Phase II study of sunitinib as second-line treatment for advanced gastric cancer

Bang, Yung-Jue,Kang, Yoon-Koo,Kang, Won K.,Boku, Narikazu,Chung, Hyun C.,Chen, Jen-Shi,Doi, Toshihiko,Sun, Yan,Shen, Lin,Qin, Shukui,Ng, Wai-Tong,Tursi, Jennifer M.,Lechuga, Maria J.,Lu, Dongrui Ray,R Springer US 2011 Investigational new drugs Vol.29 No.6

<P><B>Summary</B></P><P><I>Purpose.</I> This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy. <I>Experimental design</I>. Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life. <I>Results</I>. Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6–2.6 months) and median OS was 6.8 months (95% CI, 4.4–9.6 months). Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome. <I>Conclusions</I>. The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.</P>

Selective Laser Sintering of a Hydroxyapatite-silica Scaffold on Cultured MG63 Osteoblasts in Vitro

Fwu-Hsing Liu,Yung-Kang Shen,Jeou-Long Lee 한국정밀공학회 2012 International Journal of Precision Engineering and Vol. No.

This study forms hydroxyapatite-silica ceramic structure, which can generate interconnected porous 3D models suitable as bone scaffold, using a novel selective laser sintering (SLS) technique. Hydroxyapatite (HA) powder and a silica sol are first mixed into slurries. After processing by SLS, the HA particles are embedded in the gelled silica matrix to form green parts. The processed parts are analyzed by scanning electron microscopy (SEM). The number of cells attached on this scaffold surface is obtained by the in vitro cultured cells test. The higher number of viable cells are obtained when the sintering temperature of the scaffold was 1200°C at day 4 of cell culturing. The proposed technology can be applied to generate a bone scaffold model of porous bio-ceramics for biomedicine.

Study on Cellar Behaviors on Different Nanostructures by Nanoporous Alumina Template

Chiung-Fang Huang,Yung-Kang Shen,Hsin-Chung Cheng,Yi Lin,Chih-Wei Wu 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Nanoporous anodic aluminum oxide (AAO) templates are fabricated using an nodization method. The mean diameters of nanoporousanodic aluminum oxide templates are 100 nm and 200 nm by various processing parameters of the anodization method. A moldedplastic thin film nanostructure is fabricated by nanoimprinting using the AAO template as a mold insert. The surface properties ofthe molded plastic thin film are discussed using various nanoimprinting process parameters. Contact angles of the molded plastic thinfilm with the nanostructure exceed those without the nanostructure. The molded plastic thin films with a nanostructure and ahydrophobic surface are formed, and their contact angles exceed 90o. This study observes the behavior of osteoblast-like cells (MG63)cultured on nanostructure thin films, i.e., AAO, polylactic acid (PLA) and polycarbonate (PC). Cell growth behavior indicates thatthe AAO template with a 200 nm nanostructure is best. This study shows that cell adhesion and spreading are influenced by surfacetopography in the nanometer feature.

3D Scaffold with PCL Combined Biomedical Ceramic Materials for Bone Tissue Regeneration

Ming-Jyh Chern,Liang-Yo Yang,Yung-Kang Shen,Jia-Hsiang Hung 한국정밀공학회 2013 International Journal of Precision Engineering and Vol. No.

Three-dimensional porous biodegradable polymer scaffolds have been widely used for tissue engineering of bone repair or regeneration. The primary function of scaffolds is to provide structure support for the cells adhesion and proliferation. This study selects the Poly-ε-caprolactone (PCL) as material, NaCl mixed with hydroxyapatite (HA) or nano-aluminum oxide (nAl2O3) for porous scaffold. This study uses the solvent casting/particulate leaching method to fabricate the porous scaffold. The authors discuss the compression mechanical properties, physical properties (porosity, moisture content, contact angle) of a pure PCL, PCL/mHA,PCL/nHA and PCL/nAl2O3 scaffolds. In vitro cell culture is used for osteoblast cell (MG63) and the microculture tetrazolium test (MTT) is undertaken in the scaffold. The scaffolds are implanted to the femur of rats and histological examination is attempted after 2 weeks. The experimental results indicate that HA and nAl2O3 can improve the hydrophilic property. In conclusion, the PCL/nHA scaffold exhibits splendid in vivo biocompatibility and osteogenesis.

Epigenetic switch from repressive to permissive chromatin in response to cold stress

Park, Junghoon,Lim, Chae Jin,Shen, Mingzhe,Park, Hee Jin,Cha, Joon-Yung,Iniesto, Elisa,Rubio, Vicente,Mengiste, Tesfaye,Zhu, Jian-Kang,Bressan, Ray A.,Lee, Sang Yeol,Lee, Byeong-ha,Jin, Jing Bo,Pardo, National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.23

<▼1><P><B>Significance</B></P><P>Phenotypic adaptations of plants in response to changes in climate are well known to be mediated by molecular mechanisms, including activation or suppression of transcription factors that control target gene expression. However, the chromatin changes that are essential for the binding of transcription factors are much less understood. Gene derepression at the chromatin level is considered to be the starting point for gene transcription. We report a mechanism of gene derepression through which HOS15 promotes the degradation of histone deacetylase HD2C in a cold-dependent manner that correlates with increased levels of acetylated histones on <I>COR</I> gene chromatin. Moreover, HOS15 directly promotes <I>COR</I> gene transcription by association of CBF transcription factors with the “open” state of the target <I>COR</I> chromatin.</P></▼1><▼2><P>Switching from repressed to active status in chromatin regulation is part of the critical responses that plants deploy to survive in an ever-changing environment. We previously reported that HOS15, a WD40-repeat protein, is involved in histone deacetylation and cold tolerance in <I>Arabidopsis</I>. However, it remained unknown how HOS15 regulates cold responsive genes to affect cold tolerance. Here, we show that HOS15 interacts with histone deacetylase 2C (HD2C) and both proteins together associate with the promoters of cold-responsive <I>COR</I> genes, <I>COR15A</I> and <I>COR47</I>. Cold induced HD2C degradation is mediated by the CULLIN4 (CUL4)-based E3 ubiquitin ligase complex in which HOS15 acts as a substrate receptor. Interference with the association of HD2C and the <I>COR</I> gene promoters by HOS15 correlates with increased acetylation levels of histone H3. HOS15 also interacts with CBF transcription factors to modulate cold-induced binding to the <I>COR</I> gene promoters. Our results here demonstrate that cold induces HOS15-mediated chromatin modifications by degrading HD2C. This switches the chromatin structure status and facilitates recruitment of CBFs to the <I>COR</I> gene promoters. This is an apparent requirement to acquire cold tolerance.</P></▼2>