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1.  Langerhans Cell Sarcoma Arising from Langerhans Cell Histiocytosis: A Case Report 
Journal of Korean Medical Science  2006;21(3):577-580.
Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells that have overtly malignant cytologic features. It is a very rare disease and theoretically, it can present de novo or progress from an antecedent Langerhans cell histiocytosis (LCH). However, to our knowledge, LCS arising from an antecedent LCH has not been reported on. We present here a case of LCS arising from a pulmonary LCH. A 34 yr-old man who was a smoker, had a fever and a chronic cough. Computed tomographic (CT) scan revealed multiple tiny nodules in both lungs. The thoracoscopic lung biopsy revealed LCH. The patient quit smoking, but he received no other specific treatment. One year later, the follow up chest CT scan showed a 4 cm-sized mass in the left lower lobe of the lung. A lobectomy was then performed. Microscopic examination of the mass revealed an infiltrative proliferation of large cells that had malignant cytologic features. Immunohistochemical stains showed a strong reactivity for S-100 and CD68, and a focal reactivity for CD1a. We think this is the first case of LCS arising from LCH.
doi:10.3346/jkms.2006.21.3.577
PMCID: PMC2729972  PMID: 16778410
Histiocytosis, Langerhans-Cell; Sarcoma; Lung
2.  Surgical Management of Bilateral Exudative Retinal Detachment Associated with Central Serous Chorioretinopathy 
Purpose
To report a case of bilateral bullous exudative retinal detachment in central serous chorioretinopathy (CSC) which was attached by vitrectomy and internal drainage of the subretinal fluid.
Methods
A 47-year-old man affected by bilateral atypical CSC with a bullous retinal detachment with subretinal exudate. A fluorescein angiogram (FAG) showed multiple points of leakage and staining of subretinal fibrosis. A tentative diagnosis of Vogt-Koyanagi-Harada (VKH) syndrome was made and the patient was treated with systemic corticosteroids and immunosuppressive agents. However, the subretinal fluid was not absorbed. He was then treated with vitrectomy and internal drainage of subretinal fluid.
Results
The retina was attached successfully in both eyes. Visual acuity improved to 20/50 in his left eye but did not improve in the right eye due to subretinal fibrotic scarring and atropic changes on the macula.
Conclusions
Our case suggests that the surgical management of bullous exudative retinal detachment is safe and necessary.
doi:10.3341/kjo.2006.20.2.131
PMCID: PMC2908829  PMID: 16892652
Bullous retinal detachment; Central serous chorioretinopathy; Subretinal fluid drainage; Vitrectomy
3.  Transcriptome analysis and identification of genes associated with ω-3 fatty acid biosynthesis in Perilla frutescens (L.) var. frutescens 
BMC Genomics  2016;17:474.
Background
Perilla (Perilla frutescens (L.) var frutescens) produces high levels of α-linolenic acid (ALA), a ω-3 fatty acid important to health and development. To uncover key genes involved in fatty acid (FA) and triacylglycerol (TAG) synthesis in perilla, we conducted deep sequencing of cDNAs from developing seeds and leaves for understanding the mechanism underlying ALA and seed TAG biosynthesis.
Results
Perilla cultivar Dayudeulkkae contains 66.0 and 56.2 % ALA in seeds and leaves, respectively. Using Illumina HiSeq 2000, we have generated a total of 392 megabases of raw sequences from four mRNA samples of seeds at different developmental stages and one mature leaf sample of Dayudeulkkae. De novo assembly of these sequences revealed 54,079 unique transcripts, of which 32,237 belong to previously annotated genes. Among the annotated genes, 66.5 % (21,429 out of 32,237) showed highest sequences homology with the genes from Mimulus guttatus, a species placed under the same Lamiales order as perilla. Using Arabidopsis acyl-lipid genes as queries, we searched the transcriptome and identified 540 unique perilla genes involved in all known pathways of acyl-lipid metabolism. We characterized the expression profiles of 43 genes involved in FA and TAG synthesis using quantitative PCR. Key genes were identified through sequence and gene expression analyses.
