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Autophagy contributes to bone homeostasis and development under physiological conditions. Although previous studies have demonstrated the induction of the autophagy machinery by endogenous glucocorticoids (GCs), the precise mechanisms involved have not yet been clarified. The current study aimed to explore the effect of a low dose of GC (10-8 M dexamethasone, Dex) on autophagy in mouse embryonic osteoblastic precursor cells (MC3T3-E1 cells) and the potential mechanisms. The results showed that 10-8 M Dex induced significant time-dependent increases in the expression and activation of serum- and glucocorticoid-induced kinase-1 (SGK1) in MC3T3-E1 cells and that these effects were accompanied by increased cell viability and decreased apoptosis. The autophagy inhibitor 3-MA significantly inhibited Dex-mediated promotion of viability. Moreover, Dex increased LC3II and Beclin-1 levels and decreased SQSTM/p62 levels in a time-dependent manner, and these effects were attenuated by pretreatment with 3-MA. Transfection of Dex-treated MC3T3-E1 cells with shRNA-SGK1 resulted in a significant reduction in cell viability and an increase in apoptosis. 3-MA further exacerbated these effects of SGK1 inhibition. Knocking down SGK1 before Dex exposure significantly reduced the phosphorylated forkhead box O3a (p-FOXO3a)/FOXO3 ratio, suppressed LC3II and Beclin-1 levels, and increased SQSTM/p62 levels in MC3T3-E1 cells, and these effects were amplified by 3-MA. In conclusion, the results revealed that low-dose GC treatment increased osteoblast viability by activating autophagy via the SGK1/FOXO3a pathway.
Assuntos
Dexametasona , Glucocorticoides , Animais , Camundongos , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Dexametasona/farmacologia , Proteína Beclina-1/metabolismo , Linhagem Celular , Transdução de Sinais , Autofagia , Osteoblastos/metabolismo , ApoptoseRESUMO
BACKGROUND: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported. METHODS: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF. RESULTS: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells. CONCLUSION: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.
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The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT-associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up-regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann-like cell through Twist/S100A4 axis in SACC.
Assuntos
Carcinoma Adenoide Cístico/patologia , Quimiocina CXCL12/metabolismo , Transição Epitelial-Mesenquimal , Proteínas Nucleares/metabolismo , Receptores CXCR4/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Neoplasias das Glândulas Salivares/patologia , Células de Schwann/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Animais , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Células de Schwann/patologia , Transdução de Sinais , Taxa de Sobrevida , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Fatty acid synthase (FASN) has been shown to be selectively up-regulated in cancer cells to drive the development of cancer. However, the role and associated mechanism of FASN in regulating the malignant progression of salivary adenoid cystic carcinoma (SACC) still remains unclear. In this study, we demonstrated that FASN inhibition attenuated invasion, metastasis and EMT of SACC cells as well as the expression ofPRRX1, ZEB1, Twist, Slug and Snail, among which the level of PRRX1 changed the most obviously. Overexpression of PRRX1 restored migration and invasion in FASN knockdown cells, indicating that PRRX1 is an important downstream target of FASN signalling. Levels of cyclin D1 and c-Myc, targets of Wnt/ß-catenin pathway, were significantly decreased by FASN silencing and restored by PRRX1 overexpression. In addition, FASN expression was positively associated with metastasis and poor prognosis of SACC patients as well as with the expression of PRRX1, cyclin D1 and c-Myc in SACC tissues. Our findings revealed that FASN in SACC progression may induce EMT in a PRRX1/Wnt/ß-catenin dependent manner.
