One of the characteristics of cancer cells important for tumorigenesis is their metabolic plasticity. Indeed, in various stress conditions, cancer cells can reshape their metabolic pathways to support the increased energy request due to continuous growth and rapid proliferation. Moreover, selective pressures in the tumor microenvironment, such as hypoxia, acidosis, and competition for resources, force cancer cells to adapt by complete reorganization of their metabolism. In this review, we highlight the characteristics of cancer metabolism and discuss its clinical significance, since overcoming metabolic plasticity of cancer cells is a key objective of modern cancer therapeutics and a better understanding of metabolic reprogramming may lead to the identification of possible targets for cancer therapy.

• Klíčová slova
• Cancer metabolism, Cell death, Glutaminolysis, Metabolic symbiosis, Mitochondrial bioenergetics, Warburg effect,
• MeSH
• energetický metabolismus MeSH
• lidé MeSH
• metabolické sítě a dráhy MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádorové mikroprostředí * MeSH
• nádory * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: A general characteristic of cancer metabolism is the skill to gain the essential nutrients from a relatively poor environment and use them effectively to maintain viability and create new bio-mass. The changes in intracellular and extracellular metabolites that accompany metabolic reprogramming associated with tumor growth subsequently affect gene expression, cell differentiation, and tumor microenvironment. During carcinogenesis, cancer cells face huge selection pressures that force them to constantly optimize dominant metabolic pathways and undergo major metabolic reorganizations. In general, greater flexibility of metabolic pathways increases the ability of tumor cells to satisfy their metabolic needs in a changing environment. PURPOSE: In this review, we discuss the metabolic properties of cancer cells and describe the tumor promoting effect of the transformed metabolism. We assume that changes in metabolism are significant enough to facilitate tumorigenesis and may provide interesting targets for cancer therapy.

• Klíčová slova
• Krebs cycle, Metabolism, Warburg effect, anaplerosis, cancer, glutaminolysis, malignancy, oncogenesis, oncometabolite,
• MeSH
• karcinogeneze metabolismus   MeSH
• lidé MeSH
• metabolické sítě a dráhy MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádorové mikroprostředí MeSH
• nádory * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Coherent vibration states in biological systems excited in nonlinear electrically polar structures by metabolic energy supply were postulated by H. Fröhlich. Fröhlich's requirements for coherent vibrations and generation of electromagnetic field are satisfied by microtubules whose subunits are electric dipoles. Static electric field around mitochondria and "wasted energy" efflux from them provide nonlinear conditions and coherent excitation. Numerical models are used for analysis of coherent vibration states. A hypothesis is presented that dysfunction of mitochondria (i.e., extinction of the zones of the static electric field and of the efflux of "wasted energy") and disintegration of the cytoskeleton on the pathway of cancer transformation result in disturbances of coherence of the cellular electrically polar oscillations and of the generated electromagnetic field with consequences in cellular organization and interactions between cells. Local invasion, detachment, and metastasis of cancer cells are subsequent events of disturbed electromagnetic interactions.

• MeSH
• biofyzikální jevy * MeSH
• biologické modely MeSH
• cytoskelet metabolismus   účinky záření   MeSH
• elektromagnetická pole škodlivé účinky   MeSH
• lidé MeSH
• mitochondrie metabolismus   účinky záření   MeSH
• nádorová transformace buněk účinky záření   MeSH
• nádorové buněčné linie MeSH
• nádory patologie   MeSH
• nelineární dynamika MeSH
• vibrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Physical processes in living cells were not taken into consideration among the essentials of biological activity, regardless of the fact that they establish a state far from thermodynamic equilibrium. In biological system chemical energy is transformed into the work of physical forces for various biological functions. The energy transformation pathway is very likely connected with generation of the endogenous electrodynamic field as suggested by experimentally proved electrodynamic activity of biological systems connected with mitochondrial and microtubule functions. Besides production of ATP and GTP (adenosine and guanosine triphosphate) mitochondria form a proton space charge layer, strong static electric field, and water ordering around them in cytosol - that are necessary conditions for generation of coherent electrodynamic field by microtubules. Electrodynamic forces are of a long-range nature in comparison with bond and cohesive forces. Mitochondrial dysfunction leads to disturbances of the electromagnetic field; its power and coherence may be diminished, and frequency spectrum altered. Consequently, defective electrodynamic interaction forces between cancer and healthy cells may result in local invasion of cancer cells. Further deformation of interaction forces connected with experimentally disclosed spatial disarrangement of the cytoskeleton and disordered electrodynamic field condition metastatic process. Cancer therapeutic strategy targeting mitochondria may restore normal physiological functions of mitochondria and open the apoptotic pathway. Apoptosis of too much damaged cancer cells was observed. Considerable experience with DCA (dichloroacetate) cancer treatment in humans was accumulated. Clinical trials should assess DCA therapeutic potential and collect data for development of novel more effective drugs for mitochondrial restoration of various cancers.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• elektrofyziologické jevy MeSH
• energetický metabolismus MeSH
• guanosintrifosfát metabolismus   MeSH
• kyselina dichloroctová terapeutické užití   MeSH
• lidé MeSH
• mikrotubuly metabolismus   fyziologie   MeSH
• mitochondrie metabolismus   fyziologie   MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádory farmakoterapie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adenosintrifosfát MeSH
• guanosintrifosfát MeSH
• kyselina dichloroctová MeSH

