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1.
Eur J Nucl Med Mol Imaging ; 50(4): 1228-1239, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36477400

RESUMO

BACKGROUND: Recently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours. METHODS: This is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi'an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60-90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded. RESULTS: Physiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management. CONCLUSION: [99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases.


Assuntos
Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Sistema Digestório , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
2.
Med Sci Monit ; 25: 7209-7217, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553714

RESUMO

BACKGROUND Hepatocellular carcinoma (HCC) is a commonly occurring liver malignancy. Its prognosis remains unsatisfactory. Accumulating evidence has revealed that exosomal microRNAs (miRNAs) act as biomarkers and play crucial roles in the advancement of HCC. The current study explored the biological role and fundamental mechanism of exosomal miR-744 in HCC. MATERIAL AND METHODS The serum exosomes of HCC patients were isolated by differential ultracentrifugation. MiR-744 expression in HCC tissues, cell lines and serum exosomes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU (5-ethynyl-2'-deoxyuridine) assay and Cell Counting Kit-8 (CCK-8) assay were conducted to show the impacts of miR-744 or exosomal miR-744 on proliferation and sorafenib resistance in HepG2 cells. The target of miR-744 was ascertained by regulating the level of miR-744 in HepG2 cells. RESULTS MiR-744 is downregulated in HCC tissues and cell lines as well as in exosomes derived from patient serum and HepG2 cells. Additionally, downregulated miR-744 promotes HepG2 cell proliferation and inhibits the chemosensitivity of HepG2 cells to sorafenib. PAX2 was identified as the functional target of miR-744. Interestingly, miR-744 is decreased in exosomes derived from sorafenib-resistant HepG2 cells. Furthermore, when treated with the miR-744-enriched exosomes, the proliferation of HepG2 cells was significantly suppressed, and the sorafenib resistance was reduced. CONCLUSIONS MiR-744 has an imperative role in the propagation and chemoresistance of HCC. Serum exosomal miR-744 might act as a biomarker of HCC, and exosomal miR-744 might offer an innovative strategy for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Fator de Transcrição PAX2/genética , Sorafenibe/farmacologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Exossomos/metabolismo , Exossomos/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Fator de Transcrição PAX2/metabolismo , Prognóstico
3.
Surg Innov ; 24(6): 582-589, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28933252

RESUMO

BACKGROUND: The technical feasibility and oncological safety of laparoscopic surgery for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm has not been adequately studied. Therefore, we performed this retrospective study to investigate the clinical outcomes of gastric GIST patients treated with laparoscopic surgery compared with those who underwent open surgery. METHODS: We retrospectively evaluated the outcomes of 48 consecutive patients who underwent gastric resection for gastric GISTs larger than 5 cm. The patients were divided into 2 groups based on the surgery performed: the laparoscopic resection group (LAPG) and the open resection group (OG). We assessed all available patient data, including baseline information, tumor characteristics, surgical outcomes, pathological results, postoperative complications, and long-term patient survival. RESULTS: The 2 groups had similar baseline data. No differences were found in tumor size, location, mitotic count, and risk grade according to Fletcher's risk classification. The LAPG was superior to the OG in blood loss, time to first flatus, time to oral intake, and length of postoperative hospital stay. Perioperative complications, recurrence rate, and long-term survival, however, did not differ significantly between the groups. The mean operation time in the LAPG was 28 minutes longer than that in the OG. CONCLUSIONS: In patients with primary gastric GISTs larger than 5 cm, laparoscopic resection is a technically feasible and oncologically safe surgery when performed by experienced surgeons.


Assuntos
Gastrectomia , Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
4.
Tumour Biol ; 37(9): 12141-12151, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27220320

RESUMO

MicroRNAs have been documented playing key roles in cancer development and progression. Here, we investigate the role of miR-125b in gastric cancer metastasis. We found that the expression of miR-125b was up-regulated in gastric cancer tissue specimens compared with their corresponding nontumorous tissues, and the up-regulated miR-125b level was significantly associated with TNM stage and lymph node-metastasis. Overexpression of miR-125b promoted gastric cancer cell migration and invasion in vitro and metastasis in vivo. STARD13 and NEU1 were identified as direct target genes of miR-125b by luciferase assays, and they were involved in the cell migration and invasion regulated by miR-125b in gastric cancer. Taken together, miR-125b functions as an oncogene in gastric cancer and represents a new potential therapeutic target for gastric cancer.