Assuntos
Carcinoma Adenoide Cístico/patologia , Transição Epitelial-Mesenquimal , Ácido Graxo Sintases/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias das Glândulas Salivares/patologia , Via de Sinalização Wnt , Animais , Apoptose/genética , Carcinoma Adenoide Cístico/genética , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias das Glândulas Salivares/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Macrophage migration inhibitory factor (MIF) has been shown to closely associate with the malignant progression of a variety of human carcinomas. However, the role and its underlying molecular mechanisms of MIF in the invasion and metastasis of oral squamous cell carcinoma (OSCC) still remains unclear. Here, we found that MIF silencing reduced the cell proliferation, migration, and invasion, as well as matrix metalloprotein-2 (MMP-2) and MMP-9 in OSCC cells. Overexpression of MMP-2 or MMP-9 restored the migration and invasion of MIF-knockdown cells, indicating that MMP-2 and MMP-9 are downstream targets of MIF. In the xenograft model, MIF silencing inhibited tumor growth and in lymph metastasis model, MIF silencing reduced tumor metastasis. More importantly, immunohistochemistry staining in a tissue microarray (TMA) demonstrated that MIF expression was positively correlated with clinic stage, recurrence, metastasis, and poor prognosis of patients with OSCC as well as with the levels of MMP-2 or MMP-9 in TMA. Therefore, our findings suggest that MIF may promote the invasion and metastasis of OSCC through the activation of MMP-2 and MMP-9 and prompt further investigation into the therapeutic value of MIF for OSCC treatment.
Assuntos
Carcinoma de Células Escamosas/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Bucais/genética , Idoso , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial-to-mesenchymal transition (EMT)-related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA-mediated MIF silence, and the occurrence of EMT and Schwann-like cell differentiation was also inhibited by MIF silence in SACC-LM cells. Overexpression of MIF in SACC-83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann-like cell differentiation of SACC cells.
Assuntos
Carcinoma Adenoide Cístico/patologia , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Neoplasias das Glândulas Salivares/patologia , Células de Schwann/citologia , Carcinoma Adenoide Cístico/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Invasividade Neoplásica , Neoplasias das Glândulas Salivares/metabolismo , Células de Schwann/patologiaRESUMO
BACKGROUND: Salivary adenoid cystic carcinoma (SACC) can recur after removal of the primary tumor and treatment, where they can keep no clinical symptoms and dormant state for 10-15 years. NR2F1 has been demonstrated to regulate the tumor cell dormancy in various malignant tumors and has a potential impact on recurrence and metastasis of carcinoma. However, the role and significance of NR2F1 in SACC dormancy still remain unknown. METHODS: A total number of 59 patients with a diagnosis of SACC were included to detected expression of NR2F1, Ki-67 by immunohistochemical (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL). Fisher's exact test was used to examine the NR2F1 expression and clinicopathologic parameters of SACC. In vitro, SACC cell lines were transfected NR2F1 and knockdown NR2F1 respectively. CCK-8, flow cytometry, wound healing assay and transwell invasion determined SACC cell proliferation, apoptosis, cell cycle, migration and invasion respectively. Chromatin immunoprecipitation (ChIP) assays were utilized to demonstrate the potential role of NR2F1 in SACC invasion via CXCL12/CXCR4 axis. In vivo, xenografts of nude mice via subcutaneous injection or tail vein injection were used to testify the results in vitro. RESULTS: Among the 59 patients with SACC, 23.73% (14/59) were positive to NR2F1 expression, a lower rate of expression compared with 60% (6/10) in normal salivary gland samples. NR2F1 was correlated with metastasis, relapse and dormancy of SACC. SACC cells with transfected NR2F1 remained dormant, as well as enhanced invasion and metastasis. Knockdown of NR2F1 via siRNA after NR2F1 overexpression restored the proliferation and the cell number in G2/M phases, and reduced the abilities of migration and invasion. In addition, NR2F1 promoted the expression of CXCL12 and CXCR4, and overexpression of CXCL12 at least partly rescued the proliferation, migration, and invasion activities induced by NR2F1 silencing. CONCLUSIONS: NR2F1 may be an underlying mechanism of SACC recurrence and metastasis via regulating tumor cell dormancy through CXCL12/CXCR4 pathway.
Assuntos
Fator I de Transcrição COUP/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Quimiocina CXCL12/metabolismo , Recidiva Local de Neoplasia/metabolismo , Receptores CXCR4/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Animais , Apoptose , Fator I de Transcrição COUP/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Estudos de Coortes , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais , Transfecção , Adulto JovemRESUMO
A total of 258 malaria cases with 2 deaths were reported during 2007-2014, including 148 vivax malaria cases, 106 falciparum malaria cases, and 4 ovale malaria cases. During 2007-2009, 86.0% (135/157) were vivax malaria cases with 3 indigenous cases. In 2010-2014, the proportion of falciparum malaria is increasing year by year, and all were imported cases. 98.8% were imported from Africa and other provinces in China. Most cases occurred among patients aged 20-49 years, and the male-to-female ratio was 3.16:1. Most patients were workers and commercial service personnel. The malaria epidemic situation is relatively stable in Wenzhou. Malaria control and elimination interventions should emphasize the monitoring and education of transient population to control the imported cases, and explore multi-sector coordination for malaria prevention and control.
