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- 저자 : Chinchillas-Chinchillas M. (검색결과 2 건)
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Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications
Sánchez-Fdez Adrián,Matilla-Almazán Sofía,Del Carmen Sofía,Abad Mar,Arconada-Luque Elena,Jiménez-Suárez Jaime,Chinchilla-Tábora Luis Miguel,Ruíz-Hidalgo Mª José,Sánchez-Prieto Ricardo,Pandiella Atanas 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.
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Espinoza-Moreno C. A.,Rodriguez-Rodriguez M.,Pellegrini-Cervantes M. J.,Barrios-Durstewitz C. P.,Núñez-Jaquez R. E.,Peinado-Guevara H. J.,Chinchillas-Chinchillas M.,Fajardo-San-Miguel G. 한국탄소학회 2021 Carbon Letters Vol.31 No.4
The use of recycled materials, such as the fne recycled aggregate made from concrete waste and carbon fber (CF) product of industrial waste, for the manufacture of conductive recycled mortars (CRM), transforms the mortar base cement normally made with cement:sand in a sustainable multifunctional material, conferring satisfactory mechanical and electrical properties for non-structural uses. This action provides ecological benefts, reducing the use of natural fne aggregates from rivers and the amount of concrete waste deposited in landflls resulting from construction waste. In this investigation the efect of the addition of CF on electrical properties in hardened, wet and dry state, electric percolation in dry state and fuidity of the wet mixture of a cement based CRM was evaluated: fne recycled aggregate: graphite powder, CRM specimens with dimensions of 4×4×16 cm. were manufactured for 3, 7 and 28 days of age and sand/cement ratios=1.00, graphite/cement=1.00, water/cement=0.60 and CF=0.1, 0.3, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0% compared to the weight of cement. The results demonstrated the efect of the addition of CF in CRM, reducing fuidity of the mixtures due to the opposition generated by its physical interaction of CF with recycled sand or recycled fne aggregate and graphite powder (GP), in its case, placing the electric percolation percolation at 0.30% and 0.45% of CF for CRM with and without GP, respectively. Increases in electrical conductivity (EC) without the presence of GP are defned by the contact between the CF and the conductive paths formed. In contrast, with the presence of GP, the EC is defned by the contact between the CF and the GP simultaneously, forming conductive routes with greater performance in its EC.
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