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    LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
    (NATURE PUBLISHING GROUP, 2018-09-06) Irmak, Ster
    The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease. Inhibition of collagen stabilization by itself can reduce or enhance tumor growth depending on the tumor type. The mechanistical basis for this behavior is the dependence of the individual tumor on nutritional supply on one hand and on high tissue stiffness for FAK signaling on the other.
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    Synthesis, characterization, and biological properties of composites of hydroxyapatite and hexagonal boron nitride
    (Wiley, 2018) Unal, Semra; Ekren, Nazmi; Sengil, Ahmet Z.; Oktar, Faik N.; Irmak, Ster; Oral, Ozlem; Sahin, Yesim M.
    Hydroxyapatite (HA), obtained from bovine bones, was successfully reinforced with hexagonal boron nitrite (h-BN). h-BN/HA composites, with BN content up to 1.5 wt %, were sintered at various temperatures between 1000 and 1300 degrees C, in air. Well-sintered samples were obtained after sintering at 1200 and 1300 degrees C. The presence of h-BN contributed to dense, fine, and well-crystallized microstructure. The results of X-ray diffraction analysis and FT-IR spectroscopy showed that the produced composites comprised biphasic beta-TCP/HCA (HCA: carbonate partially substituted HA). High values of mechanical properties were achieved, namely compression strength 155 MPa for the sample 0.5% h-BN/HA and Vickers microhardness of 716 HV for the samples 1.5% h-BN/HA, both sintered at 1300 degrees C. U2OS human bone osteosarcoma proliferation and cell viability showed no adverse effect in the presence of h-BN/HA, suggesting the potential use of the produced materials as safe biomaterials in bone tissue engineering. (C) 2017 Wiley Periodicals, Inc.