Publications by authors named "Yang-de Zhang"

54 Publications

The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy.

Tumour Biol 2016 Sep 14;37(9):12339-12346. Epub 2016 Jun 14.

Cancer Research Institute, Xiangya School of Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Central South University, 110 Xiangya Road, Changsha, Hunan, 410008, China.

Hepatocellular carcinomas (HCC) are commonly diagnosed at an advanced stage with unresectable tumors. Although numerous non-surgical approaches have been developed to treat HCC, the prognosis of patients with HCC is still poor. This study investigated the expression of miR-149 and PARP-2 in HCC tumor tissues and their roles in sensitizing chemo/radiotherapy. The expression of miR-149 was measured by real-time PCR, and PARP-2 protein was measured by immunohistochemistry and Western blot. The xenograft HCC mouse model was established by inoculating Hep G2 cells. Increased PARP-1 and decreased miR-149 expression was observed in HCC tissues compared to peritumoral tissues. Positive PARP-2 and low miR-149 expression correlated with larger tumor mass size (P < 0.001), capsular and vascular invasion (P < 0.001), lymph node metastasis (P = 0.02), high histological grade (P < 0.001), TNM (P < 0.001), and BCLC grade (P = 0.001). The Kaplan-Meier survival analysis showed a negative correlation between high PARP-2 expression or low miR-149 expression in HCC tissues with the survival of patients. High PARP-2 and low miR-149 correlated with a low 5-year survival rate and are poor prognosis factors. Overexpression of miR-149 or inhibition of PARP-2 expression could inhibit tumor growth but was more effective in sensitizing chemotherapy and radiotherapy in xenograft HCC animal models. Increased PARP-2 expression and loss of miR-149 expression are involved in the pathogenesis of HCC and are poor prognosis factors in patients with HCC. Although both miR-149 overexpression and PARP-2 inhibitor exert some antitumoral effect, PARP-2 inhibitor is a chemo/radio sensor and can be used to enhance chemotherapy and radiotherapy in patients with HCC.
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http://dx.doi.org/10.1007/s13277-016-5106-yDOI Listing
September 2016

Enhanced antiproliferative and apoptosis effect of paclitaxel-loaded polymeric micelles against non-small cell lung cancers.

Tumour Biol 2015 Jul 22;36(7):4949-59. Epub 2015 Feb 22.

National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.

Amphiphilic copolymer monomethoxy poly(ethylene glycol)-poly(caprolactone)-D-α-tocopheryl polyethylene glycol 1000 succinate (MPEG-PCL-TPGS) was prepared. In the present study, MPEG-PCL-TPGS was used as a novel nanovehicle for the delivery of paclitaxel (PTX) in the treatment of resistant lung cancers. The PTX-loaded MPEG-PCL-TPGS (PTX/MPT) micelles exhibited sustained release profile (168 h) with accelerated drug release at acidic pH conditions. The blank polymeric micelles showed excellent biocompatibility with cell viability of >85 %, making it suitable for all in vivo applications. PTX/MPT micelles displayed superior cytotoxicity in A-549 lung cancer cells than that of free PTX. The selective delivery of PTX to cancer cells resulted in enhanced cancer cell death. The PTX/MPT micelles showed higher cellular uptake via endocytosis pathways. The PTX-bound micelles preferentially arrested the cells at G2/M phase and showed a marked increase in sub G1 cell population (∼ 20 %). The pharmacokinetic study revealed a long blood circulation for PTX/MPT micelles. Finally, micellar formulation showed a remarkable tumor suppression effect in resistant A549/Taxol cells bearing xenograft nude mice along with no toxicity profile. The results indicate that the PTX-loaded biocompatible polymeric nanosystem could act as a potential delivery system for the treatment of lung carcinomas.
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http://dx.doi.org/10.1007/s13277-015-3142-7DOI Listing
July 2015

MicroRNA-145 inhibits lung cancer cell metastasis.

Mol Med Rep 2015 Apr 3;11(4):3108-14. Epub 2014 Dec 3.

Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, Jiangxi 330006, P.R. China.

Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR‑145 was reported to occur in various types of human cancer; however, the role of miR‑145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR‑145 on metastasis and epithelial‑mesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR‑145 regulates EMT were examined. The miR‑145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR‑145 regulates EMT, a luciferase reporter assay was performed to determine whether miR‑145 targeted Oct4. In addition, the expression of Wnt3a and β‑catenin in A549 cells was measured following transfection with small hairpin RNA‑Oct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR‑145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/β‑catenin signaling pathway.
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http://dx.doi.org/10.3892/mmr.2014.3036DOI Listing
April 2015

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation.

Mol Med Rep 2015 Mar 21;11(3):1851-8. Epub 2014 Nov 21.

Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, Jiangxi 330006, P.R. China.

Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.
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http://dx.doi.org/10.3892/mmr.2014.2992DOI Listing
March 2015

Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma.

