Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene

Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4⁺ colorectal cancer models

Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4+ tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4+ tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier

Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene

Escola d'Arquitectura de Barcelona : documentos y archivo = documents and archive = documents i arxiu

Text en castellà, anglès i catalàDescripció del recurs: 30 maig 2019Los dibujos y el fondo bibliográfico antiguo del Archivo de la Escuela de Arquitectura constituyen el principal centro de atención de este libro. Se muestran no sólo para dar a conocer unos documentes, de interés indudable por sí mismo, sino también para que nos ayuden a examinar la historia de la Escuela y a reflexionar sobre los métodos de enseñar y de aprender arquitectura. A pesar de lo fragmentario y a veces aleatorio de la procedencia del material que se expone, éste permite obtener una visión global de la Escuela. En correspondencia con este carácter, se reúnen una serie de textos que, a modo de mosaico, dan cabida a una variedad de interpretaciones. Evitando mirar únicamente el mundo de la docencia local, se busca establecer la relación de la Escuela con los métodos de enseñanza, con tendencias arquitectónicas y con el desarrollo de la ciudad.The drawings and the old bibliographical source in the Archives of the Escola d'Arquitectura de Barcelona are this book's main focus of attention, serving not only to divulge the contents of a whole documentary source, of undoubtable interest in its own right, but also to help us examine the history of the School and reflect on ways to teach and learn architecture. Despite the fragmentary and occasionally haphazard nature of the provenance of the material published here, it nonetheless allows us to obtain on overall view of the School. In harmony with this character, the accompanying texts form a kind of mosaic which accommodates a whole variety of different interpretations. Finally, in an attempt to go beyond purely local educational considerations, the book establishes links between the School, with training methods and architectural trends, and the development of the city.Els dibuixos de l'Arxiu de l'Escola d'Arquitectura i el seu fons bibliogràfic antic constitueixen el principal centre d'atenció d'aquest llibre. Es mostren no només per donar a conèixer uns documents d'interès indubtable per si mateixos, sinó també perquè ens ajudin a examinar la història de l'Escola i a reflexionar sobre els mètodes d'aprenentatge i ensenyament de l'arquitectura. Malgrat la procedència fragmentària i de vegades aleatòria dels materials que s'hi exposen, aquest recull permet tenir una visió global de l'Escola. En correspondència amb aquest caràcter, es reuneixen una sèrie de textos que, a manera de mosaic, donen cabuda a una varietat d'interpretacions. Evitant mirar únicament el món de la docència local, es busca establir la relació de l'Escola amb els mètodes d'ensenyament, amb tendències arquitectòniques i amb el desenvolupament de la ciutat

Escola d'Arquitectura de Barcelona : documentos y archivo = documents and archive = documents i arxiu

Text en castellà, anglès i catalàDescripció del recurs: 30 maig 2019Los dibujos y el fondo bibliográfico antiguo del Archivo de la Escuela de Arquitectura constituyen el principal centro de atención de este libro. Se muestran no sólo para dar a conocer unos documentes, de interés indudable por sí mismo, sino también para que nos ayuden a examinar la historia de la Escuela y a reflexionar sobre los métodos de enseñar y de aprender arquitectura. A pesar de lo fragmentario y a veces aleatorio de la procedencia del material que se expone, éste permite obtener una visión global de la Escuela. En correspondencia con este carácter, se reúnen una serie de textos que, a modo de mosaico, dan cabida a una variedad de interpretaciones. Evitando mirar únicamente el mundo de la docencia local, se busca establecer la relación de la Escuela con los métodos de enseñanza, con tendencias arquitectónicas y con el desarrollo de la ciudad.The drawings and the old bibliographical source in the Archives of the Escola d'Arquitectura de Barcelona are this book's main focus of attention, serving not only to divulge the contents of a whole documentary source, of undoubtable interest in its own right, but also to help us examine the history of the School and reflect on ways to teach and learn architecture. Despite the fragmentary and occasionally haphazard nature of the provenance of the material published here, it nonetheless allows us to obtain on overall view of the School. In harmony with this character, the accompanying texts form a kind of mosaic which accommodates a whole variety of different interpretations. Finally, in an attempt to go beyond purely local educational considerations, the book establishes links between the School, with training methods and architectural trends, and the development of the city.Els dibuixos de l'Arxiu de l'Escola d'Arquitectura i el seu fons bibliogràfic antic constitueixen el principal centre d'atenció d'aquest llibre. Es mostren no només per donar a conèixer uns documents d'interès indubtable per si mateixos, sinó també perquè ens ajudin a examinar la història de l'Escola i a reflexionar sobre els mètodes d'aprenentatge i ensenyament de l'arquitectura. Malgrat la procedència fragmentària i de vegades aleatòria dels materials que s'hi exposen, aquest recull permet tenir una visió global de l'Escola. En correspondència amb aquest caràcter, es reuneixen una sèrie de textos que, a manera de mosaic, donen cabuda a una varietat d'interpretacions. Evitant mirar únicament el món de la docència local, es busca establir la relació de l'Escola amb els mètodes d'ensenyament, amb tendències arquitectòniques i amb el desenvolupament de la ciutat