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The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Carcinoma de Células Renais , Neoplasias Renais , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Microambiente Tumoral , Humanos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Serina-Treonina Quinases TOR/metabolismo , Microambiente Tumoral/fisiologia , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Seed dormancy is an important agronomic trait under the control of complex genetic and environmental interactions, which have not been yet comprehensively understood. From the field screening of rice mutant library generated by a Ds transposable element, we identified a pre-harvest sprouting (PHS) mutant dor1. This mutant has a single insertion of Ds element at the second exon of OsDOR1 (LOC_Os03g20770), which encodes a novel seed-specific glycine-rich protein. This gene successfully complemented the PHS phenotype of dor1 mutant and its ectopic expression enhanced seed dormancy. Here, we demonstrated that OsDOR1 protein binds to the GA receptor protein, OsGID1 in rice protoplasts, and interrupts with the formation OsGID1-OsSLR1 complex in yeast cells. Co-expression of OsDOR1 with OsGID1 in rice protoplasts attenuated the GA-dependent degradation of OsSLR1, the key repressor of GA signaling. We showed the endogenous OsSLR1 protein level in the dor1 mutant seeds is significantly lower than that of wild type. The dor1 mutant featured a hypersensitive GA-response of α-amylase gene expression during seed germination. Based on these findings, we suggest that OsDOR1 is a novel negative player of GA signaling operated in the maintenance of seed dormancy. Our findings provide a novel source of PHS resistance.
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Oryza , Dormência de Plantas , Dormência de Plantas/genética , Oryza/genética , Giberelinas/metabolismo , Sementes/genética , Glicina/metabolismoRESUMO
The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.
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Antígeno B7-H1/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Renais/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , HumanosRESUMO
The AP2/EREBP family transcription factors play important roles in a wide range of stress tolerance and hormone signaling. In this study, a heat-inducible rice ERF gene was isolated and functionally characterized. The OsERF115/AP2EREBP110 was categorized to Group-IIIc of the rice AP2/EREBP family and strongly induced by heat and drought treatment. The OsERF115/AP2EREBP110 protein targeted to nuclei and suppressed the ABA-induced transcriptional activation of Rab16A promoter in rice protoplasts. Overexpression of OsERF115/AP2EREBP110 enhanced thermotolerance of seeds and vegetative growth stage plants. The OsERF115/AP2EREBP110 overexpressing (OE) plants exhibited higher proline level and increased expression of a proline biosynthesis P5CS1 gene. Phenotyping of water use dynamics of the individual plant indicates that the OsERF115/AP2EREBP110-OE plant exhibited better water saving traits under heat and drought combined stress. Our combined results suggest the potential use of OsERF115/AP2EREBP110 as a candidate gene for genetic engineering approaches to develop heat and drought stress-tolerant crops.
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Oryza/metabolismo , Termotolerância/fisiologia , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Secas , Proteínas de Choque Térmico/metabolismo , Oryza/genética , Osmorregulação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Água/fisiologiaRESUMO
Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1, which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3, and ABA4, was observed in OsRF1-OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1-OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling.
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An 82-year-old man with diabetes was admitted to the emergency department with a third-degree burn on his left leg. The deep swab specimen from his left leg was cultured on Sabouraud dextrose agar without cycloheximide and incubated at 25 °C for 5 days. On the basis of morphological characteristics and multigene phylogenetic analyses of the internal transcribed spacer region of ribosomal DNA and partial fragments of beta-tubulin and translation elongation factor 1-alpha, the causal agent of fungal skin infection was identified as Bisifusarium delphinoides, which was newly introduced by accommodating a Fusarium dimerum species complex. Thus, we describe here the first case of skin infection caused by B. delphinoides on a burn patient with diabetes mellitus based on morphological observation and molecular analysis.
