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author:("Suzuki, mayo")
1.  Individual- and community-level social gradients of edentulousness 
BMC Oral Health  2015;15:34.
Community-level factors as well as individual-level factors affect individual health. To date, no studies have examined the association between community-level social gradient and edentulousness. The aim of this study was to investigate individual- and community-level social inequalities in edentulousness and to determine any explanatory factors in this association.
We analyzed the data from the Japan Gerontological Evaluation Study (JAGES). In 2010-2012, 112,123 subjects aged 65 or older responded to the questionnaire survey (response rate = 66.3%). Multilevel logistic regression analysis was applied to determine the association between community-level income and edentulousness after accounting for individual-level income and demographic covariates. Then, we estimated the probability of edentulousness by individual- and community-level incomes after adjusted for covariates.
Of 79,563 valid participants, the prevalence of edentulousness among 39,550 men (49.7%) and 40,013 women (50.3%) were both 13.8%. Living in communities with higher mean incomes and having higher individual-level incomes were significantly associated with a lower risk of edentulousness (odds ratios [ORs] by 10,000 USD increments were 0.37 (95% confidence interval [CI] [0.22-0.63]) for community-level and 0.85 (95% CI [0.84-0.86]) for individual-level income). Individual- and community-level social factors, including density of dental clinics, partially explained the social gradients. However, in the fully adjusted model, both community- and individual-level social gradients of edentulousness remained significant (ORs = 0.43 (95% CI [0.27-0.67]) and 0.90 (95% CI [0.88-0.91]), respectively). One standard deviation changes in community- and individual-level incomes were associated with 0.78 and 0.84 times lower odds of edentulousness, respectively. In addition, compared to men, women living in communities with higher average incomes had a significantly lower risk of edentulousness (p-value for interaction < 0.001).
Individual- and community-level social inequalities in dental health were observed. Public health policies should account for social determinants of oral health when reducing oral health inequalities.
PMCID: PMC4460930  PMID: 25884467
Dental public health; Edentulous/edentulism; Income inequality; Gender differences; Multilevel analysis
2.  Bone metastasis of a gastrointestinal stromal tumor: A report of two cases 
Oncology Letters  2015;9(4):1814-1818.
Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal tumors of the GI tract. GISTs usually arise from the stomach, followed by the small intestine, rectum and other locations in the GI tract. The most common metastatic sites are the liver and peritoneum, whereas GISTs rarely metastasize to the bone. Although a small number of previous studies have described bone metastases originating from GISTs, the true prevalence is yet to be elucidated. The present study describes two cases of bone metastasis in patients with GISTs and reviews the relevant literature. Case one was of a 78-year-old male who presented with bone metastasis to the femoral neck five years after the resection of a GIST. The metastasis was completely resected and the patient remains alive nine years after the initial diagnosis of the GIST. Case 2 was of a 41-year-old male who presented with bone metastases to the ribs following resection of GISTs seven and 17 years earlier. The metastases were completely resected and the patient remains alive 17 years after the initial diagnosis. In total, only 10 cases of GISTs with metastases to the bone have been reported in the English literature. The possibility of bone metastases originating from a GIST should be considered during clinical follow-up, particularly in the presence of liver metastases. If feasible, bone metastases should be completely surgically excised.
PMCID: PMC4356394  PMID: 25789048
gastrointestinal stromal tumor; bone metastasis; surgery; imatinib
3.  Relative Deprivation, Poverty, and Subjective Health: JAGES Cross-Sectional Study 
PLoS ONE  2014;9(10):e111169.
To evaluate the association between relative deprivation (lacking daily necessities) and subjective health in older Japanese adults, we performed a cross-sectional analysis using data from the Japan Gerontological Evaluation Study (JAGES). The data were obtained from functionally independent residents aged ≥65 years from 24 municipalities in Japan (n = 24,742). Thirteen items in three dimensions were used to evaluate relative deprivation of material conditions. Approximately 28% of older Japanese people indicated that they lacked some daily necessities (non-monetary poverty). A two-level Poisson regression analysis revealed that relative deprivation was associated with poor self-rated health (PR = 1.3–1.5) and depressive symptoms (PR = 1.5–1.8) in both men and women, and these relationships were stronger than those observed in people living in relative poverty (monetary poverty). The interaction effect between relative deprivation and relative poverty was not associated with poor health. As a dimension of the social determinants of health, poverty should be evaluated from a multidimensional approach, capturing not only monetary conditions but also material-based, non-monetary conditions.
