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Gu J.,Tianjin Medical University | Gu J.,Tianjin Union Medical Center | Zhu S.,Tianjin Union Medical Center | Li X.,Tianjin Medical University | And 3 more authors.
PLoS ONE | Year: 2014

Background: Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent. Methods: By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software. Results: Seventeen trials including a total of 1167 patients (604 and 563 each arm) were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade3-4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54-0.95; p<0.00001), Grade 2-4 acute xerostomia (RR,0.70; 95%CI,0.52-0.96; p = 0.02), or late xerostomia (RR,0.60; 95%CI,0.49-0.74; p,0.00001) and Grade 3-4 dysphagia (RR,0.39; 95%CI,0.17-0.92; p= 0.03). However, subgroup analysis demonstrated that no statistically significant reduction of Grade3-4 mucositis (RR,0.97; 95% CI,0.74-1.26; p = 0.80), Grade 2-4 acute xerostomia (RR,0.35; 95%CI,0.02-5.44; p = 0.45), or late xerostomia (RR,0.40; 95%CI,0.13-1.24; p = 0.11) and Grade 3-4 dysphagia (RR,0.23; 95%CI,0.01-4.78; p = 0.35) was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89-1.17; p = 0.76) and partial response (RR,0.90; 95%CI, 0.56-1.44; p = 0.66). For the hematologic side effect, no statistical difference of Grade 3-4 leucopenia (RR,0.60; 95%CI,0.35-1.05; p = 0.07), anemia (RR,0.80; 95%CI, 0.42-1.53; p = 0.50) and thrombocytopenia (RR,0.43; 95%CI,0.16-1.15; p = 0.09) were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3-4) of 5%, 6%, 4% and 4% respectively. Conclusion: This systematic review showed that amifostine significantly reduce the serious mucositis, acute/late xerastomia and dysphagia without protection of the tumor in HNSCC patients treated with radiotherapy. And the toxicities of amifostine were generally acceptable. © 2014 Gu et al.


Chu D.,PLA Fourth Military Medical University | Zhang Z.,Tianjin Union Medical Center | Zhou Y.,PLA Fourth Military Medical University | Wang W.,PLA Fourth Military Medical University | And 5 more authors.
Annals of Oncology | Year: 2011

Background: Aberrantly activated Notch signaling has been shown to play a key role in carcinogenesis and progression of various human malignancies. In this study, we investigated the expression of Notch1 and Notch2 in colorectal cancer to determine whether they could serve as prognostic predictors. Patients and methods: The protein expression of Notch1 and Notch2 was examined by immunohistochemistry in 1003 clinical colorectal cancer specimens. Notch1 and Notch2 protein levels were investigated by immunohistochemistry. Statistical analysis was carried out to assess their prognostic value. Results: Significantly negative correlation between Notch1 and Notch2 was found in colorectal cancer (P < 0.001). Notch1 and Notch2 were proved to be inversely correlated with tumor differentiation, depth of invasion, lymph node metastases, distant metastasis, TNM (tumor-node-metastasis) stage and survival of patients, suggesting opposite function of the two receptors. Notch1 and Notch2 were proved to be adverse independent prognostic predictors (P < 0.001). Moreover, a synergistic effect of positive Notch1 and negative Notch2 coexpression on predicting poor overall survival was proved. Conclusions: Notch1 and Notch2 may be independent adverse prognostic predictors for patients with colorectal cancer. These results would contribute to identify more efficient prognostic predictors and therapeutic targets. The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology.


Chu D.,PLA Fourth Military Medical University | Zhang Z.,PLA Fourth Military Medical University | Zhou Y.,Tianjin Union Medical Center | Li Y.,Chengdu Military General Hospital | And 6 more authors.
Oncotarget | Year: 2015

The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis.Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation.These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.


Cui C.,Tianjin Haihe Hospital | Sun X.,Tianjin Haihe Hospital | Zhang J.,Tianjin Haihe Hospital | Han D.,Tianjin Haihe Hospital | Gu J.,Tianjin Union Medical Center
Journal of Cancer Research and Therapeutics | Year: 2014

Objective: The serum level of Cyfra21-1 was always elevated in patients with nonsmall cell lung carcinoma. The aim of this meta-analysis was to evaluate the serum Cyfra21-1 as a biomarker in the diagnosis of nonsmall cell lung cancer (NSCLC).Methods: All the articles associated with serum Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline, and CNKI databases. The number of patients for true positive, false positive, false negative and true negative were extracted from each individual study. The pooled sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (-lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc) curve were calculated by MetaDiSc 1.4 software.Results: After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The pooled diagnosis sensitivity, specificity, +lr, -lr and dor were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95), 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) and 22.57 (95%CI: 13.89-36.68) respectively. The area under the sroc curve was 0.95. And significant publication bias was found in this meta-analysis (P = 0.049).Conclusion: With published data, the serum Cyfra21-1 was a useful biomarker for diagnosis of NSCLC.


Wang W.H.,Tianjin Union Medical Center
Clinical nuclear medicine | Year: 2013

A 74-year-old man with right upper eyelid swell accepted FDG PET/CT examination, which showed an intensely FDG-avid soft tissue nodular mass within the eyelid. It was suggestive of malignancy. There was no evidence of active neoplastic disease elsewhere. The nodule was excised by surgery. Histopathological findings showed characteristic findings of diffuse large B-cell lymphoma. This case highlights the utility of FDG PET/CT in identifying rare types of lymphoma.