Onco Targets Ther 2013 11;6:1625-30. Epub 2013 Nov 11.

Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Background: MicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC.

Methods: miR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay.

Results: The expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival.

Conclusion: This study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC.
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http://dx.doi.org/10.2147/OTT.S53030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829675PMC
November 2013

Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Asian Pac J Trop Med 2013 Jun;6(6):473-80

Department of Hepatic Surgery, National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, China.

Objective: To identify target genes of transcription factor CCAAT enhancer-binding protein β (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Methods: A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified.

Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA.

Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.
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http://dx.doi.org/10.1016/S1995-7645(13)60077-2DOI Listing
June 2013

Downregulation of miR-124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L.

Int J Mol Med 2013 Jul 29;32(1):101-7. Epub 2013 Apr 29.

National Hepatobiliary and Enteric Surgery Research Center, Central South University, Changsha 410008, P.R. China.

microRNA-124 (miR-124) plays an important role in regulating growth, invasiveness, stem-like traits, differentiation and apoptosis of glioblastoma cells. PPP1R3L, an inhibitory member of the apoptosis-stimulating protein of p53 family (IASPP), is also able to affect growth, cell cycle progression, metastasis and apoptosis of various types of cancer. To investigate the regulation of PPP1R13L expression by miR-124 and their effects on proliferation, cell cycle transition and invasion in glioblastoma cells, U251 and U373 glioblastoma cells were transfected with miR-124 mimics, its negative control (NC) or an inhibitor. We found that miR-124 was downregulated in glioblastoma tissues, and inversely regulated PPP1R13L expression in U251 and U373 glioblastoma cells. PPP1R13L was found to be a direct target of miR-124 in glioblastoma cells. Overexpression of miR-124 inhibited proliferation, G1/S transition and invasiveness in glioblastoma cells. miR-124 downregulation-mediated malignant progression of glioblastoma was partly attributed to increased PPP1R13L expression. Consequently, our findings provide a molecular basis for the role of miR-124/PPP1R13L in the progression of human glioblastoma and suggest a novel target for the treatment of glioblastoma.
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http://dx.doi.org/10.3892/ijmm.2013.1365DOI Listing
July 2013

The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer.

Tumour Biol 2013 Jun 22;34(3):1865-71. Epub 2013 Mar 22.

Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410008, China.

Gastric cancer is the second leading cause of cancer mortality, but the molecular mechanisms underlying its progression and metastasis remain unclear. CCR7 and Dicer 1 protein expression in 80 gastric adenocarcinomas and 40 peritumoral tissues were measured by immunohistochemical staining. The expression of let-7a miRNA in serum, tumor tissues, and peritumoral tissues was measured by real-time PCR. The role of let-7a in CCR7 protein expression, migration, and invasion of gastric cancer cells was tested in vitro. Dicer 1 protein expression was found to be significantly reduced, whereas CCR7 protein expression was significantly increased in gastric adenocarcinomas compared to peritumoral tissues. The let-7a miRNA levels in the serum and tumor tissues of gastric adenocarcinoma patients were significantly lower than in the serum of healthy controls and peritumoral tissues, respectively. Dicer 1 protein positively correlated with let-7a miRNA level, but negatively correlated with CCR7 protein level in gastric adenocarcinoma. Negative Dicer 1 protein and let-7a miRNA expression and positive CCR7 protein expression significantly correlated with lymph node metastasis, depth of invasion, high clinical TNM stage, and larger tumor size. Let-7a transfection significantly inhibited CCR7 protein expression, migration, and invasion of MNK-45 cells in vitro. High expression of CCR7 protein and low expression of Dicer 1 protein and let-7a miRNA are significantly associated with the metastasis and progression of gastric cancer. High CCR7 protein expression may be caused by the loss of Dicer 1 protein expression and reduced let-7a miRNA level in gastric cancer. The serum let-7a level might be a marker for the diagnosis of gastric cancer.
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http://dx.doi.org/10.1007/s13277-013-0728-9DOI Listing
June 2013

Clinical significance of microRNA-93 downregulation in human colon cancer.

Eur J Gastroenterol Hepatol 2013 Mar;25(3):296-301

National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Hunan, People's Republic of China.

Aim: MicroRNA-93 (miR-93) has been shown to suppress proliferation and colony formation of colon cancer stem cells. The aim of this study was to examine the expression pattern and prognostic value of miR-93 in patients with colon cancer.

Materials And Methods: A quantitative real-time PCR analysis was carried out to detect the expression levels of miR-93 in 138 paired samples of tumoral and nontumoral colon tissues diagnosed with colon cancer. Associations of miR-93 expression with clinicopathological parameters and survival were also examined.

