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1.
Adv Sci (Weinh) ; : e2102666, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523247

RESUMO

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρsurf. molecule (Nsurf. molecules /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρsurf. molecule mainly induce apoptosis, while with large ρsurf. molecule they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρsurf. molecule due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρsurf. molecule greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.

2.
Expert Opin Drug Metab Toxicol ; 17(9): 1149-1156, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34372746

RESUMO

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg). METHOD: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®. RESULTS: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate. CONCLUSION: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Leuprolida/administração & dosagem , Testosterona/sangue , Adulto , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Área Sob a Curva , Preparações de Ação Retardada , Humanos , Injeções , Leuprolida/farmacocinética , Leuprolida/farmacologia , Masculino , Microesferas , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
3.
Respir Physiol Neurobiol ; 293: 103720, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34146730

RESUMO

The pathogenesis of obstructive sleep apnea (OSA) remains controversial. The role of anatomic stenosis is indisputable, and neural regulation of the upper airway remains to be elucidated. The upper airway maintains patency through the upper airway reflex. Lesions in any link of the reflex can increase the collapsibility of the upper airway. In this study, we investigated sensorimotor nerve lesions and their possible relationship with OSA. Tissue samples were obtained from the pharyngopalatine arch in 47 patients with OSA and 45 control participants to examine changes in the expression levels of myelin basic protein (MBP) and agrin through immunohistochemistry and western blotting. Downregulation of MBP in the mucosa reflects myelinated degeneration of mucosal sensory nerve axons, whereas upregulation of agrin in the neuromuscular junction reflects synaptic regeneration following denervation. The two neural factors correlate significantly with polysomnographic parameters, such as the apnea hypopnea index and lowest oxygen saturation. Our findings suggest that sensorimotor nerve damage in the upper airway of patients with OSA may be associated closely with the mechanism of OSA.

4.
J Asian Nat Prod Res ; : 1-5, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463380

RESUMO

Two new benzo[de]isoquinoline derivatives, 4-phenyl-benzo[de]isoquinoline-1,3-dione (1) and 4-(4-hydroxyphenyl)-benzo[de]isoquinoline-1,3-dione (2), were isolated from 70% ethanol extract of the rhizomes of Musa basjoo. Their chemical structures were elucidated by HRESIMS, 1 D and 2 D spectra.

5.
Artigo em Chinês | MEDLINE | ID: mdl-33254295

RESUMO

Objective:To analyze the therapeutic effect of internal carotid artery resection and one-stage revascularization in advanced cervical metastatic carcinoma. Method:Twenty-one patients with advanced head and neck malignant tumors who underwent internal carotid artery resection and one-stage revascularization were analyzed retrospectively. Among those, 11 patients suffered from hypo-pharyngeal carcinomas, 5 laryngeal carcinomas, 2 external auditory carcinomas, 1 middle ear carcinoma, and 2 parotid gland carcinomas. All patients received CT, MRI, DSA and other examinations before operation. It was found that all the internal carotid artery walls had been invaded by tumors, and there were different degrees of lumen stenosis. Autogenous saphenous vein grafts were used in 18 cases; artificial vessels were used in 3 cases. After revascularization, pedicled or free flaps were used to protect the anastomotic areas. All patients were treated with radiotherapy and chemotherapy according to different situations. Result:Among the 21 cases, 16 cases underwent reconstruction of cervical segment internal carotid and 5 cases were the skull base segment internal carotid. Twenty patients were successfully reconstructed in the first stage, and no vascular reconstruction-related nervous system complications occurred after operations. Postoperative imaging showed that the reconstructed blood vessels were well recanalized, with a success rate of 95.2%(20/21). Only 1 case received ligation of internal carotid artery after the failure of vascular reconstruction. Among all the cases, the 1-year survival rate and 3-year survival rate were 90.5% and 40.4%, respectively. Conclusion:In patients with advanced head and neck malignant tumors with cervical metastatic cancer invading the internal carotid artery, one-stage revascularization after radical resection of the tumor and the internal carotid can achieve good therapeutic effect. Careful preoperative evaluation, proficient vascular anastomosis technology, adequate risk assessment and prevention are the key to the success of the operations.


