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1.
Mol Cancer ; 21(1): 10, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983537

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC). METHODS: CircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1. RESULTS: CircRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC. CONCLUSION: The upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT.


Assuntos
Transição Epitelial-Mesenquimal , MicroRNAs/genética , Proteínas Nogo/genética , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/metabolismo , RNA Circular , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Interferência de RNA
2.
J Insect Sci ; 22(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35039857

RESUMO

We characterized the mitochondrial genome (mitogenome) and conducted phylogenetic analyses of 48 Hemiptera species by sequencing and analyzing the mitogenome of Arma custos (Fabricius) and Picromerus lewisi (Scott). The complete mitogenomes of the two predators were 16,024 bp and 19,587 bp in length, respectively, and it contained 37 classical genes, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and 22 transfer RNA genes (tRNAs), and a control region. Most PCGs in these predators use ATN as the start codon. This research revealed that the genes of the two natural enemy species have an A + T content of 75.40% and all tRNAs have a typical cloverleaf structure, with the exception of trnS1, which lacks a dihydrouridine arm. This is the first study to compare the mitochondrial genetic structure of two predatory insects; the mitochondrial genetic structure of individual predatory insects has been sequenced in previous studies. Here, phylogenetic analysis on the basis of amino acid and nucleotide sequences of 13 mitochondrial PCGs using Bayesian inference and maximum likelihood methods were conducted to generate similar tree topologies, which suggested that the two predators with close genetic relationships belong to Asopinae subfamily. Furthermore, the monophyly of the Pentatomoidea superfamily is well accepted despite limited taxon and species sampling. Finally, their complete mitogenome provided data to establish a predator-prey food web, which is the foundation of effective pest management. Our results also enhanced the database of natural enemy insects.


Assuntos
Genoma Mitocondrial , Heterópteros , Filogenia , Animais , Teorema de Bayes , Heterópteros/genética , RNA Ribossômico/genética , RNA de Transferência/genética
3.
J Cell Mol Med ; 25(14): 6602-6617, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34075693

RESUMO

N6-methyladenosine (m6A) is a well-known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT-qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down-regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock-down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16-mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.


Assuntos
Proliferação de Células/genética , Ciclina D1/genética , Metiltransferases/genética , Neoplasias Gástricas/genética , Adenosina/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Masculino , Metilação , Camundongos , Pessoa de Meia-Idade , Prognóstico , Estabilidade de RNA/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
4.
Pharmacol Res ; 159: 104984, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502637

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population is estimated at 25 %, and there is currently no effective treatment of NAFLD. Although insulin resistance (IR) is not the only factor causing the pathogenesis of NAFLD, hepatic IR has a cause-effective relationship with NAFLD. Improving hepatic IR is a potential therapeutic strategy to treat NAFLD. This review highlights the molecular mechanisms of hepatic IR in the development of NAFLD. Available data on potential drugs including glucagon-like peptide 1 receptor (GLP-1) agonists, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, farnesoid X receptor (FXR) agonists, etc. are carefully discussed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Gotículas Lipídicas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Anti-Inflamatórios/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Mediadores da Inflamação/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia
5.
Jpn J Clin Oncol ; 49(9): 823-831, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162583

RESUMO

BACKGROUND: Recent findings have shown that inflammation indices are associated with prognosis in various malignancies. However, the usefulness of inflammation indices including platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and prognostic nutritional index for gastrointestinal stromal tumors (GISTs) remains controversial. METHODS: We retrospectively reviewed 340 primary localized GIST patients who had received surgical resection between 2005 and 2015 to investigate the effect of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and prognostic nutritional index on prognosis. 206 patients were selected by propensity score matching to control selection biases. RESULTS: Kaplan-Meier analysis and the log rank test demonstrated that high prognostic nutritional index (≥43.9) was significantly correlated with better recurrence-free survival (RFS) (P<0.001). Among the three inflammatory indices, only preoperative high prognostic nutritional index was an independent prognostic factor for survival [hazard ratio (HR) 0.509; 95% confidence interval (CI) 0.266-0.872; P = 0.031] in multivariate analysis. After propensity score matching, elevated prognostic nutritional index was still a predictor for RFS (HR = 0.498; 95% CI 0.253-0.971; P = 0.042) in the multivariate analyses. In addition, prognostic nutritional index was a significant prognostic factor for GISTs within the National Institutes of Health (NIH) high and very low/low-risk categories. Incorporation prognostic nutritional index into the NIH risk criteria improved the prognostic stratification (c-index, 0.725 vs. 0.686, p = 0.039). CONCLUSIONS: High prognostic nutritional index is a predictor of improved survival for surgically resected GISTs and incorporation prognostic nutritional index into NIH risk criteria improves the predictive accuracy.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Avaliação Nutricional , Pontuação de Propensão , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Humanos , Inflamação , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
6.
Inorg Chem ; 55(6): 3040-6, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26925591

