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1
Chatterji, Madhabi, Young Ae Kwon, and Clarice Sng. "Gathering evidence on an after-school supplemental instruction program: Design challenges and early findings in light of NCLB." education policy analysis archives 14 (May 2, 2006): 12. http://dx.doi.org/10.14507/epaa.v14n12.2006.
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The No Child Left Behind (NCLB) Act of 2001 requires that public schools adopt research-supported programs and practices, with a strong recommendation for randomized controlled trials (RCTs) as the “gold standard” for scientific rigor in empirical research. Within that policy framework, this paper compares the relative utility of federally-recommended RCT versus the demonstrated extended term mixed-method (ETMM) designs as options for monitoring effects of novel programs in real-time field settings. Guided by the program’s theory of action, a year-long, two-phase study was conducted to monitor the context, processes and early outcomes of an after-school supplemental program in a New York elementary school. In both phases, the design combined a matched-groups, quasi-experiment with qualitative classroom observations and descriptive surveys. Early findings showed some positive, albeit “gross” program effects. Although findings are tentative, the ETMM approach enhanced interpretations by shedding light on relevant environmental variables, causes for program instabilities and sample attrition, and factors affecting treatment fidelity and scaling-up of the program beyond the pilot year.
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Heir, Jagtar Singh, Anupamjeet Kaur Sekhon, Dilip R. Thakar, Timothy A. Jackson, Javier D. Lasala, and Ronaldo V. Purugganan. "External Tracheal Manipulation Maneuver (ETMM) to Facilitate Endobronchial Blocker Placement." Journal of Cardiothoracic and Vascular Anesthesia 30, no. 4 (August 2016): 1061–63. http://dx.doi.org/10.1053/j.jvca.2015.11.005.
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Ji, Chao, Yanke Yao, Jianqiang Duan, and Wenxing Li. "Sustainable Mechanism of the Entrusted Transportation Management Mode on High-Speed Rail and the Impact of COVID-19: A Case Study of the Beijing–Shanghai High-Speed Rail." Sustainability 14, no. 3 (January 20, 2022): 1171. http://dx.doi.org/10.3390/su14031171.
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The transport management mode fundamentally determines the sustainable development of high-speed rail passenger transport (HSRPT), which was shocked by the COVID-19 pandemic in 2020. In order to study the sustainable development mechanism of HSRPT and the impact of COVID-19, primarily based on the data from the Beijing–Shanghai high-speed rail (HSR) taken from 2018, we adopt system dynamics (SD) to provide a scenario simulation method to examination sustainable operation status of HSRPT under the entrusted transportation management mode (ETMM) by VENSIM, and take into account the following two evaluation indicators: economic and operational. The results show the following: (1) Transportation demand and commissioned transportation management fees play a vital role in the sustainable operation of the Beijing–Shanghai HSR, causing significant changes in transportation revenue and transportation costs. (2) COVID-19 had a great impact on the sustainable operation of the Beijing–Shanghai HSR. In 2020, the turnover and transportation profit of the Beijing–Shanghai HSR fell by 74.31% and 49.19%, respectively. In 2022, the transportation profit can be restored to the level of 2019. The study results reveal that Beijing–Shanghai HSR under the ETMM has a good sustainable development capability.
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Kumar, Sachin, Antony Michealraj, Leo Kim, Jeremy Rich, and Michael Taylor. "ETMM-08 METABOLIC REGULATION OF THE EPIGENOME DRIVES LETHAL INFANTILE EPENDYMOMA." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15—i16. http://dx.doi.org/10.1093/noajnl/vdab024.064.
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Abstract Ependymomas are malignant glial tumours that occur throughout the central nervous system. Of the nine distinct molecular subgroups of ependymoma, Posterior Fossa A (PFA), is the most prevalent, occurring in the hindbrain of infants and young children. Lacking highly recurrent somatic mutations, PFAs are thought to be a largely epigenetically driven entity, defined by hypomethylation at the histone 3 lysine 27 residue. Previous transcriptional analysis of PFAs revealed an enrichment of hypoxia signaling genes. Thus, we hypothesized that hypoxic signaling, in combination with a unique metabolic milieu, drive PFA oncogenesis through epigenetic regulation. In this study, we identified that PFA cells control the availability of specific metabolites under hypoxic conditions, resulting in diminished H3K27 trimethylation and increased H3K27 acetylation in vitro and in vivo. Unique to PFA cells, transient exposure to ambient oxygen results in irreversible cellular toxicity. Furthermore, perturbation of key metabolic pathways is sufficient to inhibit growth of PFA primary cultures in vitro. PFA cells sequester s-adenosylmethionine while upregulating EZHIP, a polycomb repressive complex 2 (PRC2) inhibitor, resulting in decreased H3K27 trimethylation. Furthermore, hypoxia fine-tunes the abundance of alpha-ketoglutarate and acetyl-CoA to fuel demethylase and acetyltransferase activity. Paradoxically, a genome-wide CRISPR knockout screen identified the core components of PRC2 as uniquely essential in PFAs. Our findings suggest that PFAs thrive in a narrow “Goldilocks” zone, whereby they must maintain a unique epigenome and deviation to increased or decreased H3K27 trimethylation results in diminished cellular fitness. Previously, we showed that PFAs have a putative cell of origin arising in the first trimester of development. Using single-cell RNAseq and metabolomics, we demonstrate that PFAs resemble the natural metabolic-hypoxic milieu of normal development. Therefore, targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
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Garcia, Joseph H., Saket Jain, Erin A. Akins, Angad S. Beniwal, Kayla J. Wolfe, Jungwha Cha, Sanjay Kumar, and Manish K. Aghi. "ETMM-09 TARGETING GLIOBLASTOMA MULTIFORME METABOLISM AT THE INVASIVE TUMOR FRONT." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i16. http://dx.doi.org/10.1093/noajnl/vdab024.065.
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Abstract Glioblastoma (GBM) is a primary malignant brain tumor with a median survival under two years. The poor prognosis GBM caries is largely due to cellular invasion, which enables escape from resection and drives inevitable recurrence. Numerous factors have been proposed as the primary driving forces behind GBM’s ability to invade adjacent tissues rapidly, including alterations in its cellular metabolism. Though studies have investigated links between GBM’s metabolic profile and its invasive capabilities, these studies have had two notable limitations. First, while infiltrating GBM cells utilize adaptive cellular machinery to overcome stressors in their microenvironment, the cells at the invasive tumor front have rarely been sampled in previous studies, which have primarily used banked tissue taken from the readily accessible tumor core. Second, studies of invasion have primarily used two-dimensional (2D) culture systems, which fail to capture the dimensionality, mechanics, and heterogeneity of GBM invasion. To address these limitations, our team developed two complementary approaches: acquisition of site-directed biopsies from patient GBMs to define regional heterogeneity in invasiveness, and engineering of three dimensional (3D) platforms to study invasion in culture. Through utilization of these platforms, and by taking advantage of the system-wide, unbiased screens of metabolite profile and gene expression available, our team looked to accomplish the goal of identifying targetable metabolic factors which drive cellular invasion in GBM. Pilot RNA-Sequencing data revealed 87 of the top 250 (35%) genes preferentially expressed in the tumor invasive edge, and 30 of the top 250 (12%) genes preferentially expressed in the tumor core were involved in cellular metabolism. KEGG pathways analysis demonstrated enrichment of glycolytic, pentose phosphate, and response to amino acid starvation pathways at the tumor invasive edge. These preliminary studies demonstrate a distinct metabolic phenotype in invasive GBM cells which will be further explored with system wide screens.
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Torrini, Consuelo, Trang Nguyen, Chang Shu, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Georg Karpel-Massler, Jeffrey Bruce, Peter Canoll, and Markus Siegelin. "ETMM-05. LACTIC ACID FACILITATES GLIOBLASTOMA GROWTH THROUGH MODULATION OF THE EPIGENOME." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15. http://dx.doi.org/10.1093/noajnl/vdab024.061.
