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Objective Benefits of adjuvant treatment in pT1N1 gastric cancer (GC) remain controversial. Additionally, an effective biomarker for early GC is the need of the hour. The prognostic and predictive roles of single patient classifier (SPC) were validated in stage II/III GC. In this study, we aimed to elucidate the role of SPC as a biomarker for pT1N1 GC. Methods The present retrospective biomarker study (NCT03485105) enrolled patients treated for pT1N1 GC between 1996 and 2012 from two large hospitals (the Y cohort and S cohort). For SPC, mRNA expression of four classifier genes (GZMB, WARS, SFRP4 and CDX1) were evaluated by real-time reverse transcription-polymerase chain reaction assay. The SPC was revised targeting pT1 stages and the prognosis was stratified as high- and low-risk group by the expression of SFRP4, a representative epithelial-mesenchymal transition marker. Results SPC was evaluated in 875 patients (n=391 and 484 in the Y and S cohorts, respectively). Among 864 patients whose SPC result was available, 41 (4.7%) patients experience GC recurrence. According to revised SPC, 254 (29.4%) patients were classified as high risk [123 (31.5%) and 131 (27.1%) in the Y and S cohorts, respectively]. The high risk was related to frequent recurrence in both Y and S cohort (log-rank P=0.023, P

An increasing number of studies indicate air pollutants infiltrate into the brain. We aimed to find the association of cumulative air pollution exposure in the main body of primary brain tumor: glioblastoma (GBM). In this double‐cohort, retrospective analysis study with a protocol, we compared the health effect of air pollution on the GBM patients from the SEER (Surveillance, Epidemiology, and End Results Program) in 27 U.S. counties from 10 states and GBM patients of Severance cohort of Korea. From 2000 to 2015, 10621 GBM patients of the SEER were individually evaluated for the cumulative average exposure for each pollutant, and 9444 (88.9%) mortality events were reported. From 2011 to 2018, 398 GBM patients of the Severance with the same protocol showed 259 (65.1%) mortality events. The multi‐pollutant models show that the association level of risk with CO is increased in the SEER (HR 1.252; 95% CI 1.141‐1.373) with an increasing linear trend of relative death rate in the spline curve. The Severance GBM data showed such a statistically significant result of the health impact of CO on GBM patients. The overall survival gain of the less exposure group against CO was 2 and 3 months in the two cohorts. Perioperative exposure to CO may increase the risk of shorter survival of GBM patients of the SEER and the Severance cohort., This retrospective observational study found that chronic exposure to ambient level of carbon monoxide is associated with a shorter survival of glioblastoma patients (2‐3 months). Such association was validated in the cohorts of the United states (N=10621, HR 1.252, 95% CI 1.141‐1.373) and Korea (N=398, HR 2.874, 95% CI 1.040‐7.944).

Gallbladder carcinoma (GBC) exhibits poor prognosis due to local recurrence, metastasis, and resistance to targeted therapies. Using clinicopathological analyses of GBC patients along with molecular in vitro and tumor in vivo analysis of GBC cells, we showed that reduction of Dsg2 expression was highly associated with higher T stage, more perineural, and lymphatic invasion. Dsg2-depleted GBC cells exhibited significantly enhanced proliferation, migration, and invasiveness in vitro and tumor growth and metastasis in vivo through Src-mediated signaling activation. Interestingly, Dsg2 binding inhibited Src activation, whereas its loss activated cSrc-mediated EGFR plasma membrane clearance and cytoplasmic localization, which was associated with acquired EGFR-targeted therapy resistance and decreased overall survival. Inhibition of Src activity by dasatinib enhanced therapeutic response to anti-EGFR therapy. Dsg2 status can help stratify predicted patient response to anti-EGFR therapy and Src inhibition could be a promising strategy to improve the clinical efficacy of EGFR-targeted therapy.

Background & aims Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma (HCC). We performed a meta-analysis to determine the diagnostic performance of the CEUS LR-5 for HCC and the pooled proportions of HCCs in each CEUS LI-RADS category. Methods We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI-RADS. Random-effects model was used to determine summary estimates of the diagnostic performance of CEUS LR-5 and the pooled proportions of HCCs in each CEUS LI-RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per-observation sensitivity and specificity of the CEUS LR-5 for diagnosing HCC were 69% (95% confidence interval [CI], 64%-73%) and 92% (95% CI, 83%-96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0-0%) for LR-1, 1% (95% CI, 0%-4%) for CEUS LR-2, 26% (95% CI, 14%-39%) for CEUS LR-3, 77% (95% CI, 68%-86%) for CEUS LR-4, 97% (95% CI, 95%-98%) for CEUS LR-5, 57% (95% CI, 44%-69%) for CEUS LR-M and 100% (95% CI, 93%-100%) for CEUS LR-5V or TIV. Conclusions The CEUS LR-5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI-RADS categories.