Kinetic studies of changes in isozymic forms of hexokinase, lactate and malate dehydrogenase and in total hexokinase activity during viral carcinogenesis were carried out. The test systems were rat embryo fibroblasts infected with an oncogenic variant of human adenovirus type 12 and an infectious adenovirus type 6, intact REF cultures in different stages of growth (log and stationary phase), and hamster sarcoma A12 and rat reticulosarcoma 321-RRS cell cultures. Molecular isozymic forms of the stated enzymes and total hexokinase activity in the nuclear fraction and cytoplasm of cells in culture were investigated. It was shown that infectious and oncogenic viruses evoked a rearrangement in the spectrum of the energy metabolism enzymes in the nucleus and cytoplasm. The changes appeared in the first days of the contact of REF culture with the virus, and were more pronounced after the oncogenic rather than the infectious virus. The analysis of changes in isozymic forms of the enzymes under study in virus A12-infected REF cultures and in hamster sarcoma A12 and reticulosarcoma 321-RRS cells growing in vitro revealed that they had some features in common. The most pronounced changes were found with hexokinases. The changes described can serve as objective signs of cell transformation.

• MeSH
• buněčné jádro enzymologie   MeSH
• cytoplazma enzymologie   MeSH
• energetický metabolismus MeSH
• hexokinasa metabolismus   MeSH
• izoenzymy metabolismus   MeSH
• kinetika MeSH
• kultivované buňky MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• lidské adenoviry MeSH
• malátdehydrogenasa metabolismus   MeSH
• nádorová transformace buněk MeSH
• virová transformace buněk * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hexokinasa MeSH
• izoenzymy MeSH
• L-laktátdehydrogenasa MeSH
• malátdehydrogenasa MeSH

Biological systems are hierarchically self-organized complex structures characterized by nonlinear interactions. Biochemical energy is transformed into work of physical forces required for various biological functions. We postulate that energy transduction depends on endogenous electrodynamic fields generated by microtubules. Microtubules and mitochondria colocalize in cells with microtubules providing tracks for mitochondrial movement. Besides energy transformation, mitochondria form a spatially distributed proton charge layer and a resultant strong static electric field, which causes water ordering in the surrounding cytosol. These effects create conditions for generation of coherent electrodynamic field. The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively, and shifted and rebuilt frequency spectra. Disturbed electrodynamic interaction forces between cancer and healthy cells may favor local invasion and metastasis. A therapeutic strategy of targeting dysfunctional mitochondria for restoration of their physiological functions makes it possible to switch on the natural apoptotic pathway blocked in cancer transformed cells. Experience with dichloroacetate in cancer treatment and reestablishment of the healthy state may help in the development of novel effective drugs aimed at the mitochondrial function.

