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1.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4483-4492, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37802875

RESUMO

This study aims to investigate the effect and mechanism of hydnocarpin(HC) in treating triple negative breast cancer(TNBC). Cell counting kit-8(CCK-8), xCELLigence real-time cellular analysis(RTCA), and colony formation assay were employed to determine the effects of HC on the proliferation of two TNBC cell lines: MDA-MB-231 and MDA-MB-436. The effects of HC on the migration and invasion of TNBC cells were detected by high-content analysis, wound-healing assay, and Transwell assay. The changes in the epithelial-mesenchymal transition(EMT) and the expression of invasion-and migration-associated proteins [E-cadherin, vimentin, Snail, matrix metalloproteinase-2(MMP-2), and MMP-9] were detected by Western blot. Western blot and RT-qPCR were employed to determine the protein and mRNA levels of Yes-associated protein(YAP) and downstream targets(CTGF and Cyr61). TNBC cells were transfected with Flag-YAP for the overexpression of YAP, and the role of YAP as a key target for HC to inhibit TNBC malignant progression was examined by CCK-8 assay, Transwell assay, and wound-healing assay. The pathway of HC-induced YAP degradation was detected by the co-treatment of proteasome inhibitor with HC and ubiquitination assay. The binding of HC to YAP and the E3 ubiquitin ligase Ccr4-not transcription complex subunit 4(CNOT4) was detected by microscale thermophoresis(MST) assay and drug affinity responsive target stability(DARTS) assay. The results showed that HC significantly inhibited the proliferation, colony formation, invasion, and EMT of TNBC cells. HC down-regulated the protein and mRNA levels of CTGF and Cyr61. HC down-regulated the total protein level of YAP, while it had no effect on the mRNA level of YAP. The overexpression of YAP antagonized the inhibitory effects of HC on the proliferation, migration, and invasion of TNBC cells. HC promoted the degradation of YAP through the proteasome pathway and up-regulated the ubiquitination level of YAP. The results of MST and DARTS demonstrated direct binding between HC, YAP, and CNOT4. The above results indicated that HC inhibited the malignant progression of TNBC via CNOT4-mediated degradation and ubiquitination of YAP.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Ubiquitinação , RNA Mensageiro/metabolismo , Transição Epitelial-Mesenquimal , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Acta Pharmacol Sin ; 43(6): 1568-1580, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34522004

RESUMO

Dysregulation of the Hippo signaling pathway seen in many types of cancer is usually associated with a poor prognosis. Paris saponin VII (PSVII) is a steroid saponin isolated from traditional Chinese herbs with therapeutic action against various human cancers. In this study we investigated the effects of PSVII on human breast cancer (BC) cells and its anticancer mechanisms. We showed that PSVII concentration-dependently inhibited the proliferation of MDA-MB-231, MDA-MB-436 and MCF-7 BC cell lines with IC50 values of 3.16, 3.45, and 2.86 µM, respectively, and suppressed their colony formation. PSVII (1.2-1.8 µM) induced caspase-dependent apoptosis in the BC cell lines. PSVII treatment also induced autophagy and promoted autophagic flux in the BC cell lines. PSVII treatment decreased the expression and nuclear translocation of Yes-associated protein (YAP), a downstream transcriptional effector in the Hippo signaling pathway; overexpression of YAP markedly attenuated PSVII-induced autophagy. PSVII-induced, YAP-mediated autophagy was associated with increased active form of LATS1, an upstream effector of YAP. The activation of LATS1 was involved the participation of multiple proteins (including MST2, MOB1, and LATS1 itself) in an MST2-dependent sequential activation cascade. We further revealed that PSVII promoted the binding of LATS1 with MST2 and MOB1, and activated LATS1 in the BC cell lines. Molecular docking showed that PSVII directly bound to the MST2-MOB1-LATS1 ternary complex. Microscale thermophoresis analysis and drug affinity responsive targeting stability assay confirmed the high affinity between PSVII and the MST2-MOB1-LATS1 ternary complex. In mice bearing MDA-MB-231 cell xenograft, administration of PSVII (1.5 mg/kg, ip, 4 times/week, for 4 weeks) significantly suppressed the tumor growth with increased pLATS1, LC3-II and Beclin 1 levels and decreased YAP, p62 and Ki67 levels in the tumor tissue. Overall, this study demonstrates that PSVII is a novel and direct Hippo activator that has great potential in the treatment of BC.