PMCID: PMC4211701  PMID: 25350284
4.  Metastasis of gastrointestinal stromal tumor to skeletal muscle: a case report 
Gastrointestinal stromal tumor is the most common malignant mesenchymal tumor of the gastrointestinal tract. The most common sites of metastasis are the liver and the peritoneum, but gastrointestinal stromal tumors rarely metastasize to the skeletal muscles. Only three cases of gastrointestinal stromal tumor metastasizing to skeletal muscle have been reported in the English literature. Here we present an additional case of skeletal muscle metastasis, and the relevant literature is reviewed.
Case presentation
A 54-year-old Japanese man presented with a three-month history of an enlarging mass of the left buttock. An excisional biopsy was performed and the tumor was diagnosed as a leiomyosarcoma. However, careful examination of the gastrointestinal tract revealed a tumor located in the small intestine. Surgical resection of the small intestine tumor was performed; histopathological and immunohistochemical examinations identified it as a primary gastrointestinal stromal tumor arising from the small intestine. Despite receiving both chemotherapy and molecular-targeted therapy, our patient died of gastrointestinal bleeding six months after the initial diagnosis.
Because it is a mesenchymal tumor, it is difficult to distinguish a gastrointestinal stromal tumor metastasis to skeletal muscle from other primary soft tissue sarcomas. Although metastasis of gastrointestinal stromal tumor to skeletal muscle is rare, the likelihood of finding metastases in these unusual sites is increasing due to prolonged survival of patients with gastrointestinal stromal tumor after the introduction of imatinib therapy. We should include metastases of gastrointestinal stromal tumors as differential diagnosis of spindle cell tumor, and it is necessary to begin appropriate treatment early.
PMCID: PMC4112972  PMID: 25037940
Gastrointestinal stromal tumor; Sarcoma; Skeletal muscle metastasis
5.  Social Participation and the Prevention of Functional Disability in Older Japanese: The JAGES Cohort Study 
PLoS ONE  2014;9(6):e99638.
We examined the relationship between incident functional disability and social participation from the perspective of number of types of organizations participated in and type of social participation in a prospective cohort study.
The study was based on the Aichi Gerontological Evaluation Study (AGES) Cohort Study data. We followed 13,310 individuals aged 65 years or older for 4 years. Analysis was carried out on 12,951 subjects, excluding 359 people whose information on age or sex was missing. Social participation was categorized into 8 types.
Compared to those that did not participate in any organizations, the hazard ratio (HR) was 0.83 (95% CI: 0.73–0.95) for participation in one, 0.72 (0.61–0.85) for participation in two, and 0.57 (0.46–0.70) for participation in three or more different types of organizations. In multivariable adjusted models, participation in the following types of organization was protective for incident disability: local community organizations (HR = 0.85, 95% CI: 0.76–0.96), hobby organizations (HR = 0.75, 95% CI: 0.64–0.87), and sports organizations (HR = 0.64, 95% CI: 0.54–0.81).
Social participation may decrease the risk of incident functional disability in older people in Japan. This effect may be strengthened by participation in a variety of different types of organizations. Participating in a local community, hobby, or sports group or organization may be especially effective for decreasing the risk of disability.
PMCID: PMC4055714  PMID: 24923270
6.  Social determinants of denture/bridge use: Japan gerontological evaluation study project cross-sectional study in older Japanese 
BMC Oral Health  2014;14:63.
Studies suggest that using a denture/bridge may prevent disability in older people. However, not all older people with few remaining teeth use a denture/bridge. This cross-sectional study aimed to examine the social determinants which promote denture/bridge use among older Japanese.
A total of 54,388 (25,630 males and 28,758 females) community-dwelling individuals aged 65 or over, living independently, able to perform daily activities, and with 19 or fewer teeth. The dependent variable was denture/bridge use. Socio-demographics, number of teeth, present illness, social participation, social support, and social networks were used as individual-level independent variables. Data for social capital were aggregated and used as local district (n = 561 for males, n = 562 for females) -level independent variables. Number of dentists working in hospitals/clinics per population and population density were used as municipality (n = 28) -level independent variables. Three-level multilevel Poisson regression analysis was performed for each sex.
