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1.
Mol Cancer ; 23(1): 94, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720298

RESUMO

BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.


Assuntos
Proteínas de Transporte , Ácidos Graxos , Proteínas de Membrana , Proteínas de Neoplasias , Neoplasias Ovarianas , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Microambiente Tumoral , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Animais , Hormônios Tireóideos/metabolismo , Camundongos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Efeito Warburg em Oncologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células , Proteoglicanas
2.
Adv Sci (Weinh) ; 11(20): e2307969, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38482752

RESUMO

Non-antibiotic strategies are desperately needed to treat post-traumatic osteomyelitis (PTO) due to the emergence of superbugs, complex inflammatory microenvironments, and greatly enriched biofilms. Previously, growing evidence indicated that quorum sensing (QS), a chemical communication signal among bacterial cells, can accelerate resistance under evolutionary pressure. This study aims to develop a medical dressing to treat PTO by inhibiting QS and regulating the inflammatory microenvironment, which includes severe oxidative stress and acid abscesses, through a reactive oxygen species (ROS)-responsive bond between N1- (4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (TSPBA) and polyvinyl alcohol (PVA), and the amino side chain of hyperbranched polylysine (HBPL). Physically enclosed QS inhibitors subsequently exerted the antibacterial effects. This hydrogel can scavenge hydrogen peroxide (H2O2), superoxide anion free radical (·O2 -), hydroxyl radicals (·OH) and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) to reduce oxidative stress and inhibit "bacteria-to-bacteria communication", thus clearing planktonic bacteria and biofilms, accelerating bacterial plasmolysis, reducing bacterial virulence and interfering with membrane transport. After in vivo treatment with hydrogel, nearly all bacteria are eliminated, inflammation is effectively inhibited, and osteogenesis and bone repair are promoted to facilitate recovery from PTO. The work demonstrates the clinical translational potential of the hydrogel in the treatment of drug-resistant bacteria induced PTO.


Assuntos
Hidrogéis , Osteomielite , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Animais , Camundongos , Modelos Animais de Doenças , Antibacterianos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ratos , Masculino
3.
Dalton Trans ; 53(10): 4764-4771, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363160

RESUMO

Herein, a zeolite@mesoporous silica composite (Z@MS) with a hierarchical porous structure was synthesized and employed as the filling material in miniature loudspeakers. The material was synthesized via a simple surfactant-directed sol-gel process in which MFI zeolites with a high silica-alumina ratio (>1000) were encapsulated in mesoporous silica with worm-like pores templated by Brij 72 under acidic conditions. Pressure spray drying technology was adopted to reassemble the intermediate slurry into hierarchical porous microspheres with large particle sizes (∼200 µm). The resonance frequency of the miniature loudspeaker system decreased by 339.77 Hz upon loading Z@MS as the filling material. The excellent acoustic performance can be considered as the result of a synergy of respective energy transmission effects among hierarchical porous structures.

4.
Cell Prolif ; : e13617, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403992

RESUMO

COVID-19 has been a global concern for 3 years, however, consecutive plasma protein changes in the disease course are currently unclear. Setting the mortality within 28 days of admission as the main clinical outcome, plasma samples were collected from patients in discovery and independent validation groups at different time points during the disease course. The whole patients were divided into death and survival groups according to their clinical outcomes. Proteomics and pathway/network analyses were used to find the differentially expressed proteins and pathways. Then, we used machine learning to develop a protein classifier which can predict the clinical outcomes of the patients with COVID-19 and help identify the high-risk patients. Finally, a classifier including C-reactive protein, extracellular matrix protein 1, insulin-like growth factor-binding protein complex acid labile subunit, E3 ubiquitin-protein ligase HECW1 and phosphatidylcholine-sterol acyltransferase was determined. The prediction value of the model was verified with an independent patient cohort. This novel model can realize early prediction of 28-day mortality of patients with COVID-19, with the area under curve 0.88 in discovery group and 0.80 in validation group, superior to 4C mortality and E-CURB65 scores. In total, this work revealed a potential protein classifier which can assist in predicting the outcomes of COVID-19 patients and providing new diagnostic directions.

