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APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis and literature review
Liang, TJ;Wang, HX;Zheng, YY;Cao, YQ;Wu, XY;Zhou, X;Dong, SX
ONCOTARGET 2017年 8卷28期 页码:46468-46479 影响因子:5.008
CPG-ISLAND HYPERMETHYLATION; TUMOR-RELATED GENES; PROMOTER METHYLATION; MICROSATELLITE INSTABILITY; CHROMOSOMAL ALTERATIONS; MOLECULAR-GENETICS; EPIGENETIC CHANGES; DNA METHYLATION; COLON CANCERS; MUTATIONS
Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently observed in colorectal cancer (CRC). The association between APC promoter methylation and clinicopathological significance in CRC is under investigation. We performed a meta-analysis to quantitatively evaluate the significance of APC methylation in CRC. The study included a total of 24 articles and 2025 CRC patients. The frequency of APC promoter hypermethylation was significantly higher in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45-13.56; p<0.0001, I-2=0%. APC promoter more frequently hypermethylated in CRC stage I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20; p<0.0001, I-2=31%. The risk of incidence of CRC was significantly correlated to APC promoter hypermethylation, pooled OR was 9.80, 95% CI, 6.07-15.81; p<0.00001, I-2=43%. APC methylation was not associated with grade, stage of CRC as well as tumor location, patients' gender, and smoking behavior. The results indicate that APC promoter hypermethylation is an early event in carcinogenesis of CRC, could be a valuable diagnostic marker for early-stage CRC. APC methylation is not significantly associated with overall survival in patients with CRC. APC is a potential drug target for development of personalized treatment.
P-glycoprotein expression in ulcerative colitis patients and its role in intestinal barrier
Ma, MZ;Chen, Y;Li, L;Liang, TJ;Zhu, Q;Yang, CM
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017年 10卷4期 页码:4552-4558
INFLAMMATORY-BOWEL-DISEASE; GENE-EXPRESSION; MDR1; CYTOKINES; DIGOXIN; ARTICLE; BRAIN; LIVER
Aims: Efflux transporters such as P-glycoprotein (Pgp; MDR1/ABCB1) protect the enterocytes from potentially toxic substances. The aim of this study was to evaluate Pgp expression in inflamed mucosa of patients with active Ulcerative Colitis (UC), and to compare the results of Pgp expression with healthy subjects. We also explored the relationship between Pgp expression and the pathogenesis of UC in this study. Methods: Pgp expression was determined with real-time PCR (SYBR GREEN), immunohistochemistry (IHC-SP method) and Western blot in inflamed mucosa of newly diagnosed (n = 102) patients with UC. Expression levels of Pgp expression were compared with control subjects (n = 31). The serum endotoxin and D-lactic acid levels of newly diagnosed UC patients and control subjects were detected by ELISA and ultraviolet spectrophotometer respectively. Results: Compared with control subjects, Pgp expression was significantly reduced in inflamed mucosa of newly diagnosed patients with UC. MDR1 (Multi-Drug Resistance 1) expression depicts a similar pattern. Pgp expression was found elevated in intestinal mucosa of UC patients after two months' treatment with prednisone. The serum endotoxin and D-lactic acid levels in UC patients before and after prednisone treatment were negatively relevant with Pgp expression level. Conclusions: Compared with healthy controls, the expression of Pgp was reduced in inflamed tissue of patients with active UC. The Pgp may play a role in the pathogenesis of UC.
Gemcitabine-based polymer-drug conjugate for enhanced anticancer effect in colon cancer
Liang, TJ;Zhou, ZM;Cao, YQ;Ma, MZ;Wang, XJ;Jing, K
INTERNATIONAL JOURNAL OF PHARMACEUTICS 2016年 513卷1-2期 页码:564-571
COMPLEX MICELLES; DELIVERY; DOXORUBICIN; PHARMACOKINETICS; CHEMOTHERAPY; THERAPY
In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner. The clonogenic assay further confirmed the superior anticancer effect of GEM-PL which showed least number of colonies. GEM-PL formulation exhibited a significantly higher apoptosis of cancer cells (similar to 25%) when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA significantly enhanced the blood circulation potential in animal model compared to that of free GEM. GEM-PL could prevent quick elimination of the drug and can provide sufficient time for the greater accumulation of GEM at the tumor sites. GEM-PL showed a remarkable tumor regression effect as evident from the lowest tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates showed the potential of polymer-based drug targeting and might hold significant clinical potential in the treatment of colon cancers. (C) 2016 Elsevier B.V. All rights reserved.