RESUMO

Gadolinium gallium aluminum garnet (GGAG) is a very promising host for the highly efficient luminescence of Ce(3+) and shows potential in radiation detection applications. However, the thermodynamically metastable structure would be slanted against it from getting high transparency. To stabilize the crystal structure of GGAG, Yb(3+) ions were codoped at the Gd(3+) site. It is found that the decomposition of garnet was suppressed and the transparency of GGAG ceramic was evidently improved. Moreover, the photoluminescence of GGAG:Ce(3+),xYb(3+) with different Yb(3+) contents has been investigated. When the Ce(3+) ions were excited under 475 nm, a typical near-infrared region emission of Yb(3+) ions can be observed, where silicon solar cells have the strongest absorption. Basing on the lifetimes of Ce(3+) ions in the GGAG:Ce(3+),xYb(3+) sample, the transfer efficiency from Ce(3+) to Yb(3+) and the theoretical internal quantum efficiency can be calculated and reach up to 86% and 186%, respectively. This would make GGAG:Ce(3+),Yb(3+) a potential attractive downconversion candidate for improving the energy conversion efficiency of crystalline silicon (c-Si) solar cells.

7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(11): 3481-4, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30198251

RESUMO

The measurement system for the detection of soot production as high-temperature pyrolysis of hydrocarbon fuels behind the reflected shock wave was established. By using the laser extinction method, the soot yields of toluene/argon mixtures were measured at high temperatures. The mole fractions of toluene were 0.25% and 0.5% while the pressures were approximate 2 and 4 atm. The temperatures ranged from 1 630 to 2 273 K. The dependence of soot yield on the temperature, pressure and fuel concentration was obtained. With the changes of temperature, the soot yield is a Gauss distribution. The soot yield increases as the pressure or fuel concentration increases. The maximum of soot yield was as high as 55%. The peak temperature of soot yield was not changed dramatically with the pressure. However, it changed from 1 852 to 1 921 K as the concentration of toluene increase from 0.25% to 0.5%. Moreover, we compared the soot yield between toluene and methylcyclohexane at pressure of 4 atm with fuel concertation of 0.5%. During the pyrolysis of methylcyclohexane, the peak temperature of soot yield was 2 045 K, which is about 135 K higher than that of toluene. However, the maximum soot yield of methylcyclohexane is only 1/8 of toluene. This work provides experimental reference for the research of soot particle emission in the engines and the mechanism of soot formation.

8.
Dig Dis Sci ; 59(5): 1017-24, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24318804

RESUMO

BACKGROUND: The aim of this study was to evaluate the impact of pre-existing type-2 diabetes on postoperative recovery and prognosis in gastric cancer (GC) patients who underwent radical gastrectomy. RESEARCH DESIGN AND METHODS: From June 2001 to June 2011, a total of 1,014 eligible patients were enrolled. Among them, 67 patients were diagnosed with type-2 diabetes. The clinicopathologic features and prognostic data were compared between patients with type-2 diabetes (the DM group) and without diabetes (the non-DM group). RESULTS: Median survival was 68.3 months. The 5-year overall survival in the DM group was similar to that in the non-DM group (52.1 vs. 53.0 %, p = 0.411). Propensity score matching analysis demonstrated that the hazard ratio of death in the DM group was 1.191 (95 % confidential index 0.693-2.072; p = 0.531) compared to the-non DM group. Incidence of postoperative complications was higher in the DM group than in the non-DM group (17.9 vs. 8.1 %, p = 0.006). The DM remission rate was 46 % among patients who received Roux-en-Y reconstruction, and 13 % among patients who received Billroth II anastomosis (p = 0.009). The 5-year overall survival rate was 62.1 % for patients with cured or improved DM and 23.4 % for patients with worse or same DM status (p = 0.003). CONCLUSION: Type-2 diabetes can be cured by radical gastrectomy plus Roux-en-Y reconstruction in some GC patients. Pre-existing diabetes is associated with increased postoperative complications and decreased survival when it becomes worse after curative dissection for GC.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Feminino , Derivação Gástrica , Gastroenterostomia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
9.
Chirality ; 26(2): 121-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24420919

