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1.
Sci Immunol ; 8(80): eabm6360, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36735776

RESUMEN

Oncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of tumor-specific antigens. We show that mouse normal tissues and tumor cell lines express wide but distinct ranges of mRNA junctions between exons and TEs, some of which are tumor specific. Immunopeptidome analyses in tumor cell lines identified peptides derived from exon-TE splicing junctions associated to MHC-I molecules. Exon-TE junction-derived peptides were immunogenic in tumor-bearing mice. Both prophylactic and therapeutic vaccinations with junction-derived peptides delayed tumor growth in vivo. Inactivation of the TE-silencing histone 3-lysine 9 methyltransferase Setdb1 caused overexpression of new immunogenic junctions in tumor cells. Our results identify exon-TE splicing junctions as epigenetically controlled, immunogenic, and protective tumor antigens in mice, opening possibilities for tumor targeting and vaccination in patients with cancer.


Asunto(s)
Antígenos de Neoplasias , Elementos Transponibles de ADN , Animales , Ratones , Elementos Transponibles de ADN/genética , Antígenos de Neoplasias/genética , Exones/genética , ARN Mensajero , Línea Celular Tumoral
2.
Tuberculosis (Edinb) ; 127: 102045, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33434785

RESUMEN

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.


Asunto(s)
Corticoesteroides/sangre , Antituberculosos/uso terapéutico , Infecciones por VIH/sangre , VIH-1/patogenicidad , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Adulto , Biomarcadores/sangre , Coinfección , Citocinas/sangre , Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Interacciones Huésped-Patógeno , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Estudios Prospectivos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/microbiología , Linfocitos T Reguladores/virología , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis/sangre , Tuberculosis/inmunología , Tuberculosis/microbiología
3.
Proc Natl Acad Sci U S A ; 116(51): 25839-25849, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31776254

RESUMEN

Naive CD4+ T lymphocytes differentiate into different effector types, including helper and regulatory cells (Th and Treg, respectively). Heritable gene expression programs that define these effector types are established during differentiation, but little is known about the epigenetic mechanisms that install and maintain these programs. Here, we use mice defective for different components of heterochromatin-dependent gene silencing to investigate the epigenetic control of CD4+ T cell plasticity. We show that, upon T cell receptor (TCR) engagement, naive and regulatory T cells defective for TRIM28 (an epigenetic adaptor for histone binding modules) or for heterochromatin protein 1 ß and γ isoforms (HP1ß/γ, 2 histone-binding factors involved in gene silencing) fail to effectively signal through the PI3K-AKT-mTOR axis and switch to glycolysis. While differentiation of naive TRIM28-/- T cells into cytokine-producing effector T cells is impaired, resulting in reduced induction of autoimmune colitis, TRIM28-/- regulatory T cells also fail to expand in vivo and to suppress autoimmunity effectively. Using a combination of transcriptome and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses for H3K9me3, H3K9Ac, and RNA polymerase II, we show that reduced effector differentiation correlates with impaired transcriptional silencing at distal regulatory regions of a defined set of Treg-associated genes, including, for example, NRP1 or Snai3. We conclude that TRIM28 and HP1ß/γ control metabolic reprograming through epigenetic silencing of a defined set of Treg-characteristic genes, thus allowing effective T cell expansion and differentiation into helper and regulatory phenotypes.


Asunto(s)
Diferenciación Celular/fisiología , Reprogramación Celular/fisiología , Proteínas Cromosómicas no Histona/metabolismo , Epigénesis Genética/fisiología , Linfocitos T/metabolismo , Proteína 28 que Contiene Motivos Tripartito/metabolismo , Animales , Autoinmunidad/fisiología , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/genética , Plasticidad de la Célula/fisiología , Reprogramación Celular/genética , Homólogo de la Proteína Chromobox 5 , Colon/patología , Citocinas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Silenciador del Gen , Histonas/metabolismo , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Transcriptoma , Proteína 28 que Contiene Motivos Tripartito/genética
4.
Sci Rep ; 9(1): 187, 2019 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-30655556