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Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor with an unfavorable prognosis. While GBMs utilize glucose, there are other carbon sources at their disposal. Lactate accumulates to a significant amount in the infiltrative margin of GBMs. In the current study, we demonstrated that lactate rescued patient-derived xenograft (PDX) GBM cells from nutrient deprivation mediated cell death and inhibition of growth. Transcriptome analysis, ATAC-seq and CHIP-seq. showed that lactic acid exposure entertained a signature of cell cycle progression and oxidative phosphorylation (OXPHOS) /tricarboxylic acid (TCA)-cycle. LC/MS analysis demonstrated that U-13C-Lactate elicited substantial labeling of TCA-cycle metabolites, acetyl-CoA and histone protein acetyl-residues in PDX derived GBM cells. Given that acetyl-CoA is pivotal for histone acetylation we observed a dose-dependent elevation of histone marks (e.g. H3K27ac), which was rescued by genetic and pharmacological inhibition of lactic acid-uptake, ATP-citrate lyase, p300 histone-acetyl-transferase and OXPHOS, resulting in reversal of lactate mediated protection from cell death. CHIP-seq. analysis demonstrated that lactic acid facilitated enhanced binding of H3K27ac to gene promoters and cis-regulatory elements. Consistently, ATAC-seq. analysis highlighted enhanced accessibility of the chromatin by lactic acid. In a combined tracer experiment (U-13C-glucose and 3-C13-lactate), we made the fundamental observation that lactic acid carbons were predominantly labeling the TCA cycle metabolites over glucose, implying a critical role of lactic acid in GBMs. Finally, pharmacological blockage of the TCA-cycle, using a clinically validated drug, extended overall survival in an orthotopic PDX model in mice without induction of toxicity, implying a critical role of lactic acid in GBMs and establishing lactic acid metabolism as a novel drug target for GBM.
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Minami, Jenna, Nicholas Bayley, Christopher Tse, Henan Zhu, Danielle Morrow, William Yong, Linda Liau, Timothy F. Cloughesy, Thomas Graeber, and David A. Nathanson. "ETMM-02. PRECLINICAL MODELS REVEAL BRAIN-MICROENVIRONMENT SPECIFIC METABOLIC DEPENDENCIES IN GLIOBLASTOMA." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i14. http://dx.doi.org/10.1093/noajnl/vdab024.058.
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Abstract Metabolic reprogramming is a hallmark of cancer, and malignant cells must acquire metabolic adaptations in response to a multitude of intrinsic and extrinsic factors to fuel neoplastic progression. Mutations or changes in metabolic gene expression can impose nutrient dependencies in tumors, and even in the absence of metabolic defects, cancer cells can become auxotrophic for particular nutrients or metabolic byproducts generated by other cells in the tumor microenvironment (TME). Conventional cell lines do not recapitulate the metabolic heterogeneity of glioblastoma (GBM), while primary cultured cells do not account for the influences of the microenvironment and the blood brain barrier on tumor biology. Additionally, these systems are under strong selective pressure divergent from that in vivo, leading to reduced heterogeneity between cultured tumor cells. Here, we describe a biobank of direct-from-patient derived orthotopic xenografts (GliomaPDOX) and gliomaspheres that reveal a subset of gliomas that, while able to form in vivo, cannot survive in vitro. RNA sequencing of tumors that can form both in vivo and in vitro (termed “TME-Indifferent”) compared to that of tumors that can only form in vivo (termed “TME-Dependent”) revealed transcriptional changes associated with altered nutrient availability, emphasizing the unique metabolic programs impacted by the tumor microenvironment. Furthermore, TME-dependent tumors lack metabolic signatures associated with nutrient biosynthesis, thus indicating a potential dependency of these tumors on scavenging specific nutrients from the extracellular milieu. Collectively, these data emphasize the metabolic heterogeneity within GBM and reveal a subset of gliomas that lack metabolic plasticity, indicating a potential brain-microenvironment specific metabolic dependency that can be targeted for therapy.
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Li, Mao, Shuxin Zhang, Wanchun Yang, Yuan Yang, Dejiang Pang, Qing Mao, Mina Chen, and Yanhui Liu. "ETMM-06. ELEVATED MITOCHONDRIAL TOM20 EXPRESSION SUPPRESSES GLIOMA MALIGNANCY BY ENHANCING OXIDATIVE PHOSPHORYLATION." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15. http://dx.doi.org/10.1093/noajnl/vdab024.062.
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Abstract BACKGROUND Malignant glioma display a metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation (OXPHOs). However, the underlying mechanism for this metabolic switch in glioma is not well elucidated. Mitochondrial translocases of the outer/inner membrane (TOMs/TIMs) import proteins into mitochondria, and could thereby regulate OXPHOs. The objective of this study is to investigate the expression of TOM/TIM members in glioma, as well as their functional and therapeutic implications. METHODS Transcriptome sequencing (RNA-seq), real-time PCR, Western blot, and immunohistochemistry were used to identify Tom20 as a significantly downregulated TOM/TIM protein in 20 paired glioma/Peritumoral tissues. To study the biological function of Tom20 in glioma, we interrogated metabolic alterations in Tom20 overexpressed glioma cells by GC-MS metabolomics, acetyl-CoA assay, and Seahorse assay. We compared the cell proliferation and viability profiles between Tom20 overexpressed and control cells in vitro and in vivo. To investigate the therapeutic implication of Tom20 expression, we tested OXPHOs inhibitor metformin in Tom20 overexpressed cells and xenograft mouse models. RESULTS We find that Tom20, a critical component of the mitochondrial outer membrane translocases, is downregulated in malignant gliomas. Using an integrative approach spanning bioinformatic analysis, metabolomics, and functional approaches, we reveal that Tom20 elevation activates mitochondrial OXPHOs in glioma cells and reduces tumor malignancy. We also find that Tom20 upregulation sensitizes glioma cells to metformin in vitro, and improves the therapeutic efficacy of metformin in glioma in vivo. CONCLUSION Our work defines Tom20 as a glioma suppressor and an indicator of metformin treatment in glioma.
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Li, Kehong, Wenke Wang, Yadong Zhang, Tao Zheng, and Jin Guo. "Game Modelling and Strategy Research on the System Dynamics–based Quadruplicate Evolution for High–speed Railway Operational Safety Supervision System." Sustainability 11, no. 5 (March 1, 2019): 1300. http://dx.doi.org/10.3390/su11051300.
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In view of the entrusted transportation management model (ETMM) of China’s high–speed railway (HSR), the supervision strategy of an HSR company for its multiple agents plays a very important role in ensuring the safety and sustainable development of HSR. Due to the existence of multiple agents in ETMM, the supervision strategy for these agents is usually difficult to formulate. In this study, a quadruplicate HSR safety supervision system evolutionary game model composed of an HSR company and three agents was established through the analysis of the complex game relationship existing in the system. The behavioral characteristics and the steady state of decision–making of all stakeholders involved in the system are proved by evolutionary game theory and system dynamics simulation. The results show that there will be long–term fluctuations in the strategies selected by the four stakeholders in the static reward–penalty control scenario (RPCS), which indicates that an evolutionary stable strategy does not exist. With increases in the reward–penalty coefficient, the fluctuations are intensified. Therefore, the dynamic RPCS was proposed to control the fluctuations, and the simulation was repeated. The results show that the fluctuations can be effectively restrained by adopting the dynamic RPCS, but if the coefficients are the same, the static RPCS is better than the dynamic RPCS for increasing the safety investment rate of the three agents. This demonstrates that the HSR company should apply these two control scenarios flexibly according to the actual situation when formulating a supervision strategy in order to effectively control and enhance the safety level of HSR operations when multiple agents are involved.
10
Chi, Yudan, Jan Remsik, Vaidotas Kiseliovas, Camille Derderian, Ugur Sener, Majdi Alghader, Fadi Saadeh, et al. "ETMM-03. CANCER CELLS DEPLOY LIPOCALIN- 2 TO COLLECT LIMITING IRON IN LEPTOMENINGEAL METASTASIS." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i14. http://dx.doi.org/10.1093/noajnl/vdab024.059.
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Abstract The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)-filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. A Phase Ia/1b clinical trial focused on this novel treatment approach is underway.
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Chatterji, Madhabi. "Evidence on “What Works”: An Argument for Extended-Term Mixed-Method (ETMM) Evaluation Designs." Educational Researcher 33, no. 9 (December 2004): 3–13. http://dx.doi.org/10.3102/0013189x033009003.
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Chatterji, Madhabi. "Evidence on “What Works”: An Argument for Extended-Term Mixed-Method (ETMM) Evaluation Designs." Educational Researcher 34, no. 5 (June 2005): 14–24. http://dx.doi.org/10.3102/0013189x034005014.
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White, Brian E., Edward Liu, Hakon Hakonarson, and Russell J. Buono. "ETMM-07. HYPOXIC REGULATION OF METABOLIC AND STRUCTURAL GENES IN T98 GLIOBLASTOMA MULTIFORME CELLS BY RNA SEQUENCING." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15. http://dx.doi.org/10.1093/noajnl/vdab024.063.