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PURPOSE: The present study investigated chest computed tomography (CT) patterns and lung histological features, as well as the consistency between radiological and histological features among patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA). MATERIALS AND METHODS: The medical records of 74 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with radiological lung parenchymal lesions were reviewed along with the histological results for 28 of them. Chest CT patterns were divided according 12 items mostly suggested by radiologists and histological features were divided according to necrotising granuloma, necrotising vasculitis, eosinophilic infiltration, and hemosiderin laden macrophages as defined by a pathologist. RESULTS: The mean age was 57.1 years (22 men). The most common clinical manifestation other than lung manifestation was renal manifestation (62.2%), and the most common chest CT pattern was lung involvement of vasculitis (35.1%). In MPA patients, the major histological features were hemosiderin-laden macrophages in the alveolar space and vasculitis. In GPA patients, the major histological features were necrotizing vasculitis and necrotizing granuloma, while in EGPA patients, the major histological feature was only necrotising vasculitis. The consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%). CONCLUSION: When lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for the proper classification of AAV, due to the discordance rate between radiological and histological findings in MPA and EGPA patients, but not GPA patients.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico por imagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Few reports have described epidermal cysts (ECs) arising from scar tissues, and the standard course of treatment has not been established. We aimed to report the findings of a Korean patient series with ECs arising from scar tissues, to describe patient management in the context of previous publications, and to present a simple algorithm for managing ECs arising from scar tissues.We managed 6 patients with ECs arising from scar tissues, and retrospectively reviewed their demographic and clinical data.The scars were located on the anterior chest wall (nâ=â3), shoulder (nâ=â1), forehead (nâ=â1), and ear lobule (nâ=â1). Two patients with anterior chest wall scars, 1 with a shoulder scar, and 1 with an ear lobule scar had keloid scars, whereas the other patients had hypertrophic scars. The scar sizes ranged from 2â×â1âcm to 9â×â7âcm. The EC sizes ranged from 0.2â×â0.2âcm to 2â×â1.5âcm. Three patients underwent total scar revisions with complete EC excisions, 2 underwent partial scar tissue excisions with complete EC excisions, and 1 had laser therapy for the scar and EC. No complications occurred, and all patients' final outcomes were satisfactory during the mean follow-up period of 14.8 months.We successfully managed the patients with ECs arising from scar tissues. We recommend that surgeons and patients first decide whether the ECs and scar tissue should be completely removed. Moreover, consideration should be given to the options chosen for the management of ECs. Finally, postoperative scar care is necessary to prevent hypertrophic and keloid scar recurrences.
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Cicatriz Hipertrófica/complicações , Cisto Epidérmico/etiologia , Queloide/complicações , Complicações Pós-Operatórias , Ferida Cirúrgica/complicações , Adulto , Cicatriz Hipertrófica/cirurgia , Cisto Epidérmico/cirurgia , Feminino , Humanos , Queloide/cirurgia , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated-, systemic disease that is characterized by IgG4 plasma cell infiltration with fibrotic changes in various organs. The most affected organs are pancreas and salivary glands. Kidney can be rarely involved, and is usually represented as a renal mass and organomegaly. Usually, elevated levels of serum IgG4 more than 135 mg/dl with organ-specific features and biopsy results showing enriched infiltration of IgG4-positive plasma cells are needed to diagnose the disease. However, we experienced two unusual cases of IgG4-RD involving kidney. IgG4-related kidney disease (IgG4-RKD) was first reported as an extra pancreatic feature of autoimmune pancreatitis(AIP) in 2004. Herein, we describe two cases of such unique presentation of IgG4RKD and a literature review focusing on clinicopathologic features of IgG4RKD. Our cases are distinct in the fact that IgG4RD invades unusual organs such as perinephric capsule or scrotum. We reported the patient who showed extinct perirenal capsule invasion with multi-organ involvement including exocrine glands in comparison to previous IgG4RKD that often involved in renal parenchyma and renal pelvis lesions. And the other patient had scrotal invasion with multifocal renal parenchymes. Referring to the features observed in these two cases, we could propose that as every organ can be related to IgG4RD, we propose clinicians to confirm the disease using imaging, serologic, and pathologic studies. We also reviewed previous reports of IgG4-RKD and summarized diverse imaging findings and pathologic features.
