Enikő Vetlényi - Academia.edu (original) (raw)
Drafts by Enikő Vetlényi
Papers by Enikő Vetlényi
International Journal of Molecular Sciences
Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts ar... more Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein...
Carbonatite and associated silicate rocks occur in more than 520 localities in the Earth (WOOLEY ... more Carbonatite and associated silicate rocks occur in more than 520 localities in the Earth (WOOLEY & KJARSGAARD, 2008). One of significance of these igneous rocks is that they usually associated with mineral resources of rare earth + Y (REY) and some high field strength elements (e.g. Nb, Ta, Zr) (MORBIDELLI et al., 1995). Our main aim is to give a detailed petrographic observation on the magnetite carbonatite, collected in Jacupiranga (Brazil), in order to have solid base for further petrogenetic study. Optical microscopy, scanning electron microscopy and Raman microanalyses were carried out on the studied samples. The rock shows cumulate texture and consists mainly of calcite, dolomite and Ba-zoned phlogopite with abundant inclusions. Accessories are strontianite, celestine, apatite, forsterite, barite, chlorite, baddeleyite, geikielite, pyrophanite, uranpyrochlore, carbocernaite, vigezzite, ancylite, Mg-Al-hydrocarbonate, sphalerite and galena. It is characteristic for the sample t...
Orvosi Hetilap, Aug 1, 2020
A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcser... more A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcsere-folyamatban. Nélkülözhetetlen többek között a légzési lánc és a vasanyagcsere helyes működéséhez, a szabad gyökök eliminációjához, a hormonok, neurotranszmitterek szintéziséhez, valamint az extracelluláris mátrix stabilizálásához. A réz az oxidációs állapotváltozásra képes mivoltának köszönhetően kettős arculatú elem. A jelentősége a szervezetben a fehérjékhez kötötten vitathatatlan, azonban a szabad réz súlyos sejtkárosodást idéz elő főképpen szabad gyökös reakciók, fehérjék egyéb esszenciális fémtartalmának helyettesítése, valamint jelátviteli pályákra gyakorolt változatos hatása révén. Az emberi szervezetben jelen levő réz mennyisége kényes egyensúlyt képez. Mind hiánya, mind többlete súlyos tünetek, illetve kórképek kialakulását idézi elő. Táplálkozáseredetű rézanyagcsere-zavarok ritkán jelentkeznek, mivel az átlagos napi bevitele megfelelően fedezi a szükségletet, valamint a szervezet a rézraktárak kapacitásának köszönhetően jól tolerálja az átmeneti eltéréseket. A hiányállapot és a túlzott bevitel klinikai tüneteinek megismerésében és megértésében a rézanyagcserét érintő genetikai betegségek (Menkes-, Wilson-kór) nyújtottak segítséget. A réznek a krónikus betegségek kialakulásában betöltött szerepére egyre nagyobb figyelem irányul. Jelentősége körvonalazódik neurodegeneratív, valamint daganatos kórképek esetében is, mind kóroki tényezőként, mind terápiás célpontként.
International Journal of Molecular Sciences
Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clea... more Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correl...
Cancers
In spite of tremendous developments in breast cancer treatment, the relatively high incidence of ... more In spite of tremendous developments in breast cancer treatment, the relatively high incidence of relapsing cases indicates a great need to find new therapeutic strategies in recurrent, metastatic and advanced cases. The bioenergetic needs of growing tumours at the primary site or in metastases—accumulating genomic alterations and further heterogeneity—are supported by metabolic rewiring, an important hallmark of cancer. Adaptation mechanisms as well as altered anabolic and catabolic processes balance according to available nutrients, energy, oxygen demand and overgrowth or therapeutic resistance. Mammalian target of rapamycin (mTOR) hyperactivity may contribute to this metabolic plasticity and progression in breast carcinomas. We set out to assess the metabolic complexity in breast cancer cell lines and primary breast cancer cases. Cellular metabolism and mTOR-related protein expression were characterised in ten cell lines, along with their sensitivity to specific mTOR and other met...
