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11.
The development and the effect of immunoliposomes directed against human breast cancer cells overexpressing p185/HER2 are described. These immunoliposomes carry an antisense oligonucleotide directed toward the translational start site of dihydrofalate reductase (DHFR) RNA, which causes high cytotoxicity. To prepare the immunoliposomes, we followed two methodologies based on the high affinity between streptavidin and biotin and the use of biotinylated antibodies. In the first approach, the streptavidin molecule is covalently attached to the phospholipid DOPE, which is mixed with the cationic liposome DOTAP complexed with the antisense oligonucleotide. The second approach, which is much easier to perform, involves the binding of streptavidin to antibody and oligonucleotide, both biotinylated, and the latter complexed with DOTAP. The formation of the intermediary complexes of this immunoliposome was studied sequentially by gel electrophoresis. The uptake of the oligonucleotide carried by the immunoliposome was monitored by flow cytometry and confocal microscopy. As a model, we used SKBR3 cells that overexpress p185. The full immunoliposomes were more toxic than the antisense oligonucleotide in the absence of the antibody, thus increasing the sensitivity of the treatment. 相似文献
12.
Nicola Bertolino Stefania Ferraro Anna Nigri Maria Grazia Bruzzone Francesco Ghielmetti The Coma Research Centre multidisciplinary team 《PloS one》2014,9(8)
The purpose of this study was to investigate whether artificial neural networks (ANN) are able to decode participants’ conscious experience perception from brain activity alone, using complex and ecological stimuli. To reach the aim we conducted pattern recognition data analysis on fMRI data acquired during the execution of a binocular visual rivalry paradigm (BR). Twelve healthy participants were submitted to fMRI during the execution of a binocular non-rivalry (BNR) and a BR paradigm in which two classes of stimuli (faces and houses) were presented. During the binocular rivalry paradigm, behavioral responses related to the switching between consciously perceived stimuli were also collected. First, we used the BNR paradigm as a functional localizer to identify the brain areas involved the processing of the stimuli. Second, we trained the ANN on the BNR fMRI data restricted to these regions of interest. Third, we applied the trained ANN to the BR data as a ‘brain reading’ tool to discriminate the pattern of neural activity between the two stimuli. Fourth, we verified the consistency of the ANN outputs with the collected behavioral indicators of which stimulus was consciously perceived by the participants. Our main results showed that the trained ANN was able to generalize across the two different tasks (i.e. BNR and BR) and to identify with high accuracy the cognitive state of the participants (i.e. which stimulus was consciously perceived) during the BR condition. The behavioral response, employed as control parameter, was compared with the network output and a statistically significant percentage of correspondences (p-value <0.05) were obtained for all subjects. In conclusion the present study provides a method based on multivariate pattern analysis to investigate the neural basis of visual consciousness during the BR phenomenon when behavioral indicators lack or are inconsistent, like in disorders of consciousness or sedated patients. 相似文献
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Ana B. Lanham Ana Rita Ricardo Maria G.E. Albuquerque Filipa Pardelha Mónica Carvalheira Marta Coma Joana Fradinho Gilda Carvalho Adrian Oehmen Maria A.M. Reis 《Process Biochemistry》2013,48(11):1626-1634
For the first time, a systematic approach was conducted to determine the key factors influencing the kinetics of hydroxyalkanote (HA) extraction in biological systems. Six mixed microbial systems where polyhydroxyalkanoate (PHA) is produced were evaluated. Experiments were carried out for full-scale and lab-scale activated sludge systems using different configurations (containing floccular or granular sludge), as well as specific PHA accumulating cultures that contain high or low intracellular PHA fractions. The overall reaction was limited by the kinetics of the PHA hydrolysis in floccular cultures, whereas in granular cultures, it was limited by the cell lysis step. The monomeric composition of the polymer also had an impact on the HA extraction rate: higher acid concentration and a longer digestion time should be employed when cells accumulate monomers with more substituents, such as hydroxy-2-methylbutyrate (H2MB) and hydroxy-2-methylvalerate (H2MV). This study optimised the method for HA extraction, which impacts the assessment of the quantity and quality of PHA biopolymers. 相似文献
14.
Akio Shimizu Hironao Nakayama Priscilla Wang Courtney K?nig Tomoshige Akino Johanna Sandlund Silvia Coma Joseph E. Italiano Jr. Akiko Mammoto Diane R. Bielenberg Michael Klagsbrun 《The Journal of biological chemistry》2013,288(4):2210-2222
Glioblastomas are very difficult tumors to treat because they are highly invasive and disseminate within the normal brain, resulting in newly growing tumors. We have identified netrin-1 as a molecule that promotes glioblastoma invasiveness. As evidence, netrin-1 stimulates glioblastoma cell invasion directly through Matrigel-coated transwells, promotes tumor cell sprouting and enhances metastasis to lymph nodes in vivo. Furthermore, netrin-1 regulates angiogenesis as shown in specific angiogenesis assays such as enhanced capillary endothelial cells (EC) sprouting and by increased EC infiltration into Matrigel plugs in vivo, as does VEGF-A. This netrin-1 signaling pathway in glioblastoma cells includes activation of RhoA and cyclic AMP response element-binding protein (CREB). A novel finding is that netrin-1-induced glioblastoma invasiveness and angiogenesis are mediated by activated cathepsin B (CatB), a cysteine protease that translocates to the cell surface as an active enzyme and co-localizes with cell surface annexin A2 (ANXA2). The specific CatB inhibitor CA-074Me inhibits netrin-1-induced cell invasion, sprouting, and Matrigel plug angiogenesis. Silencing of CREB suppresses netrin-1-induced glioblastoma cell invasion, sprouting, and CatB expression. It is concluded that netrin-1 plays an important dual role in glioblastoma progression by promoting both glioblastoma cell invasiveness and angiogenesis in a RhoA-, CREB-, and CatB-dependent manner. Targeting netrin-1 pathways may be a promising strategy for brain cancer therapy. 相似文献
15.
