures, IFN-γ signatures, and tumor mutation burden (TMB) were analyzed. Clinically benefited patients were defined by those who achieved objective response assessed by RECIST v1.1/iRECIST or progression free survival more than 24 weeks. Vactosertib responsive gene signature (VRGS) that showed significantly different expression among previously identified TGF-β responsive gene signature and IFN-γ signature in responders than in non-responders was identified and VRGS score was calculated by a mean value of VRGS filtered-in gene expressions divided by 6 house-keeping gene expressions. Results As of July 1, 2020, of the total evaluable 24 patients, 71% were CMS4 subtype and 33% were with high TMB (≥10 mut/Mb). Clinical benefit rate was 33.3% including 3 PR and 1 iPR patients. No significant associations in response rate were observed with CMS subtypes or TMB status. VRGS score was significantly enriched in responders than in non-responders (P value = 0.006; AUC = 0.836). A preliminary cut-off value of 2.179 resulted in 94% specificity and 75% sensitivity with 85.7% patients correctly classifying as a responder. After treatment of vactosertib plus pembrolizumab, TGF-β-related VRGS was significantly decreased and the extent of decrease was greater in responders, compared to non-responders. Ethics Approval The study was approved by Ethics Board of Asan Medical Center, Yonsei University College of Medicine, Samsung Medical Center, and Seoul National University Bundang Hospital with approval number 2018-1215, 4-2018-0728, SMC 2018-07-146-006, and B-1808/487-003, respectively. Conclusions Development of VRGS as a predictive biomarker for this combination treatment with vactosertib and pembrolizumab is ongoing and its potential clinical utility for patient selection will be explored. Trial Registration NCT03724851

Background Targeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy. Methods Patients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1). Results By August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented. Conclusions The combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed. Trial Registration NCT03732274 Ethics Approval The study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

Children with higher socioemotional competence are more likely to build constructive relationships with others and experience more positive adjustment outcomes in later periods. Securely attached children are likely to develop better socioemotional competence, but genetic moderation of associations between attachment and later socioemotional competence has received less attention. Using structural equation modeling, this study analyzed data collected from 1,337 children (51% male) born from 1998 to 2000 in the Fragile Families and Child Wellbeing study. The results demonstrated that relations between attachment security at age 3 years and their social competence at age 5 years differed by two serotonin transporter variants (5-HTTLPR, STin2). Effect sizes of these interactions were larger than effect sizes of main effects and the benefit of having sensitive alleles was consistently supported. This implies that having more secure attachment in the early developmental period is advantageous especially for children with minor alleles who have greater environmental sensitivity.

Research demonstrates significant associations between coparenting conflict and child adjustment problems. However, the implications of youth adjustment for coparenting, especially during youth’s adolescence, remain poorly understood. Addressing several gaps in the literature, this study examines the longitudinal trajectory of mothers’ and fathers’ reported coparenting conflict from youth ages 10–17 and tests bidirectional associations between youth social anxiety, hostility, risk-taking behaviors, and mothers’ and fathers’ coparenting conflict. Participants include 757 mothers, fathers, and youth in two-parent families (M youth age = 11.28, SD = 0.49; 53% female) who participated in 5 waves of data collection when youth were in the 6th to 9th grades. Multilevel growth curve models revealed significant non-linear change in mothers’ and fathers’ coparenting conflict, such that coparenting conflict declined through youth’s transition to adolescence, leveled off in early adolescence, and declined in the mid-late adolescent years. Cross-lagged models showed significant positive associations between youth social anxiety and hostility and coparenting conflict at the following time point, but coparenting conflict did not predict later youth adjustment problems in these domains. There were significant bidirectional associations between mother-reported coparenting conflict and youth risk-taking behaviors; the associations between coparenting conflict and risk-taking were not significant for fathers. The findings demonstrate that investigating longitudinal associations between youth adjustment and coparenting conflict may provide new insights into the role of child effects for mothers’ and fathers’ coparenting experiences.

