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Complex role of NK cells in regulation of oncolytic virus–bortezomib therapy
Kim, Yangjin,Yoo, Ji Young,Lee, Tae Jin,Liu, Joseph,Yu, Jianhua,Caligiuri, Michael A.,Kaur, Balveen,Friedman, Avner National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.19
<P>In the present work, we investigated the role of natural killer (NK) cells in combination therapy with oncolytic virus (OV) and borte-zomib, a proteasome inhibitor. NK cells display rapid and potent immunity to metastatic and hematological cancers, and they overcome immunosuppressive effects of tumor microenvironment. We developed a mathematical model to address the question of how the density of NK cells affects the growth of the tumor. We found that the antitumor efficacy increases when the endogenous NKs are depleted and also when exogenous NK cells are injected into the tumor. These predictions were validated by our in vivo and in vitro experiments.</P>
Kim, Yangjin,Hibino, Kenichi,Kizaki, Toru,Sugita, Naohiko,Mitsuishi, Mamoru Elsevier 2017 Precision engineering Vol.48 No.-
<P><B>Abstract</B></P> <P>The absolute optical thickness and surface shape of optical devices are considered as the fundamental characteristics when designing optical equipment. The thickness and surface shape should be measured simultaneously to reduce cost. In this research, the absolute optical thickness and surface shape of a 6–mm-thick fused silica transparent plate of diameter 100mm was measured simultaneously by a three-surface Fizeau interferometer. A measurement method combining the wavelength tuning Fourier and phase shifting technique was proposed. The absolute optical thickness that corresponds to the group refractive index was determined by wavelength tuning Fourier analysis. At the beginning and end of the wavelength tuning, the fractional phases of the interference fringes were measured by the phase shifting technique and optical thickness deviations with respect to the ordinary refractive index and surface shape were determined. These two kinds of optical thicknesses were synthesized using the Sellmeier equation for the refractive index of fused silica glass, and the least square fitting method was used to determine the final absolute optical thickness distribution. The experimental results indicate that the all the measurement uncertainties for the absolute optical thickness and surface shape were approximately 3nm and 35nm, respectively.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The absolute optical thickness and surface shape of a transparent plate were measured simultaneously using wavelength tuning. </LI> <LI> Two kinds of signal from interferogram were separated in the frequency domain using 4<I>N</I> − 3 phase shifting algorithm. </LI> <LI> 4<I>N</I> − 3 algorithm was used for compensating the phase shift errors and coupling errors. </LI> <LI> Two kinds of optical thicknesses were synthesized using Sellmeier equation and least square fitting. </LI> </UL> </P>
The Clinical Efficacy of GOCA Scoring System in Patients with Acute Respiratory Distress Syndrome
Yangjin Jegal,Sang Il Lee,Kyung Hee Lee,Yeon Mok Oh,Tae Sun Shim,Chae Man Lim,Sang Do Lee,Woo Sung Kim,Dong Soon Kim,Won Dong Kim,Younsuck Koh 대한의학회 2008 Journal of Korean medical science Vol.23 No.3
To explore the following hypotheses: 1) Gas exchange, Organ failure, Cause, Associated disease (GOCA) score, which reflects both general health and the severity of lung injury, would be a better mortality predictor of acute respiratory distress syndrome (ARDS) than acute physiology and chronic health evaluation (APACHE II) or simplified acute physiology score (SAPS II), which are not specific to lung injury, and lung injury score (LIS) that focuses on the lung injury; 2) the performance of APACHE II and SAPS II will be improved when reinforced by LIS, we retrospectively analyzed ARDS patients (N=158) admitted to a medical intensive care unit for five years. The overall mortality of the ARDS patients was 53.2%. Calibrations for all models were good. The area under the curve of (AUC) of LIS (0.622) was significantly less than those of APACHE II (0.743) and SAPS II (0.753). The AUC of GOCA (0.703) was not better than those of APACHE II and SAPS II. The AUCs of APACHE II and SAPS II tended to further increase when reinforced by LIS. In conclusion, GOCA was not superior to APACHE II or SAPS II. The performance of the APACHE II or SAPS II tended to improve when combining a general scoring system with a scoring system that focused on the severity of lung injury.
The role of stromal cells in cancer cell invasion
Yangjin Kim,Hans G Othmer,Sookkyung Lim 한국산업응용수학회 2012 한국산업응용수학회 학술대회 논문집 Vol.7 No.1
Ductal carcinoma in situ (DCIS) is an early stage non-invasive breast cancer that originates in the epithelial lining of the milk ducts. These cells actively proliferate and stay in the duct. However, DCIS can evolve into comedo DCIS and ultimately the most common type of breast cancer, invasive ductal carcinoma, which can induce metastasis. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. Stromal tissue surrounding a duct contains the extracellular matrix (ECM), several types of cells and several types of growth factors that are known to individually affect tumor growth and invasion, but at present the complex mechanical and biochemical interactions of these stromal cells with cancer cells is poorly understood. Among those stromal cells, fibroblasts and their aggressive types, myofibroblasts, were shown to play an important role in tumor growth and invasion. Here we illustrate how hybrid models can reproduce experimental results and generate predictions that need to be verified in followup experiments. The mathematical model incorporates the cross-talk between stromal and tumor cells via growth factors and several types of proteases. The model predict how perturbations of the local biochemical and mechanical state influence tumor evolution and invasion. Epithelial cells (ECs) and stromal cells are modeled individually and their interactions are mediated by a set of partial differential equations for growth factors and proteases. Our results shed light on the biochemical and mechanical interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.
The Role of the Tumor Microenvironment in Glioblastoma: A Mathematical Model
Kim, Yangjin,Jeon, Hyejin,Othmer, Hans IEEE 2017 IEEE Transactions on Biomedical Engineering Vol.64 No.3
<P>Glioblastoma multiforme is one of the deadliest human cancers and is characterized by tumor cells that hijack immune system cells in a deadly symbiotic relationship. Microglia and glioma infiltrating macrophages, which in principle should mount an immune response to the tumor, are subverted by tumor cells to facilitate growth in several ways. In this study, we seek to understand the interactions between the tumor cells and the microglia that enhance tumor growth, and for this purpose, we develop a mathematical and computational model that involves reaction-diffusion equations for the important components in the interaction. These include the densities of tumor and microglial cells, and the concentrations of growth factors and other signaling molecules. We apply this model to a transwell assay used in the laboratory to demonstrate that microglia can stimulate tumor cell invasion by secreting the growth factor TGF-β. We show that the model can both replicate the major components of the experimental findings and make new predictions to guide future experiments aimed at the development of new therapeutic approaches. Sensitivity analysis is used to identify the most important parameters as an aid to future experimental work. This study is the first step in a program that involves development of detailed 3-D models of the mechanical and biochemical interactions between a glioblastoma and the tumor microenvironment.</P>
( Yangjin Jegal ),( Jong Sun Park ),( Song Yee Kim ),( Hongseok Yoo ),( Sung Hwan Jeong ),( Jin Woo Song ),( Jae Ha Lee ),( Hong Lyeol Lee ),( Sun Mi Choi ),( Young Whan Kim ),( Yong Hyun Kim ),( Hye 대한결핵 및 호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2
Background: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. Methods: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. Results: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. Conclusion: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.