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1.
Front Sports Act Living ; 5: 1236112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37886220

RESUMO

Introduction: This study aims to (1) determine the average and most demanding passage (MDP) load of national-level female soccer matches and (2) evaluate the relationship between average and MDP load during small-sided games (SSGs), large-sided games (LSGs), and matches. Methods: A total of 37 national-level female soccer players from a single club senior team and the U18 team participated. The average and 1-, 3-, and 5-min MDP external (total, high-speed, and very-high-speed running distances, acceleration and deceleration distances, average metabolic power, and high-metabolic load distance) and internal loads (average heart rate, rate of perceived exertion) of the 29 league matches, ten 4 vs. 4 + goalkeepers SSGs, and six 8 vs. 8 + goalkeepers LSGs were analyzed by the Polar Team Pro player tracking system. Results: In matches, the external load variables during 1-, 3-, and 5-min MDPs were 167%-1,165%, 135%-504%, and 126%-359%, of match average values, respectively. In LSGs, all external load variables reached higher average values compared with those during matches, except for the very-high-speed running distance; however, no variable reached higher values of 1-min MDP compared with those during the matches. In SSGs, the average acceleration and deceleration distances were higher compared with those during the matches. Discussion: The findings from the present study suggest that LSGs and SSGs can be used to overload the average values of the selected external load variables compared with those during the matches; however, other training options must be explored to overload 1-min match MDPs.

2.
J Sports Sci ; 41(22): 2027-2032, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38287473

RESUMO

The scientific literature lacks consensus on classification of middle- and long-distance runners. This creates situations where the sample studied may not represent the target population and could produce misleading conclusions. Thus, we present an approach for a data-driven classification of middle- and long-distance runners according to their competition results. The best annual results of middle- and long-distance track runners participating at major (Olympics, World and European Championships) and national championships (Denmark, Sweden, Finland, Norway) were gathered for the 2012-2018 period. Overall, 1920 men's and 1808 women's performance results were gathered. The results were grouped accordingly. Quadratic discriminant analysis was applied to define the limits between the groups. Three basic categories could be proposed for classification: world class, international and national. Classification provides a realistic overview of performance standards and the number of athletes for different categories in middle- and long-distance track running in real-world settings. The performance-based classification provides data-driven and unified criteria for reporting standards on athletes' proficiency levels. It allows for more consistent reporting practices on the target population in research. In addition to scientific research, the classification could also be employed for a variety of practical purposes.


Assuntos
Resistência Física , Corrida , Masculino , Humanos , Feminino , Atletas , Consenso , Finlândia
3.
J Mater Chem B ; 8(6): 1146-1156, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32011620

RESUMO

A paper-based platform was developed and tested for studies on basic cell culture, material biocompatibility, and activity of pharmaceuticals in order to provide a reliable, robust and low-cost cell study platform. It is based upon a paper or paperboard support, with a nanostructured latex coating to provide an enhanced cell growth and sufficient barrier properties. Wetting is limited to regions of interest using a flexographically printed hydrophobic polydimethylsiloxane layer with circular non-print areas. The nanostructured coating can be substituted for another coating of interest, or the regions of interest functionalized with a material to be studied. The platform is fully up-scalable, being produced with roll-to-roll rod coating, flexographic and inkjet printing methods. Results show that the platform efficiency is comparable to multi-well plates in colorimetric assays in three separate studies: a cell culture study, a biocompatibility study, and a drug screening study. The color intensity is quantified by using a common office scanner or an imaging device and the data is analyzed by a custom computer software without the need for expensive screening or analysis equipment.


