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1.
BMC Oral Health ; 24(1): 284, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418977

RESUMEN

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.


Asunto(s)
Anquilosis , Trastornos de la Articulación Temporomandibular , Articulación Temporomandibular , Animales , Ovinos/genética , Cóndilo Mandibular , Anquilosis/genética , Perfilación de la Expresión Génica , Hematoma
2.
Mol Ther ; 30(12): 3658-3676, 2022 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-35715953

RESUMEN

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.


Asunto(s)
Virus Oncolíticos , Humanos , Animales , Ratones , Virus Oncolíticos/genética , Linfocitos Infiltrantes de Tumor , Células Presentadoras de Antígenos
3.
Med Sci Monit ; 28: e934511, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35301274

RESUMEN

BACKGROUND The aims of the study were to comprehensively compare the morphology, immunophenotype, proliferation, migration, and regeneration potential of normal dental pulp stem cells (DPSCs) versus inflammatory dental pulp stem cells (iDPSCs). MATERIAL AND METHODS Healthy pulp or inflamed pulp tissue was used to isolate and culture DPSCs and iDPSCs, respectively. These cell populations were characterized by flow cytometry, colony formation assay, transwell assay, and multi-directional differentiation in vitro. RESULTS No difference was observed in the morphology, cell-surface markers, or cell migration between DPSCs and iDPSCs. DPSCs showed a higher colony-forming capacity, proliferative viability, and osteo/dentinogenesis ability compared with iDPSCs. However, iDPSCs demonstrated enhanced neurogenesis, angiogenesis, adipogenesis, and chondrogenesis capacities in comparison to DPSCs. CONCLUSIONS Our data revealed the differences of biological properties between DPSCs and iDPSCs. The highly angiogenic and neurogenic potential of iDPSCs indicate their possible use in the regeneration of the dentin-pulp complex and support the critical role of angiogenesis and neurogenesis in pulp regeneration.


Asunto(s)
Pulpa Dental/fisiología , Osteogénesis/fisiología , Células Madre/citología , Adulto , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Células Cultivadas , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Masculino , Estudios Retrospectivos , Adulto Joven
4.
Med Sci Monit ; 27: e932545, 2021 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-34400603

RESUMEN

BACKGROUND The type of traumatic temporomandibular joint (TMJ) ankylosis depends on the degree of severity of TMJ trauma. Here, we performed comprehensive differential molecular profiling between TMJ fibrous and bony ankylosis. MATERIAL AND METHODS Six sheep were used and a bilateral different degree of TMJ trauma was performed to induce fibrous ankylosis in one side and bony ankylosis in the other side. The ankylosed calluses were harvested at days 14 and 28 postoperatively and analyzed by Affymetrix OviGene-1_0-ST microarrays. DAVID was used to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Ten DEGs, including 7 hub genes from PPI analysis, were confirmed by real-time PCR. RESULTS We found 90 and 323 DEGs at least 2-fold at days 14 and 28, respectively. At day 14, bony ankylosis showed upregulated DEGs, such as TLR8, SYK, NFKBIA, PTPRC, CD86, ITGAM, and ITGAL, indicating a stronger immune and inflammatory response and cell adhesion, while genes associated with anti-adhesion (PRG4) and inhibition of osteoblast differentiation (SFRP1) had higher expression in fibrous ankylosis. At day 28, bony ankylosis showed increased biological process related to new bone formation, while fibrous ankylosis was characterized by a prolonged immune and inflammatory reaction. CONCLUSIONS This study provides a differential gene expression profile between TMJ fibrous and bony ankylosis. Further study of these key genes may provide new ideas for future treatment of TMJ bony ankylosis.


Asunto(s)
Anquilosis/genética , Fibrosis/genética , Trastornos de la Articulación Temporomandibular/genética , Traumatismos del Nervio Trigémino/genética , Animales , Anquilosis/patología , Modelos Animales de Enfermedad , Expresión Génica/genética , Fracturas Mandibulares/genética , Análisis por Micromatrices , Ovinos/genética , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/patología , Transcriptoma , Traumatismos del Nervio Trigémino/patología
5.
BMC Oral Health ; 21(1): 668, 2021 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-34961493

RESUMEN

BACKGROUND: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. MATERIAL/METHODS: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. RESULTS: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-ß), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. CONCLUSIONS: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.


