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1.  Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21 
The Oncologist  2015;20(12):1440-1447.
This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic chemotherapy-induced nausea and vomiting (CINV). The results indicated that RAD is as effective and tolerable as OAD for CINV prevention. Ramosetron could be considered one of the best partners for aprepitant.
A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron’s efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV.
Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was −15%.
A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2–5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups.
RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.
Implications for Practice:
This is the first prospective, multicenter, randomized phase III study to show that ramosetron, a new 5-hydroxytryptamine receptor type 3 antagonist, is as effective and tolerable as ondansetron when administered in combination with aprepitant and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.
PMCID: PMC4679080  PMID: 26512046
Ramosetron; Ondansetron; Aprepitant; Nausea; Vomiting; Chemotherapy
2.  Baseline neutrophil–lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer 
Scientific Reports  2016;6:38585.
We examined the predictive value of neutrophil–lymphocyte ratio (NLR) by examining their association with the baseline presence and subsequent development of brain metastases in patients with stage IV non-small cell lung cancer (NSCLC). We examined the predictive value of NLR for brain metastasis in 260 stage IV NSCLC. Logistic regression models and competing risk analysis were used to determine the association of NLR with baseline and subsequent presence of brain metastases. Multivariate analysis reveals that patients with high NLR (≥4.95) had significantly more brain metastases at diagnosis than those with low NLR (Odds Ratio = 2.59, P = 0.01). In patients who had no baseline brain metastasis, competing risks analysis revealed that patients with high NLR showed higher cumulative incidence of subsequent brain metastases, compared to those with low NLR (P = 0.017). A high NLR was associated with the baseline presence or the subsequent development of brain metastases, particularly in the group with adenocarcinoma (P = 0.013 and P = 0.044, respectively). Furthermore, an increase in NLR during treatment was associated with subsequent brain metastases (P = 0.004). The NLR is an independent predictive factor for the baseline presence of brain metastases and subsequent brain metastases in stage IV NSCLC.
PMCID: PMC5141478  PMID: 27924837
3.  Empyema necessitatis due to Aspergillus fumigatus 
BMJ Case Reports  2014;2014:bcr2014206047.
We present an extremely rare case of empyema necessitatis secondary to Aspergillus fumigatus infection. A 58-year-old woman presented to our hospital with a painful skin rash on the right thorax. Three fistulas communicating with the pleural space were found. Since she did not show a clinical improvement despite antituberculous and antibacterial treatment, we looked for other causes. Pleural fungus culture showed A. fumigatus and chest wall biopsy revealed numerous fungal hyphae. Treatment with necrotic tissue debridement and antifungal agents was successful.
PMCID: PMC4256667  PMID: 25452298
4.  k-asymmetric spin-splitting at the interface between transition metal ferromagnets and heavy metals 
Physical review. B  2016;93(17):174421.
We systematically investigate the spin-orbit coupling-induced band splitting originating from inversion symmetry breaking at the interface between a Co monolayer and 4d (Tc, Ru, Rh, Pd, and Ag) or 5d (Re, Os, Ir, Pt, and Au) transition metals. In spite of the complex band structure of these systems, the odd-in-k spin splitting of the bands displays striking similarities with the much simpler Rashba spin-orbit coupling picture. While we do not find salient correlations between the interfacial magnetic anisotropy and the odd-in-k spin-splitting of the bands, we establish a clear connection between the overall strength of the band splitting and the charge transfer between the d-orbitals at the interface. Furthermore, we show that the spin splitting of the Fermi surface scales with the induced orbital moment, weighted by the spin-orbit coupling.
PMCID: PMC4939709  PMID: 27441303
5.  Spintronics: Chiral damping 
Nature materials  2016;15(3):253-254.
The analysis of the magnetic domain wall motion in a nanostructured magnetic system with strong spin-orbit coupling shows that the energy dissipation can be chiral when the inversion symmetry is broken.