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Malária , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The first imported case of Plasmodium ovale infection in Wenzhou City was confirmed by microscopy and PCR test. The patient returned from the People's Republic of Congo to Wenzhou for three and a half months presented a history of fever with chills and rigors on April 30, 2012. The results from peripheral blood smear examination and PCR analysis confirmed a diagnosis of P. ovale infection. The patient was treated with chloroquine plus primaquine for eight days and the symptoms improved.
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Malária/diagnóstico , Malária/parasitologia , Plasmodium ovale , Adulto , China/epidemiologia , Humanos , Malária/epidemiologia , MasculinoRESUMO
Podophyllotoxin (PPT) has attracted researchers' attention because of its ability to treat various ailments. A series of podophyllotoxin derivatives (PPTs) have been synthesized as candidate drugs to improve the pharmacological characteristics of PPT. Nowadays, an increasing number of reviews have summarized structure-optimization, anticancer application, and single nano delivery of PPT and PPTs. In this review, we focus on the multidirectional pharmacological properties of PPT and PPTs, with an emphasis on the crosstalk with anticancer, anti-inflammatory, immunosuppression, and antivirals. Besides, the newly uncovered mechanisms governing PPT and PPTs in anticancer property including non-apoptotic regulated cell death are discussed. Moreover, their co-delivery nanocarriers with other antitumor drugs or biological agents that have the potential to achieve increased targeting efficacy are included. We hope that a better comprehension of this subject will help to provide a reference for improving the druggability and expanding the clinical application of podophyllotoxin and its derivatives.
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Antineoplásicos , Podofilotoxina , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Podofilotoxina/farmacologia , Podofilotoxina/uso terapêuticoRESUMO
Following the publication of this article, the authors have realized that they made an error during the compilation of the images shown in Fig. 6, and that this error was not corrected before the paper was sent to press. Specifically, in Fig. 6B, the data panels showing the results from the HUVEC + SACC83 siDll4 and HUVEC + SACCLM siDll4 experiments at 24 h were inadvertently repeated. The corrected version of Fig. 6, showing the correctly assembled data panels for Fig. 6B, is shown on the next page. The authors sincerely apologize for the errors that were introduced during the preparation of this Figure, thank the Editor for allowing them the opportunity to publish this Corrigendum, and regret any inconvenience that these errors may have caused. [the original article was published in Oncology Reports 45: 10111022, 2021; DOI: 10.3892/or.2021.7939].
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BACKGROUND: Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. METHODS: The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia-mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. RESULTS: In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. CONCLUSIONS: These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Carcinoma Adenoide Cístico/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Animais , Apoptose/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologiaRESUMO
CXCR5 played critical roles in tumorigenesis and metastasis. Nevertheless, little was known about the involvement of CXCR5 in perineural invasion (PNI) of salivary adenoid cystic carcinoma (SACC). Here, we confirmed upregulation of CXCR5 in SACC specimens and cells and identified that CXCR5 exhibited a significant positive correlation with PNI. Functionally, knockdown of CXCR5 suppressed SACC cells migration, invasion and PNI ability, whereas CXCR5 overexpression displayed the opposite effects. Moreover, CXCR5 downregulated microRNA (miR)-187, which could competitively sponge S100A4. The PNI-inhibitory effect of CXCR5 knockdown or miR-187 overexpression could be reversed by elevated expression of S100A4. Conjointly, our data revealed that CXCR5 facilitated PNI through downregulating miR-187 to disinhibit S100A4 expression in SACC.