Assuntos
MicroRNAs/fisiologia , Neuraminidase/genética , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética , Adulto , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Proteínas Ativadoras de GTPase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias
5.
Zhonghua Wai Ke Za Zhi ; 52(6): 442-5, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25219560

RESUMO

OBJECTIVE: To study radiation-enhancing effects on human gastric cancer MKN28 cell line and underlying mechanisms of ß-elemene. METHODS: Inhibition of MKN28 cell proliferation at different concentrations of ß-elemene was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC50 value and choice of 20% of the IC50 as the experimental drug concentration. Irradiation group and ß-elemene+irradiation group were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Draw the survival curve and get the radiobiological parameters D0, Dq, SF2, N and SER. Flow cytometry (FCM) was used to detect changes in the cell cycle and cell apoptosis rates was detected by Annexin-V/PI assay. RESULTS: ß-elemene exerted inhibitory effects on proliferation of gastric cancer MKN28 cells, with an IC50 of 45.6 mg/L and we chose 8 mg/L as the experimental concentration. The cell survival fraction of MKN28 cells with irradiation decreased significantly after treated with ß-elemene; D0, Dq decreased, SER = 1.3. After combined treatment of ß-elemene+irradiation, the results of FCM showed that cells could be arrested in the G2/M phase and the cell apoptosis increased significantly. CONCLUSIONS: ß-elemene can enhance the radiosensitivity of gastric cancer MKN28 cell line. Mechanistically, ß-elemene mainly influences the cell cycle distribution of MKN28 cells by inducing G2/M phase arrest, inhibits the repair of sublethal damage and induces cell apoptosis to enhance the killing effects of radioactive rays.


Assuntos
Tolerância a Radiação/efeitos dos fármacos , Sesquiterpenos/farmacologia , Neoplasias Gástricas/patologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos
6.
Mater Today Bio ; 24: 100915, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38188648

RESUMO

Objective: Abdominal wall hernias are common abdominal diseases, and effective hernia repair is challenging. In clinical practice, synthetic meshes are widely applied for repairing abdominal wall hernias. However, postoperative complications, such as inflammation and adhesion, are prevalent. Although biological meshes can solve this problem to a certain extent, they face the problems of heterogeneity, rapid degradation rate, ordinary mechanical properties, and high-cost. Here, a novel electrospinning mesh composed of polylactic acid and silk fibroin (PLA-SF) for repairing abdominal wall hernias was manufactured with good physical properties, biocompatibility and low production cost. Materials and methods: FTIR and EDS were used to demonstrate that the PLA-SF mesh was successfully synthesized. The physicochemical properties of PLA-SF were detected by swelling experiments and in vitro degradation experiments. The water contact angle reflected the hydrophilicity, and the stress‒strain curve reflected the mechanical properties. A rat abdominal wall hernia model was established to observe degradation, adhesion, and inflammation in vivo. In vitro cell mesh culture experiments were used to detect cytocompatibility and search for affected biochemical pathways. Results: The PLA-SF mesh was successfully synthesized and did not swell or degrade over time in vitro. It had a high hydrophilicity and strength. The PLA-SF mesh significantly reduced abdominal inflammation and inhibited adhesion formation in rat models. The in vitro degradation rate of the PLA-SF mesh was slower than that of tissue remodeling. Coculture experiments suggested that the PLA-SF mesh reduced the expression of inflammatory factors secreted by fibroblasts and promoted fibroblast proliferation through the TGF-ß1/Smad pathway. Conclusion: The PLA-SF mesh had excellent physicochemical properties and biocompatibility, promoted hernia repair of the rat abdominal wall, and reduced postoperative inflammation and adhesion. It is a promising mesh and has potential for clinical application.

7.
Eur J Pharmacol ; 964: 176272, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38110140

RESUMO

BACKGROUND: Postoperative abdominal adhesion (PAA) is a common postoperative complication. Clinically, various methods have been used to prevent the occurrence of PAA, such as drugs and physiotherapy; however, no satisfactory results have been obtained. Luteolin (LUT) is a natural flavonoid that reduces inflammation and acts as an antioxidant. This research aimed to examine the impact and mechanism of LUT in reducing PAA. METHODS: C57/BL6 mice were used in vivo experiments. PAA model was established using a brush friction method. Visual scoring and hematoxylin and eosin staining were used to score the severity of adhesions. Network pharmacology was used to infer potential targets and core pathways of LUT. Hydrogen peroxide (H2O2) was used to induce oxidative stress in vitro, while the reactive oxygen species (ROS) assay kit was used to evaluate oxidative stress levels. Western blotting, cell immunofluorescence, and multiple immunofluorescence assays were used to detect α-SMA, vimentin, E-cadherin, collagen I, or AKT phosphorylation level. Scratch assay was used to detect cell migration. RESULTS: LUT reduced the degree of PAA in mice. It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells. Network pharmacology analysis showed that LUT likely exerted anti-adhesion activity by regulating the PI3K-Akt signaling pathway. Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells. LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression. CONCLUSION: LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA. To this end, LUT has potential in PAA therapy.


