Pioneer Research Center
Pioneer Research Center
News Article | May 10, 2017
"Discovered nearly 35 years ago, the mutant RAS protein has been considered a highly-validated cancer drug target, but also has a reputation as being undruggable," said Yong Sung Kim, Ph.D., principle investigator on the paper, co-founder of Orum Therapeutics, and professor, Department of Molecular Science and Technology at Ajou University, Korea. The paper published today by scientists at Ajou University and Orum Therapeutics describes the preclinical characterization of a novel monoclonal antibody, called RT11-i, designed to be internalized by the cell and to directly target the activated form of RAS. The data shows that RT11-i binding is specific to activated RAS, binds these proteins inside the cell and blocks interactions with effector proteins, and results in inhibition of downstream oncogenic signaling. When given to tumor-bearing mice, RT11-i inhibited tumor growth in several xenograft models and shown to be well tolerated. Dr. Kim explained, "This data shows that with our cell penetrating antibody technology, we now have the ability to selectively inhibit activated RAS to achieve anti-tumor activity with a systemically administered monoclonal antibody. Additional data suggests the combination of RT11-i and an anti-EGFR therapy might be an effective clinical strategy for patients with advanced colon cancer who have oncogenic RAS mutations." When tested in xenograft models of human cancer, RT11-i had preferential accumulation in tumor tissue and demonstrated measureable anti-tumor activity in mice where the tumor contained an activating RAS mutation. In addition, in a xenograft mouse model of colorectal cancer resistant to cetuximab, which targets EGFR, co-adminstration of cetuximab and RT11-i was shown to overcome resistance to cetuximab. "As an anti-cancer therapy, our cell penetrating antibodies are easy to produce, allow for systemic administration that is well tolerated, and have desirable pharmacological properties," said Sung Joo Lee, Ph.D., Co-founder and CEO of Orum Therapeutics. "We believe this could be a very important first-in-class therapeutic for hard-to-treat pancreatic, colon and non-small cell lung cancers." The paper entitled, "Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumor effects after systemic administration," was published online today in Nature Communications, and can be found here: http://www.nature.com/ncomms. The DOI for this paper is 10.1038/NCOMMS15090. This work was supported by grants from the Pioneer Research Center Program (2014M3C1A3051470) and the Global Frontier Project (2013M3A6A4043874) from the National Research Foundation (NRF), funded by the Republic of Korea. Orum Therapeutics is a private biotech company developing a new class of therapeutic antibodies to bring new medicines to patients with unmet medical needs. Orum leverages its unique cell penetrating antibody platform to inhibit drug targets undruggable by small molecule or current antibody therapeutics. In contrast to other approaches, Orum's antibody platform can target specific cell types, is easily adaptable to target different cell types and different intracellular proteins, and does not require chemical modification. This provides new opportunities to treat severe genetic diseases and cancer. More information about Orum Therapeutics is available at http://www.orumrx.com. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cell-penetrating-antibodies-to-oncogenic-ras-show-anti-tumor-activity-300454705.html
Subhan F.,Pusan National University |
Subhan F.,Pioneer Research Center |
Kang H.Y.,Pusan National University |
Kang H.Y.,Pioneer Research Center |
And 14 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2017
Skin diseases associated with inflammation or oxidative stress represent the most common problem in dermatology. The present study demonstrates that fish scale collagen peptides (FSCP) protect against CoCl2-induced cytotoxicity and TNF-α-induced inflammatory responses in human HaCaT keratinocyte cells. Our study is the first to report that FSCP increase cell viability and ameliorate oxidative injury in HaCaT cells through mechanisms mediated by the downregulation of key proinflammatory cytokines, namely, TNF-α, IL-1β, IL-8, and iNOS. FSCP also prevent cell apoptosis by repressing Bax expression, caspase-3 activity, and cytochrome c release and by upregulating Bcl-2 protein levels in CoCl2- or TNF-α-stimulated HaCaT cells. In addition, the inhibitory effects of FSCP on cytotoxicity and the induction of proinflammatory cytokine expression were found to be associated with suppression of the ROS, MAPK (p38/MAPK, ERK, and JNK), and NF-κB signaling pathways. Taken together, our data suggest that FSCP are useful as immunomodulatory agents in inflammatory or immune-mediated skin diseases. Furthermore, our results provide new insights into the potential therapeutic use of FSCP in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries. © 2017 Fazli Subhan et al.
Choi D.J.,Pusan National University |
Choi D.J.,Pioneer Research Center |
Choi S.M.,Pusan National University |
Choi S.M.,Pioneer Research Center |
And 18 more authors.
