We present the performances of a 330 g zinc molybdate (ZnMoO
4
) crystal working as scintillating bolometer as a possible candidate for a next generation experiment to search for neutrinoless double ...beta decay of
100
Mo. The energy resolution, evaluated at the 2615 keV
γ
-line of
208
Tl, is 6.3 keV FWHM. The internal radioactive contaminations of the ZnMoO
4
were evaluated as <6 μBq/kg (
228
Th) and 27±6 μBq/kg (
226
Ra). We also present the results of the
α
vs
β
/
γ
discrimination, obtained through the scintillation light as well as through the study of the shape of the thermal signal alone.
We present the performances of a 330 g zinc molybdate (ZnMoO.sub.4) crystal working as scintillating bolometer as a possible candidate for a next generation experiment to search for neutrinoless ...double beta decay of sup.100Mo. The energy resolution, evaluated at the 2615 keV γ-line of sup.208Tl, is 6.3 keV FWHM. The internal radioactive contaminations of the ZnMoO.sub.4 were evaluated as < 6 µBq/kg (sup.228Th) and 27 ± 6 µBq/kg(sup.226Ra). We also present the results of the α vs β/γ discrimination, obtained through the scintillation light as well as through the study of the shape of the thermal signal alone.
We present the performances of a 330 g zinc molybdate (ZnMoO4) crystal working as scintillating bolometer as a possible candidate for a next generation experiment to search for neutrinoless double ...beta decay of 100Mo. The energy resolution, evaluated at the 2615 keV gamma-line of 208Tl, is 6.3 keV FWHM. The internal radioactive contaminations of the ZnMoO4 were evaluated as <6 microBq/kg (228Th) and 27\pm6 microBq/kg (226Ra). We also present the results of the alpha vs beta/gamma discrimination, obtained through the scintillation light as well as through the study of the shape of the thermal signal alone.
Molecular lesions in T-cell acute lymphoblastic leukemias affect regulators of cell cycle, proliferation, differentiation, survival and apoptosis in multi-step pathogenic pathways. Full genetic ...characterization is needed to identify events concurring in the development of these leukemias.
We designed a combined interphase fluorescence in situ hybridization strategy to study 25 oncogenes/tumor suppressor genes in T-cell acute lymphoblastic leukemias and applied it in 23 adult patients for whom immunophenotyping, karyotyping, molecular studies, and gene expression profiling data were available. The results were confirmed and integrated with those of multiplex-polymerase chain reaction analysis and gene expression profiling in another 129 adults with T-cell acute lymphoblastic leukemias.
The combined hybridization was abnormal in 21/23 patients (91%), and revealed multiple genomic changes in 13 (56%). It found abnormalities known to be associated with T-cell acute lymphoblastic leukemias, i.e. CDKN2A-B/9p21 and GRIK2/6q16 deletions, TCR and TLX3 rearrangements, SIL-TAL1, CALM-AF10, MLL-translocations, del(17)(q12)/NF1 and other cryptic genomic imbalances, i.e. 9q34, 11p, 12p, and 17q11 duplication, del(5)(q35), del(7)(q34), del(9)(q34), del(12)(p13), and del(14)(q11). It revealed new cytogenetic mechanisms for TCRB-driven oncogene activation and C-MYB duplication. In two cases with cryptic del(9)(q34), fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction detected the TAF_INUP214 fusion and gene expression profiling identified a signature characterized by HOXA and NUP214 upregulation and TAF_I, FNBP1, C9orf78, and USP20 down-regulation. Multiplex-polymerase chain reaction analysis and gene expression profiling of 129 further cases found five additional cases of TAF_I-NUP214-positive T-cell acute lymphoblastic leukemia.
Our combined interphase fluorescence in situ hybridization strategy greatly improved the detection of genetic abnormalities in adult T-cell acute lymphoblastic leukemias. It identified new tumor suppressor genes/oncogenes involved in leukemogenesis and highlighted concurrent involvement of genes. The estimated incidence of TAF_I-NUP214, a new recurrent fusion in adult T-cell acute lymphoblastic leukemias, was 4.6% (7/152).
This is the first report of e6a2 and e1a2 BCR/ABL1 positive chronic myeloid leukemia (CML) with cryptic deletions of the 5'ABL1 and 3'BCR in separate clones which differ in genomic regions of the ...deleted der(9). Both deletions were detected throughout monitoring. Imatinib mesylate stabilized this CML with rare genetic aberrations for a relatively long time.
The notion that gliomas could originate from mutated glial precursor cells highlights the possibility of modulating the proliferative and migratory behaviour of glioma cells by acting on the ...molecular mechanisms operative during the development of the Central Nervous System (CNS), but absent in the normal adult brain. We show that the GL15 glioblastoma derived human cell line displays a high expression of nestin which, combined with the previously demonstrated high expression of vimentin, constitutes a characteristic of astrocyte restricted precursors. We also show that, in analogy with some leukaemia cells, GL15 cells display the constitutively phosphorylated form of Janus kinase 2 (JAK2), a tyrosine kinase expressed during CNS development but undetectable in the normal adult brain. The constitutive activation of JAK2 does not result from chromosomal aberrations involving the JAK2 gene, but most probably from abnormally activated transduction systems operative in glioblastoma cells. We then investigated the effects of tyrphostin AG490, an inhibitor of JAK2 autophosphorylation, on GL15 cell growth. In the absence of exogenous growth factors and cytokines, 10 microM tyrphostin AG490 induces an S phase arrest, combined with a partial impairment of the G2 phase of the cell cycle. The abnormally activated JAK2 could then potentially represent a target for a selective pharmacological approach in glioblastoma cells in which a combination of glial precursor characteristics and genetic alterations occurs.
The challenging possibility of selectively inducing mitotic death in tumor cells by combining genotoxic agents with the inhibition of G2 checkpoints of the cell cycle is the subject of intensive ...investigation. We show that very low concentrations (3.5 and 5 nM) of okadaic acid induce mitotic death in two glioblastoma cell lines, in the absence of genotoxic agents. At the concentrations used, the main target of okadaic acid action is protein phosphatase 2A (PP2A), an enzyme deeply involved in the negative control of cell-cycle progression. The peculiar susceptibility of glioblastoma cells to induction of mitotic death by very low concentrations of okadaic acid must be related to an impairment of PP2A activity and to a specific deficiency in some cell-cycle checkpoints. In addition to its ability to induce abnormal mitoses in actively proliferating glioblastoma cells, okadaic acid possesses the ability to force semi-confluent glioblastoma cells to the M phase of the cell cycle, where they show the same abnormalities observed in actively proliferating glioblastoma cells. In semi-confluent cells the induction of mitotic death involves the activity of both the extracellular signal regulated kinases (ERKs) and the M-phase promoting factor: okadaic acid overstimulates ERK activity, and PD98059 (inhibitor of ERK activation) as well as roscovitine (S)-isomer (specific inhibitor of M-phase promoting factor activity) counteract the induction of mitotic death. Our results show that, without the use of genotoxic agents, it is possible to induce mitotic death in glioblastoma cells by activating the same uncontrolled pathways responsible for the uncontrolled proliferation.
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