5.
Risk Manag Healthc Policy ; 16: 2209-2222, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881167

RESUMO

Background: This study aimed to explore the risk factors and clinical characteristics of granulomatous mastitis (GM) using a case-control study and establish and validate a clinical prediction model (nomogram). Methods: This retrospective case-control study was conducted in three hospitals in China from June 2017 to December 2021. A total of 1634 GM patients and 186 healthy women during the same period were included and randomly divided into the modeling and validation groups in a 7:3 ratio. To identify the independent risk factors of GM, univariate and multivariate logistic analyses were conducted and used to develop a nomogram. The prediction model was internally and externally validated using the Bootstrap technique and validation cohort. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical significance of the model. Results: The average age of GM patients was 33.14 years (mainly 20-40). The incidence was high within five years from delivery and mainly occurred in the unilateral breast. The majority of the patients exhibited local skin alterations, while some also presented with systemic symptoms. On multivariate logistic analysis, age, high prolactin level, sex hormone intake, breast trauma, nipple discharge or invagination, and depression were independent risk factors for GM. The mean area under the curve (AUC) in the modeling and validation groups were 0.899 and 0.889. The internal and external validation demonstrated the model's predictive ability and clinical value. Conclusion: Lactation-related factors are the main risk factors of GM, leading to milk stasis or increased ductal secretion. Meanwhile, hormone disorders could affect the secretion and expansion of mammary ducts. All these factors can obstruct or injure the duct, inducing inflammatory reactions and immune responses. Additionally, blunt trauma, depressed mood, and diet preference can accelerate the process. The nomogram can effectively predict the risk of GM.

6.
Int J Womens Health ; 15: 1063-1075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795195

RESUMO

Background: Despite the rising incidence rate of granulomatous lobular mastitis (GLM), uncertainties persist about its etiologic and predisposing factors to guide clinical treatment and early prevention. The objective of this study is to explore the predisposing factors for GLM. Patients and methods: This case-control study was conducted from 2018 to 2021 at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients with GLM (cases) were matched with healthy examinees (controls) in a 1:1 ratio according to gender and living area. We analyzed their demographic features and investigated 75 factors that may be relevant to GLM using a standard questionnaire. Univariate and multivariable binary conditional logistic regression analyses were used to compare the differences between the two groups and evaluate the predisposing factors that may induce GLM. Results: There were 594 female GLM patients and 594 matched controls included in the study. The average age of the cases was 32.78 years (mainly 20 to 40). The incidence was high within five years after childbirth, and lesions were mainly in the unilateral breast. Univariate and multivariable conditional logistic regression analyses obtained six relevant factors and six high-risk factors. The six relevant factors included age, marriage, emotional abnormality, high prolactin, psychiatric drug intake, and sex hormone intake. Additionally, the independent high-risk factors for GLM included gestation, nipple invagination, blunt trauma, non-iatrogenic massage, lactation disorder, and nipple discharge (odds ratio (OR)=17.378, 8.518, 4.887, 3.116, 2.522, 1.685, P<0.05). Menopause was an independent protective factor (OR=0.249, P<0.05). Conclusion: The factors that increase milk and secretion production in the mammary duct are the main risk factors of GLM, especially when the nipples are invaginated. These factors can obstruct the duct and induce inflammation. Additionally, hormonal disorders, extrinsic trauma, and emotional abnormalities can accelerate the occurrence of GLM.

7.
Artigo em Chinês | MEDLINE | ID: mdl-37138404

RESUMO

To review the diagnosis and treatment of a case of hypercalcium crisis caused by primary hyperparathyroidism(PHPT) and prophylactic treatment of hungry bone syndrome. In a 32-year-old male with hypercalcemia, the main manifestations were loss of appetite, nausea, polyuria, polydipsia, fatigue, lethargy, etc. parathyroid hormone, serum calcium increased, thyroid function was normal, thyroid color ultrasound and MRI showed space-occupying behind the right thyroid, radionuclide examination showed abnormal imaging agent concentration in the right parathyroid area, there was a history of pathological fracture. Clinically diagnosed as hypercalcemia crisis secondary to PHPT.