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Abstract Glioblastoma multiforme (GBM) is the most common primary brain cancer and carries a very poor prognosis. The GBM tumor microenvironment is characterized by regions of profound hypoxia, which are associated with a variety of alterations in gene expression that confer survival, proliferation, and resistance to therapy. Multiple mechanisms have been implicated in hypoxia-associated GBM behavior including upregulation of pathways involved in angiogenesis, immunosuppression, and glucose metabolism. Our study aimed to identify changes in gene expression induced by hypoxia among T98G cells via total RNA sequencing. Human T98 GBM cell lines were cultured in a humidified incubator at 37° C and 5% CO2 and were grown in normoxia (21% O2) or hypoxia (95% N2, 5% C02) for 72 hours. Total RNA was harvested, and global gene expression was evaluated via total RNA sequencing. Standard bioinformatics analysis was performed to identify changes in expression associated with hypoxia. Hypoxia in T98 cells led to significant upregulation of genes implicated in canonical glycolysis, focal adhesion, extracellular matrix reorganization, and endoplasmic reticulum-associated protein processing. We document 690 genes and 11 associated KEGG pathways that demonstrated significant enrichment (p ≤0.01 with Bonferroni, Benjamini, and False Discovery Rate corrections) induced by hypoxia. Notably, upregulation of the IRE1-mediated unfolded protein response was observed. DrugBank database analysis identified four molecules targeting genes upregulated in hypoxic T98G cells: tenecteplase (p = 0.013, 5 gene targets), succinic acid (p = 0.02, 7 targets), artenimol (p = 0.013, 13 targets), and copper (p = 0.0015, 22 targets). We document 733 genes and 6 associated KEGG pathways significantly downregulated (p ≤0.01) in hypoxia, including genes associated with DNA replication and repair, mitotic processes, and spliceosome function. Total RNA sequencing showed hypoxic upregulation of genes involved in various pathways associated with neoplastic GBM behavior and identified multiple candidate molecules which may hold therapeutic potential.
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Silver, Daniel J., Gustavo A. Roversi, Nazmin Bithi, Chase K. A. Neumann, Katie M. Troike, Grace K. Ahuja, Ofer Reizes, J. Mark Brown, Christopher Hine, and Justin D. Lathia. "ETMM-01. CANCER STEM CELL ENRICHMENT AND METABOLIC SUBSTRATE ADAPTABILITY ARE DRIVEN BY HYDROGEN SULFIDE SUPPRESSION IN GLIOBLASTOMA." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i14. http://dx.doi.org/10.1093/noajnl/vdab024.057.
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Abstract Glioblastoma (GBM) remains among the deadliest of human malignancies. The emergence of the cancer stem cell (CSC) phenotype represents a major challenge to disease management and durable treatment response. The extrinsic, environmental, and lifestyle factors that result in CSC enrichment are not well understood. The CSC state endows cells with a fluid metabolic profile, enabling the utilization of multiple nutrient sources. Therefore, to test the impact of diet on CSC enrichment, we evaluated disease progression in tumor-bearing mice fed an obesity-inducing high-fat diet (HFD) versus an energy-balanced, low-fat control diet. HFD consumption resulted in hyper-aggressive disease that was accompanied by CSC enrichment and shortened survival. HFD consumption also drove intracerebral accumulation of saturated fats, which in turn inhibited the production and signaling of the gasotransmitter hydrogen sulfide (H2S). H2S is an endogenously produced bio-active metabolite derived from sulfur amino acid catabolism. It functions principally through protein S-sulfhydration and regulates a variety of programs including mitochondrial bioenergetics and cellular metabolism. Inhibition of H2S synthesis resulted in increased proliferation and chemotherapy resistance, whereas treatment with H2S donors led to cytotoxicity and death of cultured GBM cells. Compared to non-cancerous controls, patient GBM specimens were reduced in overall protein S-sulfhydration, which was primarily lost from proteins regulating cellular metabolism. These findings support the hypothesis that diet-regulated H2S signaling serves to suppress GBM by restricting metabolic adaptability, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H2S bioavailability concurrent with GBM standard of care may improve outcomes for GBM patients.
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Nguyen, Trang, Chang Shu, Enyuan Shang, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hasan Akman, et al. "ETMM-04. AURKA INHIBITION REPROGRAMS METABOLISM AND IS SYNTHETICALLY LETHAL WITH FATTY ACID OXIDATION INHIBITION IN GLIOBLASTOMA MODEL SYSTEMS." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15. http://dx.doi.org/10.1093/noajnl/vdab024.060.
Abstract:
Abstract Aurora kinase A (AURKA) has emerged as a viable drug target for glioblastoma (GBM), the most common malignant primary brain tumor in adults with a life expectancy of 12–15 months. However, resistance to therapy remains a critical issue, which partially may be driven by reprogramming of metabolism. By integration of transcriptome, chromatin immunoprecipitation with sequencing (CHIP-seq.), assay for transposase-accessible chromatin with sequencing (ATAC-seq.), proteomic and metabolite screening followed by carbon tracing (U-13C-Glucose, U-13C-Glutamine and U-13C-Palmitic acid) and extracellular flux analysis we provided evidence that genetic (shRNA and CRISPR/Cas9) and pharmacological (Alisertib) AURKA inhibition elicited substantial metabolic reprogramming supported in part by inhibition of MYC targets and concomitant activation of PPARA signaling. While glycolysis was suppressed by AURKA inhibition, we noted a compensatory increase in oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO). Whereas interference with AURKA elicited a suppression of c-Myc, we detected an upregulation of PGC1A, a master regulator of oxidative metabolism. Silencing of PGC1A reversed AURKAi mediated metabolic reprogramming and sensitized GBM cells to AURKAi driven reduction of cellular viability. Chromatin immunoprecipitation experiments showed binding of c-Myc to the promoter region of PGC1A, which is abrogated by AURKA inhibition and in turn unleashed PGC1A expression. Consistently, ATAC-seq. confirmed higher accessibility of a MYC binding region within the PGC1A promoter, suggesting that MYC acts as a repressor of PGC1A. Combining alisertib with inhibitors of FAO or the electron transport chain exerted substantial synergistic growth inhibition in PDX lines in vitro and extension of overall survival in orthotopic GBM PDX models without induction of toxicity in normal tissue. In summary, these findings support that simultaneous targeting of oxidative energy metabolism and AURKAi might be a potential novel therapy against GBM.
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Rizaldi, Sony, Slamet Suhartono, Syofyan Hadi, and Tomy Michael. "Role of head of states at G20 High Level Conference in utilizing environmental of sustainable development on electricity in Indonesia." Technium Social Sciences Journal 38 (December 9, 2022): 197–203. http://dx.doi.org/10.47577/tssj.v38i1.7850.
Abstract:
Dependence on fossil energy sources as fuel for power generation still dominates most systems to meet the needs of electrical energy in Indonesia. Efforts to reduce fossil fuels for power generation and switch to new and renewable energy are pursued by the government with the issuance of regulations concerning the National Energy Policy. The responsibility of the government in the context of national energy management has a very decisive role for the sustainability of the national energy supply that is safe, reliable and environmentally friendly. To implement the provisions of Chapter 11 (2) UURI Number 30 of 2007 concerning Energy. The regulation of the EBT issue is regulated in Chapter 4 (2) and (3) of the Republic of Indonesia Law Number 30/2007, where it is stated that: Chapter 4 (2) New energy resources and renewable energy resources are regulated by the State and utilized for the greatest prosperity of the people. The G20 agreed on the "Bali Compact", which was the result of the Energy Transitions Ministerial Meeting (ETMM), in Bali, last September 2022, which contained nine principles. The "Bali Compact" is an important part of accelerating the energy transition. The G20 Summit, the Bali Leader's Declaration document can be reached and agreed upon by all state leaders present.
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Wardani, Retno Sulistyo, Michael Lekatompessy, and Brent Anthony Senior. "Modified transnasal endoscopic medial maxillectomy with inferior turbinate flap for dentigerous cyst." Oto Rhino Laryngologica Indonesiana 45, no. 2 (December 31, 2015): 151. http://dx.doi.org/10.32637/orli.v45i2.119.