Asunto(s)
Anquilosis , Hemartrosis , Animales , Anquilosis/genética , Cóndilo Mandibular , Análisis por Micromatrices , Osteogénesis , Ovinos , Articulación Temporomandibular
6.
J Oral Maxillofac Surg ; 76(9): 1951.e1-1951.e24, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29908889

RESUMEN

PURPOSE: The aim of this experimental study was to investigate the role of the fibrous layer of the condylar head in the formation of temporomandibular joint (TMJ) ankylosis in a sheep model of intracapsular condylar fracture. MATERIALS AND METHODS: Six growing Xiao-wei Han sheep were used in the study, and bilateral TMJ surgery was performed in each sheep. In the left TMJ, sagittal fracture of the condyle, removal of the fibrous layer of the condylar head, excision of two thirds of the disc, and removal of the fibrous zone of the glenoid fossa were performed. In the right TMJ, the same surgical management was performed, except that in each sheep, the fibrous layer of the condylar head was preserved. Three sheep were killed humanely at 1 month postoperatively, and the other 3 sheep were killed humanely at 3 months postoperatively. The TMJ complexes were examined by histologic evaluation. RESULTS: Fibrous ankylosis was observed on the left side in 3 sheep at 1 month postoperatively and in 2 of 3 sheep at 3 months postoperatively. Fibro-osseous ankylosis was achieved on the left side in 1 sheep at 3 months postoperatively. In the right TMJ, the main postoperative histologic findings included condylar fracture healing, topical rupture or exfoliation of the fibrous layer of the condyle, and fissure between the fibrous layer and the proliferative zone of the condyle. However, no evidence of ankylosis was observed. The TMJ ankylosis scores on the right side were significantly lower than those on the left side at different time points (P < .05). CONCLUSIONS: This study showed that the presence of the fibrous layer of the condylar head prevented the development of TMJ ankylosis in a sheep model of intracapsular condylar fracture.


Asunto(s)
Anquilosis/patología , Tejido Conectivo/patología , Cóndilo Mandibular/lesiones , Cóndilo Mandibular/patología , Fracturas Mandibulares/patología , Trastornos de la Articulación Temporomandibular/patología , Animales , Modelos Animales de Enfermedad , Ovinos , Tomografía Computarizada por Rayos X
7.
J Dent Sci ; 19(4): 2090-2099, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39347028

RESUMEN

Background/purpose: Dental pulp stem cells (DPSCs) have demonstrated significant potential for neuroregeneration. However, a full understanding of the specific mechanism underpinning the neural differentiation of DPSCs is still required. The Wnt signaling is crucial for the development of the embryonic neural system and the maintenance of adult neural homeostasis. This study aimed to investigate the role of the Wnt/Ca2+ pathway in the neural differentiation of human DPSCs (hDPSCs) and its modulation of the Wnt/ß-catenin pathway. Materials and methods: hDPSCs were cultured and divided into the control group and the neurogenic induction group (Neuro group). The mRNA and protein levels of neurogenic markers, Wnt/Ca2+, and Wnt/ß-catenin pathway indicators were determined using Quantitative real-time PCR and Western blotting. After inhibition of the Wnt/Ca2+ pathway using a WNT5A short hairpin RNA (shRNA) plasmid and subsequent neurogenic induction, neurogenic markers and Wnt/ß-catenin pathway indicators in the NC-sh-Neuro group and WNT5A-sh-Neuro group were determined using Quantitative real-time PCR and Western blotting. Results: Compared with the control group, the expression of the Wnt/Ca2+ pathway indicators (WNT5A, Frizzled 2, calmodulin-dependent protein kinase IIa, and nuclear factor of active T cells 1) decreased in the Neuro group. Conversely, the expression of WNT3A, total ß-catenin and active ß-catenin in the Wnt/ß-catenin pathway increased. Moreover, compared with the NC-sh-Neuro group, the WNT5A-sh-Neuro group exhibited a greater level of mature neural differentiation alongside elevated expression of the Wnt/ß-catenin pathway indicators. Conclusion: The Wnt/Ca2+ pathway inhibited neural differentiation of hDPSCs and has a negative effect on the Wnt/ß-catenin pathway in vitro.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38553306

