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1.
Anal Chem ; 96(37): 14980-14988, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39235216

RESUMO

PD-L1-positive extracellular vesicles (PD-L1+ EVs) play a pivotal role as predictive biomarkers in cancer immunotherapy. These vesicles, originating from immune cells (I-PD-L1+ EVs) and tumor cells (T-PD-L1+ EVs), hold distinct clinical predictive values, emphasizing the importance of deeply differentiating the PD-L1+ EV subtypes for effective liquid biopsy analyses. However, current methods such as ELISA lack the ability to differentiate their cellular sources. In this study, a novel step-wedge microfluidic chip that combines magnetic microsphere separation with single-layer fluorescence counting is developed. This chip integrates magnetic microspheres modified with anti-PD-L1 antibodies and fluorescent nanoparticles targeting EpCAM (tumor cell marker) or CD45 (immunocyte marker), enabling simultaneous quantification and sensitive analysis of PD-L1+ EV subpopulations in oral squamous cell carcinoma (OSCC) patients' saliva without background interference. Analysis results indicate reduced levels of I-PD-L1+ EVs in OSCC patients compared to those in healthy individuals, with varying levels of heterogeneous PD-L1+ EVs observed among different patient groups. During immunotherapy, responders exhibit decreased levels of total PD-L1+ EVs and T-PD-L1+ EVs, accompanied by reduced levels of I-PD-L1+ EVs. Conversely, nonresponders show increased levels of I-PD-L1+ EVs. Utilizing the step-wedge microfluidic chip allows for simultaneous detection of PD-L1+ EV subtypes, facilitating the precise prediction of oral cancer immunotherapy outcomes.


Assuntos
Antígeno B7-H1 , Vesículas Extracelulares , Imunoterapia , Dispositivos Lab-On-A-Chip , Neoplasias Bucais , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análise , Neoplasias Bucais/terapia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Saliva/química , Saliva/metabolismo
2.
BMC Cancer ; 24(1): 1135, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261773

RESUMO

BACKGROUND: Due to the relative rarity of malignant sublingual gland tumors, diagnosing and treating them clinically pose challenges. Hence, there's a need to explore the pathological types, characteristics, treatment methods, and prognosis of primary malignant tumors of the sublingual gland to improve our understanding and management of these rare yet highly malignant conditions. METHODS: This study reviewed cases of primary malignant sublingual gland tumors, analyzing their characteristics. The treatment methods included surgical excision, with additional radiotherapy, or brachytherapy for advanced stages or positive surgical margins. The study also summarized different treatment approaches, including lymph node dissection and soft tissue reconstruction using free flaps such as the anterolateral thigh flap and forearm flap. RESULTS: We have gathered 23 cases of sublingual gland malignancies treated at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, from January 2013 to May 2024. The most common pathological types were adenoid cystic carcinoma and mucoepidermoid carcinoma, with rare cases of mucosa-associated lymphoid tissue (MALT) lymphoma and nonspecific salivary gland clear cell carcinoma. Early diagnosis and surgical intervention were crucial for a favorable prognosis. Marginal mandibulectomy was necessary for cases involving the mandible. Patients with positive preoperative lymph node detection required cervical lymph node dissection. Extensive tissue defects in the floor of the mouth were effectively reconstructed with free flaps to prevent oral-mandibular fistula. CONCLUSION: Surgical excision remains the preferred treatment for malignant sublingual gland tumors. Early diagnosis and comprehensive surgical management are essential for improving prognosis. The study's limitations include a small sample size and short follow-up duration, necessitating further research with larger clinical samples to confirm these findings.


Assuntos
Neoplasias da Glândula Sublingual , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias da Glândula Sublingual/patologia , Neoplasias da Glândula Sublingual/terapia , Adulto , Idoso , Prognóstico , Adulto Jovem , Excisão de Linfonodo , Carcinoma Adenoide Cístico/terapia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/diagnóstico , Estudos Retrospectivos , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia , Carcinoma Mucoepidermoide/terapia , Procedimentos de Cirurgia Plástica/métodos
3.
J Craniofac Surg ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39178419

RESUMO

The vascularized iliac crest flap has garnered widespread acclaim within the field of mandibular reconstruction attributable to its sufficient bone mass and congruent curved morphology. However, when the precise orientation of the iliac crest is imperative during mandibular reconstruction and there exists an accompanying defect within the oral soft tissue, the indispensability of an additional flap to facilitate concurrent defect repair becomes evident. In such instances, the submental island flap emerges as an exemplary candidate.

