Excellent response to dasatinib of childhood Philadelphia positive intracranial acute lymphoblastic leukaemia tumours

Bhadri, Vivek; Satharasinghe, Keshan; Sugo, Ella; Barbaric, Draga; Trahair, Toby N.

doi:10.1111/j.1365-2141.2010.08465.x

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…Another limitation of this retrospective review is the lack of available pharmacokinetic data demonstrating adequate therapeutic levels in the cerebrospinal fluid of patients. However, the doses observed in our patients are comparable to, if not higher than, those used in other studies that reported responses in intracranial leukemic lesions . In vitro studies, however, to determine the IC 50 of KIT‐expressing GCT are lacking and would be welcome.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma

Osorio

Finlay

Dhall

et al. 2013

Pediatr Blood Cancer

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Germinomas and embryonal carcinomas are central nervous system (CNS) germ cell tumors (GCT) that may overexpress the proto-oncogene c-KIT, a receptor tyrosine kinase, of which dasatinib is a potent inhibitor. This retrospective review presents the feasibility and tolerability of dasatinib administration in select patients with CNS germinoma. Between November 2008 and April 2010, six patients with newly diagnosed (n = 3) or recurrent (n = 3) CNS GCT were treated in an effort to avoid irradiation and/or delay recurrence. The daily doses administered were 100-170 mg/m(2) with mostly grade 1-2 toxicities. Dasatinib may play a role in future treatment strategies for CNS GCT.

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Section: Discussionmentioning

confidence: 99%

Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma

Osorio

Finlay

Dhall

et al. 2013

Pediatr Blood Cancer

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“…Accordingly, the drug exhibited increased efficacy in younger animals subjected to longer treatment. Dasatinib is blood-brain barrier permeable and is the first line drug for patients with Philadelphia chromosome-positive Central Nervous System (CNS) leukemia 13 – 15 , 17 and CNS chronic myeloid leukemia 16 , 19 , 20 , 22 , 23 . A factor that can limit Dasatinib’s accumulation in the brain is P-glycoprotein (P-gp, ABCB1), as ABCB1 knock out mice exhibit significantly higher amounts of Dasatinib in the brain compared to control 40 – 43 .…”

Section: Discussionmentioning

confidence: 99%

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease

Shin

Sesti

2018

Cell Death Dis

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Oxidative modification of the voltage-gated K+ channel subfamily B member 1 (KCNB1, Kv2.1) is emerging as a mechanism of neuronal vulnerability potentially capable of affecting multiple conditions associated with oxidative stress, from normal aging to neurodegenerative disease. In this study we report that oxidation of KCNB1 channels is exacerbated in the post mortem brains of Alzheimer’s disease (AD) donors compared to age-matched controls. In addition, phosphorylation of Focal Adhesion kinases (FAK) and Src tyrosine kinases, two key signaling steps that follow KCNB1 oxidation, is also strengthened in AD vs. control brains. Quadruple transgenic mice expressing a non-oxidizable form of KCNB1 in the 3xTg-AD background (APPSWE, PS1M146V, and tauP301L), exhibit improved working memory along with reduced brain inflammation, protein carbonylation and intraneuronal β-amyloid (Aβ) compared to 3xTg-AD mice or mice expressing the wild type (WT) KCNB1 channel. We conclude that oxidation of KCNB1 channels is a mechanism of neuronal vulnerability that is pervasive in the vertebrate brain.

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Non-conducting functions of potassium channels in cancer and neurological disease

Sesti,

Bortolami,

Kathera-Ibarra

2023

Current Topics in Membranes

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Excellent response to dasatinib of childhood Philadelphia positive intracranial acute lymphoblastic leukaemia tumours

Cited by 5 publications

References 9 publications

Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma

Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma

Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease

Non-conducting functions of potassium channels in cancer and neurological disease

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