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1.
Clin Cancer Res ; 30(10): 2170-2180, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38437679

RESUMEN

PURPOSE: DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. EXPERIMENTAL DESIGN: We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls. RESULTS: Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS. CONCLUSIONS: The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.


Asunto(s)
Metilación de ADN , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/diagnóstico , Estudios de Casos y Controles , Anciano , Adulto , Epigénesis Genética , Singapur/epidemiología , Mutación , Predisposición Genética a la Enfermedad , Factores de Riesgo
2.
Bioeng Transl Med ; 8(3): e10483, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37206213

RESUMEN

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis and high mortality, with no curative treatment to date as limited trafficking across the blood-brain barrier (BBB) combined with tumor heterogeneity often leads to therapeutic failure. Although modern medicine poses a wide range of drugs that are otherwise efficacious in treating other tumors, they often do not achieve therapeutic concentrations in the brain, hence driving the need for more effective drug delivery strategies. Nanotechnology, an interdisciplinary field, has been gaining immense popularity in recent years for remarkable advancements such as nanoparticle (NP) drug carriers, which possess extraordinary versatility in modifying surface coatings to home in on target cells, including those beyond the BBB. In this review, we will be highlighting recent developments in biomimetic NPs in GBM therapy and how these allowed us to overcome the physiological and anatomical challenges that have long plagued GBM treatment.

4.
Biomolecules ; 13(1)2022 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-36671442

RESUMEN

Cucurbitacins constitute a group of cucumber-derived dietary lipids, highly oxidized tetracyclic triterpenoids, with potential medical uses. These compounds are known to interact with a variety of recognized cellular targets to impede the growth of cancer cells. Accumulating evidence has suggested that inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins. Cucurbitacins may be a potential choice for investigations of synergism with other drugs to reverse cancer cells' treatment resistance. The detailed molecular mechanisms underlying these effects include interactions between cucurbitacins and numerous cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R, etc.) as well as control of a variety of intracellular signal transduction pathways. The current study is focused on the efforts undertaken to find possible molecular targets for cucurbitacins in suppressing diverse malignant processes. The review is distinctive since it presents all potential molecular targets of cucurbitacins in cancer on one common podium.


Asunto(s)
Antineoplásicos , Neoplasias , Triterpenos , Humanos , Cucurbitacinas/farmacología , Cucurbitacinas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Triterpenos/farmacología , Triterpenos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Neoplasias/patología , Transducción de Señal , Apoptosis
5.
Ann Lab Med ; 38(5): 440-445, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29797814

RESUMEN

BACKGROUND: Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for a plethora of human diseases, of which cutaneous and mucocutaneous infections are the most prevalent. In its most severe form, HSV infection can cause meningitis/encephalitis. We compared the Luminex ARIES HSV 1&2 assay (Luminex Corp., Austin, TX, USA), an automated sample-to-result molecular solution, to two non-automated HSV DNA assays. METHODS: A total of 116 artificial controls were used to determine the analytical performance of the ARIES assay. Controls were prepared by spiking universal transport medium (UTM) and cerebrospinal fluid (CSF) samples from patients who tested negative for HSV by an in-house HSV-1 and -2 DNA assay with reference materials (SeraCare Life Sciences, MA, USA; ZeptoMetrix Corp., MA, USA). Another 117 clinical samples were then used to compare the clinical performance of the ARIES assay with those of an in-house assay and the FTD Neuro 9 assay (Fast Track Diagnostics, Junglinster, Luxembourg). RESULTS: The analytical sensitivity (95% limit of detection) of the ARIES assay was 318 copies/mL (UTM samples) and 935 copies/mL (CSF samples) for HSV-1 strain 96 and 253 copies/mL (UTM samples) and 821 copies/mL (CSF samples) for HSV-2 strain 09. No cross-reactivity was observed in samples spiked with 14 non-HSV microorganisms. Compared with the reference result (agreement between the in-house and FTD Neuro 9 results), the ARIES assay had overall concordance rates of 98.2% (111/113) and 100% (113/113) for HSV-1 and HSV-2, respectively. CONCLUSIONS: The ARIES assay appears to be an excellent alternative for rapid detection and differentiation of HSV in skin and genital infections, meningitis, and encephalitis.


Asunto(s)
Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ADN Viral/líquido cefalorraquídeo , ADN Viral/metabolismo , Herpes Simple/diagnóstico , Herpes Simple/virología , Humanos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/virología
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