Search results for "45"

Evaluation of Cytochrome P450 Activities in Human Hepatocytes In Vitro

2011

Major hepatic cytochrome P450 activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) can be simultaneously examined in human hepatocytes by incubation with a cocktail of multiple specific probes. Cocktail strategy in combination with mass spectrometry is shown to be a robust, fast, and sensitive procedure for P450 activity assessment. This procedure allows a drastic reduction of the number of cells required in the assay and sample analysis time and increases throughput and reproducibility. Major applications of the probe cocktail strategy are P450 phenotyping of hepatocytes and induction studies.

Fast evaluation of enantioselective drug metabolism by electrophoretically mediated microanalysis: application to fluoxetine metabolism by CYP2D6.

2013

In this work, a capillary electrophoretic methodology for the enantioselective in vitro evaluation of drugs metabolism is applied to the evaluation of fluoxetine (FLX) metabolism by cytochrome 2D6 (CYP2D6). This methodology comprises the in-capillary enzymatic reaction and the chiral separation of FLX and its major metabolite, norfluoxetine enantiomers employing highly sulfated β-CD and the partial filling technique. The methodology employed in this work is a fast way to obtain a first approach of the enantioselective in vitro metabolism of racemic drugs, with the additional advantage of an extremely low consumption of enzymes, CDs and all the reagents involved in the process. Michaelis-Men…

Cytochrome P450 enzymes as human autoantigens

1991

Umme Dunia, un romanzo italiano del XIX secolo sulla caduta di Costantinipoli

2006

A partire dal romanzo Umme Dunia di Alberto Furse, si analizzano varie testimonianze sulla conquista turca di Costantinopoli nel 1453.

El mejor pastor descalzo, san Pascual Baylón o la incursión teatral de Ginés Campillo de Bayle

2016

Resumen: Cuando los ultimos decenios del siglo XVII iban marcando el final de la Casa de Austria en Espana, un clerigo nacido en Elche (Alicante), Gines Campillo de Bayle, intento su incursion en el mundo literario de la epoca. Su figura y obra, por un motivo u otro, siempre han estado rodeadas por un entorno de misterio, desgraciada fortuna y escasa estimacion. Valorado con precaucion por unos pocos, ignorado o criticado por la mayoria, gran parte de su produccion lirica, narrativa y teatral ha conseguido llegar, a pesar de todo, a nuestras manos. Un ejemplo de lo senalado es la comedia teatral, asi titulada por el propio autor, El mejor pastor descalzo, san Pascual Baylon ; toda una demos…

The potential of acetaminophen as a prodrug in gene-directed enzyme prodrug therapy.

2000

Acetaminophen is oxidized by human CYP1A2 to the cytotoxic metabolite N-acetylbenzoquinoneimine (NABQI). Incubation of cells transfected with human CYP1A2 (H1A2 MZ cells) with 4-20 mM acetaminophen for 6 hours at 37 degrees C caused extensive cytotoxicity (cell viability10%). In contrast, nontransfected V79 MZ cells were unaffected (viability95%). By mixing H1A2 MZ cells with V79 MZ cells in various proportions and incubating with 4 mM acetaminophen, it was shown that the NABQI released from H1A2 MZ cells also caused cytotoxicity of bystander cells. Thus, in a mixture containing 5% H1A2 MZ cells, exposure to 4 mM acetaminophen for 6 hours resulted in complete cell killing by 24 hours. A sim…

Abstract 6327: Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells

2020

Abstract Introduction: Prostate carcinoma (PCa) is the most common cancer in men. The therapeutic effect of approved compounds, such as docetaxel, is limited due to the development of therapy resistance, making new treatment options essential. Artesunate (ART), used in Traditional Chinese Medicine, has shown anti-tumor activity in several tumor types. However, little is known about the efficacy of ART on therapy-resistant PCa. Therefore, the impact of ART on docetaxel-resistant PCa cells was investigated. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, and LNCaP, were exposed to ART [1-100 µM] for 24, 48, or 72 hours. Cells not exposed to ART …

Abstract 1423: Shikonin impairs the growth of docetaxel-resistant prostate cancer cells by necroptosis

2021

Abstract Introduction: Prostate carcinoma (PCa) is the most common malignancy in men. Androgen-targeted therapy and chemotherapy are currently the treatment of choice for advanced stages. Due to resistance towards these therapies, prognosis remains poor and new treatment options are urgently required. Shikonin (SHI) from Traditional Chinese Medicine (TCM) might be promising, since it induces anti-tumor effects in different tumor entities. However, data on PCa are few, and data on resistant PCa are not existent. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1 - 1.5 μM] for 24, 48, or 72 hours. Untreated…

Phosphorylation of carcinogen metabolizing enzymes: regulation of the phosphorylation status of the major phenobarbital inducible cytochromes P-450 i…

1989

We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kinase. Most importantly the phosphorylation status of cytochromes P-450 was shown to change in the hepatocytes after treatment with glucagon, which is known to increase the level of cAMP in hepatocytes. The observed impact of the hormone glucagon on the phosphorylation of distinct cytochrome P-450 forms in intact hepatocytes reveals the possibility that the enzyme activity of cyt…

Stable expression of rat cytochrome P450IA2 cDNA and hydroxylation of 17β-estradiol and 2-aminofluorene in V79 Chinese hamster cells

1991

In continuation of our work toward the establishment of a working cell bank for metabolic and toxicological studies, V79 Chinese hamster cells were genetically engineered for stable expression of rat cytochrome P450IA2. Full-length cDNA encoding rat P450IA2 was obtained by searching a cDNA library made from Aroclor 1254-induced rat liver mRNA and by joining a small 5'-end fragment to a fragment containing the rest of the cDNA. The sequence of the cDNA was confirmed by DNA sequencing and comparison to a previously published cDNA sequence. The reconstructed full-length cDNA was inserted into a simian virus 40 early promoter-containing eukaryotic expression vector and cotransferred with the ne…