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Mechanism of thalidomide to enhance cytotoxicity of temozolomide in U251-MG glioma cells in vitro

Chinese Medical Journal 2009年第11期122卷 1260-1266页

作者： GAO Song YANG Xue-jun ZHANG Wen-gao JI Yan-wei PAN Qiang Department of Neurosurgery Tianjin Medical University General Hospital Tianjin 300052 China

Background Glioma is the most common primary brain tumor with poor prognosis. Temozolomide has been used with thalidomide to treat gliomas. We investigated the synergistic mechanism of these two drugs in vitro. Methods Human malignant glioma cells U251-MG were cultured and assigned to four groups with different treatments for 3 days： temozolomide group （100 μmol/L）, thalidomide group （100 μg/L）, temozolomide （100 μmol/L） plus thalidomide group （100 μg/L） and control group. MTT assay was applied to evaluate the cell viability. Cell cycle was analyzed by flow cytometry. The ultra-structural features of autophagosomes were observed with electron microscope. Acridine orange and monodansylcadaverine were adopted to label autophagosomes and flow cytometry was applied for quantification of autophagosomes. The expression of autophagy-associated protein was detected by Western blotting. Results Proliferation of tumor cell was obviously suppressed by temozolomide with thalidomide treatment than by either drug used alone （P=0.000 for each day）. The combination treatment induced cell cycle arrest at G0/G1 phase. Typical autophagic ultra-structural character was found after the combined treatment. Thalidomide promoted the autophagy induced by temozolomide. The autophagy-associated proteins - microtubule associated protein 1 light chain 3 （MAP1LC3） and Beclinl were more significantly up-regulated by the combined treatment than temozolomide used alone （MAP1LC3, P=0.000; Beclinl, P=0.004）. The expression level of phosphatase and tensin homolog deleted on chromosome ten （PTEN）, which promoted autophagy by suppressing PI3K/Akt/mTOR signaling pathway, was elevated by thalidomide （thalidomide group： P=0.000; combined group： P=0.002）. Conclusions Thalidomide enhances the cytotoxicity of temozolomide by promoting the autophagy induced by temozolomide. Contributing to the up-regulation of PTEN by thalidomide, the expression of autophagy associated protein-MAP1LC3 and Beclinl was enhanced,

关键词： glioma thalidomide temozolomide autophagy

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Novel immunotherapy strategy based on tumor microenvironment

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Tumor Microenvironment Research 2020年第2期2卷 34-41页

作者： Qi-Fan Luo Yi-Ming Zhao Tianjin Medical University Tianjin 300052China Department of General Surgery Tianjin Medical University General HospitalTianjin 300052China

Recent advances in molecular and cellular tumor immunology have demonstrated that immunotherapy might have great potential,which would be another important treatment strategy after surgery,radiotherapy and ***,this review mainly summarizes and discusses the classification of tumor immune microenvironment and the existing main immunotherapies,in order to provide some guidance and suggestions for accurate individualized immunotherapy.

关键词： Tumor microenvironment Immunotherapy Immune checkpoint blockade

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Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia

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World Journal of Stem Cells 2021年第8期13卷 1030-1048页

作者： Wen-Qiang Xin Wei Wei Yong-Li Pan Bao-Long Cui Xin-Yu Yang Mathias Bähr Thorsten R Doeppner Department of Neurology University Medical Center GöttingenGöttingen 37075Germany Department of Neurosurgery Tianjin Medical University General HospitalTianjin 300052China

Inflammation plays an important role in the pathological process of ischemic stroke,and systemic inflammation affects patient *** resident immune cells in the brain,microglia are significantly involved in immune defense and tissue repair under various pathological conditions,including cerebral *** the differentiation of M1 and M2 microglia is certainly oversimplified,changing the activation state of microglia appears to be an intriguing therapeutic strategy for cerebral *** evidence indicates that both mesenchymal stem cells(MSCs)and MSC-derived extracellular vesicles(EVs)regulate inflammation and modify tissue repair under preclinical stroke ***,the precise mechanisms of these signaling pathways,especially in the context of the mutual interaction between MSCs or MSC-derived EVs and resident microglia,have not been sufficiently ***,this review summarizes the state-ofthe-art knowledge on MSC-and MSC-EV-mediated regulation of microglial activity under ischemic stroke conditions with respect to various signaling pathways,including cytokines,neurotrophic factors,transcription factors,and microRNAs.

