Publications
2023
Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal–epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. Methods: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF….. link
Currently, the marketing of electronic cigarettes as a safe alternative to smoking has increased, which is associated with greater use of these devices, especially among young people and smokers interested in quitting tobacco cigarettes. Given the growing use of this type of product, there is a need to determine the consequences of electronic cigarettes on human health, especially since many of the compounds contained in the aerosol and liquid of these devices have a high potential to be carcinogenic and genotoxic. … link
In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect… link
Anaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation…. link
The transcriptomic analysis of microarray and RNA-Seq datasets followed our own bioinformatic pipeline to identify a transcriptional regulatory network of lung cancer. Twenty-six transcription factors are dysregulated and co-expressed in most of the lung cancer and pulmonary arterial hypertension datasets, which makes them the most frequently dysregulated transcription factors. Co-expression, gene regulatory, coregulatory, and transcriptional regulatory networks, along with fibration symmetries, were constructed to identify common connection patterns, alignments, main regulators, and target genes in order to analyze transcription factor complex formation, as well as its synchronized co-expression patterns in every type of lung cancer. The regulatory function of the most frequently dysregulated transcription factors over lung cancer deregulated genes was validated with ChEA3 enrichment analysis… link
2022
Puberty is a complex transitional phase in which reproductive capacity is achieved. There is a very wide variation in the age range of the onset of puberty, which follows a familial, ethnic, and sex pattern. The hypothalamic-pituitary-gonadal axis and several genetic, environmental, and nutritional factors play an important role in the onset of and throughout puberty. Recently, there has been significant progress in identifying factors that affect normal pubertal timing. Different studies have identified single nucleotide polymorphisms (SNPs) that affect pubertal timing in both sexes and across ethnic groups. Single genes are implicated in both precocious and delayed puberty, and epigenetic mechanisms have been suggested to affect the development and function of the GnRH neuronal network and responsiveness of end organs. All these factors can influence normal puberty timing, precocious puberty, and delayed puberty. The objective of this review is to describe recent findings related to the genetic and epigenetic control of puberty and highlight the need to deepen the knowledge of the regulatory mechanisms of this process in the normal and abnormal context…. link
The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs’ target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.. link
Lung cancer is the leading cause of cancer death globally. Numerous factors intervene in the onset and progression of lung tumors, among which the participation of lineage-specific transcription factors stands out. Several transcription factors important in embryonic development are abnormally expressed in adult tissues and thus participate in the activation of signaling pathways related to the acquisition of the tumor phenotype. RUNX2 is the transcription factor responsible for osteogenic differentiation in mammals. Current studies have confirmed that RUNX2 is closely related to the proliferation, invasion, and bone metastasis of multiple cancer types, such as osteosarcoma, breast cancer (BC), prostate cancer, gastric cancer, colorectal cancer, and lung cancer. Thus, the present study is aimed at evaluating the role of the RUNX2 transcription factor in inhibiting the apoptosis process. Loss-of-function assays using sh-RNA from lentiviral particles and coupled with Annexin/propidium iodide (PI) assays (flow cytometry), immunofluorescence, and quantitative PCR analysis of genes related to cell apoptosis (BAD, BAX, BCL2, BCL-XL, and MCL1) were performed. Silencing assays and Annexin/PI assays demonstrated that when RUNX2 was absent, the percentage of dead cells increased, and the expression levels of the BCL2, BCL-XL, and MCL1 genes were downregulated. Furthermore, to confirm whether the regulatory role of RUNX2 in the expression of these genes is related to its binding to the promoter region, we performed chromatin immunoprecipitation (ChIP) assays. Here, we report that overexpression of the RUNX2 gene in lung cancer may be related to the inhibition of the intrinsic apoptosis pathway, specifically, through direct transcriptional regulation of the antiapoptotic gene BCL2 and indirect regulation of BCL-XL and MCL1.… link
