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1.
Chirality ; 34(1): 61-69, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34749440

RESUMO

Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by "grafting to" strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3 )8 ) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4 -POSS-(PPI)4 was prepared by the click reaction of POSS-(N3 )8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4 -POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions.


Assuntos
Micelas , Polímeros , Cristalização , Estereoisomerismo , Água
2.
Drug Dev Ind Pharm ; 45(6): 1009-1016, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30950303

RESUMO

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.


Assuntos
Nácar/administração & dosagem , Nanopartículas/administração & dosagem , Pinctada/química , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Fibroblastos , Humanos , Nácar/química , Nanopartículas/química , Tamanho da Partícula , Pós , Coelhos , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/lesões
3.
Yi Chuan ; 41(8): 677-685, 2019 Aug 20.
Artigo em Zh | MEDLINE | ID: mdl-31447419

RESUMO

MicroRNAs (miRNAs) compose a class of non-coding transcripts with a mean length of 22 nucleotides, and play critical roles in regulating gene expression in the process of development, proliferation and differentiation of neurons. Recent genome-wide association studies (GWAS) find most of schizophrenia-associated single nucleotide polymorphisms (SNPs) locating in the non-coding regions, providing functional implications of miRNAs in the development of schizophrenia. In this review, we highlight the interplays between GWAS-SNPs and miRNAs in four perspectives: SNP in miRNA gene; miRNA located in the host gene; SNP located in the miRNA's seed sequence; SNP located in the miRNA's binding site. We also speculate on the future research on the role of miRNA in the development of schizophrenia.


Assuntos
MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Sítios de Ligação , Estudo de Associação Genômica Ampla , Humanos
4.
Yao Xue Xue Bao ; 51(2): 257-63, 2016 02.
Artigo em Zh | MEDLINE | ID: mdl-29856579

RESUMO

Mitochondrion is one of the most vital organelles in cells of human body, and it is involved in many metabolic processes. Mitochondrion dysfunction is closely related to many diseases such as cancers, neurodegenerative diseases, obesity and ischemia reperfusion injury. As a result, mitochondrial drug delivery has gained more and more attention in the drug discovery against these diseases. This review gives a brief introduction to the relationship between mitochondria and human diseases(e.g., cancer), and summarizes the latest trend of mitochondrial targeting drug delivery system(MTDDS).


Assuntos
Sistemas de Liberação de Medicamentos , Mitocôndrias/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Obesidade/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico
5.
Pharmazie ; 70(6): 379-80, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26189298

RESUMO

We investigated the enhancement effect of low-frequency sonophoresis on transdermal permeation of rivastigmine in vitro and in vivo. The in vitro permeation study showed that sonophoresis increased steady-state transdermal flux 0.31 ± 0.03 µg x cm(-2) x h(-1) and the extent of rivastigmine permeation 6.00 ± 0.56 µg x cm(-2) though excised skin (both P < 0.01). In the in vivo experiment, the C(max) 0.83 ± 0.16 µg x mL(-1) and AUC(0 --> 24 h) 12.35 ± 1.99 µg x h x mL(-1) of the sonophoresis group was also significantly higher than that of the control group (both P < 0.01). These data suggest that low-frequency sonophoresis could be an effective method to enhance rivastigmine permeation.


Assuntos
Inibidores da Colinesterase/farmacocinética , Fenilcarbamatos/farmacocinética , Absorção Cutânea/efeitos da radiação , Administração Cutânea , Animais , Cultura em Câmaras de Difusão , Humanos , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , Rivastigmina , Suínos , Ultrassom
6.
Nanomedicine ; 10(1): 215-23, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23792655

