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Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

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Cancer Biology & Medicine 2013年第4期10卷 192-205页

作者： German G.Gomez Jill Wykosky Ciro Zanca Frank B.Furnari webster k.cavenee Ludwig Institute for Cancer Research University of California San Diego

Receptor tyrosine kinases(RTks)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic *** activates downstream signaling cascades that promote tumor cell survival,proliferation and *** of EGFR signaling as a consequence of overexpression,amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant ***,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit ***,limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell ***,we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EGFR to promote tumor initiation,progression and that play a role in resistance to EGFR *** also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.

关键词：表皮生长因子受体 microRNA 治疗药物癌症患者信号网络抗药性受体抑制剂受体酪氨酸激酶

Therapeutic targeting of epidermal growth factor receptor in human cancer: successes and limitations

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Chinese Journal of Cancer 2011年第1期30卷 5-12页

作者： Jill Wykosky Tim Fenton Frank Furnari webster k. cavenee Ludwig Institute for Cancer Research University of California San Diego Department of Medicine University of California San Diego

Epidermal growth fac tor receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification, and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation, and resistance to apoptosis. Small molecule tyrosine kinase inhibitors and monoclonal antibodies are among the most common EGFR-targeting agents and have been used clinically for treating various malignancies. This review discusses the successes and challenges of targeting EGFR in human cancer. The genetic alterations of EGFR tend to occur more often in some solid tumors than others, as do the mechanisms of resistance to targeted inhibition. The clinical and basic science experiences with these agents thus far have important implications for the future of therapeutic targeting of EGFR.

关键词：表皮生长因子受体靶向治疗癌症人类酪氨酸激酶抑制剂信号转导通路恶性肿瘤临床治疗

Targeted Therapies:The Importance of Signaling Molecules

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Targeted Therapies:The Importance of Signaling Molecules

Mobile stroke care expedites intravenous thrombolysis and endovascular thrombectomy

第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议

作者： webster k. cavenee Ph.D. Professor University of California-San Diego Director Ludwig Institute for Cancer Research-San Diego BranchLa JollaCA 92093-0660

＜正＞Advances in understanding the genetic basis of cancer have led to the identification of molecules that are specifically expressed in tumors. Such molecules represent targets for therapy whose targeting might be expected to have increased selectivity for tumor cells compared to normal tissue with resultant enhancements in effect and reductions in the non - specific toxicities that lead to chemotherapeutic side effects. Two such molecules are 1) a mutated form of the epidermal growth factor receptor （EGFR）;and, 2) the dual specificity phosphatase, PTEN. Both have been found in sizable proportions of tumors of the brain, lung, prostate and breast.

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Stroke & Vascular Neurology 2022年第3期7卷 209-214页

作者： Matthew T Bender Thomas k Mattingly Redi Rahmani Diana Proper Walter A Burnett Jason L Burgett Joshua LEsperance Jeremy T Cushman webster H Pilcher Curtis G Benesch Adam G kelly Tarun Bhalla Department of Neurosurgery University of Rochester Medical CenterRochesterNew YorkUSA Department of Emergency Medicine University of Rochester Medical CenterRochesterNew YorkUSA Department of Neurology University of Rochester Medical CenterRochesterNew YorkUSA

Background The number of mobile stroke programmes has increased with evidence,showing they expedite intravenous *** questions include whether time savings extend to patients eligible for endovascular therapy and impact clinical *** Our mobile stroke unit(MSU),based at an academic medical centre in upstate New York,launched in October *** reviewed prospective observational data sets over 26 months to identify MSU and non-MSU emergency medical service(EMS)patients who underwent intravenous thrombolysis or endovascular thrombectomy for comparison of angiographic and clinical *** Over 568 days in service,the MSU was dispatched 1489 times(2.6/day)and transported 300 patients(20%of dispatches).Intravenous tissue plasminogen activator(tPA)was administered to 57 MSU patients and the average time from 911 call-to tPA was 42.5 min(±9.2),while EMS transported 73 patients who received tPA at 99.4 min(±35.7)(pknown well and would likely have been outside the window with EMS *** thrombectomy was performed on 21 MSU patients with an average 911 call-to groin puncture time of 99.9 min(±18.1),while EMS transported 54 patients who underwent endovascular thrombectomy(ET)at 133.0 min(±37.0)(p=0.0002).There was no difference between MSU and traditional EMS in modified Rankin score at 90-day clinic follow-up for patients undergoing intravenous thrombolysis or endovascular thrombectomy,whether assessed as a dichotomous or ordinal *** Mobile stroke care expedited both intravenous thrombolysis and endovascular *** is an ongoing need to show improved functional outcomes with MSU care.

