Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer.

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs.

Corrigendum to "Visualization of the Biological Behavior of Tumor-Associated Macrophages in Living Mice with Colon Cancer Using Multimodal Optical Reporter Gene Imaging" [ 18 (2016) 133-141].

[This corrects the article DOI: 10.1016/j.neo.

Visualization of the Biological Behavior of Tumor-Associated Macrophages in Living Mice with Colon Cancer Using Multimodal Optical Reporter Gene Imaging.

We sought to visualize the migration of tumor-associated macrophages (TAMs) to tumor lesions and to evaluate the effects of anti-inflammatory drugs on TAM-modulated tumor progression in mice with colon cancer using a multimodal optical reporter gene system. Murine macrophage Raw264.7 cells expressing an enhanced firefly luciferase (Raw/effluc) and murine colon cancer CT26 cells coexpressing Rluc and mCherry (CT26/Rluc-mCherry, CT26/RM) were established.

Inverse Agonist of Estrogen-Related Receptor γ Enhances Sodium Iodide Symporter Function Through Mitogen-Activated Protein Kinase Signaling in Anaplastic Thyroid Cancer Cells.

Unlabelled: Anaplastic thyroid cancer (ATC), a rare thyroid cancer with poor prognosis, is associated with insufficient function of the sodium iodide symporter (NIS). Estrogen-related receptor γ (ERRγ) is a member of the orphan nuclear receptors with important functions in cell development and homeostasis. However, there are no reports that demonstrate whether ERRγ is related to NIS function.

Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes.

We sought to evaluate the feasibility of molecular imaging using the human sodium iodide symporter (hNIS) gene as a reporter, in addition to the enhanced firefly luciferase (effluc) gene, for tracking dendritic cell (DCs) migration in living mice. A murine dendritic cell line (DC2.4) co-expressing hNIS and effluc genes (DC/NF) was established.

Combined Fluorescence and Magnetic Resonance Imaging of Primary Macrophage Migration to Sites of Acute Inflammation Using Near-Infrared Fluorescent Magnetic Nanoparticles.

Purpose: This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI).

Procedures: Primary macrophages were labeled with NIR fluorescent magnetic nanoparticles, and labeled cells were injected into mice intravenously. One day later, inflammation was induced by subcutaneous injection of 1% carrageenan (CG) solution to footpads of the right hind leg, and phosphate-buffered saline (PBS) as control treatment was subcutaneously injected to footpad of the left hind leg.

Noninvasive imaging of apoptosis induced by adenovirus-mediated cancer gene therapy using a caspase-3 biosensor in living subjects.

We attempted to visualize the serial induction of caspase-3-dependent apoptosis mediated by Fas ligand/tumor necrosis factor-related apoptosis-inducing ligand (FasL/TRAIL) adenoviral gene therapy in mice bearing human glioma xenografts using a caspase-3 biosensor and monitored its therapeutic effects. Human D54 glioma cells expressing both the caspase-3 sensor and the Renilla luciferase (Rluc) gene were established (referred to as D54-CR cells). The bioluminescence imaging (BLI) signals of the caspase-3 sensor in the D54-CR cells were increased in a time- and virus dose-dependent manner by Ad-TRAIL or Ad-FasL transduction.

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) cell-based immunotherapy is a promising strategy for cancer treatment, and caspase-3 is an important effector molecule in NK cell-mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cell-based immunotherapy by serial noninvasive imaging of apoptosis using a caspase-3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspase-3 sensor as a surrogate marker for caspase-3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54-CR cells.

Dual reporter gene imaging for tracking macrophage migration using the human sodium iodide symporter and an enhanced firefly luciferase in a murine inflammation model.

Purpose: The purpose of this study is to visualize the migration of reporter macrophages expressing both the human sodium iodide symporter (hNIS) and enhanced firefly luciferase (effluc) gene in mice with chemically induced inflammation.

Procedures: A macrophage cell line expressing both hNIS and effluc genes (Raw264.7/hNIS-effluc, herein referred to as a Raw264.

Effects of single treatment of anti-dementia drugs on sleep-wake patterns in rats.

We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30.

L-theanine partially counteracts caffeine-induced sleep disturbances in rats.

L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.

Combined E7-dendritic cell-based immunotherapy and human sodium/iodide symporter radioiodine gene therapy with monitoring of antitumor effects by bioluminescent imaging in a mouse model of uterine cervical cancer.

Using a uterine cervical cancer cell line expressing human papillomavirus (HPV) 16 E7 antigen and bioluminescent imaging (BLI), we evaluated the therapeutic potential of combined immunotherapy using transfected dendritic cells (DC-E7) and human sodium/iodide symporter (hNIS) radioiodine gene therapy in a xenograft animal cancer model. Dendritic cells expressing either E7 antigen (DC-E7) or no-insert (DC-no insert) were made for immunization materials, and murine uterine cervical cancer cell line coexpressing E7, firefly luciferase, hNIS, and EGFP genes (TC-1/FNG) were prepared for the animal tumor model. C57BL/6 mice were divided into five therapy groups (phosphate-buffered saline [PBS], DC-no insert, DC-E7, I-131, and DC-E7+I-131 groups).