This chapter explores Kim Tongin’s (re-)invention of Western aestheticism in colonial modern Korea in his literary and literary-critical works from the late 1910s to the 1930s. I relate Kim’s notion of the autonomy of art to the prevailing ideological concepts of the day—that is, the East Asian versions of the liberal concept of freedom and the social Darwinist ideology of power. The second part of the chapter considers the enduring legacy of Kim’s aestheticism in the later entrenchment of the opposition between pure art and engaged art during the authoritarian era. It argues for the potential of aestheticism in deconstructing this dichotomy and in differently politicizing art, a la Ranciere, by further diversifying and broadening the meaning of politics in/as art.

Research has shown that the transition to parenthood is a particularly challenging period of life which is often associated with a decline in relationship quality and an increase in mental health problems. Emerging parents often experience difficulties in coping with new tasks and challenges in the relationship, resulting in inadequate mutual support, stress, conflicts and even depressive symptoms. To support expectant parents in establishing an effective and strong coparenting alliance, we have employed an educational coparenting intervention to teach important coparenting skills. The intervention was a non-randomized case-control study with 126 expectant parents. The intervention group participated in a five-session intervention, whereas the control group received an information booklet and had an optional meeting postpartum. The purpose of this study was to ease the transition to parenthood in order to prevent postpartum conflict and depression. Parents in the intervention group (n = 34 couples) showed significantly fewer conflicts postpartum than before (Z = -3.28, p = 0.00), and scored better in postnatal delegated dyadic coping (β = 0.25, p = 0.00, R2 = 0.32), a form of mutual support. Neither the intervention group (Z = -0.83, p = 0.40) nor the control group (Z = -0.86, p = 0.38) showed a significant increase in depression scores after childbirth. Although conflicts during the transition to parenthood declined and postnatal delegated dyadic coping strengthened, the study design does not allow to draw conclusion on group effects. Nevertheless, the promising results of this pilot intervention are a base for future studies.

This article examines five South Korean TV programs, The Age of Global Success, Love in Asia, Asia Hunter, KOICA’s Dream, and Saving Mrs. Go Bongshil, all of which belong to varied and hybrid genres such as news magazine, serialized documentary, reality show, and television drama. Due to its partially elevated status as a middlebrow medium and its ability to combine multiple functions such as entertainment, information, education, and social engineering, South Korean television is a more socially influential popular medium than its Western counterparts. I argue that South Korean popular culture, as represented by these television programs, produces, circulates, and promotes the meanings of respective nation-states (e.g., South Korea, Vietnam, Sri Lanka) and of Asia as a bloc in relation to the region’s ongoing economic and cultural globalization. The following five aspects of South Korea’s relationship to the less developed parts of Asia emerge in the popular culture of the television medium: Southeast Asian and other Asian migrant/immigrant/off-shore labor for South Korea, and the distinct ways in which some are made visible and others invisible; popular cultural imaginings of a pan-Korean regional-global network; popular cultural production of a pan-Asian imaginary; South Korean humanitarianism and its subimperializing dimensions; and dissemination of popular culture within and outside South Korea—that is, the emergence of popular culture as a significant instrument of imaging South Korea as a subempire. I conclude by offering a couple of broad speculations on the changing and varied meanings of subempire for contemporary South Korea.

