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51. A common PDGF receptor is activated by homodimeric A and B forms of PDGF

Author

Escobedo, Jaime A., Navankasatussas, Sutip, Cousens, Lawrence S., Coughlin, Shaun R., Bell, Graeme I., and Williams, Lewis T.

Subjects
Protein research -- Research, Platelet-derived growth factor -- Research, Membrane proteins -- Research, Cell receptors -- Research, Science and technology, Research
Abstract

A Common PDGF Receptor Is Activated by Homodimeric A and B Forms of PDGF PLATELET-DERIVED GROWTH FACTOR, a major mitogen for cells of mesenchymal origin, is a 32-kD protein heterodimer [...]

Published
1988

66. Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/β-catenin signalling....

Author

Dong Yan, Wiesmann, Marion, Rohan, Michael, Chan, Vivien, Jefferson, Ann B., Lida Guo, Sakamoto, Doreen, Caothien, Roger H., Fuller, John H., Reinhard, Christoph, Garcia, Pablo D., Randazzo, Filippo M., Escobedo, Jaime, Fantl, Wendy J., and Williams, Lewis T.

Subjects
COLON cancer, NUCLEOTIDES, MESSENGER RNA, CELL lines
Abstract

Determines the activation of Wnt/beta-catenin pathway in human colon cancers. Effect of beta-catenin antisense oligodeoxynucleotides on the level of axin2 and human naked cuticle (hnkd) mRNA; Expression of axin2 and hnkd in colon cancer cell lines; Correlation of the increased expression of axin2 and hnkd with truncations in polyposis coli.

Published
2001
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68. Tightly Regulated Long-Term Erythropoietin Expression In Vivo Using Tet-Inducible Recombinant Adeno-Associated Viral Vectors

Author

Rendahl, Katherine G., Quiroz, Dulce, Ladner, Martha, Coyne, Mazie, Seltzer, Jon, Manning, William C., and Escobedo, Jaime A.

Abstract

Recombinant adeno-associated viral (rAAV) vectors containing an improved tetracycline (tet) system of transcriptional regulation are an efficient strategy for the control of long-term therapeutic gene expression. In vivo studies with the original tet-off and tet-on vectors, while promising, have failed to demonstrate complete repression in the uninduced state. To address this issue, we incorporated the tTSkid fusion of the tet repressor and a KRAB-derived transcriptional silencer into the tet-on system in the context of rAAV vectors. The tTSkid repressor and rtTA activator were expressed constituitively from a regulator vector, and the repressor and an erythropoietin (Epo) transgene were expressed inducibly via a second vector. Following intramuscular co-injection of these vectors, we observed repeated induction of serum Epo protein following drug administration and undetectable levels after its withdrawal. Four cycles of regulation were achieved over a 32-week period. Thus, the tet-on system plus the tTSkid repressor delivered via nonpathogenic rAAV vectors is a powerful tool for controlling the in vivo expression of therapeutic transgenes. In a clinical setting, the repressor could provide a mechanism for abolishing transgene expression if it were no longer needed or if the safety of a patient became compromised.

Published
2002
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69. Positive selection system to screen for inhibitors of human immunodeficiency virus-1 transcription

Author

Rosario, Merci Del, Stephans, James C., Zakel, Joan, Escobedo, Jaime, and Giese, Klaus

Abstract

We describe a transcription-based assay system to screen for antiviral drugs in vivo. The system consists of two transcription units, a cytomegalovirus promoter driving a reporter gene physically linked to an HIV-1 promoter oriented in the opposite direction. Based on the arrangement of the transcription units, enhanced HIV-1 promoter activity in the presence of the viral transactivating Tat protein downregulates reporter gene expression initiated from the CMV promoter. Inhibitors of HIV-1 transcription relieve the suppression and are identified by an increase in reporter gene expression. This positive selection system allows discrimination between drugs that nonspecifically block cellular functions by cytotoxicity and molecules that specifically repress HIV-1 promoter activity.

Published
1996
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70. Identification of a Domain in the Angiotensin II Type 1 Receptor Determining GqCoupling by the Use of Receptor Chimeras (∗)

Author

Wang, Caili, Jayadev, Suman, and Escobedo, Jaime A.