Journal of Biotechnology | Year: 2015
One of the most challenging objectives of 3D cell culture is the development of scaffolding materials with outstanding biocompatibility and favorable mechanical strength. In this study, we fabricated a novel nanofibrous scaffold composed of fish collagen (FC) and polycaprolactone (PCL) blends by using the electrospinning method. Nanofibrous scaffolds were characterized using a scanning electron microscope (SEM), and it was revealed that the diameter of nanofibers decreased as FC content was increased in the FC/PCL composite nanofibers. The cytocompatibility of the FC/PCL scaffolds was evaluated by SEM, WST-1 assay, confocal microscopy, western blot, and RT-PCR. It was found that the scaffolds not only facilitated the adhesion, spreading, protrusions, and proliferation of thymic epithelial cells (TECs), but also stimulated the expression of genes and proteins involved in cell adhesion and T-cell development. Thus, these results suggest that the FC/PCL composite nanofibrous scaffolds will be a useful model of 3D cell culture for TECs and may have wide applicability in the future for engineering tissues or organs. © 2015 Elsevier B.V.
Shin S.,Pusan National University |
Ikram M.,Pusan National University |
Ikram M.,Pioneer Research Center |
Subhan F.,Pusan National University |
And 16 more authors.
RSC Advances | Year: 2016
Hydrogels are prototypical matrices for 3D cell culture, of which alginate hydrogels are extensively used. However, ionic crosslinking agents, such as Ca2+, are required to form alginate hydrogels, but introduce Ca2+-associated cytotoxicity and long-term stability issues. Collagen is a promising biomaterial for 3D cell culture scaffolds primarily due to its biocompatibility. In the present study, the authors designed and fabricated a calcium-free, physically crosslinked, efficient, and bioactive hydrogel composed of alginate, marine collagen, and agarose (AmCA) for use in 3D cell cultures. This AmCA hydrogel was assessed by FTIR, swelling property, scanning electron microscopy, phase contrast microscopy, cell proliferation, cell viability, confocal microscopy, transparency and RT-PCR analyses. The gel was found to exhibit excellent cytocompatibility with various tumor and non-tumor cells, to generate high yields of multicellular spheroids, and to promote cellular activity. Furthermore, the transparency of the AmCA hydrogel suggests it can be used without cell-tracking chemicals in morphological studies of cell cultures. Taken together, it would appear that the described physically crosslinked AmCA hydrogel could provide a novel platform for the development of customizable, transparent, biocompatible, functional, easy-to-produce, and cost-effective scaffolds for use in 3D cultures of various cell types. © The Royal Society of Chemistry 2016.
News Article | January 30, 2016
Home > Press > A step towards keeping up with Moore's Law: POSTECH researchers develop a novel and efficient fabrication technology for cross-shaped memristor Abstract: Along with the fast development of modern information technology, charge-based memories, such as DRAM and flash memory, are being aggressively scaled down to meet the current trend of small size devices. A memory device with high density, faster speed, and low power consumption is desired to satisfy Moore's law in the next few decades. Among the candidates of next-generation memory devices, cross-bar-shaped non-volatile resistive memory (memristor) is one of the most attractive solutions for its non-volatility, faster access speed, ultra-high density and easier fabrication process. Conventional memristors are usually fabricated through conventional optical, imprint, and e-beam lithographic approaches. However, to meet Moore's law, the assembly of memristors comprised of 1-dimensional (1D) nanowires must be demonstrated to achieve cell dimensions beyond limit of state-of-art lithographic techniques, thus allowing one to fully exploit the scaling potential of high density memory array. Prof. Tae-Woo Lee (Dept. of Materials Science and Engineering) and his research team have developed a rapid printing technology for high density and scalable memristor array composed of cross-bar-shaped metal nanowires. The research team, which consists of Prof. Tae-Woo Lee, research professor Wentao Xu, and doctoral student Yeongjun Lee at POSTECH, Korea, published their findings in Advanced Materials. They applied an emerging technique, electrohydrohynamic nanowire printing (e-NW printing), which directly prints highly-aligned nanowire array on a large scale into the fabrication of microminiature memristors, with cross-bar-shaped conductive Cu nanowires jointed with a nanometer-scale CuxO layer. The metal-oxide-metal structure resistive memory device exhibited excellent electrical performance with reproducible resistive switching behavior. This simple and fast fabrication process avoids conventional vacuum techniques to significantly reduce the industrial-production cost and time. This method paved the way to the future down-scaling of electronic circuits, since 1D conductors represent a logical way to extreme scaling of data processing devices in the single-digit nanometer scale. They also succeeded in printing memristor array with various shapes, such as parallel lines with adjustable pitch, grids, and waves which can offer a future stretchable memory for integration into textile to serve as a basic building block for smart fabrics and wearable electronics. "This technology reduces lead time and cost remarkably compared with existing manufacturing methods of cross-bar-shaped nanowire memory and simplifies its method of construction," said Prof. Lee. "In particular, this technology will be used as a source technology to realize smart fabric, wearable computers, and textile electronic devices." ### This work was supported by the Center for Advanced Soft-Electronics as Global Frontier Project and the Pioneer Research Center Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.