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Long Z.,Renmin University of China | Wang B.,Fifth Hospital of Wuhan | Tao Z.,Renmin University of China
International Journal of Molecular Medicine | Year: 2014

Nasopharyngeal carcinoma (NPC) is a relatively radiosensitive disease. However, the therapeutic effects of radiotherapy are not always satisfactory due to radioresistance. The hypofractionated schema is currently widely used in clinical practice. In the present study, we investigated the effects of hypofractionated radiotherapy on NPC cells and explored the mechanisms involved. In addition, we aimed to determine the role of miR-34a in the effects of hypofractionated radiotherapy and whether these effects occur in a p53-dependent manner. For this purpose, we used CNE1 and CNE2 NPC cells which were subjected to hyperfractionated and hypofractionated radiotherapy. The viability of the cells was measured by MTT assay and acridine orange (AO) and ethidium bromide (EB) staining was used to observe morphological changes. In addition, Annexin V-propidium iodide (PI) staining and flow cytometry were used to determine the number of apoptotic cells and mRNA and protein expression was measured by qPCR and western blot analysis, respectively. The results revealed that hypofractionated radiotherapy enhanced apoptosis and increased the expression of miR-34a and p53 in the NPC cells. In addition, it stimulated p53 promoter activity and downregulated the protein expression of c-Myc in the human NPC cells. Furthermore, the knockdown of miR-34a suppressed the growth inhibitory effects induced by hypofractionated radiotherapy. Thus, our results suggest that the enhanced apoptosis of NPC cells may be associated with the miR-34a-mediated suppression of c-Myc in a p53-dependent manner.


Hong L.-F.,Peking Union Medical College | Hong L.-F.,Fifth Hospital of Wuhan | Luo S.-H.,Fifth Hospital of Wuhan | Li J.-J.,Peking Union Medical College
Journal of Geriatric Cardiology | Year: 2013

Percutaneous coronary intervention (PCI) in an anomalous right coronary artery (RCA) can be technically difficult because selective cannulation of the vessel may not be easy. We thereby present two cases with unstable angina pectoris of anomalous originated RCA. The PCI were successfully performed in two patients with a special guiding wire manipulating skill which we called "gone with the flow" combined with balloon anchoring technology, providing excellent angiographic visualization and sound guide support for stent delivery throughout the procedure without severe cardiovascular adverse effects. Our primary data suggested that PCI for geriatric patients with an anomalous origin of RCA accompanied by severe atherosclerotic lesions might also be a safe, available, and feasible strategy. ©2013 JGC All rights reserved.


He A.-B.,Fifth Hospital of Wuhan | Peng X.-L.,Fifth Hospital of Wuhan | Song J.,HAN University of Applied Sciences | Zhang J.-X.,HAN University of Applied Sciences | And 4 more authors.
World Journal of Gastroenterology | Year: 2015

AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer. METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients. Statistical analysis was performed by metaanalysis. Four randomized controlled trials met the inclusion criteria. RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response rate of S-1 vs capecitabine was 0.94 (95%CI: 0.59-1.51, P = 0.93). Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia (OR = 0.99, 95%CI: 0.65-1.49, P = 0.94) and thrombocytopenia (OR = 0.72, 95%CI: 0.31-1.67, P = 0.44). The most frequent non-hematologic toxicities included nausea (OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome (OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001). CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.


Zhong J.,Fifth Hospital of Wuhan | Yang L.,Hubei University | Liu N.,Fifth Hospital of Wuhan | Zheng J.,Fifth Hospital of Wuhan | Lin C.-Y.,Hubei University
Digestive Diseases and Sciences | Year: 2013