Assuntos
Artéria Carótida Interna , Neoplasias de Cabeça e Pescoço , Artéria Carótida Interna/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos Retrospectivos , Base do Crânio , Procedimentos Cirúrgicos Vasculares
6.
Adv Healthc Mater ; 9(20): e2001032, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32902190

RESUMO

Systemic antibiotic therapy is the main treatment for acute bacterial rhinosinusitis (ABRS). However, this treatment often causes side effects of dizziness, diarrhea, and drug resistance. In this study, a new polyethylene glycol hydrogel (PEG-H) treatment model is developed to achieve sustained release of drugs at the locality while avoiding those adverse effects. The PEG-H is composed of 4-arm-PEG-SH and silver ions through a high affinity and dynamic reversible coordination bond between the thiol and silver ion. In the initial test, PEG-H is loaded with Clarithromycin (CAM-Lips@Hydrogel) or Clarithromycin and Budesonide liposomes (CAM+BUD-Lips@Hydrogel). The results show that PEG-H maintains the characteristics of self-healing, biodegradability, moderate swelling rate, injectibility and sustained drug release. In in vivo studies, the hydrogel is injected into the maxillary sinus of ABRS rabbit models. In both a single or combined load, the hydrogel not only plays an effective role as an anti-bacterial, but also inhibits inflammatory response of local sinus mucosa. In addition, no other side effects are observed in the ABRS rabbit model through behavioral observation and drug sensitivity tests. Therefore, the injectable self-healing hydrogel with anti-bacterial and anti-inflammatory properties provides a new micro invasive therapeutic method for the clinical treatment of ABRS.


Assuntos
Hidrogéis , Polietilenoglicóis , Animais , Anti-Inflamatórios/farmacologia , Materiais Biocompatíveis , Liberação Controlada de Fármacos , Coelhos
7.
J Biomed Nanotechnol ; 15(11): 2262-2270, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31847940

RESUMO

Gold nano rods (GNRs) have showed cytotoxicity to cancer cells. At the same time, it shows little effects on non-tumor cells. Between GNRs and sub-cellular organelles, the understanding of interaction plays a very important role to determine the intracellular mechanisms. The purpose of what we done is to explain the effects of the surface properties of GNRs on specific cancer cell death. Three GNR samples with different aspect ratios were finely prepared by the seed-mediated growth method. Then the intracellular transport and the in vitro/vivo mechanisms of cancer cell death were studied by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser light scattering, and flow cytometry (FCM). It was found that GNRs700 exhibited the largest photothermal conversion efficiency. However, the GNR660 with or without light stimulation exhibited the highest cytotoxicity against cancer cells, which was contradict to the general knowledge. Detailed intracellular investigations showed that the lysosome was the key sub-organelle affecting the GNR function. Further experiments revealed that cytotoxicity was strongly affected by the GNR's surface potential. This potential was actually related to the density of surface cationic molecules, which further regulated lysosomal membrane penetration. The results obtained herein indicated that the physicochemical properties of the surface potential mediated the specific toxicity of GNRs against tumours.


Assuntos
Ouro , Nanotubos , Linhagem Celular Tumoral , Humanos , Lasers , Propriedades de Superfície
8.
Sci Adv ; 5(8): eaax3346, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31453340

RESUMO

Charge order is universal among high-T c cuprates, but its relation to superconductivity is unclear. While static order competes with superconductivity, dynamic order may be favorable and even contribute to Cooper pairing. Using time-resolved resonant soft x-ray scattering at a free-electron laser, we show that the charge order in prototypical La2-x Ba x CuO4 exhibits transverse fluctuations at picosecond time scales. These sub-millielectron volt excitations propagate by Brownian-like diffusion and have an energy scale remarkably close to the superconducting T c. At sub-millielectron volt energy scales, the dynamics are governed by universal scaling laws defined by the propagation of topological defects. Our results show that charge order in La2-x Ba x CuO4 exhibits dynamics favorable to the in-plane superconducting tunneling and establish time-resolved x-rays as a means to study excitations at energy scales inaccessible to conventional scattering techniques.