Conclusions
This work is the first report on building transcriptomes from perilla seeds. The work also provides the first comprehensive expression profiles for genes involved in seed oil biosynthesis. Bioinformatic analysis indicated that our sequence collection represented a major transcriptomic resource for perilla that added valuable genetic information in order Lamiales. Our results provide critical information not only for studies of the mechanisms involved in ALA synthesis, but also for biotechnological production of ALA in other oilseeds.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-2805-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-016-2805-0
PMCID: PMC4920993  PMID: 27342315
Perilla frutescens; Seed; ω-3 fatty acid; α-linolenic acid; Triacylglycerol; Transcriptome
4.  Whole-transcriptome analyses of the Sapsaree, a Korean natural monument, before and after exercise-induced stress 
Background
The Sapsaree (Canis familiaris) is a Korean native dog that is very friendly, protective, and loyal to its owner, and is registered as a natural monument in Korea (number: 368). To investigate large-scale gene expression profiles and identify the genes related to exercise-induced stress in the Sapsaree, we performed whole-transcriptome RNA sequencing and analyzed gene expression patterns before and after exercise performance.
Results
We identified 525 differentially expressed genes in ten dogs before and after exercise. Gene Ontology classification and KEGG pathway analysis revealed that the genes were mainly involved in metabolic processes, such as programmed cell death, protein metabolic process, phosphatidylinositol signaling system, and cation binding in cytoplasm. The ten Sapsarees could be divided into two groups based on the gene expression patterns before and after exercise. The two groups were significantly different in terms of their basic body type (p ≤ 0.05). Seven representative genes with significantly different expression patterns before and after exercise between the two groups were chosen and characterized.
Conclusions
Body type had a significant effect on the patterns of differential gene expression induced by exercise. Whole-transcriptome sequencing is a useful method for investigating the biological characteristics of the Sapsaree and the large-scale genomic differences of canines in general.
Electronic supplementary material
The online version of this article (doi:10.1186/s40781-016-0097-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s40781-016-0097-1
PMCID: PMC4832554  PMID: 27087983
NGS; Bioinformatics; RNA-Seq; Transcriptome; Exercise; Physical stress; Sapsaree
5.  Population-Based Regional Cancer Incidence in Korea: Comparison between Urban and Rural Areas 
Purpose
The purpose of this study is to investigate differences in organ-specific cancer incidence according to the region and population size in Korea.
Materials and Methods
We reviewed the data of the cancer registration program of Gyeongnam Regional Cancer Center between 2008 and 2011. Age-standardized rates of cancer incidence were analyzed according to population size of the region and administrative zone.
Results
Incidence of thyroid cancer has been increasing rapidly in both urban and rural areas. However, the thyroid cancer incidence was much lower in rural areas than in urban areas and megalopolis such as Seoul. Gastric cancer was relatively more common in rural areas, in megalopolis near the sea (Ulsan, Busan, and Incheon), and other southern provinces (Chungcheongnam-do, Gyeongsangbuk-do, and Gyeongsangnam-do). A detailed analysis in Gyeongsangnam-do revealed that rural areas have relatively low incidence of thyroid and colorectal cancer, and relatively high incidence of gastric and lung cancer compared to urban areas.
Conclusion
This study suggests that there are some differences in cancer incidence by population size. Thyroid and colorectal cancer incidence was increasing, and gastric and lung cancer was slightly decreasing in urban areas, whereas gastric and lung cancer incidence still remains high in rural areas.
doi:10.4143/crt.2015.062
PMCID: PMC4843717  PMID: 26194369
Epidemiology; Rural population; Korea; Urbanization
6.  CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer 
Purpose
The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer.
Materials and Methods
With various gastric tissues, we performed immunohistochemical staining for CD44v9.
Results
The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis.
Conclusion
This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.
doi:10.4143/crt.2014.227
PMCID: PMC4720095  PMID: 25779358
CD44 variant; Biological markers; Stomach neoplasms; Survival; Prognosis
7.  Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression 
Oncology Letters  2015;11(2):998-1006.