PMCID: PMC4814936  PMID: 26906956
6.  Conversion of aspergilloma to chronic necrotizing pulmonary aspergillosis following treatment with sunitinib: A case report 
Oncology Letters  2016;12(5):3472-3474.
Semi-invasive or invasive aspergillosis occurring following chemotherapy with sunitinib is a rare condition with unknown incidence and prognosis. Here, we report a case involving a 59-year-old male who had a history of underlying stable aspergilloma and was newly diagnosed with metastatic renal cell carcinoma. Following surgical resection for renal cell carcinoma and adjuvant chemotherapy with sunitinib for 8 months, the patient presented with hemoptysis. Chest computed tomography revealed an increased soft tissue mass and air crescent sign of the underlying aspergilloma, combined with consolidation and bronchial artery hypertrophy around the lesion. The patient underwent bronchoscopy with a biopsy of the lesion and was eventually diagnosed with chronic necrotizing pulmonary aspergillosis, which had progressed from the underlying stable aspergilloma. This case highlights the fact that clinicians should be aware of the risk of opportunistic conversion from stable aspergilloma to invasive fungal infections in patients undergoing sunitinib treatment.
PMCID: PMC5103969  PMID: 27900022
pulmonary aspergiollosis; sunitinib; opportunistic infection
7.  The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis 
PLoS ONE  2016;11(7):e0159827.
Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis.
We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included.
Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate.
Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis.
PMCID: PMC4959712  PMID: 27455053
8.  Spontaneous Anterior Thoracic Spinal Cord Herniation through Dura Defect: A Case Report 
Korean Journal of Spine  2016;13(2):77-79.
Thoracic spinal cord herniation is a rare disease cause of progressive myelopathy. Magnetic resonance image is a useful tool to diagnose preoperatively. Operation is a treatment of option. Sixty-six-year-old female visited Dong-A University Medical Center for progressive gait disturbance with falling tendency to right side. She had radiating pain and tingling sense on both leg. Sense of touch and temperature was decreased below T6 level. Both hip and knee motor power were grade IV. Magnetic resonance imaging scan showed anterior displacement of the spinal cord at T4-T5 vertebral level. Under the diagnosis of thoracic spinal cord herniation with dura defect, operation was performed for the patient with intraoperative neuromonitoring. Laminectomy at T4 and T5 level was done, and intradural exploration of the spinal cord revealed dura defect about 25mm×8mm in size. Spinal cord was released under microscope and dura defect was repaired with Lyoplant. The patient's symptom improved after the surgical procedure, but touch and temperature sense under T6 level had unchanged.
PMCID: PMC4949173  PMID: 27437019
Spinal cord; Hernia; Thorax; Paraparesis
9.  The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function 
Scientific Reports  2016;6:23757.
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a molecule enriched in the brain and neurons that regulates intracellular calcium levels via signaling through the inositol trisphosphate receptor. In the present study, we found that IP3K-A expression is highly enriched in the central nucleus of the amygdala (CeA), which plays a pivotal role in the processing and expression of emotional phenotypes in mammals. Genetic abrogation of IP3K-A altered amygdala gene expression, particularly in genes involved in key intracellular signaling pathways and genes mediating fear- and anxiety-related behaviors. In agreement with the changes in amygdala gene expression profiles, IP3K-A knockout (KO) mice displayed more robust responses to aversive stimuli and spent less time in the open arms of the elevated plus maze, indicating high levels of innate fear and anxiety. In addition to behavioral phenotypes, decreased excitatory and inhibitory postsynaptic current and reduced c-Fos immunoreactivity in the CeA of IP3K-A KO mice suggest that IP3K-A has a profound influence on the basal activities of fear- and anxiety-mediating amygdala circuitry. In conclusion, our findings collectively demonstrate that IP3K-A plays an important role in regulating affective states by modulating metabotropic receptor signaling pathways and neural activity in the amygdala.