Assuntos
Hipercalcemia , Hiperparatireoidismo Primário , Hipocalcemia , Masculino , Humanos , Adulto , Hipercalcemia/complicações , Hipercalcemia/diagnóstico , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Hormônio Paratireóideo , Hipocalcemia/complicações , Glândula Tireoide , Cálcio
8.
Front Microbiol ; 14: 1175206, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138612

RESUMO

Introduction: Granulomatous mastitis (GM) is a chronic inflammatory breast disease. In recent years, the role of Corynebacterium in GM onset has received more and more attention. This study aims to detect the dominant bacterium in GM patients and analyze the association between clinical characteristics and infectious factors. Methods: In this study, 88 samples from 44 GM patients, six acute lactation mastitis (ALM) patients, and 25 non-inflammatory breast disease (NIB) patients were divided into a GM pus group, a GM tissue group, an ALM pus group, and a NIB tissue group; then, 16S ribosomal DNA sequencing was used to explore their microbiota. The clinical data of all 44 GM patients were also retrospectively collected and analyzed to determine their relationship with infection. Results: The median age of the 44 GM patients was 33 years, and 88.6% of patients had primary-onset cases, while 11.4% were recurrences; additionally, 89.5% of patients were postpartum and 10.5% were nulliparous. The serum prolactin level was abnormal in nine patients (24.3%). Samples from 15 GM patients (34.1%) had a Corynebacterium abundance of >1% (1.08-80.08%), with eight (53.3%) displaying an abundance of >10%. Corynebacterium was the only genus with significant differences between the GM pus group and the other three groups (p < 0.05). Corynebacterium kroppenstedtii was the predominant Corynebacterium species. Among clinical characteristics, a statistical difference in breast abscess formation was observed according to Corynebacterium abundance in Corynebacterium-positive and- negative patients (p < 0.05). Discussion: This study explored the relationship between Corynebacterium infection and GM, compared the clinical characteristics between Corynebacterium-positive and- negative patients, and provided support for the role of Corynebacterium species-in particular, C. kroppenstedtii-in the pathogenesis of GM. The detection of Corynebacterium can predict GM onset, especially in patients with high prolactin levels or a history of recent lactation.

9.
Medicine (Baltimore) ; 102(1): e32589, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607848

RESUMO

Most studies on human lung infection have been performed using animal models, formalin or other fixed tissues, and in vitro cultures of established cell lines. However, the experimental data and results obtained from these studies may not completely represent the complicated molecular events that take place in intact human lung tissue in vivo. The newly developed ex vivo short-term tissue culture model can mimic the in vivo microenvironment of humans and allow investigations of different cell types that closely interact with each other in intact human lung tissues. Therefore, this kind of model may be a promising tool for future studies of different human lung infections, owing to its special advantages in providing more realistic events that occur in vivo. In this review, we have summarized the preliminary applications of this novel short-term ex vivo tissue culture model, with a particular emphasis on its applications in some common human lung infections.


Assuntos
Pulmão , Animais , Humanos , Pulmão/metabolismo , Linhagem Celular , Modelos Animais
10.
Biomol Biomed ; 23(3): 517-526, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36373623

RESUMO

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.


Assuntos
Neoplasias Colorretais , Nomogramas , Humanos , Prognóstico , Calibragem , Divisão Celular , Neoplasias Colorretais/diagnóstico
11.
World J Surg Oncol ; 20(1): 258, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35965307

RESUMO

BACKGROUND: To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2. RESULTS: Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76-88%, I2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49-68%, I2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20-39%, I2= 84%), 28% (95% CI= 20-37%, I2= 77%), and 17% (95% CI= 11-24%, I2= 66%), respectively. CONCLUSIONS: Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Panitumumabe/uso terapêutico , Neoplasias Retais/tratamento farmacológico
12.
Small ; 18(12): e2107123, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35174966

RESUMO

Supported ultrasmall metal/metal oxide nanoparticles (UMNPs) with sizes in the range of 1-5 nm exhibit unique properties in sensing, catalysis, biomedicine, etc. However, the metal-support and metal-metal precursor interactions were not as well controlled to stabilize the metal nanoparticles on/in the supports. Herein, DNA is chosen as a template and a ligand for the silica-supported UMNPs, taking full use of its binding ability to metal ions via either electrostatic or coordination interactions. UMNPs thus are highly dispersed in silica via self-assembly of DNA and DNA-metal ion interactions with the assistance of a co-structural directing agent (CSDA). A large number of metal ions are easily retained in the mesostructured DNA-silica materials, and their growth is controlled by the channels after calcination. Based on this directing concept, a material library, consisting of 50 mono- and 54 bicomponent UMNPs confined within silica and with narrow size distribution, is created. Theoretical calculation proves the indispensability of DNA with combination of several organics in the synthesis of ultrasmall metal nanoparticles. The Pt-silica and Pt/Ni-silica chosen from the library exhibit good catalytic performance for toluene combustion. This generalizable and straightforward synthesis strategy is expected to widen the corresponding applications of supported UMNPs.


