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Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cells in vitro

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Gastroenterology Report 2020年第6期8卷 465-475,I0002页

作者： Yong-Qiang Hou Ying-Ying Wang Xing-Can Wang Yao Liu Chun-Ze Zhang Zhe-Sheng Chen Zhe Zhang Wei Wang De-Xin Kong tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmaceutical SciencesTianjin Medical UniversityTianjinP.R.China Department of Otorhinolaryngology Head and Neck Institute of OtorhinolaryngologyTianjin First Central HospitalTianjinP.R.China Department of Colorectal surgery Tianjin Union Medical CenterTianjinP.R.China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA School of Medicine Tianjin Tianshi CollegeTianyuan UniversityTianjinP.R.China

Background Colorectal cancer(CRC)is one of the leading causes of cancer death *** drugs for CRC therapy are urgently *** has been in clinical use for treatment of heart failure and atrial arrhythmias for many *** reports suggested that digoxin might have antitumor efficacy on ***,we aimed to investigate the antitumor effect of digoxin on human CRC cells and the underlying *** Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay and plate colony formation *** effects of digoxin on cell-cycle distribution and apoptosis were analysed by flow *** anti-metastatic effect on tumor cells was determined by wound-healing assay and transwell ***-angiogenic effect was examined by determining the inhibition against proliferation,migration,and tube formation of human umbilical vein endothelial cells(HUVECs).Mechanism study was performed by Western blot,enzyme-linked immunosorbent assay(ELISA),and gelatin-zymography *** Digoxin potently inhibited cell proliferation,induced G1-phase and G2/M-phase arrest in colorectal-cancer HCT8 and SW620 cells,*** obvious apoptosis was observed in the treated ***-metastatic activities were shown on HCT8 cells by inhibiting the migration and ***,the expression of MMP2,MMP9,and phosphorylated Integrinb1 were *** inhibited the proliferation,migration,and tube formation of HUVECs and reduced HIF1a expression and vascular endothelial growth factor A(VEGF-A)secretion in HCT8 cells,suggesting anti-angiogenic ***,digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 *** Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.

关键词： digoxin antitumor colorectal cancer cell-cycle arrest metastasis multidrug resistance

Crosslinking of Bovine Pericardia Using Procyanidins

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Chinese Journal of Biomedical Engineering(English Edition) 2011年第2期20卷 83-89页

作者： WAN Rong-xin TIAN Cong GU Han-qing LIU Xin tianjin Medical University Tianjin 300070 China tianjin institute of urological surgery Tianjin 300211 China

The aim of this study was to evaluate the crosslinking effect of a naturally crosslinking reagent-procyanidins （PA）-on the materials of bioprosthetic heart valves. After fixing bovine pericardial tissues by procyanidins, crosslikng characteristics, mechanical properties, in vitro enzymatic degradation resistance, the hydrophilicity and hemolysis tests were examined. The results showed that the fixation of biological tissue with glutaraldehyde （GA） or procyanidins increased its denaturation temperature, the surface hydrophilieity and mechanical properties as well as in vitro enzymatic degradation resistance. There were no significant differences in denaturation temperature, mechanical properties, the hydrophilicity and the in vitro enzymatic degradation between the glutaraldehyde and procyanidins fixed tissues. However, the ultimate tensile strength of the procyanidins fixed tissues was significantly superior to the glutaraldehyde fixed tissues. The hemolysis tests showed that hemolysis rate of the proeyanidins fixed tissues was lower than that of the glutaraldehyde fixed tissues. This study shows that procyanidins can crosslink which bovine pericardiaa effectively without toxicity. Our results suggest that this method might be a useful approach for the preparation of bioprosthetic heart valve.

关键词： bovine pericardia bioprosthetic heart valves glutaraldehyde procyanidins

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 387-400页

作者： Mark N Stein Rutgers Cancer institute of New Jersey Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA. Department of Medicine Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA. Section of urologic Oncology Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA.

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer （CRPC）, it is possible to detect persistent activation of the androgen receptor （AR） through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17（^-hydroxylase and 17,20-1yase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival （OS） with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone （ACTH）, providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-1yase （orteronel, galeterone and VT-464） that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

关键词： androgen synthesis castration-resistant prostate cancer treatment

Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis

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Chinese Medical Journal 2013年第9期126卷 1683-1688页

作者： SUN Bing-sheng YOU Jian LIYue ZHANG Zhen-fa WANG Chang-li Department of Lung Cancer surgery Tianjin Cancer Institute and Hospital Tianjin Medical University Tianjin Lung Cancer Center Key Laboratory of Cancer Prevention and Therapy of Tianjin Tianjin 300060 China

Background Osteopontin （OPN） was identified as one of the leading genes that promote the metastasis of malignant tumor. However, the mechanism by which OPN mediates metastasis in non-small cell lung cancer （NSCLC） remains unknown. The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line. Methods Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line （A549）, The invasion, proliferation, and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo. The related mechanism was further investigated. Results Interestingly, OPN knockdown significantly suppressed the invasiveness of A549 cells, but had only a minor effect on the cellular migration and proliferation. Moreover, we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase （MMP）-2 and urokinase plasminogen activator （uPA）, and led to an obvious inhibition of both in vitro invasion and in vivo lung metastasis ofA549 cells （P 〈0.001）. Conclusions Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion, independent of cellular migration and proliferation. OPN could be a new treatment target of NSCLC.