9.
Biomed Pharmacother ; 117: 108998, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207579

RESUMO

It has been widely considered that reversing epithelial-to-mesenchymal transition (EMT) is a potential access to restrain cancer progression and therapeutic resistance. Here, we aim to uncover the novel mechanisms by which we can reverse EMT and inhibit metastasis in laryngeal squamous cell carcinoma (LSCC). We show that miR-98 is significantly reduced in both LSCC specimens and cell lines. Over-expression of miR-98 inhibits the EMT-related gene expression and metastasis and invasive behavior in LSCC in vitro, as well as reduces lung metastasis in mouse model. In the mechanistically study, miR-98 directly targets HMGA2 in mediating EMT. HMGA2 knock down by si-RNA method declines several EMT-related genes expression and LSCC migration and invasion. In parallel, overexpression of HMGA2 transforms LSCC cells to acquire stem cell-like features. Furthermore, we reveal that HMGA2-mediated EMT is closely linked with the expression of POSTN that inhibits EMT, as a tumor suppressor, by gene profiling analyses. POSTN is transcriptionally repressed by HMGA2. In clinic, the HMGA2 mRNA level is negatively correlated with the miR-98 level in LSCC patient cohort. In conclusion, our study confers a powerful signal: miR-98-HMGA-POSTN in LSCC, which is able to reverse EMT and inhibit metastasis, underlining the therapeutic potential of this signal.


Assuntos
Carcinoma de Células Escamosas/genética , Moléculas de Adesão Celular/metabolismo , Transição Epitelial-Mesenquimal/genética , Proteína HMGA2/metabolismo , Neoplasias Laríngeas/genética , MicroRNAs/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
10.
Onco Targets Ther ; 12: 1365-1377, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863103

RESUMO

Background: Tongue squamous cell carcinoma (TSCC) is the second most common malignancy in oral carcinoma. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was regarded as an oncogenic factor in various carcinomas. However, its underlying molecular mechanisms in the development and progression of TSCC have not been well featured till now. Methods: The expressions of MALAT1, miR-140-5p and p21 (RAC1)-activated kinase 1 (PAK1) mRNA were measured by RT-qPCR assay. The protein level of PAK1 was determined by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Transwell chamber was used to detect cell migratory and invasive capability. Luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and biotin pull-down assay were applied to evaluate the relationship between MALAT1, miR-140-5p and PAK1. Xenograft experiments were performed to assess the effect and mechanism of MALAT1 in TSCC tumor growth. Results: The expression of MALAT1 and p21 (RAC1)-activated kinase 1 (PAK1) was upregulated and microRNA-140-5p (miR-140-5p) expression was downregulated in TSCC tissues and cells. MALAT1 knockdown induced miR-140-5p expression by direct interaction. Moreover, MALAT1 knockdown inhibited proliferation, migration, and invasion by upregulating miR-140-5p expression in TSCC cells. Additionally, PAK1 was identified as a direct target of miR-140-5p. Also, MALAT1 knockdown inhibited PAK1 expression by upregulating miR-140-5p in TSCC cells. Furthermore, miR-140-5p overexpression curbed the proliferation, migration, and invasion of TSCC cells by targeting PAK1. Finally, MALAT1 knockdown inhibited tumor growth by upregulating miR-140-5p and downregulating PAK1 in mouse xenograft models of TSCC. Conclusion: MALAT1 contributed to TSCC progression via miR-140-5p-PAK1 regulatory axis, highlighting a potential target for TSCC management.

11.
Laryngoscope ; 129(11): 2669-2673, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30756404

RESUMO

OBJECTIVE: To evaluate the extent of airway improvement and voice quality in patients with bilateral vocal fold paralysis (BVFP) who underwent selective laryngeal reinnervation surgery. METHODS: Seven patients with BVFP caused by thyroid surgeries were enrolled. They underwent selective laryngeal reinnervation surgery. Videostroboscopy data, voice perceptual data (grade [G]), acoustic data, laryngeal electromyography data, and pulmonary function test data were obtained preoperatively and postoperatively. RESULTS: Videostroboscopic videos showed that six patients could achieve moderate-to-maximal abduction in the bilateral vocal folds during inspiration, whereas all patients achieved adduction in the bilateral vocal folds during phonation at 4 to 7 months postoperatively. G score was decreased significantly versus preoperative values (P < 0.05), and vocal functional parameters were improved significantly at 12 months postoperatively (P < 0.05). The aerodynamic parameter of maximum phonation time was significantly longer than the preoperative value (P < 0.05). Most parameters in pulmonary function test recovered to normal reference levels as early as 3 months postoperatively, whereas maximal inspiratory pressure (PImax) values were still slightly lower than normal levels 12 months after surgery. All of these parameters improved significantly versus preoperative values. Electromyographic data at 12 months postoperatively showed full interference potentials in bilateral posterior cricoarytenoid muscles during inspiration and full interference potentials in bilateral thyroarytenoid muscles during phonation in all patients. Moderate electric potentials were seen in left interarytenoid muscle in one failed patient. CONCLUSION: This new selective laryngeal reinnervation procedure can achieve physiological movements of the bilateral vocal folds in selected patients with BVFP. LEVEL OF EVIDENCE: 4. Laryngoscope, 129:2669-2673, 2019.


