Claudia Haydée - Academia.edu (original) (raw)
Papers by Claudia Haydée
Ciencia - Academia Mexicana de Ciencias, 2016
La genética no es el único factor que influye en el funcionamiento del organismo; el ambiente es ... more La genética no es el único factor que influye en el funcionamiento del organismo; el ambiente es fundamental, pues afecta a nuestro cuerpo incluso a nivel celular. La alimentación ejerce una influencia clave para la apropiada regulación epigenética, pues el desequilibrio nutricional genera desregulaciones que pueden dar pie a patologías como el cáncer. La forma en la que esto ocurre no se conoce a profundidad; sin embargo, muchos investigadores están preocupados por entender cómo la alimentación puede ayudar, o no, al desarrollo de ciertas enfermedades. abril-junio de 2016 • ciencia 29
Oncology Letters, May 31, 2018
Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasiz... more Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.
Cells
The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers.... more The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs pr...
Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known ... more Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function. Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) in the Saos-2 cell line (null p53) transfected as compared with p53WT transfected cells. The association between these miRNAs and the signaling pathways in which they might participate was performed through the miRPath Software. QRT-PCR was employed to validate the miRNAs profiles. In addition, we explored if the induction of cell migration and invasion by the p53R48Q mutant was dependent on the miR-182-5p. We observed that p53 mutants have an overall negative effect on miRNA expression. Likewise, we found miRNAs differentially expressed associated with regulating Oncogenic signaling pathways. We found overexpression of miR-182-5p, which is ...
How to cite Complete issue More information about this article Journal's homepage in redalyc... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System
Cell Motility and the Cytoskeleton, 2007
The ehFLN protein (previously known as EhABP-120) is the first filamin to be identified in the pa... more The ehFLN protein (previously known as EhABP-120) is the first filamin to be identified in the parasitic protozoan Entamoeba histolytica. Filamins are a family of cross-linking actin-binding proteins that organize filamentous actin in networks and stress fibers. It has been reported that filamins of different organisms directly interact with more than 30 cellular proteins and some PPIs. The biochemical consequences of such interactions may have either positive or negative effects on the cross-linking function. Besides, filamins form a link between cytoskeleton and plasma membrane. In this work, the ehFLN protein was biochemically characterized; amoebae filamin was found to associate with both PA and PI(3)P in vitro, new lipid targets for a member of the filamins. By molecular modeling analysis and protein-lipid overlay assays, K-609, 709, and 710 were determined to be essential for the PA-ehFLN1 complex stability. Also, the integrity of the 4th repeat of ehFLN is essential to keep interaction with the PI(3)P. Transfected trophozoites that overexpressed the d100, d50NH 2 , and d50COOH regions of ehFLN1 displayed both increased motility and chemotactic response to TYI-S-33 media. Together, these results suggest that short regions of ehFLN are involved in signaling events that, in cooperation with phosphatidic acid, EhPLD2 and EhPI3K, could promote cell motility.
2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2016
Gastric ischemia - reperfusion (I/R) injury is an important clinical problem, which is developed ... more Gastric ischemia - reperfusion (I/R) injury is an important clinical problem, which is developed in more than 80% of critically ill patients. I/R is caused by interruption of blood supply to an organ or tissue followed by blood reflow into the exposed area, leading to multiple organ failure and death. Gastric reactance has been proposed to measure tissue injury caused by ischemia. The present study evaluates a new method to quantify gastric tissue damage due to I/R, and assess its relation to gastric reactance changes. Twenty Wistar rats were randomly assigned to 4 groups: control, ischemia, I/R 30 min, I/R 1 h. Local gastric ischemia was induced by clamping the celiac artery for 30 min and reperfusion was done for 30-60 min. In all groups, gastric impedance was measured, and then gastric mucosa samples were taken for light microscopy. There were statistical significant differences (p <;0.05) among the groups with respect to the index of gastric injury proposed, which was greater in I/R 1 h group. Also, impedance parameters increased in I/R groups with respect to control, and ischemia groups. The proposed index of gastric injury allowed gastric mucosa damage quantification, and it was related with gastric impedance increase, which is an objective method to evaluate tissue injury.
