Molecular and functional characterization of a new 3′ end KIT juxtamembrane deletion in a duodenal GIST treated with neoadjuvant Imatinib

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Molecular and functional characterization of a new 3′ end KIT juxtamembrane deletion in a duodenal GIST treated with neoadjuvant Imatinib
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs express the receptor tyrosine kinase KIT, and the majority of GISTs present KIT gain-of-function mutations that cluster in the 5' end of the receptor juxtamembrane domain. On the other hand, little information is known about GISTs carrying mutations in the 3′ end of the KIT juxtamembrane domain. Here we report and discuss a clinical case of localized duodenal GIST whose molecular characterization revealed the presence of a new 21 nucleotide/7 amino acid deletion in the 3′ end of KIT juxtamembrane domain (Δ574–580). The patient was treated with Imatinib at standard regimen dose (400 mg/day), and responded well as the original tumor mass reduced, ultimately allowing conservative surgery. In line with these clinical evidences computer simulations, biophysical techniques and in vitro experiments demonstrated that the receptor tyrosine kinase KIT carrying the Δ574–580 mutation displays constitutive phosphorylation, which can be switched-off upon Imatinib treatment. In addition, results from this study showed that a clinical useful procedure, neoadjuvant treatment, can occasionally be of value for the understanding of the molecular pathogenesis of GIST.

Density and Viscosity of 1-Methoxy-2-Propanol, 2-Methyltetrahydrofuran, α,α,α-Trifluorotoluene, and Their Binary Mixtures with 1,1,1-Trichloroethane at Different Temperatures

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Density and Viscosity of 1-Methoxy-2-Propanol, 2-Methyltetrahydrofuran, α,α,α-Trifluorotoluene, and Their Binary Mixtures with 1,1,1-Trichloroethane at Different Temperatures

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