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1.  Gastric inverted hyperplastic polyp: A rare cause of iron deficiency anemia 
World Journal of Gastroenterology  2016;22(15):4066-4070.
Gastric inverted hyperplastic polyp (IHP) is a rare gastric polyp characterized by the downward growth of hyperplastic mucosal components into the submucosal layer. Macroscopically, a gastric IHP resembles a subepithelial tumor (SET); as a result, accurately diagnosing gastric IHP is difficult. This issue has clinical significance because gastric IHP can be misdiagnosed as SET or as malignant neoplasm In addition, adenocarcinoma can accompany benign gastric IHP. Although in most cases, gastric IHPs are asymptomatic and are found incidentally, these polyps may cause anemia secondary to chronic bleeding. Here, we report one case involving gastric IHP accompanied by chronic iron deficiency anemia that was successfully managed using endoscopic submucosal dissection.
PMCID: PMC4823259  PMID: 27099452
Stomach; Hyperplasia; Polyp; Anemia
2.  Gastrointestinal stromal tumor solitary distant recurrence in the left brachialis muscle 
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are most commonly found in the stomach. Although GISTs can spread to the liver and peritoneum, metastasis to the skeletal muscle is very rare and only four cases have previously been reported. These cases involved concurrent skeletal metastases of primary GISTs or liver metastases. Here, we report the first case of a distant recurrence in the brachialis muscle after complete remission of an extra-luminal gastric GIST following a wedge resection of the stomach, omental excision, and adjuvant imatinib therapy for one year. Ten months after therapy completion, the patient presented with swelling and tenderness in the left arm. Magnetic resonance imaging revealed a large mass in the brachialis muscle, which showed positivity for c-kit and CD34 upon pathologic examination. This is the first reported case of a solitary distant recurrence of a GIST in the muscle after complete remission had been achieved.
PMCID: PMC4445120  PMID: 26034378
Brachialis muscle; Distant recurrence; Gastrointestinal stromal tumor; Skeletal metastasis; Tyrosine kinase inhibitor
3.  A case of rapidly progressing leiomyosarcoma combined with squamous cell carcinoma in the esophagus 
Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1% of all malignant esophageal tumors. Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma. We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.
PMCID: PMC3752576  PMID: 23983445
Leiomyosarcoma; Carcinoma; Squamous cell; Esophagus; Sarcoma
4.  Altered Gut Microbiota Composition in Rag1-deficient Mice Contributes to Modulating Homeostasis of Hematopoietic Stem and Progenitor Cells 
Immune Network  2015;15(5):252-259.
Hematopoietic stem and progenitor cells (HSPCs) can produce all kind of blood lineage cells, and gut microbiota that consists of various species of microbe affects development and maturation of the host immune system including gut lymphoid cells and tissues. However, the effect of altered gut microbiota composition on homeostasis of HSPCs remains unclear. Here we show that compositional change of gut microbiota affects homeostasis of HSPCs using Rag1-/- mice which represent lymphopenic condition. The number and proportions of HSPCs in Rag1-/- mice are lower compared to those of wild types. However, the number and proportions of HSPCs in Rag1-/- mice are restored as the level of wild types through alteration of gut microbiota diversity via transferring feces from wild types. Gut microbiota composition of Rag1-/- mice treated with feces from wild types shows larger proportions of family Prevotellaceae and Helicobacterceae whereas lower proportions of family Lachnospiraceae compared to unmanipulated Rag1-/- mice. In conclusion, gut microbiota composition of lymphopenic Rag1-/- mice is different to that of wild type, which may lead to altered homeostasis of HSPCs.
PMCID: PMC4637346  PMID: 26557809
Hematopoietic stem and progenitor cells; gut microbiota; lymphopenic state
5.  Identification and Characterization of MicroRNAs in Normal Equine Tissues by Next Generation Sequencing 
PLoS ONE  2014;9(4):e93662.