High equivalent income, low number of teeth, present illness, and living in a municipality with high population density were significantly associated with denture/bridge use in both sexes in the fully adjusted models (p < 0.05). Denture/bridge use was significantly associated with high educational attainment in males and participating in social groups in females in the fully adjusted model (p < 0.05). No significant associations were observed between denture/bridge use and social capital.
Denture/bridge use was significantly associated with high economic status and present illness in both sexes, high educational attainment in males, and participation in social groups in females among community-dwelling older Japanese after adjusting for possible confounders.
PMCID: PMC4050218  PMID: 24894968
Social determinants; Dental prosthesis; Older people; Cross-sectional study
7.  Factors Associated with Falls in Community-Dwelling Older People with Focus on Participation in Sport Organizations: The Japan Gerontological Evaluation Study Project 
BioMed Research International  2014;2014:537614.
Objective. Promoting participation in sport organizations may be a population strategy for preventing falls in older people. In this study, we examined whether participation in sport organizations is associated with fewer falls in older people even after adjusting for multiple individual and environmental factors. Methods. We used the Japan Gerontological Evaluation Study data of 90,610 people (31 municipalities) who were not eligible for public long-term care. Logistic regression analysis was performed, with multiple falls over the past year as the dependent variable and participation in a sport organization as the independent variable, controlling for 13 factors. These included individual factors related to falls, such as age and sex, and environmental factors such as population density of the habitable area. Results. A total of 6,391 subjects (7.1%) had a history of multiple falls. Despite controlling for 13 variables, those who participated in a sport organization at least once a week were approximately ≥20% less likely to fall than those who did not participate at all (once a week; odds ratio = 0.82 and 95% confidence interval = 0.72–0.95). Conclusion. Participation in a sport organization at least once per week might help prevent falls in the community-dwelling older people.
PMCID: PMC4052782  PMID: 24955360
8.  DNA copy number alterations in pleomorphic leiomyosarcoma: A case report 
Oncology Letters  2014;7(6):1847-1850.
Pleomorphic leiomyosarcoma (P-LMS) is a rare morphological variant of LMS. The current study presents the cytogenetic data of a P-LMS that arose in the axillary region of a 31-year-old male. The results of array-based comparative genomic hybridization for the primary tumor showed DNA copy number alteration (DCNA) gains of 8ptel, 17ptel and 17q11.2 and losses of 2ptel, 7ptel, 7qtel, 10p15, 12p12-13.1, 13q14.2-14.3, 15q25-26 and Yq11. However, a metastatic lesion showed cytogenetic data different from the primary tumor DCNAs, with only the locus of 17ptel (282M15/SP6) in common between them. These observations add to the spectrum of DCNAs that have been reported in previous cases of LMS and provide novel cytogenetic data.
PMCID: PMC4049769  PMID: 24932246
leiomyosarcoma; comparative genomic hybridization; DNA; chromosome
9.  An intraosseous malignant peripheral nerve sheath tumor of the lumbar spine without neurofibromatosis: Case report and review of the literature 
Oncology Letters  2014;7(6):1965-1969.
A malignant peripheral nerve sheath tumor (MPNST) is defined as any malignant tumor that develops or differentiates from cells in the peripheral nerve sheath. This tumor is commonly associated with neurofibromatosis type 1 (NF1) and previous radiotherapy treatment. Primary intraosseous MPNSTs are extremely rare and a case of the lumbar spine in a patient without NF1 is reported in the present study, with a review of the intraosseous MPNST literature. A 45-year-old female presented with a 1-month history of severe lower back pain and pain radiating to the left leg. A total en bloc spondylectomy of L4 was performed. The postoperative histopathological diagnosis was MPNST with deletion of NF1, confirmed by dual-color fluorescence in situ hybridization (FISH) analysis. The tumor recurred 1 month following the surgery. Although adjuvant chemotherapy was administered, the patient succumbed due to intramedullary dissemination and carcinomatous meningitis 8 months following the initial consultation. NF1 deletion by FISH analysis may be particularly useful in distinguishing MPNST from other high-grade malignancies with overlapping morphological features.
PMCID: PMC4049692  PMID: 24932270
intraosseous malignant peripheral nerve sheath tumor; spine; total en bloc spondylectomy
10.  Pleomorphic hyalinizing angiectatic tumor arising in the thigh: A case report 
Oncology Letters  2014;7(4):1249-1252.