RESUMEN

PURPOSE: To explore the role and mechanism of heat shock protein 27 (HSP27) in SACC VM formation. STUDY DESIGN: Immunohistochemistry and double staining with cluster of differentiation 31 (CD31) and periodic acid-Schiff (PAS) were used to detect HSP27 expression and VM in 70 SACC tissue samples separately. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and immunofluorescence were used to detect gene and protein expression. HSP27 in SACC cells were overexpression or downregulated by transfecting HSP27 or short hairpin RNA target HSP27 (sh-HSP27). The migration and invasion abilities of SACC cells were detected using wound healing and Transwell invasion assays. The VM formation ability of the cells in vitro was detected using a Matrigel 3-dimensional culture. RESULTS: HSP27 expression was positively correlated with VM formation and affected the prognosis of patients. In vitro, HSP27 upregulation engendered VM formation and the invasion and migration of SACC cells. Mechanistically, HSP27 upregulation increased Akt phosphorylation and subsequently increased downstream matrix metalloproteinase 2 and 9 expressions. CONCLUSION: HSP27 may plays an important role in VM formation in SACC via the AKT-MMP-2/9 signalling pathway.


Asunto(s)
Western Blotting , Carcinoma Adenoide Quístico , Proteínas de Choque Térmico HSP27 , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Neovascularización Patológica , Proteínas Proto-Oncogénicas c-akt , Neoplasias de las Glándulas Salivales , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/genética , Línea Celular Tumoral , Movimiento Celular , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP27/genética , Inmunohistoquímica , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/genética , Transducción de Señal
9.
Sci Rep ; 14(1): 12704, 2024 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830996

RESUMEN

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.


Asunto(s)
Anquilosis , Células Madre Mesenquimatosas , Osteogénesis , Trastornos de la Articulación Temporomandibular , Animales , Células Madre Mesenquimatosas/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/genética , Anquilosis/metabolismo , Anquilosis/patología , Anquilosis/genética , Proteínas Señalizadoras YAP/metabolismo , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Ovinos , Proliferación Celular , Modelos Animales de Enfermedad , Diferenciación Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Movimiento Celular , Factores de Transcripción/metabolismo , Factores de Transcripción/genética
10.
Heliyon ; 10(10): e31071, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38803891

RESUMEN

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38019760

RESUMEN

In the treatment process of cancers like oral cancer, it is necessary to employ extensive surgical resection to achieve cancer eradication. However, this often results in damage to crucial functions such as chewing and speaking, leading to a poorer prognosis and a reduced quality of life. To address this issue, a multifunctional theranostic agent named MBPN-T-BTD has been developed by precisely modulating the excitation state energy distribution in the radiative/nonradiative decay pathways using the characteristics of twisted intramolecular charge transfer and aggregation-induced emission. This agent outperforms clinically utilized indocyanine green (ICG) in various aspects, including the second near-infrared window (NIR-II, 1000-1700 nm) fluorescence (FL) and photothermal conversion efficiency (PCE). Its nanoparticle form (BTB NPs) can be effectively used for high-contrast delineation of lymph node mapping and tongue and floor of mouth cancers using NIR-II FL, enabling surgeons to achieve more precise and thorough tumor clearance. For tumors located in close proximity to vital organs such as the tongue, the exceptional PCE (71.96%) of BTB NPs allows for targeted photothermal ablation with minimal damage to peripheral healthy tissues. This contribution provides a safer and more effective paradigm for minimally invasive or noninvasive treatment of oral cancer, ensuring the preservation of normal organ functions and showing potential for improving the overall prognosis and quality of life for cancer patients.

12.
Front Plant Sci ; 14: 1093912, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36925752

RESUMEN

Multi-rotor unmanned aerial vehicle (UAV) is a new chemical application tool for tall stalk tropical crop Areca catechu, which could improve deposit performance, reduce operator healthy risk, and increase spraying efficiency. In this work, a spraying experiment was carried out in two A. catechu fields with two leaf area index (LAI) values, and different operational parameters were set. Spray deposit quality, spray drift, and ground loss were studied and evaluated. The results showed that the larger the LAI of A. catechu, the lesser the coverage of the chemical deposition. The maximum coverage could reach 4.28% and the minimum 0.33%. At a flight speed of 1.5 m/s, sprayed droplets had the best penetration and worst ground loss. The overall deposition effect was poor when the flight altitudes were greater than 11.09 m and the flight speed was over 2.5 m/s. Comparing flight speed of 2.5 to 1.5 m/s, the overall distance of 90% of the total drift increased to double under the same operating parameters. This study presents reference data for UAV chemical application in A. catechu protection.