Results: miR-93 expression was significantly decreased in tumoral compared with nontumoral colon tissues (P<0.001). Low miR-93 expression was significantly correlated with advanced tumor stage (P=0.02), positive nodal metastasis (P=0.006), and positive distant metastases (P=0.01). In addition, Kaplan-Meier survival analysis by Cox regression showed that low miR-93 expression [hazard ratio (HR), 10.2; 95% confidence interval (CI), 1.9-42.8, P=0.003] was associated closely with poor overall survival in patients with colon cancer. Moreover, multivariate analysis showed that miR-93 decreased expression (HR, 4.3; 95% CI, 0.8-17.2, P=0.02), advanced tumor stage (HR, 3.1; 95% CI, 0.2-13.9, P=0.04), positive nodal metastasis (HR, 4.1; 95% CI, 0.7-16.8, P=0.02), and positive distant metastases (HR, 3.7; 95% CI, 0.5-14.1, P=0.03) were independent risk factors for overall survival in patients with colon cancer.

Conclusion: Our data show for the first time that the downregulation of miR-93 was significantly correlated with unfavorable clinicopathologic features and short overall survival in patients with colon cancer, suggesting that decreased expression of miR-93 be used as a novel prognostic factor for this disease.
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http://dx.doi.org/10.1097/MEG.0b013e32835c077aDOI Listing
March 2013

Green tea consumption and risk of esophageal cancer: a meta-analysis of epidemiologic studies.

BMC Gastroenterol 2012 Nov 21;12:165. Epub 2012 Nov 21.

National Hepatobiliary & Enteric Surgery Research Center of South University, 87 Xiangya Road, Changsha, China.

Background: Green tea has shown the role of chemoprevention for cancer. Recently, several studies suggested that green tea intake may have effect on esophageal cancer risk, whereas the results were inconsistent.

Methods: We performed a meta-analysis of all English and Chinese language studies of green tea consumption and esophageal cancer risk indexed in Medline, Embase, the Science Citation Index, the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After reviewing each study, extracting data, and evaluating heterogeneity (Chi-square-based Q test and Ι2) and publication bias (Begg and Egger test), a meta-analysis was performed to evaluate the association between high/medium/low green tea consumption and non-drinking esophageal cancer risk. Pooled relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effect models.

Results: Ten eligible epidemiologic studies including 33731 participants and 3557 cases for esophageal cancer were included. Eight of which were case-control studies, and two were cohort studies. Overall, there were no association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76, 95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70 to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When stratified analyses according to study design (case-control and cohort studies), country (China and Japan), participates source (population-based and hospital-based case-control), and gender (female and male), there were significant association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54. Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to 0.79), but not the others.

Conclusions: We did not found significant association between green tea consumption and non-drinking esophageal cancer risk, but an evidence of protective effect was observed among female.
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http://dx.doi.org/10.1186/1471-230X-12-165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573987PMC
November 2012

Reduced expression of Raf kinase inhibitor protein correlates with poor prognosis in pancreatic cancer.

Clin Transl Oncol 2012 Nov 24;14(11):848-52. Epub 2012 Jul 24.

National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan, China.

Aim: Raf kinase inhibitory protein (RKIP) is an inhibitor of the Raf/MEK/MAP kinase signaling cascade and a suppressor of cancer metastasis. But its function in pancreatic cancer was not yet clarified completely. The aim of this study was to investigate the involvement of RKIP in pancreatic cancer.

Methods: RKIP expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 99) of consecutive patients with pancreatic cancer. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model.

Results: RKIP expression was high in normal pancreatic epithelium and retained to varying degrees in pancreatic cancer tissues. However, in tumor tissues with lymph node metastasis (P = 0.008) and high UICC stage (P = 0.006), RKIP expression was highly significantly reduced or lost. Furthermore, the reduced expression of RKIP significantly correlated with both poor overall and disease-free survival (P = 0.008 and 0.01, respectively). Multivariate analyses revealed RKIP to be an independent prognosticator.

Conclusion: These findings suggest that RKIP could be a promising marker for predicting a better prognosis in pancreatic cancer.
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http://dx.doi.org/10.1007/s12094-012-0870-7DOI Listing
November 2012

Tumor associated glycoprotein-72 is a novel marker for poor survival in hepatocellular carcinoma.

Pathol Oncol Res 2012 Oct 21;18(4):911-6. Epub 2012 Mar 21.

National hepatobiliary and enteric surgery research center, Xiangya Hospital, The Central South University, Changsha, 410008, Hunan Province, China.