This study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P P = 0.010 [external validation]) and the merged model (0.719, P P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.

Summary Background Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer. Methods In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. Findings We identified four classifier genes related to relevant gastric cancer features ( GZMB, WARS, SFRP4 , and CDX1 ) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS , and SFRP4 ) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS , and CDX1 ) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% [95% CI 73·5–87·1] vs 64·5% [56·8–73·3]; univariate hazard ratio 0·47 [95% CI 0·30–0·75], p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% [66·5–79·9] in patients who received chemotherapy plus surgery vs 72·5% [65·8–79·9] in patients who only had surgery; 0·93 [0·62–1·38], p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (p interaction =0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort. Interpretation The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted. Funding Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.

This paper presents the development of an oscillator and a detector based on InP HBT technology operating near 300 GHz, and their application to terahertz reflection-mode imaging. The fabricated fundamental-mode common-base (CB) cross-coupled oscillator exhibits a peak output power of 5.3 dBm at 305.8 GHz, and the CB direct detector shows a responsivity higher than 40 kV/W and noise equivalent power lower than ${\text{35 pW/}}\sqrt {{\text{Hz}}} $ for a frequency range of 270–345 GHz. The imaging system employing the fabricated circuits as the signal source and detector was characterized for the resolution and dynamic range, and then, successfully applied for imaging various biological samples. The results show that low-power terahertz reflection-mode imaging based on solid-state electronic sources and detectors based on a commercial semiconductor technology is promising for various biomedical imaging applications.

We detected keratinizing squamous cell carcinoma (SCC) of the tongue using terahertz reflection imaging and reported unexpected characteristics that THz reflection intensity of tumor was low in normal regions.

Small animal positron emission tomography (PET) is a noninvasive imaging modality that enables in vivo imaging and quantification of the biological processes of small experimental animals. We have developed a small animal PET that utilizes a high-resolution multiplexed readout and charge signal transmission (CST) method. The small animal PET was composed of six detector blocks consisting of SiPMs and LYSO arrays. Six detector blocks were mounted on a PET gantry having an inner diameter of 76 mm, outer diameter of 112 mm, and axial length of 40.8 mm. The charge signals of SiPM output were transmitted to the input of multiplexed readout using 4 m flexible flat cables. The multiplexed readout was composed of six main boards, each of which included 36 detector boards, to reduce the number of readout channels by a factor of 36, with a multiplexing ratio of 144:4. The performance of the small animal PET was evaluated using NEMA NU 4-2008 standards, and its imaging capability was demonstrated by in vivo mouse imaging studies. The average energy and time resolutions were 13.2% ± 0.3% and 3.8 ns, respectively. The spatial resolution at the center of the transaxial FOV was 1.1 mm, and the peak sensitivity at the center of the axial FOV was 1.5%. The peak noise equivalent count (NEC) rate and scatter fraction were 21.1 kcps at 18.2 MBq and 21%, respectively. The acquired images demonstrated high quality tracer uptake patterns of small experimental animals. The results of performance evaluation and animal imaging indicate that the small animal PET developed in this study can provide high-quality small animal imaging with cost-effectiveness and compactness.

// Cheol Keun Park 1 , Ji Soo Park 2 , Hyo Song Kim 2 , Sun Young Rha 2 , Woo Jin Hyung 3 , Jae-Ho Cheong 3 , Sung Hoon Noh 3 , Sang Kil Lee 4 , Yong Chan Lee 4 , Yong-min Huh 5 , Hyunki Kim 1 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 YUMS-KRIBB Medical Convergence Research Institute, Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Keywords: gastric cancer, receptor tyrosine kinase, amplification, screening algorithm Received: June 17, 2016 Accepted: September 17, 2016 Published: September 27, 2016 ABSTRACT Although targeted therapy for receptor tyrosine kinases (RTKs) of advanced gastric cancers (AGCs) has been in the spotlight, guidelines for the identification of RTK-amplified gastric cancers (RA-GCs) have not been established. In this study, we investigate clinicopathologic characteristics of RA-GCs and propose a screening algorithm for their identification. We performed immunohistochemistry (IHC) for MLH1, MSH2, PMS2, MSH6, key RTKs (EGFR, HER2, MET), and p53, in situ hybridization for Epstein-Barr virus encoding RNA, and silver in situ hybridization (SISH) for EGFR , HER2 , and MET using tissue microarrays of 993 AGCs. On IHC, 157 (15.8%) 61, (6.15%), and 85 (8.56%) out of 993 cases scored 2+ or 3+ for EGFR, HER2, and MET, respectively. On SISH, 31.2% (49/157), 80.3% (49/61), and 30.6% (26/85) of 2+ or 3+ cases on IHC showed amplification of the corresponding genes. Of the 993 cases, 104 were classified as RA-GCs. RA-GC status correlated with older age ( P < 0.001), differentiated histology ( P = 0.001), intestinal or mixed type by Lauren classification ( P < 0.001), lymphovascular invasion ( P = 0.026), and mutant-pattern of p53 ( P < 0.001). The cases were divided into four subgroups using two classification systems, putative molecular classification and histologic-molecular classification , based on Lauren classification, IHC, and SISH results. The histologic-molecular classification showed higher sensitivity for identification of RA-GCs and predicted patient prognosis better than the putative molecular classification . In conclusion, RA-GCs show unique clinicopathologic features. The proposed algorithm based on histologic-molecular classification can be applied to select candidates for genetic examination and targeted therapy.

