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61.
Treatment of non small cell lung cancer (NSCLC) and colorectal cancer (CRC) have substantially changed in the last years with the introduction of epidermal growth factor receptor (EGFR) inhibitors in the clinical practice. The understanding of mechanisms which regulate cells sensitivity to these drugs is necessary for their optimal use.An in vitro model of acquired resistance to two tyrosine kinase inhibitors (TKI) targeting the EGFR, erlotinib and gefitinib, and to a TKI targeting EGFR and VEGFR, vandetanib, was developed by continuously treating the human NSCLC cell line CALU-3 and the human CRC cell line HCT116 with escalating doses of each drug. MTT, western blot analysis, migration, invasion and anchorage-independent colony forming assays were conducted in vitro and experiments with established xenografts in athymic nude mice were performed in vivo in sensitive, wild type (WT) and TKI-resistant CALU-3 and HCT116 cell lines.As compared to WT CALU-3 and HCT116 human cancer cells, TKI-resistant cell lines showed a significant increase in the levels of activated, phosphorylated AKT, MAPK, and of survivin. Considering the role of RAS and RAF as downstream signals of both the EGFR and VEGFR pathways, we treated resistant cells with sorafenib, an inhibitor of C-RAF, B-RAF, c-KIT, FLT-3, RET, VEGFR-2, VEGFR-3, and PDGFR-β. Sorafenib reduced the activation of MEK and MAPK and caused an inhibition of cell proliferation, invasion, migration, anchorage-independent growth in vitro and of tumor growth in vivo of all TKI-resistant CALU-3 and HCT116 cell lines.These data suggest that resistance to EGFR inhibitors is predominantly driven by the RAS/RAF/MAPK pathway and can be overcame by treatment with sorafenib. 相似文献
62.
G Gragnoli A M Signorini I Tanganelli G Martinelli 《Bollettino della Società italiana di biologia sperimentale》1979,55(6):564-570
The levels of glucose, immunoreactive insulin and C-peptide were studied in 13 obese patients and 10 control subjects, in basal conditions and after an oral glucose load (OGTT). The IRI and C-peptide levels were higher in the obese patients than in the controls either during fasting or during the OGTT. The C-peptide/IRI ratio decreased after the oral glucose load in both groups studied. However in the obese subjects the values for the C-peptide/IRI ratio were lower than those found in the controls during the same observation period. These results suggest the hypothesis that in the obese patients the high IRI levels which reflect an increased insulin secretion, are, at least in part, due to an early saturation of the hepatic degradation of insulin and/or to a decrease in the specific receptor sites normally present in the cell membranes. 相似文献
63.
This study reports the results of one experiment and a replication, aimed at investigating heart rate changes related to a pure intuition task. In each experiment, twelve subjects were required to guess which of the four pictures presented in sequence for about 10 seconds, was the target. Each subject performed 20 trials. In each trial the target was automatically selected using a pseudo-random algorithm. Heart rate was recorded (see Method section for details) during the pictures presentation. In the first experiment, a statistical significant increment of heart rate associated to targets with respect non targets was observed. The replication experiment with new twelve subjects confirmed the data obtained in the main experiment. These findings support the hypothesis that heart rate is related not only to overt but also to covert cognitive activity such as that involved in intuition tasks, giving convergent evidence to the models describing our intuitive cognitive activity as a double, partial independent information processing system. 相似文献
64.
Rubolini D Romano M Boncoraglio G Ferrari RP Martinelli R Galeotti P Fasola M Saino N 《Hormones and behavior》2005,47(5):592-605
Eggs of vertebrates contain steroid hormones of maternal origin that may influence offspring performance. Recently, it has been shown that glucocorticoids, which are the main hormones mediating the stress response in vertebrates, are transmitted from the mother to the egg in birds. In addition, mothers with experimentally elevated corticosterone levels lay eggs with larger concentrations of the hormone, which produce slow growing offspring with high activity of the hypothalamo-adrenal axis under acute stress. However, the effects and function of transfer of maternal corticosterone to the eggs are largely unknown. In the present study, we injected corticosterone in freshly laid eggs of yellow-legged gulls (Larus michahellis), thus increasing the concentration of the hormone within its natural range of variation, and analyzed the effect of manipulation on behavioral, morphological, and immune traits of the offspring in the wild. Eggs injected with corticosterone had similar hatching success to controls, but hatched later. Mass loss during incubation was greater for corticosterone-treated eggs, except for the last laid ones. Corticosterone injection reduced rate and loudness of late embryonic vocalizations and the intensity of chick begging display. Tonic immobility response, reflecting innate fearfulness, was unaffected by hormone treatment. Elevated egg corticosterone concentrations depressed T-cell-mediated immunity but had no detectable effects on humoral immune response to a novel antigen, viability at day 10, or growth. Present results suggest that egg corticosterone can affect the behavior and immunity of offspring in birds and disclose a mechanism mediating early maternal effects whereby stress experienced by females may negatively translate to offspring phenotypic quality. 相似文献
65.