PMCID: PMC4823716  PMID: 27053114
10.  A Rare Case of Thymic Gangliocytic Paraganglioma 
PMCID: PMC4804141  PMID: 26447134
11.  Intrinsic spin torque without spin-orbit coupling 
We derive an intrinsic contribution to the non-adiabatic spin torque for non-uniform magnetic textures. It differs from previously considered contributions in several ways and can be the dominant contribution in some models. It does not depend on the change in occupation of the electron states due to the current flow but rather is due to the perturbation of the electronic states when an electric field is applied. Therefore it should be viewed as electric-field-induced rather than current-induced. Unlike previously reported non-adiabatic spin torques, it does not originate from extrinsic relaxation mechanisms nor spin-orbit coupling. This intrinsic non-adiabatic spin torque is related by a chiral connection to the intrinsic spin-orbit torque that has been calculated from the Berry phase for Rashba systems.
PMCID: PMC4748850  PMID: 26877628
12.  Mean-variance portfolio analysis data for optimizing community-based photovoltaic investment 
Data in Brief  2016;6:840-842.
The amount of electricity generated by Photovoltaic (PV) systems is affected by factors such as shading, building orientation and roof slope. To increase electricity generation and reduce volatility in generation of PV systems, a portfolio of PV systems can be made which takes advantages of the potential synergy among neighboring buildings. This paper contains data supporting the research article entitled: PACPIM: new decision-support model of optimized portfolio analysis for community-based photovoltaic investment [1]. We present a set of data relating to physical properties of 24 houses in Oregon, USA, along with simulated hourly electricity data for the installed PV systems. The developed Matlab code to construct optimized portfolios is also provided in Supplementary materials. The application of these files can be generalized to variety of communities interested in investing on PV systems.
PMCID: PMC4749943  PMID: 26937458
Community solar; Photovoltaic system; Portfolio theory; Energy optimization; Electricity volatility
13.  Endoscopic Findings of Enteropathy-Associated T-Cell Lymphoma Type II: A Case Series 
Gut and Liver  2016;10(1):147-151.
Enteropathy-associated T-cell lymphoma (EATL) is a rare extranodal T-cell lymphoma arising from the intestine. Two types of EATL have been reported. In contrast to the classic EATL type I, EATL type II occurs sporadically, is unrelated to celiac disease, and comprises 10% to 20 % of all EATL cases. A total of five cases of EATL type II were diagnosed at our clinic from January 2009 to September 2012. Four of the five patients were diagnosed with the help of endoscopy. Among the four patients, two of the cases involved both the small and large intestines, whereas in the other two patients, EATL was limited to the small intestine. Common endoscopic findings included innumerable fine granularities (also called mosaic mucosal patterns) and diffuse thickening of the mucosa with a semicircular shallow ulceration in the lesions of the small bowel. In contrast, the endoscopic findings of the colon were nonspecific and could not distinguish EATL type II from other diseases. There are only few published reports regarding the representative endoscopic findings of EATL. Here, we present the clinical and endoscopic findings of four cases of EATL type II diagnosed by endoscopy.
PMCID: PMC4694747  PMID: 26260757
Enteropathy-associated T-cell lymphoma type II; Gastrointestinal lymphoma; Endoscopy; Double-balloon enteroscopy
14.  Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation 
Journal of Korean Medical Science  2015;30(10):1416-1422.
For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.
Graphical Abstract
PMCID: PMC4575929  PMID: 26425037
Maintenance; Leukemia; Myeloid; Acute
15.  Clinical Value of Procalcitonin in Patients with Spinal Infection 
This study was designed to evaluation the diagnostic value of procalcitonin (PCT) in patients with spinal infection, compare to the classical biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count.
All patients who were diagnosed as a spinal infection between January, 2013 and July, 2014 were included in this study. Serum PCT, CRP, ESR, and WBC count were checked at initial hospital visit and once a week serially until they were discharged. Patient's medical history, causes and pathogens of spinal infection were reviewed.
