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排序方式: 共有149条查询结果,搜索用时 46 毫秒
21.
Diana Cholico-González NoemíOrtiz Lara Mario Alberto Sánchez Miranda Ricardo Morales Es-trella Ramiro Escudero García Carlos A.León Patiño 《矿物冶金与材料学报》2021,28(4):603-611
The reduction behavior and metallization degree of magnetite concentrate with agave bagasse were investigated in an inert atmosphere. The effects of temperature, biomass content, and residence time on reduction experiments and metallization degree were investigated by X-ray diffraction and scanning electron microscopy. Compared with other types of biomass, agave bagasse had lower contents of nitrogen, sulfur, and ash. X-ray diffraction analysis showed that the metallization degree improved with increasing temperature and biomass content. Complete metallization was achieved at 1100°C for 30 min with 65:35 and 50:50 ratios of the magnetite concentrate to the agave bagasse. These results demonstrate that agave bagasse promotes the efficient metallization of magnetite concentrate without the external addition of a reducing agent. Therefore, this biomass is a technical suitable alternative to replace fossil fuels in steelmaking. 相似文献
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Tumour biology: senescence in premalignant tumours 总被引:1,自引:0,他引:1
Collado M Gil J Efeyan A Guerra C Schuhmacher AJ Barradas M Benguría A Zaballos A Flores JM Barbacid M Beach D Serrano M 《Nature》2005,436(7051):642
Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer. 相似文献
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Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer 总被引:1,自引:0,他引:1
Misale S Yaeger R Hobor S Scala E Janakiraman M Liska D Valtorta E Schiavo R Buscarino M Siravegna G Bencardino K Cercek A Chen CT Veronese S Zanon C Sartore-Bianchi A Gambacorta M Gallicchio M Vakiani E Boscaro V Medico E Weiser M Siena S Di Nicolantonio F Solit D Bardelli A 《Nature》2012,486(7404):532-536
A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance. 相似文献
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Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR 总被引:1,自引:0,他引:1
Prahallad A Sun C Huang S Di Nicolantonio F Salazar R Zecchin D Beijersbergen RL Bardelli A Bernards R 《Nature》2012,483(7387):100-103
Inhibition of the BRAF(V600E) oncoprotein by the small-molecule drug PLX4032 (vemurafenib) is highly effective in the treatment of melanoma. However, colon cancer patients harbouring the same BRAF(V600E) oncogenic lesion have poor prognosis and show only a very limited response to this drug. To investigate the cause of the limited therapeutic effect of PLX4032 in BRAF(V600E) mutant colon tumours, here we performed an RNA-interference-based genetic screen in human cells to search for kinases whose knockdown synergizes with BRAF(V600E) inhibition. We report that blockade of the epidermal growth factor receptor (EGFR) shows strong synergy with BRAF(V600E) inhibition. We find in multiple BRAF(V600E) mutant colon cancers that inhibition of EGFR by the antibody drug cetuximab or the small-molecule drugs gefitinib or erlotinib is strongly synergistic with BRAF(V600E) inhibition, both in vitro and in vivo. Mechanistically, we find that BRAF(V600E) inhibition causes a rapid feedback activation of EGFR, which supports continued proliferation in the presence of BRAF(V600E) inhibition. Melanoma cells express low levels of EGFR and are therefore not subject to this feedback activation. Consistent with this, we find that ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032. Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors. 相似文献
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Fritz JH Rojas OL Simard N McCarthy DD Hapfelmeier S Rubino S Robertson SJ Larijani M Gosselin J Ivanov II Martin A Casellas R Philpott DJ Girardin SE McCoy KD Macpherson AJ Paige CJ Gommerman JL 《Nature》2012,481(7380):199-203
The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells. 相似文献
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Bottke WF Vokrouhlický D Minton D Nesvorný D Morbidelli A Brasser R Simonson B Levison HF 《Nature》2012,485(7396):78-81
The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47?Gyr ago, four between 2.49 and 2.63?Gyr ago, and one between 1.7 and 2.1?Gyr ago. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration. E-belt survivors now make up the high-inclination Hungaria asteroids. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1?Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7?Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7?Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints. 相似文献
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