<p&amp... more <p>In geosciences, high precision isotope ratio determination provides essential information about processes in geological systems. Novel ambitions evolve closer to biological applications. Copper is an essential metal for human body taking part of several cellular processes (e.g. respiratory chain, enzyme function, iron metabolism, elimination of reactive oxygen species, cell signalling pathways etc). However, the disorder of copper homeostasis causes serious diseases like Wilson disease (Cu accumulation in liver caused by genetical disorder) and it could also promote tumour growth by supporting angiogenesis and metastasis formation [Denoyer et al., 2015]. Despite numerous experiments, focusing on copper concentration determination in different tumour tissues (e.g. breast, lung cancer, etc.) hoping to assist in tumour diagnosis, the results are not convincing enough. However, previous studies on hepatocellular cancer and oral squamous cell carcinoma showed that tumour tissue appears to be relatively enriched in <sup>65</sup>Cu compared to normal tissue whereas the δ<sup>65</sup>Cu in blood of tumorous patient decreased according to data obtained from control population [Balter et al., 2015, Lobo et al., 2017]. Our main aim is to elaborate a method to understand better the change in <sup>63</sup>Cu/<sup>65</sup>Cu stable isotope ratio during tumour growth. In this approach, we present our first results on copper isotope ratio determination in a xenograft mouse model. Our model was established in SCID (severe combined immunodeficiency disease) mice by injecting human cancer cells (1x10<sup>7</sup> cells) subcutaneously. After the tumour reached approximately 2-3 cm diameter, the tumour mass was cut it in small, equal pieces and transplanted further into 10 mice increasing the experimental set-up homogeneity. All the animals were sacrificed by cardiac puncture under deep terminal anaesthesia within four weeks. Tumour and organs were removed by ceramic knife then were frozen with liquid nitrogen and stored at -80°C. We measured the copper concentration and δ<sup>65</sup>Cu in the tumour tissue, blood, liver, kidney and brain. A clean laboratory ambience was chosen to perform the sample preparation processes decreasing the environmental contamination. Separation of copper from other biologically essential element (Na, Mg, Fe, Zn) interfering the copper isotope measurement is a serious condition of the preparation [Lauwens et al., 2017]. Effects of sodium (<sup>23</sup>Na<sup>40</sup>Ar<sup>+</sup>) and magnesium…
Pathology & Oncology Research
The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tum... more The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tumours in central nervous system. The developing resistance against recent therapies and the recurrence rate of GBMs are extremely high. In spite several new ongoing trials, GBM therapies could not significantly increase the survival rate of the patients as significantly. The presence of inter-and intra-tumoral heterogeneity of GBMs arise the problem to find both the pre-existing potential resistant clones and the cellular processes which promote the adaptation mechanisms such as multidrug resistance, stem cell-ness or metabolic alterations, etc. In our work, the in situ metabolic heterogeneity of high-grade human glioblastoma cases were analysed by immunohistochemistry using tissue-microarray. The potential importance of the detected metabolic heterogeneity was tested in three glioma cell lines (grade III-IV) using protein expression analyses (Western blot and WES Simple) and therapeutic drug (temozolomide), metabolic inhibitor treatments (including glutaminase inhibitor) to compare the effects of rapamycin (RAPA) and glutaminase inhibitor combinations in vitro (Alamar Blue and SRB tests). The importance of individual differences and metabolic alterations were observed in mono-therapeutic failures, especially the enhanced Rictor expressions after different monotreatments in correlation to lower sensitivity (temozolomide, doxycycline, etomoxir, BPTES). RAPA combinations with other metabolic inhibitors were the best strategies except for RAPA+glutaminase inhibitor. These observations underline the importance of multi-targeting metabolic pathways. Finally, our data suggest that the detected metabolic heterogeneity (the high mTORC2 complex activity, enhanced expression of Rictor, p-Akt, p-S6, CPT1A, and LDHA enzymes in glioma cases) and the microenvironmental or treatment induced metabolic shift can be potential targets in combination therapy. Therefore, it should be considered to map tissue heterogeneity and alterations with several cellular metabolism markers in biopsy materials after applying recently available or new treatments.