Total 34 (16 men, 18 women) patients were included in this study. Mean age of the patients was 65.6 year-old. Causes of spinal infection were pain block procedure (14, 41.2%) and post-operation (5, 14.7%). Out of 25 patients who showed elevated initial serum PCT level, 20 patients (80%) had a combined systemic infection. 14 patients (6.7%) had a sepsis, 3 patients (14.2%) had a urinary tract infection and 2 (9.6%) had a pneumonia. 14 patients (41.2%) showed elevation of serum PCT level during treatment. Among them, 9 patients (64.3%) had a combined infection such as sepsis and urinary tract infection.
Serum CRP showed more sensitivity compared to serum PCT in patients with spinal infection. Patients with spinal infection who showed elevated serum PCT level should be investigated for combined infection and proper antibiotics should be applied.
PMCID: PMC4630360  PMID: 26539272
Procalcitonin; C-reactive protein; Pyogenic; Spondylitis; Discitis
16.  Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer 
PLoS Genetics  2015;11(8):e1005467.
The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N = 4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH). Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5’ fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular target therapy.
Author Summary
Little is known about the molecular biology of medullary thyroid cancer (MTC), which is a rare disease. Genomics are increasingly being used to improve our knowledge about disease biology and to identify therapeutic targets in many cancers. Here, we report the largest genomic results of MTC to date. MTC tissue frequently included several mutations. For the first time, anaplastic lymphoma kinase (ALK) rearrangements were detected in MTC: one case with a glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK fusion, and another case with an echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The fusion mechanism of the novel GFPT1-ALK fusion was successfully investigated using molecular biology techniques. In addition, an inhibitor of ALK (crizotinib) dramatically decreased the number of metastatic MTC lesions harboring the EML4-ALK fusion, thus verifying the fusion as a promising target in MTC. Our findings suggest that using rapidly improving sequencing techniques and accumulated genomic data to comprehensively perform genetic analyses on rare tumors, such as MTC, will help to improve the poor prognosis of orphan diseases.
PMCID: PMC4546689  PMID: 26295973
17.  PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis 
Nature Communications  2015;6:7769.
The activity of the phosphatase and tensin homologue (PTEN) is known to be suppressed via post-translational modification. However, the mechanism and physiological significance by which post-translational modifications lead to PTEN suppression remain unclear. Here we demonstrate that PTEN destabilization is induced by EGFR- or oncogenic PI3K mutation-mediated AKT activation in cervical cancer. EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 ligase. These processes require the stabilization of MKRN1 via AKT-mediated phosphorylation. In cervical cancer patients with high levels of pAKT and MKRN1 expression, PTEN protein levels are low and correlate with a low 5-year survival rate. Taken together, our results demonstrate that PI3K/AKT signals enforce positive-feedback regulation by suppressing PTEN function.
Mutations and post-translational modifications of the PI3K/AKT pathway inhibitor PTEN are a feature of many cancers, but these have not been associated with cervical cancer. Here, the authors identify a PI3K/AKT-mediated ubiquitination degradation pathway of PTEN that occurs in patients with cervical cancer.
PMCID: PMC4518267  PMID: 26183061
18.  Simultaneous Esophageal and Gastric Metastases from Lung Cancer 
Clinical Endoscopy  2015;48(4):332-335.
We report of a patient with metastatic adenocarcinoma of the esophagus and stomach from lung cancer. The patient was a 68-year-old man receiving radiotherapy and chemotherapy for stage IV lung cancer, without metastases to the gastrointestinal (GI) tract at the time of the initial diagnosis. During the treatment period, dysphagia and melena newly developed. Upper GI endoscopy revealed geographic erosion at the distal esophagus and multiple volcano-shaped ulcers on the stomach body. Endoscopic biopsy was performed for each lesion. To determine whether the lesions were primary esophageal and gastric cancer masses or metastases from the lung cancer, histopathological testing including immunohistochemical staining was performed, and metastasis from lung cancer was confirmed. The disease progressed despite chemotherapy, and the patient died 5 months after the diagnosis of lung cancer. This is a case report of metastatic adenocarcinoma in the esophagus and stomach, which are very rare sites of spread for lung cancer.