Goentoro LA Reeves GT Kowal CP Martinelli L Schüpbach T Shvartsman SY 《Developmental cell》2006,11(2):263-272
Quantitative information about the distribution of morphogens is crucial for understanding their effects on cell-fate determination, yet it is difficult to obtain through direct measurements. We have developed a parameter estimation approach for quantifying the spatial distribution of Gurken, a TGFalpha-like EGFR ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR system shows that the shape of the Gurken gradient is controlled by a single dimensionless parameter, the Thiele modulus, which reflects the relative importance of ligand diffusion and degradation. By combining the model with genetic alterations of EGFR levels, we have estimated the value of the Thiele modulus in the wild-type egg chamber. This provides a direct characterization of the shape of the Gurken gradient and demonstrates how parameter estimation techniques can be used to quantify morphogen gradients in development. 相似文献
66.
Medici MC Aloisi A Martinelli M Abelli LA Casula F Valcavi P Dettori G Chezzi C 《The new microbiologica》2006,29(1):63-67
HBV genotypes were investigated in sera/plasma from 97 HBV positive subjects. Genotype D was revealed in 80.4% followed by E in 6.2%. Genotypes A, B, and C were also found, as well as for the first time a new combination of HBV D and G genotypes. In a cohort of subjects of this population, the relationship with lamivudine and/or famciclovir-resistant HBV mutants was also investigated. Among 12 untreated subjects, 25% carried HBV drug-resistant strains suggesting that drug-resistant variants naturally exist in untreated Italian HBV chronically infected subjects. 相似文献
67.
Carrera I Sueiro C Molist P Holstein GR Martinelli GP Rodríguez-Moldes I Anadón R 《Cell and tissue research》2006,323(2):273-281
The present immunocytochemical study provides evidence of a previously unrecognized, rich, γ-aminobutyric acid (GABA)-ergic
innervation of the pineal organ in the dogfish (Scyliorhinus canicula). In this elasmobranch, the pineal primordium is initially detected at embryonic stage 24 and grows to form a long pineal
tube by stage 28. Glutamic acid decarboxylase (GAD)-immunoreactive (-ir) fibers were first observed at stage 26, and by stage
28, thin GAD-ir fibers were detectable at the base of the pineal neuroepithelium. In pre-hatchling embryos, most fibers gave
rise to GAD-ir boutons that were localized in the basal region of the neuroepithelium, although a smaller number of labeled
terminals ascended to the pineal lumen. A few pale GAD-ir perikarya were observed within the pineal organ of stage 29 embryos,
but GAD-ir perikarya were not observed at other developing stages or in adults. In contrast, GABA immunocytochemistry revealed
the presence of GABAergic perikarya and fibers in the pineal organ of late stage embryos and adults. Although high densities
of GABAergic cells were observed in the paracommissural pretectum, posterior tubercle, and tegmentum of dogfish embryos (regions
previously demonstrated to contain pinealopetal cells), the presence of GABA-ir perikarya in the pineal organ strongly suggests
that the rich GABAergic innervation of the elasmobranch pineal organ is intrinsic. This contrasts with the central origin
of GABAergic fibers in the pineal gland of some mammals.
This work was supported by the Spanish Education and Science Ministry and FEDER (BXX2000-0453-C02 and BFU2004-03313/BF1),
the Xunta de Galicia (PGIDT99BIO20002), and NIH/NIDCD awards R01 DC01705 and P01 DC01837 (to G.R.H.). 相似文献
68.
