Posted by rob on February 25, 2010 under Uncategorized | 
Therapeutic outcome of chronic myelogenous leukemia (CML) in advanced phases and of Philadelphia chromosome-positive (Ph+) acute leukemias remains dismal, even with tyrosine kinase inhibitors (TKIs) against Bcr-Abl or hematopoietic stem cell transplantation (HSCT) with maximally myeloablative conditioning (MAST). Especially, because patients over 55 years old are not eligible for MAST, the establishment of a treatment strategy for elderly patients with acute/advanced Ph+ leukemias has long been anticipated. We here present our experience with the use of fludarabine (Flu)/busulfan (Bu) 16 conditioning regimen (FB16) and dasatinib maintenance therapy following allogenic bone marrow transplantation (BMT) for two elderly patients with Ph+ acute/advanced leukemia. (Source: Leukemia Research)
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Isolated extramedullary relapse (EMR) of chronic myelogenous leukemia (CML) after bone marrow transplantation (BMT) is rare, seen in only 0.21% of cases . EMR in the central nervous system (CNS) is a rare event, and when seen is more commonly associated with lymphoblastic cells . Only two cases of CNS myeloblastic relapse have been reported previously . To our knowledge, isolated CNS myeloid blastic crisis after allogenic BMT for CML has previously not been reported. (Source: Leukemia Research)
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The advent of molecular medicine has allowed physicians and scientists to decipher some of nature’s mysteries. Few stories are more exhilarating than that of the successes in pediatric acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML). Indeed, children with ALL are now curable without the need for cranial radiation and imatinib mesylate has changed the landscape of CML therapy . Despite these advances disease recurrence and adverse late effects continue to dampen our celebrations. Enticing dormant cancer stem cells to undergo mitosis and offering risk-directed therapy are current endeavors aimed to overcome these obstacles. (Source: Leukemia Research)
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Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal translocation (9;22) that generates the Bcr-Abl fusion gene. The Ras/Raf-1/MEK/ERK pathway is constitutively activated in Bcr-Abl-transformed cells, and Ras activity enhances the oncogenic ability of Bcr-Abl. However, the mechanism by which Bcr-Abl activates the Ras pathway is not completely understood. Raf kinase inhibitor protein (RKIP) inhibits activation of MEK by Raf-1 and its downstream signal transduction, resulting in blocking the MAP kinase pathway. In the present study, we found that RKIP was depleted in CML cells. We investigated the interaction between RKIP and Bcr-Abl in CML cell lines and Bcr-Abl+ progenitor cells from CML patients. The Abl kinase inhibitors and depletion of Bcr-Abl induced the ex…
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In this study, in vivo circulatory metabolites of meisoindigo in rat plasma, as well as excretory metabolites in rat urine and feces, were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Integration of multiple reaction monitoring with conventional metabolic profiling methodology was adopted to enable a more sensitive detection of in vivo metabolites. By comparing with the MS/MS spectra and retention times of the in vitro reduced metabolites, the major metabolites in rat plasma were proposed to form from 3,3′ double bond reduction, whereas the minor metabolites were formed from reduction followed by N-demethylation, and reduction followed by phenyl mono-oxidation. The major metabolites in the rat urine were proposed to form from reduction followed by phenyl mono-ox…
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Improvement of cytotoxicity of titanocene-functionalized mesoporous materials by the increase of the titanium content.
Dalton Trans. 2010 Mar 14;39(10):2597-2608
Authors: Kaluđerović GN, Pérez-Quintanilla D, Zižak Z, Juranić ZD, Gómez-Ruiz S
The reaction of [Ti(eta(5)-C(5)H(5))(2)Cl(2)] (), with 3-mercaptopropyltrimethoxysilane or 3-mercaptopropyltriethoxysilane in the presence of triethylamine leads to the formation of the thiolate complexes [Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OMe)(3)}(2)] () and [Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OEt)(3)}(2)] (), respectively. Complexes and have been characterized by traditional methods, in addition, structural studies based on DFT calculations are reported. have been grafted onto dehydroxylated MCM-41 to give the novel materials MCM-41/[Ti(eta(5)-C(5)H(5))(2)Cl(2)] (), MCM-41/[Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OMe)(3)}(2)] () and MCM-41/[Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OEt)(3)}(2)] () which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, SEM and TEM. Materials and present much higher values of Ti wt% (ca. 3%) than (ca. 1%), indicating the higher functionalization rate induced by the substitution of the chloro ligands by the thiolato ligands in the starting titanocene derivatives. The cytotoxicity of the non-functionalized MCM-41 and toward human cancer cell lines such as adenocarcinoma HeLa, human myelogenous leukemia K562 and human malignant melanoma Fem-x has been studied. In addition the cytoxicity of these materials on normal immunocompetent cells such as stimulated (PBMC+PHA) and non-stimulated (PBMC-PHA) peripheral blood mononuclear cells have been also studied. M(50) values (quantity of material needed to inhibit normal cell survival by 50%) of the studied surfaces show that non-functionalized MCM-41 was not active against any of the studied cells, while the functionalized surfaces were active against all the tested human cancer cells. The cytotoxic activity of surfaces and were very similar, however, showed lower cytotoxic activity. This phenomenon indicates that the cytotoxicity of the titanocene-functionalized materials strongly depends on the titanium content.
PMID: 20179853 [PubMed - as supplied by publisher]
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SUZ12 is a candidate target of the non-canonical WNT pathway in the progression of chronic myeloid leukemia.
Genes Chromosomes Cancer. 2010 Feb;49(2):107-18
Authors: Pizzatti L, Binato R, Cofre J, Gomes BE, Dobbin J, Haussmann ME, D’Azambuja D, Bouzas LF, Abdelhay E
Polycomb proteins form multiprotein complexes that repress target genes by chromatin remodeling. In this work, we report that the SUZ12 polycomb gene is over-expressed in bone marrow samples of patients at the blastic phase of chronic myeloid leukemia. We also found a direct interaction between polycomb group genes and the WNT signaling pathway in chronic myeloid leukemia transformation. Electrophoretic mobility shift assay (EMSA), Chromatin immunoprecipitation assay (ChIP), and mass spectrometry assays identified noncanonical WNT pathway members, such as WNT5A and WNT11, bound to the SUZ12 promoter. Immunohistochemistry and immunofluorescence with WNT5A and WNT11 antibodies confirmed nuclear localization. Knockdown of WNTs 1, 5A, and 11 with RNAi approaches showed that WNT members are capable of activating SUZ12 transcription with varying promoter affinities. Finally, we suggest that SUZ12 is blocking cellular differentiation, as SUZ12 knockdown release differentiation programs in chronic myeloid blastic phase (CML-BP) transformed cell line.
PMID: 19847889 [PubMed - indexed for MEDLINE]
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