PMCID: PMC4522427  PMID: 26240809
Lung neoplasms; Stomach neoplasms; Esophageal neoplasms
19.  Delayed Perforation Occurring after Endoscopic Submucosal Dissection for Early Gastric Cancer 
Clinical Endoscopy  2015;48(3):251-255.
Delayed perforation is a very rare complication of endoscopic submucosal dissection (ESD), with a reported incidence of 0.1% to 0.45%. Few reports exist on the clinical features and outcomes of delayed perforation after ESD, and it is unclear whether the optimal management strategy is emergency surgery or endoscopic closure with conservative treatment. Here, we report two cases of delayed perforation occurring after ESD for early gastric cancer. In both cases, lesions were located in the antrum, and tumor depths were confined to the mucosal layer. Total procedure times for ESD were 25 and 45 minutes, respectively. Because delayed perforation may be associated with excessive thermal damage and necrosis of the muscle layer, treatment with emergency surgery should be used instead of conservative management in cases of delayed perforation after ESD.
PMCID: PMC4461671  PMID: 26064827
Coagulation; Endoscopy; Perforation; Stomach neoplasms; Surgery
20.  Cleaved CD44 intracellular domain supports activation of stemness factors and promotes tumorigenesis of breast cancer 
Oncotarget  2015;6(11):8709-8721.
CD44 plays a role in the progression of tumors and is expressed in cancer stem cells (CSCs). However, the mechanisms underlying the crosstalk of CD44 with stemness genes in CSC maintenance remains unclear. In this study, we demonstrated how the cleaved intracellular domain of CD44 (CD44ICD) activates stemness factors such as Nanog, Sox2 and Oct4, and contributes to the tumorigenesis of breast cancer. We have found that the overexpression of CD44ICD increased mammosphere formation in breast cancer cells. Treatment with a γ-secretase inhibitor (GSI), which blocks the cleavage of CD44ICD, interfered with mammosphere formation. Interestingly, CD44ICD decreased the expression levels and nuclear localization of stemness factors, but overexpression of CD44ICD reversed these effects. In addition, we showed that nuclear localization of CD44ICD is important for transcriptional activation of the stemness factors. Furthermore, CD44ICD-overexpressed cells exhibited strong tumorigenecity and greater metastatic potential than did the control cells or CD44-depleted cells in vivo in mice models. Taken together, it was supposed that CD44 promotes tumorigenesis through the interaction and nuclear-translocation of its intracellular domain and stemness factors. We suggest that the prevention of cleavage and nuclear-translocation of CD44ICD is a potential target in treating breast cancer.
PMCID: PMC4496178  PMID: 25909162
CD44; intracellular domain; stemness factors; breast cancer
21.  Salvage rapid maxillary expansion for the relapse of maxillary transverse expansion after Le Fort I with parasagittal osteotomy 
Maxillary transverse deficiency is one of the most common deformities among occlusal discrepancies. Typical surgical methods are segmental Le Fort I osteotomy and surgically-assisted rapid maxillary expansion (SARME). This patient underwent a parasagittal split with a Le Fort I osteotomy to correct transverse maxillary deficiency. During follow-up, early transverse relapse occurred and rapid maxillary expansion (RME) application with removal of the fixative plate on the constricted side was able to regain the dimension again. RME application may be appropriate salvage therapy for such a case.
PMCID: PMC4411735  PMID: 25922822
Maxillary transverse deficiency; Le Fort osteotomy; Maxillary expansion; Salvage therapy
22.  Evaluation of the Synuclein-γ (SNCG) Gene as a PPARγ Target in Murine Adipocytes, Dorsal Root Ganglia Somatosensory Neurons, and Human Adipose Tissue 
PLoS ONE  2015;10(3):e0115830.