Assuntos
Nervo Hipoglosso/cirurgia , Regeneração Nervosa , Nervo Frênico/cirurgia , Complicações Pós-Operatórias/cirurgia , Traumatismos do Nervo Laríngeo Recorrente/cirurgia , Paralisia das Pregas Vocais/cirurgia , Adulto , Feminino , Humanos , Nervo Hipoglosso/fisiopatologia , Músculos Laríngeos/inervação , Músculos Laríngeos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fonação , Nervo Frênico/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Período Pré-Operatório , Nervo Laríngeo Recorrente , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Estroboscopia , Tireoidectomia/efeitos adversos , Resultado do Tratamento , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/fisiopatologia , Prega Vocal/inervação , Prega Vocal/fisiopatologia , Qualidade da Voz
12.
Eur Arch Otorhinolaryngol ; 275(6): 1601-1606, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29610957

RESUMO

PURPOSE: Surgical preservation of laryngeal function is very challenging in patients with advanced SCCL, especially those of stage T4a. The purpose of this study was to assess the feasibility of organ preservation surgery for patients with T4a squamous cell carcinoma of the larynx (SCCL). METHODS: We enrolled 32 patients with T4a SCCL and performed organ preservation surgery on them. Surgical details and perioperative morbidity were described, functional and oncologic outcomes were also evaluated. RESULTS: All patients underwent supracricoid subtotal laryngectomy with unilateral or bilateral neck dissection, restoring laryngeal function via direct anastomosis of the cricoid cartilage and tongue base. The patients recovered well and exhibited relatively acceptable survival duration, with a 5-year overall survival rate of 62.5%. Most patients commenced oral intake within 2 weeks, and aspiration was commonly observed. Subjective functional outcomes indicated a relatively acceptable swallowing function and voice quality. CONCLUSION: Our retrospective analysis of 32 patients with T4a SCCL showed that successful organ preservation surgery is safe and reliable, and associated with a relatively acceptable disease-free survival, normal swallowing function, and acceptable voice quality. More patients with T4a SCCL who wish to preserve the larynx should be considered for organ preservation surgery.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia , Tratamentos com Preservação do Órgão , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cartilagem Cricoide/cirurgia , Deglutição , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do Tratamento , Qualidade da Voz
13.
J Cancer Res Ther ; 13(5): 856-861, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29237917

RESUMO

BACKGROUND: Total laryngectomy is preserved for those the most advanced larynx cancer and nonsurgical cases. However, stomal recurrence is frequently occurred and leads to high mortality. Herein, we aimed to determine the risk factors for the stomal recurrence after total laryngectomy (SRAL). METHODS: Databases such as PubMed and EMBASE were comprehensively searched using the keywords "stomal recurrence" and "total laryngectomy." Based on the inclusion and exclusion criteria, qualified studies would be incorporated in this meta-analysis, followed by quality evaluation and data extraction. Risk ratios (RRs) were used. RESULTS: A total of six studies were included in the meta-analysis, and the pooled RRs showed that subglottic location increased the incidence of stomal recurrence most among the four primary locations. Expectedly, advanced tumor stage before the laryngectomy was the risk factor for stomal recurrence, while lymph node metastases showed no difference in this meta-analysis. Further, preoperative tracheostomy increased two times more risk in the stomal recurrence compared with nonpreoperative surgery. CONCLUSIONS: In this study, we proved that subglottic location, advanced tumor stage, especially T4 stage, and preoperative tracheostomy were risk factors for SRAL for larynx cancer. However, many other potential risk factors, such as surgical margins, could not be determined for inadequate records. Hence, more prospective trials should be designed to determine the risk factors for SRAL for larynx cancer.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Carcinoma de Células Escamosas/patologia , Humanos , Incidência , Neoplasias Laríngeas/patologia , Laringectomia/métodos , Metástase Linfática , Margens de Excisão , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Cuidados Pré-Operatórios/efeitos adversos , Cuidados Pré-Operatórios/métodos , Fatores de Risco , Traqueostomia/efeitos adversos , Traqueostomia/métodos
14.
Oncotarget ; 8(60): 101634-101648, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-29254192