Abstract:
Background: Dentigerous cyst is one of the most frequent types of odontogenic cyst that usually involving an impacted, supernumerary or ectopically erupted tooth. One of the non-dental sites for ectopiceruption is the maxillary sinus. The traditional approach under such circumstances is a Caldwell-Luc maxillotomy, but this type of procedure may result in significant long-term complications. Endoscopic transnasal medial maxillectomy (ETMM) has several advantages, such as good il lumination, as wellas clear and magnified visualization. The new modified endoscopic transnasal medial maxillectomy(METMM) can provide good visualization and more functional result by preserving the nasolacrimalduct and the inferior turbinate. Purpose: We present this case to introduce the METMM technique forextirpation of any tumor in the maxillary sinus. Case: One case of dentigerous cyst with an ectopicleft maxillary 3 molar tooth in a 27 year old woman who presented with sinusitis. Management:Surgery with a METMM technique to enucleate the cyst, combined with functional endoscopic sinussurgery (FESS) for the sinusitis. The patient then evaluated subjectively for epiphora and objectivelywith nasoendoscopic examination. Conclusion: In this case, METMM was effective in accessing themaxillary sinus allowing for tumor extirpation, while preserving the function of the inferior tubinate andnasolacrimal duct. Keywords : Dentigerous cyst, maxillary ectopic tooth eruption, transnasal medial maxillectomy ABSTRAKLatar belakang: Kista dentigerous merupakan salah satu jenis kista otontogenik yang paling sering ditemukan, biasanya berhubungan dengan gigi impaksi, supernumeri atau gigi yang tumbuhektopik. Salah satu tempat erupsi ektopik adalah sinus maksilaris. Pendekatan tradisional dalamkeadaan ini adalah operasi Caldwell-Luc, tetapi teknik operasi ini dapat mengakibatkan komplikasijangka panjang. Maksilektomi medial transnasal dengan endoskopi (MMTE) memiliki beberapakeunggulan, seperti visualisasi yang jelas dan diperbesar. Teknik maksilektomi medial transnasaldengan endoskopi yang dimodifikasi (MMTEM) dapat memberikan visualisasi yang baik dan hasillebih fungsional dengan mempertahankan duktus nasolakrimal dan konka inferior. Tujuan: makalahini diajukan untuk memperkenalkan teknik MMTEM untuk ekstrirpasi massa yang berada di dalamsinus maksila, karena teknik ini memberikan hasil yang lebih fungsional. Kasus: melaporkan satu kasuskista dentigerous dengan gigi molar 3 yang erupsi ektopik pada sinus maksila kiri pada wanita 27tahun. Penatalaksanaan: kasus ini ditatalaksana dengan teknik MMTEM untuk mengenukleasi kistadan BSEF untuk sinusitis. Pasien kemudian dievaluasi secara subjektif dengan anamnesis mengenaiadanya epifora dan objektif dengan pemeriksaan nasoendoskopi. Kesimpulan: MMTEM terbukti efektifuntuk ekstirpasi tumor yang berada di dalam sinus maksila, dan teknik ini juga memberikan hasil yanglebih fungsional dengan dipertahankannya konka inferior dan duktus nasolakrimal. Kata kunci : Kista dentigerous, erupsi gigi ektopik di maksila, transnasal maksilektomi medial
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Giardini, L., and M. Borin. "MAXIMUM EVAPOTRANSPIRATION (ETM) AND AGRONOMICAL MAXIMUM EVAPOTRANSPIRATION (ETMA) OF PROCESSING TOMATO AND POTATO IN THE VENETO ENVIRONMENT." Acta Horticulturae, no. 278 (June 1990): 815–24. http://dx.doi.org/10.17660/actahortic.1990.278.81.
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De Albuquerque, Adolfo Vasconcelos. "Tremor Essencial." Revista Neurociências 18, no. 3 (March 31, 2001): 401–5. http://dx.doi.org/10.34024/rnc.2010.v18.8464.
Abstract:
O tremor essencial é um dos mais frequentes motivos de consulta ao neurologista e sempre foi considerado uma desordem monosintomática e benigna. Hoje, no entanto, há fortes evidências de que o tremor essencial é uma doença heterogênea e lentamente progressiva, podendo causar importante diminuição da qualidade de vida de alguns pacientes. Pode ocorrer de forma esporádica ou com padrão familiar, até o momento há três loci cromossômicos relacionados ao tremor essencial, são eles: cromossomo 3q13 (ETM1), 2p22 (ETM2) e 6p23. O principal diagnóstico diferencial é o parkinsonismo. As drogas de escolha para o tratamento ainda são o propranolol e a primidona, mas a gabapentina, o topiramato e o alprazolam são opções terapêuticas. A cirurgia está indicada para casos graves e refratários. Neste estudo de revisão buscamos uma atualização sobre os principais aspectos do tremor essencial já que é uma doença comum na prática diária de qualquer médico.
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Bunt, Jens, Sander Lambo, Jonathan Lim, Monika Mauermann, Stefan Pfister, Linda Richards, and Marcel Kool. "ETMR-13. NFI GENES IN ETMR TUMORIGENESIS AND NEURODEVELOPMENT." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii325. http://dx.doi.org/10.1093/neuonc/noaa222.217.
Abstract:
Abstract Embryonal tumors with multilayered rosettes (ETMRs) are aggressive pediatric embryonal brain tumors with a universally poor prognosis. These tumors are commonly characterized by amplification of C19MC, but other miRNA-related aberrations, such as DICER mutations or MIR17HG amplifications, are also observed. Nevertheless, it remains unknown how these aberrations are driving the tumorigenesis. We applied miRNA target prediction to investigate the downstream targets shared by these aberrations affecting normal brain development and tumorigenesis. The nuclear factor one (NFI) family of transcription factors were found to be top candidates shared by both miRNA clusters. These genes are expressed at very low levels in ETMRs, in contrast to other brain tumors. During normal brain development these genes are expressed in radial glial progenitors and are required for the transition of proliferation to differentiation. Since radial glial progenitors are the potential cell-of-origin of ETMRs, we hypothesize that downregulation of NFI is required for the proliferative, undifferentiated state of ETMRs. Indeed, mouse models with deletion of an Nfi family member display sustained proliferation and delayed differentiation of radial glial progenitors during development. This leads into brain overgrowth, which has also been observed in humans with intellectual disabilities caused by NFI haploinsufficiency. When multiple Nfi family members are simultaneously targeted in mice, the progenitors are retained and both neurogenesis and gliogenesis are inhibited, resulting in a neuropathology similar to that of human ETMR tumors. Hence, downregulation of NFI genes resulting from miRNA aberrations could contribute to the developmental state and possibly tumorigenesis of ETMRs.
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Vehbi Umut ;YÜCER, ERKAN. "AYIRT ETME GÜCÜ." Ankara Üniversitesi Hukuk Fakültesi Dergisi 60, no. 3 (2011): 485–522. http://dx.doi.org/10.1501/hukfak_0000001636.
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Hovestadt, Volker, McKenzie L. Shaw, Alexander Beck, Sander Lambo, Olivia A. Hack, Johannes Gojo, Sibylle Madlener, et al. "ETMR-17. SINGLE-CELL TRANSCRIPTOME ANALYSIS OF ETMR PATIENT SAMPLES." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii326. http://dx.doi.org/10.1093/neuonc/noaa222.220.
Abstract:
Abstract Brain tumors are comprised of cells with heterogeneous genetic and transcriptional states, resulting in substantial phenotypic diversity. This diversity is particularly evident in embryonal tumor with multilayered rosettes (ETMR), which shows a striking bi-phasic pattern for which it is named. A better understanding of its underlying molecular makeup is urgently needed to develop more effective therapeutic strategies that eliminate all malignant cell types underlying ETMR initiation, maintenance, progression, and relapse. Furthermore, the cellular origin of ETMR is currently poorly understood. We used plate-based single-cell RNA sequencing to assess the intratumoral heterogeneity in 6 fresh and 4 snap-frozen surgical biopsies, following a workflow that we have previously established to study pediatric high grade gliomas, medulloblastomas, and ependymomas. Computational analyses conducted on >4,000 single cells identified cellular hierarchies ranging from a proliferative, undifferentiated cell population to more differentiated, predominantly neural-like progeny in all samples. Patient-derived cell line and xenograft models partially recapitulated this hierarchy. We further integrated transcriptional programs identified in single cells with available datasets of the developing normal brain, as well as with programs identified in other pediatric brain tumor entities, to inform both putative cellular origins and ETMR-specific oncogenic pathways. These timely results provide unparalleled insights into the molecular underpinnings of the phenotypic heterogeneity observed in ETMR. Analyses aimed at further integrating malignant cell type abundances with genetic alterations and clinical annotations, and therapeutical targeting of malignant cell populations using in-vitro models are currently ongoing.
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Goodyke, Austin, Shannon Kelly, Joseph Zagorski, Elizabeth VanSickle, Tyler Maser, Caryl Sortwell, Christopher Kemp, Abhinav Nagulapally, Karl Dykema, and Giselle Saulnier-Sholler. "ETMR-18. TARGETING Lin28 IN ETMR WITH ODC1 INHIBITOR DFMO." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii326. http://dx.doi.org/10.1093/neuonc/noaa222.221.