RESUMO

A doubly stereocontrolled organocatalytic asymmetric Michael addition to the synthesis of substituted succinimides is described. Starting from aldehydes and maleimides, both enantiomers of the succinimides could be obtained in high to excellent yields (up to 98%) and enantioselectivities (up to 99%) when one of the two special chiral diterpene-derived bifunctional thioureas was individually used as a catalyst. Moreover, these catalysts can be efficiently used in large-scale catalytic synthesis with the same level of yield and enantioselectivity.


Assuntos
Diterpenos/química , Succinimidas/química , Tioureia/química , Catálise , Estrutura Molecular , Estereoisomerismo
10.
Int J Med Sci ; 10(12): 1689-97, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24155657

RESUMO

BACKGROUND AND AIMS: DJ-1 and PTEN have been shown to involve in multiple cell processes and play an important role in cancer development and progression. However, their relationship with gastric carcinoma (GC) has not been identified yet. The purpose of this study is to clarify the relationship of DJ-1 and phosphatase and tensin homolog (PTEN) with clinicopathological parameters and prognosis in GC. METHODS: 114 specimens were collected from GC patients and expression of DJ-1 and PTEN in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, follow-up data of patients, was analyzed statistically. RESULTS: High expression of DJ-1 was found in 66.7% (76/114) and associated with tumor depth (P=0.003), lymph node metastasis (P=0.011), distant metastasis (P=0.001) and advanced clinical stage (P=0.001). Loss or downregulation of PTEN was found in 58.7% (67/114) and associated with advanced clinical stage (P=0.018) and high expression of DJ-1 in tumor cells (P=0.006). In univariate survival analysis, high-expression of DJ-1 or loss of PTEN was significantly associated with poor prognosis of GC patients. However, only tumor depth (P=0.011) and coexistence of DJ-1 and PTEN abnormal expression (P=0.009) emerged as strong independent prognostic factors for overall survival of GC patients. CONCLUSIONS: the present study indicates that DJ-1 and PTEN may play their roles in progression of GC in a cooperating pattern. Co-existence of abnormal DJ-1 and PTEN expression is likely to serve as an independent predictive factor for prognosis of GC patients.


Assuntos
Carcinoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas Oncogênicas/biossíntese , PTEN Fosfo-Hidrolase/biossíntese , Neoplasias Gástricas/genética , Idoso , Carcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Proteínas Oncogênicas/genética , PTEN Fosfo-Hidrolase/genética , Inclusão em Parafina , Prognóstico , Modelos de Riscos Proporcionais , Proteína Desglicase DJ-1 , Neoplasias Gástricas/patologia
11.
Hepatogastroenterology ; 60(127): 1789-96, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24624453

RESUMO

BACKGROUND/AIMS: Effects and indications of no. 12b and 12p nodes dissection for gastric cancer are not determined yet. Here we retrospectively evaluated the effect of no. 12b and 12p nodes dissection for treatment of lower third gastric cancer (LTGC). METHODOLOGY: Between 2001 and 2010, 110 LTGC patients with no. 12b and 12p nodes dissection (SHDL group) and 138 patients without no. 12b and 12p nodes dissection (non-SHDL group) were enrolled in this study. Clinicopathological features and prognostic data were compared between the two groups. RESULTS: The nodal metastatic rate was 8.2% of no. 12b and 10.9% of no. 12p. The 5-year survival rate was 62.9% in the SHDL group and 51.4% in the non-SHDL group (p = 0.16). Multivariate analysis with and without propensity score adjustment showed that SHDL was a significantly prognostic factor. The hazard ratio for death after D2 surgery plus SHDL was 0.457 (95% CI: 0.25 to 0.821; p = 0.0085) compared to D2 surgery alone. More patients in the non-SHDL group had only lymph node recurrence compared to the SHDL group (4.3% vs. 0%, p = 0.035). CONCLUSIONS: Skeletonization of the hepatoduodenal ligament is associated with superior outcomes for LTGC patients especially for those with involved local hepatoduodenal nodes.


