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1.
Nanotechnology ; 35(30)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38631306

RESUMO

Electronic transport in monolayer MoS2is significantly constrained by several extrinsic factors despite showing good prospects as a transistor channel material. Our paper aims to unveil the underlying mechanisms of the electrical and magneto-transport in monolayer MoS2. In order to quantitatively interpret the magneto-transport behavior of monolayer MoS2on different substrate materials, identify the underlying bottlenecks, and provide guidelines for subsequent improvements, we present a deep analysis of the magneto-transport properties in the diffusive limit. Our calculations are performed on suspended monolayer MoS2and MoS2on different substrate materials taking into account remote impurity and the intrinsic and extrinsic phonon scattering mechanisms. We calculate the crucial transport parameters such as the Hall mobility, the conductivity tensor elements, the Hall factor, and the magnetoresistance over a wide range of temperatures, carrier concentrations, and magnetic fields. The Hall factor being a key quantity for calculating the carrier concentration and drift mobility, we show that for suspended monolayer MoS2at room temperature, the Hall factor value is around 1.43 for magnetic fields ranging from 0.001 to 1 Tesla, which deviates significantly from the usual value of unity. In contrast, the Hall factor for various substrates approaches the ideal value of unity and remains stable in response to the magnetic field and temperature. We also show that the MoS2over an Al2O3substrate is a good choice for the Hall effect detector. Moreover, the magnetoresistance increases with an increase in magnetic field strength for smaller magnetic fields before reaching saturation at higher magnetic fields. The presented theoretical model quantitatively captures the scaling of mobility and various magnetoresistance coefficients with temperature, carrier densities, and magnetic fields.

2.
Phys Chem Chem Phys ; 26(27): 18907-18917, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38949654

RESUMO

MAX phase is a family of ceramic compounds, typically known for their metallic properties. However, we show here that some of them may be narrow bandgap semiconductors. Using a series of first-principles calculations, we have investigated the electronic structures of 861 dynamically stable MAX phases. Notably, Sc2SC, Y2SC, Y2SeC, Sc3AuC2, and Y3AuC2 have been identified as semiconductors with band gaps ranging from 0.2 to 0.5 eV. Furthermore, we have assessed the thermodynamic stability of these systems by generating ternary phase diagrams utilizing evolutionary algorithm techniques. Their dynamic stabilities are confirmed by phonon calculations. Additionally, we have explored the potential thermoelectric efficiencies of these materials by combining Boltzmann transport theory with first-principles calculations. The relaxation times are estimated using scattering theory. The zT coefficients for the aforementioned systems fall within the range of 0.5 to 2.5 at temperatures spanning from 300 to 700 K, indicating their suitability for high-temperature thermoelectric applications.

3.
Oral Dis ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243590

RESUMO

OBJECTIVES: This study investigated the miRNA expression profile in Notch-activated human dental stem pulp stem cells (DPSCs) and validated the functions of miRNAs in modulating the odonto/osteogenic properties of DPSCs. METHODS: DPSCs were treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed, and miRNA expression was validated. Odonto/osteogenic differentiation was examined using alkaline phosphatase staining, Alizarin Red S staining, as well as odonto/osteogenic-related gene and protein expression. RESULTS: Fourteen miRNAs were differentially expressed in Jagged1-treated DPSCs. Pathway analysis revealed that altered miRNAs were associated with TGF-ß, Hippo, ErbB signalling pathways, FoxO and Ras signalling. Target prediction analysis demonstrated that 7604 genes were predicted to be targets for these altered miRNAs. Enrichment analysis revealed relationships to various DNA bindings. Among differentially expressed miRNA, miR-296-3p and miR-450b-5p were upregulated under Jagged1-treated conditions. Overexpression of miR-296-3p and miR-450b-5p enhanced mineralization and upregulation of odonto/osteogenic-related genes, whereas inhibition of these miRNAs revealed opposing results. The miR-296-3p and miR-450b-5p inhibitors attenuated the effects of Jagged1-induced mineralization in DPSCs. CONCLUSIONS: Jagged-1 promotes mineralization in DPSCs that are partially regulated by miRNA. The novel understanding of these miRNAs could lead to innovative controlled mechanisms that can be applied to modulate biology-targeted dental materials.