Abstract:
Abstract Embryonal tumor with multilayered rosettes (ETMR), is an aggressive brain tumor primarily occurring in young patients (<4 years of age) and characterized by C19MC amplification and Lin28 overexpression. These genetic hallmarks have been shown to participate in driving ETMR in a C19MC-Lin28-MYCN circuit. Reducing Lin28 disrupts this circuit and reduces cell viability in ETMR models. Investigation of therapeutic agents targeting this pathway is required to provide new treatment options for this deadly disease. We present data showing the effect of DFMO (α-difluoromethylornithine) in ETMR, an ODC1 inhibitor known to reduce Lin28 in neuroblastoma. DFMO treatment of the ETMR cell line BT-183 resulted in a significant reduction of intracellular Lin28 protein levels (P<0.05) as indicated by flow cytometry. In concert with this reduction in Lin28, there was a as significant reduction in viable cells (P<0.05), and the number of CD133+ cells were reduced 2-fold (P<0.05). High throughput drug testing of BT-183 identified a number of additional therapeutic agents with potential therapeutic efficacy for ETMR and combining these with cytostatic agent DFMO demonstrated the potential use of these drugs in combination. These in vitro data were complemented by testing of DFMO in an in vivo stereotaxic xenograft ETMR model, with inhibition of tumor burden monitored by bioluminescent imaging of the tumors. Together this work shows that Lin28 targeting agents such as DFMO merit further examination and integrating these types of agents into treatment strategies for ETMR may lead to better outcomes.
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Kirchin, Simon. "For ETMP Spring 2018." Ethical Theory and Moral Practice 21, no. 2 (April 2018): 201–2. http://dx.doi.org/10.1007/s10677-018-9889-3.
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McElwee, Brian. "ETMP BSET 2018 Editorial." Ethical Theory and Moral Practice 21, no. 5 (November 2018): 1033–34. http://dx.doi.org/10.1007/s10677-019-09974-w.
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Cocito, Carolina, Esteban Uceda Arias-Stella, Christopher C. Padilla, Xiaohu Zhang, Crystal McKnight, Zina Itkin, Carleen Klumpp-Thomas, et al. "ETMR-05. DEVELOPMENT OF NOVEL PRECLINICAL MODELS AND THERAPEUTIC STRATEGIES FOR ETMR." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.175.
Abstract:
Abstract BACKGROUND Embryonal Tumor with Multilayered Rosettes (ETMR) is a very rare, aggressive pediatric brain tumor with a dismal 5-year overall survival rate. Few genetic aberrations in miRNA clusters and processing machinery have been detected in ETMRs with 90% of ETMR patients having the C19MC amplification. ETMRs show unique histopathological features which, together with the detection of C19MC or DICER alterations, are necessary for diagnosis. The cellular and molecular mechanisms underlying ETMR development are poorly understood, and targeted therapeutics have not been developed due to scarcity of preclinical models. To expand knowledge of ETMR biology and accelerate the design of novel and therapies, it is thus essential to develop preclinical models. METHODS We have generated two novel patient-derived ETMR cell lines from resected patient derived tumor samples (CTBP-03A and CBTP-139) and created three patient-derived xenograft (PDX) models (CTBP-03A, CBTP-139 and CBTP-38). We have used these unique patient-derived cell lines to identify mechanisms driving ETMR development and progression. To identify novel therapeutic targets, we conducted high-throughput drug screening (HTDS) utilizing 2480 approved and investigational drugs, against the CBTP-03A and CBTP-139 lines. RESULTS Among the candidate drugs showing an inhibitory effect on both lines, compounds were selected based on their activity, CNS penetration ability, mechanism of action, and bioavailability, if known. The top selected hits were screened in an all-versus-all format, totaling 1953 combinations. The rapidity of action and efficacy of the top choice compounds used as single agent or in double and triple combination was assessed by caspase glow and cell titer glow assays. This initial combination screen identified DNA replication stress, retinoid receptor agonist and FGF signaling as potential combinatorial targets. Data are currently being validated in vivo. CONCLUSIONS This is the first combinatorial HTDS on two novel patient-derived cell lines which highlighted potential drug combination strategies for the treatment of ETMR.
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Minoda, Masahiko, Tomomi Otsubo, Yohei Yamamoto, Jianxin Zhao, Yoshitomo Honda, Tomonari Tanaka, and Jin Motoyanagi. "The First Synthesis of Periodic and Alternating Glycopolymers by RAFT Polymerization: A Novel Synthetic Pathway for Glycosaminoglycan Mimics." Polymers 11, no. 1 (January 5, 2019): 70. http://dx.doi.org/10.3390/polym11010070.
Abstract:
This study concerned the controlled synthesis of periodic glycopolymers by reversible addition-fragmentation chain transfer (RAFT) copolymerization. To this end, maltose- and lactose-substituted vinyl ethers (MalVE and LacVE, respectively) and maltose-substituted maleimide (MalMI) were newly synthesized. RAFT copolymerization of MalVE and ethyl maleimide (EtMI) (monomer feed ratio: MalVE:EtMI = 1:1) afforded periodic glycopolymers (poly(MalVE-co-EtMI)) consisting of major parts of alternating structure (-(MalVE-EtMI)n-) and a small part of consecutive sequences of EtMI (–EtMI-EtMI-). Occurrence of the latter sequences was caused by the homopolymerizability of maleimide under the present polymerization condition, and the formation of the consecutive sequences of EtMI was successfully suppressed by varying the monomer feed ratio. RAFT copolymerization of LacVE and EtMI was also found to proceed and similarly yielded periodic glycopolymers (poly(LacVE-co-EtMI)). Moreover, RAFT copolymerization of LacVE and MalMI (monomer feed ratio: LacVE:MalMI = 1:1) was performed to give copolymers (poly(LacVE-co-MalMI)) having composition ratio of LacVE/MalMI ≈ 36/64. The resultant periodic glycopolymers poly(MalVE-co-EtMI) and poly(LacVE-co-EtMI) were subjected to lectin binding assay using concanavalin A and peanut agglutinin, exhibiting the glycocluster effect. Moreover, these glycopolymers obtained from the copolymerization of VE and MI were found to be non-cytotoxic.
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de Faria, Flavia W., Carolin Walter, Marta Interlandi, Viktoria Melcher, Nicole Riedel, Monika Graf, Natalia Moreno, et al. "ETMR-05. Single-cell transcriptomics of ETMR reveals developmental cellular programs and tumor-pericyte communications in the microenvironment." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i50. http://dx.doi.org/10.1093/neuonc/noac079.183.
Abstract:
Abstract BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) are pediatric brain tumors bearing a grim prognosis, despite intensive multimodal therapeutic approaches. Insights into cellular heterogeneity and cellular communication of tumor cells with cells of the tumor microenvironment (TME), by applying single-cell (sc) techniques, potentially identify mechanisms of therapy resistance and target-directed treatment approaches. MATERIAL AND METHODS: To explore ETMR cell diversity, we used single-cell RNA sequencing (scRNA-seq) in human (n=2) and murine ETMR (transgenic mode; n=4) samples, spatial transcriptomics, 2D and 3D cultures (including co-cultures with TME cells), multiplex immunohistochemistry and drug screens. RESULTS: ETMR microenvironment is composed of tumor and non-tumor cell types. The ETMR malignant compartment harbour cells representing distinct transcriptional metaprograms, (NSC-like, NProg-like and Neuroblast-like), mirroring embryonic neurogenic cell states and fuelled by neurogenic pathways (WNT, SHH, Hippo). The ETMR TME is composed of oligodendrocyte and neuronal progenitor cells, neuroblasts, microglia, and pericytes. Tumor-specific ligand-receptor interaction analysis showed enrichment of intercellular communication between NProg-like ETMR cells and pericytes (PC). Functional network analyses reveal ETMR-PC interactions related to stem-cell signalling and extracellular matrix (ECM) organization, involving factors of the WNT, BMP, and CxCl12 networks. Results from ETMR-PC co-culture and spatial transcriptomics pointed to a pivotal role of pericytes in keeping ETMR in a germinal neurogenic state, enriched in stem-cell signalling. Drug screening considering cellular heterogeneity and cellular communication suggested novel therapeutic approaches. CONCLUSION: ETMR demonstrated diversity in the microenvironment, with enrichment of cell-cell communications with pericytes, supporting stem-cell signalling and interfering in the organization of the tumor extracellular matrix. Targeting ETMR-PC interactions might bring new opportunities for target-directed therapy.
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Sterbies, Nicolas, Flavia Watusi de Faria, Nicole Riedel, Daniel Münter, Lea Altendorf, Carolin Göbel, Clara Inserte, et al. "ETMR-08. DECODING TUMOR-NEURONAL COMMUNICATION IN PEDIATRIC BRAIN TUMORS: INSIGHTS FROM ETMR 3D MODEL REVEALING MECHANO-SIGNALING DYNAMICS AND THERAPEUTIC OPPORTUNITIES." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.178.
