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1.
World J Gastrointest Endosc ; 15(10): 614-622, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37900113

RESUMO

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

2.
World J Gastrointest Surg ; 15(4): 712-722, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37206074

RESUMO

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

4.
Cancer Treat Res Commun ; 32: 100536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35567912

RESUMO

BACKGROUND: Intestinal Fusobacterium nucleatum (F. nucleatum) infection has been implicated into the progression of colorectal cancer (CRC). However, F. nucleatum as a biomarker in 5-fluorouracil (5-FU) resistance of CRC has not been fully analyzed by comparing with other types of gut microbiota. In order to further reduce the random error and bias of individual research, this meta­analysis aimed to compare the diagnostic performance of intestinal Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli in 5-FU resistance to colorectal cancer and provide evidence­based data to clinical practice. METHODS: Comprehensive searches of PubMed, Embase, Cochrane Library and Web of Science databases were conducted. A total of 11 studies were selected according to the preestablished inclusion and exclusion criteria and analyzed by Review Manager 5.4 software, which included mapping of forest plots, heterogeneity tests, meta­regression, sensitivity analysis and publication bias. RESULTS: Overall sensitivity and specificity of F. nucleatum detection in 5-FU resistance of CRC were 0.65 (95% CI:0.60-0.69) and 0.70 (95% CI:0.59-0.87), respectively. Its positive likelihood ratio (PLR) and negative likelihood ratio (NLR) in detecting colorectal cancer were 2.57 (95% CI:1.47-3.21) and 0.52 (95% CI:0.43-0.63). The diagnostic odds ratio (DOR) was 4.92 (95% CI:2.23-7.33), which significantly exceeds the performance of B. fragilis (DOR: 0.53, 95% CI:0.31-0.82) and E. coli (DOR: 0.63, 95% CI: 0.57-0.76) for indicating 5-FU resistance of CRC. CONCLUSION: Compared with intestinal B. fragilis and intestinal E. coli, intestinal F. nucleatum is more reflective of 5-FU resistance to colorectal cancer.


Assuntos
Neoplasias Colorretais , Fusobacterium nucleatum , Bacteroides fragilis , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Escherichia coli , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos
5.
Transl Vis Sci Technol ; 10(14): 23, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34932116

RESUMO

Purpose: Drug delivery to posterior ocular tissues via topical eye drop administration is arduous due to the unique anatomy and physiology of the eye. Therefore, treatments for posterior eye disease have to be administered via intravitreal injection or systemic route, both of which have their drawbacks. Herein, the objective of this work was to demonstrate that a specially designed eye drop formulation could effectively deliver small-molecule vascular endothelial growth factor (VEGF) inhibitor to posterior ocular tissues for antiangiogenic therapy. Methods: The unique eye drop formulation, termed ITRI AXN eye drops, was obtained from self-assembly of (2-hydroxypropyl)-ß-cyclodextrin with a VEGF tyrosine kinase inhibitor, a hydrophilic polymer, hypromellose, and a complex stabilizer, caffeine. In vivo ocular pharmacokinetics studies were performed with New Zealand White (NZW) rabbits and Non Human Primates (NHP). The antiangiogenesis effect was evaluated on the Long-Evans rat with laser-induced choroidal neovascularization and pigmented Dutch-Belted rabbits with VEGF-induced retinal neovascularization. Results: The successful drug transport from ocular surface to posterior ocular cavity was indicated by a drug biodistribution pattern in pharmacokinetic studies. Excellent drug exposure in the choroid and retina with the concentrations of 900- and 750-fold greater than drug IC50 0.5 hours post the eye drop administration (drug level: 0.8%) was observed on the NHP study. The obtained formulation also demonstrated a comparable antiangiogenic outcome with the intravitreal injection of anti-VEGF antibody on rat and rabbit disease models. Conclusions: Our eye drop formulation has demonstrated great promise in antiangiogenic therapy against retinal and choroidal neovascularization in animal models. The results suggest that the aim of this work can be successfully achieved by the novel eye drop formulation. Translational Relevance: The preclinical results provide evidence that ITRI AXN eye drops could effectively deliver therapeutics to the choroid and retina for antiangiogenic therapy.