Assuntos
Gastrectomia/métodos , Ligamentos/cirurgia , Excisão de Linfonodo/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Ligamentos/patologia , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
Zhonghua Yi Xue Za Zhi ; 93(16): 1214-8, 2013 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-23902610

RESUMO

OBJECTIVE: To screen and collect the familial gastric cancer (FGC) kindreds for exploring its clinicopathological characteristics and prognosis. METHODS: A cross-sectional study was performed among 3640 patients with gastric cancer at 5 hospitals in Guangdong province between 2000 and 2007 and FGC kindreds were diagnosed according to the Amsterdam criteria. Their pedigree features and cancer incidence were analyzed. Clinical characteristics and prognosis were compared between FGC and sporadic gastric cancer (SGC) patients. Survival curves and overall five-year survival rates were established according to the Kaplan-Meier and Log-rank methods. Hazard ratios for death were calculated by Cox regression analysis. RESULTS: A total of 112 FGC kindreds (3.1%) were diagnosed among 3640 gastric cancer patients. In these 112 FGC families, 182 malignant tumors were diagnosed in the first- and second-degree relatives. Gastric cancer (n = 154, 84.6%), esophageal cancer (n = 8, 4.4%) and lung cancer (n = 6, 3.3%) were most common tumors. Tumor types in male proband families did not differ from those in female counterparts (P = 0.644). Most tumors occurred in the first-degree relatives and the ratio of male-to-female was 106:44. The mean age of FGC patients at 54 years was 10 years younger than that of SGC patients. No differences existed in tumor size, tumor location, Borrmann type, pT or pN between the FGC and SGC patients. The overall 5-year survival was 56.0% for FGC patients and 48.8% for SGC patients. Univariable (P = 0.287) and multivariable (HR = 1.101, P = 0.807) analyses demonstrated that FGC was not a significant prognostic factor. CONCLUSIONS: Gastric cancer is the most common cancer in FGC families. The first-degree male relatives are at a high risk of developing gastric cancer. Not particular clinical characteristics but pedigree examination facilitates the diagnosis of FGC.


Assuntos
Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prognóstico , Neoplasias Gástricas/genética , Adulto Jovem
13.
Zhonghua Wai Ke Za Zhi ; 51(5): 447-51, 2013 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-23958170

RESUMO

OBJECTIVE: To evaluate efficacy of adjuvant chemotherapy after D2 dissection on survival for patients with gastric cancer. METHODS: Randomized clinical trials (RCT) that compared adjuvant chemotherapy after D2 dissection with D2 dissection alone for gastric cancer were searched with Pubmed, Cochrane, Embase and CBM databases. Eligible trials published between 1990 and 2012 were included in the study. The quality of RCTs was assessed by the Jadad scale. Data synthesis and statistical analysis were performed by RevMan 5.1 software. RESULT: Eight RCTs with 3633 patients were included in this study. Among them, 1824 patients received adjuvant chemotherapy and 1809 patients didn't. Adjuvant chemotherapy was associated with a significant benefit in terms of overall survival (RR = 0.76, 95% CI: 0.69-0.84), disease free survival (RR = 0.72, 95%CI: 0.66-0.80) and recurrence rate (RR = 0.69, 95% CI: 0.62-0.77). CONCLUSION: Adjuvant chemotherapy was associated with survival benefit for gastric cancer after D2 dissection.