Melissa Postal Anne H.S. Martinelli Arlete B. Becker-Ritt Rodrigo Ligabue-Braun Diogo R. Demartini Suzanna F.F. Ribeiro Giancarlo Pasquali Valdirene M. Gomes Celia R. Carlini 《Peptides》2012
Ureases (EC 3.5.1.5) are metalloenzymes that hydrolyze urea into ammonia and CO2. These proteins have insecticidal and fungicidal effects not related to their enzymatic activity. The insecticidal activity of urease is mostly dependent on the release of internal peptides after hydrolysis by insect digestive cathepsins. Jaburetox is a recombinant version of one of these peptides, expressed in Escherichia coli. The antifungal activity of ureases in filamentous fungi occurs at submicromolar doses, with damage to the cell membranes. Here we evaluated the toxic effect of Canavalia ensiformis urease (JBU) on different yeast species and carried out studies aiming to identify antifungal domain(s) of JBU. Data showed that toxicity of JBU varied according to the genus and species of yeasts, causing inhibition of proliferation, induction of morphological alterations with formation of pseudohyphae, changes in the transport of H+ and carbohydrate metabolism, and permeabilization of membranes, which eventually lead to cell death. Hydrolysis of JBU with papain resulted in fungitoxic peptides (∼10 kDa), which analyzed by mass spectrometry, revealed the presence of a fragment containing the N-terminal sequence of the entomotoxic peptide Jaburetox. Tests with Jaburetox on yeasts and filamentous fungi indicated a fungitoxic activity similar to ureases. Plant ureases, such as JBU, and its derived peptides, may represent a new alternative to control medically important mycoses as well as phytopathogenic fungi, especially considering their potent activity in the range of 10−6–10−7 M. 相似文献
69.
Luciana F. Alves Marco A. Assis Juliano van Melis Ana L. S. Barros Simone A. Vieira Fernando R. Martins Luiz A. Martinelli Carlos A. Joly 《Ecological Research》2012,27(2):323-332
Lianas play a key role in forest structure, species diversity, as well as functional aspects of tropical forests. Although
the study of lianas in the tropics has increased dramatically in recent years, basic information on liana communities for
the Brazilian Atlantic Forest is still scarce. To understand general patterns of liana abundance and biomass along an elevational
gradient (0–1,100 m asl) of coastal Atlantic Forest, we carried out a standard census for lianas ≥1 cm in five 1-ha plots
distributed across different forest sites. On average, we found a twofold variation in liana abundance and biomass between
lowland and other forest types. Large lianas (≥10 cm) accounted for 26–35% of total liana biomass at lower elevations, but
they were not recorded in montane forests. Although the abundance of lianas displayed strong spatial structure at short distances,
the present local forest structure played a minor role structuring liana communities at the scale of 0.01 ha. Compared to
similar moist and wet Neotropical forests, lianas are slightly less abundant in the Atlantic Forest, but the total biomass
is similar. Our study highlights two important points: (1) despite some studies have shown the importance of small-scale canopy
disturbance and support availability, the spatial scale of the relationships between lianas and forest structure can vary
greatly among tropical forests; (2) our results add to the evidence that past canopy disturbance levels and minimum temperature
variation exert influence on the structure of liana communities in tropical moist forests, particularly along short and steep
elevational gradients. 相似文献
70.
Apoptosis, cell proliferation and vitellogenesis during the folliculogenesis and follicular growth in teleost fish 总被引:1,自引:0,他引:1
Thomé RG Domingos FF Santos HB Martinelli PM Sato Y Rizzo E Bazzoli N 《Tissue & cell》2012,44(1):54-62
Aiming to better understand folliculogenesis, this study evaluated cell death and proliferation of ovarian cells, besides cathepsin-D expression in Prochilodus argenteus captured in two sites of the São Francisco River downstream from the Três Marias Dam, Brazil. In the site immediately following the Dam (S1), low levels of dissolved oxygen were registered in the rainy period. The water temperature was higher in the São Francisco River immediately after the confluence with the Abaeté River (S2), regardless of the period. In S1, the ovaries showed smaller oocytes, high caspase-3 enzymatic activity and apoptosis, lower cells in proliferation and GSI, as well as a lesser quantity of cathepsin-D when compared to females captured from S2. Regarding relative frequency of ovarian structures, in the dry period, only oogonia and perinucleolar oocytes were found in fish ovaries from both sites. On the other hand, in the rainy period, the relative frequency of oogonia and perinucleolar oocytes decreased and the vitellogenic oocytes increased in S2. Postovulatory follicles were observed only in S2, whereas atretic follicles occurred at a higher frequency in S1. Our results showed that apoptosis, cell proliferation and cathepsina-D evaluation can be used as biomarkers of environmental impact. 相似文献