Assuntos
Degeneração Macular , Fator A de Crescimento do Endotélio Vascular , Animais , Corioide , Degeneração Macular/tratamento farmacológico , Soluções Oftálmicas , Coelhos , Ratos , Ratos Long-Evans , Distribuição Tecidual
6.
Oncogene ; 39(29): 5214-5227, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32546724

RESUMO

Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD (p < 0.001). Then the regulatory mechanism was explored in CRC models of villin-SphK2 Tg mice, SphK2-/-mice, and human CRC cells xenografted nude mice. Assays of ChIP-Seq and luciferase reporter gene demonstrated that high SphK2 upregulated DPD through promoting the HDAC1-mediated H3K56ac, leading to the degradation of intracellular 5-FU into inactive α-fluoro-ß-alanine (FBAL). Lastly, inhibition of SphK2 by SLR080811 exhibited excellent inhibition on DPD expression and potently reversed 5-FU resistance in colorectal tumors of villin-SphK2 Tg mice. Overall, this study manifests that SphK2high conferred 5-FU resistance through upregulating tumoral DPD, which highlights the strategies of blocking SphK2 to overcome 5-FU resistance in CRC.


Assuntos
Neoplasias Colorretais/genética , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/uso terapêutico , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Humanos , Camundongos , Regulação para Cima
7.
World J Gastroenterol ; 25(40): 6107-6115, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686766

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been widely used in pediatric patients with cholangiopancreatic diseases. AIM: To evaluate the efficacy, safety, and long-term follow-up results of ERCP in symptomatic pancreaticobiliary maljunction (PBM). METHODS: A multicenter, retrospective study was conducted on 75 pediatric patients who were diagnosed with PBM and underwent therapeutic ERCP at three endoscopy centers between January 2008 and March 2019. They were divided into four PBM groups based on the fluoroscopy in ERCP. Their clinical characteristics, specific ERCP procedures, adverse events, and long-term follow-up results were retrospectively reviewed. RESULTS: Totally, 112 ERCPs were performed on the 75 children with symptomatic PBM. Clinical manifestations included abdominal pain (62/75, 82.7%), vomiting (35/75, 46.7%), acholic stool (4/75, 5.3%), fever (3/75, 4.0%), acute pancreatitis (47/75, 62.7%), hyperbilirubinemia (13/75, 17.3%), and elevated liver enzymes (22/75, 29.3%). ERCP interventions included endoscopic sphincterotomy, endoscopic retrograde biliary or pancreatic drainage, stone extraction, etc. Procedure-related complications were observed in 12 patients and included post-ERCP pancreatitis (9/75, 12.0%), gastrointestinal bleeding (1/75, 1.3%), and infection (2/75, 2.7%). During a mean follow-up period of 46 mo (range: 2 to 134 mo), ERCP therapy alleviated the biliary obstruction and reduced the incidence of pancreatitis. The overall effective rate of ERCP therapy was 82.4%; seven patients (9.3%) were lost to follow-up, eight (11.8%) re-experienced pancreatitis, and eleven (16.2%) underwent radical surgery, known as prophylactic excision of the extrahepatic bile duct and hepaticojejunostomy. CONCLUSION: ERCP is a safe and effective treatment option to relieve biliary or pancreatic obstruction in symptomatic PBM, with the characteristics of minor trauma, fewer complications, and repeatability.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Má Junção Pancreaticobiliar/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Ductos Biliares/anormalidades , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Fluoroscopia , Seguimentos , Humanos , Lactente , Masculino , Ductos Pancreáticos/anormalidades , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/cirurgia , Má Junção Pancreaticobiliar/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Cell Death Differ ; 26(11): 2179-2193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30770877

RESUMO

It was found in this study that long intergenic non-protein coding RNA 346 (LINC00346) was an lncRNA aberrantly expressed in gastric cancer (GC) based on multiple Gene Expression Omnibus (GEO) databases of GC cohorts. The LINC00346 gene was recurrently amplified and upregulated in GC, and its expression was positively correlated with poor pathologic stage, large tumor size, and poor prognosis. In addition, the oncogenic transcription factors KLF5 and MYC could bind to the LINC00346 promoter and enhance its expression. Gene Set Enrichment Analysis (GSEA) in the GEO datasets revealed that cell cycle and focal adhesion genes were enriched in patients with high LINC00346 expression. In vitro and in vivo assays of LINC00346 alterations revealed a complex integrated phenotype affecting cell growth, migration and invasion. Strikingly, high-throughput sequencing analysis after LINC00346 alterations highlighted alterations in cell cycle and focal adhesion pathways in GC cells. Mechanistically, argonaute 2 (Ago2) was recruited by LINC00346, which functioned as a molecular sponge for miR-34a-5p by antagonizing its ability to repress CD44, NOTCH1, and AXL protein translation. Taken together, our findings support a model in which the KLF5, MYC/LINC00346/miR-34a-5p cross-talk served as critical effectors in GC tumorigenesis and progression, suggesting a new therapeutic direction in the treatment of GC.