Assuntos
Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Masculino , Recidiva Local de Neoplasia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
14.
Biofabrication ; 15(3)2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36888998

RESUMO

Basic pre-clinical research based on 2D cultures have been very valuable in colorectal cancer (CRC) research but still have failed to improve patient prognostic outcomes. This is because they simply do not replicate what happensin vivo, i.e.2D cultured cells system cannot replicate the diffusion constraints usually found in the body. Importantly, they also do not mimic the dimensionality of the human body and of a CRC tumour (3D). Moreover, 2D cultures lack the cellular heterogeneity and the tumour microenvironment (TME) such as stromal components, blood vessels, fibroblasts, and cells of the immune system. Cells behave differently whether in 2D and 3D, in particular their different genetic and protein expression panels are very different and therefore we cannot fully rely on drug tests done in 2D. A growing field of research based on microphysiological systems involving organoids/spheroids or patient-derived tumour cells has become a solid base for a better understanding of the TME and as a result is a step towards personalized medicine. Furthermore, microfluidic approaches have also started to open possibilities of research, with tumour-on-chips and body-on-chips being used in order to decipher complex inter-organ signalling and the prevalence of metastasis, as well as CRC early-diagnosis through liquid biopsies. Herein, we focus on the state-of-the-art of CRC research with emphasis on 3D microfluidicin vitrocultures-organoids, spheroids-drug resistance, circulating tumour cells and microbiome-on-a-chip technology.


Assuntos
Neoplasias Colorretais , Sistemas Microfisiológicos , Humanos , Esferoides Celulares , Organoides , Fibroblastos , Microambiente Tumoral
15.
Biofabrication ; 15(4)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37699408

RESUMO

Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more 'organs' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.


Assuntos
Trato Gastrointestinal , Sistemas Microfisiológicos , Estados Unidos , Humanos , Estômago , Fígado , Organoides
16.
Front Oncol ; 13: 1003977, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816974

RESUMO

Background: Although the overall global incidence of gastric cancer has been declining, the number of new cases in people under the age of 50 is increasing, which is related to metastasis, late pathological stages, and poor prognosis. There is a scarcity of large-scale studies to evaluate and predict distant metastasis in patients with early-onset gastric cancer. Methods: From January 2010 to December 2019, data on early-onset GC patients undergoing surgery were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the independent risk factors for distant metastasis in patients with early-onset gastric cancer. Based on these risk factors, we developed a nomogram to predict distant metastasis. The model underwent internal validation on the test set and external validation on 205 patients from the First Affiliated Hospital of Sun Yat-sen University and the seventh Affiliated Hospital of Sun Yat-sen University. The novel nomogram model was then evaluated using the receiver operating characteristic (ROC) curve, calibration, the area under the curve (AUC), and decision curve analysis (DCA). The training set nomogram score was used to classify the different risk clusters of distant metastasis. Results: Our study enrolled 2217 patients after establishing the inclusion and exclusion criteria, with 1873 having no distant metastasis and 344 having distant metastasis. The tumor size, total lymph nodes, whether or not receiving radiotherapy and chemotherapy, T stage, and N stage were significant predictors of advanced distant metastasis (p < 0.05). The AUC of the ROC analysis demonstrated our model's high accuracy. Simultaneously, the prediction model shows high stability and clinical practicability in the calibration curve and DCA analysis. Conclusions: We developed an innovative nomogram containing clinical and pathological characteristics to predict distant metastasis in patients younger than 50 years old with gastric cancer. The tool can alert clinicians about distant metastasis and help them develop more effective clinical treatment plans.

