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Curierul Medical Vol 56 No 1 | Glycolysis | Positron Emission Tomography

The journal was founded by the Ministry of Health of the Republic of Moldova in Sincethe Nicolae Testemitsanu State University of Medicine and Pharmacy has become the co-publisher of this journal. The journal publishes official papers as well as independently submitted scientific articles, editorials, clinical studies and cases, lectures, paraziti v mozku guides, reviews, brief reports and correspondences.

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Revista Curierul medical Este o revist tiinifico-practic acreditat de Consiliul Naional de Acreditare i Atestare certificat de nregistrare de Stat nr. Revista a fost fondat de ctre Ministerul Sntii al Republicii Moldova paraziti v mozku anul Revista public comunicri oficiale i, totodat, sunt editate diverse publicaii, inclusiv independente: articole tiinifice, editoriale, cercetri i prezentri de cazuri clinice, prelegeri, ndrumri metodice, articole de sintez, relatri scurte, corespondene i recenzii.

Paraziti v mozku of Editorial Office Bd. Lpuneanu, 2 Tel. All articles are doubleblind peer reviewed by 2 independent experts. Articles must be sent electronically with a cover letter written to Editor-in-Chief, Boris Topor, MD, PhD, Professor, from the author who is responsible for correspondence.

The letter should contain a statement saying that the manuscript has been seen and approved by all authors and that the article has not been previously published. Articles from countries outside of the Republic of Moldova are published at the price of 40 per page in the journal pages of the manuscript sent by the authorincluding tables paraziti v mozku figures. If revisions are necessary, an additional fee will be applied, depending on the volume of corrections.

The authors are responsible for the content of the articles. Papers describing research involving animal or human subjects should state in the cover letter that rules of work with animals were respected and informed consent was obtained from the patients and approval was obtained from the designated board of the institution involved.

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The abstracts should be included on the title page in English and Russian, and be words long. They should end with 3 to 6 key words. The text of clinical or experimental articles less than 16 pages long paraziti v mozku consist of: an Introduction, Material and Methods, Results, Discussion, Conclusions and no more than 40 References. However, review articles paraziti v mozku not exceed 25 pages and contain no more than references.

Tables and figures must be typed, numbered consecutively with explanatory text. Figures that need to paraziti v mozku comparison or emphasize details will be published in color. If colored figures are necessary, the author must pay an additional fee of 95 per page figures on a page. References are listed in order of appearance in the text, and the appropriate numbers are inserted in the text in [square brackets] at the proper places.

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Foaia de titlu conine prenumele i numele autorilor, titlul i gradul tiinific, instituia, numrul de telefon i adresa electronic a autorului corespondent. Rezumatele n limba englez i rus cuvinte se prezint consecutiv pe foaia de titlu, inclusiv cuvinte-cheie, de la 3 pn la 6.

Textul articolelor clinice, experimentale pn la 15 pagini cuprinde: Introducere; Material i metode; Rezultate obinute; Discuii; Concluzii i Bibliografie pn la 40 de referine. Alt structur se accept, dac aceasta corespunde coninutului materialului.

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Figurile care necesit contrastare sau evidenierea detaliilor sunt executate color. Figurile color se public din sursele autorului 95figuri pe pagin. Referinele, n conformitate cu cerinele International Committee of Medical Journal Editors, se expun n ordinea apariiei paraziti v mozku text. Address of the Journal Office Adresa redaciei Bd.

Akhtemiychuk, Ye. Ruda, G. Stepanyuk, O. Gaina, R. Shatilov, N. Tsubanova, S. Calaras, V. Botnaru, O. Matraguna, O. Erohina, O. Gurduza, S. Cojocari, L.

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Mincu, D. Textbook Managament of perioperative paraziti v mozku. Author: Adrian Belii Monografie Hepatoprotectoare entomologice. Autor: Nicolae Bacinschi Manuscript received October 23, ; revised December 15, Abstract Tumor cell energy metabolism is often invoked as marker of aggressiveness and resistance in the study of cancer. Warburg was the first researcher to propose the high consumption of glucose and reduction of tumor cell oxidative metabolism as paraziti v mozku feature of cancer paraziti synevo. In clinical practice, this feature is used in PET imaging positron emission tomography to visualize the 2-FDG antimetabolite enhancing lesions.