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Doenças Autoimunes/complicações , Imunoglobulina G/imunologia , Nefropatias/imunologia , Doenças Autoimunes/imunologia , Humanos , Imunoglobulina G/sangue , Nefropatias/patologia , Masculino , Pâncreas , PancreatiteRESUMO
OBJECTIVE: To determine the functional relevance of diffusion tensor imaging (DTI) metrics and conventional MRI (signal intensity change in T2, compression ratio) by measuring the correlation of these parameters with clinical outcome measured by the modified Japanese Orthopedic Association (mJOA) score. MATERIALS AND METHODS: A total of 20 cervical myelopathy (CM) patients participated in this prospective cohort study. The severities of CM were assessed using the mJOA score. Conventional MRIs (T2-weighted images) measuring the signal changes of spinal cords and the degree of compression at the lesion level and DTI metrics [fractional anisotropy (FA), apparent diffusion coefficient (ADC)] at each lesion and below each lesion (C7/T1) level were acquired using a 3-T Achieva MRI. These parameters were correlated with the mJOA scores to determine the functional relevance. RESULTS: Ninety percent of CM patients showed signal changes and 30 % of patients noted a more than 40% canal compression ratio in conventional MRIs at the lesion level; however, these findings were not correlated with the mJOA score (p < 0.05). In contrast, FA values on DTI showed high sensitivity to CM (100%), which was well correlated with the mJOA score (p = 0.034, r = 0.475) below the lesion level (C7/T1). CONCLUSIONS: This study showed a meaningful symptomatic correlation between mJOA scores and FA values below the lesion levels in CM patients. It could give us more understanding of the pathological changes in spinal cords matched with various clinical findings in CM patients than the results from conventional MRI.
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Vértebras Cervicais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Compressão da Medula Espinal/diagnóstico por imagem , Estenose Espinal/diagnóstico por imagem , Anisotropia , Vértebras Cervicais/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Compressão da Medula Espinal/patologia , Estenose Espinal/patologiaRESUMO
Autogenous microfat grafting is widely used to augment depressed deformities or for other cosmetic purposes. Since the microfat survival rate is unpredictable due to absorption and calcification, previously cryopreserved fat is widely used for secondary procedures. Sphingosylphosphorylcholine (SPC) is a lysophospholipid, which has a role in several cellular responses, and is known to stimulate DNA synthesis and proliferation. Since endothelial progenitor cells (EPCs) are known to enhance the survival rate of transplanted fat tissue, the present study assessed the effects of SPC on EPCs, in order to verify its positive effects on proliferation. Cryopreserved human fat tissues mixed with various concentrations of SPC were grafted into the nude mouse model. After grafting, the viability of each SPC mixed group was determined and compared with that of the nonSPC group. SPC exhibited a positive effect on EPC proliferation and angiogenic potential over 3 days when used at specific concentrations. The fat grafts of the 3 µM SPCtreated group weighed significantly more and the volume was markedly increased, as compared with the control group. A reverse transcriptionquantitative polymerase chain reaction was conducted on the total RNA extracted from SPCtreated fat tissues, which detected increased mRNA expression levels of matrix metallopeptidase9 and tumor necrosis factorα compared with in the control group. These results indicate that specific concentrations of SPC may exert favorable effects on grafted cryopreserved human fat tissue, which may be due to the increased mRNA expression levels of genes associated with angiogenesis.