The ACE2 protein acts as a gateway for SARS-CoV-2 in the host cell, playing an essential role in susceptibility to infection by this virus. Genetics and epigenetic mechanisms related to the ACE2 gene are associated with changes in its expression and, therefore, linked to increased susceptibility to infection. Although some variables such as sex, age, and obesity have been described as risk factors for COVID-19, the molecular causes involved in the disease susceptibility are still unknown….. link
Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin‑dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)‑dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non‑senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl‑transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene… link
Descripción: los trastornos del desarrollo sexual (DSD, disorders of sex development) son condiciones congénitas que se caracterizan por la discordancia entre la apariencia externa (masculinidad o feminidad) y la constitución cromosómica o sexo gonadal. Estas manifestaciones están relacionadas con alteraciones a nivel del desarrollo gonadal y del tracto urinario-genital e incluso del sistema reproductivo-endocrino. Dentro de las causas de estas se encuentran las genéticas, las cuales son provocadas por anomalías cromosómicas, en particular de los cromosomas sexuales, o por alteración de genes involucrados con el desarrollo embrionario de los órganos sexuales; como también, anomalías que generen la interrupción de la síntesis de hormonas específicas… link
An adequate bioinformatic pipeline is a valuable tool for understanding cancer mechanisms and identifying transcriptomic biomarkers of cancer and specific to lung cancer. The bioinformatic pipeline was applied to analyze multiple transcriptomic studies and to identify an important group of winning transcription factors coexpressed in gene networks of lung cancer, breast cancer and leukemia, capable of forming coregulatory complexes associated with the regulation of genes involved in tumorigenic processes related to the acquisition of the hallmarks of cancer, as well as lung cancer patients survival. The establishment of a general and specific transcriptional regulatory network is essential to develop key molecular tools for prevention, early diagnosis, and treatment aimed at precision personalized medicine of cancer… link
2021
Isodicentric Y chromosome [idic(Y)] is one of the most common structural abnormalities of the Y chromosome and has been observed in patients with reproductive disorders and in patients with disorders of sexual development. Most idic(Y) chromosomes are found in mosaic form with a 45,X cell line. These chromosomes are highly unstable during mitosis due to the presence of 2 centromers, which explains their probable loss in early mitosis or mitosis of the embryo and therefore the presence of the 45,X line. It has been hypothesized that the proportion of 45,X cells in various tissues probably influences the phenotypic sex of individuals carrying an idic(Y) chromosome, ranging from infertile men, hypospadias, ambiguous genitalia, and Turner syndrome to sex reversal. In this article we present 5 cases of patients with idic(Y) referred for suspected disorder of sex development (DSD), 3 with a male assignment and 2 with a female assignment. All cases have variable clinical characteristics, which were assessed by the transdisciplinary group of Disorders of Sex Development of the Hospital Universitario San Ignacio, Bogotá, Colombia. Patients were analyzed by conventional and molecular cytogenetics using high-resolution G-band and FISH techniques. Our findings highlight the importance of cytogenetic studies in the diagnosis of DSD patients….. link
La etiología de la disgenesia gonadal y el síndrome ovotesticular se desconoce en la mayoría de los casos. Para realizar la caracterización citogenética y molecular de un grupo de pacientes con síndrome ovotesticular y disgenesia gonadal completa a partir de muestras de sangre periférica y tejido gonadal.. link
La interrupción de los procesos de determinación o diferenciación sexual por cualquier factor genético o ambiental puede resultar en un trastorno del desarrollo sexual (TDS) con discordancia entre el sexo cromosómico, gonadal y anatómico. Dicha discordancia tendrá diferentes expresiones en el fenotipo, incluidas anomalías en los genitales internos y/o genitales externos..… link
