967 resultados para Phosphorylation de c-Met


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The articles collected here in this special edition Epithelial-Mesenchymal (EMT) and Mesenchymal-Epithelial Transitions (MET) in Cancer provide a snapshot of the very rapidly progressing cinemascope of the involvement of these transitions in carcinoma progression. Pubmed analysis of EMT and cancer shows an exponential increase in the last few years in the number of papers and reviews published under these terms (Fig. 1). The last few years have seen these articles appearing in high calibre journals including Nature, Nature Cell Biology, Cancer Cell, PNAS, JNCI, JCI, and Cell, signaling the acceptance and quality of work in this field.

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The cation\[Si,C,O](+) has been generated by 1) the electron ionisation (EI) of tetramethoxysilane and 2) chemical ionisation (CI) of a mixture of silane and carbon monoxide. Collisional activation (CA) experiments performed for mass-selected \[Si,C,O](+), generated by using both methods, indicate that the structure is not inserted OSiC+; however, a definitive structural assignment as Si+-CO, Si+-OC or some cyclic variant is impossible based on these results alone. Neutralisation-reionisation (+NR+) experiments for EI-generated \[Si,C,O](+) reveal a small peak corresponding to SiC+, but no detectable SiO+ signal, and thus establishes the existence of the Si+-CO isomer. CCSD(T)//B3LYP calculations employing a triple-zeta basis set have been used to explore the doublet and quartet potential-energy surfaces of the cation, as well as some important neutral states The results suggest that both Si+-CO and Si+ - OC isomers are feasible; however, the global minimum is (2)Pi SiCO+. Isomeric (2)Pi SiOC+ is 12.1 kcal mol(-1) less stable than (2)Pi SiCO+, and all quartet isomers are much higher in energy. The corresponding neutrals Si-CO and Si-OC are also feasible, but the lowest energy Si - OC isomer ((3)A") is bound by only 1.5 kcal mol(-1). We attribute most, if nor all, of the recovery signal in the +NR' experiment to SiCO+ survivor ions. The nature of the bonding in the lowest energy isomers of Si+ -(CO,OC) is interpreted with the aid of natural bond order analyses, and the ground stale bonding of SiCO+ is discussed in relation to classical analogues such as metal carbonyls and ketenes.

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Cellular plasticity is fundamental to embryonic development. The importance of cellular transitions in development is first apparent during gastrulation when the process of epithelial to mesenchymal transition transforms polarized epithelial cells into migratory mesenchymal cells that constitute the embryonic and extraembryonic mesoderm. It is now widely accepted that this developmental pathway is exploited in various disease states, including cancer progression. The loss of epithelial characteristics and the acquisition of a mesenchymal-like migratory phenotype are crucial to the development of invasive carcinoma and metastasis. However, given the morphological similarities between primary tumour and metastatic lesions, it is likely that tumour cells re-activate certain epithelial properties through a mesenchymal to epithelial transition (MET) at the secondary site, although this is yet to be proven. MET is also an essential developmental process and has been extensively studied in kidney organogenesis and somitogenesis. In this review we describe the process of MET, highlight important mediators, and discuss their implication in the context of cancer progression.

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This study evaluated the validity of the Previous Day Physical Activity Recall (PDPAR) self-report instrument in quantifying after-school physical activity behavior in fifth-grade children. Thirty-eight fifth-grade students (mean age, 10.8 +/- 0.1; 52.6% female; 26.3% African American) from two urban elementary schools completed the PDPAR after wearing a CSA WAM 7164 accelerometer for a day. The mean within-subject correlation between self-reported MET level and total counts for each 30-min block was 0.57 (95% C.I., 0.51-0.62). Self-reported mean MET level during the after-school period and the number of 30-min blocks with activity rated at greater than or equal to 6 METs were significantly correlated with the CSA outcome variables. Validity coefficients for these variables ranged from 0.35 to 0.43 (p <.05). Correlations between the number of 30-min blocks with activity rated at greater than or equal to 3 METs and the CSA variables were positive but failed to reach statistical significance (r = 0.19-0.23). The PDPAR provides moderately valid estimates of relative participation in vigorous activity and mean MET level in fifth-grade children. Caution should be exercised when using the PDPAR to quantify moderate physical activity in preadolescent children.

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As yet, there is no cure for metastatic breast cancer. Historically, considerable research effort has been concentrated on understanding the processes of metastasis, how a primary tumour locally invades and systemically disseminates using the phenotypic switching mechanism of epithelial to mesenchymal transition (EMT); however, much less is understood about how metastases are then formed. Breast cancer metastases often look (and may even function) as 'normal' breast tissue, a bizarre observation against the backdrop of the organ structure of the lung, liver, bone or brain. Mesenchymal to epithelial transition (MET), the opposite of EMT, has been proposed as a mechanism for establishment of the metastatic neoplasm, leading to questions such as: Can MET be clearly demonstrated in vivo? What factors cause this phenotypic switch within the cancer cell? Are these signals/factors derived from the metastatic site (soil) or expressed by the cancer cells themselves (seed)? How do the cancer cells then grow into a detectable secondary tumour and further disseminate? And finallyCan we design and develop therapies that may combat this dissemination switch? This review aims to address these important questions by evaluating long-standing paradigms and novel emerging concepts in the field of epithelial mesencyhmal plasticity.