4.
Phys Chem Chem Phys ; 25(6): 5203-5210, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36723101

RESUMO

Finding a suitable material for hydrogen storage under ambient atmospheric conditions is challenging for material scientists and chemists. In this work, using a first principles based cluster expansion approach, the hydrogen storage capacity of the Ti2AC (A = Al, Ti, Cr, Mn, Fe, Co, Ni, Cu, and Zn) MAX phase and its alloys was studied. We found that hydrogen is energetically stable in Ti-A layers in which the tetrahedral site consisting of one A atom and three Ti atoms is energetically more favorable for hydrogen adsorption than other sites in the Ti-A layer. Ti2CuC has the highest hydrogen adsorption energy than other Ti2AC phases. We find that the 83.33% Cu doped Ti2AlxCu1-xC alloy structure is both energetically and dynamically stable and can store 3.66 wt% hydrogen under ambient atmospheric conditions, which is higher than that stored by both Ti2AlC and Ti2CuC phases. These findings indicate that the hydrogen capacity of the MAX phase can be significantly improved by doping an appropriate atom species.

5.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361910

RESUMO

Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR-34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR-34a mimic than in non-transfected cells, and the B[a]P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR-34a and thereby suppresses B[a]P-induced DNA damage.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , MicroRNAs , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Benzo(a)pireno/toxicidade , Quercetina/farmacologia , Regulação para Baixo , Dano ao DNA , Adutos de DNA , Mutagênicos/toxicidade , MicroRNAs/genética
6.
J Comput Chem ; 42(29): 2116-2129, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34406662

RESUMO

We present a modular and extendable software suite, DJMol, for performing molecular simulations and it is demonstrated with DFTB+, Siesta, Atomic Simulation Environment, and OpenMD codes. It supports many of the standard features of an integrated development environment and consists of a structure builder and viewer, which could be connected with these electronic structure codes along with a set of data analyzers. This program comprises Java and Python modules and its libraries to carry out a different set of modeling tasks in materials science and chemistry. By adopting a Python interpreter into the software, a range of scriptable Python codes, such as Pymatgen can be incorporated into this programmable modeling platform. DJMol, through its common application programming interface (API), supports multiple modeling codes in the backend and several post-processing tools. It benefits an experienced user by increasing efficiency, while a nonexpert user by easy to use API.

7.
Phys Chem Chem Phys ; 23(6): 3802-3809, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33533337

RESUMO

Chemisorption on ferromagnetic and non-magnetic surfaces is discussed within the Newns-Anderson-Grimley model along with the Stoner model of ferromagnetism. In the case of ferromagnetic surfaces, the adsorption energy is formulated in terms of the change in surface magnetic moments. Using such a formulation, we address the issue of how an adsorbate's binding strength depends on the magnetic moments of the surface and how the adsorption process reduces/enhances the magnetic moments of the surface. Our results indicate a possible scaling relationship of adsorption energy in terms of surface magnetic moments. In the case of non-magnetic surfaces, we formulate a modified Stoner criterion and discuss the condition for the appearance of magnetism due to chemisorption on an otherwise non-magnetic surface.

8.
J Chem Phys ; 154(10): 104111, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33722030

RESUMO

We formulate Wannier orbital overlap population and Wannier orbital Hamilton population to describe the contribution of different orbitals to electron distribution and their interactions. These methods, which are analogous to the well-known crystal orbital overlap population and crystal orbital Hamilton population, provide insight into the distribution of electrons at various atom centers and their contributions to bonding. We apply this formalism in the context of a plane-wave density functional theory calculation. This method provides a means to connect the non-local plane-wave basis to a localized basis by projecting the wave functions from a plane-wave density functional theory calculation to a localized Wannier orbital basis. The main advantage of this formulation is that the spilling factor is strictly zero for insulators and can systematically be made small for metals. We use our proposed method to study and obtain bonding and electron localization insights in five different materials.

9.
Phys Chem Chem Phys ; 22(32): 17960-17968, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32747888

RESUMO

The scaling relationships between the adsorption energies of different reaction intermediates have a tremendous effect in the field of surface science, particularly in predicting new catalytic materials. In the last few decades, these scaling laws have been extensively studied and interpreted by a number of research groups which makes them almost universally accepted. In this work, we report the breakdown of the standard scaling law in magnetic bimetallic transition metal (TM) surfaces for hydrogenated species of oxygen (O), carbon (C), and nitrogen (N), where the adsorption energies are estimated using density functional theory (DFT). We propose that the scaling relationships do not necessarily rely solely on the adsorbates, they can also be strongly dependent on the surface properties. For magnetic bimetallic TM surfaces, the magnetic moment plays a vital role in the estimation of adsorption energy, and therefore towards the linear scaling relation.