RESUMO

Cisplatin is a platinum-based drug that is used for the treatment of human gynecological cancers. However, molecular mechanisms of chemo-resistance in ovarian cancer are poorly understood. The aim of the study is to examine the role of coiled coil domain containing protein 69 (CCDC69) in the underlying mechanism of chemoresistance. Heavy CpG methylation (73.1% and 74.3%) was found in A2780 and A2780cis cells assessing by bisulfite sequencing. Restoration in the expression of CCDC69 was found in A2780 and A2780cis cells after 5-Aza-dC treatment. In fact, the expression levels of CCDC69 were about 3-4 fold higher in cisplatin-resistant A2780cis cells than its parental cisplatin-sensitive A2780 cells. When knockout CCDC69 in cisplatin-resistant A2780cis and SKOV3 cells by CRISPR/Cas9, the CCDC69 knockout cisplatin-resistant A2780cis and CCDC69 knockout SKOV3 cells were also shown increased sensitive to cisplatin treatment. Moreover, treating CCDC69 knockout A2780cis cells with cisplatin, abrogated G1 and G2/M arrest, increased of cleaved caspase 3&8, greater ΔΨm loss and higher levels of Bax were observed. When restoring CCDC69 expression in CCDC69 knockout A2780cis cells by transient transfection, it attenuated sensitivity to cisplatin. By immunoblotting, we found that depletion of CCDC69 increased p53 acetylation at K382 site and Bax mitochondrial redistribution. Additionally, inhibition of c-Myc enhanced cisplatin sensitivities in CCDC69 knockout A2780cis cells, overexpression of c-Myc reduced apoptosis in CCDC69 knockout SKOV3 cells. Our results showed that CCDC69 inhibition might interfere with the effectiveness of combination therapy with platinum drugs.

15.
Nanomedicine (Lond) ; 12(4): 295-315, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28093940

RESUMO

AIM: To target both head and neck squamous cell carcinoma (HNSCC) cells and cancer stem cells (CSCs) by salinomycin-loaded DSPE-PEG-MTX (synthesized using DSPE-PEG2000-NH2 and methotrexate) nanomicelles (M-SAL-MTX). MATERIALS & METHODS: The characterization, antitumor activity and mechanism of M-SAL-MTX were evaluated. RESULTS & CONCLUSION: M-SAL-MTX showed enhanced inhibitory effect toward both HNSCC CSCs and non-CSCs compared with a single treatment of methotrexate and salinomycin. In nude mice-bearing HNSCC xenografts, M-SAL-MTX suppressed tumor growth more effectively than other controls including combination of methotrexate and salinomycin. Therefore, M-SAL-MTX may provide a strategy for treating HNSCC by targeting both HNSCC CSCs and HNSCC cells.


Assuntos
Antibacterianos/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Portadores de Fármacos/química , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Piranos/administração & dosagem , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Células-Tronco Neoplásicas/patologia , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Piranos/farmacologia , Piranos/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço
17.
Artigo em Inglês | MEDLINE | ID: mdl-27402638

RESUMO

INTRODUCTION: The effects of renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent. METHODS: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case-control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer. RESULTS: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73-0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92-1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75-0.97) but not for other sites of cancer. The relative risk of cancer associated with renin-angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55-0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89-1.09). CONCLUSIONS: The significant benefits of renin-angiotensin system blockade observed in case-control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Sistema Renina-Angiotensina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Estudos Observacionais como Assunto , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
18.
Acta Otolaryngol ; 136(8): 841-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27066846