Abstract

The angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors belong to the seven transmembrane receptor superfamily. Previous studies have suggested that the AT1R couples to a Gqsignaling pathway, whereas the AT2R does not associate with Gq. To identify the role that individual intracellular domains play in AT1R function, AT1R/AT2R chimeric receptors were prepared by substitution of intracellular loops. CHO cells expressing these chimeras were used to test angiotensin II-induced c-fosexpression and Ca2+mobilization which are involved in the AT1R signaling pathway through Gqcoupling. Substitution of the second intracellular loop (IC2) and the cytoplasmic tail between the two receptors did not affect AT1R function. However, exchange of the third intracellular loop (IC3) resulted in the loss of function in the AT1R and conferred to the AT2R the ability to constitutively activate the fospromoter. These findings suggest that the third intracellular loop of the AT1R is critical for Gqcoupling. Substitution of discrete amino acid sequences of the third intracellular loop indicate that its N-terminal and C-terminal portions, especially the seven amino acids 219-225 in the N-terminal portion, are important for AT1R function, and that the intermediate portion of this loop is not required for Gqcoupling.

Published
1995
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71. Plan estratégico del subsector infraestructura vial en el Perú 2016-2020

Author

Figueroa Salvador, Hernán Freddy, Crovetto Villacorta, Juan Erick, Ortiz Escobedo, Jaime Enrique, Pérez Smith, Carlos Guillermo, Figueroa Salvador, Hernán Freddy, Crovetto Villacorta, Juan Erick, Ortiz Escobedo, Jaime Enrique, and Pérez Smith, Carlos Guillermo

Abstract

El Sub Sector Infraestructura Vial en el Perú se encuentra marcada con una gran brecha lo que resta competitividad al país generando incluso malestar en la calidad de vida de sus pobladores y retrayendo el desarrollo del sector empresarial. En el siguiente plan estratégico se ha proyectado como objetivo una visión para el año 2025, la misma que consiste en cerrar la brecha en el sector vial que en la actualidad marca la cifra de US$ 57,499 millones. Esto permitirá que el país cambie de rumbo competitivo y se vuelva un referente en la región mostrando una alta capacidad de ejecución de sus diferentes proyectos viales, además de facilitar el libre acceso a diferentes zonas con carreteras acorde a los estándares internaciones que permitirán el intercambio comercial de las diferentes regiones, generando alianzas estratégicas para la formación de corredores económicos en aras del desarrollo económico, social y competitivo de la nación. La promoción de obras por impuesto, Alianzas Publico Privados, la reformación del SNIP son algunas de las claves que permitirá el mejoramiento del Sub Sector, generando mayores facilidades de ejecución de los diversos paquetes de proyectos que están ya formulados y presupuestados. Los organismos participantes en el desarrollo del Sub Sector deben de estar enmarcadas de solidos valores lo que permita la disminución de diferentes actos corruptivos que se han vivenciado en los últimos años lo que retrasa el avance competitivo del país. Se concluye que la reforma de diversos organismos y la mayor inversión en el desarrollo del Sub Sector Infraestructura Vial permitirán ir cerrando la brecha que separa al país de ser un referente competitivo en la región y en el mundo, lo que permitirá ver al Perú como un país donde se pueda desarrollar cualquier actividad económica generando el desarrollo del país, The Sub-Sector Road Infrastructure in Peru is marked by a large gap that cut down on the country's competitiveness even causing discomfort in the quality of life of its residents and retracting the development of the business sector. In the next strategic plan, a vision for the year 2025 has been projected, which is to close the gap in the road sector that currently marks the figure of US $ 57.499 million. This will allow the country to change its competitive course and become a benchmark in the region by showing a high capacity of execution of its different road projects, as well as facilitating free access to different areas with highways according to international standards that will allow commercial exchange among the different regions, generating strategic alliances for the formation of economic corridors on the way to economic, social, and competitive development of the nation. The promotion of works by tax, Public Private Partnerships, the reform of the SNIP are some of the keys that will allow the improvement of the Sub Sector, generating greater facilities of execution of the diverse project lists that are already formulated and budgeted. The organisms participating in the development of the Sub-Sector must be represented by solid values that allow the reduction of different corruptive acts that have been experienced in recent years, which delays the country's competitive advance. Given these points we conclude that the reform of various agencies and greater investment in the development of the Sub-Sector Road Infrastructure will allow closing the gap that separates the country from being a competitive benchmark in the region and in the world, which will allow Peru to be seen as a Country where any economic activity can be developed generating the development of the country, Tesis

72. Plan estratégico del subsector infraestructura vial en el Perú 2016-2020

Author

Figueroa Salvador, Hernán Freddy, Crovetto Villacorta, Juan Erick, Ortiz Escobedo, Jaime Enrique, Pérez Smith, Carlos Guillermo, Figueroa Salvador, Hernán Freddy, Crovetto Villacorta, Juan Erick, Ortiz Escobedo, Jaime Enrique, and Pérez Smith, Carlos Guillermo

