6 results on '"Valladares M"'
Search Results
2. Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer
- Author
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Borrero-Palacios, A., Cebrián, A., Gómez del Pulgar, M. T., García-Carbonero, R., Garcia-Alfonso, P., Aranda, E., Elez, E., López-López, R., Cervantes, A., Valladares, M., Nadal, C., Viéitez, J. M., Guillén-Ponce, C., Rodríguez, J., Hernández, I., García, J. L., Vega-Bravo, R., Puime-Otin, A., Martínez-Useros, J., Del Puerto-Nevado, L., Rincón, R., Rodríguez-Remírez, M., Rojo, F., and García-Foncillas, J.
- Published
- 2019
- Full Text
- View/download PDF
3. Microbial community in resistant and susceptible Churra sheep infected by Teladorsagia circumcincta.
- Author
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Castilla Gómez de Agüero V, Esteban-Blanco C, Argüello H, Valderas-García E, Andrés S, Balaña-Fouce R, Arranz JJ, Gutiérrez-Gil B, and Martínez-Valladares M
- Subjects
- Sheep genetics, Animals, RNA, Ribosomal, 16S genetics, DNA, Bacterial, Ostertagia, Feces, Disease Susceptibility, Butyrates, Sheep Diseases genetics, Nematoda genetics, Microbiota
- Abstract
Gastrointestinal nematodes (GIN) are a major threat to health and welfare in small ruminants worldwide. Teladorsagia circumcincta is a nematode that inhabits the abomasum of sheep, especially in temperate regions, causing important economic losses. Given that T. circumcincta and microbiome share the same niche, interactions between them and the host are expected. Although it is known that within a sheep breed there are animals that are more resistant than others to infection by GIN, it is not known if the microbiome influences the phenotype of these animals. Under this condition, 12 sheep were classified according to their cumulative faecal egg count (cFEC) at the end of a first experimental infection, 6 as resistant group (RG) and 6 as susceptible group (SG) to T. circumcincta infection. Then, all sheep were experimentally infected with 70,000 L3 of T. circumcincta and at day 7 days post-infection were euthanized. At necropsy, gastric mucosa and gastric content from abomasum were collected to extract bacterial DNA and sequence V3-V4 region from 16S rRNA gene using Ilumina technology. After bioanalysis performed, results showed that α-diversity and β-diversity remained similar in both groups. However, resistant phenotype sheep showed a higher number of bacteria butyrate-fermenting species as Clostridium sensu stricto 1 (abundance in RG: 1.29% and in SG: 0.069%; p = 0.05), and Turicibacter (abundance in RG: 0.31% and in SG: 0.027%; p = 0.07) in gastric content but also Serratia spp in gastric mucosa (abundance in RG: 0.12% and in SG: 0.041%; p = 0.07). A trend towards a significant negative correlation between cFEC and Clostridium sensu stricto 1 abundance in gastric content was detected (r = - 0.537; p = 0.08). These data suggest that microbiome composition could be another factor associated with the development of the resistant phenotype modifying the interaction with the host and the in last instance affecting the individual risk of infection., (© 2022. The Author(s).)
- Published
- 2022
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- View/download PDF
4. Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus.
- Author
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Valderas-García E, Escala N, Álvarez-Bardón M, Castilla-Gómez de Agüero V, Cambra-Pellejà M, González Del Palacio L, Vallejo García R, de la Vega J, San Feliciano A, Del Olmo E, Martínez-Valladares M, and Balaña-Fouce R
- Subjects
- Animals, Benzimidazoles pharmacology, Benzimidazoles therapeutic use, Gerbillinae, Mice, Sheep, Anthelmintics pharmacology, Anthelmintics therapeutic use, Haemonchiasis drug therapy, Haemonchiasis veterinary, Haemonchus, Nematoda, Sheep Diseases drug therapy
- Abstract
The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
5. SOX9 promotes tumor progression through the axis BMI1-p21 CIP .
- Author
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Aldaz P, Otaegi-Ugartemendia M, Saenz-Antoñanzas A, Garcia-Puga M, Moreno-Valladares M, Flores JM, Gerovska D, Arauzo-Bravo MJ, Samprón N, Matheu A, and Carrasco-Garcia E
- Subjects
- Adenocarcinoma, Cell Line, Tumor, Cell Proliferation, Cell Survival, Disease Progression, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Neoplasms metabolism, Neoplastic Processes, Pancreatic Neoplasms, SOX9 Transcription Factor genetics, Stomach Neoplasms, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Neoplasms genetics, Polycomb Repressive Complex 1 metabolism, SOX9 Transcription Factor metabolism
- Abstract
The developmental regulator SOX9 is linked to cancer progression mainly as a result of its role in the regulation of cancer stem cells (CSCs). However, its activity in the differentiated cells that constitute the heterogeneous tumor bulk has not been extensively studied. In this work, we addressed this aspect in gastric cancer, glioblastoma and pancreatic adenocarcinoma. SOX9 silencing studies revealed that SOX9 is required for cancer cell survival, proliferation and evasion of senescence in vitro and tumor growth in vivo. Gain of-SOX9 function showed that high levels of SOX9 promote tumor cell proliferation in vitro and in vivo. Mechanistically, the modulation of SOX9 changed the expression of the transcriptional repressor BMI1 in the same direction in the three types of cancer, and the expression of the tumor suppressor p21
CIP in the opposite direction. In agreement with this, SOX9 expression positively correlated with BMI1 levels and inversely with p21CIP in clinical samples of the different cancers. Moreover, BMI1 re-establishment in SOX9-silenced tumor cells restored cell viability and proliferation as well as decreased p21CIP in vitro and tumor growth in vivo. These results indicate that BMI1 is a critical effector of the pro-tumoral activity of SOX9 in tumor bulk cells through the repression of p21CIP . Our results highlight the relevance of the SOX9-BMI1-p21CIP axis in tumor progression, shedding novel opportunities for therapeutic development.- Published
- 2020
- Full Text
- View/download PDF
6. Comparative proteomic analysis of compartmentalised Ras signalling.
- Author
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Hernandez-Valladares M and Prior IA
- Subjects
- HeLa Cells, Humans, Proteomics, Endoplasmic Reticulum metabolism, Golgi Apparatus metabolism, Mitochondria metabolism, Signal Transduction physiology, ras Proteins metabolism
- Abstract
Ras proteins are membrane bound signalling hubs that operate from both the cell surface and endomembrane compartments. However, the extent to which intracellular pools of Ras can contribute to cell signalling is debated. To address this, we have performed a global screen of compartmentalised Ras signalling. We find that whilst ER/Golgi- and endosomal-Ras only generate weak outputs, Ras localised to the mitochondria or Golgi significantly and distinctly influence both the abundance and phosphorylation of a wide range of proteins analysed. Our data reveal that ~80% of phosphosites exhibiting large (≥1.5-fold) changes compared to control can be modulated by organellar Ras signalling. The majority of compartmentalised Ras-specific responses are predicted to influence gene expression, RNA splicing and cell proliferation. Our analysis reinforces the concept that compartmentalisation influences Ras signalling and provides detailed insight into the widespread modulation of responses downstream of endomembranous Ras signalling.
- Published
- 2015
- Full Text
- View/download PDF
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