In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia

Berényi, E; Benkö, Ilona; Vámosi, György; Géresi, Krisztina; Tárkányi, Ilona; Szegedi, István; Lukács, Levente; Juhász, István; Kiss, Csongor; Fésüs, László; Aradi, J.

doi:10.1016/j.bbrc.2011.06.056

Cited by 1 publication

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“…In our previous work we found that it had a promising antileukemic effect in vivo on acute lymphoid leukemia human cell lines transplantated them into mice with serious combined immune deficiency (SCID). Therapeutic index was good based on the 14-fold less toxicity of 4-thiouridylate on healthy human CFU-GM progenitors than JY leukemic cell line [21]. Fourthiouridylate, analogously to the previously tested cytotoxic drugs, resulted in a dosedependent decrease in CFU-GM colony numbers in bone marrow cell cultures of both control and db/db mice and, also correspondingly to the anticancer drugs, the sensitivity of CFU-GM cells of obese db/db mice was higher to 4-thiouridylate (Fig.…”

Section: Page 11 Of 33 Cancer Chemotherapy and Pharmacologymentioning

confidence: 99%

Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model of obesity-associated diabetes mellitus

Géresi

Megyeri

Szabo

et al. 2015

Cancer Chemother Pharmacol

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PurposeSome authors observed increased carboplatin-associated myelotoxicity in obese patients which was exclusively attributed to elevated AUC. To investigate the potential contribution of functional changes of cells primarily responsible for myelopoiesis, granulocyte-macrophage progenitors (CFU-GM) were studied in obesity-associated diabetes mellitus (DMT2). MethodsThe most frequently used animal model of human obesity with DMT2 is db/db mouse. Cellularity, frequency of CFU-GM and total CFU-GM content of femoral bone marrow was measured after 100 mg/kg dose of carboplatin in vivo. To exclude influence of pharmacokinetic changes direct toxicity of carboplatin on CFU-GM was also determined in vitro and was compared with other anticancer agents, namely doxorubicin, 5-fluorouracil and 4-thiouridylate. ResultsAfter intraperitoneal administration of carboplatin, each measured characteristics of bone marrow function were more significantly suppressed and the induced neutropenia were more serious in db/db mice than in the controls. The increased myelotoxicity seemed to be a direct effect on myeloid progenitor cells since their increased in vitro sensitivity was found in db/db mice. This was not specific for carboplatin, a similar double to 5-fold increase in myelotoxicity of each cytotoxic drug with different mechanism of action was observed. Four-thiouridylate, a promising antileukemic molecule with good therapeutic index, was by far the least toxic for CFU-GM of db/db mice.Conclusions A serious disorder of CFU-GM progenitors was suggested in obese mice with DMT2, which eventually might lead to more severe myelotoxicity and neutropenia. Weight loss and normalization of glucose homeostasis may be important before chemotherapy of malignant diseases in obesity with DMT2.

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Section: Page 11 Of 33 Cancer Chemotherapy and Pharmacologymentioning

confidence: 99%