Pleomorphic hyalinizing angiectatic tumors (PHATs) are rare non-metastasizing tumors of uncertain lineage. The current study presents a case of PHAT arising in the thigh of a 68-year-old female and examines the clinicopathological characteristics of the tumor. Magnetic resonance imaging (MRI) revealed an intramuscular mass located in the adductor longus. The tumor was surrounded by lipomatous tumor. Wide resectioning was performed for the internal tumor, whereas intralesional resectioning was performed for the external tumor. Histopathologically, the internal lesion was diagnosed as a PHAT and the external lesion was diagnosed as an hemosiderotic fibrolipomatous lesion (HFLL). No recurrence or metastases were identified during the 6-year follow-up period. As the adipose tissue surrounding the PHAT resembled a HFLL, therefore, the association between ‘early PHAT’ and HFLL is discussed. Although PHATs may represent low-grade sarcomas, HFLLs may be benign tumors.
PMCID: PMC3961218  PMID: 24944701
pleomorphic hyalinizing angiectatic tumor; hemosiderotic fibrohistiocytic lipomatous lesion; imaging
11.  Giant Invasive Sacral Schwannoma Showing Chromosomal Numerical Aberrations [-14,+18,+22] 
Asian Spine Journal  2013;7(3):227-231.
Here, we report on a rare case of a giant invasive sacral schwannoma. The patient was a 58-year-old woman who had a 6-year history of non-specific buttock pain. Histological investigation confirmed the diagnosis of cellular schwannoma. The following numerical aberration was detected using the GTG-banding method for karyotypes: 47,XX,-14,+18,+22. Cytogenetic studies of schwannomas have indicated a complete or partial loss of chromosome 22 as the most common abnormality, but this case is cytogenetically rare because of the recurrence of trisomy 22.
PMCID: PMC3779776  PMID: 24066220
Sacrum; Neurilemmoma; Cytogenetics
12.  Structural Basis of α-Catenin Recognition by EspB from Enterohaemorrhagic E. coli Based on Hybrid Strategy Using Low-Resolution Structural and Protein Dissection 
PLoS ONE  2013;8(8):e71618.
Enterohaemorrhagic E. coli (EHEC) induces actin reorganization of host cells by injecting various effectors into host cytosol through type III secretion systems. EspB is the natively partially folded EHEC effector which binds to host α-catenin to promote the actin bundling. However, its structural basis is poorly understood. Here, we characterize the overall structural properties of EspB based on low-resolution structural data in conjunction with protein dissection strategy. EspB showed a unique thermal response involving cold denaturation in the presence of denaturant according to far-UV circular dichroism (CD). Small angle X-ray scattering revealed the formation of a highly extended structure of EspB comparable to the ideal random coil. Various disorder predictions as well as CD spectra of EspB fragments identified the presence of α-helical structures around G41 to Q70. The fragment corresponding to this region indicated the thermal response similar to EspB. Moreover, this fragment showed a high affinity to C-terminal vinculin homology domain of α-catenin. The results clarified the importance of preformed α-helix of EspB for recognition of α-catenin.
PMCID: PMC3743801  PMID: 23967227
13.  Extracapsular wide resection of a femoral neck osteosarcoma and its reconstruction using a pasteurized autograft-prosthesis composite: A case report 
Oncology Letters  2013;6(4):1147-1151.
The requirement for an extracapsular resection is indicated for malignant bone tumors that have disseminated intracapsularly. Extracapsular resections are often performed for malignant tumors arising from the knee joint, but there are relatively few studies that have described an extracapsular resection of a tumor arising from the hip joint. The present study describes a case of extracapsular wide resection of the hip joint using rotational acetabular osteotomy. The patient was a 17-year-old female and the diagnosis was an osteoblastic osteosarcoma with a pathological fracture of the femoral neck. The joint was reconstructed using an allograft-implant composite graft and total hip arthroplasty. Although the patient presented a slight Trendelenburg gait, no recurrence or metastases were identified during a follow-up period of 3 years. The clinical features and surgical procedure of the case are described.
PMCID: PMC3796432  PMID: 24137479
extracapsular resection; total hip arthroplasty; osteosarcoma
14.  Cutaneous angiosarcoma of the buttock complicated by severe thrombocytopenia: A case report 
Molecular and Clinical Oncology  2013;1(5):903-907.