Assuntos
Luteolina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Caderinas/metabolismo , Colágeno , Peróxido de Hidrogênio/farmacologia , Luteolina/farmacologia , Luteolina/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vimentina/metabolismo
8.
Int J Med Robot ; : e2584, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37792998

RESUMO

OBJECTIVE: To evaluate the feasibility and application value of mixed reality technology (MR) in Primary retroperitoneal tumour (PRT) surgery. METHODS: From 276 patients who underwent PRT resection at the First Affiliated Hospital of Xi'an Jiaotong University, we screened 46 patients who underwent MR-assisted retroperitoneal tumour resection and 46 patients who underwent tumour resection without MR assistance. The intraoperative and postoperative recovery of the patients in both groups were compared, and the reliability and validity of the application of MR were further examined using the Likert scale. RESULTS: There was a significant difference in the mean intraoperative bleeding volume between the two groups, but it was reduced in the MR group. The results of the Likert scale showed higher scores in the MR group than non-MR group. CONCLUSIONS: MR can be used to assist PRT resection and has great potential to improve the rate of complete retroperitoneal tumour resection.

9.
Front Oncol ; 13: 1175151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293593

RESUMO

Purpose: Silent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD). Materials and methods: Human immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism. Results: SGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. Conclusion: The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.

10.
Dig Liver Dis ; 54(7): 896-904, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34987010

RESUMO

BACKGROUND: Gastric cancer (GC) is a common malignant tumor of the digestive system. Increasing reports have demonstrated the crucial roles of circRNAs in tumorigenesis and progression of GC. METHODS: The relative expression of circ-ABCB10 in GC tissues and cell lines was detected by qRT-PCR. A series of in vitro assays and a xenograft model in vivo were applied to explore the function of circ-ABCB10 in GC cells. RESULTS: Circ-ABCB10 expression was upregulated in GC tissues and cell lines and positively correlated with poor survival of GC patients. Circ-ABCB10 downregulation decreased cell viability, inhibited cell growth, invasion, and migration, while promoted cell apoptosis of GC cell lines SGC-7901 and MKN-48. Circ-ABCB10 could upregulate Rac1 expression by directly sponging miR-1915-3p. Rescue experiments revealed that miR-1915-3p inhibitor obviously reversed the inhibitory effect of si-circ-ABCB10, and Rac1 overexpression obviously reversed the inhibitory effect of miR-1915-3p mimics on cell growth, invasion, migration, apoptosis, and cell cycle progression. Moreover, si-circ-ABCB10 effectively inhibited tumor growth in a xenograft model. CONCLUSIONS: Our study revealed that circ-ABCB10 promoted GC progression via targeting the miR-1915-3p/Rac1 axis, and circ-ABCB10 might be a potential target for GC diagnosis and treatment.


Assuntos
Transportadores de Cassetes de Ligação de ATP , MicroRNAs , RNA Circular , Neoplasias Gástricas , Proteínas rac1 de Ligação ao GTP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Gástricas/patologia , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
11.
Cancer Manag Res ; 13: 4191-4201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079372

RESUMO

BACKGROUND: Inflammation and nutrition play vital roles in the development of gastric cancer (GC). We combined the preoperative fibrinogen with prognostic nutritional index (PNI) to create a novel scoring system named as the fibrinogen and prognostic nutritional index (FPNI) score and establish a more effective model. PATIENTS AND METHODS: A total of 689 patients with gastric adenocarcinoma who underwent gastrectomy from January 2012 to December 2016 were reviewed. We measured correlations between FPNI score and clinicopathological variables and overall survival (OS). A nomogram predicting OS was constructed. Its predictive performance was verified using the concordance index, calibration curves, receiver operating characteristic curves, decision curve analysis and time-dependent receiver operating characteristic analysis. RESULTS: We observed that the FPNI score was an independent predictor of OS in patients with gastric cancer (P < 0.05). A high FPNI score was significantly related to older age at surgery, tumor size ≥4.6 cm, high ASA score, advanced TNM stage and poor outcome (both P < 0.05). And the FPNI score remained an independent indicator at various TNM stages (P < 0.05). Ultimately, the nomogram based on FPNI score, age, tumor size, histological grade and TNM stage showed a better predictive ability than TNM alone. CONCLUSION: The preoperative FPNI score is a novel, simple, and effective predictor of OS in patients with GC. Furthermore, the nomogram involving FPNI score will help clinicians to optimize individualized treatment plans.