4.
J Craniofac Surg ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39133251

RESUMO

The removal of tumors at the root of the tongue can be challenging due to anatomic constraints (deep location of the root of the tongue, obstruction by the mandible), leading to poor surgical visibility. Clear visibility of the surgical field is crucial for complete excision to reduce recurrence, hence the need to choose an appropriate surgical approach based on the tumor's location and size. In this report, the authors describe a case where a midline mandibulotomy and temporary midline glossectomy were utilized to expose and resect a tumor at the root of the tongue. This approach allowed for the complete removal of the tumor while preserving the anterior tongue tissue and bilateral lingual arteries. The defect was then reconstructed using an anterolateral thigh flap. The patient showed good postoperative recovery with significant improvement in swallowing and speech functions. The authors emphasize that the surgical treatment of squamous cell carcinoma (SCC) at the root of the tongue should strive to ensure radical tumor removal while preserving surrounding healthy tissues and critical anatomic structures, particularly the lingual arteries, to facilitate better postoperative recovery for patients.

5.
J Craniofac Surg ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221954

RESUMO

A 32-year-old male presented with a painless swelling on his nasal dorsum, persisting for over 3 months. He reported a gradual increase in the size of the mass, with no identifiable triggers except occasional skin redness. He denied nosebleeds, rhinorrhea, nasal obstruction, trauma, prior surgery, or spontaneous pain. His medical history revealed gout, managed with colchicine and diclofenac. Despite dietary and pharmaceutical interventions, he continued to have bouts of hyperuricemia, with blood uric acid levels measuring 739 µmol/L. Multiple tophi were evident, especially on the left first metatarsophalangeal joint (Figure 1A). Examination revealed an irregularly shaped, immobile, hard swelling at the nasal radix, measuring 3 cm×2 cm. Computerized tomography (CT) imaging of the nose showed bilateral nasal bone destruction from the lesion. Given its impact on the patient's appearance and his history of gout, the mass was initially diagnosed as unusual gouty tophus. The patient requested surgical removal of the lesion, and the dissection revealed a mass partly encased by a capsule-like connective tissue adherent to the nasal bone. As the lesion damaged the nasal bone, removal of the lesion led to defect of nasal bone. After an extensive rinse of the surgery site, the incision was sutured.

6.
BMC Oral Health ; 24(1): 963, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154010

RESUMO

BACKGROUND: In recent years, the utilization of autogenous vascularized iliac crest flap for repairing jaw defects has seen a significant rise. However, the visual monitoring of iliac bone flaps present challenges, frequently leading to delayed detection of flap loss. Consequently, there's a urgent need to develop effective indicators for monitoring postoperative complications in iliac crest flaps. METHODS: A retrospective analysis was conducted on 160 patients who underwent vascularized iliac crest flap transplantation for jawbone reconstruction from January 2020 to December 2022. We investigated the changes in D-dimer levels among patients with or without postoperative complications. Additionally, multivariable logistic regression analysis was performed to explore potential individual risk factors, including surgical duration, age, pathology type, absolute and relative D-dimer levels, and gender, culminating in the development of a nomogram. RESULTS: On the first day following surgery, patients who experienced thrombosis exhibited a substantial increase in plasma D-dimer levels, reaching 3.75 mg/L, 13.84 times higher than the baseline. This difference was statistically significant (P < 0.05) compared to patients without postoperative complications. Furthermore, the nomogram we have developed and validated effectively predicts venous thrombosis, assigning individual risk scores to patients. This predictive tool was assessed in both training and validation cohorts, achieving areas under the curve (AUC) of 0.630 and 0.600, with the 95% confidence intervals of 0.452-0.807 and 0.243-0.957, respectively. CONCLUSIONS: Our study illustrates that postoperative plasma D-dimer levels can serve as a sensitive biomarker for monitoring thrombosis-induced flap loss. Moreover, we have developed a novel prediction model that integrates multiple factors, thereby enhancing the accuracy of early identification of patients at risk of thrombosis-associated flap loss. This advancement contributes to improving the overall management and outcomes of such procedures.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Ílio , Nomogramas , Complicações Pós-Operatórias , Retalhos Cirúrgicos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Ílio/transplante , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Idoso
7.
BMC Oral Health ; 24(1): 106, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238723