Angiosarcoma (AS) is an aggressive, malignant endothelial cell tumor of vascular or lymphatic origin, the presentation and clinical behavior of which may vary according to its location. This is the case report of a 56-year-old woman with cutaneous angiosarcoma (CAS) of the buttock complicated by severe thrombocytopenia. A review of the literature revealed that only nine cases of CAS with thrombocytopenia have been previously reported. The prognosis of CAS complicated by thrombocytopenia is poor, even after treatment with combined chemotherapy and radiotherapy (RT). The composite karyotype was 46,XX,t(12;20)(p13;p11.2)[3]/47,X,add(X)(q13),del(6)(q?),add(12)(p13),−21,+2mar[2]/45,XX,der(1)add(1)(p36.3)del(1)(q41),−20[1]/46,XX[13]. Only 13 cytogenetic cases of AS, including the present case, have been reported in the English literature thus far. In this case report, the clinical presentation and cytogenetic findings are described and the relevant literature on AS is reviewed.
PMCID: PMC3915322  PMID: 24649268
cutaneous angiosarcoma; thrombocytopenia; karyotype
15.  Participation in Sports Organizations and the Prevention of Functional Disability in Older Japanese: The AGES Cohort Study 
PLoS ONE  2012;7(11):e51061.
We sought to examine prospectively the difference in the association between incident functional disability and exercise with or without sports organization participation.
The study was based on the Aichi Gerontological Evaluation Study (AGES) Cohort Study data. In October 2003, self-reported questionnaires were mailed to 29,374 non-disabled Japanese individuals aged 65 years or older. Of these, 13,310 individuals were introduced to the Study, and they were followed for 4 years. Analysis was carried out on 11,581 subjects who provided all necessary information for the analysis.
Analysis was carried out on incident functional disability by 4 groups of different combinations of performance of exercise and participation in a sports organization Active Participant (AP), Exercise Alone (EA), Passive Participant (PP) and Sedentary (S). Compared to the AP group, the EA group had a hazard ratio (HR) of 1.29 (1.02–1.64) for incident functional disability. No significant difference was seen with the PP group, with an HR of 1.16 (0.76–1.77). When a measure of social networks was added to the covariates, the HR of the EA group dropped to 1.27 (1.00–1.61), and significant differences disappeared. In contrast, it showed hardly any change when social support was added.
The results suggested that, even with a regular exercise habit, incident functional disability may be better prevented when a person participates in a sports organization than when he/she does not. In addition, participation in a sports organization correlates positively with social networks, which may lead to a small decrease in incident functional disability.
PMCID: PMC3511372  PMID: 23226458
16.  Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors 
The genetic pathways of aggressive changes of bone tumors are still poorly understood. It is very important to analyze DNA copy number alterations (DCNAs), to identify the molecular events in the step of progression to the aggressive change of bone tissue.
Genome-wide array-based comparative genomic hybridization (array CGH) was used to investigate DCNAs of 14 samples from 13 aggressive bone tumors, such as giant cell tumors (GCTs) and osteosarcoma (OS), etc.
Primary aggressive bone tumors had copy number gains of 17.8±12.7% in the genome, and losses of 17.3±11.4% in 287 target clones (threshold for each DCNA: ≦085, 1.15≦). Genetic unstable cases, which were defined by the total DCNAs aberration ≧30%, were identified in 9 of 13 patients (3 of 7 GCTs and all malignant tumors). High-level amplification of TGFβ2, CCND3, WI-6509, SHGC-5557, TCL1A, CREBBP, HIC1, THRA, AFM217YD10, LAMA3, RUNX1 and D22S543, were commonly observed in aggressive bone tumors. On the other hand, NRAS, D2S447, RAF1, ROBO1, MYB, MOS, FGFR2, HRAS, D13S319, D13S327, D18S552, YES1 and DCC, were commonly low. We compared genetic instability between a primary OS and its metastatic site in Case #13. Metastatic lesion showed increased 9 DCNAs of remarkable change (m/p ratio ≧1.3 folds), compared to a primary lesion. D1S214, D1S1635, EXT1, AFM137XA11, 8 M16/SP6, CCND2, IGH, 282 M15/SP6, HIC1 and LAMA3, were overexpressed. We gave attention to HIC1 (17p13.3), which was common high amplification in this series.
Our results may provide several entry points for the identification of candidate genes associated with aggressive change of bone tumors. Especially, the locus 17p11-13 including HIC1 close to p53 was common high amplification in this series and review of the literature.