RESUMO

This study aims to investigate the efficacy of chitosan nanoparticles (CS-NPs) as a vehicle for transcutaneous antigen delivery in anti-tumor therapy. Ovalbumin (OVA) or gp100 (melanocyte-associated antigen gp100 protein)-loaded CS-sodium tripolyphosphate (TPP)-grafted NPs were prepared by crosslinking low-molecular-weight CS with TPP. Compared with the FITC-OVA solution, the encapsulated fluorescein isothiocyanate (FITC)-OVA-loaded NPs expressed much stronger cellular uptake ability in vitro and higher ability to migrate to lymph nodes in vivo. After transcutaneous administration, OVA-loaded NPs, with imiquimod as an adjuvant, increased the anti-OVA immunoglobulin G titer to levels similar to those induced by the OVA solution. The gp100-loaded NPs promoted the survival of tumor-bearing mice. These results provided evidence of CS-NPs as promising carriers for transcutaneous vaccine delivery, partly contributing to the increased uptake of NPs by skin antigen-presenting cells as well as their enhanced migration to the surrounding lymph nodes. FROM THE CLINICAL EDITOR: In this study the efficacy of chitosan nanoparticle based vehicles for transcutaneous antigen delivery is investigated in anti-tumor therapy. Authors demonstrate that such nanoparticles may be efficient carriers partly due to their increased uptake by antigen-presenting cells in the skin and their enhanced migration to surrounding lymph nodes.


Assuntos
Antígenos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Imunização , Células de Langerhans/efeitos dos fármacos , Animais , Antígenos/química , Antígenos/imunologia , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Células de Langerhans/imunologia , Linfonodos/efeitos dos fármacos , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química
7.
Mol Pharm ; 10(8): 3090-102, 2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-23808658

RESUMO

The success of gene therapy largely relies on a safe and effective gene delivery system. The objective of this study is to design a highly efficient system for the transfection of epidermal stem cells (ESCs) and investigate the transfected ESCs (TESCs) as a therapeutic agent and gene delivery reservoir for wound treatment. As a nonviral vector, ß-cyclodextrin-linked polyethylenimines (CYD-PEI) was synthesized by linking ß-cyclodextrin with polyethylenimines (600 Da). Gelatin scaffold incorporating ß-tricalcium phosphate (ß-TCP) was utilized as a substrate for the culture and transfection of ESCs. With the CYD-PEI/pDNA-VEGF165 polyplexes incorporated gelatin/ß-TCP scaffold based 3D transfection system, prolonged VEGF expression with a higher level was obtained at day 7 in ESCs than those in two-dimensional plates. Topical application of the TESCs significantly accelerated the skin re-epithelization, dermal collagen synthesis, and hair follicle regeneration. It also exhibited a potential in scar inhibition by regulating the distribution of different types of collagen. In contrast to ESCs, an additive capacity in stimulating angiogenesis at the wound site was observed in the TESCs. The present study provides a basis for the TESCs as a promising therapeutic agent and gene delivery reservoir for wound therapy.


Assuntos
Fosfatos de Cálcio/química , Células Epidérmicas , Gelatina/química , Polietilenoimina/química , Células-Tronco/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Cicatrização/efeitos da radiação , beta-Ciclodextrinas/química , Animais , Células Cultivadas , Técnicas de Transferência de Genes , Terapia Genética , Nanopartículas/química , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/fisiologia , Cicatrização/fisiologia
8.
Yao Xue Xue Bao ; 48(5): 746-51, 2013 May.
Artigo em Zh | MEDLINE | ID: mdl-23888700

RESUMO

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.


Assuntos
Sistemas de Liberação de Medicamentos , Estradiol/farmacocinética , Absorção Cutânea , Administração Cutânea , Aerossóis , Animais , Azepinas/química , Varredura Diferencial de Calorimetria , Celulose/análogos & derivados , Celulose/química , Citratos/química , Estradiol/administração & dosagem , Plastificantes/química , Polímeros/química , Suínos
9.
Yao Xue Xue Bao ; 48(8): 1209-20, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24187826

RESUMO

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.


Assuntos
Terapia Genética/métodos , Células-Tronco Mesenquimais/citologia , Neoplasias/terapia , Animais , Movimento Celular/genética , Portadores de Fármacos , Marcação de Genes/métodos , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Neoplasias/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfecção
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 523-9, 2013 Sep.
Artigo em Zh | MEDLINE | ID: mdl-24167133

RESUMO

OBJECTIVE: To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. METHODS: Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. RESULTS: Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/µg protein which had significant difference with control group [(38.54 ± 0.34)ng/µg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/µg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/µg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. CONCLUSION: Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.


