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  • Ovid Technologies (Wolters Kluwer Health)  (66)
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  • 1
    Online Resource
    Online Resource
    Soluble FLT1 Gene Therapy Alleviates Brain Arteriovenous Malformation Severity
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. 5 ( 2017-05), p. 1420-1423
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 5 ( 2017-05), p. 1420-1423
    Abstract: Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. Excessive vascular endothelial growth factor has been implicated in bAVM pathophysiology. Because soluble FLT1 binds to vascular endothelial growth factor with high affinity, we tested intravenous delivery of an adeno-associated viral vector serotype-9 expressing soluble FLT1 (AAV9-sFLT1) to alleviate the bAVM phenotype. Methods— Two mouse models were used. In model 1, bAVM was induced in R26CreER; Eng 2f/2f mice through global Eng gene deletion and brain focal angiogenic stimulation; AAV2-sFLT02 (an AAV expressing a shorter form of sFLT1) was injected into the brain at the time of model induction, and AAV9-sFLT1, intravenously injected 8 weeks after. In model 2, SM22αCre; Eng 2f/2f mice had a 90% occurrence of spontaneous bAVM at 5 weeks of age and 50% mortality at 6 weeks; AAV9-sFLT1 was intravenously delivered into 4- to 5-week-old mice. Tissue samples were collected 4 weeks after AAV9-sFLT1 delivery. Results— AAV2-sFLT02 inhibited bAVM formation, and AAV9-sFLT1 reduced abnormal vessels in model 1 (GFP versus sFLT1: 3.66±1.58/200 vessels versus 1.98±1.29, P 〈 0.05). AAV9-sFLT1 reduced the occurrence of bAVM (GFP versus sFLT1: 100% versus 36%) and mortality (GFP versus sFLT1: 57% [12/22 mice] versus 24% [4/19 mice] , P 〈 0.05) in model 2. Kidney and liver function did not change significantly. Minor liver inflammation was found in 56% of AAV9-sFLT1–treated model 1 mice. Conclusions— By applying a regulated mechanism to restrict sFLT1 expression to bAVM, AAV9-sFLT1 can potentially be developed into a safer therapy to reduce the bAVM severity.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.116.015713
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 2
    Online Resource
    Online Resource
    Efficacy of fulvestrant 500 mg in Chinese postmenopausal women with advanced/recurrent breast cancer and factors associated with prolonged time-to-treatment failure : A retrospective case series
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Medicine Vol. 99, No. 29 ( 2020-07-17), p. e20821-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 29 ( 2020-07-17), p. e20821-
    Abstract: This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure. Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed. Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response ( P  = .002, .026, .007, respectively). Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000020821
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2049818-4
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  • 3
    Online Resource
    Online Resource
    MicroRNA‐206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto‐oncogene and cyclin‐dependent kinase 6 in mice
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Hepatology Vol. 66, No. 6 ( 2017-12), p. 1952-1967
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. 6 ( 2017-12), p. 1952-1967
    Abstract: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here, we report that microRNA‐206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell‐cycle progression and the cMet signaling pathway. MicroRNA‐206 was underexpressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines. Combining bioinformatic prediction and molecular and cellular approaches, we identified cMET (Met proto‐oncogene), cyclin D1 ( CCND1 ), and cyclin‐dependent kinase 6 ( CDK6 ) as functional targets of microRNA‐206. By inhibiting expression of cMET , CCND1 , and CDK6 , microRNA‐206 delayed cell‐cycle progression, induced apoptosis, and impaired proliferation of three distinct human HCC cell lines. Systemic administration of microRNA‐206 completely prevented HCC development in both cMyc and V‐Akt murine thymoma viral oncogene homolog 1/neuroblastoma RAS viral oncogene homolog (AKT/Ras) HCC mice, whereas 100% of control mice died from lethal tumor burdens. Conversely, reintroduction of cMet or Cdk6 into livers of cMyc and AKT/Ras HCC mice recovered growth of HCC inhibited by microRNA‐206. These results strongly suggested that cMet and Cdk6 were two functional targets that mediated the inhibitory effect of microRNA‐206 on the development of HCC. MicroRNA‐206 overexpression demonstrated a profound therapeutic effect on HCC in xenograft and cMyc HCC mice. Conclusion: In summary, this study defines a potentially critical role of microRNA‐206 in preventing the growth of HCC and suggests its use as a potential therapeutic strategy for this malignancy. (H epatology 2017;66:1952–1967)
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.29374
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1472120-X
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  • 4
    Online Resource
    Online Resource
    Abstract W P413: Intravenous Delivery of the AAV9-sFLT Vector Reverses the Phenotype of Spontaneously Developed Brain Arteriovenous Malformation in Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. suppl_1 ( 2015-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. suppl_1 ( 2015-02)