RESUMEN

CD8+T cells contribute to tuberculosis (TB) infection control by inducing death of infected macrophages. Mycobacterium tuberculosis (Mtb) infection is associated with increased PD-1/PD-L1 expression and alternative activation of macrophages. We aimed to study the role of PD-1 pathway and macrophage polarization on Mtb-specific CD8+T cell-induced macrophage death. We observed that both PD-L1 on CD14+ cells and PD-1 on CD8+T cells were highly expressed at the site of infection in pleurisy TB patients' effusion samples (PEMC). Moreover, a significant increase in CD8+T cells' Mtb-specific degranulation from TB-PEMC vs. TB-PBMC was observed, which correlated with PD-1 and PDL-1 expression. In an in vitro model, M1 macrophages were more susceptible to Mtb-specific CD8+T cells' cytotoxicity compared to M2a macrophages and involved the transfer of cytolytic effector molecules from CD8+T lymphocytes to target cells. Additionally, PD-L1 blocking significantly increased the in vitro Ag-specific CD8+T cell cytotoxicity against IFN-γ-activated macrophages but had no effect over cytotoxicity on IL-4 or IL-10-activated macrophages. Interestingly, PD-L1 blocking enhanced Mtb-specific CD8+ T cell killing of CD14+ cells from human tuberculous pleural effusion samples. Our data indicate that PD-1/PD-L1 pathway modulates antigen-specific cytotoxicity against M1 targets in-vitro and encourage the exploration of checkpoint blockade as new adjuvant for TB therapies.


Asunto(s)
Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/inmunología , Muerte Celular , Macrófagos/microbiología , Mycobacterium tuberculosis/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Recolección de Muestras de Sangre , Linfocitos T CD8-positivos/microbiología , Humanos , Macrófagos/patología , Derrame Pleural/microbiología , Linfocitos T Citotóxicos/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control
5.
Sci Rep ; 8(1): 6692, 2018 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-29703963

RESUMEN

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.


Asunto(s)
Coinfección/complicaciones , Coinfección/patología , Deshidroepiandrosterona/sangre , Enfermedades del Sistema Endocrino/patología , Infecciones por VIH/patología , Tuberculosis/patología , Recuento de Linfocito CD4 , Cromatografía Líquida de Alta Presión , Deshidroepiandrosterona/análogos & derivados , Infecciones por VIH/complicaciones , Humanos , Factores Inmunológicos/sangre , Plasma/química , Espectrometría de Masas en Tándem , Tuberculosis/complicaciones
6.
Front Immunol ; 8: 528, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28536578

RESUMEN

Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4+CD25-FoxP3+ Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4+CD25+FoxP3+ Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg. Also, IL-10, TGF-ß, IFN-γ production, and the suppressor capacity of uTregs were analyzed in cocultures with effector lymphocytes and compared with the effect of regulatory T cells (Tregs). We found diminished expression of CD39 and higher levels of PD1 on uTreg compared to cTreg in both HIV-TB and healthy donors (HD). In addition, uTreg and cTreg showed differences in maturation status in both HIV-TB and HD groups, due to the expansion of effector memory uTregs. Interestingly, both HIV-TB and HD showed a pronounced production of IFN-γ in uTreg population, though no significant differences were observed for IL-10 and TGF-ß production between uTreg and cTreg. Moreover, IFN-γ+ cells were restricted to the CD39- uTreg population. Finally, when the suppressor capacity was evaluated, both uTreg and cTreg inhibited polyclonal T cell-proliferation and IFN-γ production in a similar extent. These findings suggest that uTregs, which are expanded during HIV-TB coinfection, exert regulatory functions in a similar way to cTregs despite an altered surface expression of Treg characteristic markers and differences in cytokine production.

7.
Eur J Immunol ; 45(9): 2529-41, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26047476

RESUMEN

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection.


Asunto(s)
Deshidroepiandrosterona/farmacología , Infecciones por VIH/inmunología , Tuberculosis Latente/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Tuberculosis Pulmonar/inmunología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Linfocitos T CD4-Positivos/virología , Diferenciación Celular/efectos de los fármacos , Coinfección , Estudios Transversales , Femenino , Infecciones por VIH/microbiología , Infecciones por VIH/virología , VIH-1/inmunología , Interacciones Huésped-Patógeno , Humanos , Tuberculosis Latente/microbiología , Tuberculosis Latente/virología , Activación de Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Cultivo Primario de Células , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/microbiología , Linfocitos T Citotóxicos/virología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/virología
8.
Biomed Res Int ; 2015: 461093, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26075241

