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1.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151170

RESUMO

Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.


Assuntos
Técnicas de Cultura de Células , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Compostos Organosselênicos , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Imunofluorescência , Humanos , Compostos Organosselênicos/química , Polímeros , Esferoides Celulares
2.
Int J Mol Sci ; 19(9)2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-30149618

RESUMO

Several efforts have been made on the development of bioscaffolds including the polydimethylsiloxane (PDMS) elastomer for supporting cell growth into stable sheets. However, PDMS has several disadvantages, such as intrinsic surface hydrophobicity and mechanical strength. Herein, we generated a novel PDMS-based biomimetic membrane by sequential modifications of the PMDS elastomer with graphene oxide (GO) and addition of a hexagonal micropillar structure at the bottom of the biomembrane. GO was initially homogenously mixed with pure PDMS and then was further coated onto the upper surface of the resultant PDMS. The elastic modulus and hydrophilicity were significantly improved by such modifications. In addition, the development of hexagonal micropillars with smaller diameters largely improved the ion permeability and increased the motion resistance. We further cultured retinal pigment epithelial (RPE) cells on the surface of this modified PDMS biomembrane and assayed its biocompatibility. Remarkably, the GO incorporation and coating exhibited beneficial effect on the cell growth and the new formation of tight junctions in RPE cells. Taken together, this GO-modified PDMS scaffold with polyhexagonal micropillars may be utilized as an ideal cell sheet and adaptor for cell cultivation and can be used in vivo for the transplantation of cells such as RPE cells.


Assuntos
Dimetilpolisiloxanos/química , Grafite/química , Óxidos/química , Polímeros/química , Materiais Biomiméticos/química , Biomimética , Teste de Materiais , Espectroscopia de Infravermelho com Transformada de Fourier , Alicerces Teciduais
3.
Ann Biomed Eng ; 51(3): 517-526, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36036857

RESUMO

This study proposes a new diagnostic tool for automatically extracting discriminative features and detecting temporomandibular joint disc displacement (TMJDD) accurately with artificial intelligence. We analyzed the structural magnetic resonance imaging (MRI) images of 52 patients with TMJDD and 32 healthy controls. The data were split into training and test sets, and only the training sets were used for model construction. U-net was trained with 100 sagittal MRI images of the TMJ to detect the joint cavity between the temporal bone and the mandibular condyle, which was used as the region of interest, and classify the images into binary categories using four convolutional neural networks: InceptionResNetV2, InceptionV3, DenseNet169, and VGG16. The best models were InceptionV3 and DenseNet169; the results of InceptionV3 for recall, precision, accuracy, and F1 score were 1, 0.81, 0.85, and 0.9, respectively, and the corresponding results of DenseNet169 were 0.92, 0.86, 0.85, and 0.89, respectively. Automated detection of TMJDD from sagittal MRI images is a promising technique that involves using deep learning neural networks. It can be used to support clinicians in diagnosing patients as having TMJDD.


Assuntos
Inteligência Artificial , Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/patologia , Côndilo Mandibular/patologia , Imageamento por Ressonância Magnética/métodos
4.
Int J Mol Sci ; 13(3): 3277-3290, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489152

RESUMO

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC(50) in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Bucais/tratamento farmacológico , Compostos de Mostarda Nitrogenada/farmacologia , Animais , Antineoplásicos Alquilantes/administração & dosagem , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem , Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Compostos de Mostarda Nitrogenada/administração & dosagem , Fosforilação , Proteínas Quinases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Front Nutr ; 9: 814315, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495912