12.
Sci Rep ; 11(1): 10301, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986408

RESUMO

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.


Assuntos
Fibrinogênio/metabolismo , Inflamação/patologia , Nomogramas , Neoplasias Gástricas/patologia , Humanos , Neoplasias Gástricas/sangue , Análise de Sobrevida
13.
Drug Des Devel Ther ; 12: 639-645, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636598

RESUMO

PURPOSE: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a ß-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. METHODS: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting. RESULTS: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups. CONCLUSION: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2.


Assuntos
Propranolol/uso terapêutico , Radiossensibilizantes/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Propranolol/administração & dosagem , Radiossensibilizantes/administração & dosagem , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
14.
Oncol Rep ; 40(6): 3561-3572, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272296

RESUMO

In the present study, we investigated whether miRNA­300 (miR­300) is an oncogene in human liver cancer and sought to determine the mechanism underlying its activity. We also investigated the effect of miRNA­300 on the growth in liver cancer. To identify its target molecule, we performed luciferase assays. The downstream signaling pathway was detected by immunohistochemical (IHC) analysis in human HCC tissues, and the protein levels of AKT, 4E­BP1, S6K1, SNAIL and MMP2 were determined using western blotting. miR­300 levels were higher in patients with high­stage HCC, and miR­300 promoted cell growth both in vitro and in vivo. miRNA­300 inhibited the luciferase activity of FOXO1 by targeting its 3'­untranslated region (UTR), and overexpression of miR­300 upregulated the protein levels of phospho­AKT, phospho­4E­BP1, phospho­S6K1, SNAIL and MMP2. These data revealed that miRNA­300 functions as an oncogene in liver cancer by inhibiting FOXO1 and interacting with the AKT/mTOR signaling pathway.


Assuntos
Carcinoma Hepatocelular/patologia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Regulação para Cima , Regiões 3' não Traduzidas , Adulto , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Transdução de Sinais
15.
Oncol Rep ; 40(6): 3625-3634, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272362

RESUMO

Recently, long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been recognized to function as an oncogene in several human tumors, and FOXD2­AS1 dysregulation has been closely associated with carcinogenesis and tumor progression. Nevertheless, the correlation between the aberrant expression of FOXD2­AS1 and the prognosis of hepatocellular carcinoma (HCC) has not yet been elucidated. In the present study, FOXD2­AS1 was found to be overexpressed in HCC tissues, and FOXD2­AS1 overexpression resulted in significantly shortened patient survival. FOXD2­AS1 overexpression enhanced the viability and metastasis of HCC cells in vitro and in vivo, as revealed by MTT, wound healing and cell migration assays. In addition, mechanistic studies revealed that FOXD2­AS1 upregulated the expression of the miR­206 target gene annexin A2 (ANXA2) by acting as a miR­206 sponge. In summary, FOXD2­AS1 was concluded to function as an oncogene in HCC and to upregulate ANXA2 expression in part by 'sponging' miR­206.


Assuntos
Anexina A2/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Regulação para Cima , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Prognóstico , Análise de Sobrevida
16.
Medicine (Baltimore) ; 97(17): e0568, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29703047

RESUMO

Improved prediction of prognosis for primary gastrointestinal stromal tumors (GISTs) after curative resection is an important goal in clinical practice. Coagulation factor of fibrinogen may inform prognosis of tumor patients as blood-based biomarker. Here, we aimed to analyze the prognostic value of fibrinogen levels in patients with GIST and to explore potential threshold of fibrinogen on postoperative clinical outcome.A retrospective study was performed including data from 91 patients with newly diagnosed GISTs who underwent curative resection. Patients were followed-up for a median period of 2 years. Cox regression and competing risk analysis were applied to study the association between fibrinogen and risk of death or recurrence. Smoothing plot and threshold effect analysis were applied to learn the relationship further and explore potential threshold.High levels of fibrinogen are associated with decreased overall survival (OS) and recurrence free survival (RFS) in patients with GISTs. We discovered a nonlinear relationship between levels of fibrinogen and the risk of death or recurrence. Further, we detected a threshold for fibrinogen (3.7 g/L) on the prognosis of GISTs patients. When fibrinogen was above the inflection point, the increase in fibrinogen levels was strongly associated with increase in the risk of death or recurrence.Elevated fibrinogen can serve as an independent prognostic biomarker for a worse clinical outcome in GIST patients.