Assuntos
Transformação Celular Neoplásica/genética , Fatores de Transcrição Kruppel-Like/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Proteínas Argonautas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Receptores de Hialuronatos/antagonistas & inibidores , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor Notch1/antagonistas & inibidores , Neoplasias Gástricas/patologia , Receptor Tirosina Quinase Axl
9.
Acta Biomater ; 86: 280-290, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616077

RESUMO

Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies. STATEMENT OF SIGNIFICANCE: Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstrated that a trastuzumab-loaded hydrogel possessed the ability of controlled release of trastuzumab and maintained antitumor efficacy same as that of trastuzumab. These results implied that a γ-PGA-MA and 4-arm PEG-SH-based hydrogel has great potential in serving as a carrier for the local or systemic delivery of therapeutic proteins or antibodies.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Reagentes de Ligações Cruzadas/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Injeções , Trastuzumab/administração & dosagem , Trastuzumab/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Feminino , Humanos , Maleimidas/síntese química , Maleimidas/química , Camundongos SCID , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/síntese química , Ácido Poliglutâmico/química , Ratos Sprague-Dawley , Reologia , Trastuzumab/química , Trastuzumab/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Int Immunopharmacol ; 65: 284-294, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30342345

RESUMO

Geniposide (GE) is an active component isolated from the fruit of Gardenia jasminoides Ellis that has anti-inflammatory and other pharmacological effects; however, the underlying mechanism of GE action has not been elucidated in rheumatoid arthritis (RA). Previous studies have shown that GE plays a therapeutic role in RA via regulation of the integrin beta 1 (Itgß1)-mediated Ras-Erk1/2 signalling pathway. However, the specific mechanism of GE action on Itgß1 has not been clarified. Recent evidence indicates that microRNAs (miRNAs) are involved in the development of RA. In this study, we developed a miRNA-124a-based synoviocyte repair strategy. We demonstrated that miRNA-124a can directly inhibit the expression of the Itgß1 gene and decrease TNF-α-stimulated cell proliferation in vitro. MH7A cells were obtained from the patient with RA and treated with GE in the presence of TNF-α (10 ng/mL). Additionally, we demonstrated that the expression of miRNA-124a can be regulated by GE. GE upregulated the expression of miRNA-124a and decreased the expression of Itgß1 at the mRNA and protein levels. The results of the present study are the first to suggest that GE inhibits TNF-α-stimulated cell proliferation and blocks the activation of the Ras-Erk1/2 pathway via the upregulation of miRNA-124a expression. Our study elucidates the role of miRNA-124a as a protected miRNA in RA and may provide a novel strategy for the diagnosis and treatment of RA in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/fisiologia , Iridoides/farmacologia , MicroRNAs/genética , Sinoviócitos/fisiologia , Linhagem Celular , Proliferação de Células , Gardenia/imunologia , Regulação da Expressão Gênica , Humanos , Integrina beta1/metabolismo , Sistema de Sinalização das MAP Quinases , Proteína Oncogênica p21(ras)/metabolismo , Fator de Necrose Tumoral alfa/imunologia
11.
Oncogene ; 37(36): 5020-5036, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29789713

RESUMO

Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression. Loss of FOXD2-AS1 function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1 expression promoted cancer progression. The enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins were found to serve as binding partners of FOXD2-AS1 and mediators of FOXD2-AS1 function. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis.


Assuntos
Carcinogênese/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histona Desmetilases/genética , RNA Longo não Codificante/genética , Receptor EphB3/genética , Neoplasias Gástricas/genética , Regulação para Cima/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Epigênese Genética/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/genética , Neoplasias Gástricas/patologia
12.
Mol Med Rep ; 16(5): 6467-6471, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901436