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Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , MicroRNAs/metabolismo , Receptores CXCR5/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Sequência de Bases , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diferenciação Celular/genética , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Células de Schwann/metabolismo , Células de Schwann/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
High expression of δlike ligand 4 (Dll4) is reportedly related to the invasion, metastasis, and clinical prognosis of various malignant tumours. Our previous study revealed that collective cell invasion was a common pattern in salivary adenoid cystic carcinoma (SACC). However, the roles of the Dll4/Notch1 signalling pathway in the collective invasion of SACC remain unclear. The present study revealed that Dll4 expression was higher at the invasive front of SACC, and that this upregulation was associated with solid tumour type, high TNM grade, and high rates of metastasis and recurrence. Furthermore, the expression levels of Notch1 and Dll4 were positively correlated at the invasive front, and a threedimensional (3D) culture model revealed that leader cells showed high expression of Dll4, while follower cells showed high expression of Notch1. Moreover, silencing of Dll4 expression using small interfering RNA reduced the migration, invasion, and collective invasion of SACC cells, and these abilities were rescued by Notch1 overexpression. Finally, SACC collective invasion was increased via the Dll4/Notch1 signalling pathway in experiments that involved a stiff 3D gel, hypoxia and coculture with human endothelial cells. These findings indicated that the Dll4/Notch1 signalling pathway may be involved in the collective invasion of SACC, which may help to provide possible targets for the treatment of SACC.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Adenoide Cístico/genética , Receptor Notch1/metabolismo , Neoplasias das Glândulas Salivares/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/genética , Proteínas de Ligação ao Cálcio/genética , Carcinoma Adenoide Cístico/patologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Técnicas de Cocultura , Células Endoteliais , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Transdução de Sinais/genética , Hipóxia Tumoral/genética , Regulação para CimaRESUMO
PURPOSE: The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy. METHODS: Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly(carbonate-ester) copolymers. Two types of anticancer drug-loaded poly(carbonate-ester) nanospheres I and II were further prepared by dialysis method and high-voltage electrostatic field-assisted atomization, respectively, using HPCP-SD as polymeric carriers. These carriers and anticancer drug-loaded nanospheres were characterized, and their properties in vitro and in vivo were evaluated. RESULTS: These anticancer drug-loaded poly(carbonate-ester) nanospheres had steady drug release rates and good controlled release properties. Moreover, anticancer drug-loaded poly(carbonate-ester) nanospheres II had faster drug release rates than those of anticancer drug-loaded nanospheres I. These anticancer drug-loaded nanospheres possessed lower cytotoxicity to HEK 293 cells and exhibited obviously higher anticancer efficiencies to the HeLa tumor cells than that of 5-fluorouracil. Anticancer drug-loaded nanospheres I possessed lower cytotoxicity to HEK 293 cells and higher anticancer activity to HeLa cells than those of anticancer drug-loaded nanospheres II. CONCLUSIONS: These anticancer drug-loaded poly(carbonate-ester) nanospheres showed the potential as drug delivery systems for cancer therapy.
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Antineoplásicos/administração & dosagem , Caproatos/administração & dosagem , Carbonatos/administração & dosagem , Lactonas/administração & dosagem , Nanopartículas , Polímeros/administração & dosagem , Antineoplásicos/química , Varredura Diferencial de Calorimetria , Linhagem Celular , Portadores de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância MagnéticaRESUMO
PURPOSE: To evaluate the impact of health education with children popular oral science short drama on 10-year-old children's oral health knowledge, attitude, practice (KAP), and provide evidence for oral health education methods for children. METHODS: A oral health education short drama for children was filmed. 10-year-old children from a primary school in Minhang district, Shanghai were selected as the study subjects. The groups were asked to watch the drama on campus at enrollment and the first month for health education. Self-made questionnaires were used to conduct corresponding oral health KAP surveys at the time of enrollment, the first month and the sixth month. The survey results were compared using SPSS 21.0 software package for t test and Chi-square test, to compare the changes in oral health KAP scores and the accuracy of each question before and after oral health education. RESULTS: One hundred and seventy-four children were followed-up. Before the intervention, the subjects' oral health knowledge, attitude, and behavior scores were (21.02±12.54), (74.48±19.87), (31.90±22.39), and (57.05±17.56), (85.06±14.97), (55.03±29.32) at the first month; and (71.76±16.27), (91.49±12.40), (73.99±27.46) at the 6th month, respectively. Compared with those before the intervention, significant increases were observed (P<0.001). Before the intervention, there was no significant difference in KAP scores between different genders, but there were significant differences in knowledge and behavior scores at 1 and 6 months after intervention between different genders(P<0.05). CONCLUSIONS: School oral health education through children oral science short drama has a good effect on improving the knowledge, attitude and behavior of oral health care for 10-year-old children, and it is more effective when repeat.
