Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights

Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML). However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR) at 45 mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine), FLT3 inhibitor (sorafenib), farnesyl-transferase inhibitor (tipifarnib), histone deacetylase inhibitor (vorinostat), lenalidomide, as well as DNA methyltransferase inhibitors (decitabine, azacitidine), were recently reported for AML treatment in the 2009 ASH annual meeting. This review also summarizes the updates of the clinical trials on novel agents including voreloxin, AS1413, behenoylara-C, ARRY520, ribavirin, AZD1152, AZD6244, and terameprocol (EM-1421) from the 2009 ASH annual meeting

New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer

DNA methylation and histone acetylation are two well known epigenetic chromatin modifications. Epigenetic agents leading to DNA hypomethylation and histone hyperacetylation have been approved for treatment of hematological disorders. The first histone deacetylase inhibitor, vorinostat, has been licensed for cutaneous T cell lymphoma treatment. More than 11 new epigenetic agents are in various stages of clinical development for therapy of multiple cancer types. In this review we summarize novel histone deacetylase inhibitors and new regimens from clinical trials for epigenetic therapy of cancer

Three dimensional spider-web-like superconducting filamentary paths in KxFe2−ySe2K_xFe_{2-y}Se_2 single crystals

Since the discovery of high temperature superconductivity in F-doped LaFeAsO, many new iron based superconductors with different structures have been fabricated2. The observation of superconductivity at about 32 K in KxFe2-ySe2 with the iso-structure of the FeAs-based 122 superconductors was a surprise and immediately stimulated the interests because the band structure calculation8 predicted the absence of the hole pocket which was supposed to be necessary for the theoretical picture of S+- pairing. Soon later, it was found that the material may separate into the insulating antiferromagnetic K2Fe4Se5 phase and the superconducting phase. It remains unresolved that how these two phases coexist and what is the parent phase for superconductivity. In this study we use different quenching processes to produce the target samples with distinct microstructures, and apply multiple measuring techniques to reveal a close relationship between the microstructures and the global appearance of superconductivity. In addition, we clearly illustrate three dimensional spider-web-like superconducting filamentary paths, and for the first time propose that the superconducting phase may originate from a state with one vacancy in every eight Fe-sites with the root8*root10 parallelogram structure.Comment: 22 pages, 7 figure

Hypoacetylation, Hypomethylation, and Dephosphorylation of H2B Histones and Excessive Histone Deacetylase Activity in DU-145 Prostate Cancer Cells

BACKGROUND: Hypoacetylation on histone H3 of human prostate cancer cells has been described. Little is known about the modifications of other histones from prostate cancer cells. METHODS: Histones were isolated from the prostate cancer cell line DU-145 and the non-malignant prostatic cell line RC170N/h. Post-translational modifications of histone H2B were determined by liquid chromatography-mass spectrometry (LC-MS)/MS. RESULTS: The histone H2B of the prostate cancer cell line DU-145 was found to have hypoacetylation, hypomethylation, and dephosphorylation as compared to the non-malignant prostatic cell line RC170N/h. H2B regained acetylation on multiple lysine residues, phosphorylation on Thr19, and methylation on Lys23 and Lys43 in the DU-145 cells after sodium butyrate treatment. CONCLUSIONS: The histone H2B of DU-145 prostate cancer cells are hypoacetylated, hypomethylated, and dephosphorylated. Histone deacetylase inhibitor reversed this phenotype. Epigenetic agent may therefore be useful for prostate cancer therapy and worth further investigation

Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents

Hands-off, artificial construction, or penalty? How to deal with the increasingly polluted coastal wetland ecosystem in China

As the destruction of coastal wetlands in China becomes more and more serious, the government needs to strengthen the management of the wetland ecosystem. Considering that pollution is an important factor in the destruction of coastal wetlands in China, the government can deal with the problem of wetland pollution through three modes: hands-off, artificial construction, and penalty. In this article, the differential game model is constructed under these three modes. The balanced social benefits of the government and polluting enterprises under the three modes are obtained, and the applicable conditions of various wetland treatment paths are compared. The results show that when the revenue generated by taxation and the indirect income generated by artificial construction are small, the government will choose the laissez-faire mode. However, with the gradual increase of indirect income generated by artificial construction, the government will be inclined to choose the artificial construction mode. When the income from government fines is small, the social benefits of polluters in the hands-off mode are greater than those in the penalty mode. With the increase of fines, the social benefits of polluting enterprises will first decrease and then increase, which will eventually be greater than the social benefits under the hands-off mode

Growth of the Tian Shan drives migration of the conglomerate-sandstone transition in the southern Junggar foreland basin

International audienceIn an orogenic belt-foreland basin setting, sediments from the mountain are transported downstream and accumulate in foreland basins. Sediments routing through the network of rivers display downstream grain size fining due to sorting and abrasion (Paola et al., 1992). A grain size transition from gravel to sand, termed the gravel-sand transition (GST; Ferguson et al., 1996), occurs in a short downstream distance from the sediment source. The GST is preserved in the stratigraphy of a sedimentary basin as the conglomerate-sandstone transition (CST; e.g., Dubille & Lavé, 2015). The position of the CST in a foreland basin succession is determined by basin subsidence, sediment supply, and grain size (Allen et al., 2013; Armitage et al., 2011), and all these factors depend on the interactions of tectonics in the adjacent mountains and regional climate (Dingle et al., 2016, 2017; Duller et al., 2010; Quick et al., 2020). The propagation of the orogenic wedge toward to the foreland drives the forelandward migration of the coupled foreland basin system as well as sedimentary facies (Flemings & Jordan, 198

Mesures in-situ par incandescence induite par Laser des tailles de nano-particules lors de la synthèse de nanotubes de carbone par dépôt chimique en phase vapeur

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