10.
Sensors (Basel) ; 19(24)2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861223

RESUMO

Silicon shows very high detection efficiency for low-energy photons, and the silicon pixel sensor provides high spatial resolution. Pixelated silicon sensors facilitate the direct detection of low-energy X-ray radiation. In this study, we developed junction field effect transistors (JFETs) that can be integrated into a pixelated silicon sensor to effectively handle many signal readout channels due to the pixelated structure without any change in the sensor resolution; this capability of the integrated system arises from the pixelated structure of the sensor. We focused on optimizing the JFET's switching function, and simulated JFETs with different fabrication parameters. Furthermore, prototype JFET switches were designed and fabricated on the basis of the simulated results. It is important not only to keep the low leakage currents in the JFET but also reduce the current flow as much as possible by providing a high resistance when the JFET switch is off. We determined the optimal fabrication conditions for the effective switching of the JFETs. In this paper, we present the results of the measurement of the switching capability of the fabricated JFETs for various design variables and fabrication conditions.

11.
J Biol Chem ; 291(10): 5157-71, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26703469

RESUMO

A network model for the determination of tumor metabolic fluxes from (13)C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-(13)C2]glucose under normoxic conditions at 37 °C and monitored by (13)C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼ 50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼ 6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism.


Assuntos
Melanoma/metabolismo , Fosforilação Oxidativa , Trifosfato de Adenosina/metabolismo , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Modelos Teóricos , Mutação de Sentido Incorreto , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética
12.
Biochim Biophys Acta ; 1866(2): 151-162, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27497601

RESUMO

Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and photodynamic-therapy and hyperthermia. Although the mechanism of action remained unclear, LND treatment has been known to target metabolic pathways in cancer cells. It has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibited l-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Recent studies have demonstrated that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki 2.5µM) and cooperatively inhibits l-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill coefficient values of 36-40µM and 1.65-1.85, respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50~7µM) than other substrates including glutamate (IC50~20µM). LND inhibits the succinate-ubiquinone reductase activity of respiratory Complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through Complex II and has been reported to promote cell death by suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated l-lactic acid efflux, Complex II and glutamine/glutamate oxidation.


Assuntos
Antineoplásicos/farmacologia , Indazóis/farmacologia , Animais , Hexoquinase/antagonistas & inibidores , Humanos , Concentração de Íons de Hidrogênio , Indazóis/toxicidade , Proteínas de Membrana Transportadoras/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ácido Pirúvico/metabolismo
13.
Phys Chem Chem Phys ; 19(32): 21282-21286, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28776619

RESUMO

Being a member of the van der Waals class of solids, bilayer MoS2 exhibits polytypism due to different possible stacking arrangements, namely, 2Hc, 2Ha and 3R-polytypes. Unlike monolayer MoS2, these bilayers exhibit indirect band gaps. Band extrema states originate from a linear combination of Mo-(d) and S-(p) orbitals which are sensitive to the interlayer interactions. We have studied the impact of stacking pattern on the electronic structure and electron/hole transport properties of these polytypes. Based on first-principles computations coupled with the Boltzmann transport formalism, we found that a strong electron-hole anisotropy can be realised in the 2Ha-MoS2 polytype unlike in a monolayer which is isotropic in nature. A staggered arrangement between two layers results in a higher relaxation time for electrons compared to holes leading to anisotropy which is of importance in device engineering.

14.
Food Microbiol ; 52: 159-68, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26338131

RESUMO

The ability of nine commercial broths to enrich healthy and 90% sanitizer-injured Salmonella Typhimurium and Salmonella cocktail on mung bean sprouts was evaluated to select an optimum broth for detection. Results showed that S. Typhimurium multiplied faster and reached a higher population in buffered peptone water (BPW), Salmonella AD media (AD) and ONE broth-Salmonella (OB), compared with other broths. Healthy and 90% sanitizer-injured Salmonella at low concentrations increased by 4.0 log CFU/ml in these three broths. However, no Salmonella growth was observed in lactose broth (LB). Further investigation showed that during incubation, pH of LB dropped from 6.7 to 4.2, due to production of lactic (66 mM) and acetic acids (62 mM) by lactic acid bacteria that were identified as dominant microbiota in bean sprouts. Though no cell membrane damage was detected by propidium monoazide combined with real-time PCR, it was found that LB inhibited Salmonella growth, especially from low inoculum levels. This study suggests that in consideration of effectiveness and cost, BPW would be a suitable enrichment broth to use for isolating and detecting Salmonella on mung bean sprouts, while using LB might cause false negative results in Salmonella detection by either PCR or standard cultural method.