Abstract:
Abstract INTRODUCTION Exploring tumor-neuronal interactions is essential for comprehending brain tumor proliferation, chemotherapy resistance, and patient survival. While glioma research has made significant strides, our understanding of tumor-neuronal interactions in pediatric brain tumors, notably Embryonal Tumors with Multilayered Rosettes (ETMRs), remains limited. METHODS To elucidate tumor-neuronal interactions in ETMRs, we developed a 3D model by co-aggregating the human ETMR cell line BT-183 with human induced pluripotent stem cells (iPSCs) and allowing them to mature into forebrain organoids for 30 days, forming ETMR-forebrain organoids (ETMR-FBO). We further employed single-cell RNA sequencing to compare the gene expression profile of healthy forebrain organoids (FBO) with the ETMR-FBOs. Additionally, we conducted immunohistochemistry of 3D model sections for comparative evaluation and spatial transcriptomics of murine and human primary ETMR samples. RESULTS Our integrated dataset of 48,764 cells of healthy FBOs (n = 4) and ETMR-FBOs (n = 6) revealed that ETMR tumor cells impeded the neuronal differentiation of the FBO cells. The ETMR-FBOs exhibited a significant enrichment of neuro-stem cells (67% vs 49%), accompanied by a reduction of more differentiated neuronal cells. Comparative trajectory analysis confirmed a blockage of neuronal maturation/differentiation in ETMR-FBOs compared to controls without ETMR cells. Immunohistochemistry further confirmed an enrichment of SOX2-positive/synaptophysin-negative neuronal progenitors in the organoid areas closest to the tumor border. Additionally, we identified upregulated extracellular matrix-related pathways, particularly integrin and YAP/TEAD signaling, in the neuro-stem cell compartment of ETMR-FBOs. This implies a tumor-specific mechano-signaling mechanism influencing the neuronal differentiation state of the tumor microenvironment. CONCLUSION Our findings suggest that mechano-signaling-related tumor-neuronal interactions in ETMR contribute to the formation of an immature neuronal niche. Targeting mechano-signaling may hold promise for innovative therapies by disrupting tumor architecture and enhancing susceptibility to chemotherapy.
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Kılıç Akça, Nazan, and Dilek Arslan. "Pain and Coping Methods of Individuals under 65 Years of Age on Hemodialysis Treatment." Turkish Nephrology Dialysis Transplantation 24, no. 3 (September 26, 2015): 278–82. http://dx.doi.org/10.5262/tndt.2015.1003.04.
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Ran, Xueqin, Jixuan Yang, Mohamad Akbar Ali, Lei Yang, and Yonghua Chen. "Rational Design of Lewis Base Electron Transport Materials for Improved Interface Property in Inverted Perovskite Solar Cells: A Theoretical Investigation." Nanomaterials 13, no. 9 (May 5, 2023): 1560. http://dx.doi.org/10.3390/nano13091560.
Abstract:
Electron transport materials (ETMs) play a vital role in electron extraction and transport at the perovskite/ETM interface of inverted perovskite solar cells (PSCs) and are useful in power conversion efficiency (PCE), which is limited by interface carrier recombination. However, strategies for passivating undercoordinated Pb2+ at the perovskite/ETM interface employing ETMs remain a challenge. In this work, a variety of heteroatoms were used to strengthen the Lewis base property of new ETMs (asymmetrical perylene-diimide), aimed at deactivating non-bonded Pb2+ at the perovskite surface through Lewis acid-base coordination. Quantum chemical analysis revealed that novel ETMs have matched the energy level of perovskite, which enables electron extraction at the perovskite/ETM interface. The results also suggest that the large electron mobility (0.57~5.94 cm2 V−1 s−1) of designed ETMs shows excellent electron transporting ability. More importantly, reinforced interaction between new ETMs and Pb2+ was found, which is facilitating to passivation of the defects induced by unsaturated Pb2+ at the perovskite/ETM interface. Furthermore, it is found that MA (CH3NH3+), Pb, and IPb (iodine substituted on the Pb site) defects at the perovskite/ETM interface could be effectively deactivated by the new ETMs. This study provides a useful strategy to design ETMs for improving the interface property in PSCs.
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Hartman, Lisa L. R., Derrick M. Oaxaca, Benjamin Carcamo, Harry L. Wilson, Jeremy A. Ross, Elisa Robles-Escajeda, and Robert A. Kirken. "Integration of a Personalized Molecular Targeted Therapy into the Multimodal Treatment of Refractory Childhood Embryonal Tumor with Multilayered Rosettes (ETMR)." Case Reports in Oncology 12, no. 1 (February 28, 2019): 211–17. http://dx.doi.org/10.1159/000497380.
Abstract:
Embryonal tumor with multilayered rosettes (ETMR) are rare pediatric brain tumors with increased malignant potential. Despite the advances in multimodal treatment schemes the overall 5-year event free survival rates for ETMR are not favorable. Further, therapeutic regimes are limited to a case by case basis due to the limited amount of literature and guidelines available for treating childhood ETMR. We report one patient with refractory ETMR who was successfully treated by implementing a molecular profiling approach which identified the tyrosine kinase inhibitor dasatinib as a viable therapy. Our results suggest that utilizing this precision medicine approach might prove useful in treating patients with refractory ETMR.
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YAZAR, Sevtap. "Gelin Kaynana Manilerinde Alay Etme." Journal of Turkish Studies 13, Volume 13 Issue 20 (January 1, 2018): 827–43. http://dx.doi.org/10.7827/turkishstudies.13800.
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UĞUR, Aynaz. "Yabancılar Hukukunda Sınırdışı Etme İşlemi." International Journal of Social Sciences 6, no. 24 (February 20, 2022): 118–32. http://dx.doi.org/10.52096/usbd.6.24.7.
Abstract:
According to souvereign state doctrine in international law, the state decides to permit or deport a foreigner. The most important thihg is the obeidance of state to the local and international law. There are a lot of international convention for protecting foreigners from deport. In Turkish foreigners law the state has a great discretion about deport. At that time the foreigners feels that there is no legal security. Because of this state should comply with the law during its power of discretion. In Türkish law the deport procedure is organized with four different codes: YİSHK/5683-PK/5682-TVK/403-CİK/647. The most important one is YİSHK. Article 19 of it contains uncertain words. Because of this it causes a lot of cases. Deport is an extra-ordinary application which causes big scars in foreigners life. Then it shoul be determined more seriously by law. Keywords: Citizenship, Foreigner, Deport, Administrative Act, Power of Discretion
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TÜZÜN, Melihat. "POSTMODERNİZM VE KENDİNE MAL ETME." Social Sciences Studies Journal 7, no. 92 (January 1, 2021): 5564–73. http://dx.doi.org/10.26449/sssj.3749.
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Abdurrahman, Sebahattin. "Yunan Parlamentosunda etkin temsil etme." History Studies International Journal of History 6, Volume 6 Issue 2 (January 1, 2014): 1. http://dx.doi.org/10.9737/historys1170.
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JENKINS, D. E. P. "European Technology Management Initiative (ETMI)." European Journal of Engineering Education 18, no. 1 (January 1993): 81. http://dx.doi.org/10.1080/03043799308923213.
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DEMİR, Ayşenur. "DİLENCİLERE YARDIM ETME SIKLIĞI ÜZERİNDE." Ekev Akademi Dergisi, no. 82 (January 1, 2020): 61–76. http://dx.doi.org/10.17753/ekev1429.
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Hesham, Dina, and Shahenda El-Naggar. "Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes." Genes 11, no. 9 (September 22, 2020): 1108. http://dx.doi.org/10.3390/genes11091108.
Abstract:
Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.
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Na, Moon Kyong, Myeong Sang Ahn, and Hoy Yul Park. "Properties of Sol-Gel Coating Film from Colloidal Silica-Silane Sol." Materials Science Forum 544-545 (May 2007): 813–16. http://dx.doi.org/10.4028/www.scientific.net/msf.544-545.813.
Abstract:
Two kinds of colloidal silica(CS)/silane sol solutions were prepared. Two sol solutions are involved with the kinds of silane such as methyltrimethoxysilane(MTMS) and -Glycidoxypropyl trimethoxysilane(ETMS) using LS CS. MTMS was added to two sol solutions. Whether ETMS was added or not, two kinds of sol solutions were synthesized. Using two kinds of sol solutions, sol-gel coating films were formed on glass substrates via dip-coating process. Here, seasoning effect of for enhancing properties of sol-gel coating layer on glass was investigated while such sol-gel solutions were left for 7days. Also, their properties such as surface free energy, roughness, thermal property, potential hardness and elastic portion were characterized in order to understand the effect of addition of ETMS. In this case of LS/MTMS sol, the coating film had low surface free energy and more enhanced flat surface than that of the case of LS/MTMS/ETMS sol. ETMS forms hydrophilic hydroxyl group in sol solution, then surface free energy of LS/MTMS/ETMS coating film increased. In the beginning of reaction sol solution seemed to be unstable, but 4days later their coating film properties such as surface free energy and roughness enhanced. The elastic portion of coating films obtained from LS/MTMS/ETMS sol increased with addition of ETMS, but thermal stability decreased.
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Ogbeibu, Samuel, Abdelhak Senadjki, Jude Emelifeonwu, and Paramjeet Singh Vohra. "Inspiring Creativity in Diverse Organizational Cultures: An Expatriate Integrity Dilemma." FIIB Business Review 9, no. 1 (January 14, 2020): 28–41. http://dx.doi.org/10.1177/2319714519891668.
Abstract:
Employee creativity can bolster organizational competitiveness and survival. Although, when in host countries, expatriate top management leaders (ETML) are often challenged to constantly exhibit integrity that positively impacts the creativity of employees, despite prevalent organizational cultures’ (OCs) influences. Varying influences of distinct OCs and questionable ETML integrity have also been argued to have unpredictable influences on the creativity prowess of several emerging economies like Nigeria. It is, thus, unclear from the literature how ETML and distinct OCs act to inspire employee creativity. This study investigated the relationship between ETML integrity, OC and employee creativity. A cross-sectional survey design was administered to 439 participants from 22 manufacturing organizations in Nigeria, and data analysis was executed by leveraging partial least square path modelling (SmartPLS 3). Results indicated that ETML integrity and adhocracy OC have positive associations with employee creativity. Equally, clan and market OCS reflect negative associations with employee creativity. Surprisingly, ETML integrity dampens the positive relationships between adhocracy OC and hierarchy OC, and employee creativity. Furthermore, ETML integrity reinforces the association of clan OC and market OC with employee creativity. This study offers substantive and significant contributions that can be applied to emerging economies with similar concerns and context.
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FIRAT, Z. Mehmet. "Investigation of the Effect of Scout Leaders' Level of Acceptance of Differences on Their Innovative Behavior." Uluslararası Egzersiz Psikolojisi Dergisi 5, no. 2 (December 31, 2023): 53–68. http://dx.doi.org/10.51538/intjourexerpsyc.1319025.
Abstract:
Bu araştırmanın amacı izci liderlerinin farklılıkları kabul etme ve yenilikçi davranış düzeylerini çeşitli demografik özelliklere göre araştırmak ve onların farklılıkları kabul etmelerinin yenilikçi davranışları üzerinde bir etkisi olup olmadığını ortaya çıkarmaktadır. Araştırmanın çalışma grubunu Kocaeli'nde faaliyette bulunan 166 izci lideri oluşturmuştur. Araştırmaya 82 kadın ve 84 erkek izci katılmıştır. Katılımcılar çoğunlukla genç ve bekârdır. Araştırmada veri toplama aracı olarak “Farklılıkları Kabul Etme Ölçeği” ve “Yenilikçi Davranış Ölçeği” kullanılmıştır. Araştırmada Tek Yönlü Varyans Analizi (ANOVA), Bağımsız Örneklem T-Testi, Korelasyon Analizi ve Çoklu Regresyon Analizi uygulanmıştır. Bu kapsamda; farklı dini/etnik yapıları kabul etme medeni duruma göre değişmektedir. Farklı dış görünüşleri kabul etme cinsiyete göre farklılaşmaktadır. Statü göz önüne alındığında farklı dini/etnik yapıları kabul etme konusunda farklılık görülmüştür. Statü farklı düşünceleri/değerleri kabul etme konusunda da rol oynamaktadır. Farklı dini/etnik yapıların kabulü ve farklı düşüncelerin/değerlerin kabulü açısından cinsiyete göre anlamlı bir fark yoktur. İzci olarak görev süresi yenilikçi davranış sergilemede farklılık gösterir. Yenilikçi davranış açısından cinsiyet, medeni durum, yaş ve statüye göre anlamlı bir fark yoktur. Farklılıkları kabul etmenin üç boyutunun da yenilikçi davranış üzerinde bir etkisi olmadığı görülmüştür.
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Hanson, Derek, Nicolas Andre, Susan Chi, Mariella Filbin, Michael Fisher, Lindsey Hoffman, Ziad Khatib, et al. "ETMR-08. INTERNATIONAL CONSENSUS PROTOCOL FOR EMBRYONAL TUMOR WITH MULTILAYER ROSETTES." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii324. http://dx.doi.org/10.1093/neuonc/noaa222.212.
Abstract:
Abstract Embryonal tumors with multilayer rosettes (ETMR) are rare and highly-aggressive central nervous system (CNS) neoplasms which occur primarily in young children and carry a dismal prognosis. To date, no large clinical investigations have been conducted to determine the optimal therapy for ETMR. Data from retrospective case series suggest that our most aggressive standard therapies are not sufficient for cure in the majority of cases. New treatment approaches incorporating pre-clinical data and the known biology of ETMR are therefore urgently needed. A German drug screen using the patient-derived ETMR BT183 cell line and its xenograft revealed anti-tumor activity of topotecan, doxorubicin, and actinomycin D; three agents used infrequently for treating infant CNS tumors. Additional results from a small series of ETMR patients suggest that optimization of induction chemotherapy using these active agents may improve response and survival outcomes. In 2019, an international panel of pediatric neuro-oncology experts convened to advance therapy for ETMR. A consensus protocol was developed incorporating maximal safe surgical resection, induction chemotherapy with active pre-clinical agents, intrathecal chemotherapy, radiotherapy, and high-dose chemotherapy. This international consensus protocol represents the first prospective clinical investigation specific to ETMR and will be available through a treatment registry globally and as a clinical trial at select centers. The study aims to improve survival by providing aggressive, optimized therapy for ETMR and will serve as a platform to explore new biologically-promising agents. The investigation will also provide valuable prospective outcome data and correlative biological studies to serve as baseline comparators for future clinical trials.
44
Choi, Yun-Jeong. "Design and Implementation of Text Classification System based on ETOM+RPost." Journal of the Korea Academia-Industrial cooperation Society 11, no. 2 (February 28, 2010): 517–24. http://dx.doi.org/10.5762/kais.2010.11.2.517.
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Liapis, Evangelos, Kelly C. O’Neill, Annapurna Pamreddy, Allison Maas, Derek R. Hanson, and Claire L. Carter. "ETMR-20. CARDIOLIPIN ACYL CHAIN MODULATION AS A NOVEL MITOCHONDRIAL-FOCUSED THERAPEUTIC TARGET IN ETMR." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.190.
Abstract:
Abstract Embryonal tumor with multilayered rosettes (ETMR) is a highly aggressive CNS neoplasm that occurs almost exclusively in infants and is associated with an extremely poor prognosis. Dysregulated mitochondrial bioenergetics and dynamics have been associated with the initiation and progression of diverse cancers and studies have linked metabolic rewiring to chemotherapy resistance. Cardiolipins are mitochondrial-specific lipids that reside in the mitochondrial membrane and their fatty acid composition has been extensively shown to regulate mitochondrial function and dynamics. Despite the known functional significance of cardiolipin structure, their role in mitochondrial regulation of brain tumors remains ill-defined. Using mass spectrometry imaging, we identified a shift to shorter acyl chain cardiolipins within the rapidly proliferating embryonal tumor cells in patient samples and patient-derived cell lines grown as 3D tumorspheres. Western blot analysis of the enzymes involved in cardiolipin synthesis and remodeling identified a significant increase in the expression of the cardiolipin remodeling enzyme, LCLAT1/ALCAT1. Orthogonal imaging techniques including immunohistochemistry, transmission electron microscopy and super-resolution microscopy correlated shorter acyl chain remodeling of cardiolipin with fragmented mitochondria (increased fission) and aberrant cristae structure. Further studies identified increased expression of the fission protein Drp1, decreased expression of respiratory chain enzymes and altered respiration in the embryonal tumor cells. Ongoing studies will utilize multiple methods to modulate cardiolipin acyl chain structure and use MS and MSI to correlate cardiolipin fatty acid structure to mitochondrial function and growth inhibition in the embryonal tumor cells.
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Brasileiro-Santos, Maria do Socorro, Anna Myrna Jaguaribe de Lima, Manuela Barros da Silveira Hunka, Thayse Silva Neves, Maria do Amparo Andrade, and Amilton da Cruz Santos. "Atividade mioelétrica dos músculos respiratórios em crianças asmáticas durante manobra inspiratória máxima." Revista Brasileira de Saúde Materno Infantil 12, no. 3 (September 2012): 251–57. http://dx.doi.org/10.1590/s1519-38292012000300005.
Abstract:
OBJETIVOS: avaliar a atividade dos músculos escalenos e esternocleidomastóideo (ETMD) no período basal e durante manobra de pressão inspiratória máxima (PImax) em crianças asmáticas. MÉTODOS: foram estudadas 15 crianças, divididas em grupo asma (n=8) e grupo controle (n=7). Foi realizada a análise da função pulmonar e da PImax através da espirometria e da manovacuometria, respectivamente. A atividade mioelétrica dos músculos escaleno e ETMD foram realizadas pela eletromiografia de superfície durante período basal e manobra de PImax. RESULTADOS: a eletromiografia de superfície (EMGs) basal do músculo escaleno é maior no grupo asma quando comparado ao grupo controle. Diferentemente, a EMGs basal do músculo ETMD não apresentou diferença significativa nos grupos estudados. O percentual da EMGs dos músculos escaleno e ETMD durante manobra de PImax foi maior no grupo asma quando comparado ao grupo controle. CONCLUSÕES: EMGs do escaleno durante o período basal está aumentada em crianças asmáticas. A atividade eletromiográfica do músculo ETMD no período basal é similar em ambos os grupos estudados. A EMGs dos músculos ETMD e escaleno na geração de pressão intratorácica, durante a manobra de PImax, está aumentada em crianças asmáticas.