RESUMO

OBJECTIVE: This study aims to discuss the characteristics and treatment methods of malignant tumors in the parotid region, as well as the therapeutic effects of immediate free flap reconstruction of soft tissue for postoperative defects. MATERIALS AND METHODS: A retrospective review was conducted on 11 cases of soft tissue flap reconstruction for postoperative defects following the resection of malignant tumors in the parotid region. Statistical analysis was performed based on clinical data. RESULTS: Among the 11 cases of malignant tumors in the parotid region, there were 2 cases of secretory carcinoma (SC) of the salivary gland, 2 cases of squamous cell carcinoma (SCC), 2 cases of carcinosarcoma, 1 case of mucoepidermoid carcinoma (MEC), 1 case of epithelial-myoepithelial carcinoma (EMC), 1 case of salivary duct carcinoma (SDC), 1 case of basal cell carcinoma (BCC), and 1 case of osteosarcoma. Among these cases, 4 were initial diagnoses and 7 were recurrent tumors. The defect repairs involved: 8 cases with anterolateral thigh free flap (ALTF), 2 cases with pectoralis major muscle flaps, and 1 case with forearm flap. The size of the flaps ranged from approximately 1 cm × 3 cm to 7 cm × 15 cm. The recipient vessels included: 4 cases with the facial artery, 4 cases with the superior thyroid artery, and 1 case with the external carotid artery. The ratio of recipient vein anastomosis was: 57% for branches of the internal jugular vein, 29% for the facial vein, and 14% for the external jugular vein. Among the 8 cases that underwent neck lymph node dissection, one case showed lymph node metastasis on pathological examination. In the initial diagnosis cases, 2 cases received postoperative radiotherapy, and 1 case received 125I seed implantation therapeutic treatment after experiencing two recurrences. Postoperative follow-up revealed that 2 cases underwent reoperation due to local tumor recurrence, and there were 2 cases lost to follow-up. The survival outcomes after treatment included: one case of distant metastasis and one case of death from non-cancerous diseases. CONCLUSION: Immediate soft tissue flap reconstruction is an important and valuable option to address postoperative defects in patients afflicted with malignant tumors in the parotid region.


Assuntos
Carcinoma de Células Escamosas , Transplante de Pele , Humanos , Região Parotídea/patologia , Região Parotídea/cirurgia , Recidiva Local de Neoplasia/cirurgia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Algoritmos
8.
Cancer Sci ; 114(7): 2739-2749, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37010195

RESUMO

Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Although anti-angiogenic therapy (AAT) has been approved for treating various advanced cancers, this potential strategy has limited efficacy due to resistance over time. Therefore, there is a critical need to understand how resistance develops. Extracellular vesicles (EVs) are nano-sized membrane-bound phospholipid vesicles produced by cells. A growing body of evidence suggests that tumor cell-derived EVs (T-EVs) directly transfer their cargoes to endothelial cells (ECs) to promote tumor angiogenesis. Importantly, recent studies have reported that T-EVs may play a major role in the development of resistance to AAT. Moreover, studies have demonstrated the role of EVs from non-tumor cells in angiogenesis, although the mechanisms involved are still not completely understood. In this review, we provide a comprehensive description of the role of EVs derived from various cells, including tumor cells and non-tumor cells, in tumor angiogenesis. Moreover, from the perspective of EVs, this review summarized the role of EVs in the resistance to AAT and the mechanisms involved. Due to their role in the resistance of AAT, we here proposed potential strategies to further improve the efficacy of AAT by inhibiting T-EVs.


Assuntos
Células Endoteliais , Vesículas Extracelulares , Humanos , Células Endoteliais/metabolismo , Neovascularização Patológica/patologia , Vesículas Extracelulares/metabolismo , Comunicação Celular
9.
Br J Cancer ; 129(6): 925-934, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37532831

RESUMO

BACKGROUND: The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs. METHODS: sEVs were isolated from different clinical samples of head and neck squamous cell carcinoma (HNSCC) patients, the level and cellular origins of PD-L1-positive sEVs were assessed. Co-expression of CD80 on PD-L1-positive sEVs was examined to evaluate the immunosuppressive and tumor-promotive effects. RESULTS: PD-L1-positive sEVs in HNSCC patients had various cellular origins, including tumor cell, T cell, B cell, dendritic cell and monocyte/macrophage. However, PD-L1-positive sEVs derived from immune cells did not exert immunosuppressive functions due to the co-expression of CD80. It was verified that co-expression of CD80 disrupted the binding of sEV PD-L1 to its receptor PD-1 on T cells and attenuated the immunosuppression mediated by sEV PD-L1 both in vitro and in vivo. CONCLUSION: The study suggests that PD-L1-positive sEVs have the cellular origin and functional heterogeneity. Co-expression of CD80 could restrict the immunosuppressive effect of sEV PD-L1. A greater understanding of PD-L1-positive sEV subsets is required to further improve their clinical application.