Assuntos
Nanopartículas Metálicas , Dióxido de Silício , Catálise , DNA , Nanopartículas Metálicas/química , Óxidos/química , Dióxido de Silício/química
13.
Genes (Basel) ; 12(5)2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068248

RESUMO

Despite the fact that imbalance between case and control groups is prevalent in genome-wide association studies (GWAS), it is often overlooked. This imbalance is getting more significant and urgent as the rapid growth of biobanks and electronic health records have enabled the collection of thousands of phenotypes from large cohorts, in particular for diseases with low prevalence. The unbalanced binary traits pose serious challenges to traditional statistical methods in terms of both genomic selection and disease prediction. For example, the well-established linear mixed models (LMM) yield inflated type I error rates in the presence of unbalanced case-control ratios. In this article, we review multiple statistical approaches that have been developed to overcome the inaccuracy caused by the unbalanced case-control ratio, with the advantages and limitations of each approach commented. In addition, we also explore the potential for applying several powerful and popular state-of-the-art machine-learning approaches, which have not been applied to the GWAS field yet. This review paves the way for better analysis and understanding of the unbalanced case-control disease data in GWAS.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Estudos de Casos e Controles , Genoma/genética , Genômica/métodos , Humanos , Modelos Lineares , Aprendizado de Máquina , Fenótipo
14.
Artif Cells Nanomed Biotechnol ; 48(1): 824-833, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32456481

RESUMO

Zinc pyrithione (ZPT) is widely used as an antimicrobial. Zinc is a necessary trace element of the human whose homeostasis associated with several cancers. However, the anticancer effect of increased Zinc in ovarian cancer is still unclear. This study focussed on the anti-tumour effects of ZPT combined with Zinc in SKOV3 and SKOV3/DDP cells. The cell viability, apoptosis, migration, and invasion assays were detected by CCK-8, flow cytometry, wound healing and transwell assay, respectively. The distribution of Zinc in cells was monitored by staining of Zinc fluorescent dye and lysosome tracker. The changes in lysosomal membrane stability were reflected by acridine orange fluorescence and cathepsin D reposition. Expression of the proteins about invasion and apoptosis was evaluated by western blot. The results indicated that ZPT combined with Zinc could notably reduce cell viability, inhibit migration and invasion in SKOV3 and SKOV3/DDP cells. Besides, ZPT performed as a Zinc carrier targeted lysosomes, caused the increase of its membrane permeability and the release of cathepsin D accompanied by mitochondrial apoptosis in SKOV3/DDP cells. In conclusion, our work suggests that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma.


Assuntos
Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Piridinas/farmacologia , Tionas/farmacologia , Zinco/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Ionóforos/farmacologia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Invasividade Neoplásica
15.
Int J Biol Sci ; 16(5): 777-789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071548

RESUMO

Loco-regional recurrence of nasopharyngeal carcinoma (NPC) after radiation therapy is one of the main types of treatment failure. This study is aimed to explore the possible causes of inside-field recurrence of NPC patients in order to develop effective treatment methods. Our study indicated that CD44 and autophagy proteins in tumor tissues of patients with recurrent NPC are higher than that of the relapse free patients. The in vitro experiments further confirmed that cancer stem cells (CSCs) were more radioresistant with enhanced autophagy activity. Treatment with clioquinol (CQ) combined with zinc could obviously enhance the radiosensitivity of CNE-2s cells through autophagy inhibition, activation of the caspase system and impairment of DNA damage repair. The in vivo experiments have further consolidated our findings. Our results suggest that CSCs and enhanced autophagy activity may be involved in the inside-field recurrence of NPC, and CQ combined with zinc could be an important therapeutic approach for recurrent NPC.