Study of the absorption spectrum in film dosimetry is important because the spectral absorbance of the film is related to the film’s total absorption dose. We investigated the absorption spectra of Gafchromic EBT2 film at various rotational angles in a visible wavelength band. The film was irradiated with 6- MV photon beams for a total dose of 300 cGy. The absorption spectra for different angles of rotation were obtained 24 h after the irradiation and we fitted the spectra by using Lorentzian functions. Two dominant absorption peaks, one at approximately 586 nm (green) and the other at 634 nm (red) were observed. The measured spectrum was decomposed into peaks at 542 nm, 558 nm, 578 nm, 586 nm, 626 nm, 634 nm, and 641 nm. The maximum total area of the red absorption band occurred at 45° (225°) and the minimum at 90° (270°). As the angle of rotation changed, the intensities and integrated areas of the blue and the green peaks also changed with a 180° period, with minima at 90° and 270°, and maxima at 0° and 180°, although the overall absorbance was very low. The spectral peak wavelengths remained constant within ±1.2 nm for all angles. The absorption spectrum of the film should no hysteresis of; spectra taken at 0° and 360° were substantially the same and showed similar behaviors for all rotational angles. The change in the absorbance with the rotational angle of the film affected the dosimetric properties, resulting in rotational variations of the film’s dosimetry in each red-green-blue channel.

A decade ago, cancer stem cells (CSCs) were introduced as target cells for an innovative cancer treatment. Particularly, there have been a lot of biological researches on glioblastoma (GBM) CSCs. However, as there is a comprehensive change in the concept of CSCs, it is required to review how the different CSCs for patients can be clinically used, or clinical credentialing, and summarize the possibilities of clinical credentialing. In this regard, this review aims to introduce the tumorsphere obtained from GBM specimen and summarize the clinical dilemma and clinically applicable areas.

Purpose Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. Materials and Methods Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. Results There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. Conclusion SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.

It has been reported that cancer stem cells (CSCs) can be isolated from primitive neuroectodermal tumor (PNET) specimens. Moreover, mesenchymal stem-like cells (MSLCs) have been isolated from Korean glioma specimens. Here, we tested whether tumor spheres and MSLCs can be simultaneously isolated from a single PNET specimen, a question that has not been addressed.We isolated single-cell suspensions from PNET specimens, then cultured these cells using methods for MSLCs or CSCs. Cultured cells were analyzed for surface markers of CSCs using immunocytochemistry and for surface markers of bone marrow-derived mesenchymal stem cells (BM-MSCs) using fluorescence-activated cell sorting (FACS). Tumor spheres were exposed to neural differentiation conditions, and MSLCs were exposed to mesenchymal differentiation conditions. Possible locations of MSLCs within PNET specimens were determined by immunofluorescence analysis of tumor sections.Cells similar to tumor spheres and MSLCs were independently isolated from one of two PNET specimens. Spheroid cells, termed PNET spheres, were positive for CD133 and nestin, and negative for musashi and podoplanin. PNET spheres were capable of differentiation into immature neural cells and astrocytes, but not oligodendrocytes or mature neural cells. FACS analysis revealed that adherent cells isolated from the same PNET specimen, termed PNET-MSLCs, had surface markers similar to BM-MSCs. These cells were capable of mesenchymal differentiation. Immunofluorescence labeling indicated that some CD105(+) cells might be closely related to endothelial cells and pericytes.We showed that both tumor spheres and MSLCs can be isolated from the same PNET specimen. PNET-MSLCs occupied a niche in the vicinity of the vasculature and could be a source of stroma for PNETs.

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems.