Cancer Cell International
Background: Glioma is the most common highly aggressive, primary adult brain tumour. Clinical dat... more Background: Glioma is the most common highly aggressive, primary adult brain tumour. Clinical data show that therapeutic approaches cannot reach the expectations in patients, thus gliomas are mainly incurable diseases. Tumour cells can adapt rapidly to alterations during therapeutic treatments related to their metabolic rewiring and profound heterogeneity in tissue environment. Renewed interests aim to develop effective treatments targeting angiogenesis, kinase activity and/or cellular metabolism. mTOR (mammalian target of rapamycin), whose hyperactivation is characteristic for many tumours, promotes metabolic alterations, macromolecule biosynthesis, cellular growth and survival. Unfortunately, mTOR inhibitors with their lower toxicity have not resulted in appreciable survival benefit. Analysing mTOR inhibitor sensitivity, other metabolism targeting treatments and their combinations could help to find potential agents and biomarkers for therapeutic development in glioma patients. Methods: In vitro proliferation assays, protein expression and metabolite concentration analyses were used to study the effects of mTOR inhibitors, other metabolic treatments and their combinations in glioma cell lines. Furthermore, mTOR activity and cellular metabolism related protein expression patterns were also investigated by immunohistochemistry in human biopsies. Temozolomide and/or rapamycin treatments altered the expressions of enzymes related to lipid synthesis, glycolysis and mitochondrial functions as consequences of metabolic adaptation; therefore, other anti-metabolic drugs (chloroquine, etomoxir, doxycycline) were combined in vitro. Results: Our results suggest that co-targeting metabolic pathways had tumour cell dependent additive/synergistic effects related to mTOR and metabolic protein expression patterns cell line dependently. Drug combinations, especially rapamycin + doxycycline may have promising anti-tumour effect in gliomas. Additionally, our immunohistochemistry results suggest that metabolic and mTOR activity alterations are not related to the recent glioma classification, and these protein expression profiles show individual differences in patients' materials. Conclusions: Based on these, combinations of different new/old drugs targeting cellular metabolism could be promising to inhibit high adaptation capacity of tumour cells depending on their metabolic shifts. Relating to this, such a development of current therapy needs to find special biomarkers to characterise metabolic heterogeneity of gliomas.
Orvosi Hetilap
Absztrakt: A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számo... more Absztrakt: A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcsere-folyamatban. Nélkülözhetetlen többek között a légzési lánc és a vasanyagcsere helyes működéséhez, a szabad gyökök eliminációjához, a hormonok, neurotranszmitterek szintéziséhez, valamint az extracelluláris mátrix stabilizálásához. A réz az oxidációs állapotváltozásra képes mivoltának köszönhetően kettős arculatú elem. A jelentősége a szervezetben a fehérjékhez kötötten vitathatatlan, azonban a szabad réz súlyos sejtkárosodást idéz elő főképpen szabad gyökös reakciók, fehérjék egyéb esszenciális fémtartalmának helyettesítése, valamint jelátviteli pályákra gyakorolt változatos hatása révén. Az emberi szervezetben jelen levő réz mennyisége kényes egyensúlyt képez. Mind hiánya, mind többlete súlyos tünetek, illetve kórképek kialakulását idézi elő. Táplálkozáseredetű rézanyagcsere-zavarok ritkán jelentkeznek, mivel az átlagos napi bevitele megfelelően fedezi a szükségletet, valam...
International Journal of Molecular Sciences
Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts ar... more Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein...
Carbonatite and associated silicate rocks occur in more than 520 localities in the Earth (WOOLEY ... more Carbonatite and associated silicate rocks occur in more than 520 localities in the Earth (WOOLEY & KJARSGAARD, 2008). One of significance of these igneous rocks is that they usually associated with mineral resources of rare earth + Y (REY) and some high field strength elements (e.g. Nb, Ta, Zr) (MORBIDELLI et al., 1995). Our main aim is to give a detailed petrographic observation on the magnetite carbonatite, collected in Jacupiranga (Brazil), in order to have solid base for further petrogenetic study. Optical microscopy, scanning electron microscopy and Raman microanalyses were carried out on the studied samples. The rock shows cumulate texture and consists mainly of calcite, dolomite and Ba-zoned phlogopite with abundant inclusions. Accessories are strontianite, celestine, apatite, forsterite, barite, chlorite, baddeleyite, geikielite, pyrophanite, uranpyrochlore, carbocernaite, vigezzite, ancylite, Mg-Al-hydrocarbonate, sphalerite and galena. It is characteristic for the sample t...
Orvosi Hetilap, Aug 1, 2020
A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcser... more A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcsere-folyamatban. Nélkülözhetetlen többek között a légzési lánc és a vasanyagcsere helyes működéséhez, a szabad gyökök eliminációjához, a hormonok, neurotranszmitterek szintéziséhez, valamint az extracelluláris mátrix stabilizálásához. A réz az oxidációs állapotváltozásra képes mivoltának köszönhetően kettős arculatú elem. A jelentősége a szervezetben a fehérjékhez kötötten vitathatatlan, azonban a szabad réz súlyos sejtkárosodást idéz elő főképpen szabad gyökös reakciók, fehérjék egyéb esszenciális fémtartalmának helyettesítése, valamint jelátviteli pályákra gyakorolt változatos hatása révén. Az emberi szervezetben jelen levő réz mennyisége kényes egyensúlyt képez. Mind hiánya, mind többlete súlyos tünetek, illetve kórképek kialakulását idézi elő. Táplálkozáseredetű rézanyagcsere-zavarok ritkán jelentkeznek, mivel az átlagos napi bevitele megfelelően fedezi a szükségletet, valamint a szervezet a rézraktárak kapacitásának köszönhetően jól tolerálja az átmeneti eltéréseket. A hiányállapot és a túlzott bevitel klinikai tüneteinek megismerésében és megértésében a rézanyagcserét érintő genetikai betegségek (Menkes-, Wilson-kór) nyújtottak segítséget. A réznek a krónikus betegségek kialakulásában betöltött szerepére egyre nagyobb figyelem irányul. Jelentősége körvonalazódik neurodegeneratív, valamint daganatos kórképek esetében is, mind kóroki tényezőként, mind terápiás célpontként.