Assuntos
Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1/metabolismo , Linfócitos T , Vesículas Extracelulares/metabolismo
10.
Anal Chem ; 95(2): 1016-1026, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36534080

RESUMO

Small extracellular vesicles (sEVs) are heterogeneous membrane-bound vesicles that carry numerous bioactive molecules. Studies have reported that sEVs carrying PD-L1 on the surface could contribute to immunosuppression; however, the precise mechanisms are unclear. To fully dissect their mode of action, it requires qualified methods to specifically isolate natural PD-L1-positive sEVs from heterogeneous sEVs. This study reported an aptamer-assisted capture-and-release strategy for traceless isolation of PD-L1-positive sEVs. The PD-L1 aptamer-anchored magnetic microspheres enable the specific capture of PD-L1-positive sEVs. The traceless release of captured PD-L1-positive sEVs was triggered by competition of complementary oligonucleotides, endowing the obtained label-free PD-L1-positive sEVs with natural properties. Benefited from this traceless isolation strategy, the distinct molecule profiles in adhesion and immuno-regulation between PD-L1-positive and PD-L1-negative sEVs were revealed. Compared to PD-L1-negative sEVs, PD-L1-positive sEVs were much more concentrated in cadherin binding, accompanied by increased adhesion to lymphatic endothelial cells and T cells but decreased adhesion to the extracellular matrix. Moreover, PD-L1-positive sEVs could transfer their enriched immunosuppressive "synapse"-related proteins to antigen-presenting cells, thereby inducing a tolerogenic-like phenotype. In summary, the present work dissects the subpopulation signature and action mode of PD-L1-positive sEVs for the first time and provides a general approach to the traceless isolation of sEV subpopulations.


Assuntos
Células Endoteliais , Vesículas Extracelulares , Antígeno B7-H1/metabolismo , Vesículas Extracelulares/metabolismo , Fenótipo , Aptâmeros de Peptídeos/química , Aptâmeros de Peptídeos/farmacologia
11.
Analyst ; 148(15): 3543-3550, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37387232

RESUMO

Dopamine (DA) is an important small-molecule neurotransmitter, which is closely related to the development of many neurological diseases and has received increasing attention in the diagnosis of neurological diseases. Currently, the assays of the detection of dopamine such as electrochemical and colorimetric methods have low sensitivity, poor selectivity and susceptibility to interference, which limit the accurate quantification of dopamine. Fluorescence anisotropy immunoassay is a traditional analytical method in which the quantification is based on the change in fluorescence anisotropy values observed when fluorescence molecules are bound to a certain volume and mass of the material. Since dopamine is a small molecule with small volume and mass, we took advantage of the good photostability of the second near-infrared window (NIR-II) quantum dots (QDs) and the low spontaneous interference of the substrate, and designed a biosensor dopamine fluorescence anisotropy probe streptavidin biosensor (DFAP-SAB) based on the NIR-II QDs combined with streptavidin signal amplification to achieve rapid and separation-free detection of dopamine in human serum. The detection signal has a good linearity between 50 nM and 3000 nM with a detection limit of 11.2 nM. The application of NIR-II QDs provides the possibility of biosensor applications for complex samples. The construction of the streptavidin signal amplification device provides a new idea for small molecule detection.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Humanos , Pontos Quânticos/química , Dopamina , Estreptavidina , Técnicas Biossensoriais/métodos , Imunoensaio , Limite de Detecção
12.
Oral Dis ; 29(4): 1542-1549, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35247026