13.
Oral Oncol ; 140: 106395, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37068412

RESUMEN

OBJECTIVE: To evaluate whether the pedicle submental island flap (SIF) can be safely used in the oral tongue squamous cell carcinoma (OTSCC) patients with pathologically node-positive (pN+) neck, especially pN+ at level I. METHODS: Retrospectively, 101 OTSCC patients with SIF reconstruction were enrolled. Oncological outcomes included the total locoregional recurrence, the SIF related locoregional recurrence (SRLR) which referred to the local recurrence at flap and ipsilateral neck recurrence at level I, recurrence free survival (RFS), overall survival (OS), and disease specific survival (DSS). RESULTS: Sixty-one patients were pathologically node-negative (pN0) and 40 were pN+. Thirteen patients experienced locoregional recurrence, of which 5 had a SRLR. The pN+ group had a significantly higher locoregional recurrence rate, lower 5-year RFS, OS and DSS than pN0 group (P < 0.05). Patients with pN0 had a significantly higher neck RFS when compared to those with pN+ either at level I (P = 0.005) or at other levels (P < 0.001). However, the neck RFS was similar between the two subgroups of pN+ (P = 0.550). Especially, patients with pN+ at level I had a significantly higher SRLR rate (P = 0.006) compared to those with pN0 at level I. Multivariate analysis showed that pN+ was an unfavorable factor for tumor recurrence and OS. CONCLUSION: Our data did not support the use of SIF in OTSCC patients with pN+ neck at level I due to an significantly increased SRLR rate compared to those with pN0 neck at level I.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Procedimientos de Cirugía Plástica , Neoplasias de la Lengua , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Estudios Retrospectivos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Neoplasias de la Lengua/cirugía , Neoplasias de la Lengua/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Colgajos Quirúrgicos/cirugía , Neoplasias de Cabeza y Cuello/cirugía
14.
Mol Ther Oncolytics ; 30: 275-285, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37701851

RESUMEN

Bispecific T cell engagers (BiTEs) represent a promising immunotherapy, but their efficacy against immunologically cold tumors such as pancreatic ductal adenocarcinoma remains unclear. Oncolytic viruses (OVs) can transform the immunosuppressive tumor microenvironment into the active state and also serve as transgene vectors to selectively express the desired genes in tumor cells. This study aimed to investigate whether the therapeutic benefits of tumor-targeting Claudin18.2 BiTE can be augmented by combining cancer selectively and immune-potentiating effects of OVs. Claudin18.2/CD3 BiTE was inserted into herpes simplex virus type 1 (HSV-1) to construct an OV-BiTE. Its expression and function were assessed using reporter cells and peripheral blood mononuclear cell (PBMC) co-culture assays. Intratumoral application of OV-BiTE restrained tumor growth and prolonged mouse survival compared with the unarmed OV in xenograft models and syngeneic mice bearing CLDN18.2-expressing KPC or Pan02 pancreatic cancer cells. Flow cytometry of tumor-infiltrating immune cells suggested both OV-BiTE and the unarmed OV remodeled the tumor microenvironment by increasing CD4+ T cell infiltration and decreasing regulatory T cells. OV-BiTE further reprogrammed macrophages to a more pro-inflammatory antitumor state, and OV-BiTE-induced macrophages exhibited greater cytotoxicity on the co-cultured tumor cell. This dual cytotoxic and immunomodulatory approach warrants further development for pancreatic cancer before clinical investigation.

