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1.
BMC Cancer ; 19(1): 37, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621619

RESUMO

BACKGROUND: Findings remain unclear whether neutrophil-to-lymphocyte ratio (NLR) detrimentally affects advanced nasopharyngeal carcinoma (NPC) prognosis. We aim to evaluate the prognostic value of NLR in patients with NPC based on a large-scale cohort from an endemic area. METHODS: We selected patients retrospectively from a cohort examining long-term cancer outcomes following diagnosis. Neutrophil counts and lymphocyte counts were assessed prior to treatment. Kaplan-Meier method and log-rank test were used to calculate and compare survival outcomes. Additionally, Cox proportional hazards model was utilized to carry out univariate and multivariate analyses. RESULTS: Between October 2009 and August 2012, we enrolled 1550 consecutive NPC patients staged II-IVB. The median value of NLR was 2.27 (interquartile range [IQR], 1.71-3.12). Determined by operating characteristic curve using overall survival (OS) as an endpoint, the cutoff value for NLR was 2.50. At 5 years, NLR > 2.50 was associated with inferior OS (90.3% vs 82.5%; P < 0.001), distant metastasis-free survival (DMFS, 89.4% vs 85.0%; P = 0.014), and progression-free survival (PFS, 80.9% vs 76.5%; P = 0.031) than NLR ≤2.50. In multivariate analysis, NLR was found to be a significant prognostic factor for OS (HR, 1.72; 95% CI, 131-2.24; P < 0.001), DMFS (HR, 1.45; 95% CI, 1.10-1.92; P = 0.009), and PFS (HR, 1.29; 95% CI, 1.04-1.59; P = 0.021). CONCLUSION: Pretreatment NLR independently affects survival. Our findings suggest that NLR measurements will be of great clinical significance in the management of NPC.


Assuntos
Linfócitos/patologia , Carcinoma Nasofaríngeo/patologia , Neutrófilos/patologia , Prognóstico , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue
2.
Int J Syst Evol Microbiol ; 65(11): 4250-4255, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333922

RESUMO

A Gram-stain-positive, rod-shaped, facultatively anaerobic, endospore-forming bacterium (designated strain SC03T) was isolated from the aerobic treatment sludge of a coking plant (Shaoguan City, China). The optimal pH and temperature for growth were pH 7.0 and 35 °C. On the basis of 16S rRNA gene sequence analysis, strain SC03T was related to the genus Lysinibacillus and the similarity between strain SC03T and the most closely related type strain, Lysinibacillus macroides LMG 18474T, was 94.4 %. The genomic G+C content of the DNA of strain SC03T was 41.2 mol%. Chemotaxonomic data supported the affiliation of strain SC03T to the genus Lysinibacillus. These properties include MK-7 as the predominant menaquinone; iso-C15 : 0 and iso-C16 : 0 as major fatty acids; A4α (l-Lys-d-Asp) as the cell-wall peptidoglycan type; and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine plus three unknown phospholipids as polar lipids. The phenotypic, phylogenetic and chemotaxonomic characters enable the differentiation of strain SC03T from recognized Lysinibacillus species. Thus, strain SC03T represents a novel species of the genus Lysinibacillus, for which the name Lysinibacillus cresolivorans sp. nov. is proposed. The type strain is SC03T ( = NRRL B-59352T = CCTCC M 208210T).


Assuntos
Bacillaceae/classificação , Coque , Cresóis/metabolismo , Filogenia , Esgotos/microbiologia , Águas Residuárias/microbiologia , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácidos Graxos/química , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
3.
Acta Biomater ; 158: 599-610, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603734

RESUMO

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. STATEMENT OF SIGNIFICANCE: Autophagy is a "double-edged sword" in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Espécies Reativas de Oxigênio/metabolismo , Retroalimentação , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Autofagia , Porfirinas/farmacologia , Nanopartículas/uso terapêutico
4.
ACS Appl Mater Interfaces ; 14(48): 53501-53510, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36399048

RESUMO

Lipid peroxide (LPO) is the hallmark of ferroptosis, which is a promising antitumor modality for its unique advantages. However, a cellular defense system would weaken the antitumor efficacy of ferrotherapy. Herein, a GPX4 inhibitor of ML162 and a photosensitizer of chlorine e6 (Ce6) are used to prepare the self-delivery nanomedicine (C-ML162) through hydrophobic and electrostatic interactions to enhance ferroptosis by photodynamic therapy (PDT). Specifically, carrier-free C-ML162 improves the solubility, stability, and cellular uptake of antitumor agents. Upon light irradiation, the internalized C-ML162 generates large amounts of reactive oxygen species (ROS) to oxidize cellular unsaturated lipid into LPO. More importantly, C-ML162 can directly inactivate GPX4 to enhance the accumulation of toxic LPO, inducing ferroptotic cell death. Additionally, C-ML162 is capable of accumulating at a tumor site for effective treatment. This self-delivery system to amplify lipid peroxidation via GPX4 inactivation for PDT initiated ferrotherapy might provide an appealing strategy against malignancies.