How to cite Complete issue More information about this article Journal's homepage in redalyc... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System
Frontiers in Cell and Developmental Biology, 2021
The p53 roles have been largely described; among them, cell proliferation and apoptosis control a... more The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants. Furthermore, recent studies have revealed how p53 mutants regulate gene expression and exert oncogenic effects by unbalancing specific microRNAs (miRNAs) levels that provoke epithelial-mesenchymal transition, chemoresistance, and cell survival, among others. In this review, we discuss recent evidence of the crosstalk between miRNAs and mutants of p53, as well as the consequent cellular processes dysregulated.
The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates... more The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates the development and maintenance of the nervous system. Mutations or amplification in ALK promote tumorogenesis and progression of diverse types of cancer, which makes it an attractive therapeutic target against cancer diseases. Inhibition of its tyrosine kinase activity with small molecules, such as crizotinib, reveals tumor reversion; however, secondary mutations and amplification of the gene mediate resistance to treatment. In this article, we discuss the emerging role of possible therapeutic targets that could overcome the resistance to ALK inhibition in cancer, such as inhibition of other kinases involved in the pathway, inhibition of ALK mutant proteins through the development of new drugs based on its crystallography, and the use of antibodies against ALK.
Entreciencias: Diálogos en la Sociedad del Conocimiento, 2021
Objetivo: evaluar el impacto de una intervención educativa que se llevó a cabo durante el segundo... more Objetivo: evaluar el impacto de una intervención educativa que se llevó a cabo durante el segundo trimestre de 2018 con alumnos universitarios de distintas licenciaturas para mejorar su actitud respecto a la lactancia materna (LM).Diseño metodológico: es un estudio exploratorio transversal que busca comparar las actitudes hacia la LM determinadas por la Escala de Actitudes hacia la Alimentación Infantil Iowa (IIFAS, por sus siglas en inglés) entre 2 grupos, uno de ellos expuesto a una intervención educativa. Esta escala ha sido validada previamente para la población mexicana.Resultados: los alumnos que participaron en la intervención educativa mostraron una actitud más positiva hacia la LM que los alumnos que no participaron.Limitaciones de la investigación: el número de estudiantes que respondieron el cuestionario es relativamente bajo comparado con la población universitaria por lo que los resultados pueden no ser ampliamente generalizables. Pueden existir sesgos no identificables...
Colloids and Surfaces B: Biointerfaces, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Cancer letters, Jan 6, 2018
RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attra... more RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration of miR-204 in MDA-MB-231 cells leads to a potent inhibition of VM and reduction of number of branch points and patterned 3D channels. Further analysis of activation state of multiple signaling pathways using Phosphorylation Antibody Arrays revealed that miR-204 reduced the expression and phosphorylation levels of 13 proteins involved in PI3K/AKT, RAF1/MAPK, VEGF, and FAK/SRC signaling. In agreement with phospho-proteomic profiling, VM was impaired following pharmacological administration of PI3K and SRC inhibitors. Mechanistic studies conf...
Oncology & Hematology Review (US), 2013
The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates... more The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates the development and maintenance of the nervous system. Mutations or amplification in ALK promote tumorogenesis and progression of diverse types of cancer, which makes it an attractive therapeutic target against cancer diseases. Inhibition of its tyrosine kinase activity with small molecules, such as crizotinib, reveals tumor reversion; however, secondary mutations and amplification of the gene mediate resistance to treatment. In this article, we discuss the emerging role of possible therapeutic targets that could overcome the resistance to ALK inhibition in cancer, such as inhibition of other kinases involved in the pathway, inhibition of ALK mutant proteins through the development of new drugs based on its crystallography, and the use of antibodies against ALK.