RESUMO

With increased age, the appetite, chewing, swallowing, and digestive ability gradually decrease. Previous studies have shown that poor oral health is associated with an inadequate intake of macro and micronutrients and malnutrition. Therefore, improving the diet of elderly people and promoting nutrient absorption will help to improve the quality of life for elderly people. However, few studies have predicted their oral ability based on different food textures and other factors. The purpose of this study was to explore the correlation between oral assessment and texture parameters of high-protein black soybean koji products in elderly people in a nursing home. We used cross-sectional study design for seventy-nine residents aged 65 years and older were recruited. Three different texture of cookies, including normal cookie hardness (1.4 × 105 N/m2), minced cookie hardness (4.4 × 104 N/m2), and pureed cookie hardness (1.4 × 104 N/m2) were provided to participants to test the oral status. An oral assessment scale was used by a dentist to evaluate the oral status of the elderly participants. Different cookie textures showed a significant positive correlation with pronunciation (r = 0.237, p < 0.05), face (r = 0.371, p < 0.01), tongue (r = 0.362, p < 0.01), pharynx (r = 0.256, p < 0.05), swallowing (r = 0.272, p < 0.05), breathing (r = 0.315, p < 0.01), and the total oral score (r = 0.339, p < 0.01). We also used the high-protein black soybean koji products combined with elderly people's comprehensions in a predictive model that had a moderately high correlation to predict the oral status in the elderly group (r = 0.612). We concluded that the high-protein black soybean koji product was associated with the oral ability of elderly people in a nursing home in Taiwan. Our findings indicated that elderly people could immediately understand the correct food texture.

6.
Exp Gerontol ; 115: 1-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415067

RESUMO

Swallowing is a complex movement consisting of the sequential and orderly activation of the swallowing muscles. Neuroimaging evidence has revealed a complex cortical and subcortical representation of voluntary swallowing. The repetitive saliva swallowing test (RSST) is a convenient and simple method for assessing swallowing performance in older people. It remains unclear whether individual differences in swallowing performance are associated with variations in structural brain signatures. We aimed to investigate the association between swallowing efficiency (SWE, measured by the RSST) and gray matter volume (GMV) in healthy older adults. Forty healthy older adults (52-82 years old, 28 female) underwent T1-weighted magnetic resonance imaging (MRI) and clinical assessments of SWE, stimulated/unstimulated salivary flow rate, masticatory cycle, and walking speed. GMV was quantified using a voxel-based morphometry (VBM) approach based on the MRI data. SWE was significantly negatively correlated with age. The association between SWE and hand grip strength, but not the other clinical metrics, was statistically significant. The GMV of the left posterior cerebellum (from cerebellum crus to lobule VIII) was significantly positively correlated with SWE, as evidenced by the results of whole-brain and cerebellum-specific VBM analyses. SWE was significantly positively correlated with the cerebellar volume in the region-of-interest analyses based on automated segmentation. In healthy older adults, swallowing efficiency was positively correlated with cerebellar GMV. The findings suggested that in older people, structural variations of the brain may play a key role in individual differences in swallowing performance.


Assuntos
Envelhecimento/patologia , Cerebelo/patologia , Deglutição , Substância Cinzenta/patologia , Força da Mão , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Feminino , Avaliação Geriátrica , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Saliva
7.
Cell Transplant ; 28(11): 1345-1357, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31313605

RESUMO

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.


Assuntos
Canais de Cálcio/metabolismo , Curcumina/farmacologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Distrofia Macular Viteliforme/metabolismo , Bestrofinas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/enzimologia , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Fagocitose/efeitos dos fármacos , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
8.
Sci Rep ; 8(1): 114, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29311578

RESUMO

Periodontal disease may cause considerable destruction of alveolar bone, periodontal ligaments (PDLs) and cementum and even lead to progressive oral dysfunction. Periodontal tissue regeneration is the ultimate goal of periodontal disease treatment to reconstruct both structures and functions. However, the regenerative efficiency is low, possibly due to the lack of a proper periodontal microenvironment. In this study, we applied an injectable and thermosensitive chitosan/gelatin/glycerol phosphate hydrogel to provide a 3D environment for transplanted stem cells and to enhance stem cell delivery and engraftment. The iPSCs-BMP-6-hydrogel complex promoted osteogenesis and the differentiation of new connective tissue and PDL formation. In animal models of maxillary-molar defects, the iPSCs-BMP-6-hydrogel-treated group showed significant mineralization with increased bone volume, trabecular number and trabecular thickness. Synergistic effects of iPSCs and BMP-6 increased both bone and cementum formation. IPSCs-BMP-6-hydrogel-treated animals showed new bone synthesis (increased ALP- and TRAP-positive cells), new PDL regeneration (shown through Masson's trichrome staining and a qualification assay), and reduced levels of inflammatory cytokines. These findings suggest that hydrogel-encapsulated iPSCs combined with BMP-6 provide a new strategy to enhance periodontal regeneration. This combination not only promoted stem cell-derived graft engraftment but also minimized the progress of inflammation, which resulted in highly possible periodontal regeneration.