PMCID: PMC3576288  PMID: 23199169
Osteosarcoma; Giant cell tumor; Bone tumors; Microarray; Comparative genomic hybridization
17.  Minimum 10-Year Follow-up Study of Anterior Lumbar Interbody Fusion for Degenerative Spondylolisthesis: Progressive Pattern of the Adjacent Disc Degeneration 
Asian Spine Journal  2012;6(2):105-114.
Study Design
Retrospective study.
The aims of the current study are to evaluate the minimum 10-year follow-up clinical results of anterior lumbar interbody fusion (ALIF) for degenerative spondylolisthesis.
Overview of Literature
ALIF has been widely used as a treatment regimen in the management of lumbar spondylolisthesis. Still much controversy exists regarding the factors that affect the postoperative clinical outcomes.
The author performed a retrospective review of 20 patients with degenerative spondylolisthesis treated with ALIF (follow-up, 16.4 years). The clinical results were assessed by the Japanese Orthopaedic Association (JOA) score for low back pain, vertebral slip and disc height index on the radiographs.
The mean preoperative JOA score was 7.1 ± 1.8 points (15-point-method). At 1 year, 5 years, and 10 years or more after surgery, the JOA scores were assessed as 12.4 ± 2.2 points, 12.7 ± 2.6 points, 12.0 ± 2.5 points, respectively (excluding the data of reoperated cases). The adjacent disc degeneration developed in all cases during the long-term follow-up. The progressive pattern of disc degeneration was divided into three types. Initially, disc degeneration occurred due to disc space narrowing. After that, the intervertebral discs showed segmental instability with translation at the upper level. But the lower discs showed osteophyte formation, and occasionally lead to the collapse or spontaneous union.
The clinical results of the long-term follow-up data after ALIF became worse due to the adjacent disc degeneration. The progressive pattern of disc degeneration was different according to the adjacent levels.
PMCID: PMC3372545  PMID: 22708014
Spondylolisthesis; Lumbar regions; Intervertebral disc disease
18.  Myxoid Liposarcoma-Associated EWSR1-DDIT3 Selectively Represses Osteoblastic and Chondrocytic Transcription in Multipotent Mesenchymal Cells 
PLoS ONE  2012;7(5):e36682.
Liposarcomas are the most common class of soft tissue sarcomas, and myxoid liposarcoma is the second most common liposarcoma. EWSR1-DDIT3 is a chimeric fusion protein generated by the myxoid liposarcoma-specific chromosomal translocation t(12;22)(q13;q12). Current studies indicate that multipotent mesenchymal cells are the origin of sarcomas. The mechanism whereby EWSR1-DDIT3 contributes to the phenotypic selection of target cells during oncogenic transformation remains to be elucidated.
Methodology/Principal Findings
Reporter assays showed that the EWSR1-DDIT3 myxoid liposarcoma fusion protein, but not its wild-type counterparts EWSR1 and DDIT3, selectively repressed the transcriptional activity of cell lineage-specific marker genes in multipotent mesenchymal C3H10T1/2 cells. Specifically, the osteoblastic marker Opn promoter and chondrocytic marker Col11a2 promoter were repressed, while the adipocytic marker Ppar-γ2 promoter was not affected. Mutation analyses, transient ChIP assays, and treatment of cells with trichostatin A (a potent inhibitor of histone deacetylases) or 5-Aza-2′-deoxycytidine (a methylation-resistant cytosine homolog) revealed the possible molecular mechanisms underlying the above-mentioned selective transcriptional repression. The first is a genetic action of the EWSR1-DDIT3 fusion protein, which results in binding to the functional C/EBP site within Opn and Col11a2 promoters through interaction of its DNA-binding domain and subsequent interference with endogenous C/EBPβ function. Another possible mechanism is an epigenetic action of EWSR1-DDIT3, which enhances histone deacetylation, DNA methylation, and histone H3K9 trimethylation at the transcriptional repression site. We hypothesize that EWSR1-DDIT3-mediated transcriptional regulation may modulate the target cell lineage through target gene-specific genetic and epigenetic conversions.
This study elucidates the molecular mechanisms underlying EWSR1-DDIT3 fusion protein-mediated phenotypic selection of putative target multipotent mesenchymal cells during myxoid liposarcoma development. A better understanding of this process is fundamental to the elucidation of possible direct lineage reprogramming in oncogenic sarcoma transformation mediated by fusion proteins.
PMCID: PMC3343026  PMID: 22570737
19.  CD99-positive soft tissue sarcoma with chromosomal translocation between 1 and 16 and inversion of chromosome 5 
Oncology Letters  2012;3(6):1213-1215.