Assuntos
Cumarínicos/farmacocinética , Tensoativos/farmacocinética , Tiazóis/farmacocinética , Ânions , Cátions , Emulsões , Endocitose , Células HeLa , Humanos
11.
Biol Pharm Bull ; 35(6): 881-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22687479

RESUMO

Topical delivery of therapeutic agents at the time of injury to accelerate skin repair and prevent the formation of scars during the wound healing process has received increasing attention and represents a novel regenerative and prophylactic strategy for wound treatment. The aim of this study was to invesigate, for the first time, the influence of topical astragaloside IV-releasing hydrogel on the wound repair and regeneration. Using the sodium alginate-gelatin as a hydrogel vehicle, the astragaloside IV was incorporated into the topical carrier and kept releasing with a sustained manner at the wound site. With the rat skin excision model, regulation of the astragaloside IV hydrogel on the wound repair and regeneration were investigated. It was found that the astragaloside IV hydrogel was effective in the skin wound repair, leading to a significant improvement on the wound closure, collagen synthesis and skin tensile strength recovery. Meanwhile, for the first time, that functions of astragaloside IV hydrogel in activating the skin appendages regeneration and increasing the transforming growth factor-ß(1) (TGF-ß(1)) level in serum were shown. Results of this study provided evidence for the alginate-gelatin hydrogel as efficient carrier for the topical delivery of bioactive molecules to the injured site. The astragaloside IV releasing hydrogel was shown a promising therapeutic formulation for wound healing, as well as its regenerative feature and underlying mechanism contribute to the skin regeneration were disclaimed.


Assuntos
Hidrogéis/administração & dosagem , Saponinas/administração & dosagem , Pele/efeitos dos fármacos , Triterpenos/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Tópica , Alginatos/química , Animais , Feminino , Gelatina/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Ratos , Ratos Sprague-Dawley , Pele/lesões , Pele/patologia , Resistência à Tração , Fator de Crescimento Transformador beta/sangue
12.
Gastroenterol Rep (Oxf) ; 10: goac023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686174

RESUMO

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

13.
Pharm Res ; 28(7): 1577-90, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21347566

RESUMO

PURPOSE: To enhance the level and prolong the duration of gene expression for gene-engineered rat mesenchymal stem cells (MSCs) using non-viral vector. METHODS: A novel transfection system based on reverse transfection method and three-dimensional (3D) scaffold was developed. The reverse gene transfection system was evaluated for transfection efficiency compared to conventional methods. Collagen sponge and polyethylene terephthalate non-woven fabric were introduced as scaffolds to perform 3D culture with reverse transfection. pDNA coding TGFß-1 was delivered to MSCs to assess its ability in inducing chondrogenesis with the 3D non-viral reverse transfection system. RESULTS: The reverse transfection method induced higher transgene levels than the conventional transfection in the presence of serum. The electric charge of the anionic gelatin plays an important role in this system by affecting the release pattern of the gene complexes and through the adsorption of serum protein to the substrate. During a long-time in vitro culture, MSCs cultured on 3D scaffolds exhibited a higher transgene expression level and more sustained transgene expression than those cultured and transfected on the two-dimensional substrate. CONCLUSIONS: The combination of reverse transfection system with 3D cell culture scaffold benefits the cell proliferation and long-time gene transfection of MSCs.