The role of microRNAs (miRNAs) as a post-transcriptional gene regulator has been elucidated in a broad range of organisms including domestic animals. Characterization of miRNAs in normal tissues is an important step to investigate the functions of miRNAs in various physiological and pathological conditions. Using Illumina Next Generation Sequencing (NGS) technology, we identified a total of 292 known and 329 novel miRNAs in normal horse tissues including skeletal muscle, colon and liver. Distinct sets of miRNAs were differentially expressed in a tissue-specific manner. The miRNA genes were distributed across all the chromosomes except chromosomes 29 and 31 in the horse reference genome. In some chromosomes, multiple miRNAs were clustered and considered to be polycistronic transcript. A base composition analysis showed that equine miRNAs had a higher frequency of A+U than G+C. Furthermore, U tended to be more frequent at the 5′ end of miRNA sequences. This is the first experimental study that identifies and characterizes the global miRNA expression profile in normal horse tissues. The present study enriches the horse miRNA database and provides useful information for further research dissecting biological functions of miRNAs in horse.
PMCID: PMC3973549  PMID: 24695583
6.  KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes 
Oncotarget  2014;5(5):1226-1240.
Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes.
PMCID: PMC4012722  PMID: 24713374
Tumor-initiating cells; hepatocellular carcinoma; KIAA1114; cell surface marker; monoclonal antibody
7.  A case of ascending colon variceal bleeding treated with venous coil embolization 
A 38-year-old female with a history of alcoholic liver cirrhosis visited our hospital with a massive hematochezia. An esophagogastroduodenoscopy did not demonstrate any bleeding source, and a colonoscopy showed a massive hemorrhage in the ascending colon but without an obvious focus. The source of the bleeding could not be found with a mesenteric artery angiography. We performed an enhanced abdominal computed tomography, which revealed a distal ascending colonic varix, and assumed that the varix was the source of the bleeding. We performed a venous coil embolization and histoacryl injection to obliterate the colon varix. The intervention appeared to be successful because the vital signs and hemoglobin laboratory data remained stable and because the hematochezia was no longer observed. We report here on a rare case of colonic variceal bleeding that was treated with venous coil embolization.
PMCID: PMC3547563  PMID: 23345957
Colon ascending; Varicose veins; Liver cirrhosis; Therapeutic embolization
8.  Characteristics of the Aragonitic Layer in Adult Oyster Shells, Crassostrea gigas: Structural Study of Myostracum including the Adductor Muscle Scar 
Myostracum, which is connected from the umbo to the edge of a scar, is not a single layer composed of prismatic layers, but a hierarchically complex multilayered shape composed of minerals and an organic matrix. Through the analysis of the secondary structure, the results revealed that a β-antiparallel structure was predominant in the mineral phase interface between the myostracum (aragonite) and bottom folia (calcite). After the complete decalcification and deproteinization, the membrane obtained from the interface between the myostracum buried in upper folia, and the bottom folia was identified as chitin. The transitional zone in the interface between the adductor muscle scar and folia are verified. The myostracum disappeared at the edge of the scar of the posterior side. From this study, the entire structure of the myostracum from the adult oyster shell of Crassostrea gigas could be proposed.
PMCID: PMC3118482  PMID: 21716680
9.  Hepatic angiosarcoma manifested as recurrent hemoperitoneum 
Angiosarcoma is a rare tumor that account for less than 1% of all sarcomas. Although hepatic angiosarcoma usually presents with unspecific symptoms, it rapidly progresses and has a high mortality. We report a rare case of primary hepatic angiosarcoma manifested as recurrent hemoperitoneum.
PMCID: PMC2710744  PMID: 18473427
Angiosarcoma; Hemoperitoneum; Primary hepatic tumor
10.  Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B 
AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naïve chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone.
METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group.
RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by ≥ 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups.
CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.
PMCID: PMC2695919  PMID: 18350610
Adefovir dipivoxil; Chronic hepatitis B; Hepatitis B virus DNA; Overlap
11.  Incidence and Clinical Outcomes of Clostridium difficile Infection after Treatment with Tuberculosis Medication 
Gut and Liver  2015;10(2):250-254.