Recent evidence in adipocytes points to a role for synuclein-γ in metabolism and lipid droplet dynamics, but interestingly this factor is also robustly expressed in peripheral neurons. Specific regulation of the synuclein-γ gene (Sncg) by PPARγ requires further evaluation, especially in peripheral neurons, prompting us to test if Sncg is a bona fide PPARγ target in murine adipocytes and peripheral somatosensory neurons derived from the dorsal root ganglia (DRG). Sncg mRNA was decreased in 3T3-L1 adipocytes (~68%) by rosiglitazone, and this effect was diminished by the PPARγ antagonist T0070907. Chromatin immunoprecipitation experiments confirmed PPARγ protein binding at two promoter sequences of Sncg during 3T3-L1 adipogenesis. Rosiglitazone did not affect Sncg mRNA expression in murine cultured DRG neurons. In subcutaneous human WAT samples from two cohorts treated with pioglitazone (>11 wks), SNCG mRNA expression was reduced, albeit highly variable and most evident in type 2 diabetes. Leptin (Lep) expression, thought to be coordinately-regulated with Sncg based on correlations in human adipose tissue, was also reduced in 3T3-L1 adipocytes by rosiglitazone. However, Lep was unaffected by PPARγ antagonist, and the LXR agonist T0901317 significantly reduced Lep expression (~64%) while not impacting Sncg. The results support the concept that synuclein-γ shares some, but not all, gene regulators with leptin and is a PPARγ target in adipocytes but not DRG neurons. Regulation of synuclein-γ by cues such as PPARγ agonism in adipocytes is logical based on recent evidence for an important role for synuclein-γ in the maintenance and dynamics of adipocyte lipid droplets.
PMCID: PMC4355072  PMID: 25756178
23.  Tuning Locality of Pair Coherence in Graphene-based Andreev Interferometers 
Scientific Reports  2015;5:8715.
We report on gate-tuned locality of superconductivity-induced phase-coherent magnetoconductance oscillations in a graphene-based Andreev interferometer, consisting of a T-shaped graphene bar in contact with a superconducting Al loop. The conductance oscillations arose from the flux change through the superconducting Al loop, with gate-dependent Fraunhofer-type modulation of the envelope. We confirm a transitional change in the character of the pair coherence, between local and nonlocal, in the same device as the effective length-to-width ratio of the device was modulated by tuning the pair-coherence length ξT in the graphene layer.
PMCID: PMC4348647  PMID: 25737106
24.  Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy 
BMB Reports  2014;47(12):697-702.
Recently, the interest in natural products for the treatment of cancer is increasing because they are the pre-screened candidates. In the present study, we demonstrate the therapeutic effect of celastrol, a triterpene extracted from the root bark of Chinese medicine on gastric cancer. The proliferation of AGS and YCC-2 cells were most sensitively decreased in six kinds of gastric cancer cell lines after the treatment with celastrol. Celastrol inhibited the cell migration and increased G1 arrest in cell-cycle populations in both cell lines. The treatment with celastrol significantly induced autophagy and apoptosis and increased the expression of autophagy and apoptosis-related proteins. We also found an increase in phosphorylated AMPK following a decrease in all phosphorylated forms of AKT, mTOR and S6K after the treatment with celastrol. Moreover, gastric tumor burdens were reduced in a dose-dependent manner by celastrol administration in a xenografted mice model. Taken together, celastrol distinctly inhibits the gastric cancer cell proliferation and induces autophagy and apoptosis. [BMB Reports 2014; 47(12): 697-702]
PMCID: PMC4345515  PMID: 24667175
Apoptosis; Autophagy; Celastrol; Chemo therapy; Gastric cancer
25.  Supratentorial Hemangioblastoma with Unusual Features 
Korean Journal of Pathology  2014;48(6):462-465.
PMCID: PMC4284497  PMID: 25588642

Results 1-25 (51)