Myoferlin is a protein that is associated with cellular repair following injury. The expression of myoferlin in breast cancer and pancreatic adenocarcinoma has been reported to correlate with tumor invasiveness, epithelial to mesenchymal transition and an adverse prognosis. In the present study, myoferlin expression was investigated in non-small cell lung carcinoma (NSCLC), along with its association with patient prognosis and the expression of a number of other proteins. A total of 148 patients exhibiting NSCLC were enrolled in the present study. The survival data of all patients was examined, and myoferlin, vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor, E-cadherin, β-catenin, thyroid transcription factor-1 and tumor protein p63 expression was investigated via immunohistochemical staining of tissue microarrays. Myoferlin expression was detected in the cytoplasm of 75/148 (50.7%) of the NSCLC cases. In the adenocarcinoma cases, myoferlin-positive patients possessed a poorer prognosis (odds ratio, 2.94; P=0.339). In the squamous cell carcinoma cases, myoferlin expression was significantly associated with VEGFR-2 expression (P=0.001). Immunohistochemical staining for VEGFR-2 and myoferlin expression indicated similar features and cytoplasmic staining in tumor cells. As VEGFR-2 is a significant target for novel anticancer therapies, it is anticipated that myoferlin may also possess the potential to become a novel clinical target for the treatment of NSCLC.
doi:10.3892/ol.2015.3988
PMCID: PMC4734036  PMID: 26893682
myoferlin protein; vascular endothelial growth factor receptor-2; non-small cell lung cancer; prognosis; tissue array analysis
8.  Cellular defense against latent colonization foiled by human cytomegalovirus UL138 protein 
Science Advances  2015;1(10):e1501164.
Cells have a defense against latent human cytomegalovirus, but the viral UL138 protein inactivates it to allow lifelong persistence.
Intrinsic immune defenses mediated by restriction factors inhibit productive viral infections. Select viruses rapidly establish latent infections and, with gene expression profiles that imply cell-autonomous intrinsic defenses, may be the most effective immune control measure against latent reservoirs. We illustrate that lysine-specific demethylases (KDMs) are restriction factors that prevent human cytomegalovirus from establishing latency by removing repressive epigenetic modifications from histones associated with the viral major immediate early promoter (MIEP), stimulating the expression of a viral lytic phase target of cell-mediated adaptive immunity. The viral UL138 protein negates this defense by preventing KDM association with the MIEP. The presence of an intrinsic defense against latency and the emergence of a cognate neutralizing viral factor indicate that “arms races” between hosts and viruses over lifelong colonization exist at the cellular level.
doi:10.1126/sciadv.1501164
PMCID: PMC4681346  PMID: 26702450
cytomegalovirus; herpes; Epigenetics; transcription; restriction
9.  The value of diagnostic ultrasonography in the assessment of a glomus tumor of the subcutaneous layer of the forearm mimicking a hemangioma: a case report 
Introduction
A glomus tumor is a rare, benign tumor with atypical clinical symptoms. Because of its small size, it is difficult to diagnose and treat early; therefore, it leads to poor quality of life. Glomus tumors are known to commonly affect the hand and rarely manifest in other areas. Because they simulate neuromas, hemangiomas, and neurofibromatosis, the differential diagnosis is difficult. We performed marginal resection of a solitary forearm mass previously suspected to be a hemangioma or glomus tumor on the basis of ultrasound findings and histologically diagnosed to be a glomus tumor afterward. We report this case to demonstrate the good prognosis of the procedure we used, and we review the relevant literature.
Case presentation
A 68-year-old Asian man without a particular medical history visited our hospital with a mass with focal tenderness in his left distal forearm that had developed 8 years earlier. The tumor was observed with suspicion of being a hemangioma or glomus tumor based on the location, clinical symptoms, and ultrasound findings taken into consideration together. The biopsy results led us to conclude that the lesion was a glomus tumor.
Conclusions
A glomus tumor located in the forearm is very rare. It is often clinically overlooked and is likely to be misdiagnosed as another disease. The patient’s quality of life deteriorates, and, though the disease is rare, it has serious sequelae. Therefore, a quick diagnosis and appropriate treatment must be conducted early. If a mass occurs with serious pain in subcutaneous soft tissue of not the hands but the limbs, it is important to conduct examinations with suspicion of a glomus tumor. Ultrasonography performed quickly may be useful for making the differential diagnosis.
doi:10.1186/s13256-015-0672-y
PMCID: PMC4563903  PMID: 26351259
10.  Dietary Patterns and Risk for Metabolic Syndrome in Korean Women 
Medicine  2015;94(34):e1424.
Abstract
Dietary patterns are a risk factor for metabolic syndrome (MetS). The prevalence of MetS has increased in Korea, and this condition has become a public health issue. Therefore, the present cross-sectional study aimed to identify the associations between dietary patterns and the risk of MetS among Korean women.