Assuntos
Proteína Morfogenética Óssea 6/administração & dosagem , Regeneração Óssea , Calcificação Fisiológica , Células-Tronco Pluripotentes Induzidas/metabolismo , Dente Molar/fisiologia , Animais , Biomarcadores , Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular , Cemento Dentário , Expressão Gênica , Hidrogéis , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Modelos Animais , Osteogênese , Doenças Periodontais/diagnóstico , Doenças Periodontais/etiologia , Doenças Periodontais/metabolismo , Doenças Periodontais/terapia , Ligamento Periodontal , Ratos , Microtomografia por Raio-X
9.
J Chin Med Assoc ; 80(9): 569-574, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28687157

RESUMO

BACKGROUND: To evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution. METHODS: We retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence. RESULTS: The median follow-up duration was 47 months (range, 2-131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control. CONCLUSION: Local in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Gengivais/radioterapia , Mucosa Bucal/patologia , Neoplasias Bucais/radioterapia , Recidiva Local de Neoplasia/etiologia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Feminino , Seguimentos , Neoplasias Gengivais/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Estudos Retrospectivos
11.
Acta Biomater ; 13: 228-44, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25463491

RESUMO

MicroRNA122 (miR122), a liver-specific microRNA, plays critical roles in homeostatic regulation and hepatic-specific differentiation. Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but it remains unknown whether non-viral vector-mediated miR122 delivery can enhance the differentiation of iPSCs into hepatocyte-like cells (iPSC-Heps) and rescue thioacetamide-induced acute hepatic failure (AHF) in vivo. In this study, we demonstrated that embedment of miR122 complexed with polyurethane-graft-short-branch polyethylenimine copolymer (PU-PEI) in nanostructured amphiphatic carboxymethyl-hexanoyl chitosan (CHC) led to dramatically enhanced miR122 delivery into human dental pulp-derived iPSCs (DP-iPSCs) and facilitated these DP-iPSCs to differentiate into iPSC-Heps (miR122-iPSC-Heps) with mature hepatocyte functions. Microarray and bioinformatics analysis further indicated that CHC/PU-PEI-miR122 promoted the gene-signature pattern of DP-iPSCs to shift into a liver-specific pattern. Furthermore, intrahepatic delivery of miR122-iPSC-Heps, but not miR-Scr-iPSC-Heps, improved liver functions and rescued recipient survival, and CHC-mediated delivery showed a better efficacy than that using phosphate buffered saline as a delivery vehicle. In addition, these transplanted miR122-iPSC-Heps remained viable and could produce circulatory albumin for 4 months. Taken together, our findings demonstrate that non-viral delivery of miR122 shortens the time of iPSC differentiation into hepatocytes and the delivery of miR122-iPSC-Heps using CHC as a vehicle exhibited promising hepatoprotective efficacy in vivo. miR122-iPSC-Heps may represent a feasible cell source and provide an efficient and alternative strategy for hepatic regeneration in AHF.