In this study, we report the cytogenetic analysis of a 31-year-old male with a rare translocation between chromosomes 1 and 16 and inversion of chromosome 5 in CD99-positive soft tissue sarcoma of the thigh, which metastasized to the lung. Histologically, the tumor showed ovoid or short-spindle atypical cells with positivities of CD99, vimentin and bcl-2. Cytogenetically, all 20 analyzed cells showed the clonal aberrations add(1)(q23), t(1;16)(p21;p11.2), inv(5)(q11.2;q15). This finding adds to the new karyotype spectrum of CD99-positive soft tissue sarcomas.
PMCID: PMC3392573  PMID: 22783420
CD99; karyotype; chromosome; sarcoma
20.  Vertebroplasty Using Calcium Phosphate Cement for Osteoporotic Vertebral Fractures: Study of Outcomes at a Minimum Follow-up of Two Years 
Asian Spine Journal  2012;6(1):34-42.
Study Design
A case-series study.
To assess the long-term clinical and radiographic outcomes after vertebroplasty using calcium phosphate cement (CPC) for treatment of osteoporotic vertebral fractures (OVF).
Overview of Literature
Vertebroplasty has become common for the treatment of OVF. However, few studies have reported the clinical application of CPC to vertebroplasty.
We reviewed 86 consecutive patients undergoing 99 vertebroplasties using CPC. Following repositioning and curettage of the pathological soft tissue of the vertebral body (VB), vertebroplasty using CPC was performed in patients with osteoporotic burst fracture and pseudoarthrosis (procedure A). Vertebroplasty was also performed in patients with osteoporotic compression fractures (procedure B). Back pain and lower back pain were evaluated using the visual analogue scale (VAS). The VB deformity index was measured in a lateral radiograph as the ratio of the VB's height to its longitudinal diameter.
The mean age at time of surgery was 77 years old. The mean duration of follow-up was forty-four months. All patients reported decreased pain according to the VAS immediately after vertebroplasty, and pain relief was maintained at the last follow-up in all patients without new OVFs. Complete bone union was observed in all cases by six months after surgery. The mean recovery rate of deformity index was 5.9% in procedure A and 0.02% in procedure B at the final follow-up visit.
Vertebroplasty using CPC gave a satisfactory outcome and no delayed complications in elderly patients with osteoporotic vertebral fractures at follow-up times of at least two years.
PMCID: PMC3302913  PMID: 22439086
Osteoporosis; Vertebral fracture; Biodegradable bone cement substitutes; Calcium phosphate cement; Vertebroplasty
21.  Skeletal metastasis of carcinoid tumors: Two case reports and review of the literature 
Oncology Letters  2012;3(5):1105-1108.
Carcinoid tumors are neuroendocrine neoplasms derived from enterochromaffin cells. Skeletal metastases from carcinoid tumors are considered to be extremely rare. In this study, we present two cases of carcinoid tumors that metastasized to the bone. Furthermore, we review 50 published case reports and reveal the features of skeletal metastasis of carcinoid tumors. The first case involved a 59-year-old man with a history of multiple metastases of a lung carcinoid tumor. The patient complained of back pain and numbness in the lower limbs. Magnetic resonance imaging revealed metastases in the thoracic spine. A spinal decompression was performed and the symptoms were resolved. The second case involved a 74-year-old man had been diagnosed with a lung carcinoid tumor 15 years previously and complained of left thigh pain. A radiograph showed osteolytic lesions in the shaft of the left femur. We repaired the femur using an intramedullary nail following curettage of the tumor. A radiograph of the femur revealed a callus on the pathological fracture. The patient was able to walk using a crutch 3 months after surgery. We reviewed 50 cases that described skeletal metastasis from carcinoid tumors. The average age of the patients was 54.9 years and 33 patients (66%) were male. The most common site of skeletal metastasis was the spine. We also investigated the survival rate of patients who developed skeletal metastasis from carcinoid tumors. The findings showed that survival of patients who developed osteolytic skeletal metastasis was worse than that of patients who developed osteosclerotic skeletal metastasis.
PMCID: PMC3389625  PMID: 22783400
carcinoid tumor; skeletal metastasis; prognosis
22.  Extraskeletal myxoid chondrosarcoma of the thigh with a t(9;17) translocation 
Oncology Letters  2011;3(3):621-624.