Assuntos
Neoplasias da Mama , Saponinas , Animais , Autofagia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Feminino , Via de Sinalização Hippo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Proteínas Serina-Treonina Quinases , Saponinas/farmacologia , Saponinas/uso terapêutico
3.
Molecules ; 27(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35744808

RESUMO

With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (1O2) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.


Assuntos
Complexos de Coordenação , Rutênio , Complexos de Coordenação/farmacologia , DNA , Clivagem do DNA , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Rutênio/farmacologia
4.
Zhongguo Zhong Yao Za Zhi ; 47(6): 1650-1657, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35347964

RESUMO

The present study investigated the mechanism of polyphyllin A(PPA) in inhibiting gastric cancer(GC) cells. GC cells(SGC7901 and MGC803 cell lines) were treated with PPA at different concentrations. The effect of PPA on the proliferation of GC cells was detected by MTT assay, real-time cell analysis(RTCA) assay, and clone-forming assay, respectively. Reactive oxygen species(ROS) of GC cells was detected by flow cytometry. The change of mitochondrial membrane potential was detected by JC-1 assay. The expression and phosphorylation levels of apoptosis-related proteins(caspase-9, caspase-3, and PARP) and proteins related to the signaling pathway(ETS-1, CIP2 A, and Akt) were detected by Western blot. The binding sites of PPA to ETS-1 were analyzed by molecular docking. The affinity of PPA and ETS-1 was detected by drug affinity responsive target stability(DARTS) assay. PPA had a significant inhibitory effect on the proliferation and colony formation of GC cells at a low concentration. The PPA groups showed increased ROS and decreased mitochondrial membrane potential. PPA down-regulated the precursor expression of caspase-9 and caspase-3 and promoted the cleavage of PARP, suggesting that PPA induced the apoptosis of GC cells through the mitochondrial pathway. PPA significantly reduced expression levels of CIP2 A and the phosphorylation of downstream Akt. Molecular docking showed that PPA bound to the ETS domain of ETS-1, the transcription factor of CIP2 A, and formed hydrogen bonds with Pro319 and Asp317. DARTS assay further confirmed that PPA significantly prevented the hydrolysis of ETS-1 by pronase, which was inductive of the direct binding effect of PPA and ETS-1. PPA inhibits the proliferation and induces the apoptosis of GC cells by directly targeting ETS-1 to down-regulate the ETS-1/CIP2 A/Akt signaling pathway.


Assuntos
Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Simulação de Acoplamento Molecular , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 47(21): 5890-5899, 2022 Nov.
Artigo em Zh | MEDLINE | ID: mdl-36472008