Marta?Herreros-VillanuevaEmail author Noemí?Gomez-Manero Pilar?Mu?iz Carlos?García-Girón Maria?Jesús?Coma del Corral 《Molecular biology reports》2011,38(2):1347-1351
The objective of the work was to study PIK3CA mutations in wild type KRAS and BRAF colorectal cancer. Clinicopathological data and paraffin-embedded specimens were collected on 73 patients who underwent colorectal
resections at General Yagüe Hospital in Burgos. KRAS, BRAF and PIK3CA status were analyzed by real-time PCR in all patients. PIK3CA mutations were present in 8.22% of wild type KRAS and BRAF colorectal cancers. The most frequent mutation is E545K/D in exon 9 which represents 83.3% of all mutations. By contrast,
we did not found any tumour harbouring H1047R mutation in exon 20. Among the patients who undergo a curative resection of
colorectal cancer, PIK3CA mutation is present in an important percentage of KRAS and BRAF wild type tumours. PIK3CA mutation may be considered as it could be a hypothetic reason to be not responder to anti-EGFR antibodies. 相似文献
16.
Theobald AJ Caballero I Coma I Colmenarejo G Cid C Gamo FJ Hibbs MJ Bass AL Thomas DA 《Biochemistry》2012,51(23):4764-4771
Plasmodium falciparum is the most prevalent and deadly species of the human malaria parasites, and thioredoxin reductase (TrxR) is an enzyme involved in the redox response to oxidative stress. Essential for P. falciparum survival, the enzyme has been highlighted as a promising target for novel antimalarial drugs. Here we report the discovery and characterization of seven molecules from an antimalarial set of 13533 compounds through single-target TrxR biochemical screens. We have produced high-purity, full-length, recombinant native enzyme from four Plasmodium species, and thioredoxin substrates from P. falciparum and Rattus norvegicus. The enzymes were screened using a unique, high-throughput, in vitro native substrate assay, and we have observed selectivity between the Plasmodium species and the mammalian form of the enzyme. This has indicated differences in their biomolecular profiles and has provided valuable insights into the biochemical mechanisms of action of compounds with proven antimalarial activity. 相似文献
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In recent years, particular attention has been paid to coupling and energy transfer between benthos and plankton. Because of their abundance, certain benthic suspension feeders have been shown to have a major impact in marine ecosystems. They capture large quantities of particles and might directly regulate primary production and indirectly regulate secondary production in littoral food chains. Suspension feeders develop dense, three-dimensional communities whose structural complexity depends on flow speed. It has been postulated that these communities can self-organize to enhance food capture and thus establish boundary systems capable of successfully exploiting a less structured system, namely, the plankton. 相似文献
19.
Ribes Marta; Coma Rafel; Zabala Mikel; Gili Josep-Maria 《Journal of plankton research》1996,18(5):659-671
Seasonal changes in small-scale spatial distribution patternsof abundance and composition of Hemimysis speluncola Ledoyer(1963) (Crustacea, Mysidacea) were studied in a population ofcave-dwelling mysids off the Medes Islands (NW MediterraneanSea). The distribution pattern was characterized all year roundby marked spatial segregation of juveniles, which occupied areascloser to the cave entrance, while adults were concentratedmainly in the innermost part of the cave. The small-scale spatialheterogeneity observed appears to be regulated by biologicalfactors, particularly social and reproductive behaviour. Nevertheless,a certain adaptation of the distribution of the swarms to hydrodynamicfactors suggests that physical factors may also play a role.The heterogeneous aggregation pattern recorded would clearlyappear to be an adaptive strategy by the population to enableit to thrive within its habitat. That adaptation is designedto reduce predation mortality, enhance mating efficiency andregulate the population generally. Marked seasonal fluctuationsin the density and composition of the population were recorded,with high density levels in winter and throughout the spring.Two methods were employed to quantify the population: haulswith plankton nets towed by divers and collection of faecalpellets. The patterns observed using both these methods weresimilar, although the latter method yielded total density valuesthat were an order of magnitude greater. 相似文献
20.
Cristina Guardia-Laguarta Mireia Coma Marta Pera Jordi Clarimón Lidia Sereno José M. Agulló Laura Molina-Porcel Eduard Gallardo† Amy Deng‡ Oksana Berezovska‡ Bradley T. Hyman‡ Rafael Blesa Teresa Gómez-Isla Alberto Lleó 《Journal of neurochemistry》2009,110(1):220-230
It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP–Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP–PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. 相似文献