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XBP1 splicing contributes to endoplasmic reticulum stress-induced human islet amyloid polypeptide up-regulation

Genes & Diseases 2024年第5期11卷 350-359页

作者： Yun Zhang susan Lin Jing Yao Wantong Cai Huaqiu Chen Ailikemu Aierken Zhe Wang Weihong Song National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

As a pathological hallmark of type 2 diabetes mellitus(T2DM),islet amyloid is formed by the aggregation of islet amyloid polypeptide(IAPP).Endoplasmic reticulum(er)stress interacts with IAPP aggregates and has been implicated in the pathogenesis of *** examine the role of er stress in T2DM,we cloned the hIAPP promoter and analyzed its promoter activity in human *** found that er stress significantly enhanced hIAPP promoter activity and expression in human b-cells via triggering X-box binding protein 1(XBP1)*** identified a binding site of XBP1 in the hIAPP *** of this binding site by substitution or deletion mutagenesis significantly diminished the effects of er stress on hIAPP promoter *** of XBP splicing by MKC3946 treatment inhibited er stress-induced hIAPP up-regulation and improved human b-cell survival and *** study uncovers a link between er stress and IAPP at the transcriptional level and may provide novel insights into the role of er stress in IAPP cytotoxicity and the pathogenesis of T2DM.

关键词： b-cell function Endoplasmic reticulum stress Islet amyloid polypeptide Type 2 diabetes mellitus XBP1

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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 pot.er-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

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Is nasopharyngeal cancer really a “Cantonese cancer”?

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Chinese Journal of Cancer 2010年第5期29卷 517-526页

作者： Joseph Tien Seng Wee Tam Cam Ha susan Li er Loong Chao-Nan Qian Division of Clinical Trials & Epidemiological Sciences National Cancer Centre Singapore 169610 Singapore Department of Radiation Oncology National Cancer Centre Singapore 169610 Singapore NCCS-VARI Translational Cancer Research Laboratory Humphrey-Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Singapore State Key Laboratory of Oncology in South China Guangzhou Guangdong 510060 P.R. China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer Center Guangzhou Guangdong 510060 P.R. China

Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the *** journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through ***,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese *** searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of *** migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical *** and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common *** studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern *** these populations have a high incidence of *** early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

关键词：鼻咽癌广东省全国人民代表大会中国南部发病率个人资料指纹识别格陵兰岛

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Regulation and role of the er chaperone BiP

Regulation and role of the ER chaperone BiP

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Third Congress of the Asian-Pacific Organization for Cell Biology

作者： Mary-Jane Gething Leon Helfenbaum Amanda Lim Carolyn McNees susan Shahin Department of Biochemistry and Molecular Biology University of MelbourneParkvilleVictoria 3052Australia

The major stress-responsive protein in the endoplasmic reticulum (er) is BiP, an HSP70 molecular chaperone required both for translocatinn of nascent proteins across the er membrane and for their subsequent folding and assembly. Nuclear transcription of the genes encoding BiP and other er chaperones is increased many fold when unfolded proteins accumulate within the er. The promoters of these genes all contain an unfolded protein response element (UPRE). Thus a novel intracellular sensing system exists that monitors events in the

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乳腺疾病基础知识(三) 早期乳腺癌的内科治疗(Ⅲ):化疗

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英国医学杂志中文版 2006年第4期9卷 246-248页

作者： Ian Smith susan Chua 王佳玉

对于年龄小于70岁的具有中、高度危险因素的乳腺癌患者来说，辅助化疗具有显著的生存益处，并且患者越年轻受益越大。这是因为年轻患者往往具有一些特殊的生物学表现，如：雌激素受体（er）阴性，组织学分级Ⅲ级等，这些因素提示高危。... 详细信息

对于年龄小于70岁的具有中、高度危险因素的乳腺癌患者来说，辅助化疗具有显著的生存益处，并且患者越年轻受益越大。这是因为年轻患者往往具有一些特殊的生物学表现，如：雌激素受体（er）阴性，组织学分级Ⅲ级等，这些因素提示高危。另外，化疗诱导的卵巢功能减退，对于那些er阳性的患者来说似乎是一种有益因素。50岁以上高危患者也可从化疗中受益，但是除了肿瘤分化差、人表皮生长因子受体2（Her-2）过表达或腋淋巴结转移数目多的患者以外，其中许多患者单用内分泌治疗即可有效。由于化疗的毒性较大，考虑风险及受益始终是重要的，目前的治疗共识标准有助于选择患者进行治疗。

