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Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

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Cellular & Molecular Immunology 2010年第3期7卷 211-220页

作者： Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng christina K Chan Kathy R Braun John A Gebe Gerald T nepom Thomas n Wight Benaroya Research Institute SeattleWAUSA

Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and *** hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC *** primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA ***,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA *** effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFn-c)and tumor necrosis factor a(TnF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th *** data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell *** also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen *** data point to a pivotal role for HA in DC–T cell interactions at the IS.

关键词： dendritic cell hyaluronan immune synapse pericellular matrix Th1

Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine

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Cancer Biology & Medicine 2020年第1期17卷 132-141页

作者： Tingting Chen Kan Liu Jiangyao Xu Tianying Zhan Maixian Liu Li Li Zhiwen Yang Shuping Yuan Wenyi Zou Guimiao Lin Dennis ACarson christina CnWu Xiaomei Wang Department of Physiology School of Basic Medical SciencesShenzhen University Health Sciences CenterShenzhen UniversityShenzhen 518060China Carson Lab Moores Cancer CenterUCSDLa Jolla 92093CAUSA

Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant ***,at present,there is no immune vaccine targeting these ***-binding transcription factor 4(OCT4),a marker of embryonic stem cells and germ cells,often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine ***:To identify the optimal carrier and adjuvant combination,we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein,keyhole limpet hemocyanin(KLH),combined with Toll-like receptor 9 agonist(TLR9).Results:Immunization with OCT4-3+TLR9 produced the strongest immune response in *** prevention assays,significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3+TLR9(Pntly,the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with ***,multiple cytokines[such as interferon(IFn)-γ(Pnterleukin(IL)-12(Pnd IL-6(Png cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3+***,we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation ***:Collectively,these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response,leading to the suppression of primary tumor growth in testis embryonic carcinoma.

关键词： Cancer prevention cancer immunology OCT4 TLR9 agonist

Treating refractory depression in Parkinson’s disease:a meta-analysis of transcranial magnetic stimulation

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Translational neurodegeneration 2018年第1期7卷 75-80页

作者： Alexandra M.Lesenskyj Megan P.Samples Jill M.Farmer christina R.Maxwell Rowan University School of Osteopathic Medicine StratfordNJ 08048USA Drexel neurosciences Institute 245 N 15th Street ms 423PhiladelphiaPA 19102USA

Background:Parkinson’s disease(PD)is often accompanied by clinically identified *** effective pharmacotherapies that concomitantly treat both motor and psychological symptoms can pose a challenge to *** this reason,alternatives to standard anti-depressant treatments,such as repetitive transcranial magnetic stimulation(rTMS),have been evaluated within the Parkinson’s ***:A literature search was conducted on the PubMed database for all studies that evaluated rTMS as a treatment in patients with both depression and PD.A meta-analysis was performed on all studies that reported mean pre-and post-rTMS depression inventory *** used depression inventories included both self-report and clinician-administered *** size for individual study groups and across all studies was ***:Six of 7 studies meeting inclusion criteria reported significantly improved depression scores,large effect sizes,and significant *** weighted average effect size was calculated at 1.32 across all study groups that applied ***:Across all but one study,rTMS appears to effectively reduce depression scores among self-reported and clinician administered *** total weight average effect size showed that,when considering study sample sizes and degree of findings,this form of neurostimulation can relieve PD patients of their depressive ***,rTMS is a promising alternative to traditional anti-depressant therapies when treating refractory depression in patients with PD.

关键词： Parkinson’s disease Depression Transcranial magnetic stimulation

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妊娠合并糖尿病的新疗法

英国医学杂志中文版 2019年第9期22卷 518-530页

作者： Maisa n Feghali christina M Scifres 刘煜婕(译) 丁宇(校) 王超凡(校) 翁建平(校) Department of Obstetrics Gynecology and Reproductive Sciences Magee-Womens Research Institute University of Pittsburgh School of Medicine Pittsburgh PA USA Department of Obstetrics and Gynecology University of Oklahoma College of Medicine Oklahoma City OK USA 中国科学技术大学附属第一医院(安徽省立医院) 南京医科大学第一附属医院中山大学附属第三医院

糖尿病是妊娠常见的并发症之一,目前全世界各种类型的糖尿病患病率均在上升。妊娠合并糖尿病与母婴短期及长期的不良结局相关。妊娠合并糖尿病的治疗目标是尽量减少高血糖相关的母婴不良事件。糖尿病的类型决定了治疗方式各有侧重,既有... 详细信息

糖尿病是妊娠常见的并发症之一,目前全世界各种类型的糖尿病患病率均在上升。妊娠合并糖尿病与母婴短期及长期的不良结局相关。妊娠合并糖尿病的治疗目标是尽量减少高血糖相关的母婴不良事件。糖尿病的类型决定了治疗方式各有侧重,既有关注改变妊娠期糖尿病患者的生活方式,也有关注糖尿病合并妊娠患者的持续血糖监测及胰岛素泵的应用。然而,考虑到不同类型的妊娠合并糖尿病均存在高血糖,因此治疗方法存在相当大的重叠。此外,尽管针对妊娠合并糖尿病治疗的研究已进行数十年,但是受限于患者群体特征的改变,不同治疗方法的局限性依然很突出。具体而言,尽管肥胖和糖尿病同时发生,包括血糖控制目标在内的治疗建议没有相应地改变,此外也没有针对每种类型的妊娠合并糖尿病单一最佳治疗策略。因此,妊娠期间的糖尿病女性更需要个体化的治疗,以最大限度地保证母婴的短期及长期健康。本文将回顾近期的临床研究,总结妊娠合并糖尿病的治疗策略和新的治疗方式。