Disorders of sexual development are a group of congenital diseases that affect the normal formation of genital structures. Within the pathophysiologic mechanisms described, there are genetic factors caused by chromosomal or sex-determining gene alterations. Therefore, chromosomal analysis is an essential priority in the diagnostic approach. Alterations in the chromosomes and the SRY gene as a cause of disorder of sexual development was analyzed herein….. link
Fanconi anemia is a genetic syndrome clinically characterized by congenital malformations that affect several human systems, leads to progressive bone marrow failure and predisposes an individual to cancer, particularly in the urogenital area as well as the head and neck. It is commonly caused by the biallelic compromise of one of 22 genes involved in the FA/BRCA repair pathway in most cases. The diagnosis is based on clinical suspicion and confirmation using genetic analysis, where the chromosomal breakage test is considered the gold standard. Other diagnostic methods used include western blotting, multiplex ligation‑dependent probe amplification and next‑generation sequencing. This genetic condition has variable expressiveness, which makes early diagnosis difficult in certain cases. Although early diagnosis does not currently allow for improved cure rates for this condition, it does enable healthcare professionals to perform a specific systematic follow‑up and, if indicated, a bone marrow transplantation that improves the mobility and mortality of affected individuals. The present review article is a theoretical revision of the pathophysiology, clinical manifestations and diagnosis methods intended for different specialists and general practitioners to improve the diagnosis of this condition…. link
Descripción: los trastornos del desarrollo sexual (DSD, disorders of sex development) son condiciones congénitas que se caracterizan por la discordancia entre la apariencia externa (masculinidad o feminidad) y la constitución cromosómica o sexo gonadal. Estas manifestaciones están relacionadas con alteraciones a nivel del desarrollo gonadal y del tracto urinario-genital e incluso del sistema reproductivo-endocrino. Dentro de las causas de estas se encuentran las genéticas, las cuales son provocadas por anomalías cromosómicas, en particular de los cromosomas sexuales, o por alteración de genes involucrados con el desarrollo embrionario de los órganos sexuales; como también, anomalías que generen la interrupción de la síntesis de hormonas específicas… link
An adequate bioinformatic pipeline is a valuable tool for understanding cancer mechanisms and identifying transcriptomic biomarkers of cancer and specific to lung cancer. The bioinformatic pipeline was applied to analyze multiple transcriptomic studies and to identify an important group of winning transcription factors coexpressed in gene networks of lung cancer, breast cancer and leukemia, capable of forming coregulatory complexes associated with the regulation of genes involved in tumorigenic processes related to the acquisition of the hallmarks of cancer, as well as lung cancer patients survival. The establishment of a general and specific transcriptional regulatory network is essential to develop key molecular tools for prevention, early diagnosis, and treatment aimed at precision personalized medicine of cancer… link
2020
Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as ‘other’ since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad‑spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations…. link
Disorders of sexual development (DSD) are conditions with an atypical chromosomal, gonadal or phenotypic sex, which leads to differences in the development of the urogenital tract and different clinical phenotypes. Some genes have been implicated in the sex development during gonadal and functional differentiation where the maintenance of the somatic sex of the gonad as either male or female is achieved by suppression of the alternate route. The diagnosis of DSD requires a structured approach, involving a multidisciplinary team and different molecular techniques. We discuss the dimorphic genes and the specific pathways involved in gonadal differentiation, as well as new techniques for genetic analysis and their diagnostic value including epigenetic mechanisms, expanding the evidence in the diagnostic approach of individuals with DSD to increase knowledge of the etiology… link
Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra‑osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS‑FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS‑FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS‑FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS‑FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS‑FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS‑FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region..… link
