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1.
Front Oncol ; 12: 830420, 2022.
Article in English | MEDLINE | ID: mdl-35356223

ABSTRACT

Disorders of miR-484 expression are observed in cancer, different diseases or pathological states. There is accumulating evidence that miR-484 plays an essential role in the development as well as the regression of different diseases, and miR-484 has been reported as a key regulator of common cancer and non-cancer diseases. The miR-484 targets that have effects on inflammation, apoptosis and mitochondrial function include SMAD7, Fis1, YAP1 and BCL2L13. For cancer, identified targets include VEGFB, VEGFR2, MAP2, MMP14, HNF1A, TUSC5 and KLF12. The effects of miR-484 on these targets have been documented separately. Moreover, miR-484 is typically described as an oncosuppressor, but this claim is simplistic and one-sided. This review will combine relevant basic and clinical studies to find that miR-484 promotes tumorigenesis and metastasis in liver, prostate and lung tissues. It will provide a basis for the possible mechanisms of miR-484 in early tumor diagnosis, prognosis determination, disease assessment, and as a potential therapeutic target for tumors.

3.
Article in English | MEDLINE | ID: mdl-32587849

ABSTRACT

As a gene therapy strategy, RNA interference (RNAi) offers tremendous tumor therapy potential. However, its therapeutic efficacy is restricted by its inferior ability for targeted delivery and cellular uptake of small interfering RNA (siRNA). This study sought to develop a dual-ligand nanoparticle (NP) system loaded with siRNA to promote targeted delivery and therapeutic efficacy. We synthesized a dual receptor-targeted chitosan nanosystem (GCGA), whose target function was controlled by the ligands of galactose of lactobionic acid (LA) and glycyrrhetinic acid (GA). By loading siPAK1, an siRNA targeting P21-activated kinase 1 (PAK1), a molecular-targeted therapeutic dual-ligand NP (GCGA-siPAK1) was established. We investigated the synergistic effect of these two targeting units in hepatocellular carcinoma (HCC). In particular, GCGA-siPAK1 enhanced the NP targeting ability and promoted siPAK1 cell uptake. Subsequently, dramatic decreases in cell proliferation, invasion, and migration, with an apparent increase in cell apoptosis, were observed in treated cells. Furthermore, this dual-ligand NP gene delivery system demonstrated significant anti-tumor effects in tumor-bearing mice. Finally, we illuminated the molecular mechanism, whereby GCGA-siPAK1 promotes endogenous cell apoptosis through the PAK1/MEK/ERK pathway. Thus, the dual-target property effectively promotes the HCC therapeutic effect and provides a promising gene therapy strategy for clinical applications.

4.
Biochem Biophys Res Commun ; 526(1): 98-104, 2020 05 21.
Article in English | MEDLINE | ID: mdl-32197838

ABSTRACT

Photodynamic therapy (PDT) is an effective oncotherapy and has been approved for clinical application. Unfortunately, its therapeutic efficacy is usually overshadowed by tumor angiogenesis. Thus, a detailed understanding of the tumor angiogenesis upon PDT is imperative. This study aimed to investigate the potential contribution and mechanism of P-21-activated kinase 1 (PAK1) in PDT-induced tumor angiogenesis. Firstly, we found that PAK1 was upregulated upon PDT and associated with tumor angiogenesis. Then, we elucidated the underlying molecular mechanism. Activation of PAK1 prevents hypoxia-inducible factor 1 alpha (HIF-1α) protein from ubiquitin-mediated degradation. Thereafter, HIF-1α accumulation results in the upregulation of vascular endothelial growth factor (VEGF), thus promoting tumor angiogenesis. More importantly, we determined that PAK1 knockdown effectually repressed tumor angiogenesis, which contributes to enhance the therapeutic effect of PDT. Together, PAK1 is a potential novel pharmaceutical target for inhibiting PDT-induced tumor angiogenesis, and PAK1 suppression in combination with PDT may be a potentially effective strategy for anti-tumor therapy.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/metabolism , Photochemotherapy/adverse effects , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , p21-Activated Kinases/metabolism , Cell Line, Tumor , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Ubiquitination
5.
J Huazhong Univ Sci Technolog Med Sci ; 37(1): 44-50, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28224425

ABSTRACT

Fluorescence intraoperative cholangiography (IOC) is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green (ICG). However, the dynamic process and mechanism of fluorescence IOC have not been elucidated in previous publications. Herein, the optical properties of the complex of ICG and bile, dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated. The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration. Extrahepatic bile ducts could fluoresce 2 min after intravenous injection, and the fluorescence intensity reached a peak at 8 min. In addition, biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum. Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein. Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells, excretion of ICG into the bile and then its interaction with protein molecules in the bile. Moreover, fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models. All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.