Introduction: Desmoid tumor is a rare aggressive tumor where there is no satisfying systemic treatment. Previous studies showed increased expression of transforming growth factor-β (TGF-β) in the desmoid tumor. Here, we analyzed genomic and transcriptomic data of tumor samples from patients with desmoid tumor to evaluate therapeutic applicability of inhibition of TGF-β response. Methods: We collected pre-treatment desmoid tumor samples from 31 patients in Yonsei cancer center, (YCC)-desmoid cohort and performed targeted next-generation sequencing and whole RNA sequencing. To compare the data with other cancer types, we used whole exome sequencing and whole RNA sequencing data from sarcoma patients from Yonsei Cancer Center (YCC-sarcoma cohort, n = 17 and n =53, respectively) and The Cancer Genome Atlas (TCGA, n = 9,235). Transcriptomic data was normalized throughout the three cohorts to reduce batch effect. To evaluate the enrichment of TGF-β responsive signature (TBRS) in tumor and microenvironment, we calculated the mean expression values of fibroblast-TBRS (F-TBRS) from previous study. Results: In the two sarcoma cohorts (YCC-desmoid and YCC-sarcoma cohorts), desmoid tumor samples had the highest F-TBRS score among the various types of sarcoma. When compared with other cancer types in TCGA, desmoid tumor samples showed the higher F-TBRS than all other cancer types except for pancreatic adenocarcinoma. In the desmoid tumor samples, CTNNB1, GNAQ, and APC mutations were the top 3 frequent mutations (23, 19, and 2 samples, respectively). In the merged two sarcoma cohorts, CTNNB1/APC mutation and GNAQ mutation were both associated with higher enrichment in F-TBRS (p < 0.001, respectively). Conclusion: Desmoid tumors are enriched with expression of genes associated with TGF-β response of fibroblast compared with other cancer types including other sarcomas. In addition, CTNNB1, APC and GNAQ mutations were associated with higher enrichment in TBRS. Therapeutic intervention to decrease the TGF-β response of fibroblast by using TGF-β receptor inhibitor may show clinical benefit in patients with desmoid tumors. Citation Format: Changhee Park, Kum-Hee Yun, Sanghoon Song, Jin Kyung Lee, Jiyeon Ryu, Bitna Oh, Sunjin Hwang, Ki Baik Hahm, Seung-Jin Kim, Seung Hyun Kim, Chan-Young Ock, Hyo-Song Kim. Genomic and transcriptomic analyses of desmoid tumor reveals enrichment of transforming growth factor beta responsive signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2250.

The purpose of this study was to compare the conceptual structures of Life Science 1 textbook and teacher’s lecture. Research data were from cell respiration in the Life Science 1 textbook that was developed for scientifically gifted students reflecting a curriculum of Science High School and the teacher’s 8 lectures on the topic. This data was all transcribed and conceptual network analysis was established for these transcribed data using Concept Relation Analyzer and Gephi software. The results showed that conceptual structure of the textbook mainly contained detail concepts in molecular level and there were hierarchically inadequate high-ranked concepts. In addition, the conceptual network of the textbook showed that the cell-respiration-related metabolic process of molecular level concept was sequentially described. Whereas the conceptual structure of teacher’s lecture mainly showed that the lecture was focused on the place and mechanism of the cell respiration. The textbook didn’t show systematic concept structure. And the teacher’s lecture which based on the textbook had some problems not showing concepts systematically either.

Although it has been proposed that the beneficial effect of HER2-targeted therapy in HER2-negative breast cancer is associated with the molecular subtype conversion, the underlying mechanism and the clinical biomarkers are unclear. Our study showed that breast cancer stem cells (BCSCs) mediated HER2 subtype conversion and radioresistance in HER2-negative breast cancer cells and evaluated serum HER2 as a clinical biomarker for HER2 subtype conversion. We found that the CD44+/CD24-/low BCSCs from HER2-negative breast cancer MCF7 cells overexpressed HER2 and EGFR and showed the radioresistant phenotype. In addition, we showed that trastuzumab treatment sensitized the radioresistant phenotype of the CD44+/CD24-/low cells with decreased levels of HER2 and EGFR, which suggested that HER2-targeted therapy in HER2-negative breast cancer could be useful for targeting BCSCs that overexpress HER2/EGFR. Importantly, our clinical data showed that serial serum HER2 measurement synchronously reflected the disease relapse and the change in tumor burden in some patients who were initially diagnosed as HER2-negative breast cancer, which indicated that serum HER2 could be a clinical biomarker for the evaluation of HER2 subtype conversion in patients with recurrent HER2-negative breast cancer. Therefore, our data have provided in vitro and in vivo evidence for the molecular subtype conversion of HER2-negative breast cancer.