Analysis of patients with chromosomal abnormalities, including Turner syndrome and Klinefelter syndrome, has highlighted the importance of X-linked gene dosage as a contributing factor for disease susceptibility. Escape from X-inactivation and X-linked imprinting can result in transcriptional differences between normal men and women as well as in patients with sex chromosome abnormalities….. link
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VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development…. link
Hexanucleotide repeat expansions of the G4C2 motif in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Tissues from C9ALS/FTD patients and from mouse models of ALS show RNA foci, dipeptide-repeat proteins, and notably, widespread alterations in the transcriptome. Epigenetic processes regulate gene expression without changing DNA sequences and therefore could account for the altered transcriptome profiles in C9ALS/FTD; here, we explore whether the critical repressive marks H3K9me2 and H3K9me3 are altered in a recently developed C9ALS/FTD BAC mouse model (C9BAC)…. link
El proceso transición epitelio mesénquima (TEM) permite que una célula epitelial de manera temporal, adquiera un fenotipo mesenquimal como respuesta a un estímulo interno o externo. Este proceso se caracteriza por la activación y represión de genes involucrados en diferentes vías de señalización asociadas con migración, invasión y apoptosis, entre otros. En este proceso la epigenética cumple un papel fundamental. La epigenética comprende cuatro mecanismos: metilación de ADN, modificación covalente de histonas, ARN no codificantes (ARNnc) y complejos remodeladores de la cromatina, que regulan la expresión de un gen sin alterar su secuencia. En esta revisión de tema los autores describen los principales mecanismos epigenéticos involucrados en la regulación de la expresión de genes que se activan y reprimen concomitantemente en las tres fases del proceso TEM: fase no migratoria, fase premigratoria y fase migratoria… Link
2019
Two sisters phenotypically normal females, presenting with tumor abdominal mass with histopathological findings of teratoma and gonadoblastoma associated to 46,XY male-to-female sex reversal syndrome, secondary to a duplication in DAX-1, possibly inherited of maternal gonadal mosaicism. Copy number variation and functional effects of the duplication were done by MLPA multiplex ligation-dependent probe amplification and real time PCR. DAX-1, also known as dosage sensitive sex reversal gene (DSS), is considered the most likely candidate gene involved in XY gonadal dysgenesis when overexpressed. The excess of DAX-1 gene disturbs testicular development by down regulation of SF-1, WT1, and SOX9. This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9–SF1….. link
Epidemiological and clinical evidence points cancer comorbidity with pulmonary chronic disease. The acquisition of some hallmarks of cancer by cells affected with lung pathologies as a cell adaptive mechanism to a shear stress, suggests that could be associated with the establishment of tumoral processes…. link
Expression of Runx2/p57 is a hallmark of the osteoblast-lineage identity. Although several regulators that control the expression of Runx2/p57 during osteoblast-lineage commitment have been identified, the epigenetic mechanisms that sustain this expression in differentiated osteoblasts remain to be completely determined. Here, we assess epigenetic mechanisms associated with Runx2/p57 gene transcription in differentiating MC3T3 mouse osteoblasts. Our results show that an enrichment of activating histone marks at the Runx2/p57 P1 promoter is accompanied by the simultaneous interaction of Wdr5 and Utx proteins, both are components of COMPASS complexes. Knockdown of Wdr5 and Utx expression confirms the activating role of both proteins at the Runx2-P1 promoter. Other chromatin modifiers that were previously described to regulate Runx2/p57 transcription in mesenchymal precursor cells (Ezh2, Prmt5, and Jarid1b proteins) were not found to contribute to Runx2/p57 transcription in full-committed osteoblasts. We also determined the presence of additional components of COMPASS complexes at the Runx2/p57 promoter, evidencing that the Mll2/COMPASS- and Mll3/COMPASS-like complexes bind to the P1 promoter in osteoblastic cells expressing Runx2/p57 to modulate the H3K4me1 to H3K4me3 transition…… link
The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.
