Emerging Trends in Cancer Prevention Agent Development

Miller Mark Steven,Mohammed Altaf 대한암예방학회 2023 Journal of cancer prevention Vol.28 No.1

Advances in omics and immunology over the past 20 years have revolutionized the approach to cancer prevention, with the goal now focused on identifying populations at higher risk for developing cancer in their lifetime as a result of either extensive exposure to environmental carcinogens or harboring precancer lesions or inherited genetic mutations that predispose them to specific types of cancer(s). Thus, the naïve idea that cancer could be “prevented” in the general population has evolved to a more practical approach based on the understanding that the target population for preventive agents will be individuals who already have alterations, in gene pathways, whether inherited or environmentally caused, and the goal will be to “intercept” these lesions at the earliest stages in the path from an initial genetic lesion to full-blown cancer. The Division of Cancer Prevention of the National Cancer Institute and the Office of Disease Prevention at the National Institutes of Health recently sponsored the second biennial “Translational Advances in Cancer Preventive Agent Development Meeting,” held virtually from September 7–9th. In this Meeting Report, we highlight the scientific sessions of this meeting that covered the most recent advances in preventive agent development that also highlighted these rapidly emerging trends in this research area.

Anemia Screening, Prevalence, and Treatment in Pediatric Inflammatory Bowel Disease in the United States, 2010-2014

Miller, Steven D.,Cuffari, Carmelo,Akhuemonkhan, Eboselume,Guerrerio, Anthony L.,Lehmann, Harold,Hutfless, Susan The Korean Society of Pediatric Gastroenterology 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: We examined the prevalence of anemia, annual screening for anemia, and treatment of anemia with iron among children with inflammatory bowel disease (IBD). Methods: A retrospective study of U.S. pediatric patients with IBD was performed in the MarketScan commercial claims database from 2010-2014. Children (ages 1-21) with at least two inpatient or outpatient encounters for IBD who had available lab and pharmacy data were included in the cohort. Anemia was defined using World Health Organization criteria. We used logistic regression to determine differences in screening, incident anemia, and treatment based on age at first IBD encounter and sex. Results: The cohort (n=2,446) included 1,560 Crohn's disease (CD) and 886 ulcerative colitis (UC). Approximately, 85% of CD and 81% of UC were screened for anemia. Among those screened, 51% with CD and 43% with UC had anemia. Only 24% of anemia patients with CD and 20% with UC were tested for iron deficiency; 85% were iron deficient. Intravenous (IV) iron was used to treat 4% of CD and 4% UC patients overall and 8% of those with anemia. Conclusion: At least 80% of children with IBD were screened for anemia, although most did not receive follow-up tests for iron deficiency. The 43%-50% prevalence of anemia was consistent with prior studies. Under-treatment with IV iron points to a potential target for quality improvement.

Anemia Screening, Prevalence, and Treatment in Pediatric Inflammatory Bowel Disease in the United States, 2010–2014

Steven D. Miller,Carmelo Cuffari,Eboselume Akhuemonkhan,Anthony L. Guerrerio,Harold Lehmann,Susan Hutfless 대한소아소화기영양학회 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: We examined the prevalence of anemia, annual screening for anemia, and treatment of anemia with iron among children with inflammatory bowel disease (IBD). Methods: A retrospective study of U.S. pediatric patients with IBD was performed in the MarketScan commercial claims database from 2010–2014. Children (ages 1–21) with at least two inpatient or outpatient encounters for IBD who had available lab and pharmacy data were included in the cohort. Anemia was defined using World Health Organization criteria. We used logistic regression to determine differences in screening, incident anemia, and treatment based on age at first IBD encounter and sex. Results: The cohort (n=2,446) included 1,560 Crohn's disease (CD) and 886 ulcerative colitis (UC). Approximately, 85% of CD and 81% of UC were screened for anemia. Among those screened, 51% with CD and 43% with UC had anemia. Only 24% of anemia patients with CD and 20% with UC were tested for iron deficiency; 85% were iron deficient. Intravenous (IV) iron was used to treat 4% of CD and 4% UC patients overall and 8% of those with anemia. Conclusion: At least 80% of children with IBD were screened for anemia, although most did not receive follow-up tests for iron deficiency. The 43%–50% prevalence of anemia was consistent with prior studies. Under-treatment with IV iron points to a potential target for quality improvement.

Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting

Mark Steven Miller,Peter J. Allen,Powel H. Brown,Andrew T. Chan,Margie L. Clapper,Roderick H. Dashwood,Shadmehr Demehri,Mary L. Disis,Raymond N. DuBois,Robert J. Glynn,Thomas W. Kensler,Seema A. Khan 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.1

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

비교의 (불)가능성. 서울-베를린 대화에 대한 회고

밀러 스티븐스(J. Miller Stevens) 대한건축학회 2022 建築 Vol.67 No.1

광도와 Frankia 질소고정균 및 Alpova diplophloeus 외생균근균의 (外生菌根菌) 접종이 루브라 오리나무 묘목내 (苗木內) 삼자공생관계 발달에 미치는 영향

구창덕(Chang Duck Koo),Randy Molina(Randy Molina),Steven Miller(Steven Miller) 한국산림과학회 1995 한국산림과학회지 Vol.84 No.3

To investigate the effect of low light intensities and the inoculation of Frankia and/or Alpova diplophloeus on the symbioses development and their host growth, red alder(Alnus rubra Bong.) seedlings were grown in an air - filtered walk - in growth chamber with either N₂ - fixing Frankia inoculation or N - fertilization and live or dead spore inoculation of the ectomycorrhizal fungus: A. diplophloeus(Zeller & Dodge) Trappe & Smith. When they were 20 weeks old, the seedlings were grown under three levels of light intensities of 680, 320 and 220μ㏖/㎡/s PPFD(photosynthetic photon flux density) for three weeks. PPFD of 220 significantly decreased the development of A. aiplophloeus mycorrhizae and nodules, the rates of N₂ - fixation and CO₂ exchange, and the growth of tile seedlings. PPFD 320 significantly decreased the CO₂ exchange rate only. Frankia inoculation significantly increased mycorrhiza formation and seedling growth. Alpoaa inoculation significantly increased seedling growth but not nodule development and N₂- fixation. None of the symbionts affected CO₂ exchange rates. Frankia was more critical for seedling growth and mycorrhizal development than the mycorrhizal fungus for seedling growth and nodule development.

High-density single-nucleotide polymorphism maps of the human genome

Miller, Raymond D.,Phillips, Michael S.,Jo, Inho,Donaldson, Miriam A.,Studebaker, Joel F.,Addleman, Nicholas,Alfisi, Steven V.,Ankener, Wendy M.,Bhatti, Hamid A.,Callahan, Chad E.,Carey, Benjamin J.,C Elsevier 2005 Genomics Vol.86 No.2

<P><B>Abstract</B></P><P>Here we report a large, extensively characterized set of single-nucleotide polymorphisms (SNPs) covering the human genome. We determined the allele frequencies of 55,018 SNPs in African Americans, Asians (Japanese–Chinese), and European Americans as part of The SNP Consortium's Allele Frequency Project. A subset of 8333 SNPs was also characterized in Koreans. Because these SNPs were ascertained in the same way, the data set is particularly useful for modeling. Our results document that much genetic variation is shared among populations. For autosomes, some 44% of these SNPs have a minor allele frequency ≥10% in each population, and the average allele frequency differences between populations with different continental origins are less than 19%. However, the several percentage point allele frequency differences among the closely related Korean, Japanese, and Chinese populations suggest caution in using mixtures of well-established populations for case–control genetic studies of complex traits. We estimate that ∼7% of these SNPs are private SNPs with minor allele frequencies <1%. A useful set of characterized SNPs with large allele frequency differences between populations (>60%) can be used for admixture studies. High-density maps of high-quality, characterized SNPs produced by this project are freely available.</P>

Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription

Josefowicz, Steven Z.,Shimada, M.,Armache, A.,Li, Charles H.,Miller, Rand M.,Lin, S.,Yang, A.,Dill, Brian D.,Molina, H.,Park, H.S.,Garcia, Benjamin A.,Taunton, J.,Roeder, Robert G.,Allis, C. Cell Press 2016 Molecular cell Vol.64 No.2

<P>The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide. Using pharmacological and genetic approaches, we identified mitogen-and stress-activated protein kinases (MSKs) as primary mediators of H3S28ph in macrophages. Cell-free transcription assays demonstrated that H3S28ph directly promotes p300/CBP-dependent transcription. Further, MSKs can activate both signal-responsive transcription factors and the chromatin template with additive effects on transcription. Specific inhibition of MSKs in macrophages selectively reduced transcription of stimulation-induced genes. Our results suggest that MSKs incorporate upstream signaling inputs and control multiple downstream regulators of inducible transcription.</P>

Combined Dust Detection Algorithm for Asian Dust Events Over East Asia Using GK2A/AMI: a Case Study in October 2019

장재철,이수봉,손은하,노유정,Steven D. Miller 한국기상학회 2022 Asia-Pacific Journal of Atmospheric Sciences Vol.58 No.1

A combined algorithm comprising multiple dust detection methods was developed using infrared (IR) channels onboard the GEOstationary Korea Multi-Purpose SATellite 2A equipped with the Advanced Meteorological Imager (GK2A/AMI). Six cloud tests using brightness temperature difference (BTD) were utilized to reduce errors caused by clouds. For detecting dust storms, three standard BTD tests (i.e., BT12.3 - BT10.5, BT8.7 - BT10.5, and BT11.2 - BT10.5 ) were combined with the polarized optical depth index (PODI). The combined algorithm normalizes the indices for cloud and dust detection, and adopts weighted combinations of dust tests depending on the observation time (day/night) and surface type (land/sea). The dust detection results were produced as quantitative confidence factors and displayed as false color imagery, applying a dynamic enhancement background reduction algorithm (DEBRA). The combined dust detection algorithm was qualitatively assessed by comparing it with dust RGB imageries and ground-based lidar data. The combined algorithm especially improved the discontinuity in weak dust advection to the sea and considerably reduced false alarms as compared to previous dust monitoring methods. For quantitative validation, we used aerosol optical thickness (AOT) and fine mode fraction (FMF) derived from low Earth orbit (LEO) satellites in daytime. For both severe and weakened dust cases, the probability of detection (POD) ranged from 0.667 to 0.850 and it indicated that the combined algorithm detects more potential dust pixels than other satellites. In particular, the combined algorithm was advantageous in detecting weak dust storms passing over the warm and humid Yellow Sea with low dust height and small AOT.

외생균근이 수분결핍된 루브라 오리나무 묘목의 생리활동에 미치는 영향

구창덕,Molina, Randy,Miller, Steven L. 한국임학회 2000 한국산림과학회지 Vol.89 No.4

Red alder (Alnus rubra Bong.) seedlings inoculated with Frankia pure cultures were grown in a walk-in growth chamber for sixteen weeks. Half were inoculated with the spores of the ectomycorrhizal fungus Alpova diplophloeus (Zeller & Dodge) Trappe & Smith. The mycorrhizal seedlings were significantly larger than nonmycorrhizal plants in diameter, and nodule and shoot dry weight by 6 to 16% when their heights were very similar. The mycorrhizal effects on water relations of red alder seedlings were explored in a 30 hours water stress. Mycorrhizal and nonmycorrhizal seedlings did not significantly differ in leaf water potentials, CO₂ exchange rates or N₂-fixation rates during the drought. Our results suggests that A. diplophloeus mycorrhizas increased red alder seedling growth under well-watered conditions but do not affect water relations of the plant under water-stress.