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Tecido Adiposo/transplante , Indutores da Angiogênese/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/efeitos dos fármacos , Animais , Proliferação de Células , Criopreservação , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilcolina/farmacologia , Esfingosina/farmacologiaRESUMO
Human mesenchymal stem cells (MSCs) are a promising tool for therapeutic applications in cell-based therapy and regenerative medicine, and MSCs from the human palatine tonsils have recently been used as a new tissue source. However, the understanding of the proliferation and differentiation capacity of tonsil-derived MSCs (T-MSCs) is limited. In this study, we compared the proliferative potential of T-MSCs with those of bone marrow MSCs (BM-MSCs) and adipose tissue-derived MSCs (A-MSCs). Additionally, we investigated the underlying mechanism of T-MSC function. We showed that T-MSCs proliferated faster than A-MSCs and BM-MSCs in methylthiazolyl diphenyl-tetrazolium (MTT) assays, cell count assays, and cell cycle distribution analyses. DNA microarray and real-time PCR analyses revealed that the expression of fibroblast growth factor-5 (FGF5) was significantly elevated in T-MSCs compared with those in A-MSCs and BM-MSCs. Cell growth curves showed a difference in cell growth between untreated cells and siFGF5-treated T-MSCs. The administration of recombinant human FGF5 (rhFGF5) to the cells transfected with siFGF5 led to a significant increase in the proliferation rates. The administration of rhFGF5 to T-MSCs led to an increase in the levels of phosphorylated ERK1/2. However, treatment with siFGF5 resulted in an overall decrease in the level of phosphorylated ERK1/2. The osteogenic differentiation of T-MSCs was reduced following siFGF5 transfection, and it recovered to near-normal levels when rhFGF5 was added. These findings indicate that T-MSCs show significantly higher proliferative potential compared with those of BM-MSCs and A-MSCs. FGF5 facilitates cell proliferation through ERK1/2 activation, and it influences the osteogenic differentiation of T-MSCs.
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Fator 5 de Crescimento de Fibroblastos/metabolismo , Células-Tronco Mesenquimais/citologia , Tonsila Palatina/citologia , Tecido Adiposo/citologia , Adulto , Células da Medula Óssea/citologia , Diferenciação Celular/genética , Proliferação de Células/genética , Criança , Pré-Escolar , Fator 5 de Crescimento de Fibroblastos/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Osteogênese/genética , Adulto JovemRESUMO
BACKGROUND/AIMS: Although tonsil-mesenchymal stem cells (T-MSCs) have been studied as a new autologous or homologous source of MSCs, research on specific markers of MSCs and localization for purified T-MSC isolation has not yet been reported. This study investigates the expression of W5C5 (SUSD2) in tonsil stromal cells and the colony-forming ability and differentiation potential of W5C5+ cells to determine the usefulness of W5C5+ MSCs as a marker that can be used for the purification of T-MSCs. In addition, the location of W5C5+ cells expressed in the tonsil tissues is examined. METHODS: T-MSCs were isolated from the tonsillar tissues of 12 patients undergoing tonsillectomy. The colony-forming ability, surface markers, proliferation potential, and differentiation capacities of purified W5C5+ MSCs, W5C5- MSCs, and unselected T-MSCs were evaluated. The location of the W5C5+ cells in the tonsillar tissues was also investigated by immunohistochemistry. RESULTS: W5C5 was expressed in 2.5±0.4% of fresh human tonsil stromal cells. W5C5+ cells formed many colonies, but W5C5- cells did not form any colonies. The colony-forming number of W5C5+ cells (74.4 ± 9.8) was significantly higher than that of unselected tonsil stromal cells (23.6 ± 3.7). However, the differences in proliferation potential, surface marker expression, and differentiation potential between W5C5+ T-MSCs and unselected T-MSCs were not significant. W5C5+ cells were identified in the perivascular area around the blood vessels. CONCLUSION: W5C5+ T-MSCs possessed typical MSC properties with high colony-forming efficiency, and niches of W5C5+ T-MSCs were located in the perivascular area of tonsil tissues. These findings suggest that W5C5 is a useful single marker for the isolation of purified T-MSCs.