关键词：妊娠合并糖尿病治疗方式疗法糖尿病患病率妊娠期糖尿病治疗方法高血糖不良结局

Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

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Asian Journal of Urology 2016年第4期3卷 229-239页

作者： Takeshi Hirata Seung Chol Park Michelle T.Muldong christina n.Wu Tomonori Yamaguchi Amy Strasner Omer Raheem Hiromi Kumon Robert L.Sah nicholas A.Cacalano Catriona H.M.Jamieson Christopher J.Kane Koichi Masuda Anna A.Kulidjian christina A.M.Jamieson Department of Urology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayamaJapan Department of Urology Wonkwang University School of Medicine and HospitalIksanSouth Korea Moores Cancer Center University of CaliforniaSan DiegoLa JollaCAUSA Department of Urology University of CaliforniaSan DiegoLa JollaCAUSA Department of Surgery University of CaliforniaSan DiegoLa JollaCAUSA Department of Medicine University of CaliforniaSan DiegoLa JollaCAUSA Department of Orthopaedic Surgery School of MedicineUniversity of CaliforniaSan DiegoLa JollaCAUSA Department of Bioengineering University of CaliforniaSan DiegoLa JollaCAUSA Department of Radiation Oncology University of California at Los AngelesLos AngelesCAUSA

Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and *** metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer ***,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel *** microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were ***:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male ***:Bone lesions formed only in femurs of mice injected with PCSD1 *** volume(BV)was significantly decreased at the proximal and distal ends of the femurs(pnd bone shaft diameter(pnificantly increased along the femur ***:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur ***,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone *** approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.

关键词： Bone metastatic prostate cancer Patient-derived xenograft microenvironment Microstructural CT Osteolytic lesions Osteoblastic lesions

Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates

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World Journal of Hepatology 2017年第26期9卷 1108-1114页

作者： Fang Kuan Chiou christina Ong Kong Boo Phua Fares Chedid Ajmal Kader Gastro-enterology Service Paediatric Medicine KK Women’s and Children’s Hospital neonatal Medicine Al Jalila Children’s Specialty Hospital Pediatric Gastroenterology Dubai Hospital

AIM To describe the etiology and characteristics of earlyonset conjugated hyperbilirubinemia(ECHB) presenting within 14 d of life in term *** Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia(CHB) at a tertiary center over a 5-year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin(CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 μmol/L. ECHB is defined as CHB detected within 14 d of life. "Late-onset" CHB(LCHB) is detected at 15-28 d of life and served as the comparison *** Total of 117 patients were recruited: 65 had ECHB, 52had LCHB. neonates with ECHB were more likely to be clinically unwell(80.0% vs 42.3%, P nd associated with non-hepatic causes(73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury(75.0%) and sepsis(17.3%) were the most common causes of ECHB in clinically unwell infants, majority(87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare(5.8%) but associated with high mortality(100%) in our series. In the subgroup of clinically well infants(n = 13) with ECHB, biliary atresia(BA) was the most common diagnosis(61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB. COnCLUSIOn Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice.

关键词： Conjugated hyperbilirubinemia Biliary atresia Cholestasis Direct hyperbilirubinemia neonatal jaundice

KIT-negative gastrointestinal stromal tumors with a long term follow-up:A new subgroup does exist

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World Journal of Gastroenterology 2007年第7期13卷 1098-1102页

作者： Katerina Kontogianni-Katsarou Constantina Lariou Eugenia Tsompanaki christina Vourlakou Evi Kairi-Vassilatou Costas Mastoris Georgia Pantazi Agatha Kondi-Pafiti Department of Pathology Athens Medical School Areteion University Hospital 76 Vas. Sophias Ave. Athens 11528 Greece Department of Pathology Evaggelismos General Hospital Ipsiladou 45-47 Athens 10676 Greece Department of Statistics School of Economics and Business Athens University Patision 76 Athens 10434 Greece

AIM: To investigate the incidence of KIT immunoho- stochemical staining in (GI) stromal tumors (GISTs), and to analyze the clinical manifestations of the tumors and prognostic indicators. METHODS: We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT (CD117 antigen), CD34, SMA, desmin, S-100, nSE, PCnA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors. RESULTS: Fifteen tumors (30%) were negative in KIT staining. A significant association was observed between gender (male patients: 14/15) and KIT-negative staining (P = 0.003).The patients's mean age was 56.6 years. Tumors developed in stomach (n = 8), small intestine (n = 5), large intestine (n = 1) and oesophagus (n = 1). The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF (mean: 3.4) and 73% of tumors showed no necrosis. The majority of the tumors (67%) had dual or epithelioid differentiation. Tumors were classified as very low or low risk (n = 7), intermediate risk (n = 5), and high risk (n = 3) groups. Twelve (80%) patients were alive without evidence of residual tumor for an average period of 40.25 mo (12-82 mo); three patients developed metastatic disease to the liver and eventually died within 2-12 mo (median survival: 8.6 mo).COnCLUSIOn: A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations.