Ginkgetin is a natural biflavonoid isolated from the leaves of Ginkgo biloba, and is characterized by its anti-inflammatory and anti-viral activities. Although numerous studies state that it has also antitumor activity, the anti-proliferative effect of ginkgetin and the underlying mechanism in breast cancer cells have not yet been investigated. In the present study, ginkgetin inhibited the cell viability of MCF-7 and T-47D cells dose-dependently, and suppressed the expression of the estrogen receptor (ER) at the mRNA and protein levels. Among the targets of the ER, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), cyclin D1 and survivin were also downregulated by ginkgetin treatment. The anti-proliferative effects of ginkgetin were sufficient to suppress the growth by estradiol stimulation. However, ginkgetin did not significantly affect the viability of MDA-MB-231 cells, which are ER-negative cells. Furthermore, the knockdown of the ER and an inhibitor of PFKFB3 significantly sensitized MCF-7 and T-47D cells to ginkgetin. These findings suggest that ginkgetin induces cell death in ER-positive breast cancer cells via the inhibition of ER expression and that it is a promising agent for breast cancer treatment.

This study attempted to improve the performance of pouch-type lithium iron phosphate battery (LiFePO 4 ) through analysis on its degradation mechanism at a high rate (10 C) for the purpose of observing resistance and electrochemical changes in each material when a battery was manufactured considering the low electrical conductivity and of lithium iron phosphate and properties of cathode materials. For this, the life and safety of lithium batteries are evaluated after forming dendrites through the reduction of lithium at the negative electrode (graphite) as resistance in LiFePO 4 . The components of LiFePO 4 , which generate this kind of resistance includes tab, electrolytes, cathode active materials, anode active materials, binders and conductive materials. The main cathode (lithium-ion phosphate) and anode (natural graphite) materials were fabricated in 90% and 96% respectively, using conductive materials and binders. For a case, a 20 Ah Al pouch was fabricated. A full cell was fabricated with the best materials and components through analysis on resistance characteristic. Then, LiFePO 4 was thermally safer with a long lifespan than the conventional high-rate output. For analysis on materials, in addition, basic material analysis was performed through impedance, X-ray diffraction (XRD), X-Scan and field emission scanning electron (FESEM). After tracing heat generated within the battery using infrared radiation (IR), the degree of degradation was examined. Then, the degradation rates of lithium batteries and reliability of measurements were comparatively assessed. When analyzed with an infrared camera, temperature rapidly rose up to over 80 °C during charge and discharge. A battery was fabricated using an industrial engineering method which can secure internal resistance-lowering slurry and coating dispersion processes and reduce resistance in the binder and tab joint. As a result, it was able to substitute conventional LiFePO 4 with high internal resistance, disperse heat inside the cell and increase its lifespan.

Background: Germline mutations in CDH1 are associated with hereditary and early onset- diffuse gastric cancer. However, the frequency of CDH1 germline mutation in unselected gastric cancer cases is not well established. Aim: The aim of this study was to investigate the frequency and clinical characteristics of germline CDH1 V832M mutation carriers in unselected Korean gastric cancer cases. Methods: Direct sequencing was performed to determine the presence of CDH1 V832M in 305 unselected Korean gastric cancer patients. Lauren's histologic type, family history of gastric cancer, and age of cancer diagnosis were compared between V832M carriers and non-carriers. Results: In the study population, seven gastric cancer patients (7/305, 2.29%) were found to have the CDH1 V832M mutation. The CDH1 V832M mutation carrier state was not significantly associated with phenotypes including Lauren's histologic type, family history of gastric cancer, age of cancer diagnosis, and other cancer history in a patient. Conclusion: This study demonstrates that the germline CDH1 V832M mutation is common in sporadic, late onset, and intestinal type gastric cancer as well as familial, early onset, and diffuse type gastric cancer. Our finding suggests that guidelines for managing CDH1 mutation carriers should be refined through additional data on penetration according to CDH1 mutation type in sporadic cases.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyses the conversion of prostaglandin E

The manufacturing process of large scaled Al 7050 alloy is difficult for the occurrence of solidification crack during casting. The aims of this study are the evaluations of microstructure and mechanical properties of extruded Al 7050 billet and ring forged one with large scale. Large scaled Al 7050 billet was casted by direct-chill casting process. The extruded and ring forged specimens were prepared from the casted ingot after residual stress relief and homogenization heat treatment, respectively. Microstructures, hardness and tensile test of the surface, middle and center part of each specimen were performed at room temperature. Sheared and elongated type grains were observed at the edge parts of surface and center area and its aspect ratios of grains were low and similar as 0.21 while that of middle area was closed to 0.92 value in ring forged Al 7050 alloy. The mechanical properties of extruded Al 7050 alloy were superior than those of ring forged one. The hardness values of surface and center part were slightly higher than that of middle part in ring forged Al 7050 alloy.

