Human erythropoietin gene delivery for cardiac remodeling of myocardial infarction in rats

Lee, Y.,McGinn, A.N.,Olsen, C.D.,Nam, K.,Lee, M.,Shin, S.K.,Kim, S.W. Elsevier Science Publishers 2013 Journal of controlled release Vol.171 No.1

Considerable efforts have been made to exploit cardioprotective drugs and gene delivery systems for myocardial infarction (MI). The promising cardioprotective effects of recombinant human erythropoietin (rHuEPO) protein in animal experiments have not been consistently reproduced in clinical human trials of acute MI; however, the mechanisms underlying the inconsistent discrepancies are not yet fully understood. We hypothesized that the plasmid human erythropoietin gene (phEPO) delivered by our bioreducible polymer might produce cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of phEPO by an arginine-grafted poly(disulfide amine) (ABP) polymer in infarcted rats preserves cardiac geometry and systolic function. The reduced infarct size of phEPO/ABP delivery was followed by decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. In addition, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of phEPO/ABP administration. Furthermore, phEPO/ABP delivery induced prominent suppression on Ang II and TGF-β activity in all subdivisions of cardiac tissues except for the central zone of infarct. These results of phEPO gene therapy delivered by a bioreducible ABP polymer provide insight into the lack of phEPO gene therapy translation in the treatment of acute MI to human trials.

Targeted Gene Delivery to Ischemic Myocardium by Homing Peptide-Guided Polymeric Carrier

Won, Young-Wook,McGinn, Arlo N.,Lee, Minhyung,Bull, David A.,Kim, Sung Wan American Chemical Society 2013 Molecular pharmaceutics Vol.10 No.1

<P>Myocardial ischemia needs an alternative treatment such as gene therapy for the direct protection of cardiomyocytes against necrosis or apoptosis and to prevent the development of myocardial fibrosis and cardiac dysfunction. Despite the utility of gene therapy, its therapeutic use is limited due to inadequate transfection in cardiomyocytes and difficulty in directing to ischemic myocardium. Here, we present a polymeric gene carrier that is capable of targeting ischemic myocardium, resulting in high localization within the ischemic zone of the left ventricle (LV) of an ischemia/reperfusion (I/R) rat model upon systemic administration. Cystamine bisacrylamide-diamino hexane (CD) polymer was modified with the ischemic myocardium-targeted peptide (IMTP) and <SMALL>d</SMALL>-9-arginine (9R) for dual effects of the homing to ischemic myocardium and enhanced transfection efficiency with minimized polymer use. Conjugation of IMTP and 9R to CD led to an increase in transfection under hypoxia and significantly reduced the amount of polymer required for high transfection. Finally, we confirmed targeting of IMTP-CD–9R/DNA polyplex to ischemic myocardium and enhanced gene expression in LV of the I/R rat after tail vein injection. This study provides a clue that gene therapy for the treatment of myocardial ischemia can be achieved by using homing peptide-guided gene delivery systems.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2013/mpohbp.2013.10.issue-1/mp300500y/production/images/medium/mp-2012-00500y_0007.gif'></P>

조합화학 기법을 이용한 연료전지 촉매 개발

전민구,( James S. Cooper ),( Paul J. Mcginn ) 한국공업화학회 2010 한국공업화학회 연구논문 초록집 Vol.2010 No.-

Raspberry-like Metamolecules Exhibiting Strong Magnetic Resonances

Qian, Zhaoxia,Hastings, Simon P.,Li, Chen,Edward, Brian,McGinn, Christine K,Engheta, Nader,Fakhraai, Zahra,Park, So-Jung American Chemical Society 2015 ACS NANO Vol.9 No.2