To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection.
This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication.
C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26).
The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.
PMCID: PMC4780455  PMID: 26260753
Enterocolitis; pseudomembranous; Clostridium difficile; Tuberculosis; Rifampin
12.  Suppression of Subthalamic Nucleus Activity by Micromagnetic Stimulation 
Magnetic stimulation delivered via 0.5-mm diameter coils was recently shown to activate retinal neurons; the small coil size raises the possibility that micromagnetic stimulation (μMS) could underlie a new generation of implanted neural prosthetics. Such an approach has several inherent advantages over conventional electric stimulation, including the potential for selective activation of neuronal targets as well as less susceptibility to inflamma-tory responses. The viability of μMS for some applications, e.g., deep brain stimulation (DBS), may require suppression (rather than creation) of neuronal activity, however, and therefore we explore here whether (μMS) could, in fact, suppress activity. While single pulses elicited weak and inconsistent spiking in neurons of the mouse subthalamic nucleus (in vitro), repetitive stimulation effectively suppressed activity in ~70% of targeted neurons. This is the same percentage suppressed by conventional electric stimulation; with both modalities, suppression occurred only after an initial increase in spiking. The latency to the onset of suppression was inversely correlated to the energy of the stimulus waveform: larger amplitudes and lower frequencies had the fastest onset of suppression. These findings continue to support the viability of μMS as a next-generation implantable neural prosthetic.
PMCID: PMC4467829  PMID: 25163063
Deep brain stimulation (DBS); magnetic stimulation; neural prosthesis; Parkinson's disease (PD); repetitive transcranial magnetic stimulation (rTMS); subthalamic nucleus (STN)
13.  4-1BB Ligand Signaling to T cells Limits T cell Activation 
4-1BB ligand (4-1BBL) and its receptor, 4-1BB, are both induced on T cells after activation, however, little is known about the role of 4-1BBL. We now show that 4-1BBL can transmit signals that limit T cell effector activity under tolerogenic conditions. Cross-linking 4-1BBL inhibited IL-2 production in vitro, primarily with suboptimal TCR stimulation. Furthermore, naïve 4-1BBL-deficient OT-II transgenic T cells displayed a greater conversion to effector T cells in vivo when responding to soluble OVA peptide in WT hosts, whereas development of Foxp3+ Treg cells was not altered. A greater number of effector T cells also differentiated from naïve WT OT-II T cells when transferred into 4-1BB-deficient hosts, suggesting APC-derived 4-1BB is likely to trigger 4-1BBL. Indeed, effector T cells that could not express 4-1BBL accumulated in larger numbers in vitro when stimulated with 4-1BB-expressing mesenteric lymph node DCs. 4-1BBL was expressed on T cells when antigen presentation was limiting, and 4-1BBL was aberrantly expressed at very high levels on T cells that could not express 4-1BB. Trans-ligation, antibody-capture, and endocytosis experiments additionally showed that T cell intrinsic 4-1BB regulated internalization of membrane 4-1BBL, implying that the strong induction of 4-1BB on T cells may counteract the suppressive function of 4-1BBL by limiting its availability. These data suggest that 4-1BBL expressed on T cells can restrain effector T cell development, creating a more favorable Treg to effector cell balance under tolerogenic conditions, and this may be particularly active in mucosal barrier tissues where 4-1BB-expressing regulatory DCs present antigen.
PMCID: PMC4272921  PMID: 25404362
14.  Organic–inorganic hybrid nanoflowers: types, characteristics, and future prospects 
Organic–inorganic hybrid nanoflowers, a newly developed class of flower-like hybrid nanoparticles, have received much attention due to their simple synthesis, high efficiency, and enzyme stabilizing ability. This article covers, in detail, the types, structural features, mechanism of formation, and bio-related applications of hybrid nanoflowers. The five major types of hybrid nanoflowers are discussed, i.e., copper–protein, calcium–protein, and manganese–protein hybrid nanoflowers, copper–DNA hybrid nanoflowers, and capsular hybrid nanoflowers. The structural features of these nanoflowers, such as size, shape, and protein ratio generally determine their applications. Thus, the specific characteristics of hybrid nanoflowers are summarized in this review. The interfacial mechanism of nanoflower formation is examined in three steps: first, combination of metal ion and organic matter; second, formation of petals; third, growth of nanoflowers. The explanations provided herein can be utilized in the development of innovative approaches for the synthesis of hybrid nanoflowers for prospective development of a plethora of hybrid nanoflowers. The future prospects of hybrid nanoflowers in the biotechnology industry, medicine, sensing, and catalysis are also discussed.