Extraskeletal myxoid chondrosarcomas (EMC) are relatively rare. We report a case of EMC of the thigh. A 41-year-old man presented with a tumor history of more than 4 months. Following open biopsy, wide resection of the tumor was performed. Histopathologically, the tumor had a multinodular architecture consisting of myxomatous areas demarcated by fibrous septa. Proliferation of uniform, round tumor cells with oval nuclei was observed. Well-formed hyaline cartilage and rhabdoid-like cells were not visible. Immunohistochemically, the tumor cells were positive for vimentin and S-100. The composite karyotype was 46,XY,t(9;17)(q22;q11),t(9;21)(q21;p13), and the diagnosis of EMC was made. No recurrence of the mass or metastasis was observed during a follow-up period of 4 years and 7 months. Only 50 cytogenetic cases of EMC, including our case, have been reported in the English literature thus far. Clinical presentation, radiological features and histopathological and cytogenetic findings are described, and the relevant literature is reviewed.
PMCID: PMC3362353  PMID: 22740963
extraskeletal myxoid chondrosarcoma; karyotype; prognosis
23.  Variation in myxoid liposarcoma: Clinicopathological examination of four cases with detectable TLS-CHOP or EWS-CHOP fusion transcripts whose histopathological diagnosis was other than myxoid liposarcoma 
Oncology Letters  2011;3(2):293-296.
Liposarcomas are separated into clinicopathological entities by a characteristic morphological spectrum and distinctive genetic changes. Myxoid liposarcoma (MLS) represents one such entity with specific chromosomal translocations leading to the generation of fusion genes, the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) or the Ewing sarcoma (EWS)-CHOP. In the present study, four cases of liposarcoma with detection of TLS-CHOP or EWS-CHOP, whose postoperative diagnosis was other than MLS (one well-differentiated liposarcoma, two de-differentiated liposarcomas and one unclassified) were examined for medical records, imaging data and histopathology. Clinical records demonstrated that three of the four cases were considerably difficult to diagnose definitively, and histopathological re-examination pointed out areas of myxomatous change as a minor component (<10%). Their dominant components (>90%) resembled pleomorphic sarcoma, pleomorphic malignant fibrous histiocytoma and monophasic synovial sarcoma. The current cases may represent an extreme variant of the morphological spectrum within MLS. In cases of difficulty in making definitive diagnosis of soft tissue sarcoma by standard histopathological examination and identification of myxoid stroma even as a minor component, analyzing TLS-CHOP and EWS-CHOP fusion genes may aid the diagnosis of unusual MLS.
PMCID: PMC3362345  PMID: 22740897
Ewing sarcoma-CCAAT/enhancer binding homologous protein; histopathology; myxoid liposarcoma; reverse transcription-polymerase chain reaction; human translocation liposarcoma-CCAAT/enhancer binding homologous protein; variation
24.  Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization 
The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS.
PMCID: PMC2660296  PMID: 19239720
25.  Mice Intranasally Immunized with a Recombinant 16-Kilodalton Antigen from Roundworm Ascaris Parasites Are Protected against Larval Migration of Ascaris suum  
Infection and Immunity  2003;71(9):5314-5323.
Protective immunity to the pig roundworm, Ascaris suum, has been demonstrated by immunization of pigs with antigens derived from the parasite's larval stages. We identified a protective antigen commonly expressed in the human and pig Ascaris infections as a 16-kDa protein (As16), which has no similarity at the amino acid level to mammalian proteins but has some similarity to those of the filarial parasites and Caenorhabditis elegans gene product. Localization analysis revealed that the native As16 was highly expressed in the adult worm intestine, hypodermis, and cuticles. In addition, As16 was detected in the parasite excretory and secretory products. Mice intranasally vaccinated with Escherichia coli-expressed recombinant As16 (rAs16), coupled with cholera toxin B subunit, generated a significant increase in the level of rAs16-specific immunoglobulin G (IgG) and IgE in serum. Mucosal IgA levels were also increased. The recombinant protein evoked a mixed (both Th1 and Th2) type of immune response characterized by elevated levels of gamma interferon and interleukin-10 in the culture supernatants of activated spleen cells. An increased level of IgG1 and IgG2a in serum was also observed. The vaccinated mice showed a reduction by 58% in the recovery of challenged larvae compared to a nonvaccinated control. These results suggest the possibility of developing a mucosal vaccine for human and pig ascariasis.
PMCID: PMC187325  PMID: 12933879

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