Assuntos
Fibrinogênio/análise , Neoplasias Gastrointestinais/sangue , Tumores do Estroma Gastrointestinal/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco
17.
J Laparoendosc Adv Surg Tech A ; 26(8): 614-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27128311

RESUMO

BACKGROUND: Postoperative urinary dysfunction after total mesorectal excision (TME) is lessened by preservation of the autonomic nerves, but in T4 rectal tumors such injury often cannot be prevented. This retrospective study evaluated the recovery of urinary function of patients with injury to a single pelvic autonomic nerve subsequent to laparoscopic TME, relative to patients without nerve damage. METHODS: Patients with T4 rectal cancer who underwent laparoscopic TME were divided according to the presence of a single pelvic autonomic nerve injury (37 cases) or no injury to autonomic nerves (54 cases; control). Urinary function was evaluated before surgery and at 1 and 6 months after surgery based on catheter indwelling time, urodynamics, International Prostate Symptom Score (IPSS; men only), and Urogenital Distress Inventory (UDI-6) score (women). RESULTS: One month after surgery in the injured and control groups, the postoperative catheter indwelling time was 6.2 ± 2.0 and 1.9 ± 1.2 days, respectively; the maximal urinary flow rates were 16.6 ± 5.8 and 19.7 ± 5.5 mL/s; the voided volumes were 181.6 ± 65.9 and 211.7 ± 63.2 mL; and the residual volumes were 15.0 ± 8.5 and 10.8 ± 8.0 mL. However, at the 6-month follow-up, all urodynamic parameters of the two groups were statistically similar and indicated recovery, and the IPSS and UDI-6 scores were also not statistically different. CONCLUSION: Damage to a single pelvic autonomic nerve during laparoscopic TME does not lead to long-term urinary dysfunction.


Assuntos
Vias Autônomas/lesões , Laparoscopia/efeitos adversos , Sintomas do Trato Urinário Inferior/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Neoplasias Retais/cirurgia , Urodinâmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora , Feminino , Seguimentos , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo
18.
Medicine (Baltimore) ; 95(32): e4362, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27512848

RESUMO

BACKGROUND: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. METHODS: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi'an Jiaotong University from 1998 to 2014 were analyzed retrospectively. RESULTS: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. CONCLUSIONS: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage.


Assuntos
Hérnia Diafragmática Traumática/etiologia , Hérnia Diafragmática Traumática/fisiopatologia , Herniorrafia/métodos , Tomografia Computadorizada Multidetectores/métodos , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/terapia , Adulto , Diagnóstico Tardio/prevenção & controle , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Traumatismos Torácicos/complicações , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/terapia , Fatores de Tempo , Resultado do Tratamento
19.
Dis Markers ; 2016: 6869415, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28070138

RESUMO

Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients' samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC.


Assuntos
Autofagia , Biomarcadores Tumorais/metabolismo , Sirtuína 1/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Biomarcadores Tumorais/genética , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Masculino , Pessoa de Meia-Idade , Sirtuína 1/genética , Neoplasias Gástricas/patologia
20.
Oncol Rep ; 35(6): 3577-85, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27108607

RESUMO

A long non-coding RNA named HOTTIP (HOXA transcript at the distal tip) coordinates the activation of various 5' HOXA genes which encode master regulators of development through targeting the WDR5/MLL complex. HOTTIP acts as an oncogene in several types of cancers, whereas its biological function in gastric cancer has never been studied. In the present study, we investigated the role of HOTTIP in gastric cancer. We found that HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. Moreover, downregulation of HOTTIP led to decreased expression of homeobox protein Hox-A13 (HOXA13) in gastric cancer cell lines. HOXA13 was involved in HOTTIP­induced malignant phenotypes of gastric cancer cells. Our data showed that the levels of HOTTIP and HOXA13 were both markedly upregulated in gastric cancer tissues compared with their counterparts in non-tumorous tissues. Furthermore, the expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. Spearman analyses indicated that HOTTIP and HOXA13 had a highly positive correlation both in non-tumor mucosae and cancer lesions. Collectively, these findings suggest that HOTTIP and HOXA13 play important roles in gastric cancer progression and provide a new insight into therapeutic treatment for the disease.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Homeodomínio/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/biossíntese , Humanos , Metástase Linfática/genética , Invasividade Neoplásica/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Regulação para Cima
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