RESUMO

This study aims to investigate the effect of ethoxysanguinarine(Eth) on cisplatin(DDP)-resistant human gastric cancer cells and decipher the underlying mechanism. The human gastric cancer cell line SGC7901 and the DDP-resistant cell line SGC7901/DDP were used as the cell models. Western blot was employed to determine the expression levels of multidrug resistance-related proteins, and methyl thiazolyl tetrazolium(MTT) assay to detect the proliferation of SGC7901 and SGC7901/DDP cells exposed to DDP. After treatment with different concentrations of Eth, the proliferation of SGC7901 and SGC7901/DDP cells was detected by MTT assay, trypan blue exclusion assay, colony formation assay, and high-content imaging and analysis system. The apoptosis of SGC7901/DDP cells was detected by flow cytometry with Annexin V-FITC/PI staining. GFP-LC3 transfection was carried out to detect the effect of Eth on the autophagy of SGC7901/DDP cells. The expression levels of the multidrug resistance-related protein P-glycoprotein(P-gp), the apoptosis-related proteins [caspase-9, caspase-3, and poly(ADP-ribose) polymerase(PARP)], the autophagy-related protein light chain 3-Ⅱ(LC3-Ⅱ), the key effectors [mammalian target of rapamycin(mTOR), 70 kDa ribosomal protein S6 kinase(P70 S6 K), and 4 E binding protein 1(4 E-BP1)] of the mammalian target of rapamycin complex 1(mTORC1) signaling pathway, cancerous inhibitor of protein phosphatase 2A(CIP2A), and protein kinase B(Akt) were measured by Western blot. The mRNA level of CIP2A in the SGC7901/DDP cells exposed to Eth for 24 h was analyzed by RT-qPCR. After SGC7901/DDP cells were transfected with CIP2A expression vector pcDNA3.1-HA-CIP2A and treated with different concentrations of Eth, MTT assay was used to determine the prolife-ration of SGC7901/DDP cells and Western blot to detect the expression levels of related proteins. The interaction sites of Eth and CIP2A were predicted by molecular docking. The affinity between Eth and CIP2A was determined by drug affinity responsive target stability(DARTS) assay. The pharmacokinetic properties and drug-like activity of Eth were predicted by SwissADME. The results indicated that SGC7901/DDP cells were more sensitive to Eth than SGC7901 cells. Eth significantly inhibited proliferation and colony formation and changed the morphology, roundness, and area of SGC7901/DDP cells. Eth treatment caused the nucleus shrinking and significantly increased the apoptosis rate of the cells. Furthermore, Eth down-regulated the expression of caspase-9 and caspase-3 precursors and promoted the cleavage of PARP, which suggested that Eth induced the apoptosis of SGC7901/DDP cells. The GFP-LC3 in Eth-treated cells showed speckled aggregation. The up-regulated expression of LC3-Ⅱ by Eth indicated that Eth activated the autophagy of SGC7901/DDP cells. Eth down-regulated the expression of P-gp, the phosphorylation of mTOR, P70 S6K, and 4E-BP1, the expression of CIP2A, and the phosphorylation of Akt. Additionally, it increased the activity of PP2A, and had no significant effect on the expression of CIP2A in SGC7901/DDP cells. CIP2A overexpression antagonized the inhibition of cell proliferation and the activation of autophagy by Eth. Molecular docking suggested that Eth bound to CIP2A. The results of DARTS assay further proved the above binding effect. Eth has potential drug-like activity. The above results demonstrated that Eth inhibited the proliferation, induced the apoptosis, and activated the autophagy of SGC7901/DDP cells by targeting CIP2A and then down-regulating PP2A/mTORC1 signaling pathway. This study provided a new target for the treatment of cisplatin-resistant gastric cancer.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Caspase 9/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Caspase 3/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Simulação de Acoplamento Molecular , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Autofagia , Apoptose , Proliferação de Células , Proteínas Reguladoras de Apoptose/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Linhagem Celular Tumoral
6.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200469

RESUMO

The photophysical and biological properties of two new phenanthroline-based ligand ruthenium complexes were investigated in detail. Their DNA interaction modes were determined to be the intercalation mode using spectra titration and viscosity measurements. Under irradiation, obvious photo-reduced DNA cleavages were observed in the two complexes via singlet oxygen generation. Furthermore, complex 2 showed higher DNA affinity, photocleavage activity, and singlet oxygen quantum yields than complex 1. The two complexes showed no toxicity towards tumor cells (HeLa, A549, and A375) in the dark. However, obvious photocytotoxicities were observed in the two complexes. Complex 2 exhibited large PIs (phototherapeutic indices) (ca. 400) towards HeLa cells. The study suggests that these complexes may act as DNA intercalators, DNA photocleavers, and photocytotoxic agents.


Assuntos
Clivagem do DNA/efeitos dos fármacos , DNA/efeitos dos fármacos , Fenantrolinas/farmacologia , Compostos de Rutênio/farmacologia , Células A549 , Linhagem Celular Tumoral , Células HeLa , Humanos , Substâncias Intercalantes/farmacologia , Ligantes , Compostos Organometálicos/farmacologia , Oxigênio Singlete/metabolismo
7.
Yi Chuan ; 43(1): 94-99, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33509778