关键词：胃肠基质肿瘤基因突变免疫组织化学治疗

Mining citizen science data to explore stopover sites and spatiotemporal variation in migration patterns of the red-footed falcon

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Current Zoology 2020年第5期66卷 467-475页

作者： Anastasios Bounas Maria Solanou Michele PAnUccio Sanja BARisic Taulant Bino Kiraz Erciyas-Yavuz Petar Iankov christina Ieronymidou Christos Barboutis Department of Biological Applications and Technology University of loanninaloannina45110Greece bManagement Body of Cyclades Protected Areas Tsiropina's MansionPoseidoniaSyros84100Greece MEDRAPT0RS(Mediterranean Raptor Migration network) via Mario Fioretti 18Rome00152Italy Institute of Ornithology Croatian Academy of Sciences and ArtsZagrebCroatia Faculty of Urban Planning and Environmental Management Polis UniversityRr.Bylis 12TiranaAlbania Ornithology Research Center Ondokuz Mayis UniversityAtakumSamsun55137Turkey Bulgarian Society for Protection of Birds/BirdLife Bulgaria Yavorov Complexbl.71vh.4PO Box 50Sofia1111Bulgaria BirdLife Cyprus PO Box 12026Nicosia2340Cyprus Hellenic Ornithological Society/BirdLife Greece Antikythira Bird ObservatoryThemistokleous 80AthensGR-10681Greece

Citizen scienee data have already been used to effectively address questions regarding migration,a fun dame ntal stage in the life history of *** this study,we use data from eBird and from 3 additional regional citizen scienee databases to describe the migration routes and timing of the red-footed falcon Falco vespertinus in the Mediterranean region across 8years(2010-2017).We further examine the seasonal and yearly variation in migration patterns and explore sites used during the species *** results suggest that the autumn passage is spatially less variable and temporally more consistent among years than in spring and that birds migrate faster in spring than in *** species seems to be more prevalent along the Central Mediterranean during spring migration,probably as a result of the clockwise loop migration that red-footed falcons *** was a high variation in annual median migration dates for both seasons as well as in migration routes across years and *** variation was exhibited in the longitudinal component thus indicating flexibility in migration *** additi on,our results showed the species'preference for I owl a nds covered with cropla nd and mosaics of cropland and natural vegetation as stopover sites during *** areas predicted from our distribution modeling highlight the importance of the Mediterranean islands as stopover sites for sea-crossing raptors,such as the red-footed *** study is the first to provide a broad-scale spatiotemporal perspective on the species migration across seasons,years and flyways and dem on strates how citize n science data can inform future monitori ng and conservation strategies.

关键词： distribution modeling eBird Maxent Mediterranean opportunistic data raptors

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机器人在结直肠手术中的作用

英国医学杂志中文版 2018年第11期21卷 643-652页

作者： christina L Cheng Craig Rezac 公磊(译) Colon and Rectal Clinic Swedish Medical Center1101Madison AvenueSte 510SeattleWA98104USA Virginia Hospital Center Physician Group 1625N George Mason DriveSte 334ArlingtonVA22205USA 北京清华长庚医院外科

研究支持结直肠手术使用腹腔镜途径。与开腹手术相比,腹腔镜手术减少了术后并发症发生率,缩短了住院时间,同时可以获得相同的肿瘤治疗效果。尽管如此,大部分结直肠手术仍然以开放手术方式进行。部分原因可能是腹腔镜手术存在技术挑战,... 详细信息

研究支持结直肠手术使用腹腔镜途径。与开腹手术相比,腹腔镜手术减少了术后并发症发生率,缩短了住院时间,同时可以获得相同的肿瘤治疗效果。尽管如此,大部分结直肠手术仍然以开放手术方式进行。部分原因可能是腹腔镜手术存在技术挑战,尤其是在像骨盆这样的狭窄腔隙中工作时。另外,现在一些文献对直肠癌腹腔镜手术的肿瘤治疗效果提出质疑。机器人手术被认为是一种可以克服这些挑战的微创治疗方式。它的优势是可以提供三维图像,使用可以扭曲的器械,并且具有计算机平台,可以做出流畅而且精准的动作。总体而言,目前的证据表明机器人技术在结直肠手术中是安全可行的,并且其短期和长期效果与腹腔镜手术相似。关于机器人手术的成本研究显示出了自相矛盾的结果,这是机器人应用的最大缺点之一。由于机器人技术是一项相对较新的技术,现在鲜有大规模高质量研究。这一领域发表的多数研究包括回顾性评论、案例匹配研究和国家数据库综述。还需要进行大型随机前瞻性研究来进一步支持其使用。

关键词：机器人手术直肠癌机器人技术治疗效果腹腔镜计算机平台机器人应用治疗方式