Assuntos
Clioquinol/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Células-Tronco Neoplásicas/patologia , Zinco/uso terapêutico , Animais , Apoptose/genética , Apoptose/fisiologia , Autofagia/genética , Autofagia/fisiologia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/radioterapia , Células-Tronco Neoplásicas/metabolismo , Tolerância a Radiação
16.
J Cancer ; 10(13): 3062-3069, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281484

RESUMO

Objective: To explore the risk factors of cervical lymph node metastasis in oral squamous cell carcinoma (OSCC) patients with clinical negative cervical lymph nodes(cN0) and provide a reference for clinical treatment. Methods: The clinical data of 161 OSCC patients with cN0 were retrospectively analyzed. All patients underwent extended primary resection combined with cervical lymph node dissection. The level and number of cervical lymph node metastasis were confirmed by postoperative pathology. The risk factors of cervical lymph node metastasis in patients were analyzed by univariate and multivariate Logistic regression analysis. Results: Thirty-one out of 161 cases (19%) were confirmed cervical lymph node metastasis. Among them, there were 28 cases of lymph node metastasis in one cervical level and 3 cases in two cervical levels. A total of 42 positive lymph nodes were detected in 34 cervical levels. The level number of positive areas in the IA, IB, IIA, IIB, III, IV and V levels was 2, 15, 12, 1, 4,0, and 0, respectively. The corresponding regional metastasis rates were 5.9%, 44.1%, 35.3%, 2.9%, 11.8%, 0% and 0%, respectively. The number of positive lymph node metastases in the corresponding levels were 2, 17, 17, 1, 5, 0, and 0 respectively. Univariate analysis showed that gender, age, lesion location, T stage, and perineural invasion/lymphvascular invasion (PNI/PVI) had no significant effect on cervical lymph node metastasis (P>0.05). The growth pattern, degree of differentiation, depth of invasion, neutrophil/lymphocyte ratio (NLR) and the short/long axis diameter ratio (S/L ratio) of lymph nodes were important factors influencing the cervical lymph node metastasis in cN0 OSCC patients (P<0.05). Multivariate Logistic regression analysis indicated that the growth pattern, degree of differentiation, depth of invasion, NLR, and the S/L ratio of lymph nodes were independent risk factors for cervical lymph node metastasis (P<0.05). Conclusion: The growth pattern, degree of differentiation, depth of invasion, neutrophil/lymphocyte ratio, and the short/long axis diameter ratio of lymph nodes were the independent risk factors for pathological cervical lymph node metastasis in oral squamous cell carcinoma patients with cN0. If patients with the above risk factors receive nonstandard radical neck dissection or no dissection, it may be necessary for them to receive the corresponding regional postoperative radiotherapy.

17.
Cancer Cell Int ; 17: 115, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225515

RESUMO

BACKGROUND: We have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice. NF-κB plays important roles in genesis, growth, development and metastasis of cancer. NF-κB is also involved in the development of treatment resistance in tumors. Here we investigated the antitumor activity of APS in human non-small cell lung cells (A549 and NCI-H358) and the related mechanisms of action. METHODS: The dose-effect and time-effect of antitumor of APS were determined in human lung cancer cell line A549 and NCI-H358. The inhibition effect of APS on the P65 mRNA and protein was detected by reverse transcriptase-PCR (RT-PCR) and Western blot in A549 cells respectively. The inhibition effect of APS on the p50, CyclinD1 and Bcl-xL protein was detected by Western blot in A549 cells respectively. The effect of APS on NF-κB transcription activity was measured with NF-κB luciferase detection. Finally, the nude mice A549 xenograft was introduced to confirm the antitumor activity of APS in vivo. RESULTS: Cell viability detection results indicated that APS can inhibit the proliferation of human lung cancer cell line A549 and NCI-H358 in the concentration of 20 and 40 mg/mL. NF-κB activator Phorbol 12-myristate13-acetate (PMA) can attenuate the antitumor activity of APS in both cell lines, but NF-κB inhibitor BAY 11-7082 (Bay) can enhance the effect of APS in both cell lines. In vivo APS can delay the growth of A549 xenograft in BALB/C nude mice. APS can down-regulate the expression of P65 mRNA and protein of A549 cells and decrease the expression of p50, CyclinD1 and Bcl-xL protein. The luciferase detection showed that the APS could reduce the P65 transcription activity in A549 cells. PMA can partially alleviate the inhibition activity of P65 transcription activity of APS in A549 cells, and Bay can enhance the down-regulation of the P65 transcription activity induced by APS in A549 cells. CONCLUSION: APS has a significant antitumor activity in human lung cancer cells A549 and NCI-H358. NF-κB inhibition may mediate the antitumor effect.

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