miR-494 inhibits invasion and proliferation of gastric cancer by targeting IGF-1R
Zhao, XQ;Liang, TJ;Fu, JW
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES 2016年 20卷18期 页码:3818-3824
CELL-PROLIFERATION; HEPATOCELLULAR-CARCINOMA; GROWTH; SENSITIVITY; PROGRESSION; SUPPRESSES; MICRORNAS; MIGRATION; RECEPTOR; PTEN
OBJECTIVE: The aim of this study was to investigate the target gene of miR-494 and its roles in tumor growth of gastric cancer (GC).;-;PATIENTS AND METHODS: Expression of miR-494 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in gastric cancer tissues and cell lines. Then, luciferase reporter assay was used to elucidate whether insulin-like growth factor 1 receptor (IGF1R) is a target gene of miR-494. Finally, the roles and mechanism of miR-494 in the regulation of tumor invasion were further investigated.;-;RESULTS: Relative miR-494 level was found to be significantly lower in patients with GC than healthy controls (p < 0.01). Over-expression of miR-494 could inhibit gastric cancer cell proliferation, migration, and invasion in vitro. Furthermore, we demonstrated that miR-494 binds to the 3'-untranslated region (UTR) of IGF1R and inhibits the expression of the IGF1R protein.;-;CONCLUSIONS: Our data showed that miR-494 acted as a tumor suppressor in GC.
Comparison of nerve combing and percutaneous radiofrequency thermocoagulation in the treatment for idiopathic trigeminal neuralgia
Zhou, XC;Liu, YQ;Yue, ZY;Luan, DH;Zhang, H;Han, J
BRAZILIAN JOURNAL OF OTORHINOLARYNGOLOGY 2016年 82卷5期 页码:574-579
MICROVASCULAR DECOMPRESSION; COMPRESSION; MANAGEMENT; RHIZOTOMY; GANGLION; ROOTLETS
Introduction: Idiopathic trigeminal neuralgia (ITN) is a common pain disease in elderly people. Many methods have been used to alleviate the pain of patients, but few studies in the literature have compared the effect of nerve combing and percutaneous radiofrequency thermocoagulation.;-;Objective: The purpose of this study was to describe and evaluate the clinical outcome of idiopathic trigeminal neuralgia after nerve combing (NC) and compare them with those obtained using percutaneous radiofrequency thermocoagulation (RF).;-;Methods: The study included 105 idiopathic trigeminal neuralgia patients with similar symptom, age and underlying disease, which were divided into two groups. One group was treated by nerve combing (50 patients), the other by RF (55 cases). All patients were considered medical failures prior to the surgeries. A questionnaire was used to assess the long-term outcomes: pain relief, recurrence, complication and need for additional treatment.;-;Results: The median duration of follow-up in both groups was 90 months. Satisfactory relief was noted in 41 patients (82%), 5 patients (10%) initially experienced pain relief, then recurred, and four patients (8%) were designated poor among the group NC. In the group RF, satisfactory relief was noted in 42 patients (76.4%). There were eight "pain free with recurrence patients (14.5%) and 5 poor cases (9.1%). No statistically significant differences existed in the outcomes between both groups (p>0.05). Postoperative morbidity included dysesthesia, diplopia, partial facial nerve palsy, hearing loss, tinnitus, cerebrospinal fluid leak, meningitis and mortality.;-;Conclusion: Nerve combing and RF are both satisfactory treatment strategies for patients with ITN. Because of the higher risk of sensory morbidity and surgical risk as open surgery, RF is preferred as the recommended procedure for patients with ITN. (C) 2015 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
High-volume hemofiltration combined with early goal-directed therapy improves alveolar-arterial oxygen exchange in patients with refractory septic shock
Ren, HS;Li, M;Zhang, YJ;Wang, L;Jiang, JJ;Ding, M;Wang, CT
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES 2016年 20卷2期 页码:355-362
RESPIRATORY-DISTRESS-SYNDROME; SEVERE SEPSIS; RESUSCITATION BUNDLE; SHORT-TERM; DEFINITIONS; FAILURE; GUIDELINES; MANAGEMENT; OUTCOMES; PREVENT
OBJECTIVE: This study is to evaluate the effect of high-volume hemofiltration (HVHF) and early goal-directed therapy (EGDT) on alveolar-arterial oxygen exchange in patients with refractory septic shock.;-;PATIENTS AND METHODS: Patients were classified into two groups by a prospective cohort study: 86 received both HVHF and EGDT (the HVHF group), and 81 treated with EGDT only (the control group). Alveolar-arterial oxygen pressure was taken at baseline and at days 1, 3, and 7, and respiratory index (RI, ratio of PaO2 alveolar-arterial oxygen pressure difference (PA-aDO2) to arterial oxygen pressure (PaO2) was calculated.;-;RESULTS: At day 7, the levels of central venous and arterial blood oxygen content were significantly higher in the HVHF vs. the control group (both with p < 0.05). The level of oxygen extraction ratio (O2ER) was significantly higher in the HVHF than the control group (p < 0.01). The levels of PA-aDO2 and RI were significantly lower in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). RI and the ratio of PaO2 to the fraction of inspired oxygen were significantly higher in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). The acute physiology and chronic health evaluation score and the sequential organ failure assessment score in the HVHF group were significantly lower compared to the control group (p < 0.01 and p < 0.05, respectively). At day 28, the mortality rate was lower in the HVHF vs. the control group (p < 0.01).;-;CONCLUSIONS: These findings demonstrated that HVHF, when used as an adjunctive therapy to the EGDP protocol, could improve alveolar-arterial oxygen exchange, clinical outcome and survival in patients with refractory septic shock.
Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice
Liu, H;Xu, HW;Zhang, YZ;Huang, Y;Han, GQ;Liang, TJ;Wei, LL;Qin, CY;Qin, CK
WORLD JOURNAL OF GASTROENTEROLOGY 2015年 21卷36期 页码:10367-10374
PRIMARY BILIARY-CIRRHOSIS; GLOBAL CANCER STATISTICS; NF-KAPPA-B; CYTOCHROME-C; COLON-CANCER; CHENODEOXYCHOLIC ACID; CELL-SURVIVAL; PATHWAY; DERIVATIVES; MODULATION
AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC).;-;METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L x W-2) x 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3.;-;RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 +/- 89 mm(3); 30 mg/kg per day, 612 +/- 46 mm(3); 50 mg/kg per day, 563 +/- 38 mm(3); and 70 mg/kg per day, 221 +/- 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% +/- 0.3%; 30 mg/kg per day, 2.9% +/- 0.5%; 50 mg/kg per day, 3.15% +/- 0.7%, and 70 mg/kg per day, 4.86% +/- 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA.;-;CONCLUSION: UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.
Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells
Zhao, XQ;Zhang, YF;Xia, YF;Zhou, ZM;Cao, YQ
ONCOLOGY LETTERS 2015年 10卷3期 页码:1287-1292
COLORECTAL-CANCER; HEME OXYGENASE-1; TET PROTEINS; KEAP1; NRF2; 5-FLUOROURACIL; IDENTIFICATION; CHEMOTHERAPY; ACTIVATION; EXPRESSION
The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET) 1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.
Nemo-like kinase expression predicts poor survival in colorectal cancer
Chen, JB;Han, YW;Zhao, XQ;Yang, MY;Liu, B;Xi, XP;Xu, XL;Liang, TJ;Xia, LJ
MOLECULAR MEDICINE REPORTS 2015年 11卷2期 页码:1181-1187
PROGNOSTIC-SIGNIFICANCE; MISMATCH-REPAIR; GASTRIC-CANCER; COLON-CANCER; STATISTICS; MARKERS; IMPACT; CELLS; BRAF
Nemo-like kinase (NLK), a serine/threonine protein kinase, was previously reported to be associated with tumor proliferation and invasion. The present study aimed to evaluate whether NLK participates in the tumorigenesis and progression of colorectal cancer (CRC). NLK expression was examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis in 50 paired CRC tissues as well as immunohistochemical analysis of 406 cases of primary CRC tissues and paired non-cancerous tissues. Correlations between NLK expression, the clinicopathological features of CRC patients and clinical outcome were then analyzed. NLK expression was found to be significantly higher in CRC tissues as well as associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with NLK-positive tumors demonstrated higher rates of recurrence and mortality than patients with NLK-negative tumors. Multivariate analyses revealed that NLK expression was an independent factor for overall survival [hazard ratio (HR)=0.035; 95% confidence interval (CI)=0.02-0.19; P<0.001] and disease-free survival (HR=0.033; 95% CI=0.007-0.09; P<0.001) in CRC patients. In conclusion, the results of the present study indicated that NLK may serve as a novel biomarker for tumor recurrence and survival for CRC patients.
Gene Expression Analysis of Colorectal Cancer by Bioinformatics Strategy
Cui, M;Yuan, JH;Li, J;Sun, B;Li, T;Li, YT;Wu, GL
HEPATO-GASTROENTEROLOGY 2014年 61卷135期 页码:1942-1945
SIGNALING PATHWAYS; HUMAN COLON; ENDOCYTOSIS; STATISTICS
Background/Aims: We used bioinformatics technology to analyze gene expression profiles involved in colorectal cancer tissue samples and. healthy controls. Methodology: In this paper, we downloaded the gene expression profile GSE4107 from Gene Expression Omnibus (GEO) database, in which a total of 22 chips were available, including normal colonic mucosa tissue from normal healthy donors (n=10), colorectal cancer tissue samples from colorectal patients (n=33). To further understand the biological functions of the screened D6Es, the KEGG pathway enrichment analysis were conducted. Then we built a transcriptome network to study differentially co-expressed links. Results: A total of 3151 DEGs of CRC were selected. Besides, total 164 DCGs (Differentially Coexpressed Gene, DCG) and 29279 DCLs (Differentially Co-expressed Link, DCL). were obtained. FUrthermore, the significantly enriched KEGG pathways were Endocytosis, Calcium signaling pathway, Vascular smooth muscle contraction, Linoleic acid metabolism, Arginine and proline metabolism, Inositol phosphate metabolism and MAPK signaling pathway. Conclusion: Our results show that the generation of CRC involves multiple genes, Ts- and pathways. Several signal and immune pathways are linked to CRC and give us more clues in the process of CRC. Hence, our work would pave ways for novel diagnosis of CRC, and provided theoretical guidance into cancer therapy.
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