17.
J Cancer Res Clin Oncol ; 149(7): 2743-2756, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35776198

RESUMO

PURPOSE: Nicotinamide adenine dinucleotide (NAD+) is closely related to the pathogenesis of tumors. However, the effect of NAD+ metabolism of gastric cancer (GC) cells on immune cells remains unexplained. We targeted nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD+ synthesis salvage pathway, to observe its effect in the immune microenvironment. METHODS: NAMPT of GC cell lines was inhibited by using the small molecule inhibitor (FK866) and short hairpin RNA (shRNA). CCK-8 test and flow cytometry were performed to detect cell viability and apoptosis. Immunofluorescence was used to observe changes in mitochondrial membrane potential (MMP).The transfected GC cells (AGS) and patient-derived organoids (PDOs) were cocultured with activated PBMCs, followed by flow cytometric analysis (FCA) for cytokines and inhibitory marker. The level of NAD and ATP of GC cells (AGS & MKN45) was tested combined with NMN and CD39 inhibitor. RESULTS: Targeting NAD+ by FK866 obviously reduced MMP, which ultimately inhibited proliferation and increased the apoptosis of GC cells. NAMPT silencing reduced intracellular NAD and ATP,further decreased extracellular adenosine. Meawhile, the cytokines of CD8+T cells were significantly increased after cocultured with transfected AGS, and the expression of PD-1 was distinctly decreased. NMN reversed the effect of shNAMPT and enhanced the immunosuppression. Consistent results were obtained by coculturing PBMCs with PDOs. CONCLUSION: Restraining the function of NAMPT resulted in the functional improvement of effector CD8+ T cells by decreasing extracellular adenosine levels and inducing apoptosis of GC cells simultaneously. Therefore, this study demonstrates that NAMPT can be an effective target for gastric cancer immunotherapy.


Assuntos
NAD , Neoplasias Gástricas , Humanos , NAD/metabolismo , Adenosina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral , Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Trifosfato de Adenosina/metabolismo , Linfócitos T CD8-Positivos/metabolismo
18.
Cancer Sci ; 103(1): 73-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22017425

RESUMO

Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor.


Assuntos
Ilhas de CpG/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/genética , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori/genética , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Fenótipo , Prognóstico , RNA Neoplásico , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Fator Natriurético Atrial/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/virologia , Taxa de Sobrevida , Fatores de Transcrição/genética
19.
Zhonghua Yi Xue Za Zhi ; 92(16): 1112-5, 2012 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-22781770

RESUMO

OBJECTIVE: To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection. METHODS: Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into fast-track group (n = 35) and conventional care group (n = 35). The clinical parameters and markers of humeral immune function were evaluated in both groups postoperatively. RESULTS: Sixty-two patients finally completed the study, including 32 in the fast-track group and 30 in the conventional care group. There was a significantly faster recovery of postoperative humoral immunity: blood levels of globulin (24.1 ± 2.4 vs 22.1 ± 3.3 g/L, P = 0.025), immunoglobulin G (10.79 ± 2.39 vs 8.66 ± 2.09 g/L, P = 0.007) and complement 4 (0.24 ± 0.09 vs 0.17 ± 0.05 g/L, P = 0.035) at Day 3 postoperation were higher in the fast-track group than in the conventional care group. And there was also a significantly shorter length of postoperative stay (6.0 ± 1.0 vs 11.7 ± 3.8 d, P < 0.001) in patients undergoing fast-track rehabilitation. CONCLUSION: Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.


Assuntos
Neoplasias Colorretais/imunologia , Imunidade Humoral , Idoso , Formação de Anticorpos/imunologia , Neoplasias Colorretais/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Resultado do Tratamento
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(5): 1166-9, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22827046

RESUMO

Using an intensified spectroscopic detector CCD and a heated shock tube, transient emission spectra of n-decane in the combustion reaction were measured in a spectral range of 200-850 nm. Experiments were conducted at temperatures of 1100-1600 K, a pressure of 2.0 atm, an initial fuel mole fraction of 1.0% and an equivalence ratio of 1.0. Results show that the main emission bands are attributed to OH, CH and C2 radicals produced during the combustion process of n-decane. Emission intensities of the three radicals reached their maximums only after 5 micros from the onset of their ignitions. After about 30 micros had passed, the band of OH radical was still observed, but the bands of CH and C2 radicals almost disappeared. Time histories of spectral emission intensities represent the time histories of concentrations of the three radicals during the process of combustion The emission peak ratio of OH (306.4 nm)/CH(431.4 nm) is approximately 27/100 in the combustion of n-decane, which is much greater than the corresponding ratio of about 7/100 in the combustion of n-heptane. This result reveals that the two fuels have different reaction mechanisms. High resolution characteristic spectra of CH and C2 were also acquired in the present experiment, the spectra show the rotational structures of the bands clearly. Current results are valuable for understanding the property and validating the mechanism of n-decane combustion reaction

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