PMCID: PMC4559159  PMID: 26337651
Biosynthesis; Nanoflowers; Organic–inorganic hybrid
15.  Ice-templated Self-assembly of VOPO4–Graphene Nanocomposites for Vertically Porous 3D Supercapacitor Electrodes 
Scientific Reports  2015;5:13696.
A simple ice-templated self-assembly process is used to prepare a three-dimensional (3D) and vertically porous nanocomposite of layered vanadium phosphates (VOPO4) and graphene nanosheets with high surface area and high electrical conductivity. The resulting 3D VOPO4–graphene nanocomposite has a much higher capacitance of 527.9 F g−1 at a current density of 0.5 A g−1, compared with ~247 F g−1 of simple 3D VOPO4, with solid cycling stability. The enhanced pseudocapacitive behavior mainly originates from vertically porous structures from directionally grown ice crystals and simultaneously inducing radial segregation and forming inter-stacked structures of VOPO4–graphene nanosheets. This VOPO4–graphene nanocomposite electrode exhibits high surface area, vertically porous structure to the separator, structural stability from interstacked structure and high electrical conductivity, which would provide the short diffusion paths of electrolyte ions and fast transportation of charges within the conductive frameworks. In addition, an asymmetric supercapacitor (ASC) is fabricated by using vertically porous VOPO4–graphene as the positive electrode and vertically porous 3D graphene as the negative electrode; it exhibits a wide cell voltage of 1.6 V and a largely enhanced energy density of 108 Wh kg−1.
PMCID: PMC4558581  PMID: 26333591
16.  A Nano-Thin Film-Based Prototype QCM Sensor Array for Monitoring Human Breath and Respiratory Patterns 
Sensors (Basel, Switzerland)  2015;15(8):18834-18850.
Quartz crystal microbalance (QCM) sensor array was developed for multi-purpose human respiration assessment. The sensor system was designed to provide feedback for human respiration. Thorough optimization of measurement conditions: air flow, temperature in the QCM chamber, frequency measurement rate, and electrode position regarding to the gas flow—was performed. As shown, acquisition of respiratory parameters (rate and respiratory pattern) could be achieved even with a single electrode used in the system. The prototype system contains eight available QCM channels that can be potentially used for selective responses to certain breath chemicals. At present, the prototype machine is ready for the assessment of respiratory functions in larger populations in order to gain statistical validation. To the best of our knowledge, the developed prototype is the only respiratory assessment system based on surface modified QCM sensors.
PMCID: PMC4570348  PMID: 26263994
quartz crystal microbalance sensor; nano-thin film; respiratory measurement; lung function test
17.  The response of L5 pyramidal neurons of the PFC to magnetic stimulation from a micro-coil 
Magnetic stimulation of the nervous system, e.g. transcranial magnetic stimulation (TMS), has been used both to unravel basic structure and function of the nervous system as well as to treat neurological diseases, i.e. clinical depression. Despite progress in both areas, ongoing advancements have been limited by a lack of understanding of the mechanism by which magnetic stimulation alters neural activity. Here, we report responses of cortical neurons to magnetic stimulation arising from a sub-millimeter coil. Cell attached patch clamp was used to record neural activity of layer 5/6 pyramidal neurons of the prefrontal cortex (PFC) in the in vitro mouse brain slice preparation. The fields arising from the small coil were quite different from those arising during clinical TMS but nevertheless allowed the responses of cortical neurons to magnetic stimulation to be probed. For example, the focal nature of induced fields allowed the sensitivity of different regions within targeted pyramidal neurons, e.g. apical dendrite, soma and axon hillock, to be compared. We found that PFC pyramidal neurons were not sensitive to single pulses of stimulation regardless of coil location. However, regions of the apical dendrite and proximal axon were both sensitive to repetitive stimulation as long as the orientation of the induced electric field was aligned with the long axis of the neuron. These results suggest that neurons of the PFC are sensitive to weak magnetic fields and further, that this type of approach may be useful for unraveling some of the mechanisms underlying TMS.
