RESUMEN
Capnocytophaga canimorsus is a commensal organism of canine and feline oral flora known to cause severe infections most frequently reported in immunocompromised hosts. We describe a case of bacterial aortitis secondary to C. canimorsus in an 80-year-old immunocompetent female, who presented with fever, non-specific lower back, and pelvic pain. Infection was confirmed with positive blood cultures and serial imaging.
Asunto(s)
Aortitis , Mordeduras y Picaduras , Enfermedades de los Gatos , Enfermedades de los Perros , Infecciones por Bacterias Gramnegativas , Anciano de 80 o más Años , Animales , Antibacterianos/uso terapéutico , Aortitis/tratamiento farmacológico , Mordeduras y Picaduras/complicaciones , Mordeduras y Picaduras/tratamiento farmacológico , Capnocytophaga , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , HumanosRESUMEN
Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in childhood. Despite the advances in treatment, about 20% of patients relapse and/or die, indicating the need for different therapies for this group. Zebularine (ZB) is a potent DNA methyltransferase (DNMT) inhibitor and has been associated with gene demethylation and enhancement of tumor chemosensitivity. This study aimed to evaluate the effects of ZB, alone or combined with chemotherapeutics (methotrexate and vincristine), on childhood ALL cell lines. Cell proliferation, apoptosis, and clonogenic capacity were studied in Jurkat and ReH cell lines. Bisulfite modification, followed by methylation-specific PCR was carried out to evaluate aryl hydrocarbon receptor (AhR) methylation status. Gene expression of DNMT1, DNMT3a, DNMT3b, and AhR was assessed using qRT-PCR. Both cell cultures were sensitive to ZB, showing a dose-dependent and time-dependent response (P<0.05). ZB induced apoptosis and decreased clonogenic capacity in both cell lines. Combination with methotrexate resulted in a strong synergistic effect, whereas combination with vincristine led to an antagonistic response in both cell lines. ZB treatment decreased gene expression of the three DNMTs and induced AhR gene promoter demethylation and its re-expression. These results indicate that ZB may be a promising drug for the adjuvant treatment of ALL, mainly when combined with methotrexate.
Asunto(s)
Antineoplásicos/farmacología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Citidina/análogos & derivados , Metilasas de Modificación del ADN/antagonistas & inhibidores , Metotrexato/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Apoptosis/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular Tumoral , Citidina/farmacología , Antagonismo de Drogas , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Humanos , Metilación , Receptores de Hidrocarburo de Aril/genética , Vincristina/farmacologíaRESUMEN
The present study evaluated the expression profile of 19 genes previously reported in microarray studies and associated with resistance or sensitivity to vincristine (RPLP2, CD44, TCFL5, KCNN1, TRIM24), prednisolone (F8A, CDK2AP1, BLVRB, CD69), daunorubicin (MAP3K12, SHOC2, PCDH9, EGR1, KCNN4) and l-asparaginase (GPR56, MAN1A1, CLEC11A, IGFBP7, GATA3). We studied 140 bone marrow samples at diagnosis from children with acute lymphoblastic leukemia (ALL) treated according to the Brazilian Childhood Leukemia Treatment Group (GBTLI) ALL-99 protocol. The expression profiles of the genes listed above were analyzed by real-time quantitative polymerase chain reaction (PCR) and then related to the clinical and biological prognostic factors. The results showed significant associations (p ≤ 0.05) between the expression levels of genes GPR56, BLVRB, IGFBP7 and white blood cell (WBC) count at diagnosis; GATA3, MAN1A1, CD44, MAP3K12, CLEC11A, SHOC2 and CD10 B-lineage ALL; TCFL5 and bone marrow status at day 14; MAP3K12 and TRIM24 and bone marrow status at day 28; and CD69, TCFL5 and TRIM24 genes and ETV6/RUNX1 positive ALL. The up-regulation of SHOC2 was also associated with better 5-year event-free survival (EFS) in univariate and multivariate analysis (p = 0.02 and p = 0.03, respectively). These findings highlight genes that could be associated with clinical and biological prognostic factors in childhood ALL, suggesting that these genes may characterize and play a role in the treatment outcome of some ALL subsets.