The data of 5189 participants were analyzed to determine dietary intake and lifestyle. A principal components analysis was employed to determine participant dietary patterns with regard to 106 food items. MetS was diagnosed using the National Cholesterol Education Program, Adult Treatment Panel III. Logistic regression analyses were applied to evaluate the associations between dietary pattern quintiles and MetS and to generate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for potential confounders.
Three dietary patterns were identified: “traditional,” “western,” and “prudent.” The “prudent” dietary pattern consisted of a high intake of fruits and fruit products as well as nuts, dairy, and a low consumption of grains; this pattern was negatively associated with the risk of MetS. The highest quintile of the “prudent” dietary pattern was significantly less likely to develop MetS (OR: 0.5, 95% CI: 0.36–0.68, P for trend <0.001) compared with the lowest quintile. This pattern was also negatively associated with all of the MetS diagnostic criteria: abdominal obesity (OR: 0.52, 95% CI: 0.41–0.65), blood pressure (OR: 0.72, 95% CI: 0.59–0.87), triglycerides (OR: 0.67, 95% CI: 0.52–0.85), fasting glucose (OR: 0.64, 95% CI: 0.43–0.95), and high-density lipoprotein cholesterol (OR: 0.53, 95% CI: 0.42–0.68). However, the “traditional” and “western” dietary patterns were not associated with the risk of MetS.
The “prudent” dietary pattern was negatively associated with the risk of developing MetS among Korean women.
doi:10.1097/MD.0000000000001424
PMCID: PMC4602901  PMID: 26313795
11.  D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy 
Medicine  2015;94(30):e951.
Abstract
Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level.
We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx.
The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 μg/mL was significantly longer than that of patients with D-dimer levels ≥1.5 μg/mL (22.0 vs 7.9 months, P = 0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 μg/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 μg/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0 μg/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 μg/mL (22.0 vs 7.0 months, P = 0.009). The lower D-dimer levels (<1.0 μg/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (P = 0.037).
This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.
doi:10.1097/MD.0000000000000951
PMCID: PMC4554111  PMID: 26222870
12.  Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma 
Oncology Letters  2015;9(4):1699-1706.
Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1α (HIF-1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1α, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1α and CA9 is associated with poor prognosis, and that HIF-1α overexpression is an independent unfavorable prognostic factor in STS.
doi:10.3892/ol.2015.2914
PMCID: PMC4356356  PMID: 25789026
soft tissue sarcoma; carbonic anhydrase 9; hypoxia; hypoxia-inducible factor 1α; glucose transporter-1; vascular endothelial growth factor
13.  Direct Induction of Hematoendothelial Programs in Human Pluripotent Stem Cells by Transcriptional Regulators 
Nature communications  2014;5:4372.
Advancing pluripotent stem cell technologies for modeling hematopoietic stem cell development and blood therapies requires identifying key regulators of hematopoietic commitment from human pluripotent stem cells (hPSCs). Here, by screening the effect of 27 candidate factors, we reveal two groups of transcriptional regulators capable of inducing distinct hematopoietic programs from hPSCs: panmyeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1). In both cases, these transcription factors directly convert hPSCs to endothelium, which subsequently transforms into blood cells with pan-myeloid or erythromegakaryocytic potential. These data demonstrate that two distinct genetic programs regulate the hematopoietic development from hPSCs and that both of these programs specify hPSCs directly to hemogenic endothelial cells. Additionally, this study provides a novel method for the efficient induction of blood and endothelial cells from hPSCs via overexpression of modified mRNA for the selected transcription factors.
doi:10.1038/ncomms5372
PMCID: PMC4107340  PMID: 25019369
14.  Monostotic fibrous dysplasia in the proximal tibial epiphysis: a case report 
Introduction
Fibrous dysplasia is one of many well-known disorders in which there is a defect in the remodeling process of immature bone to mature into lamellar bone, and it often exists in metaphyseal and diaphyseal parts of the long bone. In this report, we describe a rare case where fibrous dysplasia was found only in the proximal part of the epiphysis of the tibia without other bony lesions.