International Journal of Molecular Sciences
Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clea... more Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correl...
Cancers
In spite of tremendous developments in breast cancer treatment, the relatively high incidence of ... more In spite of tremendous developments in breast cancer treatment, the relatively high incidence of relapsing cases indicates a great need to find new therapeutic strategies in recurrent, metastatic and advanced cases. The bioenergetic needs of growing tumours at the primary site or in metastases—accumulating genomic alterations and further heterogeneity—are supported by metabolic rewiring, an important hallmark of cancer. Adaptation mechanisms as well as altered anabolic and catabolic processes balance according to available nutrients, energy, oxygen demand and overgrowth or therapeutic resistance. Mammalian target of rapamycin (mTOR) hyperactivity may contribute to this metabolic plasticity and progression in breast carcinomas. We set out to assess the metabolic complexity in breast cancer cell lines and primary breast cancer cases. Cellular metabolism and mTOR-related protein expression were characterised in ten cell lines, along with their sensitivity to specific mTOR and other met...
<p&amp... more <p>In geosciences, high precision isotope ratio determination provides essential information about processes in geological systems. Novel ambitions evolve closer to biological applications. Copper is an essential metal for human body taking part of several cellular processes (e.g. respiratory chain, enzyme function, iron metabolism, elimination of reactive oxygen species, cell signalling pathways etc). However, the disorder of copper homeostasis causes serious diseases like Wilson disease (Cu accumulation in liver caused by genetical disorder) and it could also promote tumour growth by supporting angiogenesis and metastasis formation [Denoyer et al., 2015]. Despite numerous experiments, focusing on copper concentration determination in different tumour tissues (e.g. breast, lung cancer, etc.) hoping to assist in tumour diagnosis, the results are not convincing enough. However, previous studies on hepatocellular cancer and oral squamous cell carcinoma showed that tumour tissue appears to be relatively enriched in <sup>65</sup>Cu compared to normal tissue whereas the δ<sup>65</sup>Cu in blood of tumorous patient decreased according to data obtained from control population [Balter et al., 2015, Lobo et al., 2017]. Our main aim is to elaborate a method to understand better the change in <sup>63</sup>Cu/<sup>65</sup>Cu stable isotope ratio during tumour growth. In this approach, we present our first results on copper isotope ratio determination in a xenograft mouse model. Our model was established in SCID (severe combined immunodeficiency disease) mice by injecting human cancer cells (1x10<sup>7</sup> cells) subcutaneously. After the tumour reached approximately 2-3 cm diameter, the tumour mass was cut it in small, equal pieces and transplanted further into 10 mice increasing the experimental set-up homogeneity. All the animals were sacrificed by cardiac puncture under deep terminal anaesthesia within four weeks. Tumour and organs were removed by ceramic knife then were frozen with liquid nitrogen and stored at -80°C. We measured the copper concentration and δ<sup>65</sup>Cu in the tumour tissue, blood, liver, kidney and brain. A clean laboratory ambience was chosen to perform the sample preparation processes decreasing the environmental contamination. Separation of copper from other biologically essential element (Na, Mg, Fe, Zn) interfering the copper isotope measurement is a serious condition of the preparation [Lauwens et al., 2017]. Effects of sodium (<sup>23</sup>Na<sup>40</sup>Ar<sup>+</sup>) and magnesium…
Pathology & Oncology Research
The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tum... more The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tumours in central nervous system. The developing resistance against recent therapies and the recurrence rate of GBMs are extremely high. In spite several new ongoing trials, GBM therapies could not significantly increase the survival rate of the patients as significantly. The presence of inter-and intra-tumoral heterogeneity of GBMs arise the problem to find both the pre-existing potential resistant clones and the cellular processes which promote the adaptation mechanisms such as multidrug resistance, stem cell-ness or metabolic alterations, etc. In our work, the in situ metabolic heterogeneity of high-grade human glioblastoma cases were analysed by immunohistochemistry using tissue-microarray. The potential importance of the detected metabolic heterogeneity was tested in three glioma cell lines (grade III-IV) using protein expression analyses (Western blot and WES Simple) and therapeutic drug (temozolomide), metabolic inhibitor treatments (including glutaminase inhibitor) to compare the effects of rapamycin (RAPA) and glutaminase inhibitor combinations in vitro (Alamar Blue and SRB tests). The importance of individual differences and metabolic alterations were observed in mono-therapeutic failures, especially the enhanced Rictor expressions after different monotreatments in correlation to lower sensitivity (temozolomide, doxycycline, etomoxir, BPTES). RAPA combinations with other metabolic inhibitors were the best strategies except for RAPA+glutaminase inhibitor. These observations underline the importance of multi-targeting metabolic pathways. Finally, our data suggest that the detected metabolic heterogeneity (the high mTORC2 complex activity, enhanced expression of Rictor, p-Akt, p-S6, CPT1A, and LDHA enzymes in glioma cases) and the microenvironmental or treatment induced metabolic shift can be potential targets in combination therapy. Therefore, it should be considered to map tissue heterogeneity and alterations with several cellular metabolism markers in biopsy materials after applying recently available or new treatments.