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Células-Tronco Mesenquimais/citologia , Tonsila Palatina/citologia , Adolescente , Antígenos CD/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
OBJECTIVES: Human mesenchymal stem cells (MSCs) are efficacious in various cellular therapeutic applications and have been isolated from several tissues. Recent studies have reported that human tonsil tissue contains a new source of progenitor cells, potentially applicable for cell-based therapies. Information about the effects of donor age, long-term passage and cryopreservation are essential for clinical applications and cell-based therapies. Therefore, the authors investigated how the morphology, cell-surface markers, proliferation potential and differentiation capacity of tonsil-derived MSCs (T-MSCs) were affected by donor age, long-term passage, and cryopreservation. MATERIALS AND METHODS: T-MSCs were isolated from tonsillar tissue of 20 patients undergoing tonsillectomy. Authors evaluated the effects of donor-age, long-term passage, and cryopreservation on the morphology, surface markers, proliferation potential and differentiation capacities of T-MSCs. RESULTS: T-MSCs exhibited a fibroblast-like, spindle-shaped appearance. There were no significant morphological differences according to donor age, long-term passage or cryopreservation. T-MSCs isolated from donors of various ages were positive for markers CD90, CD44, and CD73, but negative for CD45, CD31, and HLA-DR. There were no significant differences in the expression of positive and negative surface markers as a function of donor age, long-term passage and cryopreservation. T-MSCs from different donor age groups showed similar proliferation potentials after passage 2. After long-term passage and cryopreservation, there were no significant morphological differences. Cryopreservation did not affect the proliferation potential of T-MSCs, but there was a significant decrease in the proliferation potential in long-term passage T-MSCs (passage 15). The effect of donor age, long-term passage and cryopreservation on the in vitro adipogenic, osteogenic, and chondrogenic differentiation potential of T-MSCs was not significant. CONCLUSION: The effect of donor age, long-term passage culture, and cryopreservation on T-MSC properties are negligible, except for the proliferation capacity of long-term cultured T-MSCs. Therefore, T-MSCs are considered to be promising MSCs that can be used as future alternative sources for autologous or allogenic MSCs.
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Técnicas de Cultura de Células/métodos , Criopreservação/métodos , Células-Tronco Mesenquimais/fisiologia , Tonsila Palatina/citologia , Doadores de Tecidos , Fatores Etários , Biomarcadores/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Criança , Humanos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Tonsila Palatina/cirurgia , Fatores de TempoRESUMO
BACKGROUND: The use of cryopreserved adipose tissue for soft tissue augmentation is common, but unpredictability of fat graft viability remains a limitation. Adipose-derived stem cell (ADSC) and stromal vascular fraction (SVF) have been introduced to enhance viability and improve the survival of transplanted fat tissue. OBJECTIVE: To investigate whether supplementation with ADSC or SVF improved the survival of cryopreserved fat grafts. METHODS: The cryopreserved fat grafts were treated with ADSC, SVF, or normal saline in 30 six-week-old male nude mice to test whether ADSC and SVF could improve the survival of the transplanted fat tissue. The authors examined the weight, volume, and histological features of each group (n = 10) at 8 weeks after transplantation to evaluate the survival of the fat tissue. RESULTS: There was no difference between the control and SVF groups with respect to weight, volume, and histological findings. However, the ADSC group showed a significant increase in weight and volume compared with the control and SVF groups. Histological examination showed that the ADSC supplementation improved the quality of the transplanted fat grafts. CONCLUSION: Taken together, these results suggest a potential clinical utility of ADSC but no advantage of SVF in facilitating cryopreserved fat transfer.