Caused corrosion by hydrogen on stainless steel using nondestructive technique is one of issues to be clarified in nuclear fusion industry. In this study, an ultrasonic wave was used to evaluate the degree of corrosion by hydrogen charging of stainless steel. The mechanical properties of hydrogen charged material including tensile strength and strain were discussed, and the change of surface of specimen according to the hydrogen charging quantities was observed. The relationship between fractography and ultrasonic wave characteristics on hydrogen charged material discussed. In addition, acoustic emission technique was applied to clarify the dynamic behavior such as dislocation, deformation and crack in material by loading. AE parameters of event, energy, amplitude and frequency were analyzed according to the degree of load, and optical AE parameter was derived to evaluate the degree of the damage of hydrogen charged stainless steel.

// Sang Hyeok Woo 1, * , Sung-Keum Seo 1, * , Yoonhwa Park 1, 2 , Eun-Kyu Kim 3 , Min-Ki Seong 4 , Hyun-Ah Kim 4 , Jie-Young Song 1 , Sang-Gu Hwang 1 , Jin Kyung Lee 5 , Woo Chul Noh 4 , In-Chul Park 1 1 Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, 01812, Republic of Korea 2 School of Life Science and Biotechnology, Korea University, Seongbuk-gu, Seoul, 02841, Republic of Korea 3 Department of Surgery, Breast Cancer Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang-gu, Seongnam, 13620, Republic of Korea 4 Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, 01812, Republic of Korea 5 KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, 01812, Republic of Korea * These authors contributed equally to this work Correspondence to: In-Chul Park, email: parkic@kcch.re.kr Keywords: tamoxifen, breast cancer, dichloroacetate, epidermal growth factor receptor, pyruvate dehydrogenase kinase Received: May 18, 2016 Accepted: July 22, 2016 Published: August 01, 2016 ABSTRACT Metabolic reprogramming in cancer cells has recently been recognized as an essential hallmark of neoplasia. In this context, metabolic alterations represent an attractive therapeutic target, and encouraging results with drugs targeting various metabolic processes have been obtained in preclinical studies. Recently, several studies have suggested that dichloroacetate (DCA), a specific pyruvate dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large number of diverse tumors. However, the precise mechanism is not fully understood, which is important for the use of DCA in cancer treatment. In the present study, we found that DCA sensitized MCF7 breast cancer cells to tamoxifen-induced cell death by decreasing epidermal growth factor receptor (EGFR) expression. The downregulation of EGFR was caused by degradation of the protein. Furthermore, p38 mitogen-activated protein kinase played an important role in DCA/tamoxifen-induced EGFR degradation. Finally, DCA also promoted comparable tamoxifen-induced cell death in tamoxifen-resistant MCF7 cells, which were established by long-term treatment with tamoxifen. In summary, our results suggest that DCA is an attractive potential drug that sensitizes cells to tamoxifen-induced cell death and overcome tamoxifen resistance via downregulation of EGFR expression in breast cancer cells.

Background Industrial radiography is known to be one of the most vulnerable lines of work among the range of different radiation work. According to the relevant law in Korea, every worker registered in this work should check their blood cell counts every year in addition to their thermoluminescent dosimeter (TLD) doses. Since the law was enacted, however, few follow-up studies have been carried out based on the obtained results. Objectives To ascertain the clinical usefulness of complete blood cell count (CBC) results and suggest a proper protocol of health protection for radiation workers. Methods After reviewing all the consecutive results of CBC and TLD doses from radiation workers registered nationwide, we selected two groups of high-risk radiation workers, CBC-high risk (CBC-HR) and TLD-high risk (TLD-HR) groups. A control group of unexposed healthy adults was also included. We compared the absorbed doses calculated by cytogenetic biodosimetry among those three groups, and examined possible confounding factors for each group. Results Both groups of high-risk radiation workers, CBC-HR and TLD-HR, showed higher chromosome aberrations than the control group. In the control group, previous medical history of a CT scan increased the frequency of chromosome aberrations. In contrast, the frequency of chromosome aberrations in the high-risk radiation workers was affected not by the previous CT history but only by the duration of their work. Conclusions We ascertain that reviewing consecutive results of blood cell counts and cytogenetic biodosimetry are useful complementary tools to TLD doses for health protection regulation. Several confounding factors including work duration and previous medical history need to be considered for the interpretation of biodosimetry results.