Subject(s)
Bile Duct Diseases/diagnostic imaging , Bile Ducts, Extrahepatic/injuries , Cholangiography/methods , Fluorescent Dyes/administration & dosage , Indocyanine Green/administration & dosage , Animals , Bile Duct Diseases/etiology , Bile Ducts, Extrahepatic/diagnostic imaging , Bile Ducts, Extrahepatic/surgery , Cholecystectomy, Laparoscopic/adverse effects , Disease Models, Animal , Iatrogenic Disease , Injections, Intravenous , Intraoperative Period , Rats , Signal-To-Noise Ratio
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-238401

ABSTRACT

Fluorescence intraoperative cholangiography (IOC) is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green (ICG).However,the dynamic process and mechanism of fluorescenceIOC have not been elucidated in previous publications.Herein,the optical properties of the complex of ICG and bile,dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated.The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration.Extrahepatic bile ducts could fluoresce 2 min after intravenous injection,and the fluorescence intensity reached a peak at 8 min.Inaddition,biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum.Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein.Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells,excretion of ICG into the bile and then its interaction with protein molecules in the bile.Moreover,fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models.All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.

7.
J Huazhong Univ Sci Technolog Med Sci ; 36(6): 859-864, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27924511

ABSTRACT

Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.


Subject(s)
Fluid Therapy/adverse effects , Hepatectomy/adverse effects , Pleural Effusion/epidemiology , Postoperative Complications/epidemiology , Rehydration Solutions/adverse effects , Adult , Aged , Female , Hepatectomy/methods , Humans , Male , Middle Aged , Operative Time , Pleural Effusion/etiology , Postoperative Complications/etiology , Rehydration Solutions/administration & dosage
8.
J Cancer Res Clin Oncol ; 140(7): 1159-70, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24752339

ABSTRACT

PURPOSE: To assess the beneficial and harmful effects of transarterial embolization (TAE) or transarterial chemoembolization (TACE) for curative resection of hepatocellular carcinoma (HCC). METHODS: The authors conducted an extensive search of studies on this strategy. All randomized controlled trials comparing TACE or TAE plus operation versus operation only were considered for inclusion, regardless of blinding, language, or publication status. Results were performed with disease-free survival (DFS) and overall survival (OS) as the primary endpoint. Tumor response and adverse events were secondary endpoints. RESULTS: A total of 10 studies involving 909 HCC participants finally fulfilled the predefined inclusion criteria. Four trials assessed preoperative TACE versus control and six trials assessed postoperative TACE versus control. There were significant improvements for DFS [HR 0.62 (95 % CI 0.49-0.79)] and OS [HR 0.60 (0.46-0.79)] in the postoperative TACE compared with the control when the mean tumor size was bigger than 5 cm. However, preoperative TACE did not improve DFS [HR 0.92 (0.71-1.20)] and OS [HR 1.07 (0.78-1.46)] for curative resection of HCC. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. Fever (26.7-85.9 %), abdominal pain (19.3-71.2 %), and nausea/vomiting (27.4-66.3 %) were common adverse events. Relatively rare but more serious complications were also reported. CONCLUSIONS: Postoperative TACE offers potential benefits for curative resection of HCC when the mean tumor size is bigger than 5 cm.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/adverse effects , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/methods , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Humans , Liver Neoplasms/mortality , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic/statistics & numerical data , Survival Analysis
9.
Hepatol Res ; 44(3): 259-69, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23607290

ABSTRACT

AIM: Available published work on the benefit of adjuvant antiviral therapy after curative treatment of hepatocellular carcinoma (HCC) reports controversial results. The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. METHODS: We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event outcomes with 95% confidence intervals using RevMan 5. RESULTS: We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group compared with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. CONCLUSION: Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed.

10.
Front Med China ; 4(4): 457-62, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21191748

ABSTRACT

This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1(st), 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval = 1.10-1.46), and the Z-score for overall effect was 13.83 (P<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval = 0.411-5.264) and Z-score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.