Case presentation
A 14-year-old Asian girl was referred to our hospital after slipping down with pain on the left knee. A radiograph showed an abnormal finding of a central radiolucent lesion with a marginal sclerotic border near the proximal tibial spine. A magnetic resonance image showed the lesion at low signal intensity on a T1-weighted image and at high signal intensity on a T2-weighted image. The biopsy results led us to conclude that the lesion was a fibrous dysplasia.
Conclusion
If an abnormal lesion on the epiphysis, especially in long bones, is detected on a radiograph, several differential diagnoses can be made. Although fibrous dysplasia is usually not encountered as an epiphyseal lesion, it is important to incorporate all the clinical, radiographic and pathologic features to diagnose monostotic fibrous dysplasia when the lesion is located at the epiphyseal location.
doi:10.1186/1752-1947-8-452
PMCID: PMC4307750  PMID: 25526966
Bone tumor; Epiphysis; Fibrous dysplasia
15.  Can Thymidine Phosphorylase Be a Predictive Marker for Gemcitabine and Doxifluridine Combination Chemotherapy in Cholangiocarcinoma? 
Medicine  2014;93(28):e305.
Abstract
Unresectable cholangiocarcinoma is poorly responded to chemotherapy, especially for the case refractory to gemcitabine and cisplatin. Here, we tested whether high expression of thymidine phosphorylase (TP) can be a predictive biomarker for the indicator for gemcitabine and doxifluridine combination chemotherapy in the cholangiocarcinoma refractory to gemcitabine and cisplatin.
Immunohistochemical staining for TP was performed with a biopsy specimen. We accepted the result as positive when more than 10% of cancer cells were stained with moderate intensity.
Here, we report 2 cases of TP-positive cholangiocarcinoma well controlled with gemcitabine and doxifluridine combination chemotherapy, which had been refractory to the first line treatment with gemcitabine and cisplatin combination chemotherapy.
doi:10.1097/MD.0000000000000305
PMCID: PMC4603134  PMID: 25526478
16.  Contralateral referred pain in a patient with intramedullary spinal cord metastasis from extraskeletal small cell osteosarcoma 
Context
Referred pain has been observed in some patients after cordotomy, wherein noxious stimulus applied to a region rendered analgesic by cordotomy produces pain at a spot different from the one where the noxious stimulus is applied. We report a patient who had intramedullary spinal cord metastasis of extraskeletal small cell osteosarcoma, a rare form of metastatic disease, and experienced contralateral referred pain.
Findings
Initially, the patient had a mass in the left posterior neck region and later developed a large extradural mass at the C3–C7 level. The masses were excised, and the histological findings led to a diagnosis of small cell osteosarcoma. He underwent chemotherapy and radiation therapy. He experienced numbness in his left leg; subsequently, the numbness slowly spread up the thigh to the left side of the abdomen. When pinched in the numb area on the left side of the body, he felt as though he had been pinched in both that area and the corresponding area on the right side. A magnetic resonance imaging scan showed an enhancing lesion in the right side of the cord at the C6–C7 level.
Conclusion/clinical relevance
An intramedullary spinal cord metastasis can arise from primary extraskeletal small cell osteosarcoma and cause contralateral referred pain, especially in a mirror-image location. Contralateral referred pain may be caused by a subsidiary pathway comprising ascending chains of short neurons that link the dorsal horn neurons longitudinally and latitudinally.
doi:10.1179/2045772312Y.0000000087
PMCID: PMC3831333  PMID: 24090113
Cervical vertebrae; Neoplastic metastasis; Osteosarcoma; Referred pain; Spinal cord neoplasms; Intramedullary cordotomy
17.  Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions 
Stem Cell Reports  2014;3(6):1073-1084.
Summary
The recent identification of hemogenic endothelium (HE) in human pluripotent stem cell (hPSC) cultures presents opportunities to investigate signaling pathways that are essential for blood development from endothelium and provides an exploratory platform for de novo generation of hematopoietic stem cells (HSCs). However, the use of poorly defined human or animal components limits the utility of the current differentiation systems for studying specific growth factors required for HE induction and manufacturing clinical-grade therapeutic blood cells. Here, we identified chemically defined conditions required to produce HE from hPSCs growing in Essential 8 (E8) medium and showed that Tenascin C (TenC), an extracellular matrix protein associated with HSC niches, strongly promotes HE and definitive hematopoiesis in this system. hPSCs differentiated in chemically defined conditions undergo stages of development similar to those previously described in hPSCs cocultured on OP9 feeders, including the formation of VE-Cadherin+CD73−CD235a/CD43− HE and hematopoietic progenitors with myeloid and T lymphoid potential.
