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Phospholipid dynamics in ex vivo lung cancer and normal lung explants
Lesko Julia,Triebl Alexander,Stacher-Priehse Elvira,Fink-Neuböck Nicole,Lindenmann Jörg,Smolle-Jüttner Freyja-Maria,Köfeler Harald C.,Hrzenjak Andelko,Olschewski Horst,Leithner Katharina 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully 13 C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2 , respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.
Iryna, Lychenko,Natalia, Lesko,Nataliia, Pavliuk,Zoryana, Dobosh,Rostyslav, Bundz International Journal of Computer ScienceNetwork S 2022 International journal of computer science and netw Vol.22 No.12
The main purpose of the study is to identify the key aspects of legislative support standards in the countries of the European Union in the field of building a system of local self-government. The European Union during the history of its existence has developed a set of standards on which the systems of local self-government of the European Union member states and applicants for this status are built. The complexity and at the same time the importance of legislative regulation of the functioning of this system is evidenced by the fact that the legislation and principles of international law used by the European Union in the field of local self-government are among the "youngest". This is due to the role played by local self-government in the development of a democratic political system, as well as the search for an optimal balance between centralization and decentralization. Thus, the main task of the study is to analyze the legislative support standards in the countries of the European Union in the field of building a system of local self-government. As a result of the study, current trends and prerequisites for the legislative support standards in the countries of the European Union in the field of building a system of local self-government were investigated.
Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation
Frueh, Felix W.,Lesko, Lawrence J.,Burckart, Gilbert J. The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.
The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of sup-porting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.
Metodiev, Metodi D.,Lesko, Nicole,Park, Chan Bae,Cá,mara, Yolanda,Shi, Yonghong,Wibom, Rolf,Hultenby, Kjell,Gustafsson, Claes M.,Larsson, Nils-Gö,ran Elsevier 2009 Cell metabolism Vol.9 No.4
<P><B>Summary</B></P><P>The 3′ end of the rRNA of the small ribosomal subunit contains two extremely highly conserved dimethylated adenines. This modification and the responsible methyltransferases are present in all three domains of life, but its function has remained elusive. We have disrupted the mouse <I>Tfb1m</I> gene encoding a mitochondrial protein homologous to bacterial dimethyltransferases and demonstrate here that loss of TFB1M is embryonic lethal. Disruption of <I>Tfb1m</I> in heart leads to complete loss of adenine dimethylation of the rRNA of the small mitochondrial ribosomal subunit, impaired assembly of the mitochondrial ribosome, and abolished mitochondrial translation. In addition, we present biochemical evidence that TFB1M does not activate or repress transcription in the presence of TFB2M. Our results thus show that TFB1M is a nonredundant dimethyltransferase in mammalian mitochondria. In addition, we provide a possible explanation for the universal conservation of adenine dimethylation of rRNA by showing a critical role in ribosome maintenance.</P>
Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation
( Gilbert J. Burckart ),( Felix W. Frueh ),( Lawrence J. Lesko ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.1
The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of supporting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.