Assuntos
Nanomedicina , Fotoquimioterapia , Peroxidação de Lipídeos
5.
Adv Healthc Mater ; 11(3): e2102038, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729950

RESUMO

Glutamine metabolism of tumor cells plays a crucial role in maintaining cell homeostasis and reducing oxidative damage. Herein, a valid strategy of inhibiting glutamine metabolism is proposed to amplify the oxidative damage of photodynamic therapy (PDT) to tumor cells. Specifically, the authors develop a drug co-delivery system (designated as CeV) based on chlorine e6 (Ce6) and V9302 via the self-assembly technology. In spite of the strong hydrophobicity of therapeutic agents, the assembled CeV holds a favorable dispersibility in water and an improved cellular uptake capability. Under light irradiation, the internalized CeV is capable of generating abundant reactive oxygen species (ROS) for PDT. More importantly, CeV can reduce the uptake of glutamine through V9302-mediated alanine-serine-cysteine transporter of type-2 (ASCT2) inhibition, leading to a reduced glutathione (GSH) production and an amplified oxidative stress. As a result, CeV has a robust PDT efficacy on tumor inhibition by the blockade of glutamine transport. Notably, CeV exhibits a superiority on tumor suppression over the single treatment as well as the combined administration of Ce6 and V9302, which indicates the advantage of CeV for synergistic treatment. It may serve as a novel nanoplatform for developing a drug co-delivery system to improve PDT efficiency by inhibiting cell metabolism.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Glutamina , Nanomedicina , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia
6.
Radiother Oncol ; 137: 137-144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31102988

RESUMO

PURPOSE: To compare clinical features and survival outcomes in patients with ascending type (type A) and descending type (type D) nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: A total of 5194 patients with type A and type D NPC treated at Sun Yat-sen University Cancer Center were randomly selected. Tumors that were mainly advanced local disease (T3-4 stage) with early stage cervical lymph node involvement (N0-1 stage) were determined as type A, while tumors with advanced lymph node disease (N2-3 stage) but early stage local invasion (T1-2 stage) were classified as type D NPC. Kaplan-Meier's analysis was used to evaluate survival rates, and log-rank test survival curves were used for comparison. In the multivariate analysis Cox proportional hazard models were developed. RESULTS: There was a larger proportion of type A tumors (82%) than type D tumors (18%). Compared to patients with type A tumors, those with type D tumors had increased likelihood of distant metastasis, regional recurrence, disease recurrence, and death (P < 0.001 for all), however, not for local recurrence (P < 0.001). The HR (hazard ratio) for death following recurrence of disease for type D tumors were 1.6 compared to type A tumors. Multivariate analysis revealed that elevated EBV DNA, elevated lactate dehydrogenase, alcohol consumption, and no family history of cancer attributed to the development of type D tumors. Annual hazard rate in type A patients increased, peaking at 12-18 months after initial treatment and downward thereafter. Similar trend also occurred in type D during the first 5 years following treatment. Notably, a minor peak was also observed 7-8 years post treatment. CONCLUSIONS: In the IMRT era, recurrence patterns differed across tumor types. Type D NPC had a more aggressive clinical course and worse outcomes compared with type A NPC.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adulto , Big Data , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Taxa de Sobrevida
7.
Am J Rhinol Allergy ; 29(1): e1-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25590304

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinuses and mucosa with unclear pathogenesis. Interleukin (IL)-21 is mainly expressed in activated cluster of differentiation (CD)4(+) T cells and has potent regulatory effects on the immune system. OBJECTIVE: This study is to determine whether IL-21 in the blood is correlated with CRS. METHODS: The blood samples from CRS patients and normal controls were analyzed in correlation with clinical features. The eosinophil percentage was counted, and serum levels of total immunoglobulin E (IgE) and IL-21 were analyzed by enzyme-linked immunosorbent assay (ELISA). In addition, IL-21 and interferon (IFN)-γ secreted from stimulated peripheral blood mononuclear cells (PBMCs) were measured by ELISA, and their mRNA expression levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Disease severity was scored based on computed tomography (CT) scan, nasal endoscopy, and global osteitis scoring scale (GOSS). RESULTS: A total of 55 CRS and 37 healthy subjects were recruited. The average levels of serum total IgE were 20 kU/L in normal group, 290 kU/L in CRS with nasal polys (CRSwNP), and 187 kU/L in CRS without nasal polys (CRSsNP). IL-21 levels were 28 pg/mL in normal group, 54 pg/mL in CRSwNP, and 71 pg/mL in CRSsNP. Both IgE and IL-21 were significantly elevated in both CRS patient subgroups. However, no significant difference was found between these two patient subgroups. The serum IL-21 levels correlated well with the disease severity in the patients. In addition, the secreted IL-21 was enhanced significantly in the patient's PBMCs stimulated by phytohemagglutin (PHA). CONCLUSION: IL-21 could be a target for diagnosis and treatment of CRS.