Background: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. Methods: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. Results: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. Conclusion: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

// Junjeong Choi 1, 2, * , Ji-Hyun Lee 3, * , Ilkyoo Koh 4, * , Jin-Kyoung Shim 3 , Junseong Park 3 , Jeong Yong Jeon 5 , Mijin Yun 5 , Se Hoon Kim 6 , Jong In Yook 7 , Eui Hyun Kim 3 , Jong Hee Chang 3 , Sun Ho Kim 3 , Yong Min Huh 8 , Su Jae Lee 9 , Michael Pollak 10 , Pilnam Kim 4 , Seok-Gu Kang 3 , Jae-Ho Cheong 11 1 Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea 2 Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea 3 Departments of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea 5 Departments of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Departments of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 7 Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Republic of Korea 8 Departments of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 9 Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea 10 Department of Oncology and Medicine, McGill University, Gerald Bronfman Centre, Montreal, Quebec, Canada 11 Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Pilnam Kim, email: pkim@kaist.ac.kr Seok-Gu Kang, email: seokgu9@gmail.com Keywords: biguanide, glioblastoma, HL156A, invasion, tumorsphere Received: January 26, 2016 Accepted: August 13, 2016 Published: August 25, 2016 ABSTRACT Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.

We designed and fabricated a novel terahertz (THz) otoscope to help physicians to diagnose otitis media (OM) with both THz diagnostics and conventional optical diagnostics. We verified the potential of this tool for diagnosing OM using mouse skin tissue and a human tympanic membrane samples prior to clinical application. (C) 2016 Optical Society of America

The isolation from brain tumors of tumor mesenchymal stem-like cells (tMSLCs) suggests that these cells play a role in creating a microenvironment for tumor initiation and progression. The clinical characteristics of patients with primary glioblastoma (pGBM) positive for tMSLCs have not been determined. This study analyzed samples from 82 patients with pGBM who had undergone tumor removal, pathological diagnosis, and isolation of tMSLC from April 2009 to October 2014. Survival, extent of resection, molecular markers, and tMSLC culture results were statistically evaluated. Median overall survival was 18.6 months, 15.0 months in tMSLC-positive patients and 29.5 months in tMSLC-negative patients (P=0.014). Multivariate cox regression model showed isolation of tMSLC (OR = 2.5, 95% CI = 1.1~5.6,P=0.021) showed poor outcome while larger extent of resection (OR = 0.5, 95% CI = 0.2~0.8,P=0.011) has association with better outcome. The presence of tMSLCs isolated from the specimen of pGBM is associated with the survival of patient.

We estimated the photothermal transduction efficiency of gold nanorod (GNR) solutions for different GNR concentrations and irradiation laser power. In particular, we verified that the degree of cell death area could be modulated by GNR concentration and irradiation laser power. The efficacy of GNR-produced photothermal ablation of cancer cells was evaluated by irradiating GNRs in the presence of MDA-MB-231 breast cancer cells with a near-infrared (NIR) laser at different laser power densities and irradiation times. GNR-induced photothermal ablation was applied successfully to cancer cells at various NIR laser power densities and irradiation times and was characterized with live-dead cell staining. Through these techniques, we established the system for not only verification of induced photothermal effect using NIR laser and thermocouple, but also identification of uptake efficiency for GNRs and cell viability using dark field and fluorescence imaging, respectively.

We obtained the diagnostic images of cancerous tumors by employing the THz molecular imaging (TMI) technique which measured the THz response change by surface plasmon resonance induced on the surface of nanoparticles with a irradiation of near-infrared (NIR) beam. To demonstrate the principle of the TMI technique, THz images of tissues with nanoprobes were observed and compared with THz only images. The sensitivity of TMI was further enhanced by adopting a THz differential measurement technique, which was realized by modulating the NIR beams. By employing this differential TMI technique, the diagnostic images of cancerous tumors were obtained ex vivo and in vivo in the preclinical stage. These images indicated the feasibility of applying the differential TMI technique in the clinical stage.

High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expressing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens.We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling.GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1](+), CD9(+), CD45(-), CD11b(-), CD31(-), and nerve/glial antigen 2 [NG2](-)). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes.Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.

Purpose The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. Materials and Methods We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. Results Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P

At magnetic resonance (MR) imaging and multidetector computed tomography (CT), artifacts arising from metallic orthopedic hardware are an obstacle to obtaining optimal images. Although various techniques for reducing such artifacts have been developed and corroborated by previous researchers, a new era of more powerful MR imaging and multidetector CT modalities has renewed the importance of a systematic consideration of methods for artifact reduction. Knowledge of the factors that contribute to artifacts, of related theories, and of artifact reduction techniques has become mandatory for radiologists. Factors that affect artifacts on MR images include the composition of the metallic hardware, the orientation of the hardware in relation to the direction of the main magnetic field, the strength of the magnetic field, the pulse sequence type, and other MR imaging parameters (mainly voxel size, which is determined by the field of view, image matrix, section thickness, and echo train length). At multidetector CT, the factors that affect artifacts include the composition of the hardware, orientation of the hardware, acquisition parameters (peak voltage, tube charge, collimation, and acquired section thickness), and reconstruction parameters (reconstructed section thickness, reconstruction algorithm used, and whether an extended CT scale was used). A comparison of images obtained with different hardware and different acquisition and reconstruction parameters facilitates an understanding of methods for reducing or overcoming artifacts related to metallic implants.