PMCID: PMC4465444  PMID: 25571395
18.  Electrochemical polymerization of pyrene derivatives on functionalized carbon nanotubes for pseudocapacitive electrodes 
Nature Communications  2015;6:7040.
Electrochemical energy-storage devices have the potential to be clean and efficient, but their current cost and performance limit their use in numerous transportation and stationary applications. Many organic molecules are abundant, economical and electrochemically active; if selected correctly and rationally designed, these organic molecules offer a promising route to expand the applications of these energy-storage devices. In this study, polycyclic aromatic hydrocarbons are introduced within a functionalized few-walled carbon nanotube matrix to develop high-energy, high-power positive electrodes for pseudocapacitor applications. The reduction potential and capacity of various polycyclic aromatic hydrocarbons are correlated with their interaction with the functionalized few-walled carbon nanotube matrix, chemical configuration and electronic structure. These findings provide rational design criteria for nanostructured organic electrodes. When combined with lithium negative electrodes, these nanostructured organic electrodes exhibit energy densities of ∼350 Wh kg−1electrode at power densities of ∼10 kW kg−1electrode for over 10,000 cycles.
Electrochemically active organic molecules are an important class of electrode materials for energy storage. Here, the authors report organic electrodes made of polycyclic aromatic hydrocarbons and functionalized few-walled carbon nanotubes, which show promising electrochemical performance.
PMCID: PMC4432658  PMID: 25943905
19.  Crucial Roles of Interleukin-7 in the Development of T Follicular Helper Cells and in the Induction of Humoral Immunity 
Journal of Virology  2014;88(16):8998-9009.
T follicular helper (Tfh) cells are specialized providers of cognate B cell help, which is important in promoting the induction of high-affinity antibody production in germinal centers (GCs). Interleukin-6 (IL-6) and IL-21 have been known to play important roles in Tfh cell differentiation. Here, we demonstrate that IL-7 plays a pivotal role in Tfh generation and GC formation in vivo, as treatment with anti-IL-7 neutralizing antibody markedly impaired the development of Tfh cells and IgG responses. Moreover, codelivery of mouse Fc-fused IL-7 (IL-7-mFc) with a vaccine enhanced the generation of GC B cells as well as Tfh cells but not other lineages of T helper cells, including Th1, Th2, and Th17 cells. Interestingly, a 6-fold-lower dose of an influenza virus vaccine codelivered with Fc-fused IL-7 induced higher antigen-specific and cross-reactive IgG titers than the vaccine alone in both mice and monkeys and led to markedly enhanced protection against heterologous influenza virus challenge in mice. Enhanced generation of Tfh cells by IL-7-mFc treatment was not significantly affected by the neutralization of IL-6 and IL-21, indicating an independent role of IL-7 on Tfh differentiation. Thus, IL-7 holds promise as a critical cytokine for selectively inducing Tfh cell generation and enhancing protective IgG responses.
IMPORTANCE Here, we demonstrate for the first time that codelivery of Fc-fused IL-7 significantly increased influenza virus vaccine-induced antibody responses, accompanied by robust expansion of Tfh cells and GC B cells as well as enhanced GC formation. Furthermore, IL-7-mFc induced earlier and cross-reactive IgG responses, leading to striking protection against heterologous influenza virus challenge. These results suggest that Fc-fused IL-7 could be used for inducing strong and cross-protective humoral immunity against highly mutable viruses, such as HIV and hepatitis C virus, as well as influenza viruses.