RESUMO

CONCLUSION: The findings suggest that a pectoralis major flap combined with a free flap is a safe and reliable method of reconstruction after total pharyngolaryngectomy; with this technique, one can help these patients remain disease free, with normal swallowing function, for a relatively acceptable survival duration. OBJECTIVES: To determine the functional and oncological outcomes of a combined flap for the extensive defects after total pharyngolaryngectomy in patients with advanced squamous cell carcinoma of the hypopharynx (SCCHP). METHOD: This study determined the perioperative morbidity and functional and oncologic outcomes of 21 patients with advanced SCCHP who underwent total laryngopharyngectomy and reconstruction using a combination of a pectoralis major flap and a free flap. RESULTS: The free flap and pectoralis major flap were used to reconstruct the defects for all 21 patients. Fourteen patients were reconstructed with jejunal free flaps and pectoralis major flaps; in the remaining seven patients, anterolateral thigh flaps and pectoralis major flaps were used. All the combined flaps worked well, and patients recovered normal swallowing function a mean 19.4 days after surgery. After an overall mean follow-up time of 31.3 months, 30% of patients were still alive at the time of this analysis, with no evidence of disease.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Laringectomia , Faringectomia , Retalhos Cirúrgicos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos/métodos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento
19.
Yi Chuan ; 38(2): 155-62, 2016 02.
Artigo em Chinês | MEDLINE | ID: mdl-26907779

RESUMO

Nitrogen, an essential macronutrient for the growth and development of plants, affects above- ground biomass accumulation dramatically. Thus, it is very important to reveal the molecular mechanisms of how plants resist or adapt to low nitrogen availability. The NAC1(NAM, ATAF, CUC 1) gene, located in the upstream regulatory network, has been reported to resist low nitrogen by regulating expression of key downstream genes and thus root growth in (Populus tremula × alba).In this study, we detected the responses of miR164 and its target gene NAC1 under nitrate-starvation condition using the Betula luminifera somaclones G49-3 as material. The NAC1 gene which contains 1497 bp sequence, encodes 358 amino acids and contains a highly conserved NAM domain at N terminal was cloned by the RACE method. The NAC1 was then validated to be the target gene of miR164 via 5'-RACE, and the cleavage site was between the 10(th) and 11(th) base. The expression patterns of miR164 and its target gene NAC1 were further detected under nitrate-starvation condition through qRT-PCR analysis. The results showed that miR164 expression was repressed by nitrate-starvation at the beginning of the treatment (4 d) and then ascended. However, the expression pattern of miR164 in roots was different from that in shoots and leaves. Moreover, the expression levels of target gene NAC1 and miR164 were negatively correlated. The expression level of miR164 in root was increased while that of NAC1 was decreased under Re treatment, which indicated that miR164 and its target gene NAC1 play a regulatory role in response to low nitrate availability. The findings of our study may help elucidate the molecular mechanisms by which miR164 regulates target gene NAC1 at post-transcriptional level, and provide valuable information for further study of the regulatory roles of miR164-NAC1 under nitrate-starvation condition.


Assuntos
Betula/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Nitratos/metabolismo , Proteínas de Plantas/genética , RNA de Plantas/genética , Sequência de Aminoácidos , Clonagem Molecular , Perfilação da Expressão Gênica/métodos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Fatores de Tempo
20.
Int J Clin Exp Med ; 8(4): 6024-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131199

RESUMO

BACKGROUND: The expression and clinical significance of TIP30 and p53 in laryngeal squamous cell carcinoma (LSCC) have not been investigated. METHOD: We determined immunohistochemically the expression of TIP30 and p53 in surgical specimens from 105 patients with LSCC. Survivals were estimated using the Kaplan-Meier method. RESULTS: TIP30 protein expression in LSCC patients was significantly less in tumor tissues than that of adjacent normal tissues (46.7% vs. 79.0%), while p53 protein expression was significantly increased in LSCC (15.2% vs. 63.8%) compared with adjacent normal tissues. The TIP30 expression levels were also significantly correlated with tumor stage, differentiation, and the presence of lymph nodes. The expression of TIP30 was significantly negatively correlated with that of p53 (r = -0.249, P = 0.010). LSCC patients with lower expression level of TIP30 had a significantly higher recurrence and worse overall survival than those with elevated TIP30 expression (P = 0.014 and P = 0.040, respectively). Furthermore, multivariable analysis found that patients with high expression of TIP30 had a greater than approximately 2.2-fold increased risk for death overall or recurrence than those with low expression of TIP30, supporting that down-regulation of TIP30 expression in tumors may involve in development and progression and predict poor prognosis of patients with LSCC. CONCLUSION: Our results may suggest that down-expression of TIP30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of LSCC.

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