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Objective: To investigate the effects of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma. Methods: We reviewed the records of 48 patients who received sunitinib treatment for metastatic renal cell carcinoma between April 2007 and December 2010 at our institution. Patients' data including diabetic status, diabetes mellitus medication and mean blood glucose levels before, during and after the treatment with sunitinib were assessed. Results: In 10 of the 48 (20.8%) patients who were diabetic, the blood glucose level was observed to be significantly decreased after 4 weeks of sunitinib treatment with the mean decrease in blood glucose level being 76.1 + 29.0 mg/dl (P ¼ 0.002). Subsequently, after a 2-week off-treatment period, the mean blood glucose level rebound and increased (21.9 + 6.3 mg/dl, P ¼ 0.038) in these 10 patients. With sunitinib treatment, one patient was able to discontinue diabetes mellitus medication completely during a 4-week treatment period, and three other patients had dosages of their oral diabetes mellitus medication reduced. Among 38 non-diabetic patients, no significant changes in blood glucose levels were observed during both the 4-week sunitinib treatment period and the 2-week off-treatment period. No severe hypoglycemic episode was observed among our subjects. Conclusions: Sunitinib treatment in diabetic patients with metastatic renal cell carcinoma may result in significantly decreased blood glucose levels. Thus, blood glucose levels should be checked more vigilantly in diabetic patients undergoing sunitinib treatment to adjust diabetes mellitus medications as needed. Further investigation via a larger scaled, prospective study would be needed.

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Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion in vivo. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and in situ nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that in situ magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both in vitro and in vivo, with reversible control. Furthermore, we unravel that in situ magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes in vivo.

We identified important genes related to the development and progression of ameloblastoma through a large-scale gene expression analysis. This study will stimulate further investigations on genes significant for early diagnosis and prognosis of ameloblastoma.

Natural extracellular matrix (ECM) can regulate the interactions between cells and ligands by exhibiting heterogeneous nano-sequences periodically displaying adhesive ligands, such as RGD ligand in vivo. [1,2] Cell-adhesive ECM proteins, such as fibronectin, vitronectin, and collagen, were shown to form periodically sequenced RGD ligand-bearing nanostructures (67-100 nm). [1] Periodic structure in reflectance was also observed from native tissues. [2] The ligation of integrin with adhesive ligand mediates the assembly of cytoskeletal actin filaments and focal adhesion (FA) complexes to activate mechanosensing signaling pathways that can regulate cellular differentiation. [3,4] Strategically developing materials with heterogeneously sequenced ligand nanostructures can emulate ECM [5] microenvironment to help elucidate the interactions between cells and nano-ligands with tunable frequency and sequences. This can effectively regulate diverse cellular adhesion and functionality in vivo, such as FA, mechanosensing, and differentiation of stem cells. [6] The native extracellular matrix (ECM) can exhibit heterogeneous nanosequences periodically displaying ligands to regulate complex cell-material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nanosegments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.