Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor

Natural killer (NK) cellâ based immunotherapy is a promising strategy for cancer treatment, and caspaseâ 3 is an important effector molecule in NK cellâ mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cellâ based immunotherapy by serial noninvasive imaging of apoptosis using a caspaseâ 3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspaseâ 3 sensor as a surrogate marker for caspaseâ 3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54â CR cells. Human NK92 cells were used as effector cells. Treatment with NK92 cells resulted in a timeâ and effector numberâ dependent increase in bioluminescence imaging (BLI) activity of the caspaseâ 3 sensor in D54â CR cells in vitro. Caspaseâ 3 activation by NK92 treatment was blocked by Zâ VAD treatment in D54â CR cells. Transfusion of NK92 cells induced an increase of the BLI signal by caspaseâ 3 activation in a doseâ and timeâ dependent manner in D54â CR tumorâ bearing mice but not in PBSâ treated mice. Accordingly, sequential BLI with the Rluc reporter gene revealed marked retardation of tumor growth in the NK92â treatment group but not in the PBSâ treatment group. These data suggest that noninvasive imaging of apoptosis with a caspaseâ 3 sensor can be used as an effective tool for evaluation of therapeutic efficacy as well as for optimization of NK cellâ based immunotherapy.â Lee, H. W., Singh, T. D., Lee, S.â W., Ha, J.â H., Rehemtulla, A., Ahn, B.â C., Jeon, Y.â H., Lee, J. Evaluation of therapeutic effects of natural killer (NK) cellâ based immunotherapy in mice using in vivo apoptosis bioimaging with a caspaseâ 3 sensor. FASEB J. 28, 2932â 2941 (2014). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154541/1/fsb2fj13243014.pd

High Prevalence of Opisthorchis viverrini Infection in a Riparian Population in Takeo Province, Cambodia

Opisthorchis viverrini infection was found to be highly prevalent in 3 riverside villages (Ang Svay Chek A, B, and C) of the Prey Kabas District, Takeo Province. This area is located in the southern part of Cambodia, where the recovery of adult O. viverrini worms was recently reported. From May 2006 until May 2010, fecal examinations were performed on a total of 1,799 villagers using the Kato-Katz thick smear technique. In the 3 villages, the overall positive rate for helminth eggs ranged from 51.7 to 59.0% (av. 57.4%), and the percentage positive for O. viverrini was 46.4-50.6% (47.5%). Other helminths detected included hookworms (13.2%), echinostomes (2.9%), Trichuris trichiura (1.3%), Ascaris lumbricoides (0.6%), and Taenia spp. (0.06%). The prevalence of O. viverrini eggs appeared to reflect a lower infection in younger individuals (<20 years) than in the adult population (>20 years). Men (50.4%) revealed a significantly higher (P=0.02) prevalence than women (44.3%). The Ang Svay Chek villages of the Prey Kabas District, Takeo Province, Cambodia have been confirmed to be a highly endemic area for human O. viverrini infection

Effects of Combined Therapy with Ezetimibe Plus Simvastatin After Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337±227 vs. 443±366 cells, P=0.292), but neointima area was significantly smaller (1.00±0.49 mm2 vs. 1.69±0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3±10% vs. 39±19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99±0.79 vs. 1.81±0.88, P=0.49), endothelial score (1.75±0.66 vs. 1.80±0.59, P=0.79), and the percent of endothelium covered lumen (43±21% vs. 45±21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model

Deep-learning-based enhanced optic-disc photography.

Optic-disc photography (ODP) has proven to be very useful for optic nerve evaluation in glaucoma. In real clinical practice, however, limited patient cooperation, small pupils, or media opacities can limit the performance of ODP. The purpose of this study was to propose a deep-learning approach for increased resolution and improved legibility of ODP by contrast, color, and brightness compensation. Each high-resolution original ODP was transformed into two counterparts: (1) down-scaled 'low-resolution ODPs', and (2) 'compensated high-resolution ODPs' produced via enhancement of the visibility of the optic disc margin and surrounding retinal vessels using a customized image post-processing algorithm. Then, the differences between these two counterparts were directly learned through a super-resolution generative adversarial network (SR-GAN). Finally, by inputting the high-resolution ODPs into SR-GAN, 4-times-up-scaled and overall-color-and-brightness-transformed 'enhanced ODPs' could be obtained. General ophthalmologists were instructed (1) to assess each ODP's image quality, and (2) to note any abnormal findings, at 1-month intervals. The image quality score for the enhanced ODPs was significantly higher than that for the original ODP, and the overall optic disc hemorrhage (DH)-detection accuracy was significantly higher with the enhanced ODPs. We expect that this novel deep-learning approach will be applied to various types of ophthalmic images

Evaluation of the Reversal of Multidrug Resistance by MDR1 Ribonucleic Acid Interference in a Human Colon Cancer Model Using a Renilla Luciferase Reporter Gene and Coelenterazine

The reversal effect of multidrug resistance (MDR1) gene expression by adenoviral vector-mediated MDR1 ribonucleic acid interference was assessed in a human colon cancer animal model using bioluminescent imaging with Renilla luciferase (Rluc) gene and coelenterazine, a substrate for Rluc or MDR1 gene expression. A fluorescent microscopic examination demonstrated an increased green fluorescent protein signal in Ad-shMDR1- (recombinant adenovirus that coexpressed MDR1 small hairpin ribonucleic acid [shRNA] and green fluorescent protein) infected HCT-15/Rluc cells in a virus dose-dependent manner. Concurrently, with an increasing administered virus dose (0, 15, 30, 60, and 120 multiplicity of infection), Rluc activity was significantly increased in AdshMDR1-infected HCT-15/Rluc cells in a virus dose-dependent manner. In vivo bioluminescent imaging showed about 7.5-fold higher signal intensity in Ad-shMDR1-infected tumors than in control tumors (p < .05). Immunohistologic analysis demonstrated marked reduction of P-glycoprotein expression in infected tumor but not in control tumor. In conclusion, the reversal of MDR1 gene expression by MDR1 shRNA was successfully evaluated by bioluminescence imaging with Rluc activity using an in vivo animal model with a multidrug resistance cancer xenograft