关键词： Extracellular vesicles Mesenchymal stem cells Microglial activation M2 polarization Ischemic stroke

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Effects of Pemetrexed and Docetaxel Combined with Cisplatin in the Treatment of Non-small Cell Lung Cancer

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Proceedings of Anticancer Research 2018年第3期2卷 19-22页

作者： Lei Wang Diansheng Zhong Tianjin Chest Hospital Tianjin300052China Tianjin Medical University General Hospital Tianjin300052China

The purpose of this study was to compare the clinical effects of pemetrexed and docetaxel combined with cisplatin in the treatment of patients with non-small cell lung cancer.A total of 58 patients with non-small cell lung cancer who were enrolled between January 2017 and January 2018 were enlisted into a randomized digital table.29 patients who have received treatment with combined pemetrexed and cisplatin were assigned to the pemetrexed group,whereas for the other 29 patients which were treated with docetaxel and cisplatin combined,were assigned to the docetaxel group to verify the calculated clinical treatment efficiency of the patients with non-small cell lung cancer,soluble vascular cell adhesion molecule 1(SVCAM-1),and activated leukocyte cell adhesion molecule-1(alCAM-1)concentrations and to evaluate the quality of life scores of the patients after half a year as well as the incidences of adverse reactions following the treatments *** differences in SVCAM-1 and alCAM-1 concentrations and incidence of adverse reactions in patients with non-small cell lung cancer in the docetaxel group as compared with patients in the pemetrexed group after the treatments were statistically significant(P0.05,demonstrated no analytical *** pemetrexed combined with cisplatin and docetaxel in combination with cisplatin as forms of treatments demonstrated significant effects in patients with non-small cell lung ***,based on our study,it was found that the combined treatment involvi

关键词： pemetrexed docetaxel cisplatin non-small cell lung cancer

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Enhanced invasion in vitro and the distribution patterns in vivo of CD133＋ glioma stem cells

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Chinese Medical Journal 2011年第17期124卷 2599-2604页

作者： YU Sheng-ping YANG Xue-jun ZHANG Bin MING Hao-lang CHEN Cong REN Bing-cheng LIU Zhi-feng LIU Bin Department of Neurosurgery Tianjin Medical University General Hospital Tianjin 300052 China

Background Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. This study aimed to assess invasive ability of glioma stem cells （GSCs） derived from C6 glioma cell line and the distribution patterns of GSCs in Sprague-Dawley （SD） rat brain tumor. Methods Serum-free medium culture and magnetic isolation were used to gain purely CD133＋ GSCs. The invasive ability of CD133＋ and CD133- C6 cells were determined using matrigel invasion assay. Immunohistochemical staining for stem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns of GSCs in brain tumor of rats and the relationship among GSCs, vessels, and white matter tracts. The results of matrigel invasion assay were estimated using the Student＇s t test and the analysis of Western blotting was performed using the one-way analysis of variance （ANOVA） test. Results CD133＋ GSCs （number： 85.3±4.0） were significantly more invasive in vitro than matched CD133- cells （number： 25.9=~3.1）（t=14.5, P 〈0.005）. GSCs invaded into the brain diffusely and located in perivascular niche of tumor-brain interface or resided within perivascular niche next to white fiber tracts. The polarity of glioma cells containing GSCs was parallel to the white matter tracts. Conclusions Our data suggest that CD133＋ GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probably disseminate along the long axis of blood vessels and transit through the white matter tracts. The therapies targeting GSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach for avoiding mali qnant glioma recurrence.

关键词： glioma glioma stem cell invasion white matter tracts

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Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps

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Chinese Medical Journal 2016年第20期129卷 2427-2433页

作者： Hai-Long Cao Xue Chen Shao-Chun Du Wen-Jing Song Wei-Qiang Wang Meng-Que Xu Si-Nan Wang Mei-Yu Piao Xiao-Cang Cao Bang-Mao Wang Department of Gastroenterology and Hepatology Tianjin Institute of Digestive DiseaseTianjin Medical University General HospitalTianjin 300052China Department of Pathology Tianjin Medical University General HospitalTianjin 300052China