RESUMEN

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Coinfección , Citocinas/inmunología , Sistema Endocrino/inmunología , Infecciones por VIH , VIH-1/inmunología , Hormonas/inmunología , Tuberculosis , Coinfección/inmunología , Coinfección/terapia , Infecciones por VIH/inmunología , Infecciones por VIH/terapia , Humanos , Tuberculosis/inmunología , Tuberculosis/terapia
9.
Rev Alerg Mex ; 61(1): 14-23, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24912998

RESUMEN

DRESS syndrome (Drug rash with Eosinophilia and Systemic Symptoms) is an idiosyncratic reaction (type B), characterized by peripheral eosinophilia and systemic symptoms, such as fever, rash, lymphadenopathy, hepatitis, atypical lymphocytes and elevation of liver enzymes at least twice its normal level or increase of alanine amino transferase (ALT) >100 U/L. Its incidence is of 1/1,000 to 10,000 exposures and its mortality is of 10%-20%. Treatment is based on steroids and on the suspension of the suspect drug. This paper reports the cases of six patients with DRESS syndrome attended at Centro Medico Nacional Siglo XXI, Mexico City, from September 2012 to September 2013, which accounted for 12.5% of patients attended with adverse reactions to drugs.


El síndrome DRESS (exantema inducido por fármacos con eosinofilia y síntomas sistémicos) es una reacción idiosincrática (tipo B), que se distingue por eosinofilia periférica y síntomas sistémicos, como fiebre, exantema, linfadenopatía, hepatitis, linfocitos atípicos y elevación de enzimas hepáticas al menos dos veces su valor normal o incremento de la alanina aminotransferasa (ALT) >100 U/L. La incidencia es de 1 por cada 1,000 a 10,000 exposiciones y su mortalidad es de 10 a 20%. El tratamiento se basa en esteroides y en la suspensión del fármaco sospechoso. Se comunican los casos de seis pacientes con síndrome DRESS atendidos en el Centro Médico Nacional Siglo XXI, de septiembre de 2012 a septiembre de 2013, que correspondieron a 12.5% de los pacientes atendidos con reacciones adversas a fármacos.


Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos/epidemiología , Corticoesteroides/uso terapéutico , Anciano , Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Diagnóstico Diferencial , Susceptibilidad a Enfermedades , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Modelos Biológicos , Fenitoína/efectos adversos , Prevalencia , Población Urbana , Adulto Joven
10.
Int Immunol ; 25(7): 405-11, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23446847

RESUMEN

Cell-mediated immunity, cytokines induced during the specific immune response and T-cell populations are crucial factors for containing Mycobacterium tuberculosis infection. Recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids and dehydroepiandrosterone, DHEA) and the function of antigen-presenting cells (APCs). Therefore, we investigated the role of adrenal hormones on the functional capacity of M. tuberculosis-induced dendritic cells (DCs). Cortisol significantly inhibited the functions of M. tuberculosis-induced DCs. Interestingly, the presence of DHEA enhanced the M. tuberculosis-induced expression of MHC I, MHC II and CD86 and also increased ERK1/2 phosphorylation. Moreover, DHEA improved the production of IL-12 in response to M. tuberculosis stimulation, diminished IL-10 secretion and could not modify TNF-α synthesis. Importantly, we observed that DHEA enhanced the antigen-specific T-cell proliferation and IFN-γ production induced by M. tuberculosis-stimulated DC. These data show for the first time the relevance of the adrenal axis (especially of DHEA) in the modulation of DC function in the context of tuberculosis, a disease where the induction of a Th1 environment by APCs is crucial for the development of an effective immune response to the mycobacteria.


Asunto(s)
Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Mycobacterium tuberculosis/inmunología , Esteroides/farmacología , Tuberculosis/inmunología , Células Cultivadas , Citocinas/metabolismo , Deshidroepiandrosterona/farmacología , Células Dendríticas/citología , Células Dendríticas/metabolismo , Humanos , Hidrocortisona/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Fenotipo , Esteroides/administración & dosificación , Tuberculosis/microbiología
11.
Chem Biol Interact ; 199(3): 185-91, 2012 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-22940207