Mullerian Ducts; Anti-Mullerian Hormone; Persistent Mullerian duct syndrome [Supplementary Concept]; Disorders of Sex Development…. link
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unt‑related transcription factor (RUNX) proteins belong to a transcription factors family known as master regulators of important embryonic developmental programs. In the last decade, the whole family has been implicated in the regulation of different oncogenic processes and signaling pathways associated with cancer. Furthermore, a suppressor tumor function has been also reported, suggesting the RUNX family serves key role in all different types of cancer. In this review, the known biological characteristics, specific regulatory abilities and experimental evidence of RUNX proteins will be analyzed to demonstrate their oncogenic potential and tumor suppressor abilities during oncogenic processes, suggesting their importance as biomarkers of cancer. Additionally, the importance of continuing with the molecular studies of RUNX proteins’ and its dual functions in cancer will be underlined in order to apply it in the future development of specific diagnostic methods and therapies against different types of cancer….. link
2018
Lung cancer is the leading cause of cancer death in the world. The high mortality rate of this pathology is directly related to its late detection, since its symptoms can be masked by other diseases of lower risk. Although in recent years the number of research related to this subject has increased, molecular mechanisms that trigger this disease remains poorly understood. Experimental models are therefore vital for use in research. Immortalized cell lines have inherent limitations. Explanted tumoral cells obtained by transthoracic needle biopsy can be a potential source of primary culture of human lung tumor cells. Tumor specimens from 14 patients suspected of primary or metastatic lung cancer were obtained by CT-guided transthoracic lung biopsy. Solid tumors were mechanically disaggregated under a stereoscope. Cells were cultured in Base C growth media supplemented with 5% fetal bovine serum in 24-well cell culture plates. Primary lung cancer cell culture was successfully cultured from 12 out of 14 patients. Once a confluent monolayer was obtained, cells were enzymatically harvested and passaged to Petri culture dishes. These primary cell cultures were characterized by cytogenetic tests and gene expression analysis of diagnostic markers. These primary cell cultures revealed chromosome rearrangements and changes in their chromosome complement typical of tumoral cells. Additionally, Fluorescence in situ hybridization analysis demonstrated that three cultures exhibited EGFR amplification. Finally, expression profiles of CK7, NAPSIN A, TTF1, and P63 genes allowed in some cases to confirm sample tumor phenotype. These results demonstrate that primary lung cancer cell culture is possible from percutaneous puncture and provides an important biological source to asses and investigate the molecular mechanisms of lung cancer…… link
2017
En el mundo, el cáncer de pulmón es la principal causa de muerte por neoplasias, y ello se debe a que su detección ocurre en los estadios más avanzados de la enfermedad (III o IV). Dentro de los factores de riesgo descritos en la generación de este cáncer se encuentran el consumo de tabaco, la inhalación y posterior acumulación de radón y asbestos en el tejido pulmonar, la contaminación ambiental y la presencia de alteraciones genéticas y de factores epigenéticos que regulan la expresión o represión de genes involucrados con el desarrollo tumoral. Los mecanismos de regulación epigenética que pueden intervenir en la progresión tumoral son: la metilación del ADN, la modificación covalente de histonas y la presencia de ARN no codificantes. En las diferentes etapas de progresión tumoral se ha descrito la participación de los mecanismos epigenéticos
como reguladores de procesos relacionados con proliferación, transición epitelio-mesénquima, metástasis, apoptosis, entre otros. Esta revisión de tema se enfoca en describir el papel de la epigenética en la progresión tumoral pulmonar y plantea la importancia de ampliar el conocimiento en esta disciplina con fines de diagnóstico y tratamiento…. link
Los desórdenes del desarrollo sexual (DDS) se presentan en 0,76 por cada 4.500 nacimientos. El manejo es complejo y requiere de la habilidad de múltiples especialidades, lo cual tendrá un impacto positivo en el pronóstico y reducción de la discapacidad de estos pacientes. El objetivo del presente trabajo es describir una población manejada por un grupo transdisciplinario de DDS en nuestro medio y establecer las limitantes que enfrentan nuestros pacientes en la atención de sus condiciones… Link
