A randomized phase 2 trial of nintedanib and low-dose cytarabine in elderly patients with acute myeloid leukemia ineligible for intensive chemotherapy.

We investigated the safety and efficacy of nintedanib added to low-dose cytarabine (LDAC) in a phase 1/2 study in patients 60 years or older with newly diagnosed or relapsed/refractory (r/r) AML ineligible for intensive chemotherapy. The results of the dose-finding phase 1 part have been previously published. Patients were randomized 1:1 to LDAC plus nintedanib or LDAC plus placebo stratified by AML status (newly diagnosed vs r/r).

In vitro proinflammatory gene expression changes in human whole blood after contact with plasma-treated implant surfaces.

Background: The aim of this in vitro study was to identify changes in gene expression of proinflammatory cytokines in human whole blood after contact with titanium implant surfaces after plasma treatment.

Materials And Methods: Grade 4 titanium dental implants were conditioned with low-pressure plasma (LPP) and atmospheric-pressure plasma (APP) and submerged in human whole blood in vitro. Unconditioned implants and blood samples without implants served as control and negative control groups, respectively.

A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia.

Unlabelled: Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles.

Laser schlieren deflectometry for temperature analysis of filamentary non-thermal atmospheric pressure plasma.

The heat convection generated by micro filaments of a self-organized non-thermal atmospheric pressure plasma jet in Ar is characterized by employing laser schlieren deflectometry (LSD). It is demonstrated as a proof of principle, that the spatial and temporal changes of the refractive index n in the optical beam path related to the neutral gas temperature of the plasma jet can be monitored and evaluated simultaneously. The refraction of a laser beam in a high gradient field of n(r) with cylindrical symmetry is given for a general real refraction index profile.

Damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid.

Background: Mono-unsaturated fatty acids (MUFAs) like oleic acid have been shown to cause apoptosis of cultured endothelial cells by activating protein phosphatase type 2C alpha and beta (PP2C). The question arises whether damage of endothelial or other cells could be observed in intact animals fed with a trioleate-enriched diet.

Methodology/principal Findings: Dunkin-Hartley guinea pigs were fed with a trioleate-enriched diet for 5 months.

Influence of various fatty acids on the activity of protein phosphatase type 2C and apoptosis of endothelial cells and macrophages.

In previous work we have demonstrated that protein phosphatase type 2C (PP2C) alpha and beta can be activated by mono-unsaturated fatty acids (MUFAs) leading to apoptosis of cultured endothelial cells. In the present paper we could show that saturated fatty acids (SFAs) did not activate PP2C and did not cause apoptosis both in endothelial cells and macrophages. However, long-chain SFAs (>16 C-atoms) were capable of inhibiting both, activation of PP2C as well as apoptosis of human umbilical vein endothelial cells (HUVECs) and macrophages caused by oleic acid.

Unsaturated fatty acids liberated from VLDL cause apoptosis in endothelial cells.

Certain unsaturated fatty acids (UFAs), cleaved from lipoproteins, are known to activate the serine/threonine protein phosphatase type 2C (PP2C) alpha- and beta-isoforms. To investigate the role of UFAs in apoptosis of endothelial cells, we cocultured human umbilical vein endothelial cells (HUVECs) with THP-1 monocytes. Phorbol-12-myristic-13-acetate (PMA)-treated THP-1 monocytes differentiated into macrophages and synthesized lipoprotein lipase (LPL), the major enzyme for hydrolysis of triglycerides.