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In vivo (Athens, Greece) · 2017

Induction of TGF-β by Irradiation or Chemotherapy in Fanconi Anemia (FA) Mouse Bone Marrow Is Modulated by Small Molecule Radiation Mitigators JP4-039 and MMS350.

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Epperly Michael W, Rhieu Byung-Han, Franicola Darcy, Dixon Tracy, Cao Shaonan, Zhang Xichen, Shields Donna, Wang Hong, Wipf Peter, Greenberger Joel S

Аннотация

BACKGROUND/AIM: Total-body irradiation and/or administration of chemotherapy drugs in bone marrow transplantation induce cytokines that can suppress engraftment. Fanconi Anemia (FA) patients have a hyperactive responsiveness to the inhibitory cytokine, transforming growth factor-beta (TGF-β). Small molecule radiation mitigator drugs, JP4-039 and MMS350, were evaluated for suppression of irradiation or drug-induced TGF-β.

MATERIALS AND METHODS: In vivo induction of TGF-β by total-body ionizing irradiation (TBI), L-phenylalanine mustard (L-PAM), busulfan or fludarabine, was quantified. In parallel, mitigator drug amelioration of TGF-β induction in FA D2-/- (FANCD2-/-) mouse bone marrow, was studied in vitro. Tissue culture medium, cell lysates, and mouse plasma were analyzed for TGF-β levels.

RESULTS: Induction of TGF-β levels in FANCD2-/- and FANCD2+/+ mice and in mouse bone marrow were modulated by both JP4-039 and MMS350.

CONCLUSION: Bone marrow transplantation in FA recipients may benefit from administration of small molecule agents that suppress TGF-β induction.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты