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1.  Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1 
Cell Research  2011;21(9):1305-1315.
Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differentiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data support that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4.
doi:10.1038/cr.2011.107
PMCID: PMC3193470  PMID: 21709693
reprogramming; transdifferentiation; neural stem cells; induced pluripotent stem cells; Bmi1; Oct4
2.  Identification of Nasal Bone Fractures on Conventional Radiography and Facial CT: Comparison of the Diagnostic Accuracy in Different Imaging Modalities and Analysis of Interobserver Reliability 
Iranian Journal of Radiology  2013;10(3):140-147.
Background
There has been no study to compare the diagnostic accuracy of an experienced radiologist with a trainee in nasal bone fracture.
Objectives
To compare the diagnostic accuracy between conventional radiography and computed tomography (CT) for the identification of nasal bone fractures and to evaluate the interobserver reliability between a staff radiologist and a trainee.
Patients and Methods
A total of 108 patients who underwent conventional radiography and CT after acute nasal trauma were included in this retrospective study. Two readers, a staff radiologist and a second-year resident, independently assessed the results of the imaging studies.
Results
Of the 108 patients, the presence of a nasal bone fracture was confirmed in 88 (81.5%) patients. The number of non-depressed fractures was higher than the number of depressed fractures. In nine (10.2%) patients, nasal bone fractures were only identified on conventional radiography, including three depressed and six non-depressed fractures. CT was more accurate as compared to conventional radiography for the identification of nasal bone fractures as determined by both readers (P <0.05), all diagnostic indices of an experienced radiologist were similar to or higher than those of a trainee, and κ statistics showed moderate agreement between the two diagnostic tools for both readers. There was no statistical difference in the assessment of interobserver reliability for both imaging modalities in the identification of nasal bone fractures.
Conclusion
For the identification of nasal bone fractures, CT was significantly superior to conventional radiography. Although a staff radiologist showed better values in the identification of nasal bone fracture and differentiation between depressed and non-depressed fractures than a trainee, there was no statistically significant difference in the interpretation of conventional radiography and CT between a radiologist and a trainee.
doi:10.5812/iranjradiol.6353
PMCID: PMC3857976  PMID: 24348599
Nasal Bone, Fractures, Bone; Radiography
3.  Anticonvulsant Effects of β-Hydroxybutyrate in Mice 
Journal of Epilepsy Research  2012;2(2):29-32.
Background and Purpose:
The ketogenic diet was formulated to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies. Recent research data suggest that the anticonvulsant efficacy of the KD may be due in part to the direct actions of ketone bodies. This study was designed to investigate the anticonvulsant effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in mature mice.
Methods:
Eighty-two male ICR mice at postnatal day 49 were used. All mice were pretreated with scopolamine methylbromide prior to pilocarpine injection. Experimental mice (n=42) were injected intraperitoneally with BHB (20 mmol/kg) 15 min prior to pilocarpine administration, while control animals (n=40) with normal saline. Pilocarpine (300 mg/kg) was administered intraperitoneally and mice were monitored for 2 h after pilocarpine injection.
Results:
All mice developed typical seizure behaviors. The mean (±SD) latency to the onset of seizures was significantly prolonged in the BHB-treated mice compared with controls (4.83±1.95 min vs. 3.67±1.90 min, p<0.01).
Conclusions:
This study demonstrates that treatment with BHB prolongs the latency to the onset of seizures induced by pilocarpine in mature mice and suggests that BHB, one of the ketone bodies, may have direct anticonvulsant effects.
doi:10.14581/jer.12008
PMCID: PMC3952323  PMID: 24649459
Ketone body; 3-hydroxybutyric acid; Pilocarpine; Mice; Seizure
4.  Printable, wide band-gap chalcopyrite thin films for power generating window applications 
Scientific Reports  2014;4:4408.
Printable, wide band-gap chalcopyrite compound films (CuInGaS2, CIGS) were synthesized on transparent conducting oxide substrates. The wide band-gap and defective nature of the films reveal semi-transparent and bifacial properties that are beneficial for power generating window applications. Importantly, solar cell devices with these films demonstrate a synergistic effect for bifacial illumination resulting in a 5.4–16.3% increase of the apparent power conversion efficiency compared to the simple sum of the efficiencies of the front and rear side illumination only. We also confirmed that this extra output power acquisition due to bifacial irradiation is apparently not influenced by the light intensity of the rear side illumination, which implies that weak light (e.g., indoor light) can be efficiently utilized to improve the overall solar cell efficiency of bifacial devices.
doi:10.1038/srep04408
PMCID: PMC3957128  PMID: 24637380
5.  Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities 
Blood research  2014;49(1):22-28.
Background
The coexistence of t(9;22)(q34;q11.2) and inv(16)(p13q22) chromosomal abnormalities is extremely uncommon, and only a small number of such cases have been reported. Here, we characterized 7 cases of hematologic malignancy exhibiting t(9;22) and inv(16) coexistence.
Methods
We reviewed the cytogenetic data for hematologic malignancies treated at the Catholic Blood and Marrow Transplantation Center between January 2004 and June 2013. We identified 7 cases exhibiting t(9;22) and inv(16) coexistence. In addition, we analyzed mutations in the IKZF1, NPM1, FLT3, N-RAS, K-RAS, c-KIT, and TP53 genes.
Results
Four cases of chronic myelogenous leukemia (CML; 1 chronic phase, 2 accelerated phase, and 1 blast phase) and 3 cases of acute myeloid leukemia (AML; 1 de novo and 2 therapy-related) were identified. The percentages of circulating blasts and bone marrow eosinophils were higher in AML cases than in CML cases (53% vs. 5% and 30% vs. 5.5%, respectively). The proportions of each chromosomal abnormality were used along with follow-up karyotyping results to identify secondary changes. In BCR/ABL, a p210 fusion transcript was associated with CML, whereas a p190 fusion transcript was associated with AML. One patient with AML harbored 2 mutations: c-KIT D816V and TP53 E11Q. All patients except 1 with CML blast phase sustained clinical remission after treatment, which included an imatinib mesylate regimen.
Conclusion
This study shows that observations of bone marrow morphology, initial and follow-up cytogenetic studies, and karyotyping of BCR/ABL1 and CBFB/MYH11 provide valuable information for characterizing hematologic malignancies exhibiting t(9;22) and inv(16) coexistence.
doi:10.5045/br.2014.49.1.22
PMCID: PMC3974952  PMID: 24724063
Chronic myelogenous leukemia; Acute myeloid leukemia; t(9;22); BCR/ABL1; inv(16); CBFB/MYH11
6.  Focal Cortical Dysplasia and Epilepsy Surgery 
Journal of Epilepsy Research  2013;3(2):43-47.
Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. With advances in neuroimaging techniques, in particular MRI, recent studies have revealed a higher prevalence of FCD than previously estimated and have improved the preoperative identification and classification of these abnormalities. However, MRI frequently does not show any abnormalities in patients with pathologically proven FCD. In this situation, functional neuroimaing such as FDG-PET and ictal SPECT can be helpful. FCD is thought to be intrinsically epileptogenic, because the dysplastic tissues contain aberrant neural networks that are highly susceptible to abnormal excitation. The response to the medical treatment of epilepsy has been documented as consistently poor. Therefore, surgical resection has been an important alternative treatment for patients with intractable epilepsy related to FCD. Incomplete resection of FCD has been consistently known to be a poor prognostic factor. However, the complete removal of FCD is often difficult because the demarcation of the lesion is frequently poor, and dysplastic tissues tend to be more extensive than is apparent on MRI. Evidence indicates that even patients with MRI abnormalities who have resective epilepsy surgery for FCD have worse surgical outcomes than those of patients who have surgery for other focal lesional epilepsy syndromes. Careful planning of evelauation using intracranial electrodes is necessary for successful epilepsy surgery.
doi:10.14581/jer.13009
PMCID: PMC3952251  PMID: 24649472
Focal cortical dysplasia; Epilepsy; Surger
7.  An atypical case of rare salivary malignancy, hyalinizing clear cell carcinoma 
As an uncommon, malignant salivary gland tumor with female predominance, hyalinizing clear cell carcinoma (HCCC) is regarded as an indolent tumor. The diagnosis of this rare tumor is challenging, and it depends on microscopic and immunohistochemical (IHC) studies. Although it is regarded as an indolent tumor, there are reports of unconventional forms with aggressive clinical courses. We report an atypical case of this rare tumor, HCCC, in a male patient who had a relatively large-sized mass (3.8×3.0 cm) on the right mouth floor with ipsilateral neck node metastasis. The clinical, radiological, pathological, and IHC features together with the clinical course are described.
doi:10.5125/jkaoms.2013.39.6.283
PMCID: PMC3912786  PMID: 24516818
Adenocarcinoma; Clear cell; Sublingual gland; Head and neck neoplasms
8.  Autophagy Controls an Intrinsic Host Defense to Bacteria by Promoting Epithelial Cell Survival: A Murine Model 
PLoS ONE  2013;8(11):e81095.
Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigella spp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella infection. In this study, however, we found Shigella could invade the terminal ileum of the mouse small intestine by 1 hour after infection and be rapidly cleared within 24 h. These early phase events occurred shortly after oral infection resulting in epithelial shedding, degranulation of Paneth cells, and cell death in the intestine. During this process, autophagy proceeded without any signs of inflammation. In contrast, blocking autophagy in epithelial cells enhanced host cell death, leading to tissue destruction and to inflammation, suggesting that autophagic flow relieves cellular stress associated with host cell death and inflammation. Herein we propose a new concept of “epithelial barrier turnover” as a general intrinsic host defense mechanism that increases survival of host cells and inhibits inflammation against enteric bacterial infections, which is regulated by autophagy.
doi:10.1371/journal.pone.0081095
PMCID: PMC3834267  PMID: 24260541
9.  Draft Genome Sequence of Beta-Hemolytic Streptococcus iniae KCTC 11634 
Genome Announcements  2013;1(6):e00897-13.
Streptococcus iniae is a beta-hemolytic, Gram-positive coccus, which affects a broad range of freshwater and marine fish species, causing substantial economic losses in the aquaculture industry worldwide. Thus, it is very important to derive a complete genome sequence of the bacterium to aid in the development of vaccines and methods for preventing fish streptococcosis and zoonotic infections in humans. Here, we present the draft genome sequence of S. iniae KCTC 11634 (1,955,615 bp, with a G+C content of 36.6%), which contains 1,868 putative coding sequences.
doi:10.1128/genomeA.00897-13
PMCID: PMC3820773  PMID: 24201192
10.  Genome Sequence of Marine Bacterium Idiomarina sp. Strain 28-8, Isolated from Korean Ark Shells 
Genome Announcements  2013;1(5):e00772-13.
Idiomarina sp. strain 28-8 is an aerobic, Gram-negative, flagellar bacterium isolated from the bodies of ark shells (Scapharca broughtonii) collected from underwater sediments in Gangjin Bay, South Korea. Here, we present the draft genome sequence of Idiomarina sp. 28-8 (2,971,606 bp, with a G+C content of 46.9%), containing 2,795 putative coding sequences.
doi:10.1128/genomeA.00772-13
PMCID: PMC3790083  PMID: 24092779
11.  Genome Sequence of Streptococcus parauberis Strain KCTC11980, Isolated from Diseased Paralichthys olivaceus 
Genome Announcements  2013;1(5):e00780-13.
Streptococcus parauberis is a coccoid, nonmotile, alpha-hemolytic, Gram-positive bacterium of the Streptococcaceae family. Streptococcus parauberis strain KCTC11980 was isolated from the kidney of a diseased olive flounder collected from an aquaculture farm on Jeju Island in 2010. The 2.12-Mb genome sequence consists of 44 large contigs in 16 scaffolds and contains 2,214 predicted protein-coding genes, with a G+C content of 35.4%.
doi:10.1128/genomeA.00780-13
PMCID: PMC3790086  PMID: 24092782
12.  The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma 
Blood research  2013;48(3):198-205.
Background
Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear.
Methods
We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy.
Results
Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum β2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes.
Conclusion
These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.
doi:10.5045/br.2013.48.3.198
PMCID: PMC3786280  PMID: 24086940
Multiple myeloma; Novel agents; Autologous stem cell transplantation; Induction and maintenance treatment
13.  The Validity and Reliability of Characterizing Epilepsy Based on an External Review of Medical Records 
Epidemiology and Health  2013;35:e2013006.
OBJECTIVES
Our goal is to validate diagnosing and characterizing epilepsy based on a medical record survey by external reviewers.
METHODS
We reviewed medical records from 80 patients who received antiepileptic drugs in 2009 at two hospitals. The study consisted of two steps; data abstraction by certified health record administrators and then verification by the investigators. The gold standard was the results of the survey performed by the epileptologists from their own hospital.
