Search results for "I3"
showing 8 items of 278 documents
Targeting GSK3 and Associated Signaling Pathways Involved in Cancer
2020
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer a…
Capacidad predictiva y pronóstica de factores moleculares en cáncer de mama HER2 positivo tratado con quimioterapia neoadyuvante basada en antracicli…
2017
El tratamiento neoadyuvante del cáncer de mama (CM) permite estudiar marcadores subrogados que puedan predecir respuesta clínica y supervivencia. La respuesta completa patológica (RCp) definida como la ausencia de tumor infiltrante en la mama y axila en la pieza quirúrgica se asocia a mejor supervivencia. En los tumores HER2 positivo el tratamiento de elección es la combinación de quimioterapia, antraciclinas y taxanos son los esquemas con mayor evidencia, con terapia anti-HER2 (trastuzumab (TTZ)) alcanzando tasas de RCp del 30-60%. No disponemos de factores predictivos que identifiquen qué subgrupo obtendrá mayores tasas de RCp . Existe evidencia que los tumores con receptores hormonales (…
Organizational Wellness Modeling
2009
The aim of the present paper is to establish certain mathematical models for organizational wellness as well as to create some wellness optimization problems applicable to any type of organization (including universities) that might be mathematically solved resorting to aspects of operational research of mathematical analysis. The results obtained associated with a mathematical apparatus enable one to perform analyses, comparisons, interpretations, predictions. All of us have, consciously or not, a genuine curiosity in creating and shaping organizational wellness. This concept represents a highly topical issue since professional activity, irrespective of its field, holds a very significant …
Caracterización funcional de mutaciones oncogénicas de PI3K
2015
El cáncer es una enfermedad compleja originada por alteraciones genéticas en proto-oncogenes y/o supresores tumorales. El proto-oncogén PI3K se encuentra alterado en numerosos cánceres. La PI3K de clase I son quinasas, formadas por una subunidad catalítica (p110) y una reguladora (p85), que catalizan la conversión de PtdIns(4,5)P2 en PtdIns(3,4,5)P3 en las membranas celulares. Este último es un segundo mensajero que recluta a la quinasa de Ser/Thr AKT, la cual activa a numerosos efectores y desencadena una respuesta proliferativa y de supervivencia celular, por lo que mutaciones que causen la hiperactivación de esta ruta conllevan la transformación de células normales en células tumorales. …
The paradox of endogenous poverty line in the poverty indices
2007
february 23-25, 2007; When measuring poverty, the poverty line is considered to be relatively determined as a percentage of the median income or as a percentage of the average income so as to allow international comparisons. The poverty line relative to the median income may be described as endogenous in contrast with the poverty line relative to the average income which may be described as exogenous because it is independent of the normalized distribution of incomes. As the existing literature is focused on the properties of the indices but not on the respective interest of the endogenous and exogenous poverty lines, this paper compares the two definitions of the relative poverty. The Rela…
Synthesis and Antitumor Evaluation of Menthone-Derived Pyrimidine-Urea Compounds as Potential PI3K/Akt/mTOR Signaling Pathway Inhibitor.
2022
A series of novel menthone derivatives bearing pyrimidine and urea moieties was designed and synthesized to explore more potent natural product-derived antitumor agents. The structures of the target compounds were confirmed by FTIR, NMR, and HRMS. The in vitro antitumor activity was tested by standard methyl thiazolytetrazolium assay and showed that 4i, 4g, 4s, and 4m are the best compounds with IC50 values of 6.04 ± 0.62µM, 3.21 ± 0.67µM, 19.09 ± 0.49µM, and 18.68 ± 1.53µM, against Hela, MGC-803, MCF-7, and A549, respectively. The results of the preliminary action mechanism studies showed that compound 4i, the representative compound, could induce cell apoptosis in Hela cells in a dose-dep…
A novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo
2015
AbstractShort peptide sequences from complementarity-determining regions (CDRs) of different immunoglobulins may exert anti-infective, immunomodulatory and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). In this sense, they resemble early molecules of innate immunity. C36L1 was identified as a bioactive light-chain CDR1 peptide by screening 19 conserved CDR sequences targeting murine B16F10-Nex2 melanoma. The 17-amino acid peptide is readily taken up by melanoma cells and acts on microtubules causing depolymerization, stress of the endoplasmic reticulum and intrinsic apoptosis. At low concentrations, C36L1 inhibited migration, invasion and proli…
MTOR inhibitor-based combination therapies for pancreatic cancer
2018
Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…