Assuntos
Materiais Revestidos Biocompatíveis/economia , Dimetilpolisiloxanos/economia , Teste de Materiais , Papel , Preparações Farmacêuticas/economia , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Dimetilpolisiloxanos/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Preparações Farmacêuticas/química , Propriedades de Superfície
4.
Br J Dermatol ; 182(3): 658-670, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31049937

RESUMO

BACKGROUND: The incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. OBJECTIVES: To study the role of the complement classical pathway components C1q, C1r and C1s in the progression of cSCC. METHODS: The mRNA levels of C1Q subunits and C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes, cSCC tumours in vivo and normal skin were analysed with quantitative real-time polymerase chain reaction. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analysed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. RESULTS: Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared with normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumours in vivo compared with normal skin. Abundant expression of C1r and C1s by tumour cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of extracellular signal-related kinase 1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumours in vivo. CONCLUSIONS: These results provide evidence for the role of tumour-cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC. What's already known about this topic? The incidences of actinic keratosis, cutaneous squamous cell carcinoma (cSCC) in situ and invasive cSCC are increasing globally. Few specific biomarkers for progression of cSCC have been identified, and no biological markers are in clinical use to predict the aggressiveness of actinic keratosis, cSCC in situ and invasive cSCC. What does this study add? Our results provide novel evidence for the role of complement classical pathway components C1r and C1s in the progression of cSCC. What is the translational message? Our results identify complement classical pathway components C1r and C1s as biomarkers and putative therapeutic targets in cSCC.


Assuntos
Carcinoma de Células Escamosas , Ceratose Actínica , Neoplasias Cutâneas , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Humanos , Queratinócitos , Neoplasias Cutâneas/genética
5.
Sci Rep ; 8(1): 10033, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968751

RESUMO

We report development and microwave characterization of rf SQUID (Superconducting QUantum Interference Device) qubits, consisting of an aluminium-based Josephson junction embedded in a superconducting loop patterned from a thin film of TiN with high kinetic inductance. Here we demonstrate that the systems can offer small physical size, high anharmonicity, and small scatter of device parameters. The work constitutes a non-tunable prototype realization of an rf SQUID qubit built on the kinetic inductance of a superconducting nanowire, proposed in Phys. Rev. Lett. 104, 027002 (2010). The hybrid devices can be utilized as tools to shed further light onto the origin of film dissipation and decoherence in phase-slip nanowire qubits, patterned entirely from disordered superconducting films.

6.
Scand J Med Sci Sports ; 28(1): 203-211, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28415143

RESUMO

This study examined the associations of cardiorespiratory fitness (CRF) and leisure-time physical activity (LTPA) with health-related quality of life (HRQoL) in women at risk for gestational diabetes mellitus (GDM). The participants were 39 women planning pregnancy with a history of GDM and/or BMI >29 kg/m2 . We assessed CRF by measuring maximal oxygen consumption (VO2max ) during incremental cycle ergometer exercise until voluntary fatigue. LTPA was self-reported, and HRQoL assessed with the SF-36 Health Survey (SF-36). The mean (SD) VO2max was 27 (6) mL·kg-1 ·min-1 , and the mean LTPA was 2.6 (1.7) h/wk. After controlling for BMI, VO2max was positively associated with the SF-36 General Health scale (ß 1.27, 95% CI: 0.09, 2.44, P=.035) and the Physical Component Summary (ß 0.48, 95% CI: 0.14, 0.82, P=.007). The General Health scale (P=.023) and the Physical Component Summary (P=.011) differed even between those with very poor and poor CRF. After controlling for BMI, LTPA was positively associated with the SF-36 Physical Functioning scale (rs =.34, P=.039), the General Health scale (ß 3.74, 95% CI: 0.64, 6.84, P=.020), and the Physical Component Summary (ß 1.13 95% CI: 0.19, 2.06, P=.020). To conclude, CRF and LTPA were positively associated with perceived general health and physical well-being in women planning pregnancy and at risk for GDM. Even a slightly better CRF would be beneficial for well-being among women with low levels of CRF.