Assuntos
Diferenciação Celular , Quitosana/análogos & derivados , Técnicas de Transferência de Genes , Hepatócitos , Células-Tronco Pluripotentes Induzidas/metabolismo , Falência Hepática/terapia , MicroRNAs , Poliuretanos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Quitosana/farmacologia , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/transplante , Xenoenxertos , Humanos , Falência Hepática/genética , Falência Hepática/metabolismo , Falência Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/biossíntese , MicroRNAs/genética
12.
Cell Transplant ; 24(8): 1431-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24898358

RESUMO

Anaplastic astrocytoma (AA) is a grade III glioma that often occurs in middle-aged patients and presents a uniformly poor prognosis. A small subpopulation of cancer stem cells (CSCs) possessing a self-renewing capacity is reported to be responsible for tumor recurrence and therapeutic resistance. An accumulating amount of microRNAs (miRNA) were found aberrantly expressed in human cancers and regulate CSCs. Efforts have been made to couple miRNAs with nonviral gene delivery approaches to target specific genes in cancer cells. However, the efficiency of delivery of miRNAs to AA-derived CSCs is still an applicability hurdle. The present study aimed to investigate the effectiveness and applicability of nonviral vector-mediated delivery of Let-7a with regard to eradication of AA and AA-derived CSC cells. Herein, our miRNA/mRNA microarray and RT-PCR analysis showed that the expression of Let-7a, a tumor-suppressive miRNA, is inversely correlated with the levels of HMGA2 and Sox2 in the AA side population (SP(+)) cells. Luciferase reporter assay showed that Let-7a directly targets the 3'-UTRs of HMGA2 in AA-SP(+) cells. Knockdown of HMGA2 significantly suppressed the protein expression of Sox2 in AA-SP(+) cells, whereas overexpression of HMGA2 upregulated Sox2 expression in AA-SP(-). Nuclear localization signal (NLS) peptides can facilitate nuclear targeting of DNA and are used to improve gene delivery. Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic delivery vehicle, we conjugated NLS with Let-7 and successfully delivered it to AA-SP(+) cells, resulting in significantly suppressed expression of HMGA2 and Sox2, tumorigenicity, and CSC-like abilities. This treatment facilitated the differentiation of AA-SP(+) cells into non-SP CSCs. Furthermore, PU-PEI-mediated delivery of NLS-conjugated Let-7a in AA-SP(+) cells suppressed the expression of drug-resistant and antiapoptotic genes, and increased cell sensitivity to radiation. Finally, the in vivo delivery of PU-PEI-NLS-Let-7a significantly suppressed the tumorigenesis of AA-SP(+) cells and synergistically improved the survival rate of orthotopically AA-SP(+)-transplanted immunocompromised mice when combined with radiotherapy. Therefore, PU-PEI-NLS-Let-7a is a potential novel therapeutic approach for AA.


Assuntos
Proteína HMGA2/metabolismo , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Sinais de Localização Nuclear/química , Polietilenoimina/química , Poliuretanos/química , Adulto , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Astrocitoma/tratamento farmacológico , Astrocitoma/metabolismo , Astrocitoma/patologia , Sequência de Bases , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cisplatino/uso terapêutico , Cisplatino/toxicidade , Feminino , Proteína HMGA2/antagonistas & inibidores , Proteína HMGA2/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/química , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/transplante , Radiação Ionizante , Alinhamento de Sequência , Células da Side Population/citologia , Células da Side Population/metabolismo , Células da Side Population/transplante , Células Tumorais Cultivadas
13.
J Chin Med Assoc ; 77(12): 618-25, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25441769

RESUMO

BACKGROUND: A recent research breakthrough has demonstrated that the ectopic expression of four genes is sufficient to reprogram human fibroblasts into inducible pluripotent stem cells (iPSCs). However, whether human dental pulp cells (DPCs) could be reprogrammed into iPSCs remains an open question. In this study, we demonstrated that DPCs from deciduous and permanent teeth can be reprogrammed into iPSCs without c-Myc and had the capacity to differentiate into neuron-like cells. METHODS: DPCs were obtained from donors and reprogrammed into iPSCs using retroviral transduction with SOX2, OCT4, and KLF4. Then, these iPSCs were differentiated into neuron-like cells. Microarray and bioinformatics were used to compare the gene expression profile among these iPSCs and iPSC-derived neuron-like cells. RESULTS: The DPCs displayed a high vitality and capability to quickly restart proliferation and expressed elevated pluripotency similar to mesenchymal stem cells. According to our results, DPC-derived iPSC colonies that could be subcultured and propagated were established as early as 10 days after transduction, in comparison with the skin fibroblast (DPC-derived iPSCs) without c-Myc presented embryonic stem cell-like properties and the pluripotent potential to differentiate into neuron-like cells, which resemble neurons both morphologically and functionally. CONCLUSION: The human DPCs from deciduous and permanent teeth can undergo reprogramming to establish pluripotent stem cell lines without c-Myc. These surgical residues, usually regarded as medical waste, can be used as an alternative source of pluripotent stem cells for personalized medicine.