Enhanced antiproliferative effects of combination hexokinase II shRNA and NIS gene therapy on vascular smooth muscle cells.

Introduction: This study was designed to determine the antiproliferative effects of combination gene therapy using sodium iodide symporter (NIS)-based radioiodine and lentivirus-mediated short hairpin RNA (shRNA) against hexokinase II (HKII) on vascular smooth muscle cells (VSMCs).

Methods: A7r5 rat VSMCs were stably transfected with a dual-expression vector of NIS and Fluc (A7r5-NL cells). Functional assessment was performed by radioiodine uptake assay, luciferase assay and confocal microscopy.

Combined Cerenkov luminescence and nuclear imaging of radioiodine in the thyroid gland and thyroid cancer cells expressing sodium iodide symporter: initial feasibility study.

Radioiodine (RI) such as (131)I or (124)I, can generate luminescent emission and be detected with an optical imaging (OI) device. To evaluate the possibility of a novel Cerenkov luminescence imaging (CLI) for application in thyroid research, we performed feasibility studies of CLI by RI in the thyroid gland and human anaplastic thyroid carcinoma cells expressing sodium iodide symporter gene (ARO-NIS). For in vitro study, FRTL-5 and ARO-NIS were incubated with RI, and the luminometric and CLI intensity was measured with luminometer and OI device.

Human sodium iodide symporter added to multidrug resistance 1 small hairpin RNA in a single gene construct enhances the therapeutic effects of radioiodine in a nude mouse model of multidrug resistant colon cancer.

The objective of this study was to investigate the therapeutic potential of ¹³¹I added to doxorubicin therapy in multidrug resistance (MDR) mouse colon cancer coexpressing the MDR1 small hairpin RNA (shRNA) and human sodium iodide symporter (hNIS) gene in a single gene construct and to visualize the antitumor effects using molecular nuclear imaging. HCT-15 coexpressing shRNA for MDR1 gene (MDR1 shRNA) and hNIS gene with a single construct was established (referred to as MN61 cell). Inhibition of P-gp function by MDR1 shRNA and functional activity of hNIS gene was assessed using a ⁹⁹(m)Tc sestamibi uptake and ¹²⁵I uptake, respectively.

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 Ad-shMDR1-infected HCT-15/Rluc cells in a virus dose-dependent manner.

Trafficking macrophage migration using reporter gene imaging with human sodium iodide symporter in animal models of inflammation.

Unlabelled: The aim of this study was to investigate the feasibility of nuclear molecular imaging using the human sodium iodide symporter (hNIS) as a reporter gene to monitor macrophage migration toward the inflammatory foci.

Methods: A stable macrophage cell line coexpressing hNIS and green fluorescent protein (GFP) genes (RAW264.7/hNIS-GFP and R(NIS) cell) was established from an immortalized macrophage cell line (RAW264.

Enhanced antitumor effects by combination gene therapy using MDR1 gene shRNA and HSV1-tk in a xenograft mouse model.

The use of a novel therapeutic vector containing HSV1-thymidine kinase (HSV1-tk) and a short hairpin RNA for the MDR1 gene (shMDR) was proposed previously. We investigated the antitumor effects in an in vivo mouse model of colon cancer and assessed treatment response by serial non-invasive imaging. shMDR-TK expressing (MTKG) tumors for the dual therapy group mice with ganciclovir and doxorubicin showed a decrease in size, while tumors in the single therapy group mice showed a moderate increase (p<0.

Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP.

The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP.

In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells.

The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells. Apigenin (50% inhibition concentration, IC(50) = 1.

Inhibition of radiation-induced apoptosis via overexpression of SMP30 in Smad3-knockout mice liver.

Apoptosis occurs early after irradiation and may be a good indicator of radiation damages. Since elevated levels of TGF-beta are associated with radiation-induced inflammation, the null mice of Smad3, a key downstream mediator of TGF-beta, show accelerated healing of irradiated injury. In order to evaluate resistance to radiation-induced liver injuries in Smad3-null mice, we determined the occurrence of apoptosis and the expression of senescence marker protein-30 (SMP30), as an anti-apoptotic marker, after irradiation to the liver.

Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined.

Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells.

This study examined the comparative anticancer effects of flavonoids and diazepam in the cultured cancer cells. In the SNU-C4 colorectal and MDA-MB-231 breast adenocarcinoma cells, apigenin and fisetin, flavonoids, and diazepam inhibited cancer cell survival concentration and incubation-time dependently. Diazepam consistently inhibited FAS activity, a known anticancer mechanism of flavonoids, in a concentration dependent manner.

Direct comparison of adenosine and adenosine 5'-triphosphate as pharmacologic stress agents in conjunction with Tl-201 SPECT: Hemodynamic response, myocardial tracer uptake, and size of perfusion defects in the same subjects.

Background: Adenosine 5'-triphosphate (ATP), a potent and inexpensive coronary vasodilator, was introduced as a pharmacologic stress agent for thallium 201 single photon emission computed tomography (SPECT). However, there has been no direct comparison of ATP and adenosine as myocardial stressors in the same subjects.

Methods And Results: Thirty-six patients underwent consecutive Tl-201 SPECT imaging with adenosine and ATP in a randomly assigned order.