RESULTS
The specificity was more than 90.0% for diagnosis and activity, and for new-onset seizures. The sensitivity was 97.0% or more for diagnosis and activity and 66.7-75.0% for new-onset epilepsy. This method accurately classified epileptic syndromes in 90.2-92.9% of patients, causes in 85.4-92.7%, and age of onset in 78.0-81.0%. Kappa statistics for inter-rater reliability and test-retest reliability ranged from 0.641-0.975, which means substantial to near-perfect agreement in all items.
CONCLUSIONS
Our data suggest that epilepsy can be well identified by external review of medical records. This method may be useful as a basis for large-scale epidemiological research.
doi:10.4178/epih/e2013006
PMCID: PMC3753460  PMID: 23991344
Validity; Epilepsy; Epidemiology; Sensitivity; Specificity; Reliability
14.  Evidence for multiple waves of global transmission within the seventh cholera pandemic 
Nature  2011;477(7365):462-465.
Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year (http://www.who.int/wer). Historically there have been seven acknowledged cholera pandemics; included in the 7th and ongoing pandemic are the recent outbreaks in Zimbabwe and Haiti1. Only serogroup O1 isolates (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O1392,3 can cause epidemic cholera2. It is believed that the first six cholera pandemics were caused by the classical biotype but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic1. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the 7th pandemic appear superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic we identified high resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny we show that the 7th pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950’s and identify multiple transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped the pandemic spread and show that it was first acquired at least 10 years prior to its discovery in V. cholerae.
doi:10.1038/nature10392
PMCID: PMC3736323  PMID: 21866102
15.  Structural Properties of Polyphenols Causing Cell Cycle Arrest at G1 Phase in HCT116 Human Colorectal Cancer Cell Lines 
Plant-derived polyphenols are being tested as chemopreventive agents; some polyphenols arrest the cell cycle at G1 phase, whereas others inhibit cell cycle proliferation at G2/M phase. Therefore, polyphenols have been proposed to inhibit cell cycle progression at different phases via distinct mechanisms. Indeed, our previous studies showed that small structural differences in polyphenols cause large differences in their biological activities; however, the details of the structural properties causing G1 cell cycle arrest remain unknown. In this study, we prepared 27 polyphenols, including eight different scaffolds, to gain insight into the structural conditions that arrest the cell cycle at G1 phase in a quantitative structure–activity relationship study. We used cell cycle profiles to determine the biophores responsible for G1 cell cycle arrest and believe that the biophores identified in this study will help design polyphenols that cause G1 cell cycle arrest.
doi:10.3390/ijms140816970
PMCID: PMC3759946  PMID: 23965967
polyphenols; flavonoids; colorectal cancer; cell cycle; QSAR
16.  Secondary neutron dose measurement for proton eye treatment using an eye snout with a borated neutron absorber 
Background
We measured and assessed ways to reduce the secondary neutron dose from a system for proton eye treatment.
Methods
Proton beams of 60.30 MeV were delivered through an eye-treatment snout in passive scattering mode. Allyl diglycol carbonate (CR-39) etch detectors were used to measure the neutron dose in the external field at 0.00, 1.64, and 6.00 cm depths in a water phantom. Secondary neutron doses were measured and compared between those with and without a high-hydrogen–boron-containing block. In addition, the neutron energy and vertices distribution were obtained by using a Geant4 Monte Carlo simulation.
Results
The ratio of the maximum neutron dose equivalent to the proton absorbed dose (H(10)/D) at 2.00 cm from the beam field edge was 8.79 ± 1.28 mSv/Gy. The ratio of the neutron dose equivalent to the proton absorbed dose with and without a high hydrogen-boron containing block was 0.63 ± 0.06 to 1.15 ± 0.13 mSv/Gy at 2.00 cm from the edge of the field at depths of 0.00, 1.64, and 6.00 cm.
Conclusions
We found that the out-of-field secondary neutron dose in proton eye treatment with an eye snout is relatively small, and it can be further reduced by installing a borated neutron absorbing material.
doi:10.1186/1748-717X-8-182
PMCID: PMC3723544  PMID: 23866307
Proton; Secondary; Neutron; CR-39; Boron; Eye
17.  Global Phylogeny of Shigella sonnei Strains from Limited Single Nucleotide Polymorphisms (SNPs) and Development of a Rapid and Cost-Effective SNP-Typing Scheme for Strain Identification by High-Resolution Melting Analysis 
Journal of Clinical Microbiology  2013;51(1):303-305.