Assuntos
Aptidão Cardiorrespiratória , Diabetes Gestacional/epidemiologia , Exercício Físico , Qualidade de Vida , Adulto , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Consumo de Oxigênio , Gravidez
7.
Heliyon ; 4(12): e01049, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30603691

RESUMO

OBJECTIVES: This study aimed to investigate the effects of using hydroxyl apatite functionalized calcium carbonate (FCC) particles on occluding dentinal tubules. METHODS: Dentine specimens extracted from eighteen human molars with exposed dentinal tubules were divided into three groups (n = 6/group): a) Cut surface with smear layer; b) EDTA (smear layer removed with 17% EDTA for 1 min); and c) Grit blasted functionalized calcium carbonate (FCC) with and air pressure of 280 kPa. Microscopic dentinal tubule occlusion, tubule diameter and tubule area were evaluated using scanning electron microscopy (SEM) before and after grit blasting. Biomineralization of specimens was carried out in a simulated body fluid (SBF). Elemental analysis of occluding materials was carried out using energy-dispersive X-ray spectroscopy (EDX). X-ray diffraction (XRD) analysis was performed to demonstrate the crystal structure of the biomineralized layer on dentine. RESULTS: FCC particles showed penetration into the dentinal tubules by breakage of their original particle shape and size. EDTA treated surface had higher number and larger size tubules than those with smear layer or grit blasted (p < 0.005). SEM-EDX analysis revealed mineral precipitation of calcium phosphate on the SBF immersed dentin specimens. XRD analysis showed typical crystal structure of hydroxyl apatite for the biomineralized surface layer on dentine. CONCLUSIONS: Grit blasted FCC particles initially occluded effectively the opened dentinal tubules and biomineralization occurred in tubules primarily occluded by the FCC particles. However, in the optimal in vitro conditions in SBF, no difference between biomineralization was found between the grit blasted surface and the control surface. CLINICAL SIGNIFICANCE: Several materials and methods have been established for treatment of dentinal hypersensitivity although a golden standard treatment has not been discovered. Grit blasted functionalized calcium carbonate has a potential to occlude and remineralize exposed dentinal tubules. This could offer a more biological approach on treatment of dentin hypersensitivity.

8.
Phys Rev Lett ; 119(7): 077701, 2017 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-28949696

RESUMO

We report on combined measurements of heat and charge transport through a single-electron transistor. The device acts as a heat switch actuated by the voltage applied on the gate. The Wiedemann-Franz law for the ratio of heat and charge conductances is found to be systematically violated away from the charge degeneracy points. The observed deviation agrees well with the theoretical expectation. With a large temperature drop between the source and drain, the heat current away from degeneracy deviates from the standard quadratic dependence in the two temperatures.

9.
Eur Arch Otorhinolaryngol ; 274(11): 3933-3940, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28852841

RESUMO

The objective of this study was to evaluate associations between the breathing sound spectra and glottal dimensions in exercise-induced vocal cord dysfunction (EIVCD) during a bicycle ergometry test. Nineteen subjects (mean age 21.8 years and range 13-39 years) with suspected EIVCD were studied. Vocal folds were continuously imaged with videolaryngoscopy and breathing sounds were recorded during the bicycle exercise test. Twelve subjects showed paradoxical movement of the vocal folds during inspiration by the end of the exercise. In seven subjects, no abnormal reactions in vocal folds were found; they served as control subjects. The glottal quotient (interarytenoid distance divided by the anteroposterior glottal distance) was calculated. From the same time period, the tracheal-vocal tract resonance peaks of the breathing sound spectra were analyzed, and stridor sounds were detected and measured. Subjects with EIVCD showed significantly higher resonance peaks during the inspiratory phase compared to the expiratory phase (p < 0.014). The glottal quotient decreased significantly in the EIVCD group (p < 0.001), but not in the control group. 8 out of 12 EIVCD patients (67%) showed stridor sounds, while none of the controls did. There was a significant inverse correlation between the frequencies of the breathing sound resonance peaks and the glottal quotient. The findings indicate that the typical EIVCD reaction of a paradoxical approximation of the vocal folds during inspiration, measured here as a decrease in the glottal quotient, is significantly associated with an increase in inspiratory resonance peaks. The findings are applicable in the documentation of EIVCD findings using videolaryngoscopy, in addition to giving clinicians tools for EIVCD recognition. However, the study is limited by the small number of subjects.