Graphical Abstract
Highlights
•Hemogenic endothelium is generated in a completely defined xenogen-free system•The system reproduces all stages of hematopoietic development•Tenascin C enhances hematoendothelial development from pluripotent stem cells•Tenesacin C uniquely supports T cell specification
In this article, Slukvin and colleagues describe a feeder- and xenogene-free chemically defined platform for differentiating human pluripotent stem cells into definitive hematopoietic cells. They find that Tenascin C, a matrix protein associated with hematopoietic stem cell niches, strongly promotes hemogenic endothelium development and T lymphoid commitment in this system.
doi:10.1016/j.stemcr.2014.09.014
PMCID: PMC4263995  PMID: 25448067
19.  The Role of TWIST in Ovarian Epithelial Cancers 
Korean Journal of Pathology  2014;48(4):283-291.
Background
Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.
Methods
We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.
Results
The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.
Conclusions
Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.
doi:10.4132/KoreanJPathol.2014.48.4.283
PMCID: PMC4160591  PMID: 25214860
Ovarian epithelial cancer; TWIST transcription factor; Cadherins; HIF1α; Tumor suppressor protein p53
20.  Prognostic significance of WT1 expression in soft tissue sarcoma 
Background
Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target.
Methods
Immunohistochemical staining for WT1 was performed in 87 cases of STS using formalin-fixed, paraffin-embedded blocks. The correlation between WT1 expression and clinicopathological factors was analyzed. Survival analysis was conducted in 67 patients. We assessed the validity of WT1 immunohistochemistry as an index of WT1 protein expression using Western blot analysis.
Results
WT1 expression was noted in 47 cases (54.0%). Most rhabdomyosarcomas and malignant peripheral nerve sheath tumors showed WT1 expression (91.7% and 71.4%, respectively; P = 0.005). WT1 expression was related to higher FNCLCC histologic grade and AJCC tumor stage. In the group with high grade STS, strong WT1 expression was correlated with better survival (P = 0.025). The immunohistochemical results were correlated quantitatively with the staining score and the concentration of the Western blot band.
Conclusions
This study demonstrates that various types of STS show positive immunostaining for WT1 and that WT1 expression has a prognostic significance. So STS should be considered candidates for WT1 peptide--based immunotherapy.
doi:10.1186/1477-7819-12-214
PMCID: PMC4114094  PMID: 25026998
21.  Cyclosporine A as a Primary Treatment for Panniculitis-like T Cell Lymphoma: A Case with a Long-Term Remission 
Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a distinctive cutaneous lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic T cells, similar to panniculitis. It is well-established that patients who are diagnosed with SPTL usually respond poorly to chemotherapy, showing fatal outcome. As a first line treatment for SPTL, anthracycline-based chemotherapy was most frequently used. For the treatment of SPTL, the efficacy of cyclosporine A has been recently reported in relapsed SPTL after anthracycline-based chemotherapy. However, it is still not clear whether cyclosporine A can be used as a first-line treatment against SPTL. Here, we report a case of SPTL, which achieved complete remission for nine years after first-line cyclosporine A therapy. This study suggests that cyclosporine A can induce a complete long-term remission as a first-line treatment.
doi:10.4143/crt.2014.46.3.312
PMCID: PMC4132451  PMID: 25038767
Subcutaneous panniculitis-like T cell lymphoma; Cyclosporine A; Remission
22.  Genome-Wide SNP Calling Using Next Generation Sequencing Data in Tomato 
Molecules and Cells  2014;37(1):36-42.
The tomato (Solanum lycopersicum L.) is a model plant for genome research in Solanaceae, as well as for studying crop breeding. Genome-wide single nucleotide polymorphisms (SNPs) are a valuable resource in genetic research and breeding. However, to do discovery of genome-wide SNPs, most methods require expensive high-depth sequencing. Here, we describe a method for SNP calling using a modified version of SAMtools that improved its sensitivity. We analyzed 90 Gb of raw sequence data from next-generation sequencing of two resequencing and seven transcriptome data sets from several tomato accessions. Our study identified 4,812,432 non-redundant SNPs. Moreover, the workflow of SNP calling was improved by aligning the reference genome with its own raw data. Using this approach, 131,785 SNPs were discovered from transcriptome data of seven accessions. In addition, 4,680,647 SNPs were identified from the genome of S. pimpinellifolium, which are 60 times more than 71,637 of the PI212816 transcriptome. SNP distribution was compared between the whole genome and transcriptome of S. pimpinellifolium. Moreover, we surveyed the location of SNPs within genic and intergenic regions. Our results indicated that the sufficient genome-wide SNP markers and very sensitive SNP calling method allow for application of marker assisted breeding and genome-wide association studies.