To retrospectively determine the accuracy of coronal contrast material-enhanced fat-suppressed three-dimensional (3D) fast spoiled gradient-recalled acquisition in the steady state (SPGR) magnetic resonance (MR) imaging, as compared with that of routine transverse MR imaging, in the assessment of distal tibiofibular syndesmosis injury, with arthroscopy as the reference standard.The review board of the College of Medicine in Yonsei University approved this study; informed consent was waived. The study group comprised 45 patients (26 men, 19 women; mean age, 32.1 years; range, 18-58 years) with a chronic ankle injury who had undergone MR imaging and arthroscopic surgery. Three independent readers retrospectively reviewed the two sets of MR images (one set of gadolinium-enhanced 3D fast SPGR images and one set of routine T1-, T2-, and intermediate-weighted images). Scores from 1 to 5 in increasing order of the probability of injury were assigned to both sets. Arthroscopy was the reference standard. Syndesmotic recess height was measured on contrast-enhanced images. The two sets of images were compared for diagnostic performance with receiver operating characteristic (ROC) analysis. Dissection and histologic examination of six cadaveric ankles was performed to assess the syndesmotic area and ascertain the enhancing structure at MR imaging.At arthroscopy, syndesmotic injury was found in 24 ankles but not in 21 ankles. Areas under the ROC curve were significantly higher for the contrast-enhanced images (P.05). The contrast-enhanced set showed higher accuracy, sensitivity, and specificity compared with the routine set for the assessment of syndesmosis injury. Mean syndesmotic recess height was significantly greater (P.05) in patients with syndesmotic injury. Dissection and histologic examination revealed a highly vascular synovial fold in the syndesmotic area that is expected to enhance at MR imaging.In the assessment of chronic syndesmosis injury, coronal gadolinium-enhanced fat-suppressed 3D fast SPGR MR images were more sensitive, specific, and accurate than routine MR images.

SIMULTANEOUS functional and anatomical imaging using PET-MR system has been reported to be useful in preclinical research to investigate various in vivo biological processes [1-3]. The purpose of this study was to develop a MR compatible small animal PET insert and to evaluate the performance of the developed PET and the influence of the PET on MRI performance.

We have investigated the feasibility of THz time-domain reflectometry for the discrimination of human early gastric cancer (EGC) from the normal gastric region. Eight fresh EGC tissues, which were resected by endoscopic submucosal dissection, were studied. Of them, six lesions were well discriminated on THz images and the regions well correlated with tumor regions on pathologically mapped images. Four THz parameters could be suggested for quantitative discrimination of EGCs. (C) 2015 Optical Society of America

ObjectivesTo obtain compensatory ultra-short echo time (UTE) imaging and T2-weighted (T2W) imaging of Watanabe heritable hyperlipidemic (WHHL) rabbits following dextran-coated magnetic nanocluster (DMNC) injection for the effective in vivo detection of inflammatory vascular wall.MethodsMagnetic nanoparticle was synthesized by thermal decomposition and encapsulated with dextran to prepare DMNC. The contrast enhancement efficiency of DMNC was investigated using UTE (repetition time [TR] = 5.58 and TE = 0.07 ms) and T2W (TR = 4000 and TE = 60 ms) imaging sequences. To confirm the internalization of DMNC into macrophages, DMNC-treated macrophages were visualized by cellular transmission electron microscope (TEM) and magnetic resonance (MR) imaging. WHHL rabbits expressing macrophage-rich plaques were subjected to UTE and T2W imaging before and after intravenous DMNC (120 μmol Fe/kg) treatment. Ex vivo MR imaging of plaques and immunostaining studies were also performed.ResultsPositive and negative contrast enhancement of DMNC solutions with increasing Fe concentrations were observed in UTE and T2W imaging, respectively. The relative signal intensities of the DMNC solution containing 2.9 mM Fe were calculated as 3.53 and 0.99 in UTE and T2W imaging, respectively. DMNC uptake into the macrophage cytoplasm was visualized by electron microscopy. Cellular MR imaging of DMNC-treated macrophages revealed relative signals of 3.00 in UTE imaging and 0.98 in T2W imaging. In vivo MR images revealed significant brightening and darkening of plaque areas in the WHHL rabbit 24 h after DMNC injection in UTE and T2W imaging, respectively. Ex vivo MR imaging results agreed with these in vivo MR imaging results. Histological analysis showed that DMNCs were localized to areas of inflammatory vascular wall.ConclusionsUsing compensatory UTE and T2W imaging in conjunction with DMNC is an effective approach for the noninvasive in vivo imaging of atherosclerotic plaque.