Abstract

El Sub Sector Infraestructura Vial en el Perú se encuentra marcada con una gran brecha lo que resta competitividad al país generando incluso malestar en la calidad de vida de sus pobladores y retrayendo el desarrollo del sector empresarial. En el siguiente plan estratégico se ha proyectado como objetivo una visión para el año 2025, la misma que consiste en cerrar la brecha en el sector vial que en la actualidad marca la cifra de US$ 57,499 millones. Esto permitirá que el país cambie de rumbo competitivo y se vuelva un referente en la región mostrando una alta capacidad de ejecución de sus diferentes proyectos viales, además de facilitar el libre acceso a diferentes zonas con carreteras acorde a los estándares internaciones que permitirán el intercambio comercial de las diferentes regiones, generando alianzas estratégicas para la formación de corredores económicos en aras del desarrollo económico, social y competitivo de la nación. La promoción de obras por impuesto, Alianzas Publico Privados, la reformación del SNIP son algunas de las claves que permitirá el mejoramiento del Sub Sector, generando mayores facilidades de ejecución de los diversos paquetes de proyectos que están ya formulados y presupuestados. Los organismos participantes en el desarrollo del Sub Sector deben de estar enmarcadas de solidos valores lo que permita la disminución de diferentes actos corruptivos que se han vivenciado en los últimos años lo que retrasa el avance competitivo del país. Se concluye que la reforma de diversos organismos y la mayor inversión en el desarrollo del Sub Sector Infraestructura Vial permitirán ir cerrando la brecha que separa al país de ser un referente competitivo en la región y en el mundo, lo que permitirá ver al Perú como un país donde se pueda desarrollar cualquier actividad económica generando el desarrollo del país, The Sub-Sector Road Infrastructure in Peru is marked by a large gap that cut down on the country's competitiveness even causing discomfort in the quality of life of its residents and retracting the development of the business sector. In the next strategic plan, a vision for the year 2025 has been projected, which is to close the gap in the road sector that currently marks the figure of US $ 57.499 million. This will allow the country to change its competitive course and become a benchmark in the region by showing a high capacity of execution of its different road projects, as well as facilitating free access to different areas with highways according to international standards that will allow commercial exchange among the different regions, generating strategic alliances for the formation of economic corridors on the way to economic, social, and competitive development of the nation. The promotion of works by tax, Public Private Partnerships, the reform of the SNIP are some of the keys that will allow the improvement of the Sub Sector, generating greater facilities of execution of the diverse project lists that are already formulated and budgeted. The organisms participating in the development of the Sub-Sector must be represented by solid values that allow the reduction of different corruptive acts that have been experienced in recent years, which delays the country's competitive advance. Given these points we conclude that the reform of various agencies and greater investment in the development of the Sub-Sector Road Infrastructure will allow closing the gap that separates the country from being a competitive benchmark in the region and in the world, which will allow Peru to be seen as a Country where any economic activity can be developed generating the development of the country

75. beta-Catenin regulates vascular endothelial growth factor expression in colon cancer.

Author

Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, Wiesmann M, Garcia PD, Fuller JH, Chan V, Randazzo F, Gundel R, Warren RS, Escobedo J, Aukerman SL, Taylor RN, and Fantl WJ

Subjects
Adenocarcinoma blood supply, Adenocarcinoma etiology, Adenocarcinoma metabolism, Adenocarcinoma pathology, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli metabolism, Animals, Binding Sites, Colon metabolism, Colonic Neoplasms blood supply, Colonic Neoplasms etiology, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Cytoskeletal Proteins genetics, Endothelial Growth Factors genetics, Fibroblast Growth Factor 2 analysis, Gene Expression Regulation, Neoplastic drug effects, Genes, APC, Genes, ras, Growth Substances genetics, Humans, Intercellular Signaling Peptides and Proteins genetics, Intestinal Mucosa metabolism, Lymphokines genetics, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Neoplasm Proteins genetics, Oligodeoxyribonucleotides, Antisense pharmacology, RNA, Messenger biosynthesis, RNA, Messenger genetics, RNA, Neoplasm biosynthesis, RNA, Neoplasm genetics, Recombinant Fusion Proteins physiology, Signal Transduction, Subcellular Fractions chemistry, Trans-Activators genetics, Transfection, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured metabolism, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, beta Catenin, Adenocarcinoma genetics, Colonic Neoplasms genetics, Cytoskeletal Proteins physiology, Endothelial Growth Factors biosynthesis, Gene Expression Regulation, Neoplastic physiology, Intercellular Signaling Peptides and Proteins biosynthesis, Lymphokines biosynthesis, Neoplasm Proteins biosynthesis, Promoter Regions, Genetic genetics, Trans-Activators physiology
Abstract

To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.

Published
2003

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