To investigate the relationship of tumor associated glycoprotein-72 (TAG-72) expression with clinicopathological features in hepatocellular carcinoma (HCC) patients. Sixty pairs of HCC and paracarcinomatous (PCLT) tissues, and 10 normal liver (NL) tissues were collected for Western blot analysis, and 244 pairs of HCC and PCLT tissues were collected for immunohistochemistry analysis. TAG-72 protein expression was elevated significantly in HCC tissues compared with PCLT and NL tissues. Its increased expression was correlated with TNM stage, Edmondson-Steiner grade, vein invasion and multiple tumor nodes. It is noteworthy that the HCC patients with high TAG-72 expression had shorter overall survival and disease-free survival than the patients with low expression. Multivariate Cox regression analysis revealed that TAG-72 expression was an independent prognostic factor for HCC patients. The current study demonstrated for the first time that the increased expression of TAG-72 was correlated with poor survival in patients with HCC, indicating that TAG-72 is a novel prognostic marker for HCC.
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http://dx.doi.org/10.1007/s12253-012-9521-0DOI Listing
October 2012

Modified transurethral incision for primary bladder neck obstruction in women: a method to improve voiding function without urinary incontinence.

Urology 2012 Feb;79(2):310-3

Laboratory of Nano-Biotechnology, Central South University, Changsha, Hu'nan, China.

Objective: To describe the modified surgical technique and report the long-term outcomes of modified transurethral incision for the treatment of primary bladder neck obstruction in women.

Methods: A total of 30 women were diagnosed with primary bladder neck obstruction from the videourodynamic study findings according to the Blaivas-Groutz nomogram for female bladder outlet obstruction. Patients with neurogenic, traumatic, anatomic, or iatrogenic causes of obstruction were excluded. The transurethral incision of the bladder neck was performed in all patients, with the modification of incising at 4 different sites on the bladder neck, at the 3-, 6-, 9-, and 12-o'clock positions. The urodynamic results and clinical improvement in voiding symptoms were assessed before surgery and 3, 48, and 60 months after treatment.

Results: Follow-up data were available for 30 (100%), 28 (93%), and 25 (83%) of the 30 patients at 3, 48, and 60 months postoperatively, respectively. During the 5-year follow-up, the mean International Prostate Symptom Score decreased from 23.3 to 5.9. The mean quality of life scores decreased from 4.4 to 2.1. The mean peak urinary flow rate increased from 7.61 to 17.53 mL/s. The mean postvoid residual urine volume decreased from 185.11 to 28.75 mL. The mean voiding detrusor pressure decreased from 62.12 to 21.92 cm H2O. All 25 patients had improvement in both objective and subjective voiding functions 5 years after this modified treatment. Only 1 woman (3%) had mild stress incontinence postoperatively and was cured after the patient performed levator ani exercises.

Conclusion: The modified transurethral bladder neck incision is effective in the long term in relieving voiding difficulties owing to primary bladder neck obstruction in women without urinary incontinence.
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http://dx.doi.org/10.1016/j.urology.2011.11.004DOI Listing
February 2012

Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision.

Rev Sci Instrum 2012 Jan;83(1):015115

The Second People's Hospital of Panyu District, Panyu, Guangzhou, People's Republic of China.

In recent years, some Chinese doctors have proposed a new concept, gallstone removal without gallbladder excision, along with transition of the medical model. As there is no specialized endoscope for gallstone removal without gallbladder excision, we designed and produced a new series of gallbladder endoscopes and accessories that have already been given a Chinese invention patent (No. ZL200810199041.2). The design of these gallbladder endoscopes was based on the anatomy and physiology of the gallbladder, characteristics of gallbladder disease, ergonomics, and industrial design. This series of gallbladder endoscopes underwent clinical trials in two hospitals appointed by the State Administration of Traditional Chinese Medicine. The clinical trials showed that surgeries of gallstones, gallbladder polyps, and cystic duct calculus could be smoothly performed with these products. In summary, this series of gallbladder endoscopes is safe, reliable, and effective for gallstone removal without gallbladder excision. This note comprehensively introduces the research and design of this series of gallbladder endoscopes.
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http://dx.doi.org/10.1063/1.3673472DOI Listing
January 2012

Upregulation of a disintegrin and metalloprotease 8 influences tumor metastasis and prognosis in patients with osteosarcoma.

Pathol Oncol Res 2012 Jul 5;18(3):657-61. Epub 2012 Jan 5.

National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410078 Hunan, China.

To investigate the clinicopathological and prognostic value of a disintegrin and metalloprotease 8 (ADAM8) in osteosarcoma. ADAM8 expression in osteosarcoma tissues was examined by immunohistochemistry in 69 patients. ADAM8 was positively expressed in 61 of 69 (88.4%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (P = 0.008) and metastasis (P = 0.002). Patients with strong ADAM8 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with the patients with the weak expression of ADAM8. On multivariate analysis, ADAM8 expression was found to be an independent prognostic factor for both OS (P < 0.001) and DFS (P < 0.001). Our results suggest for the first time that ADAM8 might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with osteosarcoma.
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http://dx.doi.org/10.1007/s12253-011-9491-7DOI Listing
July 2012

NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor survival in patients with gallbladder carcinoma.

Med Oncol 2012 Sep 2;29(3):1879-85. Epub 2011 Dec 2.

Department of Genery Surgery, The Third Affiliated Hospital of Inner Mongolia Medical College, Baogang Hospital of Inner Mongolia, Shaoxian Road 20, Kun District, Baotou, Inner Mongolia, China.

Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) may reduce the metastatic potential of breast cancer and hepatocellular carcinoma cells by regulating the expression of CD24, which is expressed in a large variety of solid tumors. The aim of this study was to clarify the clinical value of NDRG2 and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24 expression. The associations of NDRG2 and CD24 expression with the clinicopathological characteristics and the overall survival of patients with GBC were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and 107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph node metastasis and lymphovascular invasion. Moreover, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion depth and higher TNM stage. There was a negative correlation between NDRG2 expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The patients with NDRG2 negative expression correlated with poor prognosis of GBC (P = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis in GBC.
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http://dx.doi.org/10.1007/s12032-011-0110-yDOI Listing
September 2012

Laparoscopic treatment of a massive fibroepithelial polyp accompanied by ureteral intussusception.

Chin Med J (Engl) 2011 Oct;124(20):3436-9

National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University of China, Changsha, Hunan 410008, China.

Ureteral fibroepithelial polyp accompanied by intussusception is a rare occurrence. Currently, most ureteral polyps could be removed readily by ureteroscopy. Nevertheless, endoscopic resection can be difficult in patient with a large polyp, especially accompanied by an intussusception. We described our experience and laparoscopic technique for treatment of a symptomatic 63-year-old woman who presented with a pedunculated, 9-cm-long, left lower ureteral, fibroepithelial polyp accompanied by a 2-cm-long intussusception.
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October 2011

[Effects of different doses of nano silver on vascular endothelial cell proliferation in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011 Jun;27(6):697-9

Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha 410000, China.

Aim: To explore the effects of different doses of nano silver of proliferation of cultured vascular endothelial cells in vitro.

Methods: The hearts of three newborn SD rats 5 day old were mechanically minced the enzymatically digested with collagenase and trypsin, then vascular endothelial cell were counted, washed and resuspended in Dulbecco's minimumes sential medium (DMEM) added with 20% heat in activated fetal calf serum, then inoculated d in 2% gelatin coated tissue culture flasks. Vascular endothelial cells at passage 3 were used in the experiment. Except for the normal control group, the vascular endothelial cells were cultured with nano silver in various concentrations (0.5, 0.25, 0.125, 0.0625, 0.03125 g/l) for 24 hours, and the morphology and the number of the cultured endothelial cells were observed. Methly thiazolyl tetrazolium (MTT) colorimetry was used to determine the proliferation of the cultured vascular endothelial cells. Flow cytometry (FCM) were used to detect the proliferation index (PI) of the vascular endothelial cells and the expressions of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemical method.

Results: The cell morphology was normal under the inverted microscoped in each group. The number and proliferation activities of vascular endothelial cells were significantly decreased by 0.5, 0.25, 0.125, 0.0625, 0.03125 g/l nano silver compared with those of the blank control group, especially the 0.25 g/l nao silver group, and there were no remarkable changes in with 0.5 g/L, 0.125 g/L, 0.0625 g/L and 0.03125 g/L nano silver groups compared to each other. The same results were seen in the positive rate of PCNA expression and PI.

Conclusion: Nano silver has dose-dependent effects on the proliferation activity of vascular endothelial cells. It inhibited the proliferation of vascular endothelial cells.
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June 2011

Expression of N-myc downstream-regulated gene 1 in primary gallbladder carcinoma and its correlation with clinicopathological features and clinical outcome.

Med Oncol 2012 Sep 7;29(3):1866-72. Epub 2011 Jul 7.

National Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Central South University, Xiangya Road 87, Changsha, Hunan, China.

N-myc downstream-regulated gene 1 (NDRG1), a member of the N-myc downstream-regulated gene family, is induced under a wide variety of stress and cell growth-regulatory conditions. In several cancers, recent studies have shown its association with inhibition of tumor metastasis and suggested it to be a tumor suppressor gene. However, its significance in primary gallbladder carcinoma (PGC) has not been studied. Therefore, the aim of this study was to investigate NDRG1 expression in PGC and its prognostic significance. We examined NDRG1 expression in tumor specimens from 138 patients with PGC by immunohistochemistry and analyzed the correlation between NDRG1 expression and clinicopathologic factors or survival. NDRG1 was expressed in 63.8% of PGC but not in the normal epithelium of the gallbladder, remarkably at the invasive front of the tumors. In addition, NDRG1 expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, positive nodal metastasis and venous/lymphatic invasion. Moreover, Kaplan-Meier curves showed that NDRG1 over-expression was significantly related to poor overall and disease-free survival (both P = 0.02). Furthermore, multivariate analyses showed that NDRG1 expression (hazard ratio, 3.338; P = 0.02) and clinical stage (hazard ratio, 3.128; P = 0.03) were independent risk factors for disease-free survival. Our data demonstrate for the first time that NDRG1 expression in PGC was significantly correlated with unfavorable clinicopathologic features and an independent poor prognostic factor for disease-free survival in patients. Taken together, our findings suggest that NDRG1 expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in PGC.
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http://dx.doi.org/10.1007/s12032-011-0017-7DOI Listing
September 2012

[Effect of Itk down regulation on cytokines production in Jurkat cell].