Background: Soft-tissue impingement syndrome is now increasingly being recognized as a significant cause of chronic ankle pain. The aim of this study was to investigate the diagnostic accuracy of contrast-enhanced, fat-suppressed, three-dimensional (3D), fast-gradient-recalled acquisition in the steady state with radio-frequency-spoiling (CE 3D-FSPGR) magnetic resonance imaging (MRI), and to evaluate the clinical outcome of arthroscopic treatment of soft-tissue impingement associated with the ankle trauma. Methods: This study reviewed 38 patients who had preoperative MRI and arthroscopic treatment of chronic ankle pain after trauma. The CE 3D-FSPGR MRI was used to evaluate the chronic ankle pain, and the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score was used to evaluate the clinical results after arthroscopic treatment. Results: The CE 3D-FSPGR MRI showed a sensitivity of 91.9%, a specificity of 84.4%, and an accuracy of 87.5% in diagnosing synovitis and soft tissue impingement. All patients had excellent or good outcomes after arthroscopic debridement. Conclusion: The results of this study suggest that a preoperative fat-suppressed CE 3D-FSPGR MRI is highly beneficial in diagnosing synovitis and soft-tissue impingement and that arthroscopic debridement of the synovitis or soft-tissue impingement has a good clinical outcome.

We demonstrated that tumors in freshly excised whole brain tissue could be differentiated clearly from normal brain tissue using a reflection-type terahertz (THz) imaging system. THz binary images of brain tissues with tumors indicated that the tumor boundaries in the THz images corresponded well to those in visible images. Grey and white-matter regions were distinguishable owing to the different distribution of myelin in the brain tissue. THz images corresponded closely with magnetic resonance imaging (MRI) results. The MRI and hematoxylin and eosin-stained microscopic images were investigated to account for the intensity differences in the THz images for fresh and paraffin-embedded brain tissue. Our results indicated that the THz signals corresponded to the cell density when water was removed. Thus, THz imaging could be used as a tool for label-free and real-time imaging of brain tumors, which would be helpful for physicians to determine tumor margins during brain surgery. (C)2014 Optical Society of America

Cancer stem cells (CSCs) have been reported to be critical in the initiation, maintenance, and progression of cancers. The expression of stem cell markers, such as podoplanin (PDPN), CD133, and nestin, may have been correlated with malignant progression. However, the effects of CSCs and stem cell markers on clinical outcomes in cancer patients remain unclear. In this study, we assessed the prognostic roles of glioma CSCs (gCSCs) isolation and stem cell markers in patients with primary glioblastoma (pGBM). A cohort of 39 patients with pGBM was separated into two groups, those positive or negative for gCSCs, and the correlation between gCSC and patient survival was evaluated. We observed significantly different cumulative survival (P=0.045) when comparing patients positive for gCSCs patients and negative for gCSC. Among the patients positive for gCSCs, we observed no significant differences in survival between those whose gCSCs were each positive or negative for PDPN, CD133, or nestin. This study strongly supports the prognostic value of gCSCs isolation on the survival of patients with pGBM.

The purpose of this study was to assess the role of inflamed synovial volume (ISV) in defining a state of remission in rheumatoid arthritis (RA) with contrast-enhanced, fatsuppression, three-dimensional (3D) gradient-recalled acquisition in the steady state with radiofrequency spoiling (SPGR) magnetic resonance (MR) imaging. Sixteen patients with RA (5 remission and 11 non-remission patients) were enrolled in this study. Contrast-enhanced, fat-suppression, 3D-SPGR MR imaging was performed before (n 5 12) and after (n 5 16) a mean 17 months of disease-modifying antirheumatic drugs (DMARDs). ISV was calculated by using a segmentation method. Statistical analysis of changes in ISVs and residual ISVs between the remission and the non-remission groups was performed. Intra- and interobserver reproducibility was tested. Residual ISVs and relative changes in ISVs were 3.23 6 1.84 cm3 and 51.4% (range 47.6‐55.2%) in the remission group and 6.26 6 2.03 cm 3 and 31.4% (range -73.5‐53.5%) in the non-remission group. Both values were significantly different between the two groups (P F 0.05 and 0.05, respectively). Volume measurement showed high reproducibility: Intra- and interobserver mean percentage errors were 5.04, 7.06, and 5.09%, respectively. Residual ISVs and relative changes in ISVs measured by MR imaging may provide objective and quantitative parameters in defining a state of remission in RA after therapy; however, the clinical utility of these measurements remains to be verified. J. Magn. Reson. Imaging 1999;10:202‐208. r 1999 Wiley-Liss, Inc.