关键词：辅助化疗内科治疗早期乳腺癌基础知识乳腺疾病人表皮生长因子受体乳腺癌患者淋巴结转移数目卵巢功能减退年轻患者

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点对核值匹配的角点检测

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计算机工程与应用 2010年第7期46卷 192-193,217页

作者：盛遵冰崔贤玉陈二龙哈尔滨工业大学现代生产技术中心哈尔滨150001

针对susan法检测X型角点能力较弱的问题,提出一种新的角点检测算法。在圆形模板区域内引入点对的概念,通过建立核值与点对的匹配规则来检测角点。给出了一个模板响应公式,加大了各点模板响应值的差别,提高了算法的抗干扰能力。实验结果... 详细信息

针对susan法检测X型角点能力较弱的问题,提出一种新的角点检测算法。在圆形模板区域内引入点对的概念,通过建立核值与点对的匹配规则来检测角点。给出了一个模板响应公式,加大了各点模板响应值的差别,提高了算法的抗干扰能力。实验结果表明,该算法对复杂的X型角点和普通角点均具有较好的检测效果。

关键词： susan算法角点检测点对

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Osteolytic effects of tumoral estrogen signaling in an estrogen receptor-positive breast cancer bone metastasis model

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 254-271页

作者： Julia N.Cheng Jennifer B.Frye susan A.Whitman Andrew G.Kunihiro Julia A.Brickey Janet L.Funk Cancer Biology Graduate Interdisciplinary Program University of ArizonaTucsonAZ 85724USA Department of Medicine University of ArizonaTucsonAZ 85724USA Department of Nutritional Sciences University of ArizonaTucsonAZ 85724USA

Aim:Estrogen receptorα-positive(er+)subtypes of breast cancer have the greatest predilection for forming osteolytic bone metastases(BMETs).Because tumor-derived factors mediate osteolysis,a possible role for tumoral erαsignaling in driving er+BMET osteolysis was queried using an estrogen(E2)-dependent er+breast cancer BMET ***:Female athymic Foxn1nu mice were inoculated with human er+MCF-7 breast cancer cells via the left cardiac ventricle post-E2 pellet placement,and age-and dose-dependent E2 effects on osteolytic er+BMET progression,as well as direct bone effects of E2,were ***:Osteolytic BMETs,which did not form in the absence of E2 supplementation,occurred with the same frequency in young(5-week-old)*** mature(16-week-old)E2(0.72 mg)-treated mice,but were larger in young mice where anabolic bone effects of E2 were ***,in mice of a single age and across a range of E2 doses,anabolic E2 bone effects were constant,while osteolytic er+BMET lesion incidence and size increased in an E2 dose-dependent *** in er+tumor-bearing(but not tumor-naive)mice increased in an E2-dose dependent fashion at the bone-tumor interface,while histologic tumor size and proliferation did not vary with E2 dose.E2-inducible tumoral secretion of the osteolytic factor parathyroid hormone-related protein(PTHrP)was dose-dependent and mediated by erα,with significantly greater levels of secretion from er+BMET-derived tumor ***:These results suggest that tumoral erαsignaling may contribute to er+BMET-associated osteolysis,potentially explaining the greater predilection for er+tumors to form clinically-evident osteolytic BMETs.

关键词： Breast cancer estrogen receptor bone metastasis estradiol osteolysis osteoclasts parathyroid hormone-related protein bone

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Design,synthesis and cytotoxic activity of novel spin-labeled camptothecin derivatives

Design,synthesis and cytotoxic activity of novel spin-labele...

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第十二届全国青年药学工作者最新科研成果交流会

作者： Mei-Juan Wang Xiao-Bo Zhao Masuo Goto susan L.Morris-Natschke Ying-Qian Liu Dan Wu Xiao-Bing Wu Zi-Long Song Gao-Xiang Zhu Kuo-Hsiung Lee School of Pharmacy Lanzhou University Natural Products Research Laboratories UNC Eshelman School of PharmacyUniversity of North Carolina Chinese Medicine Research and Development Center China Medical University and Hospital

Continuing our search for natural product-based spin-labeled antitumor drugs,a series of novel spin-labeled camptothecin derivatives were synthesized via a Cu-catalyzed one pot reaction and evaluated for cytotoxicity against four tumor cell lines（A-549,MDA-MB-231,KB and KBvin）.All target compounds（except for 9c and 91） exhibited significant in vitro cytotoxic activity against the four tested tumor cell lines,notably against the drug resistant KBvin cancer cell *** compounds 9e and 9j（IC50 0.0568 and 0.0720μM,respectively） displayed the greatest cytotoxicity against KBvin cancer cell *** on the observed cytotoxicity,preliminary structure-activity relationships have been described.

关键词： Camptothecin C-20 position spin labeled cytotoxic activity

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