Assuntos
DNA , Técnicas de Transferência de Genes , Células-Tronco Mesenquimais , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , DNA/genética , Regulação da Expressão Gênica , Células HeLa , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley
14.
Pharmazie ; 66(2): 130-5, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21434576

RESUMO

The over-expression of P-glycoprotein (P-gp) is associated with the development of multi-drug resistance (MDR) in cancer cells. In this study, we examined whether cationic submicron emulsions (CSEs) can efficiently deliver hydroxycamptothecin (HCPT) into MDR cells (SGC7901/VCR cells) via electrostatic-mediated endocytosis, thus overcoming MDR. We prepared HCPT-CSEs and rhodamine-123-CSEs (RH-123-CSEs), and examined the in vitro cytotoxic activity of HCPT-CSEs and the intracellular accumulation of HCPT and RH-123 in SGC7901/VCR cells. The HCPT-CSEs significantly increased the intracellular accumulation of HCPT (8.2-fold higher than HCPT-injection) and enhanced cytotoxic activity of HCPT (2.7-fold higher than HCPT-injection with verapamil). The fluorescence microscopic and flow cytometric detection on RH-123 supported the intracellular accumulation effect of CSEs. These results indicate CSEs may enhance drug-CSEs internalization followed by releasing their contents into the cytoplasm (near nuclear), thus lowering P-gp-mediated drug efflux. Furthermore, these in vitro results suggest that CSEs are a potentially useful drug delivery system to circumvent P-gp-mediated MDR of tumor cells.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Cátions , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Emulsões , Citometria de Fluxo , Humanos , Microscopia de Fluorescência , Nanopartículas , Tamanho da Partícula
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(4): 408-13, 2011 07.
Artigo em Zh | MEDLINE | ID: mdl-21845755

RESUMO

OBJECTIVE: To compare the differences in antitumor activity between cisplatin (CDDP)-loaded liposomes and nanoparticles in vitro. METHODS: CDDP-gelatin nanoparticles (GPs-Pt) and CDDP-liposomes with similar size, zeta potential, drug loading efficiency and in vitro release property were prepared. The uptake in A549 cells and elimination kinetics were evaluated and antitumor activity was determined by MTT test. The internalization pathways of nanocarriers were studied with inhibitors. RESULTS: Internalization of two nanocarriers was clathrin and actin dependent. Pt accumulation delivered by GPs-Pt was significantly higher than that of liposomes. However, the results of kinetic analysis showed that liposomes had longer cellular retention, and the MRT and AUC were 3 times and twice of GPs-Pt, respectively. The IC(50) of liposomes was significantly lower than GPs-Pt. The values were 2.94±0.21 and 20.70±1.05 µg/ml, respectively. CONCLUSION: Nanocarriers with similar pharmaceutical parameters can induce differences in cellular internalization and elimination, which influence the antitumor activity eventually. Compared with gelatin nanoparticle, liposome is preferable for cisplatin delivery.


Assuntos
Cisplatino/farmacologia , Portadores de Fármacos , Lipossomos , Nanopartículas , Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Humanos , Neoplasias Pulmonares/patologia
16.
Ann N Y Acad Sci ; 1484(1): 74-89, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827446

RESUMO

The long-term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.


Assuntos
Proteínas de Ciclo Celular/genética , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Idoso , Apoptose/genética , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Via de Sinalização Hippo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , Transdução de Sinais/genética , Neoplasias Gástricas/patologia
17.
World J Gastrointest Surg ; 13(5): 429-442, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34122733

RESUMO

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

18.
World J Clin Cases ; 8(19): 4331-4341, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083392

RESUMO

BACKGROUND: Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer. The pathogenesis of ovarian metastasis is incompletely understood, and the treatment options are controversial. Few studies have predicted the risk of ovarian metastasis. It is not clear which type of gastric cancer is more likely to metastasize to the ovary. A prediction model based on risk factors is needed to improve the rate of detection and diagnosis. AIM: To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features. METHODS: A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center, and patients with distant metastasis other than ovary and peritoneum metastasis were excluded. Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression. Independent risk factors were chosen to construct a nomogram which received internal validation. RESULTS: Ovarian metastasis occurred in 83 of 1696 female patients. Univariate analysis showed that age, Lauren type, whether the primary lesion contained signet-ring cells, vascular tumor emboli, T stage, N stage, the expression of estrogen receptor, the expression of progesterone receptor, serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer (all P < 0.05). Multivariate analysis showed that age ≤ 50 years, Lauren typing of non-intestinal, gastric cancer lesions containing signet-ring cell components, N stage > N2, positive expression of estrogen receptor, serum carbohydrate antigen 125 > 35 U/mL, and a neutrophil-to-lymphocyte ratio > 2.16 were independent risk factors (all P < 0.05). The independent risk factors were constructed into a nomogram model using R language software. The consistency index after continuous correction was 0.840 [95% confidence interval: (0.774-0.906)]. After the internal self-sampling (Bootstrap) test, the calibration curve of the model was obtained with an average absolute error of 0.007. The receiver operating characteristic curve of the obtained model was drawn. The area under the curve was 0.867, the maximal Youden index was 0.613, the corresponding sensitivity was 0.794, and the specificity was 0.819. CONCLUSION: The nomogram model performed well in the prediction of ovarian metastasis. Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination, to ensure early detection and treatment.

