Quanto è utile/interessante questa discussione:
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Mixel
Nuovo Arrivato
Prov.: Roma
Città: ROMA
4 Messaggi |
 Inserito il - 23 settembre 2005 : 16:00:56
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 salve a tutti, avrei bisogno di un aiuto urgentissimo!!! il mmio prof. di oncologia mi ha afidato un seminario sulle leucemie, e fin qui tutto ok, peccato chemi hanno chiesto di mmostrare il pathway PI3K/AKT in relazione al recettore FLT3. il problema è che non sono riuscita a trovare il pathway in questione, come posso fare? Ho provato su Kegg, ma non riesco a trovare il pathway che accomuni PI3K e AKt, forse c'è un metodo particlare per lanciare la ricerca crociata? Vi supplico aiutattemi (Il seminario è fra 4 giorni..... grazie mille
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Pao! |
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Elisabetta
Nuovo Arrivato
8 Messaggi |
 Inserito il - 23 settembre 2005 : 21:18:41
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Ciao,
io sono andata sul sito di PubMed ed ho trovato questi 3 articoli che ti incollo qui di seguito.
Cerca anche in altri link, ad es. Gateway o nel sito nella National Library of Medicine.
Penso che alcuni di questi articoli siano free, puoi scaricarteli e leggerli.
Elisabetta
Oncogene. 2004 Apr 22;23(19):3338-49. Related Articles, Links
FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins.
Scheijen B, Ngo HT, Kang H, Griffin JD.
Department of Medical Oncology, Dana-Farber Cancer Institute, Mayer 540, 44 Binney Street, Boston, MA 02115, USA.
In about 30% of the patients with acute myeloid leukemia, activating FLT3 receptor mutations have been identified, often as in-frame internal tandem duplications (ITD) at the juxtamembrane domain of the receptor. FLT3-ITD receptors exhibit constitutive tyrosine kinase activity in the absence of FLT3 ligand (FL) binding, and when expressed in cytokine-dependent cell lines and primary hematopoietic cells suppress programmed cell death and increase cell division. However, the signaling pathways important for transformation, in particular the nuclear targets, are unknown. Here we demonstrate that FLT3-ITD expression in Ba/F3 cells results in activation of Akt and concomitant phosphorylation of the Forkhead family member Foxo3a. Phosphorylation of Foxo proteins through FLT3-ITD signaling promotes their translocation from the nucleus into the cytoplasm, which requires the presence of conserved Akt phosphorylation sites in Forkhead transcription factors and PI3K activity. Induction of Foxo3a phosphorylation by FLT3-ITD receptors in Ba/F3 cells correlates with the suppression of Foxo-target genes p27Kip1 and the proapoptotic Bcl-2 family member Bim. Specifically, FLT3-ITD expression prevents Foxo3a-mediated apoptosis and upregulation of p27Kip1 and Bim gene expression. These data indicate that the oncogenic tyrosine kinase FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation. Copyright 2004 Nature Publishing Group
PMID: 14981546 [PubMed - indexed for MEDLINE]
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2: Acta Haematol. 2004;111(1-2):107-23. Related Articles, Links
Apoptosis induced by molecular targeting therapy in hematological malignancies.
Adachi S, Leoni LM, Carson DA, Nakahata T.
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sadachi@kuhp.kyoto-u.ac.jp
Molecular targeting therapies for hematological malignant diseases such as monoclonal antibodies and small molecules have been reviewed. Imatinib mesylate (STI571) targets the tyrosine kinase activity of the BCR-ABL fusion protein in CML, and was superior to IFN-alpha plus low-dose cytarabine in newly diagnosed chronic-phase CML in a phase III randomized study. Imatinib induced apoptosis in BCR-ABL-positive cells in vitro, and activates several signaling pathways such as PI3K/Akt, STAT5 and Ras/MAPK. Combination therapies with imatinib and new strategies for downregulation of intracellular BCR-ABL protein levels have also been investigated from the phenomenon of resistance to imatinib. Anti-CD20 (rituximab) became the first monoclonal antibody approved for the treatment of a relapsed/refractory follicular/low-grade NHL and promising results were obtained from a phase III randomized study. Although antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity are likely to be the major effectors of B-cell depletion in vivo, direct cytotoxicity by CD20 monoclonal antibody on B-cell lines in vitro has been reported. Anti-CD33 (Mylotarg) and FLT3 inhibitors for AML have also been used in clinical trials and signaling pathways induced by these agents are under intensive investigation. Arsenic trioxide, like all-TRANS-retinoic acid (ATRA), downregulates promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARalpha) fusion protein and induced apoptosis in APL cells, and promising results were obtained from ATRA-resistant APL patients. Finally we show our promising in vitro and in vivo data of R-etodolac (a non-steroidal anti-inflammatory drug lacking cyclooxygenase inhibitor activity) against chronic lymphocytic leukemia (CLL) cells. Copyright 2004 S. Karger AG, Basel
Publication Types:
Review
PMID: 14646349 [PubMed - indexed for MEDLINE]
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3: Curr Opin Hematol. 2002 Jul;9(4):274-81. Related Articles, Links
Role of FLT3 in leukemia.
Gilliland DG, Griffin JD.
Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA. james_griffin@dfci.harvard.edu
FLT3 is the most frequently mutated gene in cases of acute myelogenous leukemia (AML). About 30 to 35% of patients have either internal tandem duplications (ITDs) in the juxtamembrane domain or mutations in the activating loop of FLT3. FLT3 mutations occur in a broad spectrum of FAB subtypes in adult and pediatric AML and are particularly common in acute promyelocytic leukemia (APL). FLT3 mutations confer a poor prognosis in most retrospective studies. The consequence of either FLT3-ITD or activating loop mutations, which occur predominantly at position D835, is constitutive activation of the tyrosine kinase; FLT3 mutants confer factor-independent growth to Ba/F3 and 32D cells and activate similar transduction pathways as the native receptor in response to ligand, including the STAT, RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3; kinase (PI3K)/AKT pathways. Injection of FLT3-ITD transformed cells, such as Ba/F3 or 32D, into syngeneic recipient mice results in a leukemia-like syndrome, and expression in primary murine bone marrow cells in a retroviral transduction assay results in a myeloproliferative disorder. Mutations that abrogate FLT3 kinase activity result in loss of transforming properties in these assays. Further, FLT3-selective inhibitors impair transformation of primary AML cells that harbor these mutations, and also inhibit FLT3 transformed hematopoietic cell lines, and leukemias induced by activated FLT3 mutants in murine models. Collectively, these data indicate that FLT3 may be a viable therapeutic target for treatment of AML.
Publication Types:
Review
PMID: 12042700 [PubMed - indexed for MEDLINE]
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Mixel
Nuovo Arrivato
Prov.: Roma
Città: ROMA
4 Messaggi |
Inserito il - 28 settembre 2005 : 04:09:43
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ti ringrazio tantissimo, ti scriverò con più calma per farti sapere com'è andata ...grazie..!!!!!!!! |
Pao! |
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aiuto esame oncologia!!!
Didattica
