Understanding of the blood–brain barrier (BBB) is important to understand later how it can be affected by TKIs.
‘’Based on these results, we further investigated the preclinical and clinical effects of dasatinib in CNS leukemia. We show that dasatinib is associated with increased survival in a mouse model of intracranial CML and induces clinically meaningful responses in patients with CNS disease’’.
‘’The creation of the mouse model has enabled the group to study the molecular mechanisms by which leukemia cells invade and grow within the central nervous system. In addition, the researchers have created the first spontaneous mouse model of a serious complication of human leukemia, invasion of the brain by leukemia cells.’’
‘’Platelet-derived growth factor receptor-β (PDGFR-β) inhibitors such as the anticancer drug imatinib (Gleevec) can prevent or reverse tolerance to morphine analgesia, scientists claim.
‘’Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the blood-brain barrier (BBB) to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib.’’
Extract of Pericytes regulate the blood-brain barrier.
‘’Chronic myelogenous leukemia (CML) can be controlled for years with the tyrosine kinase inhibitor imatinib but because imatinib poorly penetrates the blood-brain barrier (BBB), on occasion, the CML clone will thrive and evolve to an accelerated phase in the resulting imatinib sanctuary within the central nervous system.…. Given glioblastoma's reliably fatal outcome within several years of diagnosis, and that 1 year after diagnosis, half of all patients are dead, BBB opening to allow higher imatinib brain tissue levels in addition to current treatments might be rewarding. After CNS relapse, CML patients may likewise benefit from methamphetamine-assisted opening of the BBB to allow better TK inhibition and more effective treatment’’
‘’Imatinib reduced the blood-brain barrier permeability associated with tPA and also expanded the window in which it can be used’’
You have watched too many Sci-Fi movies showing "adult viable pericyte-deficient mouse mutants". They are soooo scary.
What in tarnation* does an "adult viable pericyte-deficient mouse mutant" tell me about my brain? Do these mice eat ice cream? If not, what do they eat that makes them mutate? What makes them so viable -- do they take Cialis for daily use? Inquiring minds want to know.
I'm hungry. I think I'll have some Blue Bell ice cream. Made right here in Texas by mutant Texans deficient in something or other. But they make darn good ice cream. Too bad the Aussie ladies don't have any. Yum yum.
You look addicted to ice cream! “Casein, one of the proteins in milk, crosses the blood-brain barrier and becomes something called casomorphins. Yes’m, that sounds a lot like morphine—because casomorphin is also an opiod. Nature designed it that way so young mammals would enjoy nursing, come back for more, and live to reproduce themselves.” Extract of Addicted to Cheese and Ice Cream? The Opiate Qualities of Dairy
CML can cause obstructive sleep apnea if you gained too much pounds! If it’s your case, you have to read this article ‘’Rodent of the week: Mice on Cialis’’. No, Trey! For the moment, there is no contraindication with ice cream and Cialis! But if you take also Imatinib, it can amplify the effect. So, be carefull!
Note:According to Drug.com, Adcirca,another brand of tadalafil (Cialis), is used to treat pulmonary arterial hypertension and improve exercise capacity in men and women. Dasatinib can cause pulmonary arterial hypertension. See reference (PAH -dasatinib)
Enjoy the summer!
How do you explain than studies have shown Gleevec reversing PAH since its also a TKI. I was treated with opiates while on Gleevec for A 3 way compound fracture and my personal 1 man study showed they don't work for pain worth a plug nickel while taking Gleecec. However I have found Ice cream still taste really good.
‘’Moreover, expression of the PDGF receptor was found to be significantly increased in lung tissue from pulmonary arterial hypertension patients compared with healthy donor lung tissue. We conclude that STI571 reverses vascular remodeling and cor pulmonale in severe experimental pulmonary hypertension regardless of the initiating stimulus’’
‘’Platelet-derived growth factor (PDGF) and its receptor (PDGFR) have been implicated in the pathobiology of pulmonary hypertension in patients with PAH, and are potential new targets for the treatment of this disease. Imatinib, a tyrosine kinase inhibitor of PDGFR α and β kinases, Abl, DDR, and c-KIT may therefore prove efficacious in the treatment of PAH.’’
"The investigators hypothesize that bone marrow progenitor cells are mobilized into the circulation in PAH, home to the lungs and differentiate into mast cells, which promote vascular remodeling and vasoconstriction through release of renin and chymase. As a corollary to this, the investigators hypothesize that anti cKit tyrosine kinase inhibitor (TKI), nilotinib, provides clinical benefit to patients through inhibition of mast cell progenitor proliferation, mobilization and differentiation. To test this, the investigators will determine if mast cell progenitors and mast cell biomarkers are related to nilotinib clinical response"