In reality, not all tumors are characterized by high levels of glycolysis.

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To highlight certain features affected by glucose and energy, four types of cancer stem cells CSCs were isolated from the third degree of malignancy gliomas anaplastic glioma, WHO, World Health Organization. Thus, the energy status of cancer stem cells lines derived from gliomas is inversely correlated to proliferation in vitro.

Glucose dependency varied considerably among the four types of glioma stem cells. In one case, NADH levels were maintained in the absence of glucose by substitution with glutamine. DCA dichloroacetat is an energy modulator acting as a mitochondrial function stimulator. In our experiments, DCA could stimulate NADH production, showing the paraziti v mozku of mitochondrial function recovery in glioma paraziti v mozku stem cells.

Key words: cancer, glioma stem cells, tumor cell energy metabolism.

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Introduction Gliomas are represented by a heterogeneous group of tumors and made up essentially by two main populations of glial cells: oligodendrocytes paraziti v mozku astrocytes. Cancer stem cells can be isolated from particular tumors and are thought to be the cause of chemo- and radiotherapy resistance and tumor relapse. The main data concerning tumoral in vivo energetic metabolism derives from spectroscopic imagistic data SPET positron emission tomography utilizing 2-FDG fluoro-deoxy-D-glucose and methyonine as a tracer [2, 3, 4].

Based on these results, it was widely recognized that some cancer cell types show enhanced glycolysis levels [1, 10]. High glucose turnover and lactate production might represent an adaptive mechanism in response to increasing hypoxia accompanying tumoral progression.

Moreover, resulted peritumoral acidosis is regarded as one of tumoral aggressive factors for surrounding normal cells. A reduced spatial and temporal resolution of metabolic studies via PET scan imagery is incriminated by the impossibility to evaluate specific metabolic profiles for each cell type involved in tumoral formation.

Energetic metabolism of spheroids of CSCs evaluated by NADH levels depending on glucose levels in cultural media and treated with antimetabolite 2DG in some conditions was compared with neural stem cells originating from a neonatal mouse.

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Material and Methods Four cancer stem cell lines were isolated using classical methods. Each type of glioma stem cell was cultured and maintained in an atmosphere with similar CO2 and O2 contents. Great differences were revealed in the metabolic activity of stem cell lines derived from morphologically similar grade III WHO gliomas. In order to test each stem cell line dependence on main nutrients, each cell lineage was resuspended in the same D3 paraziti v mozku media with known concentrations of Glucose and Glutamine for 24 paraziti v mozku.

The same number per well were seeded In the second essay, we treated our glioma stem lines and neural stem cell lines with several modulating energy metabolism agents: DCA dichloracetatewhich accelerates the Krebs cycle by inhibiting the activity of PDK pyruvate dehydrogenase kinase ; 2 DG 2 deoxy-D-glucose an analog of glucose that blocks the first step of glycolysis; Antimycine A - a mitochondrial inhibitor which is involved in the energy-coupling site of the respiratory system by blocking the electrons flow from cytochrome b to cytochrome c1.

Paraziti v mozku Under the same cultured condition white column the NADH activity was greater for stem cell lines derived from child brain stem glioma. The dark column represents NADH activity when cultured in the original media. Interestingly, Paraziti v mozku. The CSN24 mouse neural stem cell line treated with 2DG 2-deoxy glucose shows little or no blockage of NADH activity, indicating both a low cell glycolytic activity and a relative resistance to 2DG antimetabolite fig.

Metabolic activity NADH of 4 different stem cell lines in cultured media. Metabolic activity modulation in the neural stem cell line.

In contrast, DCA stimulated Krebs cycle activity, confirming an inhibited status of mitochondria in cancer fig. Discussion Cancer cells originate from normal body cells in two phases. The first phase is the irreversible injuring of respiration. The irreversible injuring of respiration is followed, as the second phase of cancer formation. On the origin of cancer cells, Otto Warburg, It has previously been emphasized that, beyond its impact in terms of diagnosis, growth patterns analysis, and aberrant energetic metabolism evaluation provide valuable insights into the clinical manifestation and imaging of tumors.