PMCID: PMC4136280  PMID: 24899182
20.  Galectin-9 controls the therapeutic activity of 4-1BB–targeting antibodies 
The Journal of Experimental Medicine  2014;211(7):1433-1448.
Agonistic anti–4-1BB suppresses autoimmune and allergic inflammation via binding to Galectin-9, which facilitates 4-1BB aggregation, signaling, and functional activity.
Biologics to TNF family receptors are prime candidates for therapy of immune disease. Whereas recent studies have highlighted a requirement for Fcγ receptors in enabling the activity of CD40, TRAILR, and GITR when engaged by antibodies, other TNFR molecules may be controlled by additional mechanisms. Antibodies to 4-1BB (CD137) are currently in clinical trials and can both augment immunity in cancer and promote regulatory T cells that inhibit autoimmune disease. We found that the action of agonist anti–4-1BB in suppressing autoimmune and allergic inflammation was completely dependent on Galectin-9 (Gal-9). Gal-9 directly bound to 4-1BB, in a site distinct from the binding site of antibodies and the natural ligand of 4-1BB, and Gal-9 facilitated 4-1BB aggregation, signaling, and functional activity in T cells, dendritic cells, and natural killer cells. Conservation of the Gal-9 interaction in humans has important implications for effective clinical targeting of 4-1BB and possibly other TNFR superfamily molecules.
PMCID: PMC4076583  PMID: 24958847
21.  Roles of ChlR1 DNA Helicase in Replication Recovery from DNA Damage 
Experimental cell research  2013;319(14):2244-2253.
The ChlR1 DNA helicase is mutated in Warsaw breakage syndrome characterized by developmental anomalies, chromosomal breakage, and sister chromatid cohesion defects. However, the mechanism by which ChlR1 preserves genomic integrity is largely unknown. Here, we describe the roles of ChlR1 in DNA replication recovery. We show that ChlR1 depletion renders human cells highly sensitive to cisplatin; an interstrand-crosslinking agent that causes stalled replication forks. ChlR1 depletion also causes accumulation of DNA damage in response to cisplatin, leading to a significant delay in resolution of DNA damage. We also report that ChlR1-depleted cells display defects in the repair of double-strand breaks induced by the I-PpoI endonuclease and bleomycin. Furthermore, we demonstrate that ChlR1-depeleted cells show significant delays in replication recovery after cisplatin treatment. Taken together, our results indicate that ChlR1 plays an important role in efficient DNA repair during DNA replication, which may facilitate efficient establishment of sister chromatid cohesion.
PMCID: PMC3752303  PMID: 23797032
ChlR1 DNA helicase; DNA replication; DNA damage; replication recovery; sister chromatid cohesion; Warsaw breakage syndrome
22.  Ephrin-A3 Suppresses Wnt Signaling to Control Retinal Stem Cell Potency 
Stem cells (Dayton, Ohio)  2013;31(2):349-359.
The ciliary epithelium (CE) of adult mammals has been reported to provide a source of retinal stem cells (RSCs) that can give rise to all retinal cell types in vitro. A recent study, however, suggests that CE-derived cells possess properties of pigmented ciliary epithelial cells and display little neurogenic potential. Here we show that the neurogenic potential of CE-derived cells is negatively regulated by ephrin-A3, which is upregulated in the CE of postnatal mice and presents a strong prohibitory niche for adult RSCs. Addition of ephrin-A3 inhibits proliferation of CE-derived RSCs and increases pigment epithelial cell fate. In contrast, absence of ephrin-A3 promotes proliferation and increases expression of neural progenitor cell markers and photoreceptor progeny. The negative effects of ephrin-A3 on CE-derived RSCs are mediated through activation of an EphA4 receptor and suppression of Wnt3a/β-catenin signaling. Together, our data suggest that CE-derived RSCs contain the intrinsic machinery to generate photoreceptors and other retinal neurons, while the CE of adult mice expresses negative regulators that prohibit the proliferation and neural differentiation of RSCs. Manipulating ephrin and Wnt/β-catenin signaling may, thus, represents a viable approach to activating the endogenous neurogenic potential of CE-derived RSCs for treating photoreceptor damage and retinal degenerative disorders.