<P>We report a synthetic approach to produce raspberry-like plasmonic nanostructures with unusually strong magnetic resonances, termed raspberry-like metamolecules (raspberry-MMs). The synthesis based on the surfactant-assisted templated seed-growth method allows for the simultaneous one-step synthesis and assembly of well-insulated gold nanoparticles. The aromatic surfactant used for the syntheses forms a thin protective layer around the nanoparticles, preventing them from touching each other and making it possible to pack discrete nanoparticles at close distances in a single cluster. The resulting isotropic gold nanoparticle clusters (<I>i</I>.<I>e</I>., raspberry-MMs) exhibit unusually broad extinction spectra in the visible and near-IR region. Finite-difference time-domain (FDTD) modeling showed that the raspberry-MMs support strong magnetic resonances that contribute significantly to the broadband spectra. The strong magnetic scattering was also verified by far-field scattering measurements, which show that in the near-IR region the magnetic dipole resonance can be even stronger than the electric dipole resonance in these raspberry-MMs. Structural parameters such as the size and the number of gold nanoparticles composing raspberry-MMs can be readily tuned in our synthetic method. A series of syntheses with varying structure parameters, along with FDTD modeling and mode analyses of corresponding model structures, showed that the close packing of a large number of metal nanoparticles in raspberry-MMs is responsible for the unusually strong magnetic resonances observed here.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-2/nn5050678/production/images/medium/nn-2014-050678_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5050678'>ACS Electronic Supporting Info</A></P>

Blood Pressure Is a Major Risk Factor for Renal Death : An Analysis of 560 352 Participants From the Asia-Pacific Region

O'Seaghdha, Conall M.,Perkovic, Vlado,Lam, Tai Hing,McGinn, Stella,Barzi, Federica,Gu, Dong Feng,Cass, Alan,Suh, Il,Muntner, Paul,Giles, Graham G.,Ueshima, Hirotsugu,Woodward, Mark,Huxley, Rachel Ovid Technologies Wolters Kluwer -American Heart A 2009 Hypertension Vol.54 No.3

<P>Chronic kidney disease is a major worldwide public health problem that causes substantial morbidity and mortality. Studies from the Asia-Pacific region have reported some of the highest chronic kidney disease prevalence rates in the world, but access to dialysis is limited in many countries, making it imperative to identify high-risk individuals. We performed a participant-level data overview of prospective studies conducted in the Asia-Pacific region to quantify the magnitude and direction of the associations between putative risk factors and renal death. Age- and sex-adjusted Cox proportional hazards models were applied to pooled data from 35 studies to calculate hazard ratios (95% CIs) for renal death associated with a standardized change in risk factors. Among 560 352 participants followed for a median of 6.8 years, a total of 420 renal deaths were observed. Continuous and positive associations among systolic blood pressure, diastolic blood pressure, fasting blood glucose, and total cholesterol levels with renal death were observed, as well as a continuous but inverse association with high-density lipoprotein cholesterol. Systolic blood pressure was the strongest risk factor for renal death with each SD increase in systolic blood pressure (19 mm Hg) associated with >80% higher risk (hazard ratio: 1.84; 95% CI: 1.60 to 2.12). Neither cigarette smoking nor excess weight was related to the risk of renal death (P>0.10). The results were similar for cohorts in Asia and Australia. These results suggest that primary prevention strategies for renal disease should focus on individuals with elevated blood pressure, diabetes mellitus, and dyslipidemia.</P>

Quaternary Pt2Ru1Fe1M1/C (M=Ni, Mo, or W) catalysts for methanol electro-oxidation reaction

Jeon, M. K.,Lee, K. R.,Jeon, H. J.,McGinn, P. J.,Kang, K. H.,Park, G. I. KOREAN INSTITUTE OF CHEMICAL ENGINEER 2015 Korean Journal of Chemical Engineering Vol.32 No.2

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors

강윤구,류민희,홍용상,최창민,김태원,류백열,김정은,John R. Weis,Rachel Kingsford,Cheol Hee Park,Seong Jang,Arlo McGinn,Theresa L. Werner,Sunil Sharma 대한암학회 2024 Cancer Research and Treatment Vol.56 No.3

Purpose This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Materials and Methods In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. Results A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. Conclusion The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).