Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also
the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that Cilengitide purchase targeting the biophysical properties of stem cell niches is of high clinical potential since it may re-sensitize tumor initiating cells to chemotherapies
and reduce risks of cancer relapse.”
“PURPOSE. We investigated the response of retinal vessel diameters and oxygen saturation to flicker light stimulation of neuronal activity in patients with diabetic retinopathy.\n\nMETHODS. We included 18 patients with nonproliferative diabetic retinopathy (mean age 62.2 +/- 8.3 years, diabetes type 1 in 4 patients and type 2 in 14, hemoglobin A1c 7.7 +/- 0.9%, duration of diabetes 24.1 +/- 9.3 years) and 20 age-matched healthy controls (age 66.7 +/- 10.3 years). Dual Ruboxistaurin in vivo wavelength (548 and 610 nm) fundus images were taken before and during luminance flicker stimulation (12.5 Hz, modulation depth > 1: 25) for 90 seconds. Diameters (central retinal arterial [CRAE] and venous [CRVE] equivalents) and oxygen saturation (SO2) were determined, and averaged for all arterioles and venules in P005091 an annular area centered at the optic disk.\n\nRESULTS. Flicker light increased CRAE, CRVE, and venous SO2 by 0.6 +/- 6.6%, 2.7 +/- 6.1%, and 2.0 +/- 2.4% (P < 0.05), respectively, in the patients as well as 4.7 +/- 8.4% (P < 0.05), 8.7 +/- 5.2% (P < 0.05), and 4.2
+/- 3.5% (P < 0.05), respectively, in the controls. The arterial SO2 remained unchanged in both groups. The increase of the venous SO2 correlated significantly (P = 0.027) with that of the CRAE. There was a trend (P = 0.06) for lower increase of the venous SO2 with higher body mass index.\n\nCONCLUSIONS. Our results support the thesis of an impaired regulation of oxygen supply to the diabetic retina. Whereas in healthy subjects the stimulation of neuronal activity increases the vascular diameters and, subsequently, the oxygen supply, this increase is reduced in diabetic retinopathy. This may hint at the role of endothelial dysfunction in the etiology of the disease. (Invest Ophthalmol Vis Sci. 2012;53:4063-4068) DOI:10.1167/iovs.12-9659″
“Question: Inflammatory cell numbers are important endpoints in clinical studies relying on endobronchial biopsies.