RESUMO

OBJECTIVES: Depth of invasion (DOI) is the most important predictor for lymph node metastasis in early-stage oral cancer. This study aims to investigate the effects of the different classifications of AJCC 7th and 8th on predicting lymph node metastasis and the optimal cutoff point for DOI predicting the lymph node metastasis in patients with tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: We performed a retrospective study in 208 TSCC patients in early T stage without clinical or radiological signs of lymph node metastasis. Those patients were treated with elective neck dissection (END) between April 2019 and December 2020. And the relation between DOI and lymph node metastasis was analyzed. RESULTS: Metastases were found in 58 of 208 patients (27.88%). Of those 58 patients, the mean DOI was 8.311 mm compared to 5.425 mm in patients without metastases (p < 0.0001). The receiver operating characteristic curve (ROC curve) showed an area under the curve of 0.7066 with the most optimal cutoff point on a DOI of 4.050 mm (sensitivity 86.21%, specificity 52%). Linear regression analysis (1 mm ≤ DOI ≤6 mm) revealed that a DOI ≥ 3.211 mm predicated an incidence of occult lymph node metastasis greater than 20%. Regional metastases were found in 12.82% of patients with DOI ≤ 4.0 mm. Within the entire cohort, 60 cases (28.85%) got upgraded with respect to T stage. No tumor underwent downstaging. CONCLUSION: The 8th edition provides better lymph node metastasis prediction for TSCC than the 7th. And DOI is a poor predictor for regional metastasis in patients with early T stage clinically node-negative TSCC. END in patients with early-stage TSCC should be performed in patients with DOI ≥ 3.211 mm.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Metástase Linfática/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Língua , Prognóstico , Linfonodos/patologia
13.
Mikrochim Acta ; 190(12): 462, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945912

RESUMO

Fluorescent lateral flow immunoassay (LFA), one tool in point of care testing (POCT) systems for breast cancer, has attracted attention because it is quick, simple, and convenient. However, samples and the constituent material exhibit autofluorescence in the visible region, which is a very large obstacle in the development of fluorescent LFAs. The autofluorescence of biological samples is scarcely found in the second near-infrared (NIR-II) range and samples scatter and absorb less NIR-II light than visible light. Here, we report an NIR-II QD-LFA platform using the NIR-II fluorescent Ag2Se quantum dots (QDs) with 1020 nm emission encapsulated into polystyrene beads as fluorescent probes. The NIR-II LFA platform was established to detect breast cancer tumour markers (CEA and CA153) within 15 min with a low limit of detection (CEA: 0.768 ng mL-1, CA153: 1.192 U mL-1), high recoveries (93.7% ~ 108.8%), and relative standard deviations (RSDs) of less than 10%. This study demonstrated the potential of NIR-II Ag2Se polystyrene beads as a fluorescent probe in LFA for rapid and accurate identification of biomarkers. They are suited for use in professional situations.


Assuntos
Neoplasias , Poliestirenos , Biomarcadores Tumorais , Corantes Fluorescentes , Imunoensaio , Luz
14.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36768288

RESUMO

Oral cancer is one of the most common cancers worldwide, of which more than half of patients are diagnosed at a locally advanced stage with poor prognosis due to recurrence, metastasis and resistant to treatment. Thus, it is imperative to further explore the potential mechanism of development and drug resistance of oral cancer. Exosomes are small endosome-derived lipid nanoparticles that are released by cells. Since the cargoes of exosomes were inherited from their donor cells, the cargo profiles of exosomes can well recapitulate that of their donor cells. This is the theoretical basis of exosome-based liquid biopsy, providing a tool for early diagnosis of oral cancer. As an important intracellular bioactive cargo delivery vector, exosomes play a critical role in the development of oral cancer by transferring their cargoes to receipt cells. More importantly, recent studies have revealed that exosomes could induce therapy-resistance in oral cancer through multiple ways, including exosome-mediated drug efflux. In this review, we summarize and compare the role of exosomes in the diagnosis, development and therapy-resistant of oral cancer. We also highlight the clinical application of exosomes, and discuss the advantages and challenges of exosomes serving as predictive biomarker, therapy target and therapy vector in oral cancer.


Assuntos
Carcinoma de Células Escamosas , Exossomos , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resistencia a Medicamentos Antineoplásicos , Exossomos/patologia , Neoplasias de Cabeça e Pescoço/patologia
15.
Anal Chem ; 93(31): 10862-10870, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34328732