Assuntos
Acústica , Exercício Físico , Glote/anatomia & histologia , Sons Respiratórios , Disfunção da Prega Vocal/fisiopatologia , Prega Vocal/fisiopatologia , Adolescente , Adulto , Teste de Esforço , Feminino , Glote/fisiopatologia , Humanos , Laringoscopia/métodos , Masculino , Traqueia/fisiopatologia , Disfunção da Prega Vocal/diagnóstico , Disfunção da Prega Vocal/etiologia , Adulto Jovem
10.
Sci Rep ; 7(1): 8011, 2017 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-28808333

RESUMO

We demonstrate simultaneous measurements of DC transport properties and flux noise of a hybrid superconducting magnetometer based on the proximity effect (superconducting quantum interference proximity transistor, SQUIPT). The noise is probed by a cryogenic amplifier operating in the frequency range of a few MHz. In our non-optimized device, we achieve minimum flux noise ~4 µΦ0/Hz1/2, set by the shot noise of the probe tunnel junction. The flux noise performance can be improved by further optimization of the SQUIPT parameters, primarily minimization of the proximity junction length and cross section. Furthermore, the experiment demonstrates that the setup can be used to investigate shot noise in other nonlinear devices with high impedance. This technique opens the opportunity to measure sensitive magnetometers including SQUIPT devices with very low dissipation.

11.
Sci Rep ; 7: 41728, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28155895

RESUMO

We determine the thermal conductance of thin niobium (Nb) wires on a silica substrate in the temperature range of 0.1-0.6 K using electron thermometry based on normal metal-insulator-superconductor tunnel junctions. We find that at 0.6 K, the thermal conductance of Nb is two orders of magnitude lower than that of Al in the superconducting state, and two orders of magnitude below the Wiedemann-Franz conductance calculated with the normal state resistance of the wire. The measured thermal conductance exceeds the prediction of the Bardeen-Cooper-Schrieffer theory, and demonstrates a power law dependence on temperature as T4.5, instead of an exponential one. At the same time, we monitor the temperature profile of the substrate along the Nb wire to observe possible overheating of the phonon bath. We show that Nb can be successfully used for thermal insulation in a nanoscale circuit while simultaneously providing an electrical connection.

12.
Phys Rev Lett ; 115(22): 223603, 2015 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-26650305

RESUMO

A single superconducting artificial atom can be used for coupling electromagnetic fields up to the single-photon level due to an easily achieved strong coupling regime. Bringing a pair of harmonic oscillators into resonance with the transitions of a three-level atom converts atomic spontaneous processes into correlated emission dynamics. We present the experimental demonstration of two-mode correlated emission lasing in harmonic oscillators coupled via a fully controllable three-level superconducting quantum system (artificial atom). The correlation of emissions with two different colors reveals itself as equally narrowed linewidths and quenching of their mutual phase diffusion. The mutual linewidth is more than 4 orders of magnitude narrower than the Schawlow-Townes limit. The interference between the different color lasing fields demonstrates that the two-mode fields are strongly correlated.

13.
Meat Sci ; 93(2): 167-70, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23021628

RESUMO

The study investigated the water-holding (WH) in meat in the pH-NaCl (ionic strength) combinations that prevail in dry sausages during fermentation and drying. WH in raw beef homogenates, with 230% added water, was determined by centrifugation at pH values of 5.47-4.60, and ionic strengths (µ) 0.50-1.50. The minimum WH in relation to pH was at pH 4.8, but at higher pH values, the WH optimum was at 1.0-1.5 µ; at lower pH-values (<5.0) the optimum was more pronounced at 1.0 µ. The WH reducing effect by pH decrease was stronger than the effect of µ. At lower pH values, the relative effect of µ on WH was higher compared to that of pH than at higher pH values. The pH-salt combinations prevailing in fermented sausage in the beginning of the ripening produced a high WH, which decreased, first with pH decrease and then in the last period of ripening mainly due to the increase of ionic strength.