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PURPOSE To use objective monitoring of physical activity to determine the percentages of children and youth in a population that met physical activity guidelines. METHODS A total of 375 students in grades 1–12 wore an accelerometer (CSA 7164) for seven consecutive days. Bouts of continuous activity and accumulation of minutes spent in physical activity at various intensities were calculated to determine how many students met three physical activity guidelines. RESULTS Over 90% of students met Healthy People 2010, Objective 22.6 and nearly 70% met the United Kingdom Expert Consensus Group guideline, both of which recommend daily accumulation of moderate physical activity. Less than 3% met Healthy People 2010, Objective 22.7, which calls for bouts of continuous vigorous physical activity. For the United Kingdom Expert Consensus Group guideline, compliance decreased markedly with age, but gender differences were not statistically significant. CONCLUSIONS Prevalence estimates for compliance with national physical activity guidelines varied markedly for the three guidelines examined. Objective monitoring of physical activity in youth appears to be feasible and may provide more accurate prevalence rates than self-report measures.

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This study aimed to assess the efficacy of a general practice based intervention to increase physical activity (PA) levels among 50-70 year old adults. One hundred and thirty-six inactive patients (50-70 years) were randomised into three groups. All participants received brief advice and a written prescription from a GP. Group one received this 'usual care' only (GP, n=46); group two received individualised counselling and follow-up contact from an Exercise Scientist (ES, n=45); group three received a pedometer to supplement the ES counselling (PED, n=45). The Active Australia Survey was administered at baseline, after the 12- week intervention and at a 24-week follow-up. One-way ANOVA showed no significant group differences at baseline in self-reported PA. Average time spent walking increased in all three groups at the 24-week follow-up (GP, 68158min/wk, p=0.006; ES, 83160min/wk, p=0.001; PED, 87132min/wk, p<0.001). Total time in PA (weighted min/wk) also increased significantly in all three groups (GP, 98 213min/wk, p=0.003; ES, 108 182min/wk, p<0.001; PED, 158 229min/wk, p<0.001 ). The proportion of participants who initially did not meet National PA Guidelines (150 minutes and 5 sessions/week) but who met the Guidelines at the 12 and 24-week follow-up was 15% (12 weeks) and 20% (24 weeks) in the GP group compared with 36% and 24% in the ES group and 20% and 42% in the PED group. All three intervention strategies were effective in increasing PA, but the ES intervention resulted in a higher proportion of active participants after 12 weeks and the PED group resulted in a higher proportion of active participants after 24 weeks.

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This study aimed to assess the efficacy of a general practice based intervention to increase physical activity (PA) levels among 50-70 year old adults. One hundred and thirty-six inactive patients (50-70 years) were randomised into three groups. All participants received brief advice and a written prescription from a GP. Group one received this 'usual care' only (GP, n=46); group two received individualised counselling and follow-up contact from an Exercise Scientist (ES, n=45); group three received a pedometer to supplement the ES counselling (PED, n=45). The Active Australia Survey was administered at baseline, after the 12- week intervention and at a 24-week follow-up. One-way ANOVA showed no significant group differences at baseline in self-reported PA. Average time spent walking increased in all three groups at the 24-week follow-up (GP, 68158min/wk, p=0.006; ES, 83160min/wk, p=0.001; PED, 87132min/wk, p<0.001). Total time in PA (weighted min/wk) also increased significantly in all three groups (GP, 98 213min/wk, p=0.003; ES, 108 182min/wk, p<0.001; PED, 158 229min/wk, p<0.001 ). The proportion of participants who initially did not meet National PA Guidelines (150 minutes and 5 sessions/week) but who met the Guidelines at the 12 and 24-week follow-up was 15% (12 weeks) and 20% (24 weeks) in the GP group compared with 36% and 24% in the ES group and 20% and 42% in the PED group. All three intervention strategies were effective in increasing PA, but the ES intervention resulted in a higher proportion of active participants after 12 weeks and the PED group resulted in a higher proportion of active participants after 24 weeks.

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Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

