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• W133011805 abstract "In Leukemias, recent developments have demonstrated that the Hedgehog pathway plays a key-role in the peculiar ability of self renewal of leukemia stem cells. The aim of this research activity was to investigate, through a first in man, Phase I, open label, clinical trial, the role and the impact, mainly in terms of safety profile, adverse events and pharmacokinetics, of a Sonic Hedgehog inhibitor compound on a population of heavely pretreated patients affected by AML, CML, MF, or MDS, resistant or refractory to standard chemotherapy. Thirty-five patients have been enrolled. The drug was administered orally, in 28 days cycles, without rest periods. The compound showed a good safety profile. The half life was of 17-35 hours, justifying the daily administration. Significant signs of activity, in terms of reduction of bone marrow blast cell amount were seen in most of the patients enrolled. Interestingly, correlative biological studies demonstrated that, comparing the gene expression profyiling signature of separated CD34+ cells before and after one cycle of treatment, the most variably expressed genes were involved in the Hh pathway. Moreover, we observed that many genes involved in MDR (multidrug resistance)were significantly down regulated after treatment. These data might lead to future clinical trials based on combinatory approaches, including, for instance, Hh inhibitors and conventional chemotherapy." @default.
• W133011805 created "2016-06-24" @default.
• W133011805 creator A5044624520 @default.
• W133011805 date "2013-06-06" @default.
• W133011805 modified "2023-09-23" @default.
• W133011805 title "Pre-clinical and clinical development of leukemia stem cell inhibitors in acute leukemias" @default.
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• W133011805 doi "https://doi.org/10.6092/unibo/amsdottorato/5596" @default.
• W133011805 hasPublicationYear "2013" @default.
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