Assuntos
Fabaceae/microbiologia , Contaminação de Alimentos/análise , Salmonella typhimurium/crescimento & desenvolvimento , Verduras/microbiologia , Qualidade de Produtos para o Consumidor , Meios de Cultura/química , Fabaceae/crescimento & desenvolvimento , Contaminação de Alimentos/economia , Germinação , Salmonella typhimurium/genética , Salmonella typhimurium/isolamento & purificação , Sementes/crescimento & desenvolvimento , Sementes/microbiologia , Verduras/economia
15.
J Korean Med Sci ; 30(2): 207-13, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25653494

RESUMO

Using the Korean Society of Anesthesiologists database of anesthesia-related medical disputes (July 2009-June 2014), causative mechanisms and injury patterns were analyzed. In total, 105 cases were analyzed. Most patients were aged < 60 yr (82.9%) and were classified as American Society of Anesthesiologists physical status ≤ II (90.5%). In 42.9% of all cases, the injuries were determined to be 'avoidable' if the appropriate standard of care had been applied. Sedation was the sec most common type of anesthesia (37.1% of all cases), following by general anesthesia. Most sedation cases (27/39, 69.2%) showed a common lack of vigilance: no pre-procedural testing (82.1%), absence of anesthesia record (89.7%), and non-use of intra-procedural monitoring (15.4%). Most sedation (92.3%) was provided simultaneously by the non-anesthesiologists who performed the procedures. After the resulting injuries were grouped into four categories (temporary, permanent/minor, permanent/major, and death), their causative mechanisms were analyzed in cases with permanent injuries (n=20) and death (n=82). A 'respiratory events' was the leading causative mechanism (56/102, 54.9%). Of these, the most common specific mechanism was hypoxia secondary to airway obstruction or respiratory depression (n=31). The sec most common damaging event was a 'cardiovascular events' (26/102, 25.5%), in which myocardial infarction was the most common specific mechanism (n=12). Our database analysis demonstrated several typical injury profiles (a lack of vigilance in seemingly safe procedures or sedation, non-compliance with the airway management guidelines, and the prevalence of myocardial infarction) and can be helpful to improve patient safety.


Assuntos
Anestesia Geral/efeitos adversos , Imperícia , Erros Médicos , Adulto , Feminino , Humanos , Hipóxia/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , República da Coreia/epidemiologia
16.
ACS Omega ; 9(6): 6482-6491, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371824

RESUMO

In this work, we report the results of density functional theory (DFT) calculations on a van der Waals (VdW) heterostructure formed by vertically stacking single-layers of tungsten disulfide and graphene (WS2/graphene) for use as an anode material in lithium-ion batteries (LIBs). The electronic properties of the heterostructure reveal that the graphene layer improves the electronic conductivity of this hybrid system. Phonon calculations demonstrate that the WS2/graphene heterostructure is dynamically stable. Charge transfer from Li to the WS2/graphene heterostructure further enhances its metallic character. Moreover, the Li binding energy in this heterostructure is higher than that of the Li metal's cohesive energy, significantly reducing the possibility of Li-dendrite formation in this WS2/graphene electrode. Ab initio molecular dynamics (AIMD) simulations of the lithiated WS2/graphene heterostructure show the system's thermal stability. Additionally, we explore the effect of heteroatom doping (boron (B) and nitrogen (N)) on the graphene layer of the heterostructure and its impact on Li-adsorption ability. The results suggest that B-doping strengthens the Li-adsorption energy. Notably, the calculated open-circuit voltage (OCV) and Li-diffusion energy barrier further support the potential of this heterostructure as a promising anode material for LIBs.