Background：Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western ***,few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic *** aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic ***：Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were ***-square test or Fisher＇s exact test and logistic regression analysis were used for the data ***：A total of 9191 （31.7%） patients were detected with at least one colorectal *** prevalence of serrated polyps was 0.53% （153/28,981）.The proportions of hyperplastic polyp （HP）,sessile serrated adenoma/polyp （SSA/P）,and traditional serrated adenoma （TSA） of all serrated polyps were 41.2%,7.2%,and 51.6%,respectively,which showed a lower proportion of HP and SSA/P and a higher proportion of *** polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and *** proportions of large and proximal serrated polyps were 13.7% （21/153） and 46.4% （71/153）,*** total,98.9% （89/90） serrated adenomas were found with ***,14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia,and large serrated polyps （LSPs）（odds ratio：3.446,95% confidence interval：1.010-11.750,P 〈 0.05）,especially large HPs,might have an association with synchronous advanced neoplasia （AN）.Conclusions：The overall detection rate ofcolorectal serrated polyps in Chinese symptomatic patient population was low,and distribution pattern of three subtypes is different from previous ***,LSPs,especially large HPs,might be associated with an increased risk of synchronous AN.

关键词： Colorectal Cancer Colorectal Serrated Polyps Hyperplastic Polyp Traditional Serrated Adenoma Sessile Serrated Adenoma/Polyp

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Chinese Medical Journal 2010年第17期123卷 2392-2399页

作者： FENG Jing Ambrose An-Po Chiang WU Qi CHEN Bao-yuan CUI Lin-yang LIANG Dong-chun ZHANG Ze-li YAO Wo Department of Respiratory Disease Tianjin Medical University General Hospital Tianjin 300052 China Division of Pulmonary and Critical Care Medicine Duke University Medical Center Durham NC 27710 USA Tianjin Neurology Research Institute Tianjin 300052 China Tianjin Medical University Endocrinology Research Institute Tianjin 300052 China

Background Sleep disturbance is common in patients with emphysema. This study aimed to develop a novel model of sleep-related hypoxemia （SRH） in emphysema （SRHIE） with rats, and to explore the inflammatory status of SRHIE in lung, liver, pancreas, carotid artery and whole *** Seventy-five male Wistar rats were assigned to 5 groups with 15 per group according to the exposure conditions. The protocols varied with the degree of hypoxia exposure and severity of pre-existing emphysema caused by cigarette smoke exposure：（1） SRH control （SRHCtrl） group, sham smoke exposure （smoke exposure, exposed to smoke of 15 cigarettes twice everyday, 16 weeks） and SRH exposure （12.5% O2, 3 hours, SRH exposure, divide total hypoxia time （1.5 hours or 3 hours） into 4 periods evenly （22.5 minutes or 45 minutes） and distribute these hypoxia periods evenly into physiological sleep time of rats identified by electroencephalogram, week 9 to week 16）; （2） Emphysema control （ECtrl） group, smoke exposure and sham SRH exposure （21% O2, 3 hours）; （3） Short SRH in emphysema （SRHShort） group, smoke exposure and short SRH exposure （12.5% O2, 1.5 hours）; （4） Mild SRH in emphysema （SRHMild） group,smoke exposure and mild SRH exposure （15% O2, 3 hours）; （5） Standard SRH in emphysema （SRHStand） group, smoke exposure and SRH exposure （12.5% O2, 3 hours）. ECtrl, SRHShort, SRHMild and SRHStand groups were groups with emphysematous rats. Two days before the end of exposure, 5 rats in each group were randomly selected for arterial blood gas analysis. In the rest 10 rats in each group, we obtained blood samples and bronchoalveolar lavage fluid （BALF）for routine tests. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress （measuring hepatic oxidative stress enzymes, superoxide dismutase （SOD） activity, catalase （CAT） activity and malondialdehyde （MDA） concentration）.Results Emphysematous groups had higher me

关键词： sleep-related hypoxemia emphysema inflammation oxidative stress bronchoalveolar lavage fluid superoxide dismutase catalase malondialdehyde

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Irreversible electroporation versus radiofrequency ablation for malignant hepatic tumor:A prospective single-center double-arm trial

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Journal of Interventional Medicine 2022年第2期5卷 89-94页

作者： Boyu Liu Dianxun Fu Yong Fan Zhe Wang Xu Lang Department of Radiology Tianjin Medical University General HopitalAnshan Rood 154#Heping DitricTianjin300052China