RESUMO

It is widely reported that long non­coding RNAs (lncRNAs) are involved in regulating cell differentiation, proliferation, apoptosis and other biological processes. Certain lncRNAs have been found to be crucial in various types of tumor. Taurine­upregulated gene 1 (TUG1) has been shown to be expressed in a tissue­specific pattern and exert oncogenic or tumor suppressive functions in different types of cancer in humans. According to previous studies, TUG1 is predominantly located in the nucleus and may regulate gene expression at the transcriptional level. It mediates chromosomal remodeling and coordinates with polycomb repressive complex 2 (PRC2) to regulate gene expression. Although the mechanisms of how TUG1 affects the tumor genesis process remain to be fully elucidated, increasing studies have suggested that TUG1 offers potential as a diagnostic and prognostic biomarker, and as a therapeutic target in certain types of tumor. This review aims to summarize current evidence concerning the characteristics, mechanisms and associations with cancer of TUG1.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias/genética , Complexo Repressor Polycomb 2/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Proliferação de Células , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/mortalidade , Neoplasias/patologia , Especificidade de Órgãos , Complexo Repressor Polycomb 2/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Análise de Sobrevida , Transcrição Gênica
13.
Cell Death Dis ; 8(6): e2837, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28569791

RESUMO

Recent evidence indicates that E2F1 transcription factor have pivotal roles in the regulation of cellular processes, and is found to be dysregulated in a variety of cancers. Long non-coding RNAs (lncRNAs) are also reported to exert important effect on tumorigenesis. E2F1 is aberrantly expressed in gastric cancer (GC), and biology functions of E2F1 in GC are controversial. The biological characteristics of E2F1 and correlation between E2F1 and lncRNAs in GC remain to be found. In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis. Forced E2F1 expression promotes proliferation, whereas loss of E2F1 function decreased cell proliferation by blocking of cell cycle in GC cells. Mechanistic analyses indicated that E2F1 accelerates GC growth partly through induces TINCR transcription. TINCR could bind to STAU1 (staufen1) protein, and influence CDKN2B mRNA stability and expression, thereby affecting the proliferation of GC cells. Together, our findings suggest that E2F1/TINCR/STAU1/CDKN2B signaling axis contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.


Assuntos
Adenocarcinoma/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Proteínas do Citoesqueleto/genética , Fator de Transcrição E2F1/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Fator de Transcrição E2F1/metabolismo , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Prognóstico , Ligação Proteica , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Transcrição Gênica
14.
Phytother Res ; 31(8): 1249-1256, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28631356

RESUMO

Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague-Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Levels of interleukin-2 (IL-2), IL-4, and transforming growth factor-ß1 were tested by ELISA. The expression of ß2-AR, GRK2, and ß-arrestin-1 and ß-arrestin-2 was detected by western blot. Geniposide was found to relieve the secondary hind paw swelling and arthritis scores, along with attenuating histopathologic changes and decreasing IL-2 and increasing IL-4, transforming growth factor-ß1 in mesenteric lymph node (MLN) lymphocytes of AA rats. In addition, GE in vivo increased the expression of ß2-AR and decreased the expression of GRK2, ß-arrestin-1 and ß-arrestin-2, and level of cyclic adenosine monophosphate of MLN lymphocytes in AA rats. From these results, we can infer that GE on immune tolerance effects, ß2-AR desensitization, and ß2-AR-AC-cyclic adenosine monophosphate transmembrane signal transduction of MLN lymphocytes plays crucial roles in antiinflammatory and immunoregulatory pathogeneses of RA. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Tolerância Imunológica/efeitos dos fármacos , Iridoides/farmacologia , Linfócitos/efeitos dos fármacos , Animais , Artrite Reumatoide , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Gardenia/química , Interleucina-2/imunologia , Interleucina-4/imunologia , Linfonodos/citologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/imunologia , beta-Arrestina 1/metabolismo , beta-Arrestina 2/metabolismo
15.
Zhonghua Zhong Liu Za Zhi ; 34(10): 725-9, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23291063

RESUMO

OBJECTIVE: To explore the transgenic efficiency of non-viral vector Tf-PEG-PEI and the cell specific silencing effect of plasmid pPSMAe/p-shNS-ploy(A) on prostate cancer cells. METHODS: Polyethyleneimine (PEI) was modified by using polyethylene glycol and transferrin to synthesize the non-viral vector Tf-PEG-PEI. NS-specific plasmids pPSMAe/p-shNS-ploy(A) and Tf-PEG-PEI were used to transfect prostate cancer LNCap and PC-3 cells. The changes of cell morphology, proliferation ability and cell cycle were studied after down-regulating the NS gene level. RESULTS: Tf-PEG-PEI was successfully modified. After transfection, the PSMA-expressing LNCaP cells became larger and showed more pseudopodia, having a tendency to differentiate. Their cell proliferation ability was reduced, and the detection of cell cycle showed a decrease of S phase and an increase of G(1) phase after knocking down NS gene. These targets were not changed in non-PSMA-expresing PC-3 cells. CONCLUSIONS: The non-viral vector Tf-PEG-PEI has a high ability to transfer targeted gene into target cells. The cellular specificity of short-hairpin RNA transcription driven by PSMAe/p is confirmed by silencing NS gene. The use of cell specific promoter may be an effective strategy of gene therapy for prostate cancer.