Assuntos
Polpa Dentária/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Neurônios/citologia , Proteínas Proto-Oncogênicas c-myc/fisiologia , Adulto , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Criança , Humanos , Fator 4 Semelhante a Kruppel
14.
Curr Gene Ther ; 12(4): 275-84, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22856602

RESUMO

RNA interference (RNAi) is a collection of small RNA-directed mechanisms that result in sequence-specific inhibition of gene expression. RNAi delivery has demonstrated promising efficacy in the treatment of genetic disorders in cancer. Although viral vectors are currently the most efficient systems for gene therapy, potent immunogenicity, mutagenesis, and the biohazards of viral vectors remain their major risks. Various non-viral delivery vectors have been developed to provide a safer approach for gene delivery, including polymers, peptides, liposomes, and nanoparticles. However, some concerns and challenges of these non-viral gene delivery approaches remain to be overcome. In this review, we summarize the recent progress in the development of non-viral systems delivering RNAi and the currently available preclinical and clinical data, and discuss the challenges and future directions in cancer therapy.


Assuntos
Técnicas de Transferência de Genes , Terapia Genética , Neoplasias , Interferência de RNA , RNA Interferente Pequeno , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos , Humanos , Lipossomos , Nanopartículas , Neoplasias/genética , Neoplasias/terapia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico
15.
Biomaterials ; 33(5): 1462-76, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22098779

RESUMO

Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis. CD133 has been considered a putative marker of cancer stem cells (CSCs) in malignant cancers, including GBMs. MicroRNAs (miRNAs), highly conserved small RNA molecules, may target oncogenes and have potential as a therapeutic strategy against cancer. However, the role of miRNAs in GBM-associated CSCs remains mostly unclear. In this study, our miRNA/mRNA-microarray and RT-PCR analysis showed that the expression of miR145 (a tumor-suppressive miRNA) is inversely correlated with the levels of Oct4 and Sox2 in GBM-CD133(+) cells and malignant glioma specimens. We demonstrated that miR145 negatively regulates GBM tumorigenesis by targeting Oct4 and Sox2 in GBM-CD133(+). Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic-delivery vehicle, PU-PEI-mediated miR145 delivery to GBM-CD133(+) significantly inhibited their tumorigenic and CSC-like abilities and facilitated their differentiation into CD133(-)-non-CSCs. Furthermore, PU-PEI-miR145-treated GBM-CD133(+) effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation and temozolomide. Finally, the in vivo delivery of PU-PEI-miR145 alone significantly suppressed tumorigenesis with stemness, and synergistically improved the survival rate when used in combination with radiotherapy and temozolomide in orthotopic GBM-CD133(+)-transplanted immunocompromised mice. Therefore, PU-PEI-miR145 is a novel therapeutic approach for malignant brain tumors.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Glioblastoma/genética , Glioblastoma/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Polietilenoimina/análogos & derivados , Poliuretanos/química , Tolerância a Radiação , Regiões 3' não Traduzidas/genética , Idoso , Sequência de Bases , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Transferência de Genes , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Dados de Sequência Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Polietilenoimina/síntese química , Polietilenoimina/química , Poliuretanos/síntese química , Tolerância a Radiação/efeitos dos fármacos , Fatores de Transcrição SOXB1/metabolismo , Temozolomida
16.
Artigo em Inglês | MEDLINE | ID: mdl-17507260