关键词： intravenous throm endovascular

Fundamental motor skills,screen-time,and physical activity in preschoolers

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Journal of Sport and Health Science 2019年第2期8卷 114-121页

作者： E.kipling webster Corby k.Martin Amanda E.Staiano School ofkinesiology Louisiana State University Pennington Biomedical Research Center Louisiana State University

Purpose: To examine the associations among preschoolers fundamental motor skills, screen-time, physical activity(PA), and sedentary behavior(SB).Methods: Children ages 3à4 years were enrolled in a prospective observational trial of PA. Trained assessors conducted the Test of Gross Motor Development-3 rd edition(TGMD-3), and the Movement Assessment Battery for Children-2 nd edition, and parent-reported child screen-time and sociodemographic information. Children wore an accelerometer for 7 days to examine SB and total PA(TPA). TPA was further characterized as moderateto-vigorous PA(MVPA) or vigorous PA(VPA). Mixed linear models were calculated, controlling for age(for TGMD-3), sex, household income, and accelerometer wear time(for accelerometry models), with childcare center as a random effect. The primary analysis reported on the cross-sectional baseline data of 126 children with complete fundamental motor skill and screen-time data; a subanalysis included 88 children with complete accelerometry ***: Children were 3.4 § 0.5 years of age(54% girls; 46% white, 42% African American, 12% other). A total of 48% lived in households at or below the federal poverty level. Children engaged in 5.1 § 3.6 h/day of screen-time. Children's screen-time was inversely related to the Movement Assessment Battery for Children-2 nd edition, manual dexterity skills percentile(b(SE) = ?1.7(0.8), p = 0.049). In the accelerometry subsample,children engaged in 5.9 § 0.9 h/day of TPA of which 1.7 § 0.6 h/day was MVPA. Boys engaged in more MVPA and VPA and less SB compared with girls(all p kills were positively related to VPA but inversely related to screen-time. Further inquiry into the implications of

关键词： Fundamental motor skills Physical activity Preschool Screen-time

The Language of Early Childhood: Volume 4

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Characterization of Yield Stress Development of Cement Paste by Electrical Resistivity

丛书名： Collected Works of M.A.k. Halliday

2004年

作者： M.A.k. Halliday Jonathan J. webster

ISBN: (数字)9781847144041

ISBN: (纸本)9780826458704

For nearly half a century, Professor M. A. k. Halliday has been enriching the discipline of linguistics with his keen insights into the social semiotic phenomenon we call language. This ten-volume series presents the seminal works of Professor Halliday. This fourth volume contains sixteen papers that look at the development of early childhood language. They are presented in three parts: infancy and protolanguage; the transition from child tongue to mother tongue; and early language and learning. The sociolinguistic account of the early development of the mother tongue presented by Professor Halliday is based on his intensive study of the language of one particular child, Nigel, for the period from nine- to eighteen months.

关键词： Language acquisition.

来源：畅想之星图书光盘版（南... 评论

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Journal of Wuhan University of Technology(Materials Science) 2017年第6期32卷 1361-1367页

作者： Mbujje Joel webster 魏小胜 ZHOU kongjin School of Civil Engineering and Mechanics Huazhong University of Science and Technology Wuhan 430074 China State key Laboratory of Silicate Wuhan University of Technology Wuhan 430070 China

Yield stress development of cement paste is potentially governed by percolation of 3-dimensional links formed by hydration products on the surface of the particles. It rises steadily at a gradual rate before a sudden increase in rate of growth. In this study, a method was proposed to predict the yield stress development based on the diameter of spread（D） of mini slump cone test and gradient from electrical resistivity measurement（km）. To evaluate the significance of（D） and（km） in terms of yield stress, they were quantitatively compared to the initial yield stress（τ0） and rate of yield stress growth（k） obtained from a rheometer. A mathematical relationship between the yield stress of cement paste, diameter of spread and electrical resistivity characteristic gradient was developed. The equation developed can be used as an alternative method to estimate yield stress of cement paste.

关键词： fly ash electrical resistivity rheology yield stress

Studies in Chinese language /

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Studies in Chinese language /

丛书名： The collected works of M.A.k. Halliday

2005年

作者： M.A.k. Halliday edited by Jonathan webster.

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