Assuntos
Antígenos de Superfície/genética , Proliferação de Células , Proteínas de Ligação ao GTP/genética , Glutamato Carboxipeptidase II/genética , Proteínas Nucleares/genética , Neoplasias da Próstata/patologia , Interferência de RNA , Antígenos de Superfície/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/metabolismo , Vetores Genéticos , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Proteínas Nucleares/metabolismo , Plasmídeos , Polietilenoglicóis , Polietilenoimina/análogos & derivados , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transfecção , Transferrina/genética
16.
Water Res ; 40(12): 2249-58, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16790260

RESUMO

Photocatalytic processes using TiO(2) as a catalyst have attracted extensive attention for decomposition of organic contaminants. The determination of optimum reactor design and operational conditions are the major concerns for the development and potential application of the photocatalytic process. Various photoreactor types, photocatalyst arrangements, light sources, and operation conditions were reported. This study was focused on the application of the ultraviolet light emitting diode (UV-LED) as the UV light source for the photocatalytic decomposition of Reactive Red 22 (RR 22). The temporal behavior of the photocatalytic decomposition of RR 22 in aqueous solution by the UV-LED/TiO(2) with a rectangular planar fixed-film reactor operated in a recirculation mode was studied under various conditions including initial dye concentration, periodic illumination, light intensity, and arrangements of TiO(2) coating. The decomposition of RR 22 in aqueous solution by TiO(2) photocatalytic processes with the UV-LED was found to be technically feasible with a high TiO(2) coated weight (1.135g) and low pH value (pH 2). A Langmuir-Hinshelwood-type kinetic equation was adequate for modeling the photocatalytic decomposition of RR 22 by the UV-LED/TiO(2) photocatalytic processes. The experimental results indicated that the photonic efficiency with periodic illumination was much higher than those with continuous illumination. The photonic efficiencies with the quartz-liquid-catalyst (QLC) arrangement were higher than those with the quartz-catalyst-liquid (QCL) arrangement for experiments conducted at lower applied light intensity; however, the photonic efficiencies for these two arrangements were nearly identical for experiments conducted at higher light intensities.


Assuntos
Corantes/metabolismo , Fotoquímica , Triazinas/metabolismo , Triazinas/efeitos da radiação , Raios Ultravioleta , Água/metabolismo , Catálise , Concentração de Íons de Hidrogênio , Titânio/farmacologia , Purificação da Água
17.
Anticancer Drugs ; 14(10): 825-8, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14597877

RESUMO

It has been reported that arsenic trioxide (As2O3) is an apoptosis inducer and radiation sensitizer for various cancer cell lines. In this study of breast cancer patients, we examined the combined effect of topical As2O3 and radiation therapy on fungating and/or skin-infiltrating lesions of breast cancer. The dermatological, gastrointestinal, hematological, renal and hepatic toxicities of the treatment were also monitored. As2O3 gel (0.05%) was applied to tumor lesions 1 h prior to delivery of each fraction, with the gel removed about 5 min before the irradiation. Superficial radiation was delivered using an electron beam from a linear accelerator. Every week, the tumor lesions were photographed to evaluate effectiveness, and blood was sampled to monitor changes in hemogram and biochemical profile. Seven breast cancer patients with cutaneous metastasis were enrolled in this study. In terms of tumor, the rates for complete, partial response and stable disease were 42.9 (three of seven), 42.9 (three of seven) and 14.3% (one of seven), respectively. The skin pain, assessed by a visual analog scale, and secretion from all of the seven superficial and fungating wounds decreased markedly after treatment. Significant bone marrow suppression or granulocytosis was not noted. Further, changes in renal and hepatic function were also not significant. It seems reasonable to conclude that As2O3 may be an effective and safe radiosensitizer for palliative radiotherapy for skin-infiltrating lesions of breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Neoplasias da Mama/patologia , Óxidos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Trióxido de Arsênio , Arsenicais/efeitos adversos , Terapia Combinada , Feminino , Géis , Humanos , Pessoa de Meia-Idade , Óxidos/efeitos adversos , Projetos Piloto , Neoplasias Cutâneas/secundário
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