Li Q.,Tianjin Union Medical Center | Qi X.,Tianjin Union Medical Center | Jia W.,Tianjin Union Medical Center
Biochemical and Biophysical Research Communications | Year: 2016

Oxidative stress (OS) plays a crucial role in the development of myocardial disease, which can induce the dysfunction of cardiac muscle cells. 3,3′,5-triiodothyroxine (T3) is a hormone secreted from the thyroid gland that has been shown to protect cells by improving the redox state and to regulate the expression of pyruvate kinase muscle isozyme (PKM, including two isoforms PKM1 and PKM2). The present study aimed to reveal the key effects of T3 on protecting human myocardial cell lines from oxidative stress and the downstream molecular mechanism. An oxygen-glucose deprivation/reperfusion model (OGDR) and three subtypes of the deiodinase family (DIO1, DIO2, and DIO3), which convert thyroxine (T4) to T3, were tested in this model. Our results show that the expression of DIO1, DIO2 and T3 was downregulated, but DIO3 was upregulated in OGDR-treated AC16 and HCM-a cells. Then, OGDR-treated cells were treated with T3 and T4. The results show that T3 inhibited the expression of reactive oxygen species (ROS) and malonic dialdehyde (MDA), but upregulated glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The effects of T4 were not notable. T3 also protected OGDR cells from apoptosis and upregulated the PKM2/PKM1 ratio. Further mechanistic studies found that PKM2 inhibition by small interfering RNA (siRNA) could attenuate the anti-OS and anti-apoptotic effects of T3. These findings suggest that T3 can inhibit apoptosis and oxidative stress in OGDR-treated AC16 and HCM-a cells by regulating the PKM2/PKM1 ratio. © 2016 Elsevier Inc. All rights reserved.


Zheng D.-J.,Weifang Peoples Hospital | Yu G.-H.,Weifang Peoples Hospital | Gao J.-F.,Weifang Peoples Hospital | Gu J.-D.,Tianjin Medical University | Gu J.-D.,Tianjin Union Medical Center
Asian Pacific Journal of Cancer Prevention | Year: 2013

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.


Zhang Z.,Tianjin Union Medical Center
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2012

To investigate the early diagnosis and treatment of acute mesenteric ischemia. Forty-two patients with acute mesenteric ischemia from June 2007 to November 2011 were reviewed retrospectively. All patients were diagnosed with DSA and (or) CT and (or) surgery. In this group, there were 32 cases of acute occlusion of meseteric ischemia (AOMI), 9 cases of superior mesenteric venous thrombosis (SMVT) and 1 case of non-occlusive mesenteric ischemia. The patients were treated using comprehensive treatment including early intervention treatment and application of the principle of damage control. The survival of all patients was followed up for 6 months or more in outpatient. (1) Of the 32 AOMI cases, 4 cases healing by systemic anticoagulation; The 19 cases received interventional treatment, including 10 cases received simply interventional treatment, surgery after the failure of intervention in 5 cases, 3 patients died without surgery and postoperative interventional treatment one cases were cured; Eight cases received surgery treatment; One case gave up. (2) Of the 9 SMVT cases, 2 cases healing by systemic anticoagulation; The 6 cases received interventional treatment, including 1 cases received simply interventional treatment, surgery after the failure of intervention in 1 cases, 4 cases to consider intestinal necrosis received interventional treatment again after surgery; One patient died without treatment. (3) Eight cases received delay abdomen close treatment with the principle of damage control surgery. The overall mortality rate of 23.8% (10/42). Interventional treatment of 26 cases, 4 deaths, a mortality rate of 15.3%; The abdomen delayed close of 8 cases, 1 death. The results show that early diagnosis and treatment is critical to reduce AMI mortality. Comprehensive treatment of early intervention treatment and application of the principle of damage control can significantly reduce the mortality of AMI.


Zhang H.,Tianjin Union Medical Center
Journal of radiation research | Year: 2013

Ionizing radiation (IR) causes not only acute tissue damage but also residual bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to the induction of reactive oxygen species (ROS) pressure in hematopoietic cells. In this study, we examined if SB431542, a transforming growth factor β1 (TGFβ1) inhibitor, can mitigate IR-induced BM suppression in vitro. Our results showed that treatment with SB431542 protected mice bone marrow mononuclear cells (BMMNCs), hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) from IR-induced suppression using cell viability assays, clonogenic assays and competitive repopulation assays. Moreover, expression of gene-related ROS production in hematopoietic cells was analyzed. The expression of NOX1, NOX2 and NOX4 was increased in irradiated BMMNCs, and that of NOX2 and NOX4 was reduced by SB431542 treatment. Therefore, the results from this study suggest that SB431542, a TGFβ1 inhibitor, alleviates IR-induced BM suppression at least in part via inhibiting IR-induced NOX2 and NOX4 expression.


Jiang C.,Tianjin Union Medical Center | Li X.,Tianjin Medical University | Zhao H.,Tianjin Union Medical Center | Liu H.,Xinjiang Medical University
Molecular Cancer | Year: 2016

Long non-coding RNAs (lncRNAs) play important roles in malignant neoplasia. Indeed, many hallmarks of cancer define that the malignant phenotype of tumor cells are controlled by lncRNAs. Despite a growing number of studies highlighting their importance in cancer, there has been no systematic review of metastasis-associated lncRNAs in various cancer types. Accordingly, we focus on the key metastasis-related lncRNAs and outline their expression status in cancer tissues by reviewing the previous stuides, in order to summarize the nowadays research achivements for lncRNAs related to cancer metastasis. Medline, EMBASE, as well as PubMed databases were applied to study lncRNAs which were tightly associated with tumor invasion and metastasis. Up to now, a substantial number of lncRNAs have been found to have important biological functions. In this review, according to their various features in cancer, lncRNAs were roughly divided into three categories: promoting tumor invasion and metastasis, negative regulation of tumor metastasis and with dual regulatory roles. The present studies may establish the foundation for both further research on the mechanisms of cancer progression and future lncRNA-based clinical applications. © 2016 The Author(s).

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