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Purpose The purpose of this study was to examine the validity of current practice in smoking cessation for the general population i.e., a telephone counselling and nicotine replacement therapy (NRT) intervention and its applicability to people with chronic hepatitis-C. Methods A randomised controlled trial was conducted over twelve weeks. Following consent, ninety-two smokers (outpatients) with chronic hepatitis-C were recruited by the Nurse Practitioner hepatology, randomly assigned and stratified by number of cigarettes smoked (i.e., 15 and greater; <15) into the intervention group (telephone counselling and NRT) and control group (telephone counselling). Outcomes measured included socio-demographics, nicotine dependence, depression, anxiety and stress and quality of life (QOL). All statistical data were analysed using SPSS. Results After 12 weeks, the intervention group showed a sustained reduction of smoking i.e., 5.8(CI: 2.4,9.3) cigarettes less per day, whereas the control group showed 1.6(CI:-1.9,5.2) cigarette reduction. Although not statistically significantly different (F=2.9, p=0.090) the intervention group on average smoked 4.2 fewer cigarettes compared to the control group. After twelve weeks, seven patients in the intervention group and three patients in the control group reported quitting. Whilst not statistically significant (Fisher’s Exact, p=0.311) this was a clinically significant result. No differences were found for nicotine dependence or depression, anxiety and stress. The intervention group experienced no change in QOL (-0.1,CI:-0.9, 0.6), however, the environmental score for the control group decreased by 1.8(CI:1.0, 2.6,p= 0.001). This was statistically significant. Conclusion A telephone counselling and nicotine replacement therapy intervention from the nurse practitioner, hepatology reduced smoking in patients with chronic hepatitis-C. The intervention group showed a sustained reduction over the 12 weeks. A total of 10 patients quit smoking at the end of the study. QOL deteriorated in the environmental subscale for the control group. These results informed a nurse practitioner model of care for approaches to smoking cessation.

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Self-assembly of highly stoichiometric SiC quantum dots still remains a major challenge for the gas/plasma-based nanodot synthesis. By means of a multiscale hybrid numerical simulation of the initial stage (0.1-2.5 s into the process) of deposition of SiCSi (100) quantum dot nuclei, it is shown that equal Si and kst atom deposition fluxes result in strong nonstoichiometric nanodot composition due to very different surface fluxes of Si and C adatoms to the quantum dots. At this stage, the surface fluxes of Si and C adatoms to SiC nanodots can be effectively controlled by manipulating the SiC atom influx ratio and the Si (100) surface temperature. It is demonstrated that at a surface temperature of 800 K the surface fluxes can be equalized after only 0.05 s into the process; however, it takes more then 1 s at a surface temperature of 600 K. Based on the results of this study, effective strategies to maintain a stoichiometric ([Si] [C] =1:1) elemental ratio during the initial stages of deposition of SiCSi (100) quantum dot nuclei in a neutral/ionized gas-based process are proposed.

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Al-C-N-O composite thin films have been synthesized by radio frequency reactive diode sputtering of an aluminum target in plasmas of N2+O2+CH4 gas mixtures. The chemical structure and composition of the films have been investigated by means of infrared and X-ray photoelectron spectroscopy. The results reveal the formation of C-N, Al-C, Al-N and Al-O bonds. The X-ray diffraction pattern suggests that the films are of nanometer composite material and contain predominately crystalline grains of hexagonal AlN and α-Al2O3. A good thermal stability of the composite has been confirmed by the annealing treatment at temperatures up to 600 °C.

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Efficient hydrogenated diamond-like carbon (DLC) film deposition in a plasma reactor that features both the capacitive and inductively coupled operation regimes is reported. The hydrogenated DLC films have been prepared on silicon wafers using a low-frequency (500 kHz) inductively coupled plasma (LF ICP) chemical vapor deposition (CVD) system. At low RF powers, the system operates as an asymmetric capacitively coupled plasma source, and the film deposition process is undertaken in the electrostatic (E) discharge regime. The films deposited in the electrostatic mode feature graphite-like structure. Above the mode transition threshold, the high-density inductively coupled plasma is produced in the electromagnetic (H) discharge regime. Raman spectrometry suggests the possibility to control relative proportions of sp2 and sp3 hybridized carbon. Variation of the DC substrate bias results in dramatic modification of the film structure from the polymeric (unbiased substrates) to the diamond-like (optimized bias). It has been shown that the deposition rate and hardness of the DLC film are much higher in the H-mode deposition regime. For a 20 m Torr H-mode CH4+Ar gas mixture discharge, the DLC film exhibits mechanical hardness of 18 GPa, Young's modulus of 170 GPa, and compressive stress of 1.3 GPa.

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SupaCee section is one of the cold-formed steel members which is increasingly used in the construction sector. It is characterized by unique ribbed web and curved lip elements, and is claimed to be more economical with extra strength than the traditional channel sections. SupaCee sections are widely used in Australia as floor joists, bearers, purlins and girts. Many experimental and numerical studies have been carried out to evaluate the behaviour and design of conventional channel beams subject to web crippling. To date, however, no investigation has been conducted into the web crippling behaviour and strength of SupaCee sections. Current cold-formed steel design equations do not include any design procedures for SupaCee sections. Hence experimental studies were conducted to assess the web crippling behaviour and strengths of SupaCee sections under ETF and ITF load cases. Thirty six web crippling tests were conducted and the capacity results were compared with the predictions from the AS/NZS 4600 and AISI design rules developed for conventional channel sections. Comparison of ultimate web crippling capacities from tests showed that AS/NZS 4600 and AISI design equations are unconservative for SupaCee sections under ETF load case, but are overly conservative for ITF load case. Hence new equations were proposed to determine the web crippling capacities of SupaCee sections based on the experimental results from this study. Suitable design rules were also developed within the direct strength method format. This paper presents the details of this experimental study of SupaCee sections subject to web crippling and the results.