La transición epitelio mesénquima (EMT) es un proceso compuesto de diferentes fases, donde una célula epitelial adquiere un fenotipo mesenquimal. Dentro de los cambios involucrados se encuentran: pérdida de la polaridad celular, adquisición de una capacidad migratoria, capacidad invasora, resistencia a la apoptosis y aumento en la producción de componentes de la matriz extracelular. Todos estos cambios ocurren como una consecuencia de la activación y represión de genes involucrados con rutas de señalización específicas relacionadas con este evento. La EMT está relacionada con procesos fisiológicos y patológicos como el cáncer. Consta de tres fases: una de células no migratorias, células premigratorias y células migratorias; cada una de ellas producto de diferentes señales intra o extracelulares, factores de transcripción (TGF-B, Snail, TWIST, Sox, Slug, ZEB1, entre otras) y proteínas involucradas (E-cadherina, integrina, vimentina, ocludinas y claudinas)…Link
2016
During hippocampal neuron differentiation, the expression of critical inducers of non-neuronal cell lineages must be efficiently silenced. Runx2 transcription factor is the master regulator of mesenchymal cells responsible for intramembranous osteoblast differentiation and formation of the craniofacial bone tissue that surrounds and protects the central nervous system (CNS) in mammalian embryos. The molecular mechanisms that mediate silencing of the Runx2 gene and its downstream target osteogenic-related genes in neuronal cells have not been explored. Here, we assess the epigenetic mechanisms that mediate silencing of osteoblast-specific genes in CNS neurons. In particular, we address the contribution of histone epigenetic marks and histone modifiers on the silencing of the Runx2/p57 bone-related isoform in rat hippocampal tissues at embryonic to adult stages. Our results indicate enrichment of repressive chromatin histone marks and of the Polycomb PRC2 complex at the Runx2/p57 promoter region. Knockdown of PRC2 H3K27-methyltransferases Ezh2 and Ezh1, or forced expression of the Trithorax/COMPASS subunit Wdr5 activates Runx2/p57 mRNA expression in both immature and mature hippocampal cells. Together these results indicate that complementary epigenetic mechanisms progressively and efficiently silence critical osteoblastic genes during hippocampal neuron differentiation…. link
2015
Transcription factor Runx2 controls bone development and osteoblast differentiation by regulating expression of a significant number of bone-related target genes. Here, we report that transcriptional activation and repression of the Runx2 gene via its osteoblast-specific P1 promoter (encoding mRNA for the Runx2/p57 isoform) is accompanied by selective deposition and elimination of histone marks during differentiation of mesenchymal cells to the osteogenic and myoblastic lineages. These epigenetic profiles are mediated by key components of the Trithorax/COMPASS-like and Polycomb group complexes together with histone arginine methylases like PRMT5 and lysine demethylases like JARID1B/KDM5B. Importantly, knockdown of the H3K4me2/3 demethylase JARID1B, but not of the demethylases UTX and NO66, prevents repression of the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells. The epigenetically forced expression of Runx2/p57 and osteocalcin, a classical bone-related target gene, under myoblastic-differentiation is accompanied by enrichment of the H3K4me3 and H3K27ac marks at the Runx2 P1 promoter region. Our results identify JARID1B as a key component of a potent epigenetic switch that controls mesenchymal cell fate into myogenic and osteogenic lineages…. link
It´s on record that when a young aspirant asked Faraday the secret of his success as a scientific investigator, he replied: "The secret is comprised in three words - Work, Finish, Publish."
Michael Faraday
Do I need Nature or Science papers for a successful career in science?
One of the unspoken rules in research is that a successful career in science is only possible with one or more papers with an impact factor above 10 or higher. This belief creates a lot of peer pressure among young scientists and may be even one of the causes of increasing numbers of scientific fraud cases. But is it true?
Writing an Abstract
An abstract is a 150- to 250-word paragraph that provides readers with a quick overview of your essay or report and its organization. It should express your thesis (or central idea) and your key points; it should also suggest any implications or applications of the research you discuss in the paper.