Background: The inhibitor of growth (ING) family is involved in multiple cellular functions, but the role of ING2 in gastric cancer progression is unclear. Aim: To investigate the effects of ING2 gene knockdown on chemosensitivity to 5-fluorouracil (5-FU) in human gastric cancer cells and its possible mechanisms. Methods: Short hairpin RNA (shRNA) targeting ING2 (shING2) was transfected into MGC-803 cells using Lipofectamine 2000, and stable transfection cell lines were established using G418. Cell viability, cell cycle distribution, cell apoptosis, and invasive ability were measured to determine the influence of ING2 knockdown on cell biologic characteristics. Messenger RNA (mRNA) and protein levels of ING2, cyclin D1, NF-kappaB/p65, and several matrix metalloproteinases (MMPs) were determined by use of real-time polymerase chain reaction (PCR) or Western blotting, respectively. Results: Our results showed that ING2 knockdown induced cell apoptosis and inhibited cell viability significantly (P < 0.05). Additionally, ING2 knockdown induced a specific G0/G1 arrest. Furthermore, the suppression of ING2 could enhance the chemosensitivity of gastric cancer cells to 5-FU significantly. Moreover, knockdown of ING2 expression significantly reduced cellular metastatic ability and expression of MMPs in MGC-803 cells. The expression of cyclin D1 and NF-kappaB/p65 was also markedly inhibited in MGC-803/shING2 cells compared with control cells. Conclusions: ING2 not only plays an essential role in the growth and invasion of MGC-803 cells but also represents a potential approach to chemosensitization therapy in human gastric cancer. © 2013 Springer Science+Business Media New York.


Ziyan W.,Fifth Hospital of Wuhan | Yang L.,Fifth Hospital of Wuhan
Irish Journal of Medical Science | Year: 2016

Background: Recent studies have shown that microRNA-21 (miR-21) is overexpressed in solid tumors and implicated in the modulation of drug-induced resistance. Methods: In this study, we investigated the anti-tumor effects of miR-21 on the sensitivity of osteosarcoma cells to CDDP. Results: Changes in the sensitivity of osteosarcoma cells to CDDP were examined after transfection with miR-21 mimics or anti-miR-21 or bcl-2 siRNA in combination with CDDP. Osteosarcoma cells transfected with miR-21 mimics were significantly resistant to CDDP, while suppression of miR-21 in osteosarcoma cells led to enhanced CDDP cytotoxicity. Moreover, the miR-21-induced changes in chemoresponse were ameliorated by down-regulation of bcl-2 by its siRNA. Conclusion: The miR-21 in osteosarcoma cells is a significant modulator of the anti-tumor effect of CDDP by regulating the expression of bcl-2, and the study reveals a novel mechanism of osteosarcoma drug resistance. © 2014, Royal Academy of Medicine in Ireland.


Li M.H.,Fifth Hospital of Wuhan | Liu Y.,Fifth Hospital of Wuhan
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2010

OBJECTIVE: To study the clinical effects of the adjustable external fixation combined with the limited internal fixation such as ordinary screws, Kirschner wire fixation for the treatment of complex calcaneal fractures (Sanders III, IV). METHODS: From January 2003 to June 2008, 27 patients 36 feet (19 feet in the left and 17 feet in the right) with calcaneal fractures of Sanders III and IV (the age ranged from 17 to 65 years, mean 37 years)were treated with external fixator combined with ordinary screws and Kirschner wire fixation. All the patients were undergone X-ray and CT examinations and classified by Crosby-Fitzgibbons-Sanders. The changes of the Böhler and Gissane angles were analyzed by X-ray. The functional of the feet was assessed by ZHANG Tie-liang calcaneal fractures scoring system. RESULTS: Thirty-two feet were followed up for 11 to 24 months, with an average of 13 months. The Böhler and Gissane angles changed from average (8.0 +/- 7.3) degree and (130.5 +/- 10.5) degree, back to postoperative (29.6 +/- 7.4) degree and (122.5 +/- 8.6) degree. According to ZHANG Tie-liang scoring system, the result was excellent in 17 feet, good in 8 feet,fair in 5 feet and not satisfied with 2 feet. Three feet with wound infection or skin flap necrosis were healed after vacuum sealing drainage or wound dressing. CONCLUSION: The combination of external fixator and limited internal fixation is an effective treatment for complex calcaneal fractures with few complications and good functional recovery.