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2010 Oct;24(5):358-61

Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Center South University, Changsha, Hunan 410008, China.

Objective: To study the effect of Itk down regulation on Jurkat cell proliferation and inflammatory cytokines production, and provide useful data for Itk as an attractive target for potential drugs.

Methods: Three shRNAs against different region of Itk were constructed and cotransfected with pEGFP-C1-hItk. The shRNA, which can knock down Itk, was selected and packed into lentivirus. After Jurkat cells were transfected with shRNA lentivirus, the change of Itk protein expression, cell proliferation and cytokines production was observed.

Results: Itk mRNA was reduced about 55% in Jurkat cells transfected with Itk-shRNA1, compared with that in control cells shRNAnon (P < 0.05). Knocking down Itk expression had a profound inhibitory effect on Jurkat cell proliferation. In addition, there was a substantial decrease in level of cytokines, such as IL-2, IL-5, IL-10 and IFN-gamma, produced by cell transfected with Itk-shRNA1.

Conclusion: Knocking down Itk expression can inhibit Jurkat cell proliferation and inflammatory cytokines production.
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October 2010

[Phage display random peptide library for screening the peptides that specifically bind to hepatocellular carcinoma cells].

Nan Fang Yi Ke Da Xue Xue Bao 2009 Sep;29(9):1806-8

National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, China.

Objective: To screen the peptides that bind specifically to the hepatoma cells using phage display random peptides library.

Methods: Three rounds of panning were conducted in vitro targeting HepG2 cell lines. In nude mice bearing HepG2 tumor, one round of panning was conducted, and 30 phage clones were randomly selected for sequence analysis to identify the consensus sequence. Immunocytochemistry and immunohistochemistry were performed to determine the specificity of the phages to the hepatoma cells.

Results: After three rounds of panning in vitro and one round of panning in vivo, the phages binding to HepG2 cells were enriched. Sequence analysis of the randomly selected clones identified the peptide sequence VRKRSECLGAHD as the most frequent sequence. Immunocytochemistry and immunohistochemistry confirmed the specificity of the phage binding to the hepatoma cells.

Conclusions: Specific peptides against hepatoma cells can be obtained from a phage- display peptide library, which provides an experimental basis for developing therapeutic agents targeting hepatoma cells.
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September 2009

[Recombinant plasmid pEGFP-AFP-TK delivered by nano-magnetic fluids targeting killed AFP positive HepG2 cells in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2009 May;25(5):437-9

National Key Laboratory of Nanobiological Technology, Ministry of Health, Changsha, China.

Aim: To study recombinant plasmid pEGFP-AFP-TK delivered by nano-magnetic fluids targeting killed AFP positive HepG2 cells in vitro.

Methods: Constructed recombinant plasmid pEGFP-AFP-TK which was delivered by nano-magnetic fluids into AFP positive HepG2 cells and AFP negative SMMC-7721.The fluorescence was detected in order to evaluate the transfection rate, and RT-PCR and Western blot were used to detect the expression of TK gene after transfection. MTT assay was used to evaluate the effect of TK on the proliferation and bystander effect of HepG2 cells in ganciclovir (GCV). Flow cytometry was used to analysis the apoptosis of HepG2 cells.

Results: Nano-magnetic fluids delivered plasmid pEGFP-AFP-TK into HepG2 cells and TK gene was successfully expressed, and the transfection efficacy of nano-magnetic fluids was superior to that of Lipofectamine. RT-PCR and Western blot results demonstrated that TK gene was expressed in HepG2 cells after being transfected with nano-magnetic fluids/pEGFP-AFP-TK. MTT and flow cytometry results showed TK gene exerts cell-killing and bystander effect.

Conclusion: Nano-magnetic fluids could successfully deliver pEGFP-AFP-TK into HepG2 cells and induce expression of TK gene, which is promising gene vector for liver cancer gene therapy. AFP enhancer can specifically enhance the expression of target TK gene within the AFP positive cell, and induce bystander effect and apoptosis in the AFP positive HepG2 cell with with GCV.
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May 2009

[Recombinant plasmid pEGFP-AFP-TK delivered by nano-magnetic fluids targeting killed AFP positive HepG2 cells in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2009 May;25(5):437-9

National Key Laboratory of Nanobiological Technology, Ministry of Health, Changsha, China.

Aim: To study recombinant plasmid pEGFP-AFP-TK delivered by nano-magnetic fluids targeting killed AFP positive HepG2 cells in vitro.