• MeSH
• biologické modely * MeSH
• elektromagnetická pole * MeSH
• lidé MeSH
• mitochondrie účinky záření   MeSH
• nádorová transformace buněk účinky záření   MeSH
• nádory patofyziologie   MeSH
• přenos energie * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The heat shock transcription factor, HSF1, is the main regulator of the proteotoxic stress response that orchestrates the adaptation of cells to stress conditions such as elevated temperature, oxidative stress, and proteotoxic stress. As such, HSF1 regulates a large number of stress response-related genes, primarily those encoding heat shock proteins (HSPs). HSPs are molecular chaperones involved in the acquisition of native protein conformations and the prevention of protein degradation, and they also contribute to the removal of denatured proteins via the proteasome. Representative members of the HSP family are HSP70 and HSP90. The stress response is a highly conserved mechanism across all eukaryotes, and HSF1 has been linked to a number of physiological processes (ribosomal biogenesis, translation, transcription, cell cycle, and metabolism) and pathological disorders (neurodegenerative disorders such as Parkinson´s and Alzheimer´s diseases). HSF1 activation is also prominent in different types of cancer (prostate, breast, colorectal carcinoma etc.) where it correlates with tumor aggressiveness and poor prognosis. HSF1 is therefore considered a diagnostic and prognostic marker and is currently being targeted to develop new cancer therapies. Several inhibitors of HSF1 have already been synthesized, but their molecular mechanism (s) of action, specificity those of HSF1, nontoxicity in healthy tissues, and their efficacy in targeting tumor cells remain to be elucidated. PURPOSE: This review summarizes known mechanisms of HSF1 regulation and activation, the role of HSF1 during malignant transformation, and the potential of designing small molecule HSF1 inhibitors for cancer therapy. Key words: HSF1 transcription factor - molecular chaperones - cellular stress - tumor transformation - cancer This work was supported by the project MEYS - NPS I - LO1413. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 10. 8. 2018.

• Klíčová slova
• HSF1 transcription factor - molecular chaperones - cellular stress - tumor transformation - cancer This work was supported by the project MEYS - NPS I - LO1413. The authors declare they have no potential conflicts of interest concerning drugs, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 10. 8. 2018, products,
• MeSH
• lidé MeSH
• nádorová transformace buněk * MeSH
• nádory diagnóza   farmakoterapie   metabolismus   MeSH
• transkripční faktory tepelného šoku antagonisté a inhibitory   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• HSF1 protein, human MeSH Prohlížeč
• transkripční faktory tepelného šoku MeSH

Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and the effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely, alterations in the metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show the effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in a healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from the metabolism of other tissues. Findings from different tissues are, therefore, not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.

• Klíčová slova
• Cancer metabolism, Warburg effect, amino acids, cancer-associated fibroblasts, lactate, tumor microenvironment,
• MeSH
• aminokyseliny MeSH
• glykolýza MeSH
• lidé MeSH
• nádorová transformace buněk MeSH
• nádorové mikroprostředí * MeSH
• nádory * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny MeSH

Acylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.

• MeSH
• karnitin * analogy a deriváty   metabolismus   biosyntéza   MeSH
• lidé MeSH
• metabolické sítě a dráhy * MeSH
• metabolomika MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• acylcarnitine MeSH Prohlížeč
• karnitin * MeSH

Intact, growing cells of strongly acidophilic fungi Acidea extrema and Acidothrix acidophila have been successfully transformed by introduction of heterologous DNA fragment (composed of the glyceraldehyde-phosphate-dehydrogenase gene promoter from Emericella nidulans, a metallothionein-coding gene AsMt1 from Amanita strobiliformis and glyceraldehyde-phosphate-dehydrogenase gene terminator from Colletotrichum gloeosporioides) with the length of 1690 bp. The transformation procedure was based on the DNA transfer mediated by Agrobacterium tumefaciens bearing disarmed helper plasmid pMP90 and binary vector pCambia1300 with inserted DNA fragment of interest. The transformants proved to be mitotically stable, and the introduced gene was expressed at least at the level of transcription. Our work confirms that metabolic adaptations of strongly acidophilic fungi do not represent an obstacle for genetic transformation using conventional methods and can be potentially used for production of heterologous proteins. A promising role of the fast growing A. acidophila as active biomass in biotechnological processes is suggested not only by the low susceptibility of the culture grown at low pH to contaminations but also by reduced risk of accidental leaks of genetically modified microorganisms into the environment because highly specialized extremophilic fungi can poorly compete with common microflora under moderate conditions.

• MeSH
• Agrobacterium tumefaciens genetika   MeSH
• Amanita genetika   MeSH
• Ascomycota genetika   MeSH
• exprese genu MeSH
• genetické vektory MeSH
• koncentrace vodíkových iontů MeSH
• metalothionein genetika   MeSH
• plazmidy MeSH
• promotorové oblasti (genetika) MeSH
• terminace genetické transkripce MeSH
• transformace genetická * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• metalothionein MeSH