Several studies demonstrate the role of PET scan imaging based on high glycolysis cells on tumoral diagnosis hpv virus p3 kezelese prognostic evaluation [2, 7].

Thus, the 2-FDG PET scan fluoro-deoxyglucose positron emission tomography is largely utilized in clinics for evaluation of local and distant lymph node metastasis.

Finally, the great resolution of the FDG PET scan makes it a first choice exam in some cancers type: head and neck, breast, lung, colorectal, melanoma and lymphoma tumors [3, 4, 5].

Energetic metabolism and some key enzymes particularly implicated in glycolysis and oxidative phosphorilation have been studied as potential markers of tumoral aggressiveness. For paraziti v mozku, based on immunohystochemical evaluation of GAPDH glyceryl aldehyde phosphate dehydrogenasebeta-1 ATPase subunit adenosine triphosphate beta-1 and HSP heat shock protein from mitochondrial membranean energetic index has been calculated and proposed to express tumoral metabolic status and prediction marker of tumoral aggressiveness Guezva A paraziti v mozku relationship has been found between high glycolytic phenotype and tumoral aggressiveness.

Indeed, several 6 facts indicate that, either FDG captation or Lactate levels determined by spectro MRI exams, constitute negative prediction factors in tumoral behavior [8, 9, paraziti v mozku. It was stressed that Warburg effect might represent an adaptive mechanism for tumoral cells to overcome increased hypoxia rates and insufficient vascular supply. Consequently, targeting tumoral metabolism and, paraziti v mozku specifically, glycolysis is considered a promising tool in anticancer therapy.

Prior to deciding which anti-metabolite therapy would be the most productive, a thorough appreciation of energetic metabolism should be undertaken in order to confirm or infirm characteristics like: enhanced glycolysis, glutaminolysis [4].

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paraziti v mozku

However, there is a growing awareness that glycolytic phenotypes vary significantly, as many tumors cannot be visualized by FDG PET scans. Also, it has been suggested that nutrients other than glucose might be utilized as main energetic suppliers: glutamine and even lactate [5, 6, 7].

Few studies have addressed these issues or tried to explain these metabolic differences in stem cells derived from gliomas.

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Stem cells that derive from tumors being denominated as cancer stem cells are seldomly regarded as therapy resistant factors and reflect the most aggressive part of the tumor.

In our study, several paraziti v mozku of stem cells derived from different gliomas but appreciated to have the same WHO III malignancy degree have been tested for their susceptibility to glucose and glutamine withdrawal. Comparing different cell lines obtained from adult and child glioma and also normal neural stem cell lines, showed that the NADH production was constantly inferior for cancer stem cells with the highest proliferative index compared to those with the lowest ones.

Several studies capitalized on NMR spectroscopy nuclear magnetic resonance spectroscopy using 13C isotopomer for glucose labeling, drawing the conclusion that enhanced energetic and anabolic metabolism is driven by glycolysis [3]. Because glycolysis produces ATP less efficiently than aerobic respiration, tumor cells must compensate by having a much higher rate of glucose uptake than normal cells.

In some malignant rapidly-growing tumors, glycolysis rates are up to times higher than normal cells. AMPK AMP-activated protein kinase has emerged as a master regulator of cellular energy metabolism with dozens of paraziti v mozku targets.

Primarily, for an apparently similar degree of malignancy established anatomopathologically, energetic study showed significant differences in tumoral dependence on glucose and glutamine. Secondly, proliferative index correlated inversely with cellular energetic status. References 1. Imaging gliomas with positron emission tomography and single-photon emission computed tomography.

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Semin Nucl Med. Bayley JP, Devilee P.

The Warburg effect in Curr Opin Oncol. Metab Eng. Epub Nov 5. Cancer Res. Epub Jun 6. Targeting the Warburg effect in hematological malignancies: from PET to therapy. Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons.