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

Purpose: Some 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).

Methods: The most frequently used animal model of human obesity with DMT2 is db/db mouse.

P-selectin glycoprotein ligand-1 deficiency augments G-CSF induced myeloid cell mobilization.

The effect of granulocyte colony-stimulating factor (G-CSF) was investigated in P-selectin glycoprotein ligand-1 (PSGL-1) deficient (PSGL-1(-/-)) and wild-type (PSGL-1(+/+)) mice to establish the role of this mucin in myeloid cell mobilization. G-CSF activates tissue proteases that cleave adhesion molecules, thus enhances the mobilization of myeloid cells and haematopoietic stem cells. Cytopenia was induced with a single dose of cyclophosphamide.

Toxicity of cytotoxic agents to granulocyte-macrophage progenitors is increased in obese Zucker and non-obese but insulin resistant Goto-Kakizaki rats.

Increased risk of anticancer chemotherapy in seriously obese patients is known. Obesity may be among factors that predict treatment-related toxicity during chemotherapy. We investigated whether functional changes in granulopoiesis may also contribute to increased myelotoxicity in addition to the known alterations of pharmacokinetic parameters in obesity.

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

We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s(4)UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s(4)UMP on JY cells. Treatment of JY cells with s(4)UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte-macrophage progenitor cells were 14-fold less sensitive to the nucleotide.