Fu X.,Longgang District Central Hospital of Shenzhen | Feng J.,Fifth Hospital of Wuhan | Zeng D.,Longgang District Central Hospital of Shenzhen | Ding Y.,Longgang District Central Hospital of Shenzhen | And 2 more authors.
Bioscience Reports | Year: 2014

CDDP [cisplatin or cis-diamminedichloroplatinum(II)] and CDDP-based combination chemotherapy have been confirmed effective against gastric cancer. However, CDDP efficiency is limited because of development of drug resistance. In this study, we found that PAK4 (p21-activated kinase 4) expression and activity were elevated in gastric cancer cells with acquired CDDP resistance (AGS/CDDP and MKN-45/CDDP) compared with their parental cells. Inhibition of PAK4 or knockdown of PAK4 expression by specific siRNA (small interfering RNA)-sensitized CDDP-resistant cells to CDDP and overcome CDDP resistance. Combination treatment of LY294002 [the inhibitor of PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B or PKB) pathway] or PD98509 {the inhibitor of MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] pathway} with PF-3758309 (the PAK4 inhibitor) resulted in increased CDDP efficacy compared with LY294002 or PD98509 alone. However, after the concomitant treatment of LY294002 and PD98509, PF-3758309 administration exerted no additional enhancement of CDDP cytotoxicity in CDDP-resistant cells. Inhibition of PAK4 by PF-3758309 could significantly suppress MEK/ERK and PI3K/Akt signalling in CDDP-resistant cells. Furthermore, inhibition of PI3K/Akt pathway while not MEK/ERK pathway could inhibit PAK4 activity in these cells. The in vivo results were similar with those of in vitro. In conclusion, these results indicate that PAK4 confers CDDP resistance via the activation of MEK/ERK and PI3K/Akt pathways. PAK4 and PI3K/Akt pathways can reciprocally activate each other. Therefore, PAK4 may be a potential target for overcoming CDDP resistance in gastric cancer. © 2014 The Author(s).


Miao H.-L.,Guangdong Medical College | Pan Z.-J.,Fifth Hospital of Wuhan | Lei C.-J.,Guangdong Medical College | Lei C.-J.,Fifth Hospital of Wuhan | And 7 more authors.
Journal of Cellular Biochemistry | Year: 2013

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). Yes-associated protein (YAP) is also found over-expressed in HCC and has been identified as a key effector molecule in Hippo pathway, which could control the organ size in animals through the regulation of cell proliferation and apoptosis and plays an important role in the development of malignant tumors. Studies have reported that GPC3 and YAP might collaborate to regulate the development of HCC. To elucidate the role of GPC3 in the development of HCC and its relationship with YAP, siRNA technique was employed to knock down GPC3 in Huh7 HCC cells. Moreover, recombinant human YAP-1 was used to examine the effects of GPC3 on Huh7 cells. The results of flow cytometric analysis and Annexin-V-FLUOS apoptosis assay showed that knockdown of GPC3-induced apoptosis in Huh7 cells, resulting in inhibition of cell proliferation as examined by EdU incorporation assay, migration, and invasion. GPC3 knockdown also suppressed the expression of YAP in mRNA and protein levels, as examined by fluorescence quantitative PCR and Western blot analysis. Moreover, addition of recombinant human YAP-1 effectively rescued the cells from apoptosis triggered by GPC3 knockdown. Taken together, our findings suggest that GPC3 regulates HCC cell proliferation with the involvement of Hippo pathway. J. Cell. Biochem. 114: 625-631, 2013. © 2012 Wiley Periodicals, Inc.


Gao L.,University of Newcastle | Xia L.,Renmin University of China | Pan S.-Q.,Renmin University of China | Xiong T.,Fifth Hospital of Wuhan | Li S.-C.,University of Newcastle
Epilepsia | Year: 2013