RESUMO

Potassium channels, which are the most diverse group of the ion channel family, play an important role in the repolarization of cardiomyocytes. Recent studies showed that potassium channels, such as KCNQ and HERG/eag, play an important role in regulating adult heart function through shaping the action potential and maintaining the rhythm of cardiac contraction. The potassium channel protein Shaker is the first voltage-gated potassium channel found in Drosophila to maintain the electrical excitability of neurons and muscle cells, but its role in adult cardiac function is still unclear. In this study, Drosophila was used as a model to study the role of Shaker channel in the maintenance of cardiac function under stress and aging. The incidence of heart failure was observed in shaker mutant after external electrical pacing, which simulates cardiac stress. Additionally, The cardiac-specific driver hand4.2 Gal4 was used to specifically knock down the expression of the potassium channel shaker in Drosophila. The cardiac parameter was analyzed at 1, 3, 5 weeks of age on cardiac specific knockdown of shaker using Drosophila adult cardiac physiological assay. The results showed that the mutation of shaker gene seriously affect the cardiac function under stress, demonstrated by significant increase in heart failure rate under electrical stimulation. In addition, cardiac specific knockdown of shaker increased the incidence of arrhythmias in Drosophila at the age of 5 weeks. Cardiac-specific knockdown of shaker reduces life span. Therefore, the results of this study suggest a vital role of the potassium channel shaker in maintaining normal cardiac function during aging.


Assuntos
Envelhecimento , Proteínas de Drosophila/fisiologia , Drosophila , Coração/fisiologia , Superfamília Shaker de Canais de Potássio/fisiologia , Animais , Arritmias Cardíacas/genética , Técnicas de Silenciamento de Genes , Insuficiência Cardíaca/genética
8.
Inorg Chem ; 58(24): 16326-16329, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31793291

RESUMO

A new strategy for a G-quadruplex fluorescent probe based on a nitro-substituted ruthenium complex is described. G-quadruplex DNA can be distinguished from double- or single-strand DNA by the naked eye. This ability originates from variation of the degree of protection of the nitro group on the complex from water by G-quadruplex and other structure DNAs.


Assuntos
Complexos de Coordenação/química , DNA/análise , Corantes Fluorescentes/química , Quadruplex G , Nitrobenzenos/química , Colorimetria/métodos , DNA/genética , Humanos , Rutênio/química
9.
Radiology ; 282(1): 171-181, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27479804

RESUMO

Purpose To evaluate the prognostic value of the restaging system after neoadjuvant chemotherapy (NACT) in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and Methods This study was approved by the clinical research committee and a written informed consent was required before enrolling in the study. Prospectively enrolled were 412 consecutive patients with stage III-IVb NPC treated with NACT followed by concurrent chemotherapy and radiation therapy. Patients were staged before NACT and restaged after NACT. The progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. Results Post-NACT T classification (PFS, P = .001) and N classification (PFS, P < .001; DMFS, P = .001) resulted in better survival curve separations than pre-NACT T classification and N classification. Patients downstaged from N2-N3 to N0-N1 disease had a better prognosis than did patients who continued to have N2-N3 diseases (3-year PFS, 83.8% vs 66.6%, P = .001; 3-year DMFS, 88.0% vs 78.4%, P = .026). Multivariate analysis revealed that post-NACT T classification (hazard ratio [HR] = 1.67; 95% confidence interval [CI]: 1.18, 2.36; P = .003) and post-NACT N classification (HR = 1.54; 95% CI: 1.17, 2.03; P = .002) were independent prognostic factors for PFS; also, post-NACT N classification (HR = 1.48; 95% CI: 1.05, 2.07; P = .025) was an independent prognostic factor for DMFS. Multivariate analysis in patients with N2-N3 disease demonstrated that the N downstaging effects of NACT was the only independent prognostic factor for PFS (HR = 0.48; 95% CI: 0.29, 0.81; P = .006) and DMFS (HR = 0.52; 95% CI: 0.28, 0.97; P = .039). Conclusion The post-NACT stage is more representative of prognosis than the pre-NACT stage in advanced-stage NPC patients, which suggests that major clinical decisions should be based on the post-NACT stage. © RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Radioterapia de Intensidade Modulada , Taxa de Sobrevida , Taxoides , Resultado do Tratamento
10.
Ann Surg Oncol ; 22(3): 1008-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25201504