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Adipócitos/transplante , Criopreservação , Sobrevivência de Enxerto , Células-Tronco , Células Estromais/transplante , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos NusRESUMO
BACKGROUND: Vitamin D receptor (VDR) has been suggested to play a role in the pathogenesis of type 1 diabetes mellitus (T1DM). There has been no case-control study examining the association between VDR polymorphisms and T1DM among Korean subjects with a low incidence of T1DM. METHODS: Eighty-one T1DM patients and 113 unrelated healthy controls with no history of DM or other autoimmune diseases were investigated at either Pusan National University Children's Hospital or Korea University Anam Hospital between March 2009 and September 2013. Polymerase chain reaction-restriction fragment length polymorphism was utilized to genotype single nucleotide substitutions at TaqI, BsmI, and ApaI alleles. RESULTS: All frequencies in T1DM and control subjects were in Hardy-Weinberg equilibrium, although ApaI in controls and TaqI in T1DM showed relatively weak equilibrium. TaqI and BsmI differences were significant (P = 0.045 and P = 0.012, respectively) after applying Bonferroni correction. The TT genotype carrier frequency among controls was higher than among the T1DM patients (P = 0.015; OR, 2.98; 95%CI: 1.19-7.42). T allele frequency was higher among controls than T1DM patients (P = 0.019; OR, 2.78; 95%CI: 1.15-6.72). The frequency of bb genotype carriers among controls was higher than among T1DM patients (P = 0.004; OR, 4.13; 95%CI: 1.4-12.10). The frequency of the b allele among controls was higher than that among T1DM patients (P = 0.016; OR, 3.20; 95%CI: 1.19-8.60). CONCLUSIONS: T and b TaqI and BsmI alleles are protective against T1DM in Korean subjects.
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DNA/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Polimorfismo Genético , Receptores de Calcitriol/genética , Alelos , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Frequência do Gene , Genótipo , Heterozigoto , Humanos , Incidência , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/metabolismo , República da Coreia/epidemiologiaRESUMO
Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A were identified as the causes of KS in 55.8-80.0% of patients. To elucidate further the molecular characteristics of Korean patients with KS, we screened a cohort of patients with clinically defined KS for mutations in KMT2D and KDM6A. Whole-exome sequencing and direct sequencing for validation were performed in 12 patients with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11 (91.7%) patients. No recurrent mutation was observed, and 10 out of the 11 mutations found were novel. KMT2D mutations were detected in 10 patients, including four small deletions or insertions and four nonsense and two missense mutations. One girl had a novel splice-site mutation in KDM6A. Each patient had a unique individual mutation. This is the first report of mutational analysis via exome sequencing in Korean patients with KS. Because the mutation-detection rate was high in this study, rigorous mutation analysis of KMT2D and KDM6A may be an important tool for the early diagnosis and genetic counseling of Korean patients with KS.
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Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Exoma , Face/anormalidades , Doenças Hematológicas/genética , Histona Desmetilases/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Doenças Vestibulares/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Masculino , Mutação , República da CoreiaRESUMO
OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Adulto , Idoso , Anticorpos Monoclonais Murinos/análise , Calbindina 2 , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Infusões Parenterais , Masculino , Mesotelioma/química , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Imagem Multimodal , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Pemetrexede , Neoplasias Peritoneais/química , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Fatores de Risco , Proteína G de Ligação ao Cálcio S100/análise , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Narrow band imaging (NBI) is an optical endoscopic technique for predicting polyp histology during colonoscopy. However, it has not been elucidated the impact of polyp characteristics on the diagnostic capabilities of NBI. We aimed to evaluate which polyp characteristics can influence the diagnostic accuracy of NBI for discriminating neoplastic from non-neoplastic colorectal polyps. METHODOLOGY: A total of 232 colorectal polyps from 134 patients undergoing screening or surveillance colonoscopy were retrospectively analyzed. White light imaging (WLI) and NBI images of polyps were assessed by two experienced endoscopists and two trainees and then compared with histopathology. RESULTS: When classified according to polyp morphology, NBI as well as WLI had a significantly lower sensitivity and diagnostic accuracy for non-polypoid lesions than for polypoid lesions in both experienced and trainee groups. In contrast, the specificity of NBI and WLI for non-polypoid lesions was higher than that for polpyoid lesions. As for polyp size, the diagnostic accuracy of NBI for polyps ≤5mm was significantly lower than for polyps of 6 to 9mm or ≤10mm in the experienced group. CONCLUSIONS: NBI had a significantly lower diagnostic accuracy for predicting polyp histology in non-polypoid or diminutive colorectal lesions.