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Conhecimentos, Atitudes e Prática em Saúde , Saúde Bucal , Criança , China , Feminino , Educação em Saúde , Educação em Saúde Bucal , Humanos , MasculinoRESUMO
BACKGROUND: Human papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is increasing worldwide with typically higher grade and stage, while better prognosis. microRNAs (miRNAs) has been shown to play a critical role in cancer, however, their role in HPV-positive OSCC progression remains unclear. METHODS: miRNA microarray was performed to identify differentially expressed miRNAs. qRT-PCR and FISH were performed to determine the relative expression of miR-550a-3-5p. CCK-8, Flow cytometry, Wound healing, Cell invasion assays and xenograft experiments were conducted to analyze the biological roles of miR-550a-3-5p. Tumor-associated macrophages (TAMs) generation, co-culturing of cancer cells with TAMs, Western blot, Dual-luciferase reporter gene assay, Immunohistochemistry and animal studies were performed to explore the mechanisms underlying the functions of miR-550a-3-5p. RESULTS: We identified 19 miRNAs differentially expressed in HPV-positive OSCC specimens and miR-550a-3-5p was down-regulated. The low expression of miR-550a-3-5p correlated with higher tumor size and nodal metastasis of HPV-positive OSCC patients. Then, we found that miR-550a-3-5p suppressed the migration, invasion and EMT of HPV-positive OSCC cells dependent on decreasing M2 macrophages polarization. Moreover, miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited M2 macrophages polarization by YAP/CCL2 signaling, which in turn abrogating EMT program in HPV-positive OSCC cells. In addition, in both xenografts and clinical HPV-positive OSCC samples, miR-550a-3-5p levels were inversely associated with YAP, CCL2 expressions and the number of M2 macrophages. CONCLUSIONS: E6/miR-550a-3-5p/YAP/CCL2 signaling induces M2 macrophages polarization to enhance EMT and progression, revealing a novel crosstalk between cancer cells and immune cells in HPV-positive OSCC microenvironment.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Macrófagos/patologia , MicroRNAs/genética , Neoplasias Bucais/patologia , Infecções por Papillomavirus/complicações , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Proliferação de Células , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Progressão da Doença , Feminino , Humanos , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/virologia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAPRESUMO
PURPOSE: The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC. METHODS: Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured. RESULTS: The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS. CONCLUSION: These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.
Assuntos
Carcinogênese/imunologia , Neoplasias Bucais/patologia , Células Supressoras Mieloides/imunologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/patologia , Comunicação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/imunologia , Neoplasias Bucais/cirurgia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/imunologia , Cultura Primária de Células , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Células Tumorais Cultivadas , Microambiente Tumoral/imunologiaRESUMO
Obesity has become pandemic and emerged as one of the most critical global health care problems worldwide since last century. Recent studies have demonstrated that there may be a causal link between obesity and higher risks and mortality of cancers, including prostate, breast, colon, and thyroid cancers, head and neck cancer (HNC). This review focuses on the relationship between obesity and HNC, and the molecular mechanism of abnormal lipid metabolism in HNC. Elucidating the mechanism may open up new possibilities for strategies to reduce risk and mortality of HNC in an increasingly obese population.
Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Obesidade/complicações , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Fatores de RiscoRESUMO
Graphene quantum dots (GQDs) as novel nanomaterials, have received significant interest in the field of biomedical applications. It is worth noting that a large amount of research is devoted to GQDs-based nanocomposites for cancer treatment, especially for photodynamic therapy (PDT), in that they can act not only as more favorable photosensitizers (PSs) but also nanoplatforms for delivering PSs. In this review, the biological behavior and physicochemical properties of GQDs for PDT are described in detail, and the application of GQDs-based nanocomposites in improved PDT and PDT-based combination therapies is analyzed, which may provide a new strategy for designing efficient PDT systems for cancer treatment.