Purpose Generic preference-based health-related quality of life (HRQoL) instruments are increasingly used to estimate the quality-adjusted life years (QALYs) in cost-effectiveness/utility studies. However, no such tool has been used and validated in epilepsy patients in China. This study was conducted to validate a generic preference-based HRQoL instrument, namely the Quality of Well-Being Scale-Self-Administered (QWB-SA) in Chinese patients with epilepsy. Methods Accepted translation procedures were followed to develop the Chinese QWB-SA. An epilepsy group (adults with established diagnosis of epilepsy) and a control group (adults without manifested cognitive problems) were recruited between July and October, 2012, from two tertiary hospitals in China. After giving informed consent, each subject completed both the QWB-SA and the EuroQol (EQ-5D) as well as provided sociodemographic data. Construct validity was examined by six (convergent) and two (discriminative) a priori hypotheses. Sensitivity was compared by ability to differentiate epilepsy-specific variable-based subgroups. Agreement between the QWB-SA and EQ-5D was assessed by intraclass correlation coefficient (ICC) and Bland-Altman plot. Key Findings One hundred forty-four epilepsy patients and 323 control subjects were enrolled, respectively. The utility medians (interquartile range, IQR) for the QWB-SA and EQ-5D were 0.673 (0.172), 0.848 (0.275) for epilepsy group and 0.775 (0.258), 1.000 (0.152) for control group, respectively. The difference in utilities between the two measures were significant (p < 0.0001). Construct validity was demonstrated by six a priori hypotheses. In addition, the QWB-SA was able to discriminate across different seizure frequency and antiepileptic drug (AED) treatment subgroups. Agreement between the QWB-SA and EQ-5D was demonstrated by ICC (0.725). Finally, the multiple linear regression analysis indicated that group and the EQ-VAS had influences on the utility difference of these two measures, whereas seizure frequency and number of AEDs were predictors of HRQoL as measured by the QWB-SA. Significance The QWB-SA is a valid and sensitive HRQoL measure in Chinese patients with epilepsy. Compared to the EQ-5D, the QWB-SA showed superiority in coverage of health dimensions, sensitivity, and ceiling effects. However, future study is still needed to ascertain its responsiveness. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.


Pang Y.,Fifth Hospital of Wuhan | Han W.-Q.,Fifth Hospital of Wuhan
Chinese Journal of Cancer Prevention and Treatment | Year: 2015

OBJECTIVE: To observe the human papillomavirus (HPV) prevalence and its distribution character among females through screenings in Fifth Hospital of Wuhan and provide epidemiological data for the prevention of cervical cancer and development of HPV vaccine. METHODS: The clinical material consisted of 2409 women, who were from Department of Gynaecology and the health physical examination of the Fifth Hospital of Wuhan from May 2011 to Sep 2014.Their cervical exfoliated cells were checked for HPV genotypes by flow-through hybridization. The method could detect 15 kinds of high-risk subtypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and 6 kinds of low-risk subtypes (HPV6, 11, 42, 43, 44, 81). The age distribution of women infected with HPV and genotypes of HPV were analyzed. RESULTS: Out of 2409 cervical cell specimens, 422 cases were detected HPV infections with the positive rate of 17.51%, of which 82.76% was infected by high-risk subtype. In the 21 checked outs HPV43 was not detected. In fifteen types of high-risk HPV, HPV16(19.24%) were the most common subtypes, followed by 52(15.63%), 58(10.42%), 53(6.61%), 3(5.61%), 39(5.01%), 18(4.81%), 31(4.01%), 68(3.41%), 66(2.61%), 59(2.20%), 56(1.40%), 51(1.00%), 35(0.60%), 45(0.20%). Five types of low-risk HPV were detected, of which HPV81(8.22%) was the most common subtype, followed by 11(5.21%), 6(2.40%), 44(1.00%), 42(0.40%). Among the positive females, 83.64% was single type infection, of which 83.56% was high-risk infection. The positive rate of high-risk HPV in single type was less than those in other types (P<0.05). The objects were divided into five groups according to age. Among the females aged 51-60 years, the positive rate was 22.57%, which was higher than that in other groups (P<0.05). The predominant genotype was HPV16 among the females aged >40-50, which was different from other groups. CONCLUSIONS: The predominant genotypes of HPV infection in female reproductive tract are HPV16 and HPV52. The most common type of HPV infection is single type, in which the positive rate of high-risk types is the highest. The positive rate of females aged >50-60 years is the highest in all age groups and we should pay attention to screening for HPV among these females. © 2015, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.

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