15.
Biomater Adv ; 137: 212811, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35929250

RESUMEN

As the most prevalent malignant tumor of the oral and maxillofacial regions, squamous cell carcinoma (SCC) has relatively high recurrence and low survival rates. Currently, the most common treatment strategies are surgery and chemoradiotherapy. However, incomplete removal of the tumor can allow residual tumor cells to regrow and metastasis, resulting in treatment failure. Although postoperative adjuvant radiotherapy or chemotherapy can reduce recurrence, serious adverse reactions significantly compromise patients' quality of life. Large soft tissue defects after surgery are also difficult to heal. Therefore, therapies that eliminate residual tumor cells and promote tissue regeneration post-surgery are urgently needed. Indocyanine green (ICG) can convert absorbed light into heat to ablate tumor cells. Three-dimensional (3D) scaffolds are efficient drug carriers and support cell migration and proliferation. Here, we fabricated collagen/silk fibroin encapsulated ICG (I-CS) scaffolds by combining 3D printing with freeze-drying methods. The I-CS scaffolds delayed ICG decomposition and clearance, allowing the scaffolds to be used repeatedly for photothermal therapy (PTT). With the laser positioned at 4 cm from the 1.0 I-CS scaffold and irradiation for 10 min (1.0 W/cm2), temperatures above 50 °C were achieved, which effectively killed SCC-25 cells in vitro and suppressed tumor growth in vivo. Moreover, the I-CS scaffolds supported attachment and proliferation of rat buccal mucosa fibroblasts (RBMFs) and promoted the repair of buccal mucosal wounds in rats. These results suggested that I-CS scaffolds may be useful in preventing local recurrence and support regeneration of large soft tissue defects after oral SCC surgery.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Carcinoma de Células Escamosas/tratamiento farmacológico , Verde de Indocianina/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasia Residual , Calidad de Vida , Ratas , Carcinoma de Células Escamosas de Cabeza y Cuello , Andamios del Tejido , Cicatrización de Heridas
16.
Biomater Sci ; 10(8): 1929-1935, 2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35253811

RESUMEN

Fluorescence imaging has been widely used in the biomedical field owing to its merits of high sensitivity, excellent accuracy, high biosafety, etc. However, despite the good performance of fluorescent materials in the diagnosis of subcutaneous tumors or some orthotopic tumors in mice, their potential clinical application for most orthotopic tumors in humans is still limited due to their weak tissue penetration ability and the high thickness of human tissues. Given that the human tongue can extend out of the mouth and is approximately 1 cm thick, the diagnosis of tongue squamous cell carcinoma (TSCC) by fluorescence has great potential for clinical applications. However, to the best of our knowledge, a few studies have been performed to detect tongue tumors using fluorescence imaging, and most of them are administered in a subcutaneous tumor-bearing mouse model and are based on fluorescent materials with aggregation-caused quenching effects. Herein, by developing DPA-TPE-DCM with intense near-infrared fluorescence emission in the aggregation state, aggregation-induced emission materials were used for the first time in the early diagnosis of orthotopic TSCC and sentinel lymph node (SLN) mapping in an immunocompetent mouse model of orthotopic TSCC with a high signal-to-background ratio of 10.2. Moreover, with the guidance of the fluorescence of DPA-TPE-DCM NPs, SLNs smaller than 2 mm in diameter were successfully excised. This study provides new insight and a method for the early diagnosis of TSCC in clinical practice and provides more possibilities to broaden the potential clinical applications of fluorescent materials.


Asunto(s)
Carcinoma de Células Escamosas , Ganglio Linfático Centinela , Neoplasias de la Lengua , Animales , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Colorantes , Diagnóstico Precoz , Verde de Indocianina , Ratones , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela/métodos , Lengua/patología , Neoplasias de la Lengua/diagnóstico por imagen
17.
Oral Oncol ; 132: 105980, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35749804

RESUMEN

OBJECTIVES: The purpose of this retrospective study was to compare the differences in quality of life (QOL) outcomes between the conventional obturator prostheses (COP) and the pedicled submental artery island flap (SAIF) in the reconstruction of Brown IIb maxillary defects. MATERIALS AND METHODS: The QOL of 116 eligible patients who had a lapse ≥ 12 months after the cancer-related maxilla ablation was evaluated by the University of Washington quality of life scale (UW-QOL), Performance Status Scale for Head and Neck (PSS-HN), and Obturator Functioning Scale (OFS). RESULTS: Patients in the SAIF group reported statistically and clinically significant higher overall QOL scores but lower chewing scores in the UW-QOL scale when compared with those in the COP group (P < 0.05). Clinically significantly higher scores were also observed in the recreation and anxiety domains in the UW-QOL scale for the SAIF group, but there was no statistical significances. The COP group reported more complaints about the nasal leakage when swallowing and the shape of the upper lip, and had a stronger willingness to avoid family or social events in the OFS (P < 0.05). CONCLUSIONS: For patients with Brown IIb defects, SAIF reconstruction can achieve reduced nasal leakage when swallowing, improved upper-lip contour, increased social activity, and superior overall QOL than COP. The inferior chewing function in the SAIF group indicated the need for dental rehabilitation with a conventional denture or osseointegrated implants.