Lung cancer is the neoplasia with the highest incidence and mortality in men and women worldwide.... more Lung cancer is the neoplasia with the highest incidence and mortality in men and women worldwide. Lung cancer is classifi ed into two large histologic subgroups: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) according to cellular origin, molecular changes, clinical-pathological features, and response to treatments. NSCLC constitutes 80% of the all cases of lung cancer; nevertheless the molecular mechanisms underlying the tumoral etiology still remain poorly understood. MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level by repressing translation or decreasing mRNA stability in numerous biological processes. In cancer, miRNAs have differential spatial and temporal expression, which is related to several clinical, biological, molecular and genomic features of tumors. miRNA expression profi les, polymorphisms and epigenetic modifi cation in NSCLC have been studied, a...
Lung cancer is the neoplasia with higher incidence and mortality in men and women worldwide. Lung... more Lung cancer is the neoplasia with higher incidence and mortality in men and women worldwide. Lung cancer is classified into two large histologic subgroups: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) according to cellular origin, molecular changes, clinical-pathological features, and response to treatments. The NSCLC constitutes 80% of the all cases of lung cancer; nevertheless the molecular mechanisms underlying the tumoral etiology still remain poorly understood. MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level by repressing translation or decreasing mRNA stability in numerous biological processes. In cancer, miRNAs have spatial and temporal expression, which is related with several clinical, biological, molecular and genomic features of tumors. miRNAs expression profiles, polymorphisms and epigenetic modification in NSCLC have been studied, and they have i...
Cell Motility and the Cytoskeleton, 2007
Rho GTPases are critical elements involved in the regulation of signal transduction cascades from... more Rho GTPases are critical elements involved in the regulation of signal transduction cascades from extracellular stimuli to cytoskeleton. The Rho guanine nucleotide exchange factors (RhoGEFs) have been implicated in direct activation of these GTPases. Here, we describe a novel RhoGEF, denominated EhGEF3 from the parasite Entamoeba histolytica, which encodes a 110 kDa protein containing the domain arrangement of a Dbl homology domain in tandem with a pleckstrin homology domain, the DH domain of EhGEF3 is closely related with the one of the Vav3 protein. Biochemical analysis revealed that EhGEF3 is capable of stimulating nucleotide exchange on the E. histolytica EhRacA and EhRho1 GTPases in vitro, however only a partial GEF activity toward Cdc42 was observed. Conserved residue analysis showed that the N816 and L817 residues are critical for EhGEF3 activity. Cellular studies revealed that EhGEF3 colocalises with EhRacA in the rear of migrating cells, probably regulating the retraction of the uroid and promoting the activation of these GTPase during the chemotactic response toward fibronectin, and that EhGEF3 also regulates EhRacA activation during the capping of cell receptors. These results suggest that EhGEF3 should have a direct role in activating EhRacA, and in bringing the activated GTPase to specific target sites such as the uroid.
Molecular Cancer, 2013
Background All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer t... more Background All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance. Results We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Inte...
Molecular and Biochemical Parasitology, 2007
Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activ... more Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activation of Rho small GTPases. This paper reports the molecular, structural, biochemical and functional characterization of EhGEF2, a new member of the Dbl family. EhGEF2 is the second GEF studied in parasites and in the protozoan Entamoeba histolytica, and it is also the first member of the Dbl family that was found to have Arm repeats. The catalytic domain (DH) of EhGEF2 has the conserved residues T421, N590 and E591, which are important for the activation of the GTPases. Biochemical studies on EhGEF2 showed that it could activate in vitro the amoebic GTPases EhRacA, EhRacB, EhRacC, EhRacD, EhRacG, EhRacH and EhCdc42, being EhRacG its main target. It was found that the DH domain binds specifically phosphatidic acid (PA); docking and lipid dot blot studies indicated that this binding does not interfere with the contact surface of EhRacG. Functional studies showed that both the Arm repeats and the catalytic domain of EhGEF2 participate in its localization at the amoebic membrane. Expression of a negative dominant version of EhGEF2 protein in E. histolytica provoked a 30% decrease in its ability to phagocyte human erythrocytes as well as severe effects on both the proliferation and the cellular chemotaxis which suggest that EhGEF2 participates in these cellular processes.