RESUMO

Circulating small extracellular vesicles (sEVs) are naturally occurring nanosized membrane vesicles that convey bioactive molecules between cells. Conventionally, to evaluate their behaviors in vivo, circulating sEVs have to be isolated from the bloodstream, then labeled with imaging materials in vitro, and finally injected back into the circulation of animals for subsequent detection. The tedious isolation-labeling-reinfusion procedures might have an undesirable influence on the natural properties of circulating sEVs, thereby changing their behaviors and the detected kinetics in vivo. Herein, we proposed an in situ biotinylation strategy to directly label circulating sEVs with intravenously injected DSPE-PEG-Biotin, aiming to evaluate the in vivo kinetics of circulating sEVs more biofriendly and accurately. Such an analysis strategy is free of isolation-labeling-reinfusion procedures and has no unfavorable influence on the natural behaviors of sEVs. The results showed that the lifetime of generic circulating sEVs in mice was around 3 days. Furthermore, we, for the first time, revealed the distinct in vivo kinetics of circulating sEV subpopulations with different cell sources, among which erythrocyte-derived sEVs showed the longest lifespan. Moreover, compared with circulating sEVs in situ or used as autograft, circulating sEVs used as allograft had the shortest lifetime. In addition, the in situ biotinylation strategy also provides a way for the enrichment of biotinylated circulating sEVs. In summary, this study provides a novel strategy for in situ labeling of circulating sEVs, which would facilitate the accurate characterization of their kinetics in vivo, thereby accelerating their future application as biomarkers and theranositic vectors.


Assuntos
Vesículas Extracelulares , Animais , Biomarcadores/metabolismo , Biotinilação , Vesículas Extracelulares/metabolismo , Cinética , Camundongos
16.
Int J Cancer ; 145(5): 1358-1370, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785217

RESUMO

Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin-α (LT-α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The coculture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT-α secretion in the cocultured lymphocytes. In vitro data further demonstrated that LT-α promoted the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) by enhancing the PFKFB3-mediated glycolytic flux. Genetic and pharmacological inhibition of PFKFB3 suppressed the enhanced proliferation and migration of HUVECs. We further identified that LT-α induced PFKFB3 expression was dependent on the TNFR/NF-κB signaling pathway. In addition, we proved that PFKFB3 blockade decreased the density of CD31 positive blood vessels in HNSCC xenografts. Finally, the results from the human HNSCC tissue array revealed that the expression of LT-α in HNSCC samples positively correlated with microvessel density, lymphocytes infiltration and endothelial PFKFB3 expression. In conclusion, infiltrated lymphocyte secreted LT-α enhances the glycolysis of ECs in a PFKFB3-dependent manner through the classical NF-κB pathway and promotes the proliferation and migration of ECs, which may contribute to the aberrant angiogenesis in HNSCCs. Our study suggests that PFKFB3 blockade is a promising therapeutic approach for HNSCCs by targeting tumor angiogenesis.


Assuntos
Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Linfotoxina-alfa/metabolismo , Fosfofrutoquinase-2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/irrigação sanguínea , Animais , Linfócitos B/metabolismo , Ciclo Celular/fisiologia , Técnicas de Cocultura , Feminino , Glicólise , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral , Linfotoxina-alfa/biossíntese , Linfotoxina-alfa/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Linfócitos T/metabolismo , Regulação para Cima
17.
J Am Chem Soc ; 138(6): 1893-903, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26804745

RESUMO

Cell-derived microvesicles (MVs) are natural carriers that can transport biological molecules between cells, which are expected to be promising delivery vehicles for therapeutic purposes. Strategies to label MVs are very important for investigation and application of MVs. Herein, ultrasmall Mn-magnetofunctionalized Ag2Se quantum dots (Ag2Se@Mn QDs) integrated with excellent near-infrared (NIR) fluorescence and magnetic resonance (MR) imaging capabilities have been developed for instant efficient labeling of MVs for their in vivo high-resolution dual-mode tracking. The Ag2Se@Mn QDs were fabricated by controlling the reaction of Mn(2+) with the Ag2Se nanocrystals having been pretreated in 80 °C NaOH solution, with an ultrasmall size of ca. 1.8 nm, water dispersibility, high NIR fluorescence quantum yield of 13.2%, and high longitudinal relaxivity of 12.87 mM(-1) s(-1) (almost four times that of the commercial contrast agent Gd-DTPA). The ultrasmall size of the Ag2Se@Mn QDs enables them to be directly and efficiently loaded into MVs by electroporation, instantly and reliably conferring both NIR fluorescence and MR traceability on MVs. Our method for labeling MVs of different origins is universal and free of unfavorable influence on intrinsic behaviors of MVs. The complementary imaging capabilities of the Ag2Se@Mn QDs have made the long-term noninvasive whole-body high-resolution dual-mode tracking of MVs in vivo realized, by which the dynamic biodistribution of MVs has been revealed in a real-time and in situ quantitative manner. This work not only opens a new window for labeling with QDs, but also facilitates greatly the investigation and application of MVs.