The current Shigella sonnei pandemic involves geographically associated, multidrug-resistant clones. This study has demonstrated that S. sonnei phylogeny can be accurately defined with limited single nucleotide polymorphisms (SNPs). By typing 6 informative SNPs using a high-resolution melting (HRM) assay, major S. sonnei lineages/sublineages can be identified as defined by whole-genome variation.
doi:10.1128/JCM.02238-12
PMCID: PMC3536230  PMID: 23115259
18.  Ultrasound-guided fine-needle aspiration for retrojugular lymph nodes in the neck 
Background
No study on ultrasound-guided fine-needle aspiration (US-FNA) for the diagnosis of retrojugular lymph node has been reported. The present study aimed to introduce US-FNA techniques for retrojugular lymph node and to evaluate their efficacy.
Methods
Of the 788 patients who underwent US-FNA of the cervical lymph node, 41 patients underwent US-FNAs of retrojugular lymph node and were included in this study. The adequacy and efficacy of US-FNA of retrojugular lymph node and related complications during or after the procedure were assessed.
Results
Of the 41 patients, 35 (85.4%) were adequately diagnosed in cytological analysis; four predominantly cystic lymph nodes were identified. Based on cytohistopathology results, thyroglobulin measurement, tuberculosis polymerase chain reaction, and sonographic follow-up, malignant (n = 26) and benign (n = 15) lymph nodes were confirmed. When six lymph nodes with inadequate cytology were classified as benign and malignant, the sensitivity, specificity, positive and negative predictive values, and accuracy of US-FNA in differentiating malignant from benign lesions were 69.2% and 92.3%, 100% and 100%, 100% and 100%, 65.2% and 88.2%, and 80.5% and 95.1%, respectively. No substantial complications related to the US-FNA procedure were observed.
Conclusions
The present US-FNA method may be helpful for the diagnosis of retrojugular lymph node.
doi:10.1186/1477-7819-11-121
PMCID: PMC3671968  PMID: 23721570
Lymph node; Retrojugular; Fine-needle biopsy; Papillary thyroid carcinoma; Metastasis
19.  Draft Genome Sequence of Klebsiella pneumoniae subsp. pneumoniae DSM 30104T 
Journal of Bacteriology  2012;194(20):5722-5723.
Klebsiella pneumoniae is a Gram-negative, rod-shaped, nonmotile, and opportunistic pathogenic species with clinical importance. It is a part of natural flora of humans and animals. Here we report the draft genome sequence of the type strain of Klebsiella pneumoniae subsp. pneumoniae (DSM 30104T) to provide taxonomic and functional insights into the species.
doi:10.1128/JB.01388-12
PMCID: PMC3458660  PMID: 23012294
20.  Recurrent SETBP1 mutations in atypical chronic myeloid leukemia 
Nature genetics  2012;45(1):18-24.
Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16–35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.
doi:10.1038/ng.2495
PMCID: PMC3588142  PMID: 23222956
21.  Risk of second cancer from scattered radiation of intensity-modulated radiotherapies with lung cancer 
Purpose
To compare the risk of secondary cancer from scattered and leakage doses following intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with lung cancer.
Methods
IMRT, VMAT and TOMO were planned for five lung cancer patients. Organ equivalent doses (OEDs) are estimated from the measured corresponding secondary doses during irradiation at various points 20 to 80 cm from the iso-center by using radio-photoluminescence glass dosimeter (RPLGD).
Results
The secondary dose per Gy from IMRT, VMAT and TOMO for lung cancer, measured 20 to 80 cm from the iso-center, are 0.02~2.03, 0.03~1.35 and 0.04~0.46 cGy, respectively. The mean values of relative OED of secondary dose of VMAT and TOMO, which is normalized by IMRT, ranged between 88.63% and 41.59% revealing 88.63% and 41.59% for thyroid, 82.33% and 41.85% for pancreas, 77.97% and 49.41% for bowel, 73.42% and 72.55% for rectum, 74.16% and 81.51% for prostate. The secondary dose and OED from TOMO became similar to those from IMRT and VMAT as the distance from the field edge increased.
Conclusions
OED based estimation suggests that the secondary cancer risk from TOMO is less than or comparable to the risks from conventional IMRT and VMAT.
doi:10.1186/1748-717X-8-47
PMCID: PMC3599921  PMID: 23452670
IMRT; VMAT; TOMOTHERAPY; Radio-photoluminescence; Secondary dose; OED
22.  Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe 
Nature genetics  2012;44(9):1056-1059.
Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage.
doi:10.1038/ng.2369
PMCID: PMC3442231  PMID: 22863732
23.  Dextran-Conjugated Vascular Endothelial Growth Factor Receptor Antibody for In Vivo Melanoma Xenografted Mouse Imaging 
Abstract
Intact immunoglobulin G antibody has a relatively large molecule size of approximately 150 kDa that remains in the bloodstream for many weeks, which is a considerable disadvantage when it is used to carry radioactive materials for imaging. To lower background activity and increase the contrast of images, we investigated antivascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) conjugated dextran for VEGF receptor 2 imaging in tumor xenografted mice. DTPA-conjugated aminodextran was synthesized, reacted with sulfo-LC-SPDP, and then reacted with DC101. The binding affinity of DTPA-dextran-DC101 to Flk-1 was measured. The gamma imaging and biodistributions of 99mTc-DTPA-dextran-DC101, 99mTc-DTPA-DC101, and 125I-DC101 were studied in B16F10 melanoma xenografted mice. The dissociation values for DC101, DTPA-DC101, and DTPA-dextran-DC101 were 22.48, 3.05, and 14.74 pM, respectively. In gamma images, 99mTc-DTPA-dextran-DC101 showed weak liver uptake and rapid kidney elimination. In biodistribution results, the liver uptake of 99mTc-DTPA-dextran-DC101 was similar with that of 99mTc-DTPA-DC101 at each time point. However, the blood activity of 99mTc-DTPA-dextran-DC101 has shown significant differences, compared with 99mTc-DTPA-DC101 at all time points. The tumor accumulation of dextran-conjugated antibody was increased with time, whereas that of dextran nonconjugated antibody decreased. In particular, the pattern of tumor uptake of 99mTc-DTPA-dextran-DC101 was similar to that of 125I-DC101, so this was thought to reflect the kinetics of DC101, unlike the nonconjugated form. The results of this study suggested that introduction of dextran moiety to make 99mTc-radiolabeled DC101 imaging agent could provide better images with the impaired background and the steady increasing binding to the receptor. However, further studies are necessary to improve clinical pharmacokinetics, such as enhancement of tumor uptake and impaired renal uptake.
doi:10.1089/cbr.2011.0977
PMCID: PMC3304247  PMID: 22149589
DC101; dextran; vascular endothelial growth factor receptor 2
24.  Follicular Thyroid Carcinoma Presenting as Bilateral Cheek Masses 
Mandibular metastasis of thyroid carcinoma is extremely rare. We present the case of a 46-year-old woman who had bilateral huge cheek masses that had grown rapidly over several years. Intra-oral mucosal tissue biopsy and imaging work-up including computed tomography scan and magnetic resonance imaging were performed and the initial diagnosis was presumed to be central giant cell granuloma. Incidentally detected thyroid lesions were studied with ultra-sonography guided fine needle aspiration and diagnosed as simple benign nodules. Due to continuous oral bleeding and the locally destructive feature of the lesions, we decided to excise the mass surgically. To avoid functional deficit, a stepwise approach was performed: Firstly, the larger left mass was excised and the mandible was reconstructed with a fibular free flap. The final pathologic diagnosis was follicular thyroid cancer. Postoperative I-131 thyroid scan and whole body positron-emissions-tomography were performed. Right side mass was revealed as a thyroid malignancy. Multiple bony metastases were detected. Since further radioactive iodine therapy was required, additional total thyroidectomy and right side mandibulectomy with fibular free flap reconstruction was performed. The patient also underwent high dose radioactive iodine therapy and palliative extra-beam radiotherapy for the metastatic lumbar lesion. Follicular thyroid carcinoma should be considered as a differential diagnosis for mandibular mass lesions.
doi:10.3342/ceo.2013.6.1.52
PMCID: PMC3604272  PMID: 23526730
Follicular; Thyroid; Metastasis; Mandible
25.  Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation 
Blood research  2013;48(1):16-23.
Background
Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-γ), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored.
Methods
Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study.
Results
Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients.
Conclusion
This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
doi:10.5045/br.2013.48.1.16
PMCID: PMC3625005  PMID: 23589790
Suppressor of cytokine signaling proteins; Graft vs. host disease; Quantitative real-time polymerase chain reaction; Allogeneic transplantation

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