Ciencia - Academia Mexicana de Ciencias, 2016
La genética no es el único factor que influye en el funcionamiento del organismo; el ambiente es ... more La genética no es el único factor que influye en el funcionamiento del organismo; el ambiente es fundamental, pues afecta a nuestro cuerpo incluso a nivel celular. La alimentación ejerce una influencia clave para la apropiada regulación epigenética, pues el desequilibrio nutricional genera desregulaciones que pueden dar pie a patologías como el cáncer. La forma en la que esto ocurre no se conoce a profundidad; sin embargo, muchos investigadores están preocupados por entender cómo la alimentación puede ayudar, o no, al desarrollo de ciertas enfermedades. abril-junio de 2016 • ciencia 29
Oncology Letters, May 31, 2018
Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasiz... more Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.
Cells
The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers.... more The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs pr...
Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known ... more Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function. Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) in the Saos-2 cell line (null p53) transfected as compared with p53WT transfected cells. The association between these miRNAs and the signaling pathways in which they might participate was performed through the miRPath Software. QRT-PCR was employed to validate the miRNAs profiles. In addition, we explored if the induction of cell migration and invasion by the p53R48Q mutant was dependent on the miR-182-5p. We observed that p53 mutants have an overall negative effect on miRNA expression. Likewise, we found miRNAs differentially expressed associated with regulating Oncogenic signaling pathways. We found overexpression of miR-182-5p, which is ...
How to cite Complete issue More information about this article Journal's homepage in redalyc... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System
Cell Motility and the Cytoskeleton, 2007
The ehFLN protein (previously known as EhABP-120) is the first filamin to be identified in the pa... more The ehFLN protein (previously known as EhABP-120) is the first filamin to be identified in the parasitic protozoan Entamoeba histolytica. Filamins are a family of cross-linking actin-binding proteins that organize filamentous actin in networks and stress fibers. It has been reported that filamins of different organisms directly interact with more than 30 cellular proteins and some PPIs. The biochemical consequences of such interactions may have either positive or negative effects on the cross-linking function. Besides, filamins form a link between cytoskeleton and plasma membrane. In this work, the ehFLN protein was biochemically characterized; amoebae filamin was found to associate with both PA and PI(3)P in vitro, new lipid targets for a member of the filamins. By molecular modeling analysis and protein-lipid overlay assays, K-609, 709, and 710 were determined to be essential for the PA-ehFLN1 complex stability. Also, the integrity of the 4th repeat of ehFLN is essential to keep interaction with the PI(3)P. Transfected trophozoites that overexpressed the d100, d50NH 2 , and d50COOH regions of ehFLN1 displayed both increased motility and chemotactic response to TYI-S-33 media. Together, these results suggest that short regions of ehFLN are involved in signaling events that, in cooperation with phosphatidic acid, EhPLD2 and EhPI3K, could promote cell motility.
2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2016
Gastric ischemia - reperfusion (I/R) injury is an important clinical problem, which is developed ... more Gastric ischemia - reperfusion (I/R) injury is an important clinical problem, which is developed in more than 80% of critically ill patients. I/R is caused by interruption of blood supply to an organ or tissue followed by blood reflow into the exposed area, leading to multiple organ failure and death. Gastric reactance has been proposed to measure tissue injury caused by ischemia. The present study evaluates a new method to quantify gastric tissue damage due to I/R, and assess its relation to gastric reactance changes. Twenty Wistar rats were randomly assigned to 4 groups: control, ischemia, I/R 30 min, I/R 1 h. Local gastric ischemia was induced by clamping the celiac artery for 30 min and reperfusion was done for 30-60 min. In all groups, gastric impedance was measured, and then gastric mucosa samples were taken for light microscopy. There were statistical significant differences (p <;0.05) among the groups with respect to the index of gastric injury proposed, which was greater in I/R 1 h group. Also, impedance parameters increased in I/R groups with respect to control, and ischemia groups. The proposed index of gastric injury allowed gastric mucosa damage quantification, and it was related with gastric impedance increase, which is an objective method to evaluate tissue injury.