17.
ACS Appl Mater Interfaces ; 16(7): 8763-8771, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38327063

RESUMO

Despite having favorable energetics and tunable optoelectronic properties, utilization of BaTiO3 (BTO) for photocatalytic reactions is limited by its absorption only in the ultraviolet region. To address this challenge, BTO is doped with iridium (Ir) to induce visible light absorption. The visible light-induced photocatalytic H2 generation efficiency is enhanced by 2 orders of magnitude on selective conversion of the Ir valence state from Ir4+ to Ir3+. To understand such intriguing behavior, valence state-dependent changes in the optoelectronic, structural, and surface properties and electronic band structure are comprehensively investigated. The effect of electron occupancy change between Ir4+ (t2g5 eg0) and Ir3+ (t2g6 eg0) and their energetic positions within the band gap is found to significantly influence H2 generation. Besides this, converting Ir4+ to Ir3+ enhanced the photocathodic current and lowered the onset potential. Results aid in designing photocatalysts to efficiently use low-energy photons for enhancing solar H2 production in these emerging BTO-based photocatalysts. Collectively, the observations made in this work highlight the promising application of Ir3+:BTO in z-scheme photocatalysis.

18.
NMR Biomed ; 26(1): 106-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22711601

RESUMO

The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor volume, a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metabolism and has the potential to provide early and patient-specific markers of drug activity. Using human B-cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid production in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. The inhibition was time dependent and was first detectable 8 h after drug administration in cell cultures. In xenotransplants, 2 days of rapamycin treatment produced significant changes in lactic acid concentration in the tumor measured in vivo, which were followed by tumor growth arrest and tumor volume regression. The rapamycin-induced changes in lactate production were strongly correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway. These studies suggest that MRS or (18) F-fluorodeoxyglucose positron emission tomography (FDG PET) detection of changes in glucose metabolism may represent effective noninvasive methods for the monitoring of mTOR targeting therapy in lymphomas and other malignancies. Furthermore, the measurement of glucose metabolic inhibition by MRS or FDG PET imaging may also prove to be effective in monitoring the efficacy of other kinase inhibitors given that the rapamycin-sensitive mTOR lies downstream of many oncogenic signaling pathways.


Assuntos
Glicólise/efeitos dos fármacos , Ácido Láctico/metabolismo , Linfoma de Células B/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Camundongos , Camundongos SCID
19.
NMR Biomed ; 26(1): 98-105, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22745015

RESUMO

In vivo (31) P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pH(i) ) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pH(e) ) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pH(i) decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post-LND, with no significant change in pH(e) and a small transient decrease in bioenergetics (32.9 ± 10.6%, p > 0.05) at 40 min post-LND. No changes in pH(i) or adenosine triphosphate/inorganic phosphate were detected in the brain (pH(i) , bioenergetics; p > 0.1) or skeletal muscle (pH(i) , pH(e) , bioenergetics; p > 0.1) for at least 120 min post-LND. Steady-state tumor lactate monitored by (1) H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three-fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log(10) cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pH(i) and bioenergetics may sensitize melanoma to pH-dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia.


Assuntos
Concentração de Íons de Hidrogênio/efeitos dos fármacos , Indazóis/administração & dosagem , Espectroscopia de Ressonância Magnética/métodos , Melanoma/química , Melanoma/tratamento farmacológico , Melfalan/administração & dosagem , Animais , Antineoplásicos Alquilantes , Linhagem Celular Tumoral , Sinergismo Farmacológico , Metabolismo Energético/efeitos dos fármacos , Melanoma/fisiopatologia , Camundongos , Radioisótopos de Fósforo , Prótons , Resultado do Tratamento
20.
Adv Exp Med Biol ; 789: 243-249, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23852501

RESUMO

Drug treatment may alter the metabolism of cancer cells and may alter the mitochondrial redox state. Using the redox scanner that collects the fluorescence signals from both the oxidized flavoproteins (Fp) and the reduced form of nicotinamide adenine dinucleotide (NADH) in snap-frozen tumor tissues, we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2). The mice in the treatment group were treated with CHOP - cyclophosphamide (C) + hydroxydoxorubicin (H) + Oncovin (O) + prednisone (P) using the following regimen: CHO administration on day 1 followed by prednisone administration on day 1-5. On day 5 the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.049), and the Fp content of the treated group was significantly decreased (p = 0.033).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linhagem Celular Tumoral , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NAD/metabolismo , Oxirredução , Prednisona/administração & dosagem , Vincristina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
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