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| 1 | Adaptive pathways and emerging strategies overcoming treatment resistance in castration resistant prostate cancer显示文摘The therapies available for prostate cancer patients whom progress from hormonesensitive to castration resistant prostate cancer include both systemic drugs,including docetaxel and cabazitaxel,and drugs that inhibit androgen signaling such as enzalutamide and abiraterone.Unfortunately,it is estimated that up to 30%of patients have primary resistance to these treatments and over time even those who initially respond to therapy will eventually develop resistance and their disease will continue to progress regardless of the presence of the drug.Determining the mechanisms involved in the development of resistance to these therapies has been the area of intense study and several adaptive pathways have been uncovered.Androgen receptor(AR)mutations,expression of AR-V7(or other constitutively active androgen receptor variants),intracrine androgen production and overexpression of androgen synthesis enzymes such as Aldo-Keto Reductase Family 1,Member C3(AKR1C3)are among the many mechanisms associated with resistance to anti-androgens.In regards to the taxanes,one of the key contributors to drug resistance is increased drug efflux through ATP Binding Cassette Subfamily B Member 1(ABCB1).Targeting these resistance mechanisms using different strategies has led to various levels of success in overcoming resistance to current therapies.For instance,targeting AR-V7 with niclosamide or AKR1C3 with indomethacin can improve enzalutamide and abiraterone treatment.ABCB1 transport activity can be inhibited by the dietary constituent apigenin and antiandrogens such as bicalutamide which in turn improves response to docetaxel.A more thorough understanding of how drug resistance develops will lead to improved treatment strategies.This review will cover the current knowledge of resistance mechanisms to castration resistant prostate cancer therapies and methods that have been identified which may improve treatment response. | Cameron M.Armstrong Allen C.Gao | 2016 | Asian Journal of Urology2016，3，4： | 3 |
| 2 | Current strategies for targeting the activity of androgen receptor variants显示文摘Current therapies for advanced prostate cancer,such as enzalutamide and abiraterone,focus on inhibiting androgen receptor(AR)activity and reducing downstream signaling pathways to inhibit tumor growth.Unfortunately,cancer cells are very adaptable and,over time,these cells develop mechanisms by which they can circumvent therapeutics.One of the many mechanisms that have been discovered is the generation of AR variants.These variants are generated through alternative splicing of the full length AR and often lack the ligand binding domain.This leads to forms of the AR that are constitutively active that continue to promote prostate cancer cell growth even in the absence of ligand.The high prevalence of AR variants and their role in disease progression have prompted a number of studies investigating ways to inhibited AR variant expression and activity.Among these are the antihelminthic drug,niclosamide,which selectively promotes degradation of AR variants over full length AR and re-sensitizes anti-androgen resistant prostate cancer cells to treatment with enzalutamide and abiraterone.Other AR variant targeting mechanisms include interfering with AR variant co-activators and the development of drugs that bind to the DNA or N-terminal AR domains,which are retained in most AR variants.The clinical efficacy of treating prostate cancer by targeting AR variants is under investigation in several clinical trials.In this review,we provide an overview of the most relevant AR variants and discuss current AR variant targeting strategies. | Cameron M.Armstrong Allen C.Gao | 2019 | Asian Journal of Urology2019，6，1： | 3 |
| 3 | Tumour necrosis factor and inflammatory bowel disease显示文摘 | A. M.Armstrong K. R.Gardiner S. J.Kirk M. I.Halliday B. J.Rowlands | 2005 | Br J Surg2005，，8： | 1 |
| 4 | Visible-and solar-blind photodetectors using AlGaN high electron mobility transistors with a nanodot-based floating gate显示文摘AlGaN-channel high electron mobility transistors(HEMTs) were operated as visible-and solar-blind photodetectors by using GaN nanodots as an optically active floating gate. The effect of the floating gate was large enough to switch an HEMT from the off-state in the dark to an on-state under illumination. This opto-electronic response achieved responsivity >10^8 A∕W at room temperature while allowing HEMTs to be electrically biased in the offstate for low dark current and low DC power dissipation. The influence of GaN nanodot distance from the HEMT channel on the dynamic range of the photodetector was investigated, along with the responsivity and temporal response of the floating gate HEMT as a function of optical intensity. The absorption threshold was shown to be controlled by the AlN mole fraction of the HEMT channel layer, thus enabling the same device design to be tuned for either visible-or solar-blind detection. | ANDREW M.ARMSTRONG BRIANNA A.KLEIN ANDREW A.ALLERMAN ALBERT G.BACA MARY H.CRAWFORD JACOB PODKAMINER CARLOS R.PEREZ MICHAEL P.SIEGAL ERICA A.DOUGLAS VINCENT M.ABATE FRANCOIS LEONARD | 2019 | Photonics Research2019，7，6： | 0 |
| 5 | Beneficial horticultural responses from the application of solar thermotherapy to mature Huanglongbing-affected citrus trees显示文摘The detrimental effects of Huanglongbing(HLB)on citrus are well known and so is the need for effective methods to combat this disease.Solar thermotherapy(ST),one of the management methods to help alleviate some of the negative effects of HLB,is the process of heating trees to therapeutic temperatures by encompassing the tree within a plastic structure(Visqueen)to harness the sun’s natural energy.ST was applied to mature‘Valencia’citrus trees in three locations.Tree vigor,yield,and Candidatus Liberibacter asiaticus(Las)titer in leaves were monitored for two consecutive seasons post ST treatment,while fruit and juice quality were evaluated at the end of the second season.ST promoted an increase in canopy density in most groves tested and did not have a significant effect on fruit quantity,despite the prolonged exposure of the trees to increased temperatures.Moreover,Las titer was reduced in both leaves and juice processed from affected trees post ST.With respect to fruit quality,the ratio of total soluble solids to titratable acidity was higher post ST compared to controls as was the sucrose content of the juice in most treated groves,whereas limonin was higher in juice from control trees.Principal components analysis of aroma volatiles showed significant differences between juice from treated versus control trees with volatiles imparting top-note and freshness to orange juice,such as acetaldehyde,hexanal,Z-3-hexenol and linalool,being higher in juice fromtreated trees.Taste panels confirmed that flavor differences existed,ultimately showing that ST resulted in improved juice flavor in well-managed groves.Although the effects of ST on the trees appear temporary,such outcomes emphasize its utility when used as part of an integrated management strategy for HLB-affected citrus,imparting beneficial horticultural responses with minimal to positive effects on subsequent juice flavor. | Cheryl M.Armstrong Melissa S.Doud Weiqi Luo Smita Raithore Elizabeth A.Baldwin Wei Zhao Anne Plotto Jinhe Bai John A.Manthey Ed Stover Yongping Duan | 2021 | Horticultural Plant Journal2021，7，5： | 0 |
| 6 | 你从未听说过的9款最伟大的真空管显示文摘这些真空器件经历了冷战时期,推进了粒子物理学的发展,使癌症病人得到治疗,还使披头士乐队的音乐更动听。在一个由无数固态器件支撑的时代,我们还需要关注真空管吗?绝对需要!因为从丰富性、戏剧性和纯粹的辉煌来说,很少有技术能与真空管116年(还在延续)的历史媲美。●为了证明这一点,我整理了一份清单,列出了在过去六七十年里无疑改变了世界的真空器件。 | Carter M.Armstrong | 2020 | 科技纵览2020，，11： | 0 |
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