关键词： osteopontin RNA interference non-small cell lung cancer invasiveness

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery

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International Journal of Ophthalmology(English edition) 2022年第11期15卷 1806-1813页

作者： Ze-Tong Nie Bo-Shi Liu Yong Wang Qiong Chen Jiao-Ting Wei Meng Yang Shao-Fang Pang Xiao-Rong Li Bo-Jie Hu tianjin Key Laboratory of Retinal Functions and Diseases Tianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University EyeHospitalTianjin 300384China

AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A(18 patients), with the peeling area within one-half of the optic disc macular distance as the radius;group B(18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity(BCVA), light-adaptive electroretinography, macular hole(MH) closure rate, central macular thickness(CMT), retinal nerve fiber layer(RNFL) and ganglion cell complex(GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study(ETDRS) ring] before and 1, 3, and 6mo after ***: The closure rate was 94.4%(17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo(P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery(P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery(P=0.038).CONCLUSION: Enlarging the extent of ILM peeling doesn’t affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.

关键词： idiopathic macular hole internal limiting membrane light-adapted electroretinography retinal nerve fiber layer ganglion cell complex

Middle thyroid vein tumor thrombus in metastatic papillary thyroid microcarcinoma:A case report and review of literature

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World Journal of Clinical Cases 2022年第10期10卷 3213-3221页

作者： Yan Gui Jun-Yi Wang Xu-Dong Wei Department of Otorhinolaryngology Head and Neck surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Thyroid and Neck Tumor Key Laboratory of Cancer Prevention and Therapy of TianjinTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Department of Otorhinolaryngology Head and Neck surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Although papillary thyroid microcarcinoma(PTMC)is not considered a threatening tumor,in some cases,it can be *** thrombosis of papillary thyroid carcinoma,follicular thyroid carcinoma,Hürthle cell carcinoma,poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma have been reported in the literature,but there have been no reports about *** SUMMARY A 45-year-old woman presented with a thyroid mass and thrombosis in a middle thyroid vein during a physical *** had no symptoms,and the physical examination showed no positive *** ultrasonographyguided fine-needle aspiration biopsy results indicated an atypical lesion of ambiguous significance,with some actively growing cells(TBSRTCⅢ)and the BRAFV600E mutation not *** patient underwent left thyroidectomy,isthmus lobectomy,prophylactic central lymph node dissection and *** pathology showed papillary microcarcinoma of the left thyroid,and the thrombus in the middle thyroid vein was a tumor *** Middle thyroid vein tumor thrombus is an extremely rare condition in PTMC,but it does *** and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid,and we strongly suggest close follow-up of these patients.

关键词： Thyroid neoplasms Papillary carcinoma Thyroid vein Venous thrombosis surgery Case report

The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma

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Cancer Biology & Medicine 2021年第2期18卷 401-410页

作者： Xianxian Wu Hongdian Zhang Zhilin Sui Yang Wang Zhentao Yu Departments of Esophageal Cancer Department of Immunology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death *** squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer *** the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed *** C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and ***12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and *** addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor *** have shown that CXCL12 and its receptor,CXCR4,are highly expressed in *** abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening *** present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of *** article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of *** results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.

关键词： Esophageal squamous cell carcinoma C-X-C motif chemokine ligand 12 CXC chemokine receptor 4 antagonists imaging agent

Active surveillance as a management strategy for papillary thyroid microcarcinoma

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Cancer Biology & Medicine 2020年第3期17卷 543-554页

作者： Huan Zhang Xiangqian Zheng Juntian Liu Ming Gao Biyun Qian Cancer Prevention Center Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Head and Neck Tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Hongqiao International institute of Medicine Shanghai Tongren Hospital and Faculty of Clinical Research CenterShanghai Jiao Tong University School of MedicineShanghai 200025China

Active surveillance(AS)can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma(PTMC),with the absence of clinically apparent lymph nodes,extrathyroidal extensions,and distant *** reviewing the reports on AS of low risk PTMCs worldwide,we introduced AS,and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up ***,the requirement of cytological diagnosis,progression evaluation methods,necessity of thyrotropin suppression,and medical costs were issues that both clinicians and patients *** usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient *** may adopt measures like dynamic monitoring,risk stratification,and making personal follow-up schedules to minimize these potential *** appropriately selecting PTMC patients,AS can be an effective alternative treatment to immediate surgery.

关键词： Papillary thyroid carcinoma microcarcinoma active surveillance guidelines low risk

Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4235-4248页

作者： Xuantong Zhou Furong Huang Gang Ma Wenqing Wei Nan Wu Zhihua Liu State Key Lab of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021BeijingChina Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital&Institute100142BeijingChina Department of Gastric surgery Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for Cancer300060TianjinP.R.China

Whereas it is appreciated that cancer cells rewire lipid metabolism to survive and propagate,the roles of lipid metabolism in metastasis remain largely *** this study,using esophageal squamous cell carcinoma(ESCC)as a pulmonary metastasis model,we find that the enzyme fatty acid 2-hydroxylase(FA2H),which catalyzes the hydroxylation of free fatty acids(FAs),is enriched in a subpopulation of ESCC cells with high metastatic potential,and that FA2H knockdown markedly mitigates metastatic ***,increased FA2H expression is positively associated with poor survival in patients with *** analysis identifies that two dihydroceramides—Cer(d18:0/24:0)and Cer(d18:0/24:1)—are increased in FA2H-depleted metastasizing ESCC *** administration,Cer(d18:0/24:0)and Cer(d18:0/24:1)impair the formation of overt metastases in a mouse experimental metastasis ***,forkhead box protein C2(FOXC2)and FA2H are found to be co-upregulated in metastatic ESCC cell populations and ESCC specimens,and FA2H expression is further experimentally verified to be transcriptionally induced by FOXC2,which is boosted per se by tumour necrosis factorα(TNFα),a critical pro-metastasis cytokine in the tumour microenvironment,in metastasizing ***,these results demonstrate that TNFα-FOXC2-FA2H is a novel signaling axis to promote metastasis,and its downstream dihydroceramide products could be promising drugs to intervene in metastasis.

关键词： metastasis metabolism cancer