We demonstrate the use of a THz penetration-enhancing agent (THz-PEA) to enhance the terahertz (THz) wave penetration depth in tissues. The THz-PEA is a biocompatible material having absorption lower than that of water, and it is easily absorbed into tissues. When using glycerol as a THz-PEA, the peak value of the THz signal which was transmitted through the fresh tissue and reflected by a metal target, was almost doubled compared to that of tissue without glycerol. THz time-of-flight imaging (B-scan) was used to display the sequential glycerol delivery images. Enhancement of the penetration depth was confirmed after an artificial tumor was located below fresh skin. We thus concluded that the THz-PEA technique can potentially be employed to enhance the image contrast of the abnormal lesions below the skin. (C)2013 Optical Society of America

We present the medical applications of the terahertz spectroscopic imaging technology to the brain and blood system as well as to the molecular imaging for the target specific imaging.

We present a photo-thermal therapeutics control technique using terahertz (THz) imaging technology and an optical beam intensity modulation method. The heat induced in nanoparticle probes under irradiation by a near-infrared beam was monitored using a THz imaging system and was fixed by adjusting the illumination time of the optical beam. The THz-monitored optical beam modulation technique allowed the viability of cells to be controlled.

Recently, the advancement of nanotechnology has had a significant impact on clinical therapeutics. Advances in biocompatible drug carriers using organic/inorganic nanoparticles have enabled safer and more efficient delivery of anti-cancer agents. In particular, nanoparticles designed and fabricated by sophisticated processes can (as drug carriers) deliver precise doses of multiple anti-cancer agents to target cancer cells, improving therapeutic efficacy and minimizing side effects. In addition, a comprehensive understanding of cancer biology, chemo-resistance, cancer relapse, and metastasis is essential for successful development of combination therapy using nanoparticles. In this review, we discuss the species of functional nanoparticles for delivery of anti-cancer agents and their potential to improve chemotherapeutic indices via combination therapy. We also discuss novel therapeutic strategies using functional nanoparticles developed through multidisciplinary collaboration for combination chemotherapy.

We determined the optical constant of whole blood and its constituents by using terahertz spectroscopy and showed that the concentration of red blood cells in whole blood could be determined using the terahertz absorption constant.

We obtained the terahertz images of fresh brains with and without tumor by using reflection type terahertz pulses imaging system.

We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

In this paper, the principle of terahertz molecular imaging (TMI) used for the visualization of nanoparticle delivery is presented. In addition, a brief review of terahertz (THz) technology in terms of the generation, detection, and characteristics of THz waves is given. The TMI technique entails the sensitive measurement of the change in the THz optical coefficients of water induced by the surface plasmon resonance of nanoparticles. It is shown that the measured THz response is linearly proportional to the concentration of the nanoparticles. Nanoparticle delivery to acancerous tumor and the organs in a mouse is imaged by employing the TMI technique. This technique enables target-specific sensing of cancers as well as molecular diagnosis of drug delivery.

The objective of this study was to investigate the usefulness of virtual MR arthroscopy as an adjunct to conventional MR arthrography in detecting various anteroinferior glenoid labral lesions.The study group was composed of 28 patients (22 men and six women; mean age, 25 years) who underwent direct MR arthrography of the shoulder as well as arthroscopy due to recurrent shoulder dislocations. MR arthrography examinations were reviewed retrospectively with radiologists blinded to the arthroscopic diagnoses. Virtual MR arthroscopy was produced from fat-suppressed 3D gradient-recalled echo MR arthrography using volume-rendering software. The sensitivity, specificity, and accuracy for diagnosis were calculated. The diagnostic performances were validated by receiver operating characteristic curve analysis.The structure of the glenoid labrum was well visualized in a 3D perspective, and characterization of the injured anterior glenoid labrum was aided by adjunct use of virtual MR arthroscopy. The accuracy for detecting classic Bankart, anterior labroligamentous periosteal sleeve avulsion, and Perthes lesions improved to 85.7%, 85.7%, and 92.9%, respectively, with adjunct virtual MR arthroscopy with MR arthrography versus 78.6%, 82.1%, and 89.3%, respectively, with MR arthrography alone. A statistically significant improvement of the diagnostic capability of MR arthrography with adjunct virtual MR arthroscopy was proven for the detection of a classic Bankart lesion (p0.05).Having a 3D perspective to validate chronic recurrent glenoid labral injuries of the shoulder facilitated understanding of the anatomic relationships and helped diagnosis. Adjunct virtual MR arthroscopy is potentially useful for detecting and characterizing chronic recurrent glenoid labral lesions to improve diagnosis.