Objective:Irreversible electroporation(IRE)is a nonthermal ablation technique for the treatment of malignant liver *** has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular *** study aimed to compare the efficacy,safety,and intermediate-term outcomes of IRE and radiofrequency(RF)therapy in malignant liver ***:Twenty-four patients with primary or secondary liver malignancies were included in this prospective,double-arm clinical *** were randomly divided into the IRE and RF *** primary outcome was the efficacy(local ablation control evaluation at 90 days).The secondary outcomes were safety(procedure-related complications at≤90 days)and intermediate-term survival(at 24 months).Results:The ablation assessment at 90 days after surgery with m RECIST for IRE versus RF were 70%,20%,0%,and 10%versus 92.9%,7.1%,0%,and 0%(CR,PR,SD,and PD,respectively).The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%,25%,0%,8.3%,and 8.3%versus 8.3%,50%,0%,0%,and 0%(Grade I,II,Ⅲ,IV,and V,respectively).The average overall survival(OS)was 17.55 months in the IRE group(95%CI 15.13-22.37)and 18.75 months in the RF group(95%CI 12.48-22.61).There was no statistical difference between the IRE and RF groups in terms of efficacy(p=0.48),safety(p=0.887),or 24-month OS(p=0.959).Conclusions:IRE ablation revealed similar efficacy and safety in a short-term follow-up,and similar OS in midterm survival as RF ablation in treating malignant hepatic tumors.

关键词： Irreversible electroporation Radiofrequency ablation Efficacy Intermediate-term survival Prospective trial

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Pulmonary Embolism in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

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Chinese Medical Journal 2018年第14期131卷 1732-1737页

作者： Yao-Qian Cao Li-Xia Dong Jie Cao Department of Respiratory General Hospital Tianjin Medical University Tianjin 300052 China

Objective： In most cotintries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease （COPD）. which puts a huge economic burden on the society. Moreover, COPD has been considered as an independent risk factor for pulmonary embolism （PE）. In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis. Data Sources： We searched the terms ＂chronic obstructive pulmonary disease,＂＂＇pulmonary embolism,＂＂exacerbations,＂ and ＂＇thromboembolic＂ in PubMed database and collected the results up to April 2018. The language was limited to English. Study Selection： We thoroughly examined the titles and abstracts of all studies that met our search strategy. The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review. Results： The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria. Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department. PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms. However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation. Obesity and lower limb asymmetry were described as independent predictors for PE. Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation. Conclusions： According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged l

关键词： Acute Exacerbations Chronic Obstructive Pulmonary Disease Pulmonary Embolism

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Preoperative serum alkaline phosphatase： a predictive factor for early hypocalcaemia following parathyroidectomy of primary hyperparathyroidism

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Chinese Medical Journal 2014年第18期127卷 3259-3264页

作者： Sun Longhao He Xianghui Liu Tong Department of General Sugery Tianjin Medical University GeneralHospital Tianjin 300052 China

Background Postoperative hypocalcemia is one of the most common complications following parathyroidectomy for primary hyperparathyroidism （PHPT）. The aim of this study was to analyze the predictive value of biochemical parameters as indicators for episodes of hypocalcemia in patients undergoing parathyroidectomy for PHPT. Methods The patients with PHPT who underwent parathyroidectomy between February 2004 and February 2014 were studied retrospectively at a single medical center. The patients were divided into biochemical, clinical, and no postoperative hypocalcemia groups, based on different clinical manifestations, Potential risk factors for postoperative hypocalcemia were identified and investigated by univariate and multivariate Logistic regression analysis. Results Of the 139 cases, 25 patients （18.0%） were diagnosed with postoperative hypocalcemia according to the traditional criterion. Univariate analysis revealed only alkaline phosphatase （ALP） and the small area under the curve （AUG） of receiver operating characteristics （ROC） curve for ALP demonstrates low accuracy in predicting the occurrence of postoperative hypocalcemia. Based on new criteria, 22 patients were added to the postoperative hypocalcemia group and similar biochemical parameters were compared. The serum ALP was a significant independent risk factor for postoperative hypocalcemia （P=0.000） and its AUC of ROC curve was 0.783. The optimal cutoff point was 269 U/L and the sensitivity and specificity for prediction were 89.2% and 64.3%, respectively. Conclusions The risk of postoperative hypocalcemia after parathyroidectomy should be emphasized for patients with typical symptoms of hypocalcemia despite their serum calcium level is in normal or a little higher range. Serum ALP is a predictive factor for the occurrence of postoperative hypocalcemia.

关键词： primary hyperparathyroidism minimally invasive parathyroidectomy postoperative hypocalcemia alkaline phosphatase

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