PMCID: PMC3572266  PMID: 23165658
Adult stem cells; cell signaling; neural differentiation; retina; stem cell plasticity
23.  Gemcitabine-Induced Hemolytic Uremic Syndrome in Pancreatic Cancer: A Case Report and Review of the Literature 
Gut and Liver  2014;8(1):109-112.
Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS may be caused by several different conditions, including infection, malignancy, and chemotherapeutic agents, such as mitomycin, cisplatin, and most recently, gemcitabine. The outcome of gemcitabine-induced HUS is poor, and the disease has a high mortality rate. This study reports a case of gemcitabine-induced HUS in a patient with pancreatic cancer in Korea.
PMCID: PMC3916680  PMID: 24516709
Hemolytic-uremic syndrome; Gemcitabine; Pancreatic neoplasms
24.  Experience of Ultrasonography-Guided Percutaneous Core Biopsy for Renal Masses 
Korean Journal of Urology  2013;54(10):660-665.
We evaluated the safety and accuracy of ultrasonography-guided percutaneous core biopsy collection in patients with renal masses.
Materials and Methods
From June 2008 to August 2012, 30 percutaneous core biopsies of renal masses were performed. The biopsies obtained were small tumors (<4 cm) with ambiguous radiologic findings or that met classic renal biopsy indications. The biopsy results were compared with the final pathological results after definitive surgical treatment. Ultrasonography was performed on the day after biopsy collection to rule out any complications.
The mean age of the patients was 57.7 years, and the mean tumor size was 3.39 cm. Twelve of the lesions were in the left kidney, and 18 were in the right kidney. All but one core biopsy contained sufficient material for histopathological analysis. The biopsy results showed 17 renal cell carcinomas (56.7%), 3 angiomyolipomas (10.0%), 2 oncocytomas (6.7%), 1 adenocarcinoma (3.3%), and 7 benign lesions (23.3%). A total of 18 cases underwent surgery, and the pathological results confirmed the initial biopsy diagnosis for 17 of 18 cases (94.4%). The one (5.9%) inaccurate biopsy result was found to be a urothelial carcinoma of the kidney. No needle tract seeding was found in the pathological specimens or on follow-up imaging. A small perinephric hematoma (1-2 cm) was seen in 5 cases (16.7%), but all patients remained hemodynamically stable.
Ultrasonography-guided renal biopsy is a safe, effective, and accurate method for evaluating small renal masses. This procedure may help in selecting treatment modalities for small renal masses.
PMCID: PMC3806988  PMID: 24175038
Fine-needle biopsy; Kidney
25.  4-1BB Controls Regulatory Activity in Dendritic Cells through Promoting Optimal Expression of Retinal Dehydrogenase 
Dendritic cells (DC) in the gut promote immune tolerance by expressing retinal dehydrogenase (RALDH), an enzyme that promotes retinoic acid (RA), which aids differentiation of inducible Foxp3+ Treg (iTreg) in the intestinal mucosa. How RALDH expression is regulated is unclear. We found that 4-1BB (CD137), a member of the TNFR family, together with CD103, marked mesenteric lymph node DC with the highest level of RALDH activity, and ligation of 4-1BB maintained RALDH expression in these gut DC. Moreover, 4-1BB signals synergized with those through TLR2 or GM-CSFR to promote RALDH activity in undifferentiated DC. Correspondingly, 4-1BB-deficient mice were impaired in their ability to generate iTreg in the GALT when exposed to oral antigen, and 4-1BB-deficient mesenteric lymph node DC displayed weak RALDH activity and were poor at promoting iTreg development. Thus, our data demonstrate a novel activity of 4-1BB in controlling RALDH expression and the regulatory activity of DC.
PMCID: PMC3436963  PMID: 22896640

Results 1-25 (51)