RESUMO

BACKGROUND: The current American Joint Committee on Cancer staging system considers tumor cell differentiation grade to be a factor in the staging of esophageal squamous cell carcinoma (ESCC) in pathologic T0-3N0M0 cases. However, more data are essential to test its efficacy. We sought to investigate the tumor-node-metastasis categories for which tumor cell grade might affect overall survival in Chinese patients. METHODS: We conducted a retrospective review of 1,220 patients with ESCC who underwent complete resection between December 1996 and December 2008. Survival was calculated by the Kaplan-Meier method, and the log-rank test was used to assess differences in survival between groups. Subgroup analyses and the Cox proportional hazards model were used to further determine the effect of tumor cell grade on overall survival. RESULTS: The 5-year survival rates for the G1, G2, and G3 groups of pathologic T2N0M0 ESCC cases were 80.1, 61.9, and 47.4%, respectively (p = 0.015), and these rates in the pathologic T3N0M0 ESCC cases were 66.7, 61.7, and 41.2%, respectively (p = 0.020). However, the differences in the survival of the different tumor cell grade groups of the pathologic T1N0M0 (p = 0.198) and the node positive categories (p = 0.063) were not statistically significant. Multivariate Cox regression analysis confirmed that tumor cell grade independently affected the overall survival of patients with pathologic T2-3N0M0 ESCC. CONCLUSIONS: The staging of ESCC in the Chinese population should be simplified by omitting tumor cell grade as a variable in patients with pathologic T1N0M0 disease. More data are needed to verify our results.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Diferenciação Celular , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Fluoresc ; 25(5): 1527-35, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26286067

RESUMO

A new ruthenium complex with a dppz-like ligand pyidppz, [Ru(bpy)2(pyidppz)](2+) (pyidppz = 2-(pyridine-2-yl)imidazo-[4,5-b]dipyrido-[3,2-a:2',3'-c]phenazine) has been synthesized and characterized by ES-MS, elemental analysis, (1)H NMR. Intercalative mode of the complex bound to calf thymus DNA has been supported by different spectroscopic methods and viscosity measurements. The introduction of phenazine unit may be one of the main reasons for the weak emission of Ru(II) complex in aqueous solution. Under irradiation, this complex can efficiently cleave DNA. And the photocleavage reaction of the complex is found to be inhibited in the presence of singlet oxygen scavenger. Topoisomerase inhibition and DNA strand passage assay demonstrated that [Ru(bpy)2(pyidppz)](2+) and its parent complex [Ru(bpy)2(pyip)](2+) (pyip = 2-(pyridine-2-yl)imidazo[4,5-f][1,10]phenanthroline) can act as efficient catalytic inhibitor of DNA topoisomerase I.


Assuntos
Clivagem do DNA/efeitos dos fármacos , DNA/química , Luz , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fenazinas/química , Rutênio/química , Animais , Bovinos , DNA/metabolismo , Ligantes , Compostos Organometálicos/metabolismo , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/farmacologia
12.
Chin J Cancer ; 34(6): 247-53, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26063113

RESUMO

INTRODUCTION: The properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system. METHODS: Magnetic resonance (MR) images for 229 patients with locally recurrent NPC who underwent IMRT were analyzed retrospectively. RESULTS: The skull base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6% vs. 50.0%, P<0.01) and those with T3 and T4 diseases (33.0% vs. 18.0%, P=0.04) but no difference between patients with T2 and T3 diseases (50.0% vs. 33.0%, P=0.18). Patients with a tumor volume≤38 cm3 had a significantly higher survival rate compared with those with a tumor volume>38 cm3 (48.7% vs. 15.2%, P<0.01). CONCLUSIONS: A new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.


Assuntos
Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Prognóstico , Radioterapia de Intensidade Modulada , Carga Tumoral , Carcinoma , Humanos , Carcinoma Nasofaríngeo , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida
13.
BMC Cancer ; 14: 583, 2014 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-25109220

RESUMO

BACKGROUND: Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker. METHODS: We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay. RESULTS: Using the 3rd quartile values (0.8 µg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1-84.9)) vs. (69%, 95%CI (59.2-78.8)), DMFS (87%, 95%CI (83.1-90.9)) vs. (77%, 95%CI (69.2-84.8)), and overall survival (82%, 95%CI (76.1-87.9)) vs. (76%, 95%CI (66.2-85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml. CONCLUSIONS: High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.


Assuntos
Quimiorradioterapia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Carcinoma , DNA Viral/sangue , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
14.
ScientificWorldJournal ; 2014: 412534, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24511284

RESUMO

We obtain some equivalent conditions of (strictly) pseudoconvex and quasiconvex fuzzy mappings. These results will be useful to present some characterizations of solutions for fuzzy mathematical programming.