Subject(s)
Bile Duct Neoplasms/blood , Bile Duct Neoplasms/mortality , Bile Ducts, Intrahepatic , CA-19-9 Antigen/blood , Cholangiocarcinoma/blood , Cholangiocarcinoma/mortality , Bile Duct Neoplasms/surgery , Cholangiocarcinoma/surgery , Humans , Prognosis , Risk , Treatment Outcome
11.
Biochem Biophys Res Commun ; 383(2): 206-9, 2009 May 29.
Article in English | MEDLINE | ID: mdl-19348785

ABSTRACT

Congenital long QT syndrome is a cardiac disorder characterized by prolongation of QT interval on the surface ECG associated with syncopal attacks and a high risk of sudden death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of long QT syndrome (LQT1). We previously identified a hot spot mutation G314S located within the pore region of the KCNQ1 ion channel in a Chinese family with long QT syndrome. In the present study, we used oocyte expression of the KCNQ1 polypeptide to study the effects of the G314S mutation on channel properties. The results of electrophysiological studies indicate G314S, co-expressed with KCNE1 was unable to assemble to form active channel. G314S, co-expressed with WT KCNQ1 and KCNE1, suppressed I(ks) currents in a dominant-negative manner, which is consistent with long QT syndrome in the members of the Chinese family carrying G314S KCNQ1 mutation.


Subject(s)
Genes, Dominant , KCNQ1 Potassium Channel/genetics , KCNQ1 Potassium Channel/metabolism , Long QT Syndrome/genetics , Long QT Syndrome/physiopathology , Action Potentials/genetics , Amino Acid Sequence , Animals , Electrophysiological Phenomena , Glycine/genetics , Glycine/metabolism , Humans , Molecular Sequence Data , Mutation, Missense , Oocytes , Serine/genetics , Serine/metabolism , Xenopus
12.
Biochem Biophys Res Commun ; 380(1): 127-31, 2009 Feb 27.
Article in English | MEDLINE | ID: mdl-19167356

ABSTRACT

Congenital long QT syndrome is characterized by a prolongation of ventricular repolarization and recurrent episodes of life-threatening ventricular tachyarrhythmias, often leading to sudden death. We previously identified a missense mutation F275S located within the S5 transmembrane domain of the KCNQ1 ion channel in a Chinese family with long QT syndrome. We used oocyte expression of the KCNQ1 polypeptide to study the effects of the F275S mutation on channel properties. Expression of the F275 mutant, or co-expression with the wild-type S275 polypeptide, significantly decreased channel current amplitudes. Moreover, the F275S substitution decreased the rates of channel activation and deactivation. In transfected HEK293 cells fluorescence microscopy revealed that the F275S mutation perturbed the subcelluar localization of the ion channel. These results indicate that the F275S KCNQ1 mutation leads to impaired polypeptide trafficking that in turn leads to reduction of channel ion currents and altered gating kinetics.


Subject(s)
Endoplasmic Reticulum/metabolism , Long QT Syndrome/metabolism , Animals , Cell Line , Humans , KCNQ1 Potassium Channel/genetics , KCNQ1 Potassium Channel/metabolism , Long QT Syndrome/genetics , Mutation, Missense , Phenylalanine/genetics , Phenylalanine/metabolism , Protein Transport/genetics , Serine/genetics , Serine/metabolism
13.
Zhonghua Zhong Liu Za Zhi ; 29(4): 249-52, 2007 Apr.
Article in Chinese | MEDLINE | ID: mdl-17760248

ABSTRACT

OBJECTIVE: To explore the eukaryotic expression of arresten in CHO cells and to investigate its basic biological activities. METHODS: CHO cells were divided into three groups: transfected pSecTag-arresten group, transfected pSecTag group and control group without transfection. PSecTag-arresten was transfected into CHO cells by Lipofectamine 2000 method. The arresten mRNA in CHO cells was assayed by RT-PCR. The protein expression of arresten gene was examined by Western-Blot. The cells expressing arresten were screened out by Zeocin. The effect of arresten on huvec cell migration and anchoring to three-dimensional vascular structures was measured. RESULTS: The result of RT-PCR and Western-blot showed that arresten gene has been successfully transfected into CHO cells and expressed in those cells. Arrssten inhibited huvec cell migration and anchoring to three-dimensional vascular structures. CONCLUSION: CHO cells expressing arresten have been obtained successfully. Arresten can inhibit huvec cell migration and anchoring to three-dimensional vascular structures, indicating that it might be one of its anti-angiogenetic approaches.


Subject(s)
Angiogenesis Inhibitors/biosynthesis , Angiogenesis Inhibitors/pharmacology , Cell Movement/drug effects , Collagen Type IV/biosynthesis , Endothelial Cells/drug effects , Angiogenesis Inhibitors/genetics , Animals , Blotting, Western , CHO Cells , Cell Line , Cells, Cultured , Collagen Type IV/genetics , Collagen Type IV/pharmacology , Cricetinae , Cricetulus , Endothelial Cells/cytology , Endothelial Cells/physiology , Humans , Neovascularization, Physiologic/drug effects , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Transfection
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