RESUMO

Radiation-induced sarcoma (RIS) or postirradiation sarcoma has been reported rarely as a long-term complication of radiation therapy (RT). We report 4 cases of oral sarcomas or sarcomatoid tumors with a rather short latency period after radiotherapy of the prior OSCC. Histopathological evaluation and immunohistochemical study were performed using a panel of markers including vimentin, cytokeratin, S-100, desmin, myoglobin, HHF-35, p53, and p16. All reported cases were positive for vimentin and negative for cytokeratin. Two cases were positive for myoglobin, desmin, or HHF-35, and were probably myogenic origin. One case was possibly a fibrosarcoma and the subclassification of the other one was not specified. Diverse expression of p53 and p16 was further observed in these 4 cases. Report of the complicated clinical processes and the analysis of genetic markers of these cases provide useful clinical and pathogenetic insights of mesenchymal malignancies associated with a status post OSCC radiation.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/radioterapia , Neoplasias Induzidas por Radiação/patologia , Sarcoma/patologia , Idoso , Carcinoma de Células Escamosas/patologia , Evolução Fatal , Feminino , Genes p16 , Genes p53 , Neoplasias Gengivais/patologia , Neoplasias Gengivais/radioterapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/complicações , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Induzidas por Radiação/terapia , Neoplasias Palatinas/patologia , Neoplasias Palatinas/radioterapia , Sarcoma/terapia , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapia
17.
J Oral Maxillofac Surg ; 61(7): 751-8, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12856245

RESUMO

PURPOSE: The study goal was to determine which clinical features correlated with 5-year survival in patients surgically treated for oral squamous cell carcinoma (OSCC) in Taiwan. PATIENTS AND METHODS: The records of 378 OSCC patients surgically treated with or without chemotherapy and radiotherapy were reviewed retrospectively. Their 5-year survival in relation to age, gender, tumor site, lymph node involvement, presence of distant metastasis, staging, differentiation, and risk factors, including betel quid (BQ) chewing, cigarette smoking, and alcohol consumption, was analyzed. RESULTS: The majority of the patients were men (male-to-female ratio, 5.87:1) with the mean age of 57.1 +/-11.7 years. Tumors occurred mainly at the buccal mucosa (BM) (100 of 378, 26.5%), gingiva (105 of 378, 27.8%), and tongue (103 of 378, 27.2%). Neck nodal metastasis occurred frequently at the floor of the mouth (in >60% of cases), followed by the gingiva (45.7%), buccal mucosa (34%), and tongue (20.4%), whereas early distant metastasis was rare (5.3%). There were 104 (27.5%) stage 1, 96 (25.4%) stage 2, 98 (25.9%) stage 3, and 80 (21.2%) stage 4 patients. OSCC at the BM and gingiva was most (and at the tongue least) associated with risk factors of BQ use and smoking. The 5-year survival was 75%, 65.6%, 49%, and 30% for patients with stage I, II, III, and IV, respectively. The size, nodal involvement, distant metastasis, staging, differentiation, and BQ use significantly affected the survival (P <.05, Kaplan-Meier analysis). BQ use also correlated most significantly with the younger age of occurrence of OSCC patients. CONCLUSIONS: Our data suggest that early treatment is the key to increasing the survival of OSCC patients. Periodic screening of high-risk populations for OSCC represents an urgent need in Taiwan.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Areca/efeitos adversos , Carcinoma de Células Escamosas/secundário , Quimioterapia Adjuvante , Feminino , Humanos , Modelos Lineares , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
18.
Zhonghua Yi Xue Za Zhi (Taipei) ; 65(11): 548-52, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12583520

RESUMO

We describe a case with severely compromised edentulous ridge in the mandible, which previously received marginal resection and radiotherapy due to oral cancer at the mouth floor. Through careful evaluation, the patient had 30 dives of hyperbaric oxygen therapy (HBO) before implant surgery. The edentulous ridge was rehabilitated with 4 endosteal implant fixtures, and palatal mucosa grafting vestibulosulcoplasty. The case had been followed for 4 years with stability of bone and a satisfactory result of rehabilitation.


Assuntos
Implantes Dentários , Arcada Edêntula/cirurgia , Mandíbula/efeitos da radiação , Mandíbula/cirurgia , Neoplasias Bucais/terapia , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Soalho Bucal/cirurgia
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