Graft and dendronized polymers have attracted much attention in the polymer community, and there have been significant efforts to develop better synthetic methods. Herein, we report the highly efficient synthesis of graft and dendronized polymers by using Cu-catalyzed multicomponent polymerization (MCP). Based on diversity-oriented synthesis, we prepared a library of various graft and dendronized polymers from combinations of three types of monomers (mono-functionalized alkynes, bis-sulfonyl azides, and diamines/diols) that are bench stable and readily accessible. After reaction optimization, 54 samples of high-molecular-weight graft and dendronized polymers were prepared, the MCP method allowing simultaneous manipulation of the structures of both the main chains and the side chains. Moreover, because of the severe steric hindrance of the side chains, these polymers adopted extended conformations, as shown by the large shape parameter in solution. Also, the extended morphology of the single polymer chains was directly visualized by atomic force microscopy and transmission electron microscopy in the solid state. Most importantly, this diversity-oriented polymerization became possible because of highly step-economical and efficient one-step MCP, paving the way toward the easily tunable synthesis of graft and dendronized polymers.

Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells.

Guided by research on psychological safety, we used longitudinal survey data from a sample of 182 dual-earner male-female couples to examine the role of supportive coparenting in mediating relations between adult attachment orientations and parenting stress/satisfaction, and further considered whether parenting self-efficacy moderated relations between supportive coparenting and parenting stress/satisfaction. Path analyses using IBM SPSS AMOS 22 and bootstrapping techniques indicated that fathers' (but not mothers') perceptions of supportive coparenting at 3 months postpartum mediated the associations between their attachment anxiety in the third trimester of pregnancy and their parenting stress and satisfaction at 9 months postpartum. Additional tests of moderation revealed that mothers' perceptions of greater supportive coparenting were associated with lower parenting stress only when their parenting self-efficacy was low, but fathers' perceptions of greater supportive coparenting were associated with greater parenting satisfaction only when their parenting self-efficacy was high. Implications and limitations are discussed.

Recently, targeting deregulated energy metabolism is an emerging strategy for cancer therapy. In the present study, combination of DCA and metformin markedly induced cell death, compared with each drug alone. Furthermore, the expression levels of glycolytic enzymes including HK2, LDHA and ENO1 were downregulated by two drugs. Interestingly, HIF-1α activation markedly suppressed DCA/metformin-induced cell death and recovered the expressions of glycolytic enzymes that were decreased by two drugs. Based on these findings, we propose that targeting HIF-1α is necessary for cancer metabolism targeted therapy.

A stainless steel material is used as components for storing hydrogen gas and liquid hydrogen, or for transportation raw material and oil in storage container. Brittle fracture associated with hydrogen is observed for stainless steel and these phenomena of hydrogen embrittlement were very important for wide-ranging application of stainless steel. Many researchers have studied the hydrogen embrittlement from the mechanical and metallographic point of views. The aim of this study is to identify the material degradation by hydrogen embrittlement for 316L stainless steel using nondestructive evaluation. That is, the relationship between the mechanical properties of 316L stainless steel by hydrogen charging and nondestructive technique of acoustic emission technique and an ultrasonic wave is to be clarified. The relationship between fractography and ultrasonic wave characteristics on hydrogen charged material for 0hr and 24hr was discussed. SEM and optical microscope were used to inspect the fracture surface of hydrogen charged material. The fracture surface of the charged specimen became brittle, especially on the surface nearby. AE parameters of event, count, energy, amplitude and frequency were analyzed according to the degree of the damage of hydrogen charged stainless steel.