Assuntos
Modelos Estatísticos , Algoritmos
15.
Chin J Cancer ; 33(10): 511-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25104280

RESUMO

The parapharyngeal space (PPS) is an inverted pyramid-shaped deep space in the head and neck region, and a variety of tumors, such as salivary gland tumors, neurogenic tumors, nasopharyngeal carcinomas with parapharyngeal invasion, and lymphomas, can be found in this space. The differential diagnosis of PPS tumors remains challenging for radiologists. This study aimed to develop and test a modified method for locating PPS tumors on magnetic resonance (MR) images to improve preoperative differential diagnosis. The new protocol divided the PPS into three compartments: a prestyloid compartment, the carotid sheath, and the areas outside the carotid sheath. PPS tumors were located in these compartments according to the displacements of the tensor veli palatini muscle and the styloid process, with or without blood vessel separations and medial pterygoid invasion. This protocol, as well as a more conventional protocol that is based on displacements of the internal carotid artery (ICA), was used to assess MR images captured from a series of 58 PPS tumors. The consequent distributions of PPS tumor locations determined by both methods were compared. Of all 58 tumors, our new method determined that 57 could be assigned to precise PPS compartments. Nearly all (13/14; 93%) tumors that were located in the pre-styloid compartment were salivary gland tumors. All 15 tumors within the carotid sheath were neurogenic tumors. The vast majority (18/20; 90%) of trans-spatial lesions were malignancies. However, according to the ICA-based method, 28 tumors were located in the pre-styloid compartment, and 24 were located in the post-styloid compartment, leaving 6 tumors that were difficult to locate. Lesions located in both the pre-styloid and the post-styloid compartments comprised various types of tumors. Compared with the conventional ICA-based method, our new method can help radiologists to narrow the differential diagnosis of PPS tumors to specific compartments.


Assuntos
Diagnóstico Diferencial , Espectroscopia de Ressonância Magnética , Pescoço/diagnóstico por imagem , Faringe/diagnóstico por imagem , Carcinoma , Humanos , Linfoma/diagnóstico , Linfoma/diagnóstico por imagem , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/diagnóstico por imagem , Radiografia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico por imagem
16.
Acta Radiol ; 54(2): 175-80, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23091235

RESUMO

BACKGROUND: Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. The few studies reporting these tumors have focused on the clinical manifestations and do not provide a summary of characteristic computed tomography (CT) findings. PURPOSE: To investigate the CT appearances of neuroendocrine tumors of the thymus in order to improve the diagnostic and resection efficacy. MATERIAL AND METHODS: Nine cases of pathologically identified thymic neuroendocrine tumors were retrospectively analyzed by CT. All the patients underwent non-enhanced and contrast-enhanced CT. Multiple CT features were examined, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. RESULTS: A total of nine masses were examined in this study. The maximum tumor diameter ranged from 5 to 14 cm (average, 9 cm). The shapes of six masses were lobulated and three were rounded or oval and the margins of seven masses were unclear while two masses were sharp. All the masses showed hypodensity or isodensity compared to muscles in the anterior thoracic wall on non-enhanced CT images. Two masses showed homogeneous attenuation by non-enhanced CT imaging and moderate homogeneous enhancement after contrast administration, while seven masses showed heterogeneous attenuation with patchy low-attenuation foci and showed moderate to strong heterogeneous enhancement. Involvement of adjacent structures was observed in six cases. Five cases were observed to have lymph node metastases and four cases had distant metastases. CONCLUSION: Neuroendocrine tumors of the thymus are rare tumors of the anterior mediastinum with a number of distinct CT characteristics. Most importantly, the density of the tumors was heterogeneous with necrosis or cystic degeneration and moderately or strongly enhancement after bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis of neuroendocrine tumors and provide critical information for surgical planning.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Biópsia com Agulha de Grande Calibre , Meios de Contraste , Feminino , Humanos , Iohexol/análogos & derivados , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/terapia , Neoplasias do Timo/patologia , Neoplasias do Timo/terapia
17.
Eur Arch Otorhinolaryngol ; 270(4): 1455-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22983297