Assuntos
Carne/análise , Cloreto de Sódio/análise , Sódio na Dieta/análise , Água/análise , Animais , Bovinos , Fermentação , Concentração de Íons de Hidrogênio , Concentração Osmolar
14.
Anticancer Res ; 30(10): 3995-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21036713

RESUMO

BACKGROUND: Rb functions as a key controller of the G(1)-S transition of the cell cycle, and its inactivation leads to a defective G(1) checkpoint. Bladder cancer frequently displays alterations in Rb such as constitutive hyperphosphorylation which results in inactive Rb and progression of cells to the S-phase. Several protein kinase C (PKC) inhibitors are currently undergoing clinical trials as anticancer drugs. MATERIALS AND METHODS: T24 urinary bladder carcinoma cells, known to express hyperphosphorylated Rb, were treated with PKCα/ßI inhibitor Go6976. The treated cells were subjected to cell cycle analysis, cell growth assay and Western blots for Rb and cdc2 phosphorylation. RESULTS: The treatment resulted in Rb dephosphorylation at Ser 795 and Ser 807/811, and cdc2 dephosphorylation at Tyr15. Subsequent G(0/1) arrest and reduced proliferation rates were observed. CONCLUSION: The results show that Go6976 can be used to restore constantly hyperphosphorylated and therefore constantly inactive Rb function in cancer cells.


Assuntos
Carbazóis/farmacologia , Carcinoma de Células de Transição/metabolismo , Fase G1/efeitos dos fármacos , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C/antagonistas & inibidores , Proteína do Retinoblastoma/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , Genes p53 , Humanos , Fator Promotor de Maturação/metabolismo , Mutação , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Proteína Quinase C beta , Proteína Quinase C-alfa/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia
15.
Phys Rev Lett ; 105(9): 097004, 2010 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-20868187

RESUMO

We study heat transport in hybrid lateral normal-metal-superconductor-normal-metal structures. We find the thermal conductance of a short superconducting wire to be strongly enhanced beyond the BCS value due to the inverse proximity effect, resulting from contributions of elastic cotunneling and crossed Andreev reflection of quasiparticles. Our measurements agree with a model based on the quasiclassical theory of inhomogeneous superconductivity in the diffusive limit.

16.
Phys Rev Lett ; 101(6): 067002, 2008 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-18764493

RESUMO

We investigate hysteresis in the transport properties of superconductor-normal-metal-superconductor (S-N-S) junctions at low temperatures by measuring directly the electron temperature in the normal metal. Our results demonstrate unambiguously that the hysteresis results from an increase of the normal-metal electron temperature once the junction switches to the resistive state. In our geometry, the electron temperature increase is governed by the thermal resistance of the superconducting electrodes of the junction.

17.
J Bone Joint Surg Br ; 90(3): 349-55, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18310759

RESUMO

Hand function was evaluated in 105 patients who had been operated on in early infancy for brachial plexus birth palsy. The mean follow-up after surgery was for 13.4 years (5.0 to 31.5). Fine sensation, stereognosis, grip and pinch strength and the Raimondi scale were recorded. Fine sensation was normal in 34 of 49 patients (69%) with C5-6 injury, 15 of 31 (48%) with C5-7 and in 8 of 25 (32%) with total injury. Loss of protective sensation or absent sensation was noted in some palmar areas of the hand in 12 of 105 patients (11%). Normal stereognosis was recorded in 88 of the 105 patients (84%), whereas only 9 of the 105 (9%) had normal grip strength. The mean Raimondi scale scores were 4.57 (3 to 5) (C5-6), 4.26 (1 to 5) (C5-7) and 2.16 (0 to 5) in patients with total injury. The location of impaired sensation was related to the distribution of the root injury. Avulsion type of injury correlated with poor recovery of hand function.