doi:10.14348/molcells.2014.2241
PMCID: PMC3907006  PMID: 24552708
next generation sequencing (NGS); single nucleotide polymorphism (SNP); tomato
23.  Identification of Novel Pepper Genes Involved in Bax- or INF1-Mediated Cell Death Responses by High-Throughput Virus-Induced Gene Silencing 
Hot pepper is one of the economically important crops in Asia. A large number of gene sequences, including expressed sequence tag (EST) and genomic sequences are publicly available. However, it is still a daunting task to determine gene function due to difficulties in genetic modification of a pepper plants. Here, we show the application of the virus-induced gene silencing (VIGS) repression for the study of 459 pepper ESTs selected as non-host pathogen-induced cell death responsive genes from pepper microarray experiments in Nicotiana benthamiana. Developmental abnormalities in N. benthamiana plants are observed in the 32 (7%) pepper ESTs-silenced plants. Aberrant morphological phenotypes largely comprised of three groups: stunted, abnormal leaf, and dead. In addition, by employing the combination of VIGS and Agrobacterium-mediated transient assays, we identified novel pepper ESTs that involved in Bax or INF1-mediated cell death responses. Silencing of seven pepper ESTs homologs suppressed Bax or INF1-induced cell death, five of which suppressed both cell death responses in N. benthamiana. The genes represented by these five ESTs encode putative proteins with functions in endoplasmic reticulum (ER) stress and lipid signaling. The genes represented by the other two pepper ESTs showing only Bax-mediated cell death inhibition encode a CCCH-type zinc finger protein containing an ankyrin-repeat domain and a probable calcium-binding protein, CML30-like. Taken together, we effectively isolated novel pepper clones that are involved in hypersensitive response (HR)-like cell death using VIGS, and identified silenced clones that have different responses to Bax and INF1 exposure, indicating separate signaling pathways for Bax- and INF1-mediated cell death.
doi:10.3390/ijms141122782
PMCID: PMC3856090  PMID: 24256816
Bax-induced cell death; hot chili pepper (Capsicum annum); hypersensitive response; INF1; Nicotiana benthamiana; virus-induced gene silencing
24.  Adventitial Cystic Disease of the Common Femoral Artery: A Case Report and Literature Review 
Arterial adventitial cystic disease is an uncommon type of non-atherosclerotic peripheral vessel disease. Most cases of arterial adventitial cystic disease occur in the popliteal arteries; however, fewer cases have been reported in the femoral arteries. A 59-year-old male patient visited the hospital with a complaint of a swelling on the lower extremity that had begun two months earlier. Suspecting deep vein thrombosis based on a physical examination and ultrasonography from another hospital, tests were performed. Magnetic resonance imaging (MRI) was performed for exact diagnosis because venous adventitial cystic disease was suspected by computed tomography venography. The MRI indicated venous adventitial cystic disease as well. Thus, a cystic mass excision was performed. In the end, a cystic mass compressing the common femoral vein that originated from the common femoral artery was diagnosed based on the macroscopic findings. This case is reported because blood circulation in the vein was impeded due to arterial adventitial cystic disease, and the symptoms improved after the cystic mass excision and polytetrafluoroethylene roofing angioplasty.
doi:10.5090/kjtcs.2013.46.2.150
PMCID: PMC3631792  PMID: 23614104
Adventitial cystic disease; Peripheral vascular disease
25.  Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers 
Korean Journal of Pathology  2012;46(6):532-540.
Background
Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.
Methods
Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).
Results
CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.
Conclusions
The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.
doi:10.4132/KoreanJPathol.2012.46.6.532
PMCID: PMC3540330  PMID: 23323103
Ovarian epithelial cancer; Carbonic anhydrase IX; GLUT-1; Vascular endothelial growth factor A

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