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Putri Juliana, Natasya, and Kezia Arum Sary. "STRATEGI PROMOSI PENJUALAN KAPAL WISATA PESUT ETAM SAMARINDA MELALUI MEDIA SOSIAL AKUN INSTAGRAM DAN FACEBOOK PADA MASA PANDEMI COVID-19." Jurnal Sosial-Politika 3, no. 2 (December 1, 2022): 71–81. http://dx.doi.org/10.54144/jsp.v3i2.51.
Abstract:
Penelitian ini bertujuan untuk mengetahui bagaimana strategi promosi penjualan (sales promotion) yang dilakukan oleh Kapal Wisata Pesut Etam melalui media sosial akun facebook dan instagram serta untuk mengetahui ketidakefektifan atau penghambat pada masa pandemi Covid-19 dalam mempromosikan objek wisata susur sungai mahakam yaitu Kapal Wisata Pesut Etam. Penelitian ini menggunakan jenis penelitian kualitatif. Pada penelitian ini menggunakan sumber data purposive sampling, dalam menganalisis penelitian menggunakan AIDA (Attention, Interest, Desire, Action). Attention pada penelitian ini adalah cara Pesut Etam mengemas caption, hastag dan poster yang telah diunggah ke laman facebook dan instagram guna menarik perhatian dari pengguna kedua media sosial tersebut, Interest membuat Pesut Etam untuk menciptakan citra yang baik melalui reposting instastory pada akun instagram dan menyediakan fitur ulasan pada akun facebook, Desire dimana Pesut Etam melihat hasrat pengguna instagram dan facebook dengan mengukur keberhasilan melakukan interaksi melalui kolom komentar pada postingan kedua media sosial tersebut, dan Action merupakan cara untuk memengaruhi pengguna media sosial agar melakukan tindakan giveaway yang diadakan pesut etam guna memperluas pengetahuan masyarakat terhadap objek wisata Kapal Wisata Pesut Etam.Kata Kunci: Facebook, Instagram, Promosi Penjualan Masa Covid-19, Strategi Promosi Penjualan
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Cocito, Carolina, Esteban Uceda Arias-Stella, Xiaohu Zhang, Crystal McKnight, Zina Itkin, Carleen Klumpp-Thomas, Gustavo Alencastro Veiga Cruzeiro, et al. "ATRT-11. DEVELOPMENT OF NOVEL PRECLINICAL MODELS AND THERAPEUTIC STRATEGIES FOR ETMR." Neuro-Oncology 25, Supplement_1 (June 1, 2023): i3. http://dx.doi.org/10.1093/neuonc/noad073.011.
Abstract:
Abstract Embryonal Tumor with Multilayered Rosettes (ETMR) is a very rare, aggressive pediatric brain tumor with a dismal 5-year overall survival rate. Few genetic aberrations in miRNA clusters and processing machinery have been detected in ETMRs with 90% of ETMR patients having the C19MC amplification. ETMRs show heterogenous histopathological features, including regions of abundant neuropil, hypercellular regions with multilayered rosettes, and papillary structures resembling primitive neuroectoderm. This unique histology, together with the detection of C19MC or DICER alterations, are necessary for diagnosis. The cellular and molecular mechanisms underlying ETMR development is poorly understood, and targeted therapeutics have not been developed due to scarcity of preclinical models. To expand knowledge of ETMR biology and accelerate the design of novel, it is thus essential to develop preclinical models. We have generated a novel patient-derived ETMR cell line from a resected patient tumor sample (CTBP-03A) and created two patient-derived xenograft (PDX) models (CTBP-03A and CBTP-38). We have used these unique patient-derived cell lines to identify mechanisms driving ETMR development and progression. To identify novel therapeutic targets, we conducted high-throughput drug screening (HTDS) utilizing 2480 approved and investigational drugs, against the CBTP-03A cell line. Among the candidate drugs showing an inhibitory effect on CBTP-03, 63 compounds were selected based on their activity, CNS penetration ability, mechanism of action, and bioavailability, if known. The 63 potency-selected hits were screened in an all-versus-all format, totaling 1953 combinations. The rapidity of action of the top choice compounds used as single agent or in double and triple combination was assessed by caspase glow assay. This initial combination screen identified DNA replication stress and FGF signaling as potential new drug combinations for ETMR. We will thus describe the first combinatorial HTDS on two novel ETMR patient-derived cell lines and potential drug combination strategies for the treatment of ETMR.
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Kusano, Shimpei, Junya Fujimura, Megumi Fujiwara, Akinori Yaguchi, Takeshi Ishibashi, Osamu Tomita, Hiroyuki Tamaichi, Akihide Kondo, and Toshiaki Shimizu. "ETMR-15. USE OF HIGH-DOSE CHEMOTHERAPY FOR TWO CHILDREN WITH EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii326. http://dx.doi.org/10.1093/neuonc/noaa222.219.
Abstract:
Abstract Embryonal tumor with multilayered rosettes (ETMR) is new entity defined in the 4th revised edition of the WHO classification of tumors of the central nervous system. Although radical resection, radiotherapy, and multiagent chemotherapy are considered to be necessary for ETMR, the efficacy of chemotherapy for ETMR in Japan has not been established. Here, we report different clinical courses for two children with localized ETMR treated with the St. Jude medulloblastoma-96 (SJMB96) regimen, which consists of four cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation. For both children, the diagnosis of ETMR, C19MC-altered was confirmed after gross total tumor resection. Multiagent chemotherapy was administered following cranio-spinal irradiation with local boost. One month after completion of the treatment, one patient experienced local recurrence but has been in remission for over 2 years after tumor resection and stereotactic irradiation with a CyberKnife and treatment every three weeks with bevacizumab. The other patient also experienced local recurrence after the third cycle of chemotherapy and several times thereafter. Although she again underwent tumor resection and local irradiation, her tumor grew larger and invaded. Because her prognosis was very poor, her parents choose only palliative care. Based on our experience, we believe that continuous chemotherapy at conventional doses is preferred over intensive-dose chemotherapy such as SJMB96. However, the number of reports on chemotherapy for ETMR is still small, and a prospective multicenter trial is needed to establish effective chemotherapy for ETMR.
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Hanson, Derek. "PDCT-04. ETMR ONE: AN INTERNATIONAL REGISTRY AND RESEARCH PLATFORM FOR CHILDREN WITH EMBRYONAL TUMOR WITH MULTILAYER ROSETTES." Neuro-Oncology 21, Supplement_6 (November 2019): vi184. http://dx.doi.org/10.1093/neuonc/noz175.768.
Abstract:
Abstract Embryonal tumor with multilayer rosettes (ETMR) is a rare and highly-aggressive CNS neoplasm which occurs almost exclusively in young children and is associated with an extremely poor prognosis. Due to the rare nature of ETMR and its recent classification, no large clinical investigations have been conducted to determine the optimal therapy for these tumors. Historical data suggests that extensive surgical resection, radiotherapy, and high-dose chemotherapy are not sufficient treatment in the vast majority of cases with a reported 1-year EFS of 36% and 1-year OS of 45% using these approaches. New treatment regimens incorporating the known biology of ETMR must be investigated. Pre-clinical drug screens using the ETMR BT183 cell line and its xenograft have demonstrated responses to the chemotherapy agents topotecan, doxorubicin, and actinomycin D. Based on this data, a modified IRS-III chemotherapy regimen incorporating these active agents was developed and a small cohort of four children with ETMR were then treated. Three patients completed therapy without subsequent relapse and have EFS of >30 months. The ETMR One international registry and its associated consensus treatment protocol represent the first prospective evaluation of treatment outcomes for children with ETMR. The consensus regimen involves maximal feasible surgical resection, modified IRS-III chemotherapy, high-dose chemotherapy with autologous stem cell rescue, and radiotherapy (as indicated). Patients enrolled on the registry will have their cases periodically reviewed by a medical advisory board that will offer management recommendations, particularly regarding the use of radiotherapy or the need for additional surgical interventions. Through the procurement of patient tumor samples and development of additional cell lines and xenografts, the registry aims to serve as a platform for translational research. Pre-clinical findings will be used to modify the consensus protocol therapy as indicated or to generate additional biology-based phase I/II trials for ETMR.