Assuntos
Magnetismo , Pontos Quânticos , Prata/química , Animais , Materiais Biocompatíveis , Linhagem Celular Tumoral , Humanos , Camundongos , Análise Espectral/métodos
18.
Theranostics ; 14(3): 1029-1048, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250044

RESUMO

Bacterial infections remain a formidable threat to human health, a situation exacerbated by the escalating problem of antibiotic resistance. While alternative antibacterial strategies such as oxidants, heat treatments, and metal nanoparticles (NPs) have shown potential, they come with significant drawbacks, ranging from non-specificity to potential environmental concerns. In the face of these challenges, the rapid evolution of micro/nanomotors (MNMs) stands out as a revolutionary development in the antimicrobial arena. MNMs harness various forms of energy and convert it into a substantial driving force, offering bright prospects for combating microbial threats. MNMs' mobility allows for swift and targeted interaction with bacteria, which not only improves the carrying potential of therapeutic agents but also narrows the required activation range for non-drug antimicrobial interventions like photothermal and photodynamic therapies, substantially improving their bacterial clearance rates. In this review, we summarized the diverse propulsion mechanisms of MNMs employed in antimicrobial applications and articulated their multiple functions, which include direct bactericidal action, capture and removal of microorganisms, detoxification processes, and the innovative detection of bacteria and associated toxins. Despite MNMs' potential to revolutionize antibacterial research, the translation from laboratory to clinical use remains challenging. Based on the current research status, we summarized the potential challenges and possible solutions and also prospected several key directions for future studies of MNMs for antimicrobial purposes. Collectively, by highlighting the important knowns and unknowns of antimicrobial MNMs, our present review would help to light the way forward for the field of antimicrobial MNMs and prevent unnecessary blindness and detours.


Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cegueira , Taxa de Depuração Metabólica
19.
J Stomatol Oral Maxillofac Surg ; : 102046, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251069

RESUMO

Gingival squamous cell carcinoma (SCC) of the posterior mandible often requires marginal resection of the mandible in conventional surgery. However, the posterior location of the lesion can limit surgical visibility, which is critical for complete tumor removal and minimizing recurrence. Typically, marginal resection of the posterior mandible is achieved through a midline lower lip incision and mental nerve transection, providing adequate exposure but resulting in nerve damage, lip numbness, and facial scarring. In this paper, we describe a case using a submandibular incision for neck dissection, extending from the mandibular angle to the mental foramen, to fully expose the posterior mandible. The intraoral incision, extending 1 cm beyond the tumor margin, connected with the submandibular incision. Under direct vision, we performed a marginal resection of the mandible, preserving the inferior alveolar neurovascular bundle and the mental nerve, and maintaining at least 1 cm of the inferior mandibular margin. This technique achieved complete tumor removal while preserving mental nerve function and lower lip integrity, reducing surgical difficulty and patient trauma. This approach maintains nerve function and aesthetics as much as possible, with a faster postoperative recovery. In treating gingival SCC of the posterior mandible, it is essential to preserve surrounding healthy tissue and critical anatomical structures, minimizing postoperative complications while ensuring complete tumor resection.

20.
Oral Oncol ; 148: 106648, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38006689

RESUMO

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of marginal zone B-cell lymphoma that occurs outside the lymph nodes in mucosal tissue. It accounts for 6-8 % of non-Hodgkin's lymphomas. MALT lymphoma of the salivary gland is a rare disease, with primary tumors in the salivary gland accounting for 2-5 % of salivary gland tumors. The most common site is the parotid gland (80 %), followed by the submandibular gland (14 %), minor salivary glands, and sublingual gland (5 %). Patients with salivary gland MALT lymphoma often have autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Primary malignant tumors of the sublingual gland account for less than 1 % of cases, and preoperative diagnosis is difficult, often requiring biopsy for confirmation. To our knowledge, there are no reports of MALT lymphoma arising from the sublingual gland. We report a case of MALT lymphoma originating from the sublingual gland in a patient with a history of hypertension, diabetes, cerebral infarction, and non-traumatic numbness of the right lower limb.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias das Glândulas Salivares , Síndrome de Sjogren , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Glândula Sublingual/patologia , Glândulas Salivares/patologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia , Neoplasias das Glândulas Salivares/patologia
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