19.
World J Gastroenterol ; 26(11): 1185-1196, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32231422

RESUMO

BACKGROUND: Prolonged postoperative ileus (PPOI) is a prolonged state of "pathological" gastrointestinal (GI) tract dysmotility. There are relatively few studies examining the influence of preoperative nutritional status on the development of PPOI in patients who underwent GI surgery. The association between preoperative albumin and PPOI has not been fully studied. We hypothesized that preoperative albumin may be an independent indicator of PPOI. AIM: To analyze the role of preoperative albumin in predicting PPOI and to establish a nomogram for clinical risk evaluation. METHODS: Patients were drawn from a prospective hospital registry database of GI surgery. A total of 311 patients diagnosed with gastric or colorectal cancer between June 2016 and March 2017 were included. Potential predictors of PPOI were analyzed by univariate and multivariable logistic regression analyses, and a nomogram for quantifying the presence of PPOI was developed and internally validated. RESULTS: The overall PPOI rate was 21.54%. Advanced tumor stage and postoperative opioid analgesic administration were associated with PPOI. Preoperative albumin was an independent predictor of PPOI, and an optimal cutoff value of 39.15 was statistically calculated. After adjusting multiple variables, per unit or per SD increase in albumin resulted in a significant decrease in the incidence of PPOI of 8% (OR = 0.92, 95%CI: 0.85-1.00, P = 0.046) or 27% (OR = 0.73, 95%CI: 0.54-0.99, P = 0.046), respectively. Patients with a high level of preoperative albumin (≥ 39.15) tended to experience PPOI compared to those with low levels (< 39.15) (OR = 0.43, 95%CI: 0.24-0.78, P = 0.006). A nomogram for predicting PPOI was developed [area under the curve (AUC) = 0.741] and internally validated by bootstrap resampling (AUC = 0.725, 95%CI: 0.663-0.799). CONCLUSION: Preoperative albumin is an independent predictive factor of PPOI in patients who underwent GI surgery. The nomogram provided a model to screen for early indications in the clinical setting.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Íleus/diagnóstico , Nomogramas , Complicações Pós-Operatórias/diagnóstico , Albumina Sérica Humana/análise , Idoso , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Íleus/epidemiologia , Íleus/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Período Pré-Operatório , Valores de Referência , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Fatores de Tempo
20.
Yao Xue Xue Bao ; 44(8): 838-44, 2009 Aug.
Artigo em Zh | MEDLINE | ID: mdl-20055149

RESUMO

Modern drug delivery system demands high therapeutic efficacy and low toxicity which depends on efficient intracellular transportation of therapeutics to specific organisms, cells, even targeted organelles such as cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum. Intracellular barriers which prevent drug molecules accessing to their targets mainly include cell membrane, lysosomal degradation and the endomembrane system. Nanocarriers can preserve the bioactivities of protein, enzyme and DNA, and also they are easy to be modified and functionalized. In this paper, we summarized the intracellular fate of nanocarriers, especially how to bypass intracellular barriers and then target cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum by pharmaceutical modifications.


Assuntos
Portadores de Fármacos , Nanopartículas , Organelas , Animais , Sistemas de Liberação de Medicamentos , Humanos
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