Assuntos
Interleucinas/sangue , Rinite/imunologia , Sinusite/imunologia , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Imunoglobulina E/sangue , Interferon gama/biossíntese , Masculino , Pessoa de Meia-Idade
8.
Huan Jing Ke Xue ; 35(10): 3918-25, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25693402

RESUMO

It has been proposed that the increasing of water solubility of PCBs can enhance the biodegradation efficiency. The biodegradation system of PCBs by Burkholderia xenovorans LB400 in the presence of different surfactants, namely TX-100, Tween 80, RL crude and HPCD were established to investigate the effect of surfactants on the biodegradation of hydrophobic organic compounds. The results indicated that the water solubility ratios of PCB5 and PCB31 were 54.7%-100%, 59.8%-100%; 10.5%-40.8%, 6.8%-31.6%; 10.3%-19.9%, 3.3%-11.6% and 19.5%-34.2%, 4.2%-10.7%, which were accordingly enhanced by TX-100 (CMC = 194 mg · L(-1)), Tween 80 (CMC =13.1 mg · L(-1)), and RL crude (CMC = 50 mg · L(-1)) with concentrations of 1-7 CMC, respectively and HPCD with concentrations of 500-1,500 mg · L(-1). Moreover, the growth inhibition ratio of B. xenovorans LB400 was 30.3%-45.8% with TX-100 concentration of 1-7 CMC, while it was 10.0%-15.4% for Tween 80 with concentration of 0.1-1 CMC; RL crude could boost the growth of strain LB400 as substrate while HPCD exerted no impact on it. The addition of surfactants can improve the biodegradation ratios of PCB31 (5 mg · L(-1)) by 23.7%-65.5% for TX-100, 14.6%-44.3% for Tween 80, 9.6%- 27.2% for RL crude and 15.3%-20.7% for HPCD depending on the surfactant concentrations, while it had minor effects on the biodegradation ratios of PCB5 (10 mg · L(-1)). It is concluded that the promoting effects of surfactant on PCBs biodegradation are mainly due to the increased concentrations of PCBs-surfactant micelles in aqueous solution and when TX-100 and Tween 80 concentrations are set as 1 and 7 CMC, the biodegradation ratios of PCB31 can achieve 100% and 81.7% , while the growth inhibition ratios of B. xenovorans LB400 are 30.3% and 5.4%, respectively.


Assuntos
Burkholderia/metabolismo , Bifenilos Policlorados/química , Tensoativos/química , Biodegradação Ambiental , Micelas , Polietilenoglicóis/química , Polissorbatos/química , Solubilidade
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 13(5): 764-8, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16277838

RESUMO

To investigate the relationship of As(2)O(3)-induced leukemic cell apoptosis with NF-kappaB activation and expression of VEGF, MMP9, apoptosis of K562-n cells induced by As(2)O(3) was analyzed by Annexin V, the dynamic changes of NF-kappaB, MMP9 and VEGF expressions were detected by immunohistochemistry. The results showed that activity of NF-kappaB could be increased, accompanied by higher level of expression of MMP9 and VEGF when apoptosis of K562-n cells was induced by As(2)O(3). Dexamethasome not only increased significantly the apoptotic rate, but also suppressed the activation of NF-kappaB of K562-n cells induced by As(2)O(3). Furthermore, there was a positive correlation between the expression of MMP9, VEGF and the activity of NF-kappaB. It is concluded that As(2)O(3) can induce apoptosis, in the meanwhile, activate NF-kappaB and up-regulate expression of MMP9 and VEGF in K562-n cell line. The mechanism of apoptosis of K562-n cells enhanced by dexamethasome may be related to suppression of the activation of NF-kappaB and expression of MMP9 and VEGF.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , NF-kappa B/metabolismo , Óxidos/farmacologia , Trióxido de Arsênio , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Células K562 , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Zhonghua Xue Ye Xue Za Zhi ; 26(4): 227-31, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15949266

RESUMO

OBJECTIVES: To study the effect of dexamethasone (Dex) on the apoptosis and NF-kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on apoptosis. METHODS: Cell apoptosis was analysed by Annexin V. Fluctuation of NF-kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry. RESULTS: The apoptosis and activation of NF-kappaB of Raji cells could be induced by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly increased (77.5%) the apoptosis induced by As2O3 (P < 0.05). Dex suppressed the activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P < 0.05). There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB. CONCLUSIONS: As2O3 could induce apoptosis, activate NF-kappaB and up-regulate expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by Dex may be related to suppressing activation of NF-kappaB and down-regulating expression of MMP9 and VEGF.


Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Dexametasona/farmacologia , NF-kappa B/metabolismo , Óxidos/farmacologia , Trióxido de Arsênio , Linhagem Celular Tumoral , Interações Medicamentosas , Glucocorticoides/farmacologia , Humanos , Imuno-Histoquímica , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese
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