This study was carried out to observe and measure the microstructure, distance between dendrite arms, aspect ratio, and Knoop hardness change of extruded material formed by the hydro co-extrusion of Al3003/Al4004 clad material manufactured by the duo-casting method. The specimen of duo-casted Al3003/Al4004 clad materials was circle shaped, it was composed of Al3003 (outside) and Al4004 (inside) materials. The manufacturing conditions of the hydro co-extruded specimen were 423 K temperature and 6.5 ratio of extrusion. At the interface of the duo-casted Al3003/Al4004 clad material, a non-junction at the interface and non-metallic inclusions of Si- and Mn-based oxides were observed. Al3003 exhibits equiaxed crystals, Al4004 has a casted structure with dendrites before extrusion, showed slight deformation during extrusion, and then finally exhibited completely deformed structures after extrusion. In the cast material, the distance between dendrite arms increased, and the aspect ratio of dendrites tended to decrease from the surface to the center. However, in the case of the extruded material, neither Al3003 nor Al4004 changed significantly from the surface to the inside. As extrusion progressed, the Knoop hardness value at the interface of Al3003/Al4004 increased rapidly compared with those of Al3003 and Al4004 matrixes.

Redd1 is a stress response protein that functions as a repressor of mTORC1, a central regulator of protein translation, resulting in the inhibition of cell growth and metabolism. However, paradoxically, high Redd1 expression favors cancer progression and generates resistance to cancer therapy. Herein, we revealed that constitutive overexpression of Redd1 induced HSP27 and HSP70 expression in lung cancer cells. The expression of Redd1, HSP27 and HSP70 was highly increased in lung cancer tissues compared with that in normal lung tissues. Inhibition of HSP27 or HSP70 suppressed AKT phosphorylation, which was induced by constitutive overexpression of Redd1 and enhanced the inhibitory effects on viability of Redd1‑overexpressing cells. Inhibition of AKT phosphorylation resulted in a decrease of HSP27 and HSP70 expression in Redd1‑overexpressing cells. These data indicated that HSPs and AKT in Redd1‑overexpressing cells positively regulated the function and expression of each other and were involved in lung cancer cell survival. Knockdown of HSP27, HSP70 or AKT enhanced ionizing radiation (IR) sensitivity, particularly in lung cancer cells in which Redd1 was stably overexpressed. Collectively, constitutive overexpression of Redd1 led to HSP27 and HSP70 induction and AKT activation, which were involved in lung cancer cell survival and resistance to IR, suggesting that Redd1 may be used as a therapeutic target for lung cancer.

Heat shock protein 90 (HSP90) regulates the stability of various proteins and plays an essential role in cellular homeostasis. Many client proteins of HSP90 are involved in cell growth, survival, and migration; processes that are generally accepted as participants in tumorigenesis. HSP90 is also up-regulated in certain tumors. Indeed, the inhibition of HSP90 is known to be effective in cancer treatment. Recently, studies showed that HSP90 regulates transforming growth factor β1 (TGF-β1)-induced transcription by increasing the stability of the TGF-β receptor. TGF-β signaling also has been implicated in cancer, suggesting the possibility that TGF-β1 and HSP90 function cooperatively during the cancer cell progression. Here in this paper, we investigated the role of HSP90 in TGF-β1-stimulated Mv1Lu cells. Treatment of Mv1Lu cells with the HSP90 inhibitor, 17-allylamino-demethoxy-geldanamycin (17AAG), or transfection with truncated HSP90 (ΔHSP90) significantly reduced TGF-β1-induced cell migration. Pretreatment with 17AAG or transfection with ΔHSP90 also reduced the levels of phosphorylated Smad2 and Smad3. In addition, the HSP90 inhibition interfered the nuclear localization of Smads induced by constitutively active Smad2 (S2EE) or Smad3 (S3EE). We also found that the HSP90 inhibition decreased the protein level of importin-β1 which is known to regulate R-Smad nuclear translocation. These data clearly demonstrate a novel function of HSP90; HSP90 modulates TGF-β signaling by regulating Smads localization. Overall, our data could provide a detailed mechanism linking HSP90 and TGF-β signaling. The extension of our understanding of HSP90 would offer a better strategy for treating cancer.