RESUMEN

Cisplatin (Cs) is a chemotherapeutic agent able to generate reactive oxygen species (ROS) which are linked to several side effects of the drug. Even when it is known that Cs produces Leydig cell dysfunction, it is unknown whether this particular side effect is mediated by ROS. The aim of this study was to evaluate the in vitro effects of Cs on testosterone production and the participation of ROS in this effect. We demonstrate that Cs promotes the generation of ROS in a time-, and concentration-dependent fashion, not only in mouse testicular interstitial cells but also in MA-10 Leydig cells. Also, Cs inhibits testosterone synthesis in a concentration-dependent fashion (5-50 µM for 4 h) and to a similar extent, in cells exposed to human chorionic gondadotropin hormone (hCG), to an analog of the second messenger cAMP (8Br-cAMP) or to a freely diffusible cholesterol analog (22R-hydroxycholesterol). However, this treatment does not inhibit the conversion of pregnenolone to testosterone. These data suggest that Cs exerts its inhibitory action on testosterone synthesis by an action at the level of P450scc. We also demonstrated that an antioxidant impairs the inhibitory effect of Cs on the conversion of the cholesterol analog into pregnenolone and that Cs does not change the expression level of P450scc mRNA. Therefore, it is concluded that Cs inhibits testosterone synthesis by a mechanism that includes the inhibition of P450scc by ROS.


Asunto(s)
Antineoplásicos/efectos adversos , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/antagonistas & inhibidores , Cisplatino/efectos adversos , Testosterona/biosíntesis , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Animales , Secuencia de Bases , Línea Celular , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Gonadotropina Coriónica/farmacología , Humanos , Hidroxicolesteroles/farmacología , Técnicas In Vitro , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Pregnenolona/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo
12.
Int J Oncol ; 41(1): 125-34, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22485252

RESUMEN

Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Papilar/tratamiento farmacológico , Carcinoma de Células Renales/tratamiento farmacológico , Flavonoides/farmacología , Neoplasias Renales/tratamiento farmacológico , Receptores de Hidrocarburo de Aril/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Hidrocarburo de Aril Hidroxilasas/genética , Carcinoma Papilar/patología , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1 , Genes Reporteros , Humanos , Neoplasias Renales/patología , Luciferasas/biosíntesis , Luciferasas/genética , Terapia Molecular Dirigida , Regiones Promotoras Genéticas , Activación Transcripcional/efectos de los fármacos
13.
Arch. Inst. Cardiol. Méx ; 67(1): 46-50, ene.-feb. 1997. tab
Artículo en Español | LILACS | ID: lil-195863

RESUMEN

Objetivo. Se revisó la experiencia en el diagnóstico y tratamiento de la endocarditis infecciosa (EI) en el Instituto Nacional de Cardiología " Ignacio Chávez" durante un periodo de cinco años. Material y métodos. De forma retrospectiva, se revisaron los expedientes de aqellos pacientes que durante un periodo de cinco años (1990-1994) ingresaron a nuestro hospital con diagnóstico definitivo (Grupo I) y de alta probabilidad (Grupo II). Se registraron datos acerca de su historia clínica, hallazgoz microbiológicos, ecocardiográficos y quirúrgicos. Se revisó la evolución extrahospitalaria. Por último se determinó la sensibilidad de los criterios de von Reyn y de la Universidad de Duke para diagnósticar de EI. Resultados. 131 pacientes entraron a formar parte del estudio, 99 en el Grupo I y 32 en el Grupo II. La edad promedio fue de 35 años. En 88 pacientes se demostró endocarditis de vávula nativa (EVN) y en 43 pacientes endocarditis protésica (EP). El estreptococo fue el germen causal de endocaditis con más frecuencia (48.8 por ciento). Un 16.7 por ciento de las EI fueron de cultivo negativo. La sensibilidad de la ecocardiografía transesofágica fue superior a la transtorácica en el diagnóstico de vegetaciones (76 por ciento vs 55 por ciento) y abscesos (30 por ciento vs 16.5 por ciento). Los hallazgos quirúrgicos más frecuentes fueron la presencia de vegetaciones (95 por ciento) y abscesos (23 por ciento). La mortalidad en el Grupo I fue de 22 por ciento y de 45 por ciento en el Grupo II (p< 0.05). La sensibilidad diagnóstica de los criterios e von Reyn y de la Universidad de Duke fue 49 por ciento y 85.5 por ciento, respectivamente (p<0.05). Durante el seguimiento, se registraron 2 casos de endocarditis de repetición y no hubo fallecimientos. Conclusión. La EI constituye e nuestro medio una urgencia médico-quirúrgica. La alta mortalidad observada, en los pacientes que únicamente recibieron tratamiento médico, implica que el tratamiento quirúrgico deberá de plantearse de forma temprana.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Ecocardiografía , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/etiología , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Factores de Riesgo , Sensibilidad y Especificidad
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