RESUMO

Patients undergoing extensive partial laryngectomy require laryngeal reconstruction to restore function. Several techniques have been described, but they are associated with complications such as laryngeal stenosis. The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome. Eight patients requiring an extensive vertical or frontal partial laryngectomy for cancer were enrolled. Following radical tumor resection, laryngeal reconstruction was performed using the hyoid bone with a thyrohyoid membrane flap. Postoperative recovery time, complications, vocal quality, and cancer outcome were evaluated. The procedure was successful in all patients. There were no deaths, and no reports of postoperative dyspnea or dysphagia. Decannulation was performed in all patients after a median duration of 3 days (range 2-5 days). Swallowing and respiratory function were satisfactory and laryngeal stenosis did not occur during the mean follow-up period of 30.5 months. One patient had a local recurrence and required a salvage operation. A combined hyoid bone and thyrohyoid membrane flap is a reliable and relatively safe procedure that can be successfully performed for laryngeal reconstruction after extensive vertical or frontal partial laryngectomy.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Osso Hioide/transplante , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Retalhos Cirúrgicos/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Laríngeas/patologia , Laringoscopia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Invasividade Neoplásica , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Terapia de Salvação , Retalhos Cirúrgicos/transplante , Técnicas de Sutura , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
J Nanosci Nanotechnol ; 12(5): 3974-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22852335

RESUMO

A series of nanocomposite LiFe(1-2x)ZrxPO4/C (x = 0.01,0.02, 0.03, 0.04, 0.06) were prepared by carbon thermal reduction method. With this strategy, the Li3PO4 impurity phase can be obviously reduced in the Zr-doped samples and the electrochemical performance is obviously improved by Zr doping compared with the undoped one. The best electrochemical performances were observed in LiFe(0.92)Zr(0.04)PO4/C as well as good cycle stability.

19.
Chin J Cancer ; 31(1): 19-28, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22200180

RESUMO

Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness. To date, there is no consensus on the imaging characteristics of NACC. To address this, we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features. MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists. The location, shape, margin, signal intensity, lesion texture, contrast enhancement patterns, local invasion, and cervical lymphadenopathy of all tumors were evaluated. Clinical and pathologic records were also reviewed. No patients were positive for antibodies against Epstein-Barr virus (EBV). The imaging patterns of primary tumors were classified into two types as determined by location, shape, and margin. Of all patients, 7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern. The 4 tubular NACCs were all homogeneous tumors, whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images. Five patients had perineural infiltration and intracranial involvement, and only 2 had cervical lymphadenopathy. Based on these results, we conclude that NACC is a local, aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy. Furthermore, MRI features of NACC vary in locations and histological subtypes.


Assuntos
Carcinoma Adenoide Cístico/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Idoso , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/cirurgia , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos
20.
Chin J Cancer ; 31(11): 549-56, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22640624

RESUMO

This study aimed to determine and quantitate the mammographic and sonographic characteristics in 13 cases of solid neuroendocrine breast carcinoma (NEBC) and to analyze the association of radiological findings with the clinical and histopathologic findings. The clinical data and imaging findings of 13 female patients with histologically confirmed solid NEBC were reviewed. Imaging data were evaluated by two radiologists for a consensual diagnosis. All patients presented with one palpable mass; only 1 experienced occasional breast pain, and 5 complained of fluid discharge. In 7 patients, the masses were firm and mobile. Regional lymph node metastasis was noted in only 1 patient. For the 10 patients who underwent mammography, 6 had a mass, 1 had clustered small nodules with clustered punctuate microcalcifications, 2 had asymmetric focal density, and 1 had solitary punctuate calcification. Most of the masses had irregular shape with indistinct or microlobulated margins. For the 9 patients who underwent ultrasonography (US), 9 masses were depicted, all of which were hypoechoic, mostly with irregular shape and without acoustic phenomena. Different types of acoustic phenomena were also identified. One patient had developed distant metastases during follow-up. NEBC has a variety of presentations, but it is mostly observed on mammograms as a dense, irregular mass with indistinct or microlobulated margins. Sonographically, it typically presents as an irregular, heterogeneously hypoechoic mass with normal sound transmission. Histories of nipple discharge and calcification observed using imaging are not rare.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Neuroendócrino/diagnóstico por imagem , Mamografia , Ultrassonografia Mamária , Adulto , Idoso , Biópsia por Agulha Fina , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Calcinose/diagnóstico por imagem , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Cromogranina A/metabolismo , Feminino , Seguimentos , Humanos , Antígeno Ki-67/metabolismo , Metástase Linfática , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Sinaptofisina/metabolismo
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