How to cite Complete issue More information about this article Journal's homepage in redalyc... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System
Frontiers in Cell and Developmental Biology, 2021
The p53 roles have been largely described; among them, cell proliferation and apoptosis control a... more The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants. Furthermore, recent studies have revealed how p53 mutants regulate gene expression and exert oncogenic effects by unbalancing specific microRNAs (miRNAs) levels that provoke epithelial-mesenchymal transition, chemoresistance, and cell survival, among others. In this review, we discuss recent evidence of the crosstalk between miRNAs and mutants of p53, as well as the consequent cellular processes dysregulated.
The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates... more The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates the development and maintenance of the nervous system. Mutations or amplification in ALK promote tumorogenesis and progression of diverse types of cancer, which makes it an attractive therapeutic target against cancer diseases. Inhibition of its tyrosine kinase activity with small molecules, such as crizotinib, reveals tumor reversion; however, secondary mutations and amplification of the gene mediate resistance to treatment. In this article, we discuss the emerging role of possible therapeutic targets that could overcome the resistance to ALK inhibition in cancer, such as inhibition of other kinases involved in the pathway, inhibition of ALK mutant proteins through the development of new drugs based on its crystallography, and the use of antibodies against ALK.
Entreciencias: Diálogos en la Sociedad del Conocimiento, 2021
Objetivo: evaluar el impacto de una intervención educativa que se llevó a cabo durante el segundo... more Objetivo: evaluar el impacto de una intervención educativa que se llevó a cabo durante el segundo trimestre de 2018 con alumnos universitarios de distintas licenciaturas para mejorar su actitud respecto a la lactancia materna (LM).Diseño metodológico: es un estudio exploratorio transversal que busca comparar las actitudes hacia la LM determinadas por la Escala de Actitudes hacia la Alimentación Infantil Iowa (IIFAS, por sus siglas en inglés) entre 2 grupos, uno de ellos expuesto a una intervención educativa. Esta escala ha sido validada previamente para la población mexicana.Resultados: los alumnos que participaron en la intervención educativa mostraron una actitud más positiva hacia la LM que los alumnos que no participaron.Limitaciones de la investigación: el número de estudiantes que respondieron el cuestionario es relativamente bajo comparado con la población universitaria por lo que los resultados pueden no ser ampliamente generalizables. Pueden existir sesgos no identificables...
Colloids and Surfaces B: Biointerfaces, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Cancer letters, Jan 6, 2018
RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attra... more RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration of miR-204 in MDA-MB-231 cells leads to a potent inhibition of VM and reduction of number of branch points and patterned 3D channels. Further analysis of activation state of multiple signaling pathways using Phosphorylation Antibody Arrays revealed that miR-204 reduced the expression and phosphorylation levels of 13 proteins involved in PI3K/AKT, RAF1/MAPK, VEGF, and FAK/SRC signaling. In agreement with phospho-proteomic profiling, VM was impaired following pharmacological administration of PI3K and SRC inhibitors. Mechanistic studies conf...
Oncology & Hematology Review (US), 2013
The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates... more The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates the development and maintenance of the nervous system. Mutations or amplification in ALK promote tumorogenesis and progression of diverse types of cancer, which makes it an attractive therapeutic target against cancer diseases. Inhibition of its tyrosine kinase activity with small molecules, such as crizotinib, reveals tumor reversion; however, secondary mutations and amplification of the gene mediate resistance to treatment. In this article, we discuss the emerging role of possible therapeutic targets that could overcome the resistance to ALK inhibition in cancer, such as inhibition of other kinases involved in the pathway, inhibition of ALK mutant proteins through the development of new drugs based on its crystallography, and the use of antibodies against ALK.