Assuntos
Traumatismos do Nascimento/cirurgia , Neuropatias do Plexo Braquial/cirurgia , Plexo Braquial/cirurgia , Mãos/fisiopatologia , Traumatismos do Nascimento/fisiopatologia , Traumatismos do Nascimento/psicologia , Plexo Braquial/fisiopatologia , Neuropatias do Plexo Braquial/fisiopatologia , Neuropatias do Plexo Braquial/psicologia , Feminino , Seguimentos , Força da Mão , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Microcirurgia , Radiculopatia/fisiopatologia , Radiculopatia/psicologia , Radiculopatia/cirurgia , Sensação , Estatísticas não Paramétricas , Estereognose , Resultado do Tratamento
18.
Phys Rev Lett ; 98(20): 207001, 2007 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-17677730

RESUMO

We use a hysteretic Josephson junction as an on-chip detector of the third moment of shot noise of a tunnel junction. The detectable bandwidth is determined by the plasma frequency of the detector, which is about 50 GHz in the present experiment. The third moment of shot noise results in a measurable change of the switching rate when reversing polarity of the current through the noise source. We analyze the observed asymmetry assuming adiabatic response of the detector.

19.
Hum Exp Toxicol ; 26(1): 9-18, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17334176

RESUMO

Mutation analysis methods have increased in variety during the past years. High-throughput microarray methods have especially increased in popularity. However, new methods require reference points, and not all of the methods are equal in sensitivity and specificity. Furthermore, the detection of unknown missense mutations, such as unknown TP53 mutations in human tumors, for clinical purposes requires great accuracy, which may be difficult to acquire with the current high-throughput methods. For these reasons, the classical methods, such as PCR-manual sequencing and PCR-SSCP, are still valuable and necessary.


Assuntos
Genes p53 , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Proteína Supressora de Tumor p53/genética , Humanos
20.
Oncogene ; 26(36): 5267-79, 2007 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-17334397

RESUMO

Recent studies indicate that the specificity of p38 mitogen-activated protein kinase (MAPK)-mediated cellular stress responses is determined by the expression pattern of the distinct p38 isoforms. Here, we have analysed the function of distinct p38 isoforms in the growth and invasion of head and neck squamous cell carcinomas (HNSCCs). Activation of p38 MAPK by arsenite resulted in inactivation of the ERK1,2 signaling pathway by dephosphorylation of MEK1,2 in primary human epidermal keratinocytes (HEKs), whereas in HNSCC cells this p38-mediated inhibition of the ERK1,2 pathway was absent. Quantitation of p38 pathway component mRNA expression in HNSCC cell lines (n=42) compared to HEKs (n=8) revealed that p38alpha and p38delta isoforms are predominantly expressed in both cell types and that MKK3 is the primary upstream activator expressed. Inhibition of endogenous p38alpha or p38delta activity by adenoviral delivery of corresponding dominant-negative p38 isoforms potently reduced MMP-13 and MMP-1 expressions, and suppressed the invasion of HNSCC cells through collagen. Dominant-negative p38alpha and p38delta inhibited squamous cell carcinoma (SCC) cell proliferation and inhibition of p38alpha activity also compromised survival of SCC cells. p38alpha and p38delta were predominantly expressed in HNSCCs (n=24) and nonneoplastic epithelium in vivo (n=6), with MKK3 being the primary upstream activator. Activation and expression of p38alpha and p38delta by tumor cells was detected in HNSCCs in vivo (n=16). Adenoviral expression of dominant-negative p38alpha or p38delta in cutaneous SCC cells potently inhibited their implantation in skin of severe combined immunodeficiency mice and growth of xenografts in vivo. Our results indicate that p38alpha and p38delta specifically promote the malignant phenotype of SCC cells by regulating cell survival, proliferation and invasion, suggesting these p38 MAPK isoforms as potential therapeutic targets in HNSCCs.


Assuntos
Carcinoma de Células Escamosas/patologia , Divisão Celular/fisiologia , Neoplasias de Cabeça e Pescoço/patologia , Isoenzimas/fisiologia , Invasividade Neoplásica , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Sequência de Bases , Western Blotting , Carcinoma de Células Escamosas/enzimologia , Linhagem Celular Tumoral , Primers do DNA , Ativação Enzimática , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Imuno-Histoquímica , Isoenzimas/metabolismo , Queratinócitos/enzimologia , Metaloproteinases da Matriz/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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