Methods: Constructed recombinant plasmid pEGFP-AFP-TK which was delivered by nano-magnetic fluids into AFP positive HepG2 cells and AFP negative SMMC-7721.The fluorescence was detected in order to evaluate the transfection rate, and RT-PCR and Western blot were used to detect the expression of TK gene after transfection. MTT assay was used to evaluate the effect of TK on the proliferation and bystander effect of HepG2 cells in ganciclovir (GCV). Flow cytometry was used to analysis the apoptosis of HepG2 cells.

Results: Nano-magnetic fluids delivered plasmid pEGFP-AFP-TK into HepG2 cells and TK gene was successfully expressed, and the transfection efficacy of nano-magnetic fluids was superior to that of Lipofectamine. RT-PCR and Western blot results demonstrated that TK gene was expressed in HepG2 cells after being transfected with nano-magnetic fluids/pEGFP-AFP-TK. MTT and flow cytometry results showed TK gene exerts cell-killing and bystander effect.

Conclusion: Nano-magnetic fluids could successfully deliver pEGFP-AFP-TK into HepG2 cells and induce expression of TK gene, which is promising gene vector for liver cancer gene therapy. AFP enhancer can specifically enhance the expression of target TK gene within the AFP positive cell, and induce bystander effect and apoptosis in the AFP positive HepG2 cell with with GCV.
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May 2009

[Manufacture of high frequency direct current dental X-ray machine].

Zhongguo Yi Liao Qi Xie Za Zhi 2008 Nov;32(6):443-5, 448

School of Mechanical Engineering, University of South China, Hengyang, Hunan 421001, China.

This paper introduces five dental X-ray machines which are manufactured with IGBT to realize high frequency, real-time sampling and PWM to ensure the closed-loop control for tube current and Anodes's high voltage. These five machines also use microcomputer and combined X-ray tube for precise control. The sets don't have high voltage outside. The error of tube voltage is less than 1% and exposure time is less than 3%. The photos of pulp cavity and surrounding tissue can be seen clearly. These sets surely meet the requirements of perspective use in clinical.
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November 2008

[Preparation of tegafur magnetic long-circulating thermosensitive liposomes and its pharmacokinetics in rats].

Nan Fang Yi Ke Da Xue Xue Bao 2008 Oct;28(10):1864-8

National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Institute of Biomedical Engineering of Central South University, Changsha 410008, China.

Objective: To prepare tegafur magnetic long-circulating thermosensitive liposomes and study its pharmacokinetics and targeting properties in rats.

Methods: Tegafur magnetic long-circulating thermosensitive liposomes were prepared by reversed phase-ultrasound method and its concentration in various organs of rats were detected with high-performance liquid chromatography.

Results: The average size of tegafur magnetic long-circulating thermosensitive liposomes was about 126 nm, which showed strong ferromagnetism and superparamagnetism. Eight hours after administration in rats, the AUC value of tegafur magnetic long-circulating thermosensitive liposome in the liver was 17.4 times of that of the free drug, and 3.9 times of that of tegafur long-circulating liposome. The concentrations of the thermosensitive liposome in the serum and kidney were lower than those of the free drug, with a liver-targeting ratio reaching 73.9% and obviously prolonged half-life than the free drug.

Conclusion: Tegafur complex liposome can obviously increase the drug concentration in the liver and decrease the nephrotoxicity of the drug in rats.
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October 2008

[Expression of MMP-2, MMP-9 and collagen type IV and their relationship in colorectal carcinomas].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008 Sep;24(9):908-9

Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Aim: To investigate the expression of MMP-2, MMP-9 and collagen type IV and their relationship in colorectal carcinomas.

Methods: The expressions of collagen type IV, MMP-2 and MMP-9 was in normal and colorectal cancer tissues of 30 patients whose clinical stages were Dukes'B and C was detected with immunohistochennical staining. And the relationship among collagen type IV, MMP-2 and MMP-9 was analysed.

Results: The expression of collagen type IV was significantly decreased in colorectal cancer tissues. The expression of MMP-2 and MMP-9 was not detected in normal colorectal tissues but it was significantly increased in colorectal cancer tissues. There was a negative correlation between the expression of collagen type IV and MMP-9.

Conclusion: The expression of collagen type IV in colorectal cancer tissues is lower than that in normal tissues. MMP-9 may play an important role in the degradation of collagen type IV in colorectal cancer.
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September 2008

Preparation and antibacterial activity of compound chitosan-compound Yizhihao-nanoparticles.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008 May;33(5):369-74

National Key Laboratory of Nanobiological Technology, Ministry of Health, Changsha, China.

Objective: To prepare chitosan (CS)-compound Yizhihao-nanoparticles (NP) and to investigate its antibacterial activity.

Methods: CS NPs were formed by the incorporation of CS and Na3 PO4. CS-compound Yizhihao NPs were prepared by ion-cross-linking. The particle sizes and surface charges of CS NPs were determined by Malvern Zetasizer 1000-HAS and atomic force microscope (AFM), respectively. The antibacterial activity of CS-compound Yizhihao-NPs was studied in vitro and compared with that of compound Yizhihao powder.