To determine whether magnetic resonance imaging (MRI) can enable magnetically labeled mesenchymal stem cell (MSC) tracking and simultaneous in vivo functional data acquisition in rat models of myocardial infarction. Superparamagnetic iron oxide-laden human MSCs were injected into rat myocardium infarcted by cryoinjury 3 weeks after myocardial infarction. The control group received cell-free media injection. Before injection and for 3 months after, in vivo serial MRI was performed. Electrocardiography-gated gradient echo sequence MRI and cine MRI were performed for in vivo cell tracking and assessing cardiac function using left ventricular ejection fraction (LVEF), respectively. MRI revealed a persistent signal-void representing iron-laden MSCs until ten post-injection weeks. Serial follow-up MRI revealed that LVEF was significantly higher in the MSC injection group than in the control group. We conclude that MRI enables in vivo tracking of injected cells and evaluation of the long-term therapeutic potential of MSCs for myocardial infarction.

We show in this study that nanoparticle composites can be used as contrast agents to enhance the sensitivity of terahertz medical imaging. The terahertz reflection signal increases by nearly 50 % for the sample with nanoparticles upon near infrared laser beam irradiation. This is due to the hyperthermia effect induced by surface plasma polaritons. This technique facilitates cancer diagnosis with a micron resolution.

In the present study, we examined the neuroprotective effects and mechanisms of implanted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in ischemic stroke. hUC-MSCs were isolated from the endothelial/subendothelial layers of the human umbilical cord and cultured. Twenty days after the induction of in vitro neuronal differentiation, about 77.4% of the inoculated hUC-MSCs displayed morphological features of neurons and expressed neuronal cell markers like TU-20, Trk A, NeuN, and NF-M. However, functionally active neuronal type channels were not detected by electrophysiological examination. Before, during, or one day after in vitro neuronal differentiation, the hUC-MSCs produced granulocyte-colony stimulating factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. In an in vivo study, implantation of the hUC-MSCs into the damaged hemisphere of immunosuppressed ischemic stroke rats improved neurobehavioral function and reduced infarct volume relative to control rats. Three weeks after implantation, most of the implanted hUC-MSCs were present in the damaged hemisphere; some of these cells expressed detectable levels of neuron-specific markers. Nestin expression in the hippocampus was increased in the hUC-MSC-implanted group relative to the control group. Since the hUC-MSCs were both morphologically differentiated into neuronal cells and able to produce neurotrophic factors, but had not become functionally active neuronal cells, the improvement in neurobehavioral function and the reduction of infarct volume might be related to the neuroprotective effects of hUC-MSCs rather than the formation of a new network between host neurons and the implanted hUC-MSCs.

We present the sensitivity improvement of total internal reflection fluorescence microscopy for imaging intracellular molecular movements near cell membranes. We investigated employing dielectric films on a prism substrate for the enhancement of fluorescence emission intensity. A two-layer dielectric thin film structure using Al2O3 and SiO2 was designed and fabricated to provide the maximal field enhancement for 442 nm excitation at a reasonable angle of incidence (T). The field enhancement achieved by the design was 8.5 at T = 53.8o for TE polarization and confirmed experimentally using microbeads. Preliminary results in live cell imaging were obtained using quantum dots.

This paper presents based on nano-grating based field enhancement in total internal reflection fluorescence microscopy. A sample of silver grating/film on a glass substrate was used for imaging microbeads and confirmed the field enhancement.

Evanescent field enhancement was investigated experimentally based on dielectric thin films in TIRF microscopy. Field intensity enhancement measured by microbeads and live-cell imaging relative to that of a control without dielectric films was polarization dependent.

Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG-ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG-ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG-ADV and Herceptin immobilized PEG-ADV (HER-PEG-ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER-PEG-ADV exhibited more enhanced level of GFP expression than PEG-ADV did for MDA-MB-435 and MDA-MB-468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER-PEG-ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity.

Purpose To introduce and evaluate the usefulness of the adduction internal rotation (ADIR) position in MR arthrography for discriminating the following subtypes of Bankart lesions: classic Bankart lesions, anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesions, and Perthes lesions. Materials and Methods The study group consisted of 25 patients who had been referred for MR arthrography of the shoulder and then underwent arthroscopy due to recurrent episodes of shoulder dislocation. MR arthrography was performed in three different positions: neutral, abduction external rotation (ABER), and ADIR. The authors evaluated the statistical significance of the method's discriminative diagnostic ability for the subtypes of Bankart lesions according to the position changes. Results Twenty-three patients had the following single or complex labral lesions: classic Bankart (N = 8), ALPSA (N = 3), complex classic Bankart/ALPSA (N = 8), and complex ALPSA/Perthes (N = 4). Two patients had no visible anteroinferior labral lesions. The performance of ADIR positioning for differentiating ALPSA lesions was superior to the neutral or ABER positioning. The difference of the discriminative lesion detection ability was statistically significant (P