Lung cancer is the neoplasia with the highest incidence and mortality in men and women worldwide.... more Lung cancer is the neoplasia with the highest incidence and mortality in men and women worldwide. Lung cancer is classifi ed into two large histologic subgroups: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) according to cellular origin, molecular changes, clinical-pathological features, and response to treatments. NSCLC constitutes 80% of the all cases of lung cancer; nevertheless the molecular mechanisms underlying the tumoral etiology still remain poorly understood. MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level by repressing translation or decreasing mRNA stability in numerous biological processes. In cancer, miRNAs have differential spatial and temporal expression, which is related to several clinical, biological, molecular and genomic features of tumors. miRNA expression profi les, polymorphisms and epigenetic modifi cation in NSCLC have been studied, a...
Lung cancer is the neoplasia with higher incidence and mortality in men and women worldwide. Lung... more Lung cancer is the neoplasia with higher incidence and mortality in men and women worldwide. Lung cancer is classified into two large histologic subgroups: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) according to cellular origin, molecular changes, clinical-pathological features, and response to treatments. The NSCLC constitutes 80% of the all cases of lung cancer; nevertheless the molecular mechanisms underlying the tumoral etiology still remain poorly understood. MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level by repressing translation or decreasing mRNA stability in numerous biological processes. In cancer, miRNAs have spatial and temporal expression, which is related with several clinical, biological, molecular and genomic features of tumors. miRNAs expression profiles, polymorphisms and epigenetic modification in NSCLC have been studied, and they have i...
Cell Motility and the Cytoskeleton, 2007
Rho GTPases are critical elements involved in the regulation of signal transduction cascades from... more Rho GTPases are critical elements involved in the regulation of signal transduction cascades from extracellular stimuli to cytoskeleton. The Rho guanine nucleotide exchange factors (RhoGEFs) have been implicated in direct activation of these GTPases. Here, we describe a novel RhoGEF, denominated EhGEF3 from the parasite Entamoeba histolytica, which encodes a 110 kDa protein containing the domain arrangement of a Dbl homology domain in tandem with a pleckstrin homology domain, the DH domain of EhGEF3 is closely related with the one of the Vav3 protein. Biochemical analysis revealed that EhGEF3 is capable of stimulating nucleotide exchange on the E. histolytica EhRacA and EhRho1 GTPases in vitro, however only a partial GEF activity toward Cdc42 was observed. Conserved residue analysis showed that the N816 and L817 residues are critical for EhGEF3 activity. Cellular studies revealed that EhGEF3 colocalises with EhRacA in the rear of migrating cells, probably regulating the retraction of the uroid and promoting the activation of these GTPase during the chemotactic response toward fibronectin, and that EhGEF3 also regulates EhRacA activation during the capping of cell receptors. These results suggest that EhGEF3 should have a direct role in activating EhRacA, and in bringing the activated GTPase to specific target sites such as the uroid.
Molecular Cancer, 2013
Background All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer t... more Background All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance. Results We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Inte...
Molecular and Biochemical Parasitology, 2007
Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activ... more Dbl proteins are a family of factors that exchange the guanine nucleotide which promote the activation of Rho small GTPases. This paper reports the molecular, structural, biochemical and functional characterization of EhGEF2, a new member of the Dbl family. EhGEF2 is the second GEF studied in parasites and in the protozoan Entamoeba histolytica, and it is also the first member of the Dbl family that was found to have Arm repeats. The catalytic domain (DH) of EhGEF2 has the conserved residues T421, N590 and E591, which are important for the activation of the GTPases. Biochemical studies on EhGEF2 showed that it could activate in vitro the amoebic GTPases EhRacA, EhRacB, EhRacC, EhRacD, EhRacG, EhRacH and EhCdc42, being EhRacG its main target. It was found that the DH domain binds specifically phosphatidic acid (PA); docking and lipid dot blot studies indicated that this binding does not interfere with the contact surface of EhRacG. Functional studies showed that both the Arm repeats and the catalytic domain of EhGEF2 participate in its localization at the amoebic membrane. Expression of a negative dominant version of EhGEF2 protein in E. histolytica provoked a 30% decrease in its ability to phagocyte human erythrocytes as well as severe effects on both the proliferation and the cellular chemotaxis which suggest that EhGEF2 participates in these cellular processes.