Results: Malvern Zetasizer 1000-HAS and AFM demonstrated that the diameter of CS-compound Yizhihao NPs was (137.00+/-14.28)nm and CS NPs had (16.90+/-1.32)mV positive surface charges. The minimal inhibitory concentrations (MIC) of CS-compound Yizhihao NPs on Staphylococcus aureus,Pneumococcus,beta-hemolytic streptococcus, and Escherichia coli were 1:32,1:32,1:16,and 1:2, respectively. The minimal bactericidal concentrations (MBC) of CS-compound Yizhihao-NPs on Staphylococcus aureus, Pneumococcus, beta-hemolytic streptococcus, and Escherichia coli were 1:16,1:16,1:8, and 1:2, respectively. The antibacterial efficacy of CS-compound Yizhihao-NPs to Staphylococcus aureus, Pneumococcus, and beta-hemolytic streptococcus had been improved significantly (P< 0.05).

Conclusion: CS-compound Yizhihao-nanoparticles have obvious antibacterial activity to the Staphylococcus aureus,Pneumococcus,and beta-hemolytic streptococcus,which lays the experimental foundation for new preparation of traditional Chinese medicine in future research.
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May 2008

[Preparation and characterization of a polyvinylpyrrolidone water-based magnetic fluid].

Nan Fang Yi Ke Da Xue Xue Bao 2008 Mar;28(3):353-5

Institute of Biomedical Engineering, Central South University, Changsha 410008, China.

Objective: To prepare a stable water-based magnetic fluid.

Methods: A water-based magnetic fluid was prepared by addition of polyvinylpyrrolidone (PVP) as the coating agent for the magnetic particles. After preparation of Fe3O4 by co-precipitation method, PVP was added for its coating, followed by ultrasonic agitation and purification.

Results: The magnetic nanoparticles of homogeneously small size and water-based magnetic fluid were obtained, which had good dispersion in water with strong magnetism.

Conclusion: PVP can be used as a surfactant to stabilize the magnetic fluid.
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March 2008

[Sentinel lymph node mapping in colorectal cancer: study of 45 cases].

Zhonghua Yi Xue Za Zhi 2007 Nov;87(44):3125-6

National Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha 410008, China.

Objective: To discuss the sentinel lymph node (SLN) mapping technique in colorectal cancer and its feasibility and utility.

Methods: The dye lymphazurin was injected subserosally around the tumor during operation in 43 colorectal cancer, 20 males and 25 females, aged 49.5 (27 - 72) so as to find the SLNs. Fast-frozen pathology and routine pathology were performed too.

Results: SLN was successfully identified in 42 of the 45 patients, with a successful biopsy rate of 93.3%. In these 45 patients, there were 250 lymph nodes examined, of which 52 nodes were identified as SLNs. The sensitivity was 90.4% (20/22), the specificity was 95.2% [(20 + 20)/42], and the false negative rate was 15% (3/20).

Conclusion: SLN mapping in colorectal cancer plays an important role in diagnosing metastasis of lymph nodes, and can be used to direct the clinical surgery.
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November 2007

[Transhepatic arterial chemoembolization with gemcitabine and carboplatin for the treatment of stage III hepatocellular carcinoma].

Zhonghua Zhong Liu Za Zhi 2007 Aug;29(8):623-5

Department of Diagnostic Radiology, Hunan Provincial Cancer Hospital, Changsha 410013, China.

Objective: To evaluate the efficiency and safety of transhepatic arterial chemoembolization (TACE) with gemcitabine and carboplatin for the treatment of stage III hepatocellular carcinoma (HCC).

Methods: Sixty-one HCC patients were treated by TACE. During TACE, At first, intra-arterial infusion of carboplatin 300 mg/m2, then gemcitabine 1000 mg/m2 with 5-30 ml of ultra-lipoidal iodide oil emulsion was used for arterial embolization. The toxicity and hepatic damage were observed according to WHO anticancer drug toxicity criteria and Child-Pugh classification criteria, respectively. The survival time was also observed during follow-up.

Results: The blood toxicity was bone marrow suppression presented as grade I leucopenia in 39.3%, grade II in 29.5%, grade III-IV in 18.0%. Grade II-III nausea and vomiting developed in 96.8% of the patients. Hepatic function damage became aggravated in 16 patients from A to B class, in 2 from A to C class, and in 6 from B to C class according to Child-Pugh classification criteria. The median survival time was 20 months with a range of 5 to 3 5 months.

Conclusion: Transhepatic arterial chemoembolization using carboplatin and mixture of gemcitabine with ultra-lipoidal iodide oil emulsion is safe and effective in the management of stage III hepatocellular carcinoma. This regimen can also improve their quality of life.
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August 2007
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