    Abstract: Background and Purpose: Current therapies for brain arteriovenous malformation (bAVM) are invasive and have potential treatment-related morbidity. Excessive vascular endothelial growth factor (VEGF) expression is one of the key players in bAVM pathophysiology. The soluble VEGF receptor 1 (sFLT) possesses an anti-angiogenic effect. We hypothesize that intravenous delivery of adeno-associated viral vector serotype 9 (AAV9) expressing sFLT reverses the bAVM phenotype. Methods: SM22α-Cre transgenic mice were crossed with endoglin (Eng)-floxed mice to delete Eng. More than 95% of SM22 α-Cre;Eng-floxed mice spontaneously developed bAVM at age of 5 weeks. AAV9-sFLT (1x1011 viral genomes) was injected into the jugular vein of 5-week-old mice. AAV9-GFP was used as vector control. Brain vascular structure was analyzed using latex vascular casting 4 weeks after vector injection. The success of gene delivery, lymphocyte infiltration and neuronal loss was analyzed in the brain sections. Results: Due to the severity of the AVM lesion in this model, 3 of 9 AAV9-GFP-treated mice and 2 of 8 AAV9-sFLT-treated mice died during the 4-week treatment period. One paralyzed mouse in the AAV9-GFP group was euthanized before the treatment period ended. Only 1 of the 6 surviving mice in the AAV9-sFLT group had detectable bAVM, whereas all 5 mice in the AAV9-GFP group had it. GFP expression was detected in the bAVM lesion of AAV9-GFP-treated mice. Neither lymphocyte infiltration nor neuronal loss was observed. Conclusion: Because intravenous delivery of AAV9-sFLT reverses the bAVM phenotype without inducing intra-brain lymphocyte filtration and neuronal loss, AAV-mediated sFLT delivery could thus be developed into a specific, non-invasive therapy for patients with bAVM.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.46.suppl_1.wp413
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Abstract 54: Soluble FLT1 Gene Therapy Through Systemic Viral Delivery Reduces the Severity of Mouse Brain Arteriovenous Malformation
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. suppl_1 ( 2016-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Background & Purpose: Brain arteriovenous malformation (bAVM) is a risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. We tested a minimally invasive gene therapy using an adeno-associated viral vector (AAV9) to intravenously (IV) deliver an anti-angiogenic agent, soluble FLT1 (sFLT1), to two bAVM mouse models. Method: Model 1 consists of SM22α Cre; Endoglin (Eng, a bAVM causative gene)-floxed mice, which have a 90% occurrence of spontaneous bAVM after 5 weeks and 50% mortality after 6 weeks. In Model 2, bAVM is induced in RosaCreER; Eng -floxed mice through tamoxifen-mediated Eng -deletion and AAV1-VEGF-induced brain angiogenesis. AAV9-sFLT1 or AAV9-GFP was IV injected to 4-week-old Model 1 mice, or Model 2 mice 8 weeks after model induction. Brain vasculature was analyzed 4 weeks later through vessel-casting and brain section staining with CD31 antibody. Potential toxicities were assessed by analyzing brain and liver histology, and measuring serum alkaline phosphatase (ALP) and alanine transaminase (ALT) activities as well as creatinine (CR) levels. Results: sFLT1-treatment increased Model 1 mice survival. BAVMs were detected in all GFP-treated, but only in 25% of sFLT1-treated mice. In Model 2, sFLT1 treatment reduced abnormal vessels. No neuronal death or lymphocyte was detected in the brain of sFLT1-treated mice. AAV9 treatment did not cause weight loss, or alter CR levels or ALP and ALT activities. Small clusters of inflammatory cells were detected in the liver of 58% of GFP- and 56% of sFLT1-treated mice. Conclusion: Systemic sFLT1 gene therapy reduces bAVM severity with minimal adverse effect. Future studies should consider restricting sFLT1 expression in the brain to reduce liver inflammation.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.47.suppl_1.54
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 6
    Online Resource
    Online Resource
    Morphologic Analysis of the Temporomandibular Joint Between Patients With Facial Asymmetry and Asymptomatic Subjects by 2D and 3D Evaluation : A Preliminary Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Medicine Vol. 95, No. 13 ( 2016-03), p. e3052-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 13 ( 2016-03), p. e3052-
    Type of Medium: Online Resource
    ISSN: 0025-7974
    URL: Article
    DOI: 10.1097/MD.0000000000003052
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2049818-4
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  • 7
    Online Resource
    Online Resource
    Long-term High-fat High-sucrose Diet Promotes Enlarged Islets and β-Cell Damage by Oxidative Stress in Bama Minipigs
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Pancreas Vol. 44, No. 6 ( 2015-08), p. 888-895
    Details
    In: Pancreas, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 6 ( 2015-08), p. 888-895
    Type of Medium: Online Resource
    ISSN: 0885-3177
    URL: Article
    DOI: 10.1097/MPA.0000000000000349
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2053902-2
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  • 8
    Online Resource
    Online Resource
    Right hemicolectomy combined with pancreatico-duodenectomy for the treatment of colon carcinoma invading the duodenum or pancreas
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Chinese Medical Journal Vol. 119, No. 20 ( 2006-10), p. 1740-1743
    Details
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 20 ( 2006-10), p. 1740-1743
    Type of Medium: Online Resource
    ISSN: 0366-6999
    URL: Article
    DOI: 10.1097/00029330-200610020-00012
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 2108782-9
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  • 9
    Online Resource
    Online Resource
    Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD 2 Score
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Abstract: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687] ) but not in the high-risk group ( P 〉 0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.032424
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 10
    Online Resource
    Online Resource
    Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Abstract: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.042233
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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