Asunto(s)
Neoplasias , Procedimientos de Cirugía Plástica , Humanos , Maxilar/cirugía , Neoplasias/cirugía , Obturadores Palatinos , Calidad de Vida , Estudios Retrospectivos , Colgajos Quirúrgicos/cirugía
18.
Front Chem ; 10: 927595, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35774863

RESUMEN

Oral cancer is one of the most common tumours in the world threatening human life and health. The 5-years survival rate of patients with oral cancer has not been improved significantly for many years. The existing clinical diagnostic methods rarely achieve early diagnosis due to deficiencies such as lack of sensitivity. Most of the patients have progressed to the advanced stages when oral cancer is detected. Unfortunately, the traditional treatment methods are usually ineffective at this stage. Therefore, there is an urgent need for more effective and precise techniques for early diagnosis and effective treatment of oral cancer. In recent decades, nanomedicine has been a novel diagnostic and therapeutic platform for various diseases, especially cancer. The synthesis and application of various nanoagents have emerged at the right moment. Among them, polymer nanoagents have unique advantages, such as good stability, high biosafety and high drug loading, showing great potential in the early accurate diagnosis and treatment of tumours. In this review, we focus on the application of advanced polymeric nanoagents in both the diagnosis and treatment of oral cancer. Then, the future therapy strategies and trends for polymeric nanoagents applied to oral cancer are discussed, with the hope that more advanced nanomedical technology will be applied to oral cancer research and promote the development of stomatology.

19.
Anim Cells Syst (Seoul) ; 25(5): 296-311, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745436

RESUMEN

The aim of this study was to compare the functional characteristics of mesenchymal stromal cells (MSCs) from a sheep model of traumatic temporomandibular joint (TMJ) fibrous and bony ankylosis. A sheep model of bilateral TMJ trauma-induced fibrous ankylosis on one side and bony ankylosis on the contralateral side was used. MSCs from fibrous ankylosed callus (FA-MSCs) or bony ankylosed callus (BA-MSCs) at weeks 1, 2, 4, and 8 after surgery were isolated and cultured. MSCs derived from the bone marrow of the mandibular condyle (BM-MSCs) were used as controls. The MSCs from the different sources were characterized morphologically, phenotypically, and functionally. Adherence and trilineage differentiation potential were presented in the ovine MSCs. These cell populations highly positively expressed MSC-associated specific markers, namely CD29, CD44, and CD166, but lacked CD31 and CD45 expressions. The BA-MSCs had higher clonogenic and proliferative potentials than the FA-MSCs. The BA-MSCs also showed higher osteogenic and chondrogenic potentials, but lower adipogenic capacity than the FA-MSCs. In addition, the BA-MSCs demonstrated higher chondrogenic, but lower osteogenic capacity than the BM-MSCs. Our study suggests that inhibition of the osteogenic and chondrogenic differentiations of MSCs might be a promising strategy for preventing bony ankylosis in the future.

20.
Sci Rep ; 9(1): 10493, 2019 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-31324825

RESUMEN

This study aimed to describe the clinical features of different types of traumatic temporomandibular joint (TMJ) ankylosis. Seventy-one patients with 102 ankylosed joints were retrospectively reviewed and categorized into four groups according to the grades of severity: type I, non-bony ankylosis of the joint with almost-normal joint space; type II, lateral bony ankylosis marked by a normal joint space that coexists with a radiolucent line; type III, complete bony ankylosis of the joint characterized by only a radiolucent line; and type IV, extensive bony ankylosis without any radiolucent line. The period of ankylosis, maximal mouth opening (MMO), rate of complications, and histopathological changes were compared among groups. Intergroup comparison showed significant differences in the clinical features of MMO and the incidence of complications (p < 0.05). Younger trauma patients tended to develop more severe types of ankylosis than older patients. Additionally, long post-trauma periods were related to the development of severe ankylosis. MMO was highly negatively correlated with the severity of ankylosis. Significant differences were noted among the four types of ankylosis. Younger trauma patients with long post-trauma periods tended to develop more severe TMJ ankylosis, experience more complications, and face more challenges in treatment than older patients.


Asunto(s)
Anquilosis/complicaciones , Trastornos de la Articulación Temporomandibular/complicaciones , Articulación Temporomandibular/patología , Adolescente , Adulto , Anquilosis/diagnóstico por imagen , Anquilosis/patología , Anquilosis/cirugía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/cirugía , Tomografía Computarizada por Rayos X , Adulto Joven
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