Triptolide, a natural product extracted from the Chinese plant Tripterygium wilfordii , possesses antitumor properties. Despite numerous reports showing the proapoptotic capacity and the inhibition ...of NF-κB–mediated
transcription by triptolide, the identity of its cellular target is still unknown. To clarify its mechanism of action, we
further investigated the effect of triptolide on RNA synthesis in the human non–small cell lung cancer cell line A549. Triptolide
inhibited both total RNA and mRNA de novo synthesis, with the primary action being on the latter pool. We used 44K human pan-genomic DNA microarrays and identified
the genes primarily affected by a short treatment with triptolide. Among the modulated genes, up to 98% are down-regulated,
encompassing a large array of oncogenes including transcription factors and cell cycle regulators. We next observed that triptolide
induced a rapid depletion of RPB1, the RNA polymerase II main subunit that is considered a hallmark of a transcription elongation
blockage. However, we also show that triptolide does not directly interact with the RNA polymerase II complex nor does it
damage DNA. We thus conclude that triptolide is an original pharmacologic inhibitor of RNA polymerase activity, affecting
indirectly the transcription machinery, leading to a rapid depletion of short-lived mRNA, including transcription factors,
cell cycle regulators such as CDC25A, and the oncogenes MYC and Src. Overall, the data shed light on the effect of triptolide
on transcription, along with its novel potential applications in cancers, including acute myeloid leukemia, which is in part
driven by the aforementioned oncogenic factors. Mol Cancer Ther 2009;8(10):2780–90
La fonction politique des atlas est bien connue. Tout autant que les cartes et les autres instruments visuels mobilisés par les savoirs géographiques, ils ont joué un rôle majeur dans l’exercice du ...pouvoir économique et politique, dans la fabrication des territoires et dans le développement des imaginaires politiques modernes et contemporains. Car il ne s’agit pas seulement, dans un atlas, de compiler des cartes et des informations géographiques, mais aussi d’élaborer et d’organiser un « réci...
Les circonstances de la naissance du Theatrum orbis terrarum sont connues par le récit de Johan Radermacher, qui rapporte de quelle manière il a été amené à solliciter Abraham Ortelius pour le compte ...de son patron, l’armateur Gilles Hooftman : Hooftman étudiait beaucoup les cartes géographiques, dans le but de calculer les distances et les positions des lieux, pour en déduire le coût de transport des marchandises, soit du point de vue des frais, soit du point de vue du risque encouru, et au...
Comme on l’a déjà dit, l’atlas, au sens large, qui est étudié dans cet ouvrage, est une forme graphique de construction, d’organisation, de visualisation, de conservation et de transport des ...connaissances et des informations géographiques. L’atlas est un dispositif épistémique tout à la fois matériel et cognitif. Le présent ouvrage a pour ambition d’élaborer une histoire critique de la constitution et des transformations (à la fois formelles et dans les usages) de ce dispositif. C’est l’effic...
The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the ...survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg
once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.
Le but de cet article est d’étudier les rapports entretenus par l’historien du paysage américain John Brinckerhoff Jackson avec la géographie humaine de langue française, au moment où il crée la ...revue Landscape , qui va s’imposer comme une des principales revues de référence sur le paysage à partir des années 1950. On rappellera, dans un premier temps, les circonstances dans lesquelles Jackson a découvert la géographie humaine française d’avant-guerre, et comment celle-ci l’a inspiré au moment où il mettait au point sa pensée sur le paysage. Dans un second temps, en s’appuyant sur une lecture des archives de Jackson et de sa bibliothèque, on s’efforcera de décrire sa méthode de travail.
Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the ...combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer.
A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS.
The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival.
In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis.
PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.
Introducción: La lipomatosis epidural espinal es una enfermedad infrecuente caracterizada por el sobrecrecimiento del tejido adiposo no encapsulado dentro del espacio epidural. Esto genera una ...estenosis del conducto espinal que puede provocar sintomatología compresiva. La presentación típica es insidiosa a lo largo de meses o años. El objetivo de este estudio fue realizar un análisis descriptivo de la manifestación clínica inicial en pacientes con lipomatosis epidural espinal grado III de Naka. Materiales y Métodos: Estudio observacional retrospectivo en la Unidad de Patología Espinal de 4 instituciones, de 2010 a 2023. Se incluyó a pacientes >18 años, de ambos sexos, que acudieron por dolor lumbar con irradiación o sin irradiación, y presentaban lipomatosis lumbar Naka III en la resonancia magnética. Resultados: Se incorporó a 40 pacientes (edad promedio 62.5 años). El 75% era obeso, ninguno era fumador. El motivo de consulta más frecuente fue lumbalgia, con una mediana de evolución del dolor de 5.5 meses. Conclusiones: La lumbalgia fue la consulta más frecuente, con excepción del compromiso de L3-S1 que fue la lumbocruralgia. Los pacientes que sufrieron dolor más tiempo (>6 meses) eran más jóvenes y tenían un índice de masa corporal menor; sin embargo, no resultó estadísticamente significativo.
Peroxisome proliferator‐activated receptor‐α (PPARα) is a major transcriptional regulator of lipid metabolism. It is activated by diverse chemicals such as fatty acids (FAs) and regulates the ...expression of numerous genes in organs displaying high FA catabolic rates, including the liver. The role of this nuclear receptor as a sensor of whole dietary fat intake has been inferred, mostly from high‐fat diet studies. To delineate its function under low fat intake conditions (4.8% w/w), we studied the effects of five regimens with contrasted FA compositions on liver lipids and hepatic gene expression in wild‐type and PPARα‐deficient mice. Diets containing polyunsaturated FAs reduced hepatic fat stores in wild‐type mice. Only sunflower, linseed, and fish oil diets lowered hepatic lipid stores in PPARα−/− mice, a model of progressive hepatic triglyceride accumulation. These beneficial effects were associated, in particular, with dietary regulation of Δ9‐desaturase in both genotypes, and with a newly identified PPARα‐dependent regulation of lipin. Furthermore, hepatic levels of 18‐carbon essential FAs (C18:2ω6 and C18:3ω3) were elevated in PPARα−/− mice, possibly due to the observed reduction in expression of the Δ6‐desaturase and of enoyl‐coenzyme A isomerases. Effects of diet and genotype were also observed on the xenobiotic metabolism‐related genes Cyp3a11 and CAR. Conclusion: Together, our results suggest that dietary FAs represent—even under low fat intake conditions—a beneficial strategy to reduce hepatic steatosis. Under such conditions, we established the role of PPARα as a dietary FA sensor and highlighted its importance in regulating hepatic FA content and composition. (HEPATOLOGY 2007;45:767–7777.)
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