Cancer Cell International
Background: Glioma is the most common highly aggressive, primary adult brain tumour. Clinical dat... more Background: Glioma is the most common highly aggressive, primary adult brain tumour. Clinical data show that therapeutic approaches cannot reach the expectations in patients, thus gliomas are mainly incurable diseases. Tumour cells can adapt rapidly to alterations during therapeutic treatments related to their metabolic rewiring and profound heterogeneity in tissue environment. Renewed interests aim to develop effective treatments targeting angiogenesis, kinase activity and/or cellular metabolism. mTOR (mammalian target of rapamycin), whose hyperactivation is characteristic for many tumours, promotes metabolic alterations, macromolecule biosynthesis, cellular growth and survival. Unfortunately, mTOR inhibitors with their lower toxicity have not resulted in appreciable survival benefit. Analysing mTOR inhibitor sensitivity, other metabolism targeting treatments and their combinations could help to find potential agents and biomarkers for therapeutic development in glioma patients. Methods: In vitro proliferation assays, protein expression and metabolite concentration analyses were used to study the effects of mTOR inhibitors, other metabolic treatments and their combinations in glioma cell lines. Furthermore, mTOR activity and cellular metabolism related protein expression patterns were also investigated by immunohistochemistry in human biopsies. Temozolomide and/or rapamycin treatments altered the expressions of enzymes related to lipid synthesis, glycolysis and mitochondrial functions as consequences of metabolic adaptation; therefore, other anti-metabolic drugs (chloroquine, etomoxir, doxycycline) were combined in vitro. Results: Our results suggest that co-targeting metabolic pathways had tumour cell dependent additive/synergistic effects related to mTOR and metabolic protein expression patterns cell line dependently. Drug combinations, especially rapamycin + doxycycline may have promising anti-tumour effect in gliomas. Additionally, our immunohistochemistry results suggest that metabolic and mTOR activity alterations are not related to the recent glioma classification, and these protein expression profiles show individual differences in patients' materials. Conclusions: Based on these, combinations of different new/old drugs targeting cellular metabolism could be promising to inhibit high adaptation capacity of tumour cells depending on their metabolic shifts. Relating to this, such a development of current therapy needs to find special biomarkers to characterise metabolic heterogeneity of gliomas.
Orvosi Hetilap
Absztrakt: A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számo... more Absztrakt: A réz esszenciális nyomelem az emberi szervezet számára, fontos szerepet tölt be számos anyagcsere-folyamatban. Nélkülözhetetlen többek között a légzési lánc és a vasanyagcsere helyes működéséhez, a szabad gyökök eliminációjához, a hormonok, neurotranszmitterek szintéziséhez, valamint az extracelluláris mátrix stabilizálásához. A réz az oxidációs állapotváltozásra képes mivoltának köszönhetően kettős arculatú elem. A jelentősége a szervezetben a fehérjékhez kötötten vitathatatlan, azonban a szabad réz súlyos sejtkárosodást idéz elő főképpen szabad gyökös reakciók, fehérjék egyéb esszenciális fémtartalmának helyettesítése, valamint jelátviteli pályákra gyakorolt változatos hatása révén. Az emberi szervezetben jelen levő réz mennyisége kényes egyensúlyt képez. Mind hiánya, mind többlete súlyos tünetek, illetve kórképek kialakulását idézi elő. Táplálkozáseredetű rézanyagcsere-zavarok ritkán jelentkeznek, mivel az átlagos napi bevitele megfelelően fedezi a szükségletet, valam...